Objective. To report the patient demographics and nonsurgical complementary and alternative medicine treatment used at a Korean medicine hospital for low back pain (LBP) and/or sciatica after surgery. Methods. Medical records of patients who visited a spine-specialized Korean medicine hospital at 2 separate sites for continuous or recurrent LBP or sciatica following back surgery were reviewed. The demographics, MRI and/or CT scans, and treatments were assessed. Results. Of the total 707 patients, 62% were male and the average age was 50.20 years. Ninety percent of patients presented with LBP and 67% with sciatica. Eighty-four percent were diagnosed with herniated nucleus pulposus at time of surgery. Of these patients, 70% had pain recurrence 6 months or later, but 19% experienced no relief or immediate aggravation of pain after surgery. Many patients selected traditional Korean medicine treatment as primary means of postsurgery care (47%). When time to pain recurrence was short or pain persisted after surgery, return of symptoms at the same disc level and side was frequent. Conclusion. An integrative treatment model focusing on Korean medicine and used in conjunction with radiological diagnostics and conventional medicine is currently used as a treatment option for patients with pain after lumbar spine surgery. Although low back pain (LBP) is considered to have a favorable natural prognosis, lumbar spine surgery is still frequently performed. In the US, the prevalence of lumbar fusion surgery has increased 220% from 1990 to 2001 [However, with the increase of surgery cases, the interest in failure rates is also on the rise. A 10- to 22-year follow-up study by Yorimitsu et al. on the outcomes of discectomy for lumbar herniated nucleus pulposus (HNP) reported 74.6% of patients had residual LBP and 12% required reoperation(s) . In KoreOther studies on the results of back surgery reported that adequate pain relief was not achieved in up to 30% of patients receiving a single lumbar segment operation  and thatAs more patients and practitioners are taking an interest in treatment for patients with pain after surgery, discussions continue to further demarcate the somewhat controversial term, failed back surgery syndrome (FBSS). The term FBSS is usually used to describe conditions presenting as recurrent or persisting LBP with or without sciatica after one or more lumbar surgeries , and numBesides the conventional treatments listed above, there are various types of complementary and alternative medicine (CAM) originating in non-Western cultures or not yet accepted in mainstream medicine lacking scientific evidence. The UK National Health Service (NHS) website cites the US National Center for Complementary and Alternative Medicine (NCCAM) and states that when a treatment is used alongside conventional treatments to help a patient deal with a certain health condition, but not as an alternative, this use of treatment is called “complementary medicine” and when a treatment is used instead of conventional treatments with the intention of curing or treating a health condition, the use is called “alternative medicine” . TraditiJaseng Hospital of Korean Medicine is a group of Korean medicine hospitals that specialize in spine disorders and is designated by the Korean Ministry of Health and Welfare as a spine specialty hospital, treating 900,000 cases of spinal disorders  each year. Treatment mainly focuses on HNP and spine-related pain patients prior to developing postsurgery syndrome, and the hospital employs a cohesive overall treatment approach using Korean medicine as the main modality and the imaging technology of conventional medicine and treatment, as needed, for emergency care. This retrospective multicenter study assesses the demographics of the patients who visited Jaseng Hospital of Korean Medicine in Seoul, Korea, and Bucheon Jaseng Hospital of Korean Medicine in Bucheon, Korea, from January to December, 2012, for low back pain or sciatica recurrence after surgery and the treatment received through electronic medical records.Demographic characteristics included patients' sex, age, occupation, and medical history including hypertension/diabetes, site of pain, number of operations, recommendations for repeat surgery, duration of time from surgery to pain recurrence, duration of pain, limited lumbar range of motion (ROM) due to pain, pain intensity , treatments received prior to current hospital visit, primary diagnosis for surgery as reported through patient recollection, mode of onset of pain recurrence, number of MRI/CT scans performed after surgery at study setting, number of MRI/CT scans performed at other clinics or hospitals, number of patients who received inpatient treatment, and average length of hospital stay.The radiological readings of the MRI/CT scans of 288 patients evaluated by two experienced radiologists were used to categorize patients by radiological diagnosis at time of visit, level of HNP at time of spine surgery, method of surgery, and pain recurrence.Lastly, the types and frequency of treatment, number of recipient patients, and average number of treatment sessions per patient were evaluated. The treatment mainly focused on traditional Korean medicine which encompasses herbal medicine, acupuncture, electroacupuncture, pharmacopuncture, bee venom pharmacopuncture, Chuna , and physical therapy.This study was approved by the Institutional Review Board of Jaseng Hospital of Korean Medicine (SIRB2013-18) and adhered to research ethics .A total of 707 patients presented with recurrent LBP or sciatica after lumbar surgery at the two study sites in 2012, and 16% of these patients received an average 21.72 (±11.91) days of inpatient treatment. The average age was 50.20 (±15.15) yrs, and 62% were male.Of the patients who visited the hospital due to LBP or sciatica following lumbar spine surgery, 90% had a chief complaint of LBP and 67% had sciatica (with or without LBP). Of subgroups classified by pain intensity, the majority (40%) had severe pain with an NRS of 7 or higher, and 31% of the total patients showed restricted ROM with pain.Although 70% of patients had pain recurrence at 6 months or later after surgery, 22% were acute patients with pain recurring within a month. The average time to pain recurrence from surgery was 13.93 (±23.24) months.The average number of surgeries was 1.16 (±0.41). Assessments for prior treatments revealed that 47% of patients, which was the highest proportion, made Jaseng Hospital of Korean Medicine their first choice of treatment, and 17% selected other providers of traditional Korean medicine, showing that many patients chose Korean medicine as their primary means of medical care for postsurgery pain. Sixteen percent had received recommendations for repeat surgery prior to their visit to the study site. The most commonly reported diagnosis for surgery was HNP which accounted for 84%.The findings of the MRI/CT scans of 288 patients were recorded by experienced radiologists and assessed and categorized for study means. The vast majority were diagnosed with HNP (77%) and spinal stenosis (18%) through imaging. The most frequently operated disc level was L4/5 (58%). Analyses on correlations between time to pain recurrence after surgery and symptom recurrence at site of surgery and mode of onset of pain recurrence and symptom recurrence at site of surgery found that in cases with shorter periods to pain recurrence and in continuation of pain, same site and same disc level symptom recurrence was more likely to occur.The treatment methods, frequency of treatment sessions, number of recipients, and average number of treatment sessions per patient were analyzed. The main treatment modality was TKM treatment including herbal medicine, acupuncture, electroacupuncture, pharmacopuncture , bee venom pharmacopuncture, Chuna, and Korean medicine physical therapy based on traditional Korean medicine literature  therapy), and a small number of patients received conventional medicine treatment in addition to the main treatment. The records of herbal and conventional medicine intake were recorded in days and other treatments in number of sessions. The norm for outpatient treatment use was 1~2 times per week and that for inpatients was daily. Considering the relative difference in frequency, it can be inferred that inpatients received more intensive treatment in a compact amount of time than outpatients.Most patients visiting Korean medicine hospitals for postsurgery treatment in our study reported chronic conditions and intense pain. Also, a large proportion presented with more severe conditions with low back pain accompanied by sciatica. Furthermore, almost half the patients selected Jaseng Hospital of Korean Medicine or Bucheon Jaseng Hospital of Korean Medicine as their first choice for primary care, suggesting high expectation levels of TKM treatment in Korea. A practical approach using integrative TKM treatment was provided to the patients rather than a single treatment modality, and conventional medicine treatment was utilized as needed. On analysis of the MRI readings of 236 patients, the most frequent site of surgery was L4/L5.McCulloch reported in a radiological research assessing pain recurrence the incidence of recurrence at the same disc level and ipsilateral side after surgery to be between 80% and 90% . Other sThe basic treatments received were acupuncture, herbal medicine, electroacupuncture, and pharmacopuncture. The results show that patients receiving inpatient care were offered more intensive treatment means than outpatients.In an attempt to define the term FBSS, various standards have been suggested; one RCT specified FBSS as long-term continuance of chronic pain conditions , and somAlthough the need for studies on the etiology of FBSS has been well explained and agreed on, only a limited number is currently available. We had initially considered reporting the demographics of a more clearly defined group of patients, but the large variation in previous definitions of FBSS prevented us from reaching a singular conclusion. The subjects included in our study were back surgery patients visiting the hospital for postoperative pain. While subjective pain levels requiring treatment may vary, all subjects visited the hospital for treatment purposes indicating a certain level of discomfort or pain. Therefore, the demographic characteristics of all patients with recurrent pain after surgery were collected and investigated to a broader extent than previous FBSS studies. The main mode of treatment was CAM focusing on TKM, and use of this integrative model of treatment based on TKM which is not yet well-known in the Americas and Europe was investigated and analyzed.Pharmacopuncture is a relatively new form of TKM derived from a mixture of herbal medicine and acupuncture. The physical therapy referred to in our study is a Korean medicine physical therapy administered by Korean medicine doctors (KMDs) based on traditional Korean medicine literature  therapy). Therefore, pharmacopuncture and Korean medicine physical therapy fall under the category of CAM treatment as TKM modalities provided by KMDs. A small number of patients received conventional pharmacological therapy, injections, and nerve blocks through cooperative, integrative treatment with Western medicine doctors. However, the main objective of this study was not to prove the exclusive effects of CAM treatment, but to show the current use of integrative medicine at a CAM-oriented medical facility.To address a few limitations of this study, first, in the process of interviewing the patients, we were dependent on the memory of the patients regarding information of their condition at time of surgery, so the accuracy of information could not be verified. Second, data collection focused on plain symptom listings with no definite differentiation between such chronic pain disorders as complex regional pain syndrome, myofascial pain syndrome, and fibromyalgia. Third, lack of evidence on the effectiveness of the separate modalities in TKM treatment restricted further analysis and interpretation.The preference for CAM for spinal disorder treatment is increasing not only in Korea, but also in many other countries. According to a 2004 survey, 43% of peripheral neuropathy patients used CAM treatment for management of their symptoms, and the main reason for selecting CAM treatment was that many did not achieve adequate pain relief with standard conventional treatment. The most frequent CAM treatment methods used were acupuncture, chiropractic manipulation, herbal remedies, magnetic therapies, and vitamins .The extent of CAM use is largely influenced by the medical system of each country. In Korea, equal licenses and independent practice rights for Korean medicine doctors and conventional medical doctors are guaranteed by the government, which is one of the reasons why Korean medicine could take on a leading role in this integrative treatment model. In this study, patients with recurrent pain after surgery received radiological diagnosis and requested conventional medicine treatments as necessary under the supervision of KMDs with Korean medicine treatment. However this could be deemed highly unusual in other cultural backgrounds.This study showed how an integrative treatment model focused on Korean medicine treatment was used in patients with chronic and severe pain after back surgery. We hope that our study data may further understanding of FBSS patients who select Korean medicine treatment and be used as basic information in establishing an integrative treatment model for spinal disorders.


