Brain metastases produce pain due to cranial hypertension. The treatment of choice is corticosteroids. Dexamethasone in oral doses of 4 to 16 mg/day is the treatment of choice.

Brain metastases produce pain due to cranial hypertension. The treatment of choice is corticosteroids. Dexamethasone in oral doses of 4 to 16 mg/day is [HIDDEN].

A 60-year-old patient diagnosed with breast neoplasia 10 years ago. She underwent treatment with radiochemotherapy and then hormonal therapy for 5 years. A bone scan study performed for polytopic bone pain showed the presence of bone metastases. She is currently under treatment with minor opioids and NSAIDs with good pain control. She consulted for headache that did not subside with the current analgesia and a CT scan of the brain showed images compatible with brain metastases. In relation to the treatment of pain, indicate the CORRECT one:

Extra doses of opioids should be administered as necessary.

Switch to a major opioid and maintain NSAIDs.

The patient should be admitted for intravenous treatment with major opioid.

[Breast Cancer Patient with Bone Metastases Who Was Able to Return Home without Using Opioids after Administration of Strontium-89 Chloride].

A 46-year-old woman underwent mastectomy for right inflammatory breast cancer.Three years later, she was diagnosed with multiple bone metastases and was treated with systemic chemotherapy and zoledronic acid.Six years after the mastectomy, she complained of severe sacral pain, and 40 Gy external radiotherapy was applied to the sacral metastases.Oxycodone was also administered, but dose escalation was difficult because of severe nausea and fatigue.A bone scan showed increased uptake of Tc99m in an area consistent with the painful regions, and an injection of 89SrCl2 was administered.Five weeks after the injection, her severe pain was relieved and she was able to discontinue the use of opioids completely.She successfully lived at home for 100 days without using opioids.In this case, radionuclide therapy with 89SrCl2 led to remarkable pain relief with an improvement in the quality of life of the patient.

Opioid rotation

Opioid rotation or opioid switching is the process of changing one opioid to another to improve pain control or reduce unwanted side effects. This technique was introduced in the 1990s to help manage severe chronic pain and improve the opioid response in cancer patients. In order to obtain adequate levels of pain relief, patients requiring chronic opioid therapy may require an increase in the original prescribed dose for a number of reasons, including increased pain or a worsening disease state. Over the course of long term treatment, an increase in dosage cannot be continued indefinitely as unwanted side effects of treatment often become intolerable once a certain dose is reached, even though the pain may still not be properly managed. One strategy used to address this is to switch the patient between different opioid drugs over time, usually every few months. Opioid rotation requires strict monitoring in patients with ongoing levels of high opioid doses for extended periods of time,

Cancer Pain Management and Bone Metastases: An Update for the Clinician.

Breast cancer patients with bone metastases often suffer from cancer pain. In general, cancer pain treatment is far from being optimal for many patients. To date, morphine remains the gold standard as first-line therapy, but other pure μ agonists such as hydromorphone, fentanyl, or oxycodone can be considered. Transdermal opioids are an important option if the oral route is impossible. Due to its complex pharmacology, methadone should be restricted to patients with difficult pain syndromes. The availability of a fixed combination of oxycodone and naloxone is a promising development for the reduction of opioid induced constipation. Especially bone metastases often result in breakthrough pain episodes. Thus, the provision of an on-demand opioid (e.g., immediate-release morphine or rapid-onset fentanyl) in addition to the baseline (regular) opioid therapy (e.g., sustained-release morphine tablets) is mandatory. Recently, rapid onset fentanyls (buccal or nasal) have been strongly recommended for breakthrough cancer pain due to their fast onset and their shorter duration of action. If available, metamizole is an alternative non-steroid-anti-inflammatory-drug. The indication for bisphosphonates should always be checked early in the disease. In advanced cancer stages, glucocorticoids are an important treatment option. If bone metastases lead to neuropathic pain, coanalgetics (e.g., pregabalin) should be initiated. In localized bone pain, radiotherapy is the gold standard for pain reduction in addition to pharmacologic pain management. In diffuse bone pain radionuclids (such as samarium) can be beneficial. Invasive measures (e.g., neuroaxial blockage) are rarely necessary but are an important option if patients with cancer pain syndromes are refractory to pharmacologic management and radiotherapy as described above. Clinical guidelines agree that cancer pain management in incurable cancer is best provided as part of a multiprofessional palliative care approach and all other domains of suffering (psychosocial, spiritual, and existential) need to be carefully addressed («total pain»).