The somatosensory phenotype of Chinese temporomandibular disorders (TMD) patients is not sufficiently studied with the use of contemporary techniques and guidelines.A standardized quantitative sensory testing (QST) battery consisting of 13 parameters with a stringent statistical protocol developed by the German Research Network on Neuropathic Pain was performed over the most painful and corresponding contralateral sites as well as the right hand of 40 Chinese patients with TMD and pain classified according to the Diagnostic Criteria for TMD (DC/TMD). The same QST protocol was performed bilaterally over the infraorbital, mental, and hand regions of 70 age- and gender-stratified healthy Chinese controls. Z-scores and loss/gain scores were computed for each TMD patient.For patients, 82.5 % had somatosensory abnormalities in the painful facial region, while 60.0 % had abnormalities confined to the right hand. The most frequent abnormalities were somatosensory gain to pinprick (35.0 %) and pressure (35.0 %) stimuli, somatosensory loss to pinprick (25.0 %), cold (22.5 %), and heat (15.0 %) nociceptive stimuli. The most frequent loss/gain score was L0G2  for both the facial (40.0 %) and hand (27.5 %) regions. Involving side-to-side differences in the evaluation increased the diagnostic sensitivity by 2.5–25.0 % across different parameters.Somatosensory abnormalities were commonly detected in Chinese TMD pain patients both within and outside the primary painful region, strongly indicating disturbances in the central processing of somatosensory stimuli. The individual variations in somatosensory abnormalities indicate a possible need for development of individualized TMD pain management.The online version of this article (doi:10.1186/s10194-016-0632-y) contains supplementary material, which is available to authorized users. Temporomandibular disorders (TMD) pain is not only of major importance for individuals but also constitutes a major public health problem with a large impact on health-related expenses . DespiteSomatosensory sensitivity can be measured by quantitative sensory testing (QST) –12. The The aim of this study was to expand the description of the clinical phenotype and to evaluate somatosensory abnormalities in painful facial and remote regions of Chinese patients with TMD pain diagnosed with reproducible and validated criteria according to the international Diagnostic Criteria for TMD . The TMDHealthy Chinese participants between 18 and 70 years of age were recruited through advertisement in the community. Exclusion criteria were: ongoing pain or reported chronic pain in the last 6 months; serious systemic disease or previous radiotherapy or chemotherapy; intake of medicine affecting the central nervous system; fibromyalgia syndrome, or self-reported psychogenic illness. Individuals’ medical history was checked by a clinical dentist and one TMD specialist performed DC/TMD on all the participants to exclude TMD patients. One hundred and three healthy Chinese volunteers responded to the advertisement. Finally, 70 healthy participants between 24 and 69 years of age (42.3 ± 12.5 years), 36 females (43.1 ± 12.8 years) and 34 males (41.5 ± 12.3 years) met the criteria, were recruited, and finished the whole test.n = 19, >40 year n = 21) were finally recruited and finished the test. The patients were diagnosed using DC/TMD as having myalgia  and arthralgia without intra-articular joint disorders (n = 10). The self-reported TMD peak pain intensity before the test on the 0–10 cm scale was 2.9 ± 1.7 cm. The range of self-reported pain duration was 14.5 ± 21.1 months . The psychological status of patients was evaluated using the SCL-90 scale with 9 domains [From 2012 to 2014, Chinese individuals with a primary complaint of pain in the orofacial region were recruited from the Center for TMD and Orofacial Pain of Peking University School and Hospital of Stomatology, China. All patients were investigated and diagnosed  by one TMD specialist who had received extensive training and calibration in the use of the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) . Pain in domains .The study adhered to the Declaration of Helsinki II, was approved by the local Ethics Committee (PKUSSIRB-2013012), and all participants gave written informed consent.The standardized QST battery developed by DFNS and modified for the trigeminal region was used in this study –12, 15. In the present study, three skin regions of TMD pain patients were examined: the painful facial region, the mirror region on the contralateral side, and the dorsum of the right hand. The contralateral sites were tested first, followed by the painful sites. Healthy participants were investigated bilaterally on six skin regions: the infraorbital regions (V2), the mental regions (V3), and the dorsum of the hands. A standard set of instructions lasting ~1 min was read to the participants for each different modality just before the beginning of each test, i.e. there were 1-min intervals between tests –13.Thermal testing was performed using Medoc Pathway  with an Advanced Thermal Stimulator (30 mm × 30 mm) –13. CDT,The MDT was measured with a standard set of Semmes-Weinstein monofilaments  with 20 different diameters –12, 15. Weighted pinprick stimuli were delivered with seven custom-made punctate mechanical stimulators with fixed stimulus intensities (flat contact area 0.2 mm in diameter) that exerted forces of 8 to 512mN to determine the MPT –13. The MPS and DMA were evaluated using two sets of instruments in a stimulus–response assessment , 13. To To measure the WUR for repetitive pinprick stimuli, the perceived magnitude of a train of 10 pinprick stimuli repeated at 1 Hz was divided by that of a single pinprick stimulus with the same force . The WURThe vibration detection threshold (VDT) was measured tuning fork  , 13. VDTThe pressure pain threshold (PPT) was measured using a computerized pressure algometer  –13, 15. n = 32; older >40 years, n = 38), gender, and region  to allow a more detailed analysis of the somatosensory abnormalities of TMD pain patients /SDreference group [A z-transformation was performed for each variable. The sign of the resulting z-score was adjusted in such a way that those above >0 indicated a gain-of-function when the participant was more sensitive to the stimuli compared with controls , while z-scores <0 indicated a loss-of-function referring to a lower sensitivity  , 18. A zce group , 10. Z-sce group . Also, tce group . If the ce group . In accoce group , the assThe loss/gain coding system was applied , 18. Theχ2 tests with Bonferroni adjustments for multiple comparisons. Values of P <0.01 were considered statistically significant.All statistical calculations were performed using SPSS 17.0 for Windows . The distribution of frequencies of loss and gain of somatosensory function at the painful site and hand between groups according to loss/gain coding was evaluated with As expected due to natural variation, a few abnormalities were found in the reference group (mean across parameters for somatosensory loss 4.0 ± 2.0 % and for somatosensory gain 1.1 ± 2.2 %) : somatosensory gain with regard to MPS, PPT, WUR, and WDT; and somatosensory loss with regard to CPT, HPT, MDT, MPT, CDT, TSL, VDT, and WDT Table , Fig. 2.The frequencies of abnormal values in the painful region for each QST parameter in 40 TMD pain patients are shown in Fig. P <0.001). L0G2  was the most frequent coding in the TMD group (40.0 %), which was significantly different from the reference group (10.2 %) (P <0.001). The cumulative proportion of somatosensory loss without any gain  was 12.5 % in the TMD group and 19.7 % in the reference group (P = 0.399). The cumulative proportion of participants presenting with somatosensory gain without any loss  was higher in the TMD group (50.0 %) than in the reference group (10.2 %) (P <0.001). The cumulative proportion of the groups showing mixed loss and gain  was higher in the TMD group (20.0 %) than in the reference group (1.2 %) (P <0.001) . L0G2 was the most frequent coding in the TMD pain group (27.5 %), which was markedly higher than in the healthy group (4.3 %) (P = 0.001). The cumulative proportion of somatosensory loss without any gain  was 15.0 % in the TMD group and 17.1 % in the reference group (P = 0.771). The cumulative proportion of participants presenting with somatosensory gain at the hand site without any loss  was higher in the TMD group (30.0 %) than in the reference group (4.3 %) (P <0.001). The cumulative proportion in the groups showing mixed loss and gain  in the hand region was higher in the TMD group (15.0 %) than in the reference group (2.9 %) (P = 0.026)  had psychological abnormalities compared with reference data . SomatizIn this study, we applied the full battery of standardized QST consisting of 13 parameters to patients with TMD pain and age-, gender-, and region-stratified healthy participants. The main finding was that 82.5 % of the patients presented somatosensory abnormalities in terms of loss or gain of somatosensory function in the painful facial regions, while the frequency of abnormality in the right hand region was 60.0 %, compared with 31.2 % in facial and 24.3 % in hand regions of the reference population. Mechanical tests were more often associated with abnormalities than thermal tests  and relative (side-to-side difference outside 95 % CI of reference) abnormalities , 18. It 11 = 43.1 %) [Like the studies conducted by Maier et al. and Baad-Hansen et al. , 18, we Pfau’s study demonstrated differences comparing a TMD patient group and control group for CPT, PPT, MPT, MPS and MDT with TMD patients being more sensitive to painful stimuli, but less sensitive to tactile stimulation on a group level . In Kothvs Additional file Earlier studies investigating the pain sensitivity of TMD pain patients in extra-trigeminal regions reported increased experimentally-evoked pain in non-facial areas , 14, 20.3The pain mechanisms underlying TMD are not fully understood, which complicates the diagnosis, treatment, and development of targeted analgesics. For individual patients, the impairment of joint or muscles, or pain duration are not consistent with the somatosensory changes , and theIn a randomized, double-blind, placebo-controlled, and phenotype-stratified study, 83 peripheral neuropathic pain patients were tested by the same QST protocol used in the present study, and patients were grouped into an irritable nociceptor phenotype and non-irritable nociceptor phenotype according to the QST results . The irrThe concept of mechanism-based management of TMD is supported by our data: different patients suffering from the same clinical disorder presented different phenotypes of somatosensory abnormalities. The highest rate of abnormality was L0G2 , which is consistent with Baad-Hansen’s report in atypical odontalgia patients . In contA limitation of this study was the differences in the test sites between the two groups: the skin overlying the infraorbital and mental nerve regions for healthy controls, but the painful sites for TMD patients. However, the DFNS has similarly used data from the hand region to represent the upper body and data from the foot region to represent the lower body, and we suggest the reference material in this study to be equally appropriate , 7. AnotThis is the first study using the full battery of QST tests and statistical protocol recommended by the German Research Network on Neuropathic Pain in the orofacial region, to assess the somatosensory function of Chinese patients with painful temporomandibular disorders and Chinese healthy controls. Furthermore, the TMD diagnoses were based on a validated and reproducible diagnostic system (DC/TMD). Somatosensory abnormalities were detected in 82.5 % for painful sites and 60.0 % for the extra-trigeminal site in TMD pain patients, most frequently in the form of somatosensory gain to nociceptive mechanical stimuli for both regions, suggesting a more generalized sensitization in the patients. TMD pain patients presented differences in somatosensory profiles, which may support the concept of individualized pain mechanisms-based management.


To determine the occurrence of intraoperative and postoperative complications up to three years after primary phacotrabeculectomy with intraoperative use of Mitomycin C (MMC) in primary open angle (POAG) and primary angle closure glaucoma (PACG) patients, and the effect of postoperative complications on surgical outcome.n = 105) and PACG (n = 55), who underwent primary phacotrabeculectomy with MMC at the National University Hospital, Singapore, from January 1, 2008 to December 31, 2010. Data was collected using a standardized form that included patient demographic information, ocular characteristics and postoperative complications, including hypotony (defined as intraocular pressure < 6 mmHg), shallow anterior chamber (AC) and hyphema.Retrospective review of 160 consecutive patients with POAG , hyphema  and shallow AC . Five patients (3.1%) required reoperation for their complications. Early hypotony (defined as hypotony < 30 days postoperatively) was an independent risk factor for surgical failure . Hypotony with another complication was also a risk factor for surgical failure (p < 0.02).The mean age ± standard deviation (SD) of patients was 68.2 ± 8.2 years. No patient lost light perception during duration of follow-up. 77% of the postoperative complications occurred within the first month only. The commonest complications were hypotony (Hypotony, hyphema and shallow AC were the commonest postoperative complications in POAG and PACG patients after phacotrabeculectomy with MMC. Most complications were transient and self-limiting. Early hypotony within the first month was a significant risk factor for surgical failure. Cataract and glaucoma are the top two causes of blindness in the world respectively and they frequently co-exist in the same eye . In 2010Treatment for patients with concurrent cataract and glaucoma includes sequential surgery and combined phacotrabeculectomy . Combinest January 2008 and 31st December 2010 (36-months period). The inclusion criteria for our study were as follows:Diagnosed with primary open angle glaucoma or primary angle closure glaucomaDiagnosed with visually-significant cataract on slit-lamp examinationNo previous surgical or laser operation on eye except laser peripheral iridotomyIntraocular pressure (IOP) measured with either Goldmann applanation tonometry or TonoPenHave ≥ 3 IOPs recorded before operation, measured on separate visitsCompleted at least one year of follow-up duration postoperativelyThis was a retrospective review of 262 consecutive eyes of patients who had undergone primary phacotrabeculectomy with intraoperative MMC at National University Hospital (NUH) in Singapore between 1For those who underwent surgery for both eyes, only the first eye was included, consistent with the method used by similar previous studies , 9. The Glaucoma Hemifield test outside normal limits, and≥ 3 contiguous points on the pattern deviation plot depressed at P < 5% level.Glaucoma is defined as the presence of characteristic optic disc changes  and intraocular pressure (IOP) ≥ 21 mmHg on one or more visits preoperatively by Goldman applanation tonometry (GAT) with characteristic visual field changes compatible with glaucoma, defined as follows :GlaucomIn addition, PACG was defined as glaucoma in which ≥ 180° of the posterior trabecular meshwork was not visible on non-indentation gonioscopy, with or without peripheral anterior synechiae .Each medical record was reviewed and relevant data was transferred to a standardized form which included patient demographic information, type of glaucoma (POAG or PACG), relevant systemic conditions and intraoperative details. Preoperative and postoperative data were collected for best-corrected visual acuity (BCVA), IOP, as well as number and duration of glaucoma medication usage.Postoperative complications were stratified into early (≤ 1 month), late (> 1 month), or recurrent (occurring more than once after surgery) . A complPeri-bulbar or topical anaesthesiaFornix-based conjunctival flap in the superior nasal or temporal quadrantCreation of a 4 x 3 mm rectangular partial-thickness scleral flap with adequate hemostasisSponges soaked in 0.4 mg/ml (0.4%) MMC inserted in the subconjunctival pocket for 5 minutes.Sponges removed and 0.4% MMC flushed out using 20 ml of balanced saline solution.Phacoemulsification of cataract and acrylic intraocular lens implantationSclerostomy creation with straight beaver blade assisted by Kelly's punchSurgical peripheral iridectomyScleral flap closure with 10-O nylon sutures until there was a slow egress of aqueousConjunctival closure with 8-O vicryl suturesAll the patients underwent a standard operation performed by trained ophthalmologists, which comprised the following steps:After surgery, all patients were discharged with antibiotic and steroid eye drops from three-hourly to four times a day for the first week after surgery. Antibiotic eye drops were stopped one month from surgery date. Steroid eye drops were continued for up to six months with slow taper depending on the bleb morphology, IOP and AC depth as assessed by an experienced glaucoma consultant. In general, after an uncomplicated surgery, patients were reviewed at approximately one day, one week, one month, three months and every six months thereafter.The primary outcome measure was the cumulative occurrence of postoperative complications at 3-years for all patients after combined phacotrabeculectomy with MMC. All complications occurring after 3-years were censored. Secondary outcome measures included risk factors for the commonest postoperative complications, correlation between postoperative complications and failure, incidence of intraoperative complications, and number of reoperations required. Time to failure was defined as the time from surgical treatment to time to 1) loss of visual acuity to no light perception, or 2) first of two consecutive follow-up visits after one month in which the patient had persistent IOP < 6mmHg or greater than stipulated upper limit , or 3) reoperation for glaucoma, whichever occurred first.Statistical analysis was performed using SPSS 21.0 . For categorical variables, Pearson’s chi-square test or Fisher’s exact test was performed. For continuous variables, an independent t-test was performed for normally-distributed samples, while a corresponding non-parametric test was used for non-normally distributed samples. Multivariate logistics regression  was performed for the top three commonest complications. Kaplan Meier survival analysis was performed for the time to hypotony, hyphema, shallow AC, as well as time to failure. A p value of less than 0.05 was considered statistically significant.n = 32, 12.2%), preoperative IOP taken on less than three occasions , previous intraocular operation/lasers except peripheral iridotomy performed such as laser trabeculoplasty, iridoplasty, retinal detachment surgery, pterygium surgery , secondary glaucoma such as traumatic, neovascular, uveitic glaucoma . 195 eyes of 168 patients fulfilled inclusion criteria. A total of 160 first operated eyes were included in the final analysis (eight eyes were excluded due to intra-operative phacoemulsification-related complications).A total of 262 total operations were performed between January 2008 and December 2010. Of these, 67 (25.6%) were excluded due to the following reasons: postoperative follow-up duration of less than one year  and higher mean preoperative IOP (p < 0.001). Otherwise, the other demographic characteristics were similar between patients with POAG and PACG.Baseline characteristics of patients were summarized in n = 7, 4.2%; incomplete capsulorrhexis: n = 1, 0.6%), while two cases (1.2%) were trabeculectomy-related . PCRs were treated intraoperatively with vitrectomy and sulcus placement of IOL, while an extracapsular cataract extraction was performed for the patient with incomplete capsulorrhexis.Ten patients (6.0%) experienced intraoperative complications. Of these, eight (4.8%) were phacoemulsification related . The top three commonest complications were hypotony , hyphema and shallow AC . Of those with hypotony, the mean IOP was 13.1 ± 3.8 mmHg at 3 years postoperatively, as compared to a mean IOP of 14.9 ± 3.8 mmHg for those without hypotony . Seven patients (4.2%) experienced prolonged hypotony. A summary of postoperative complications was shown in Table 2. There was no significant difference in incidence of complications between POAG and PACG patients . Six patients (3.8%) had severe complications that included shallow AC, hyphema, persistent inflammation more than three months, lens malposition, with five patients (3.1%) requiring reoperation. The patient with persistent inflammation also had worsening of BCVA by ≥ 2 Snellen lines. There was no significant difference in the incidence of severe complications between POAG and PACG patients .The mean follow-up duration ± standard deviation (SD) was 47 ± 14 months for all patients. No eye lost light perception during the duration of follow-up. 69 patients (43.1%) experienced at least one complication in the postoperative period. Of a total of 95 postoperative complications, most occurred within and resolved within the first month (Table 3). However, further subgroup analysis showed that neither race nor gender was a significant risk factor for developing shallow AC with concomitant hypotony (p ≥ 0.05 for both).After adjusting for age, type of glaucoma (POAG versus PACG) and mean preoperative IOP, our results showed that male gender and non-Chinese race were independent risk factors for developing shallow AC after phacotrabeculectomy . The 3-year cumulative incidence of failure (standard error [SE]) for 21 mmHg, 18 mmHg and 15 mmHg were 10.8% (2.5%), 18.5% (3.1%) and 45.9% (4.1%) respectively. Hypotony was associated with significantly higher risk of failure at 21 mmHg (cumulative percent (SE): with hypotony: 25.3% (7.0%); without hypotony: 5.9% (2.2%), p < 0.001), but not at 18 mmHg and 15 mmHg (p = 0.09 and p = 0.88 respectively). There was no difference between the cumulative incidence of failure (SE) between POAG and PACG eyes for 21 mmHg (cumulative percent (SE): POAG: 10.7% (0.03%); PACG: 11.1% (0.04%), p = 0.92), and for other definitions of failure (p > 0.05 for both). After adjusting for age, gender, race, preoperative IOP and type of glaucoma, our results showed that among factors influencing hypotony, hypotony with another simultaneous complication was an independent risk factor for failure at 21 mmHg, while both early and late hypotony were also significantly associated with failure (Table 4).Kaplan-Meier survival analysis was performed for the success rates of combined phacotrabeculectomy at 21 mmHg, 18 mmHg and 15 mmHg respectively, and stratified according to the occurrence of hypotony postoperatively . Other trabeculectomy-related surgical interventions performed include glaucoma drainage device insertion , AC reformation , AC washout, bleb refashioning and irrigation and aspiration of hyphema . Two phacoemulsification-related interventions were performed: lens repositioning and soft lens matter removal . Other postoperative surgical procedures included the following: stitch granuloma removal, trans pars plana vitrectomy, laser peripheral iridotomy and conjunctival defect repair .18 patients (11.3%) required at least one surgical intervention postoperatively. The most commonly performed procedure was bleb needling with antimetabolite use . Most complications were self-limiting and did not necessitate further surgical intervention. The majority (77%) of postoperative complications occurred within the first month only, suggesting that the first postoperative month is the most important period for postoperative monitoring.Similarly, the Trabeculectomy Outcomes Group Audit Study Group also emphasized the importance of intensive proactive postoperative care to reduce rates of surgical complication after trabeculectomy. In