Metastatic breast cancer

Liver metastases. Typically, pain from liver metastases responds to chemotherapy and analgesia. However, in cases when chemotherapy is contraindicated or the liver metastases are refractory to chemotherapy (and pain medication fails to provide appropriate palliation of liver metastasis-related pain, radiotherapy should be considered; it may relieve pain and shrink the metastases, and perhaps extend survival in a subset of patients with a good response to radiotherapy. Brain metastases. Brain metastases occur in up to 10–15% of breast-cancer patients, and often (but not always) occur late in the disease. They require urgent treatment; brain metastases may progress rapidly, and can suddenly produce life-threatening complications such as increased intracranial pressure, herniation of the brain, and seizures. Radiotherapy is essential in the treatment of brain metastases from breast cancer, as it halts tumor progression quickly and can induce a response in the majority of patients.

Nonopioid drugs in the treatment of cancer pain.

The WHO analgesic ladder for the treatment of cancer pain provides a three-step sequential approach for analgesic administration based on pain severity that has global applicability. Nonopioids were recommended for mild pain, with the addition of mild opioids for moderate pain and strong opioids for severe pain. Here, we review the evidence for the use of nonopioid analgesic agents in patients with cancer and describe the mode of action of the main drug classes. Evidence supports the use of anti-inflammatory drugs such as acetaminophen/paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) for mild cancer pain. Adding an NSAID to an opioid for stronger cancer pain is efficacious, but the risk of long-term adverse effects has not been quantified. There is limited evidence to support using acetaminophen with stronger opioids. Corticosteroids have a specific role in spinal cord compression and brain metastases, where improved analgesia is a secondary benefit. There is limited evidence for adding corticosteroids to stronger opioids when pain control is the primary objective. Systematic reviews suggest a role for antidepressant and anticonvulsant medications for neuropathic pain, but there are methodologic issues with the available studies. Bisphosphonates improve pain in patients with bony metastases in some tumor types. Denosumab may delay worsening of pain compared with bisphosphonates. Larger studies of longer duration are required to address outstanding questions concerning the use of nonopioid analgesia for stronger cancer pain.

Management of cancer pain with analgetic adjuvant and weak opioid in prostate cancer bone metastases: A case series.

In cancer patients, cancer pain is the most common cancer complication. About 60-90% of patients with advanced stage cancer experience various levels of pain, and about 30% of patients have been suffering from persistent severe pain. Bones are the most frequent targets of metastases in patients with cancer such as breast, prostate, lung, kidney, and thyroid. In advanced prostate cancer, bone metastasis leads to bone pain, skeletal fracture, and increased mortality. At least 75% of patients with bone metastasis experience bone pain. We report three cases of cancer pain, treated with primary cancer from the prostate metastasis to the spine. All three patients had lower back pain that radiated to the left and right limbs, with mixed pain and bone pain, where early hospital admission shows the Numeric Rating Scale (NRS) pain scale 9-10. Treated with administration of adjuvant therapy (Gabapentin) and weak opioids (injections of Tramadol) as well as injections of Metylprednisolone (for 3 days), the patient's pain scale was evaluated, and the average NRS obtained on days 2-4 was 5-6. On day 5-8, treatment continued with Gabapentin and Tramadol injections, and the pain scale (NRS) decreased to 2-3. All patients on the 8-9<supth</sup day of treatment also received Biphosphonates to reduce pain, bone damage, fracture risk, and blood calcium levels. Patients can be discharged with an oral Gabapentin prescription only. A pain scale (NRS) reduction of >50% is obtained from the initial pain scale in cancer pain patients treated using a combination of adjuvant therapy and weak opioids.

[Bisphosphonate as an adjuvant therapy for the pain of bone metastases, 3 cases].