their audit of 428 eyes of 395 white patients with open-angle glaucoma, 183 out of 184 (99%) suture manipulations and 21 out of 22 (95%) of resuturings took place in the first three months, and they proceeded to recommend that close follow-up of patients and proactive intervention are necessary after trabeculectomy, though they did not specify strict duration .n = 14, 1.5%), followed by gross hyphema , and bleb leak  respectively [Several other authors have also reported complication rates after trabeculectomy or phacotrabeculectomy , 9, 13. ectively . Our higTo our knowledge, no study has established a correlation between a specific complication and success rates in combined phacotrabeculectomy. Our study has shown that occurrence of early postoperative hypotony was associated with higher risk of drainage failure (IOP > 21 mmHg). Specifically, our study has found that hypotony occurring with other complication(s) simultaneously significantly increased the risk of surgical failure at IOP > 21 mmHg, while both early and late hypotony were associated with higher risk of surgical failure at IOP > 21 mmHg. Benson et al suggested that early hypotony could result in the breakdown of the blood-aqueous barrier, resulting in the release of inflammatory mediators, where persistent conjunctival inflammation could then induce enhanced bleb scarring . In AsiaIn our study, we were unable to identify any risk factors associated with postoperative hypotony. Phacoemulsification has been demonstrated to have a modest sustained reduction in IOP for both patients with POAG and PACG eyes , 19, 20.Table 3). In view of the large variance in 95% CI for both readings, however, this study may be inadequately powered for the above assertions. Budenz et al have reported black race as a strong predictor for failure after phacotrabeculectomy [Interestingly, our study also found that male patients and being non-Chinese were independent risk factors for developing postoperative shallow AC  were lost to follow-up within the first three years. We hypothesize that these patients could have defaulted follow-up because they were most likely asymptomatic following the surgery (we noted four patients passed away in the postoperative period). A follow-up duration of three years also appears insufficient to determine the true incidence of blebitis. Longer prospective studies or randomized controlled trials would be preferred to address the above limitations, and at the same time to clearly and better define the advantages of combined phacotrabeculectomy with intraoperative MMC over other therapeutic options for glaucoma in this population.We recognize the limitations of this study. Being a retrospective study, it was impossible to standardize documentation and the complication rates may have been underreported. For example, we were unable to acquire the full data on corneal endothelial cell count in our patients before and after phacotrabeculectomy, as a reduction of corneal endothelial cell count has been reported and could compromise the safety profile of this operation , 31. MulIn conclusion, our study showed that the majority of complications from phacotrabeculectomy with MMC were transient and self-limiting, with hypotony, hyphema and shallow anterior chamber being the most common. Patients could be reassured of the safety of this operation; however, close and active monitoring is critical, especially in the early postoperative period, to prevent the occurrence of prolonged hypotony or multiple complications which may result in surgical failure.


Patients with chronic abdominal pain occasionally suffer from the anterior cutaneous nerve entrapment syndrome (ACNES). A substantial number of patients report previous visits to an emergency department (ED) with acute pain. Aim of this study was to obtain the incidence of ACNES in patients presenting with abdominal pain in the ED of a Dutch teaching hospital.In this observational study, data sets of all patients visiting Máxima Medical Center’s (MMC) ED in 2011–2012 were searched for key terms ‘ACNES’, ‘intercostal neuralgia’ or ‘abdominal wall pain’. Files of potential patients living within hospital’s adherence area were checked using accepted criteria indicating the presence of ACNES. Disease incidence was calculated as a ratio to the hospital’s adherence data. The ACNES MMC 2013’s incidence in patients evaluated in the surgical outpatient department was also calculated.During the study period, 473 ED patient files met inclusion criteria. A total of 88 patients belonging to MMC’s adherence area were diagnosed with ACNES leading to a mean 22/100.000 ACNES yearly incidence rate. About one of 50 patients with abdominal pain visiting the ED suffered from ACNES. A 35/100.000 outpatient department ACNES incidence rate was calculated in the year of 2013. Combining these two ratios, a 1:1800 ACNES incidence in the general population was obtained.In an ED setting of a Dutch teaching hospital, approximately 2% of patients presenting with acute abdominal pain suffered from ACNES. ED physicians should consider ACNES in abdominal pain patients with normal laboratory or imaging tests. A typical example is the anterior cutaneous nerve entrapment syndrome (ACNES) ,32,3].FiKnown ACNES patients who visited the ED were excluded. Patients who were suspected of having ACNES whereas history and findings at physical examination were not consistent with the syndrome were also excluded. These patients were usually referred to the ED by family physicians. To correct for spectrum bias, individuals living outside MMC’s adherence area were excluded as well.Accurate figures on MMC adherence were obtained from a market analysis. In the year of 2011, a total of 206.000 individuals were assumed to visit the MMC for medical assistance. In the year of 2012, this adherence number was officially set at 199.000 residents . These numbers are considered to be an optimal approximation of MMC’s real adherence.An additional calculation of the 2013 incidence of chronic ACNES was based on first time patient visits to the SolviMáx outpatient department. Each first SolviMáx outpatient department visit of an individual referred as possibly having ACNES is prospectively registered from January 1, 2013. Electronic patient files of all individuals diagnosed with ACNES via this system were also studied. Patients were excluded if they lived outside of MMC’s adherence area, if they were known ACNES patients, or if they had presented to MMC’s ED in an earlier stage .Data analysis was performed using SPSS 21.0 for Mac OS X . Baseline characteristics were presented as percentages, mean (SD), or median values (range) as appropriate. Adherence numbers of MMC and numbers of ACNES patients diagnosed in 2011 and 2012 were used to calculate an ACNES ED incidence and a mean incidence rate using standard calculus.In the year of 2011, 31.325 patients attended the ED of MMC (2012: 30.023). In the 2-year study period, 5.111 patient visits were registered for abdominal pain . A total of 473 ED patient files harboured the preselected keywords ‘ACNES’, ‘intercostal neuralgia’ or ‘abdominal wall pain’. A total of 186 patients  abdominal pain were diagnosed with ACNES, the majority (n = 35) belonging to MMC adherence area  belonged to the adherence area of MMC confirming its status as a referral centre for the remaining 68%. As 15 of these 85 newly diagnosed ACNES patients had attended the ED of MMC in an earlier phase, a 35/100.000 incidence rate of ACNES in the outpatient department was calculated. By combining numbers of ED and outpatient department, a total 57/100.000 ACNES incidence rate was obtained.chronic abdominal pain in our area is high [acute abdominal pain visiting our ED are also higher. Aim of the present study was to calculate the incidence of ACNES in the ED of a Dutch teaching hospital. Based on an analysis of all patients visiting during the 2011/2012 time period, a mean 22/100.000 per year incidence rate was obtained. In perspective, about one of 50 patients presenting with abdominal pain to the ED was diagnosed to suffer from ACNES. In an ED such as MMC’s hosting approximately 30 thousand patients yearly, the diagnosis ACNES is made almost once a week. An emergency physician must realize that a patient who is referred to the ED for abdominal pain of unknown origin may suffer from an abdominal wall pain syndrome such as ACNES.It is our experience that some patients who are ultimately diagnosed with chronic abdominal pain due to the anterior cutaneous nerve entrapment syndrome (ACNES) reported that they had previously attended emergency departments (ED) for earlier attacks of pain. As blood analysis, ultrasounds or CT-scans were always inconclusive, they were frequently sent home without receiving a conclusive diagnosis resulting in a substantial doctor’s delay. To this day, ACNES is consistently neglected as a cause of abdominal pain ,5,7,8. A is high ,11-17,19Most patients with chronic abdominal pain due to ACNES are diagnosed after a substantial time period. For instance, mean doctor’s delay was more than a year in one study indicating that the pain is per definition chronic . InteresHow can consciousness regarding signs characterizing ACNES be increased? A physical examination has a pivotal role in the diagnosis. If serious causes of acute abdominal pain are excluded in the ED using a combination of physical examination, blood analysis and imaging techniques, results of simple tests may point towards the presence of ACNES. A positive Carnett’s test and an area of sensory disturbances covering the painful spot are signs reflecting the neuropathic character of this pain syndrome ,18,26,27When the diagnosis ACNES is likely, ED physicians are advised to start trigger point injection therapy. A subfascial injection of 5–10 ml of 1–2% lidocaine leading to immediate pain reduction is diagnostic and occasionally therapeutic. Previous studies in chronic ACNES demonstrated permanent pain relief in one-thirds of the patients after injection therapy ,13. PatiHow does the present ACNES incidence relate to other known disease entities in the Netherlands? The calculated 57/100.000 (1:1800) total ACNES incidence is obtained in our area containing approximately 200.000 individuals. If extrapolated to the Dutch population (16.800.000 inhabitants), some 9.500 new ACNES patients may be identified yearly . In a suThe current study harbours flaws associated with its observational character including incomplete data sets. For instance, some specific characteristics of history taking and physical examination were not routinely registered possibly indicating bias. Moreover, the electronic searching strategy may have been incomplete as the number of used key words in the CS-EHIS may have been insufficient or incorrectly registered by ED physicians. Although these effects are considered minimal, an incidence underestimation rather than an overestimation may have resulted from these flaws. Another disadvantage is potentially related to the institution where this study is executed. Although groups of physicians working on MMC’s ED are rotating, there is no doubt that awareness regarding this neglected syndrome is high compared to other ED’s. Therefore, there may be a risk of ‘overdiagnosing’ patients with abdominal wall pain syndromes, also because the diagnosis ACNES is a typical clinical diagnosis lacking a gold standard. However, we strive to strictly adhere to objective criteria. Moreover, no alternative abdominal diagnoses emerged following presentation at the ED or during follow up.Approximately 2% of all patients presenting with acute abdominal pain were diagnosed with anterior cutaneous nerve entrapment syndrome (ACNES) in an emergency department setting. If patients with a localized acute abdominal syndrome demonstrate normal laboratory or imaging testing, ED physicians should consider ACNES in the differential diagnosis.


Postoperative pain is a significant concern for patients who undergo surgery via a midline posterior approach to the occipitocervical junction and spinal axis. The development of the disposable, ambulatory pain pump presents a novel alternative for treatment of postoperative pain. The authors describe a multimodal treatment algorithm for postoperative pain after posterior occipitocervical junction surgery that uses the On-Q pain catheter system  and a fentanyl patch.The On-Q PainBuster catheter system is a disposable, ambulatory device that allows for continuous anesthetic delivery directly into or adjacent to the wound. On-Q catheters are placed in the nuchal musculature for continuous infusion of 0.5% bupivacaine. The On-Q catheter infusion is continued for three days, and the catheters are then withdrawn. Patients are also provided with a transdermal fentanyl patch at the start of surgery.In regards to complications at our facility, there have been no cases of respiratory depression or arrest postoperatively and no wound infections, but one case of inadvertent subdural placement.The technique described for the use of the fentanyl patch and a continuous anesthetic delivery device in surgery of the occipitocervical junction presents a novel alternative to the current standard of care in pain control after suboccipital decompression. Postoperative pain is a significant concern for patients who undergo surgery via a midline posterior approach to the occipitocervical junction and spinal axis. Most of the pain is due to extensive soft-tissue and muscle dissection, along with intraoperative manipulation . Debilit2. The pumps exist in various volumes and flow rates. One or two catheters of different lengths may be attached to the pump [The On-Q PainBuster  catheter system is a disposable, ambulatory device that allows for continuous anesthetic delivery directly into or adjacent to the wound. This device Figure  utilizesthe pump . At our All patients undergoing posterior fossa cranial surgeries are given dexamethasone during anesthesia induction (4–8 mg), and steroids are continued postoperatively on a tapering schedule to mitigate meningeal headache. Patients are also provided with a transdermal fentanyl patch at the start of surgery, and this is continued perioperatively until the patch is exhausted. Adult opiate-naïve patients are given a 25-μg/h transdermal patch, whereas those using narcotics preoperatively are given enough additional fentanyl to cover this baseline requirement, up to a 100-μg/h transdermal patch.Once the main part of the operation is concluded and the dura is closed, On-Q catheters are placed in the nuchal musculature for continuous infusion of 0.5% bupivacaine. For patients with a midline occipitocervical wound similar to that used for Chiari decompression, 5-cm infusion catheters are placed at the start of wound closure via percutaneous insertion parallel to and approximately 1.5–2 cm lateral to the incision and coursing within the nuchal musculature at a depth of approximately 2 cm. The introducer sheaths can be curved to follow the curve of the neck, and finger palpation within the wound can be used to guide the introducer sheath within the course of the musculature Figure . Once inPatients who have undergone a posterior fossa craniotomy via a midline approach are managed initially in the neurocritical care unit for 24 hours to allow monitoring for any sign of respiratory depression or impairment of consciousness. Breakthrough surgical pain is managed initially with IV fentanyl and IV acetaminophen, and patients are transitioned to oral narcotics as tolerated (hydrocodone or oxycodone), usually within 12–24 hours. The fentanyl patch remains in place during this time, and cervical muscle spasm is managed with IV or oral diazepam and topical heating pads or ice. Steroids are tapered over a four to seven day period as tolerated. Patients are typically mobilized on postoperative day 1 and transferred to the regular nursing floor. The On-Q catheter infusion is continued for three days at a continuous and consistent drug elution, and the catheters are then withdrawn. Should a dressing change be required, it is performed in a sterile fashion.To date, this protocol has been implemented in 60 patients undergoing suboccipital craniotomies with or without C1 laminectomies for Chiari decompressions over a period of 34 months. No patients required postoperative orthotic support. We are now in the process of a complete retrospective collection and analysis of this data, assessing the degree of pain relief and satisfaction in the On-Q catheter fentanyl patch protocol group compared with those treated prior to the On-Q catheter fentanyl patch protocol. There have been no cases of respiratory depression or arrest postoperatively and no wound infections. Early in our experience, there was one case of inadvertent catheter insertion subdurally in which a loading dose (5 ml) of 0.25% bupivacaine was administered. The On-Q catheter was placed in a caudal to rostral direction. This patient remained deeply anesthetized for one hour postoperatively requiring continued ventilatory support, and there was a transient loss of all brainstem reflexes, including nonreactive dilated pupils, but no hemodynamic instability. After one hour, the patient awakened and recovered fully with no residual impairment. Postoperatively, the wound was monitored for a CSF leak, and there was no evidence of a pseudomeningocele or clinical evidence of intracranial hypotension. The risk of this complication can be avoided if the depth and trajectory of catheter insertion are carefully controlled and also if a rostral-caudal insertion path is used. The most common problem with the On-Q system in this application has been premature pull-out of one or more catheters or significant percutaneous drug leakage at the insertion site, requiring earlier than intended catheter removal.The University of Utah Institutional Review Board issued approval IRB_00051346 for the retrospective chart review, which is exempt from further IRB review under Exemption Category 7.Postoperative pain is a common and significant concern for patients undergoing posterior midline occipitocervical surgery. Debilitating pain after surgery can result in an excessive opiate requirement and its subsequent sequelae—nausea, vomiting, urinary retention, constipation, delayed mobilization, decreased oral intake, and delayed discharge . The tecOur experience also yielded several important observations. First, improved catheter design would be helpful for this application, specifically to incorporate a better means to secure the device to the scalp above the neck to prevent pull-out and back leak from the insertion site. With conventional taping and use of stay stitches, catheter pull-out was the most frequent limitation in effective utilization. Secondly, special care must be taken in this region to avoid inadvertent catheter insertion into the intradural space. We recommend always inserting from a rostral to caudal direction, away from the posterior fossa, and using visual and manual control within the wound to assure insertion into the center of the paravertebral musculature, above and lateral to the thecal sac. In one early case where inadvertent intradural passage with a catheter placed in a caudal to rostral direction and bupivacaine infusion occurred, no permanent injury resulted, although there was a prolonged emergence from anesthesia. Intraoperative fluoroscopy or X-ray confirmation of catheter placement may be utilized in the event that there is confusion in regards to catheter placement.Continuous paravertebral anesthetic infusion of bupivacaine has already been shown to decrease postoperative pain and rescue medication usage in lumbar spinal fusion surgery -5. StudiThe technique described for the use of the fentanyl patch and a continuous anesthetic delivery device in surgery of the occipitocervical junction presents a novel alternative to the current standard of care in pain control after suboccipital decompression. Its effectiveness in regards to previous pain control regimens will be assessed in a prospective trial.