Pain from bone metastases limits mobility and may cause pathological fractures that can seriously impair the patient's quality of life. Conservative treatments such as orthopedic fixation, radiotherapy, and opioids sometimes fail to give satisfactory pain relief. Bisphosphonates have been reported to reduce the severity of pain from bone metastasis due to breast cancer, prostate cancer, and multiple myeloma. Recent clinical reports demonstrated the effectiveness of bisphosphonates in reducing pain from bone metastases in various malignancies. This study presents 3 cases of refractory pain from bone metastases due to thyroid, colorectal and hepatocellular carcinoma. Primary treatment included orthopedic fixation, radiotherapy, and/or parenteral opioids that failed to reduce bone pain. Bisphosphonate therapy was considered at the start of pain control treatment using opioids. All 3 cases showed gradual reduction in pain after i.v. pamidronate administration and allowed physicians to control further pain with opioids. In 1 case, the patient was successfully withdrawn from opioids. The role of bisphosphonates in painful bone metastases remains unclear. However, recent encouraging reports have indicated that bisphosphonate may become one of the adjuvant treatments available to control refractory bone pain from various malignancies.

Cancer pain

The WHO guidelines recommend prompt oral administration of drugs when pain occurs, starting, if the person is not in severe pain, with non-opioid drugs such as paracetamol, dipyrone, non-steroidal anti-inflammatory drugs or COX-2 inhibitors. Then, if complete pain relief is not achieved or disease progression necessitates more aggressive treatment, mild opioids such as codeine, dextropropoxyphene, dihydrocodeine or tramadol are added to the existing non-opioid regime. If this is or becomes insufficient, mild opioids are replaced by stronger opioids such as morphine, while continuing the non-opioid therapy, escalating opioid dose until the person is painless or the maximum possible relief without intolerable side effects has been achieved. If the initial presentation is severe cancer pain, this stepping process should be skipped and a strong opioid should be started immediately in combination with a non-opioid analgesic. However, a 2017 Cochrane Review found that there is no

[Not Available].

Oral medication is the simplest way in treatment of chronic pain. For cancer pain oral analgesics are efficacious in more than 90% of the patients. When a causal therapy of pain (e.g. chemotherapy, operation) fails an analgesic ladder with oral analgesics is instituted. This ladder starts with a non-narcotic analgesic in a sufficient dose. The regular dose of acetylsalicylic acid or paracetamol is 4 g daily. When this dose does not work sufficiently, a weak opioid (e.g. dihydrocodeine) is given concomitantly at an individual dose. When the weak opioid fails, strong opioids are given (e.g. morphine). The drugs should be given by mouth whenever possible. The most important point is the regular application according to a time-schedule. This time-schedule is related to the action time of the drug. Patients with severe vomiting or dysphagia can receive a continuous subcutaneous infusion. These measures are based on recommendations of the WHO.The same medications can be employed in patients with chronic non-malignant pain, provided that all other conventional measures in pain treatment fail. However, many states of pain are not opioid-responsive. Pain related to the sympathetic nervous system is more responsive to antidepressants than to opioids or NSAID. Neuropathic pain as in trigeminal neuralgia responds to anticonvulsants. Pain from muscle spasm is better controlled by muscle relaxants than by analgesics. Bone pain is more sensitive to NSAID than to any other drug.In any state of pain the response to the different groups of drugs should be evaluated first. Then a stepwise pharmacological approach should be performed. In most cases pain can be treated effectively by oral drugs.

[A case of stage IV breast cancer with improved cancer pain using bevacizumab and paclitaxel].

A 65-year-old woman with a right breast tumor and right arm pain was seen in our hospital. She was diagnosed with scirrhous carcinoma (Stage IV, hormone receptor-positive, and HER2-negative) with pleural effusion and metastasis to the lung, liver, bone, and multiple lymph nodes. Systemic chemotherapy with biweekly bevacizumab and weekly paclitaxel was administered, and an opioid (oxycodone 40 mg/day) was administered for pain control. At the end of the first course, the patient's pain was improved, and the opioid dose was reduced (oxycodone 20 mg/day). The patient had a partial response (PR) over 24 treatment courses (1 year 10 months), and good pain control was obtained. Bevacizumab and paclitaxel therapy successfully brought about a rapid and good response and improved the patient's quality of life as palliative chemo- therapy.