Chronic pain has been reported in survivors of critical illness for many years after discharge from hospital. This study investigates the incidence and site of chronic pain in survivors of critical illness between 6 months and 1 year after hospitalization, including ICU admission. A retrospective analysis of the risk factors for chronic pain in this patient group was also completed.A questionnaire method was used to investigate the incidence of chronic pain and the specific body parts affected. A retrospective study and multivariable analysis were used to investigate the risk factors for chronic pain in this patient group. All survivors of a general intensive care unit (ICU) in South Wales in a 6-month period were included in this study.Chronic pain was reported in 44% of all respondents. The shoulder was the most commonly reported joint affected by pain (22%). Risk factors for chronic pain between 6 months and 1 year after ICU discharge were increasing patient age and severe sepsis.Chronic pain is a problem in survivors of critical illness, especially in the shoulder joint, and further studies are needed investigating therapeutic interventions that address this long-term problem. Intensive care medicine involves the treatment of critically ill patients with acute physiological derangement and organ failure. Critical illness is now well recognized as being associated with a number of detrimental long-term sequelae that can affect health-related quality of life for up to 5 years after ICU discharge . LimitedOne aspect of quality of life previously investigated is the experience of bodily pain . ResearcThe International Association for the Study of Pain (IASP) defines pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage" . Pain exThe first aim of this study, therefore, was to investigate the incidence and site of chronic pain in survivors of critical illness at 6 months after hospitalization, including ICU admission. The second aim of the study was to complete a retrospective analysis of the risk factors for the chronic pain experienced by the survivors of critical illness.The study was single centered, based in a large teaching hospital in South Wales . Morriston Hospital admits more than 1,000 patients to the general ICU per year and serves a population of 450,000 people. The general ICU has a broad cross section of specialities, including general medical (35%), surgical (49%), trauma (6%), neurology (4%), and renal (6%). Head-injured patients requiring surgery are transferred to another hospital and were not included in this study. The hospital has a separate burns and cardiothoracic ICU, so these patients were also excluded. No standardized protocol is now used for the assessment and measurement of acute pain on our ICU. Each patient's pain is assessed and managed on an individual basis.et al. (1995) [All patients who had been admitted between September 2011 and February 2012 were included in this study. These dates were selected so that at least 6 months had passed since the patients had been discharged from ICU. This would ensure that the definition of chronic pain by Kyranou and Puntillo (2012) was accurate and would also provide a sufficient cross section of patients regarding demographics and admission diagnoses . We alsoa priori based on previous research [The risk factors under investigation are outlined in Table research ,3-9. Thiresearch . PatientAny conditions existing before ICU admission that could cause chronic pain were analyzed as a risk factor and labeled together as preexisting conditions. These included chronic pain (reported in any joint), any inflammatory joint condition (osteoarthritis or rheumatoid arthritis), and neurologic conditions . Any surgical wounds, injuries/trauma, or ICU interventions that could potentially cause chronic pain  were also recorded. For the purpose of this study, these were categorized together under the title Wounds.To address both aims of this study, a mixed-methods approach was used: a qualitative design was used in the questionnaire study, and a quantitative design for the retrospective study.British Medical Journal [The first aim was addressed by using a questionnaire and telephone follow-up method. This part of the study was designed by following available guidelines in questionnaire research and the guidelines published in a series of articles in the  Journal ,15. A sh Journal . This inAs we did not set out to investigate either intensity of pain or the impact of the pain on quality of life, no other validated questionnaire could be identified for use in this study. We were therefore unable to use any other previously validated chronic pain questions. The questions were therefore designed according to guidelines for the assessment of pain in older people from the British Pain Society . These gTo assess the clinical sensibility of the questionnaire, it was piloted on a number of ICU survivors attending our follow-up clinic, and, as a result, a number of alterations were made to the questionnaire design. For example, we included a pictorial body chart, which allowed the respondent to highlight the exact body part in which pain was being experienced rather than trying to describe it by using words. Both closed and open-ended questions were used in the questionnaire. The respondents were asked to state whether they were experiencing any ongoing pain since discharge from the ICU (only new pains that they did not have before their ICU admission), and if so, they were requested to describe the body parts affected . They were also asked whether they had seen any healthcare professional regarding the described pain.A preaddressed envelope was included for return of the questionnaire, and all nonresponders were followed up with a telephone call after 2 months, in which the investigator completed the questionnaire according to the patient's responses. The questionnaire responses were entered onto a Microsoft Excel spreadsheet. Any questionnaires with missing demographic data were included in the study, and the remaining responses included in the analysis. If a respondent left blank the question regarding the existence of ongoing pain, this was included in the results as a lack of pain. Response rates were fully recorded, and nonresponder analysis was completed to compare the characteristics of the nonresponders and the responders. Results were presented descriptively by using numbers and percentages. Data analysis was completed by using the Microsoft Excel software. Patients were identified only by their hospital numbers, once completed questionnaires were received.a priori and consisted of the risk factors for chronic pain highlighted previously in the literature. These included patient age, APACHE II score, primary admission diagnosis, severe sepsis, ventilator days, ILOS, and HLOS. The outcome measure investigated was the incidence of chronic pain.The hospital database was used to obtain the data required to complete the retrospective study, including all risk factors and outcomes investigated. All data were recorded on a predesigned database. A validation check was completed in which an additional researcher checked the accuracy of data input for 10% of all patients, to reduce information bias. If a patient's notes had missing or incomplete data for the variables under investigation, they were still included in the database. The dataset included demographic variables such as age, gender, and injury mechanism. The independent variables examined were defined The issue of missing variables from the hospital database was overcome by retrieving the medical notes for the patient. To ensure confidentiality, patients' names were not recorded during the data-collection period. The dataset was also stored on a hospital-encrypted computer to ensure data security (safe-end protector encryption).A letter explaining the purpose and design of the study was sent to the Chairman of the South West Wales Research Ethics Committee. It was confirmed by the chairman that no ethical approval was required for this study.U test was performed for comparisons between the continuous variables  and the Fisher Exact test was performed for each of the independent variables investigated. The same statistical tests were used to complete the nonresponder analysis.Statistical analyses were performed by using SPSS Version 16 (Chicago) and the R program (version 2.14.1). Patients' demographics were analyzed by using descriptive statistics and presented as numbers and percentages for the categoric variables and means and standard deviations for the continuous variables. For the univariate analysis, Mann-Whitney P < 0.15 in the univariate analysis [P < 0.05.To identify predictors of chronic pain in survivors of critical illness, multivariable analysis was performed. For the categoric variables, the data were coded with a "1" if the variable was present and a "0" if absent. Age, APACHE II score, ventilator days, ILOS, and HLOS were analyzed as continuous variables. For the multivariable analysis, logistic regression with backward stepwise elimination by using the likelihood test statistic was used to assess potential predictors of development of chronic pain in survivors of critical illness. Continuous variables were analyzed as linear terms, as no indication of nonlinearity was found when analyzed by using the multivariable fractional polynomials function in the R program. Adjusted odds ratios and the 95% confidence intervals were calculated for each risk factor. Subgroup analysis was performed by using the same techniques for the most frequently reported body part affected by pain to investigate associated risk factors. Variables were included in the multivariable analysis only if they were statistically significant at analysis . StatistFigure Table P < 0.05) for the incidence of chronic pain at 6 months to 1 year after ICU discharge by using univariate analysis. Unadjusted odds ratios and 95% confidence intervals are included for the categoric variables. Significant risk factorsThe results of the retrospective study are outlined in Table P < 0.15 on univariate analysis were included in the multivariable analysis. These variables were sepsis, age, wound, ICU and hospital length of stay, and a primary admission diagnosis of surgery. Significant risk factors for chronic pain at 6 months to 1 year after ICU discharge include patient age and presence of severe sepsis during ICU admission. Adjusted odds ratios and the 95% confidence intervals are presented.Table Table et al., 2008 [Chronic pain is increasingly recognized as a problem in survivors of critical illness. Despite an increased awareness of its contribution to reduced quality of life, pain remains a significant problem for survivors of critical illness . Conflicl., 2008 , health-l., 2008 .This study reported that more than 20% of patients were experiencing shoulder pain at least 6 months after ICU discharge. This result is higher than that of an age-matched general population of 15% in a study in the Netherlands in 2011 and 11.7% in a British study in 2002 . In a suet al. (2006) [et al. (2009) [Nearly one third of all patients reported using healthcare resources in an attempt to address their chronic pain, which has potential cost implications for provision of ongoing care for these patients. In the survey by Breivik . (2006) , 60% of . (2006) . In a st. (2009) , it was . (2009) . Recent . (2009) .et al. (2005) [et al. (2005) [No significant differences were found between the patients with chronic pain and those without, in terms of gender, primary admission criteria, or APACHE II scores. Dowdy . (2005)  similarl. (2005)  did repoet al. (2011) [The significant risk factors for chronic pain on the univariate analysis were severe sepsis and ICU length of stay. Primary admission diagnosis of surgery, wound, ICU and hospital length of stay were dropped as significant risk factors in the multivariable analysis, and this may reflect the influence of confounding in an observational study of this design. In a study by Timmers . (2011) , ICU lenet al. (2006) [et al. (2006) [On multivariate analysis, one of the significant risk factors for chronic pain was severe sepsis. These results concur with a German study by Zimmer . (2006) , in whic. (2006) , who deset al. (2005) [et al. (2005) reported that age did not influence pain experience at 6 months after ICU discharge [The patient's age was another significant risk factor for chronic pain in patients discharged from ICU. This may be due to the normal physiologic changes associated with increased age, such as reduced muscle mass, reduced levels of blood and tissue metabolites, and a poor nutritional status. A number of studies have reported that age influences the patient's functional recovery, and these are summarized in the review by Dowdy . (2005) . In contischarge .Younger age has been reported as a risk factor in investigations of chronic pain after surgery; however, these results remain inconsistent . A numbeThis study highlighted the incidence of chronic pain and its potential risk factors at 6 months to 1 year after ICU discharge. One interesting finding of this study was that the existence of preexisting chronic pain conditions before ICU admission was not a risk factor for chronic pain after discharge from the ICU. An increased awareness of the incidence of chronic pain should ultimately result in an attempt to preempt it, through the aggressive use of therapeutic interventions for pain. Early mobilisation and rehabilitation during the ICU stay is increasingly considered one of the most effective strategies for reducing pain and functional disability after discharge, but further research is still needed . Simply The use of ICU follow-up clinics was recommended by the National Institute of Clinical Excellence (NICE) in 2009, and these clinics provide the opportunity to address ongoing pain and dysfunction . FurtherThe present study has a number of limitations. As a result of the study design and the inherent nature of patients, a number of the risk factors investigated were potentially interdependent, so an increase in one variable inadvertently results in an increase in another. Multivariable logistic regression with backward elimination techniques was used to address this issue of collinearity. In clinical research, however, this is difficult to overcome because of the nature of the study population, and therefore, the results of this study should be interpreted with this in mind.A 6- month cohort was used to include a sufficient number of patients to provide valuable results. It could be suggested that a patient's pain symptoms may potentially change over the 6- month time period used in this study; however, in a study of this nature, this is unavoidable. It is also questionable as to how significantly a patient's pain symptoms would change over a 6-month period, because of the nature of chronic pain. One method of overcoming this would be to complete a multicentered study over a shorter time period.et al. (1995) [A sample size of 100 patients with chronic pain was needed for this study according to Peduzzi . (1995) , but as No suitable previously validated questionnaire was available for use in this study. Therefore, a further limitation of this study was the use of a newly designed questionnaire. The study results may lack validity and generalizability as a result. The questionnaire was piloted on a number of survivors of critical illness to help to overcome this limitation. Another limitation of investigating outcomes in survivors of critical illness is the high mortality rate and loss to follow-up. This may introduce a degree of reporting bias, but this is unavoidable in a study of this type.In an observational study using a retrospective database analysis, the potential exists for information bias. Data may have been incorrectly entered into the database at the time of the patient's admission, or the data may be incorrectly copied for use in the study. A validation check was used in an attempt to overcome this error of data extraction and data input and thus reduce information bias. A further limitation is the potential underreporting of severe sepsis by doctors in ICU. The aim initially was also to include ARDS in our study, but because of the obvious underreporting of ARDS data, the decision was made to exclude ARDS as a risk factor from our study. Availability of further information regarding other factors important to pain experience  would have improved the reliability and validity of this study. A further prospective study would be needed to overcome these limitations, and this should be considered when interpreting the study results.In summary, two main conclusions can be drawn from this study. A high incidence of chronic pain is found in survivors of critical illness at 6 months to 1 year after ICU discharge. The risk factors for the pain experienced are increasing age and severe sepsis. These results concur with the findings of a number of previous studies but also highlight areas for further research. Potentially beneficial research would include studies that investigate various therapeutic interventions to prevent this chronic pain experienced by patients discharged from ICU. An awareness of the risk factors for the onset of chronic pain allows the healthcare professionals caring for the patient potentially to address contributing factors, such as careful handling of the shoulder in paralyzed or elderly sepsis patients.• Chronic pain was reported by 44% of patients 6 months to 1 year after ICU discharge• Shoulder pain was reported by 22% of patients 6 months to 1 year after ICU discharge• Of patients discharged from an ICU, 32% seek further input from healthcare professionals for chronic pain.• Severe sepsis and increasing patient age were the significant risk factors for chronic pain in this patient group.• Further prospective studies are needed to investigate therapeutic interventions to reduce the incidence of chronic pain in survivors of critical illness.APACHE: Acute Physiology and Chronic Health Evaluation; ARDS: acute respiratory distress syndrome; CI: confidence interval; HLOS: hospital length of stay; ICU: intensive care unit; ILOS: intensive care unit length of stay; NICE: National Institute of Clinical Excellence; OR: odds ratio.The authors declare that they have no competing interests .The study was conceived and designed by CB and HH. CB supervised the conduct of the trial. HH and SL provided the statistical advice, and CB and SL analyzed the data. CB drafted the manuscript, and HH and SL contributed substantially to its revision. CB takes overall responsibility for the article. All authors read and approved the final version of the manuscript.