Pain ladder

The WHO guidelines recommend prompt oral administration of drugs ("by the mouth") when pain occurs, starting, if the patient is not in severe pain, with non-opioid drugs such as paracetamol (acetaminophen) or aspirin, with or without "adjuvants" such as non-steroidal anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors. Then, if complete pain relief is not achieved or disease progression necessitates more aggressive treatment, a weak opioid such as codeine, dihydrocodeine or tramadol is added to the existing non-opioid regime. If this is or becomes insufficient, a weak opioid is replaced by a strong opioid, such as morphine, diamorphine, fentanyl, buprenorphine, oxymorphone, oxycodone, or hydromorphone, while continuing the non-opioid therapy, escalating opioid dose until the patient is pain free or at the maximum possible relief without intolerable side effects. If the initial presentation is severe pain, this stepping process should be skipped and a strong opioid should be

[Therapy for symptomatic pain in advanced breast cancer].

From 1983-1989, 106 patients with breast cancer were treated in our pain management unit on 6767 treatment days. Pain was caused by bone metastasis in 73% of patients. Neuropathic pain was reported by 32% of the patients. In all but four of these patients, new tumour growth was diagnosed. Patients were treated according to WHO analgesic guidelines with non-opioids on 16% of the days, non-opioids in combination with weak opioids on 36% and with strong opioids on 38% (orally 90%, parenterally 4% of the days). Due to the prevalence of bone pain non-steroidal antiinflammatory drugs were given on 56% of the days. The high incidence of neuropathic pain led to frequent use of co-analgesics (antidepressants 17%, anticonvulsants 12%, steroids 12% of the days). Adjuvant therapy for symptoms other than pain was given on 86% of the days. Whilst 92% of patients reported more than moderate pain on admission, 45% obtained complete pain relief beginning from the first days of treatment. On 92% of the days, patients described their pain as moderate or less. Side effects were treated symptomatically and played a minor role in a reason to change therapy.

[Postoperative morphine excess or rational therapy? An exceptional case of applying the morphine equivalent].

We report on a 51-year-old female with a 7 year history of breast cancer. In August 2000 surgical replacement of the 8th thoracic vertebra was performed. From November 2000 the patient developed progressive pain, due to additional spine metastases, leading to pain therapy (according to the patient record) as follows: MST 320 mg oral 4 times daily, Durogesic 100 micrograms/h transdermal, Sevredol 40 mg oral 3 times daily and Ibuprofen 800 mg oral 3 times daily. Due to the risk of spinal instability and persisting pain a thoracic spondylodesis from Th 4-L2 was performed. Parallel to arrival in the PACU the patient developed extremely intensive pain. Pain control was achieved by fractional injection of overall 660 mg morphine in the first 120 min. After interviewing the patient, opioid consumption surprisingly turned out to be 60% higher than presumed. Pain therapy was continued by infusion and PCA with morphine in a daily intravenous dosage of 600-800 mg. Consecutively the pain therapy was switched to oral morphine and co-analgesics and the patient was discharged home 14 days postoperatively. Some patients with chronic cancer pain are used to increased opioid dosages prior to planned surgery. In the perioperative setting these dosages have to be continued and adapted to current requirements, otherwise analgesic undersupply occurs. In our case report we describe a serious sequence of postoperative analgesic undersupply in an opioid consuming patient. The main principles of post-operative dosing and logistic pitfalls are illustrated.

[Management of bone metastases from breast cancer].

Bone is the most common of breast cancer metastasis. Bone metastasis causes skeletal-related events(SREs), including pain, bone fractures, spinal cord compression, and hypercalcemia. SREs significantly impair patients' quality of life. The main purpose of treatment for bone metastasis is to prevent or delay SREs and to improve patients' quality of life. Accurate diagnosis of bone metastases is important in order to choose an appropriate treatment. Treatment of bone metastasis requires a multidisciplinary approach. Analgesic medication with NSAIDs and opioids is the first choice for pain control. In addition to bisphosphonate, the receptor activator of the nuclear factor κB ligand(RANKL)inhibitor, denosumab is a novel bone-targeting agent effective in preventing SREs. Prophylactic stabilization of impending fractures provides several advantages compared with fixation of an acute fracture, in terms of short hospitalization and a quick return to baseline. In general, radiation therapy is indicated for patients for whom surgery is suitable. Radiation therapy to palliate pain from bone metastasis can reduce the intake of analgesic medications. Local radiation therapy is indicated for a limited number of bone metastases, and systemic radionuclide therapy is appropriate for multiple lesions. In summary, treatment using these modalities for bone metastasis from breast cancer should be stratified, considering the symptoms, site of bone metastasis, and patients' life expectancy and performance status.

Strontium-89

As such, intravenous or intracavity administration of 89Sr may be helpful in the palliation of painful bony metastases, as it allows for targeted radiation to metastatic lesions, inducing apoptosis of cells, membrane and protein damage. Subsequently, bone pain resulting from cytokine release at the site of lesions, bone-associated nerve compression and stretching of the periosteum may be reduced. Treatment with 89Sr has been particularly effective in patients with hormonally-resistant prostate cancer, often leading to a decreased requirement for opioid analgesics, an increase in time until further radiation, and a decrease in tumour markers. It is an artificial radioisotope which is used in treatment of bone cancer. In circumstances where cancer patients have widespread and painful bony metastases, the administration of 89Sr results in the delivery of beta particles directly to the area of bony problem, where calcium turnover is greatest.

[A Case of Recurrent Breast Cancer with Bone Metastasis Successfully Treated with Everolimus and Exemestane Therapy].

We report a case of a patient treated with everolimus and exemestane combination therapy for bone metastasis after breast surgery.The patient, a 58-year-old woman, consulted our department for back pain in October 2014.S he was diagnosed with left breast cancer when she was 41 years old.She had received Bt+Ax for left breast cancer and administered tamoxifen for 5 years.We decided on everolimus and exemestane combination therapy after observing an abnormal uptake in the 7th to 8th thoracic vertebrae on a PET-CT scan.The pain was controlled using oxycodone and fentanyl orally disintegrating tablet with zoledronic acid.After receiving treatment, the patient experienced pruritus and a Grade 2 rash, but they were managed with antihistamine administration and the treatment was continued.Four months later, the abnormal uptake on the right thoracic vertebrae shrunk; the pain almost disappeared, and oxycodone and fentanyl orally disintegrating tablet were discontinued.Subsequently, exemestane was used alone.Six months later, the range of abnormal uptake on the thoracic vertebrae progressed, and the disease was evaluated as PD.Four months later, everolimus and exemestane combination therapy was resumed, and the abnormal uptake on the thoracic vertebrae almost disappeared as observed on a PET scan.The effectiveness of the treatment was evaluated as CR because other local recurrence and new metastases were not found. Everolimus might exhibit bone resorption inhibiting effects and bone protection effects, but the decision regarding the periods of suitable use and the effects of long-term continuation of treatment are controversial, and further discussion based on experience of increasing use is required.

[Delirium is certainly not an unavoidable complication of pain control in the terminal phase of life].

In three terminal patients, a man aged 19 years who suffered from progressive osteosarcoma, a man aged 71 years with a small-cell pulmonary carcinoma, and a 68-year-old woman with cerebral metastases from a mammary carcinoma, delirium developed due to increased dosage of opioids for seemingly intractable pain (the first two patients) and dexamethasone (third patient). The delirium subsided after opioid rotation, administration of drugs for neuropathic pain, and treatment with an antipsychotic, respectively. This enhanced the patients' quality of terminal life and quality of dying. In terminal patients, analgesics-induced delirium must be considered, diagnosed and treated without delay.