IL6). The aim of the present study was to evaluate the association between IL6 (rs1800795: –174G>C) and opioid requirements in patients after total hip replacement (THR).In recent years, increasing attention has been paid to the contribution of genetic factors to variability in patient pain threshold and the efficacy of pain management. One of the genes implicated in pain pathology and treatment response is interleukin 6 (IL6 gene (–174G>C) was determined using the PCR–RFLP method.A total of 196 patients eligible for the study  were subjected to THR. The THR procedure was performed using spinal anaesthesia after implementing routine peri-operative monitoring. After the procedure each patient was individually observed, and the patient-specific chart of dynamic changes in pain perception was recorded, using the five-level Verbal Rating Scale (VRS). The multimodal analgesic treatment after THR was defined by the operating surgeons after considering indications and contraindications to the use of different groups of drugs . Postoperative pain was controlled by the patient-controlled analgesia method and VRS during the day-time, as well as night-time nurse-controlled analgesia. All medication adjustments were recorded in the individual patient files. In the case of moderate pain intensity (VRS-assessed), a patient was administered the non-opioid analgesic drug, and for high intensity pain the opioid. The analysis of pain relief therapy included information on the drugs applied, mode of dosing (single or multiple), daily dose, route of administration, and drug refusal due to the absence of pain recorded each study day, i.e. on the day of surgery and recovery in the postoperative room (day 0), and then daily from day 1 to day 6. Polymorphism rs1800795:G>C in the promoter region of the IL6 –174G allele (GG homozygote and GC heterozygote) were administered opioids significantly more often on days 0 (p = 0.0029), 3 (p = 0.019) and 4 (p = 0.031) after surgery compared with CC homozygous patients. Those patients also required a significantly higher opioid dose on days 3 (p = 0.029) and 4 (p = 0.030). Multivariate analysis demonstrated that the presence of the –174G allele was an independent factor predisposing patients to the administration of opioids during the first 24 h , on day 3  and day 4 .The patients carrying at least one IL6 gene (–174G>C) polymorphism was found to be an independent factor predisposing to a higher dose and more frequent administration of opioids in the first days after total hip replacement.The presence of the G allele  IL6). The IL-6 protein is a multifunctional cytokine that plays an important role in a wide range of biological processes. The production and concentration of IL-6 can be influenced by the –174G>C functional genetic polymorphism in IL6. In vitro studies have demonstrated the influence of the polymorphism on IL-6 mRNA levels. –174C is associated with lower IL-6 levels and a reduced response to lipopolysaccharide stimulation. The in vitro findings were paralleled by in vivo observations; healthy –174C allele carriers are characterized by significantly lower levels of plasma IL-6  and growth factors playing a major role in its pathophysiology . The firsma IL-6 .IL6 (rs1800795: –174G>C) and opioid requirements in patients after THR.The aim of the present study was to evaluate the association between 2) was 27.1 ± 4.1. Of 196 study participants, 153 were non-smokers (78.1 %) and 43 (21.9 %) were smokers. The THR procedures were performed by three experienced orthopedic surgeons, via a standardized anterolateral approach using the same non-cemented implant system , and medicated according to multimodal therapy in compliance with postsurgical analgesic treatment recommendations involving oral and/or parenteral analgesics with different mechanisms of action, i.e. opioid analgesics (OP) , non-opioid analgesics (acetaminophen and metamizole) and NSAIDs (ketoprofen and diclofenac) , on day 3  and day 4  after THR. In the same multivariate analysis, administration of NSAIDs significantly influenced the need for opioid analgesics only in the first 24 h of the postoperative period .Multivariate logistic regression analysis was performed, with age, sex, BMI, tobacco smoking status, NSAIDs, acetaminophen, and the –174G allele as the independent variables. The analysis demonstrated that the presence of the –174G allele was an independent factor predisposing patients to administration of opioids during the first 24 h [IL6 –174G allele is associated with increased gene expression, it may lead to even higher IL-6 levels in the allele carriers, resulting in increased inflammation and, as a consequence, greater stimulation of nociceptors by mediators generated in the inflammatory zone. The results of the current study are consistent with that hypothesis, as the presence of the G allele predisposed patients to higher demands for analgesics, i.e. opioid requirements in the early postoperative period.Total hip replacement involves trauma to soft and bony tissues, and can result in considerable pain. It is worth noting that the greater the amount of tissue injury, the more active the inflammation that can occur in the perisurgical region. After tissue injury, a proinflammatory cytokine, IL-6, is overproduced by many cells throughout the body , 11. HigIL6 –174CC genotype required significantly higher daily opioid doses than carriers of the G allele. However, the aforementioned study involved patients on previous opioid medication and with chronic pain, contrary to our study. Unfortunately, the current study did not involve measurements of IL-6 concentrations. However, it was previously demonstrated that the IL-6 level increases after THR, and the peak concentrations after operation occur at 12–24 h [IL6 –174GG genotype patients could be characterized by higher IL-6 levels compared with CC carriers, with resultant increased demands for opioids within 24 h of the surgery. The observation of the present study indicated that morphine doses and pain intensity gradually decreased during the postoperative period, but a subgroup of patients still suffered from pain of significant intensity. The patients carrying at least one IL6 –174G allele (GG homozygote and GC heterozygote) were administered opioids significantly more often, also on days 3 and 4, compared with CC homozygous subjects. One possible explanation may be derived from in vitro studies, which demonstrated peripheral actions of opioids such as modulation of inflammatory processes and wound healing [IL6 –174G>C polymorphism) are characterized by elevated levels of IL-6, and thus require a more intensive analgesic approach in the early postoperative period. It is known that IL-6 levels decrease gradually after surgical procedures [This observation is contrary to the results of Reyes-Gibby et al. , who rep 12–24 h . Conside healing . Opioidsocedures , 15, as IL6 genotype in breast cancer patients. Acetylsalicylic acid effects were most potent in female carriers of the wild-type IL6 –174G allele, which was associated with constitutively high IL-6 levels. It is worth noting that in the multivariate logistic regression analysis the presence of the –174G allele was an independent factor predisposing patients to administration of opioids during the first 24  and, on days 3 and 4 after THR.Our study also demonstrated that administration of NSAIDs significantly influenced the need for opioid analgesics within the first 24 h of the postoperative period. This observation is in keeping with the report of Slattery et al. , who demThe results of the present study may be biased by some confounding factors, especially by factors other than genetic ones which can affect the circulating IL-6 concentrations (e.g. other cytokines that have been shown to modulate pain), and gene polymorphisms of other pain modulators, not assessed in this study. Because of the complexity of pain pathology and inflammatory responses, most likely combinations of multiple polymorphisms would be adequate as predictors of analgesia.IL6 (rs1800795: G>C) –174 gene polymorphism has a significant influence on the overall requirement and daily doses of opioids in patients after elective THR.The


To investigate the impact of preoperative hydronephrosis and flank pain on prognosis of patients with upper tract urothelial carcinoma.In total, 472 patients with upper tract urothelial carcinoma managed by radical nephroureterectomy were included from Kaohsiung Medical University Hospital Healthcare System. Clinicopathological data were collected retrospectively for analysis. The significance of hydronephrosis, especially when combined with flank pain, and other relevant factors on overall and cancer-specific survival were evaluated.P = 0.025). Kaplan-Meier analysis showed significantly poorer overall and cancer-specific survival in patients with preoperative hydronephrosis  and in patients with flank pain  than those without. However, only simultaneous hydronephrosis and flank pain independently predicted adverse outcome  in multivariate Cox proportional hazards models. In addition, concurrent presence of hydronephrosis and flank pain was also significantly predictive of worse survival in patient with high grade or muscle-invasive disease. Notably, there was no difference in survival between patients with hydronephrosis but devoid of flank pain and those without hydronephrosis.Of the 472 patients, 292 (62%) had preoperative hydronephrosis and 121 (26%) presented with flank pain. Preoperative hydronephrosis was significantly associated with age, hematuria, flank pain, tumor location, and pathological tumor stage. Concurrent presence of hydronephrosis and flank pain was a significant predictor of non-organ-confined disease (multivariate-adjusted hazard ratio = 2.10, Concurrent preoperative presence of hydronephrosis and flank pain predicted non-organ-confined status of upper tract urothelial carcinoma. When accompanied with flank pain, hydronephrosis represented an independent predictor for worse outcome in patients with upper tract urothelial carcinoma. Upper tract urothelial carcinoma (UTUC), including tumor from urothelium of renal pelvis and ureter, is a rare malignancy. UTUC accounts for approximately 5–10% of all urothelial tumors, with an estimated incidence of 2.08 cases per 100,000 person-years in the United States , which iSeveral powerful prognostic factors for UTUC have been identified, including pathological tumor stage (pT), tumor grade, lymph node (LN) involvement, and lymphovascular invasion. These factors predict disease outcome and therefore are helpful in providing proper therapeutic strategy for patients with UTUC according to their risk of progression. However, most of them were obtained postoperatively . PrognosPrevious studies have confirmed the concept that preoperative hydronephrosis is predictive for advanced pT in UTUC –13. WithClinically, hydronephrosis and flank pain are highly correlated. Sudden occurrence of hydronephrosis can result in intense pain in the flank area. In contrast, gradual development of hydronephrosis will generally cause dull pain with no attacks of renal colic. Ataus et al. noticed that UTUC patients presenting with flank pain had significantly poorer outcome compared to those with hematuria or bladder tumor . BesidesFlank pain in UTUC is believed to be secondary to hydronephrotic distension or related to local tumor mass effect. In previous studies, preoperative hydronephrosis has never been combined with related symptoms to evaluate outcome of UTUC. Therefore, in this retrospective study, we aimed to investigate this issue by analyzing the influence of preoperative hydronephrosis and flank pain at the same time on predicting non-organ-confined (NOC) status, OS, and cancer-specific survival (CSS) of UTUC.th edition and graded using the 2004 WHO/International Society of Urologic Pathology consensus classification. All cases formerly graded by three-grade WHO system were reviewed by two pathologists and were re-classified as low or high grade according to the 2004 WHO classification. In brief, low grade tumors are evenly distributed and have uniform nuclei, mild increase of nuclear-to-cytoplasmic ratio, fine chromatin, and rare mitoses. In contrast, high grade tumors tend to show irregular distribution of tumor cells, presence of pleomorphic nuclei, coarse chromatin, and frequent mitoses. Other clinicopathological parameters were also recorded for analysis, including age, gender, smoking, preoperative estimated glomerular filtration rate (eGFR), surgery method, tumor location , pT, tumor grade, LN involvement, and adjuvant chemotherapy. eGFR was calculated with the MDRD study equation: 186 × (serum creatinine)-1.154 × (age)-0.203 ×  [2 or received regular dialysis. Regular cystoscopy, urine cytology and periodic imaging studies were mandated postoperatively in every patient following institutional guideline. In the first 2 years after radical surgery, patients were followed every 3 months, then every 6 months in the next 2 years, and annually thereafter.This study included 472 patients who underwent radical nephroureterectomy for UTUC at Kaohsiung Medical University Hospital Healthcare System between 1991 and 2013. This research was approved by the Institute Review Board of the Kaohsiung Medical University Hospital (KMUH-IRB-20120138). All patient records were anonymized and de-identified prior to analysis. Patients were not recruited into this study if they did not receive radical surgery, had evidence of metastasis at diagnosis, or died within 14 days after surgery. Dilatation of renal pelvis and calyx was determined by renal ultrasonography, computed tomography, or intravenous pyelography. As previously described, any degree of renal collecting dilatation was defined as hydronephrosis . We excl female) . PatientP values were two-sided, and < 0.05 was considered significant.Demographic and clinicopathological factors were categorized and compared between patients with and without preoperative hydronephrosis using chi-square test. Kaplan–Meier method was applied to analyze OS and CSS, and the significant differences of which were determined by the log-rank test. Preoperative parameters and potential prognostic factors were enrolled into univariate and multivariate Cox proportional hazards models to identify predictors of NOC disease (≥ pT3 and/or positive LN) and survival, respectively. Since hydronephrosis and flank pain were closely related, we divided patients into four groups  to realize the respective effect of hydronephrosis and flank pain on prognosis. SPSS software program  was used for statistical tests. All 2) and 87 (18%) received adjuvant chemotherapy. One hundred and eighty-nine (40%) tumors were located in the renal pelvis, 193 (41%) in the ureter, and 90 (19%) in both locations. As for pathological features, the stage distribution of UTUC was pTa/Tis, pT1, pT2, pT3, and pT4 in 60 (13%), 130 (27%), 112 (24%), 142 (30%), and 28 (6%) respectively. Forty-one (9%) patients had LN metastasis, and 360 (76%) had high grade tumor. UTUC patients were divided into two groups based on the presence of preoperative hydronephrosis (P = 0.016), hematuria (P < 0.001), flank pain (P = 0.002), tumor location (P < 0.001), and pT (P = 0.041).The clinicopathological characteristics of 472 patients were listed in ephrosis . Two hunP = 0.019 and 0.045, respectively), synchronous tumor location , absence of hematuria , and simultaneous presence of hydronephrosis and flank pain  were significant predictors  had NOC disease. Among them, 68% (118/173) had preoperative hydronephrosis and 32% (55/173) had flank pain. In the model to predict NOC disease before surgery, both univariate and multivariate analyses showed that male gender . The mean OS of patients with and without hydronephrosis was 106.17 and 125.62 months, with a difference of 19.45 months. The difference of mean CSS between the two groups was also clinically meaningful (11.42 months). Similarly, patients with flank pain also had worse outcome than those without . When patients were stratified by the presence of hydronephrosis and/or flank pain, Kaplan-Meier curves indicated an obvious survival decline in patients with concurrent hydronephrosis and flank pain but not in other 3 groups (P < 0.001). The differences of mean OS and CSS between those with and without symptomatic hydronephrosis were even more marked . Interestingly, survival rates were similar among patients with hydronephrosis alone, flank pain alone, and those without hydronephrosis and flank pain.During follow-up, 121 patients died of UTUC, 18 expired due to other causes, and 145 were assessed at 5 years to calculate survival. By Kaplan-Meier method, the 5-year OS and CSS were 64.2% and 69.2% in patients with preoperative hydronephrosis, compared to 75.5% and 77.1% in those without hydronephrosis (P < 0.001). The adverse outcome was also observed in patients with muscle-invasive disease (P < 0.001). These findings indicated that the presence of symptomatic hydronephrosis could identify a subset of patients with worse prognosis in high grade or high stage UTUC.As different molecular features may exist in UTUC patients based on tumor grade and stage, we attempted to analyze the effect of symptomatic hydronephrosis on survival between different pathological features. There was no difference in OS and CSS according to the presence of symptomatic hydronephrosis in low grade or non-muscle-invasive UTUC. However, in high grade UTUC, patients with concurrent hydronephrosis and flank pain had a significantly poorer OS and CSS (P = 0.015), preoperative eGFR (P = 0.041), tumor location (P = 0.032), pT (P < 0.001), LN involvement (P < 0.001), tumor grade (P < 0.001), adjuvant chemotherapy (P < 0.001), hematuria (P = 0.002), and simultaneous presence of hydronephrosis and flank pain (P < 0.001). In multivariate analysis, in addition to aging (P = 0.012), poor preoperative eGFR (P = 0.030), advanced pT (P < 0.001), and LN metastasis (P = 0.002), simultaneous presence of hydronephrosis and flank pain was an independent predictor for worse OS . The significant factors for CSS in the multivariate analysis were identical to those for OS.In UTUC is a rare malignant tumor in the urinary system worldwide. Common clinical presentations of UTUC include hematuria, flank pain, and hydronephrosis. Previous investigations have reported that approximately 70–80% of UTUC patients present with hematuria, 20–40% with flank pain , and 50–The characteristics from this cohort were comparable to other studies concerning mean age, tumor location, and prevalence of preoperative hydronephrosis. Regarding gender distribution in UTUC, our population showed a slight female predominance , which was in accordance with other Taiwanese studies but different from those in other countries . In thisIn our analysis, we found that preoperative hydronephrosis in patients with UTUC was associated with age, hematuria, flank pain, tumor location and pT. Consistent with previous studies ,16,28,29However, most studies did not validate the independently prognostic role of hydronephrosis in UTUC. For Sakano et al. and Morizane et al., hydronephrosis was significantly associated with CSS only in univariate analysis but not in multivariate model ,17. Ng eThere were limited data concerning whether flank pain is associated with oncologic outcomes in patients with UTUC. Only three previous studies evaluated the effect of flank pain on UTUC with small case numbers, and two of them suggested its predictive role on outcome ,22. RamaIn our study, preoperative hydronephrosis was significantly correlated with OS and CSS in univariate analysis, but its prognostic impact vanished in multivariate analysis. By taking the presence of flank pain into consideration, we found that concurrent presence of preoperative hydronephrosis and flank pain was significantly associated with OS and CSS in multivariate analysis and denoted a 1.98- and 1.87-fold increase in the risk of overall and cancer-specific death. The independently prognostic effect of symptomatic hydronephrosis is of value in the preoperative setting to achieve better clinical decision making. For example, tumor grade assessed by ureteroscopic biopsy provides important information before radical surgery. According to our results, the presence of symptomatic hydronephrosis can further refine the treatment strategy in patients with high grade UTUC.Another contribution of this study was that we might explain why there are diversities in the effect of preoperative hydronephrosis on prognosis in previous reports. When patients with preoperative hydronephrosis were dichotomized by the presence of flank pain, the outcome between the two groups was significantly different. As mentioned earlier, patients with symptomatic hydronephrosis did have worse OS and CSS compared to patients without preoperative hydronephrosis or flank pain. However, patients with preoperative hydronephrosis but devoid of flank pain had similar survival as those without hydronephrosis. While no previous study has stratified preoperative hydronephrosis by the presence of flank pain, the effects of hydronephrosis on survival varied consequently.It has been mentioned that obstruction in the urinary tract is the actual prognostic factor of UTUC . When coThere were several limitations in this study. First, the data were collected retrospectively. Second, the patients were treated by different physicians over the period of time. Third, we were unable to evaluate flank pain in exact quantity from patients’ subjective complaints. Fourth, we did not include other preoperative variables which may contribute to risk stratification before surgery, such as urinary cytology, endoscopic findings, or radiographic features. Nevertheless, to our limited knowledge, the effect of preoperative hydronephrosis and flank pain has never been assessed together before. This is the first study to demonstrate its excellent prognostic value, and the novel finding can further assist in individualized treatment strategies in patients with UTUC.In conclusion, preoperative hydronephrosis and flank pain are useful in predicting advanced UTUC. Compared to preoperative hydronephrosis alone, simultaneous presence of hydronephrosis and flank pain more reliably predicts adverse survival and serve as an independent prognosticator for patients with UTUC.