Vertebral compression fracture

Diagnosis Compression fractures are usually diagnosed on spinal radiographs, where a wedge-shaped vertebra may be visible or there may be loss of height of the vertebra. In addition, bone density measurement may be performed to evaluate for osteoporosis. When a tumor is suspected as the underlying cause, or the fracture was caused by severe trauma, CT or MRI scans may be performed. Treatment Conservative treatment Back brace for support while the bone heals—either a Jewett brace for relatively stable and mild injuries, or a thoracic lumbar sacral orthosis (TLSO) for more severe ones. Opioids or non-steroidal anti-inflammatory drugs (NSAIDs) for pain. For osteoporotic patients, calcitonin may be helpful. Surgical Kyphoplasty and vertebroplasty are minimally invasive procedures that inject cement into the bone of the back that is fractured. However, the data examining the effectiveness of these procedures is mixed. References Further reading

Controversies in pharmacotherapy of pain management.

Since the establishment of the WHO three-step ladder for management of cancer pain, several controversies have arisen, which are partly due to new drug development, reformulations of older analgesics, and technological advancements. As a result, clinicians need clarification of several questions. Is morphine the opioid of choice for moderate to severe pain in cancer? Should combinations of opioids be used? When should spinal opioids be used to treat pain in cancer? What are the appropriate opioid doses for breakthrough pain? Should selective cyclo-oxygenase (COX) 2 inhibitors be used? What is the best tactic to treat neuropathic pain, and what first-line adjuvant analgesic should be used? And do bisphosphonates relieve bone pain in cancers other than breast cancer and myeloma? This review addresses these questions.

Radiation therapy in the management of symptomatic bone metastases: the effect of total dose and histology on pain relief and response duration.

In order to better define variables and factors that may influence the pain response to radiation, and to look for a radiation regimen that can assure the highest percentage and the longest duration of pain relief, we performed a prospective, although not randomized, study on patients with bone metastases from various primary sites. From December 1988 to March 1994, 205 patients with a total of 255 solitary or multiple bone metastases from several primary tumors were treated in our radiotherapy center with palliative intent. Irradiation fields were treated with three main fractionation schedules: (1) Conventional fractionation: 40-46 Gy/20-23 fractions in 5-5.5 weeks; (2) Short course: 30-36 Gy/10-12 fractions in 2-2.3 weeks; (3) Fast course: 8-28 Gy/1-4 consecutive fractions. Pain intensity was self-assessed by patients using a visual analogic scale graduated from 0 (no pain) to 10 (the strongest pain one can experience). Analgesic requirement was assessed by using a five-point scale, scoring both analgesic strength and frequency (0 = no drug or occasional nonopioids; 1 = Nonopioids once daily; 2 = Nonopioids more than once daily; 3 = Mild opioids (oral codeine, pentazocine, etc.), once daily; 4 = Mild opioids more than once daily; 5 = Strong opioids (morphine, meperidine, etc.). Complete pain relief meant the achievement of a score < or = 2 in the pain scale or 0 in the analgesic requirement scale. Partial pain relief indicated a score of 3 to 4 or of 1 to 2 on the former and latter scale, respectively. Total pain relief (complete + partial) was observed in 195 (76%) sites, in 158 of which (62%) a complete response was obtained. Metastases from NSC lung tumors appeared to be the least responsive among all primary tumors, with 46% complete pain relief in comparison to 65% and 83% complete relief in breast (p = 0.04) and in prostate metastases (p = 0.002), respectively. A significant difference in pain relief was detected among the several ranges of total dose delivered to the painful metastases, with 81%, 65%, and 46% complete relief rates in the 40-46 Gy, 30-36 Gy (p = 0.03), and 8-28 Gy (p = 0.0001) dose ranges respectively. A straight correlation between total dose and complete pain relief was confirmed by the curve calculated by the logistic model which shows that doses of 30 Gy or more are necessary to achieve complete pain relief in 70% or more of bone metastases. This correlation holds also for the duration of pain control, as shown by the actuarial analysis of time to pain progression. Multivariate analyses, with complete pain relief and time to pain progression as endpoints show a highly significant effect of radiation dose (p = 0.0007) and performance status (p = 0.003), with lower rates of complete pain relief and shorter time to pain progression observed after smaller radiation total doses or higher Eastern Cooperative Oncology Group (ECOG) scores. Although single-dose or short course irradiation is an attractive treatment in reducing the number of multiple visits to radiotherapy departments for patients with painful bone metastases, it is nevertheless clear that aggressive protracted treatments seem to offer significant advantages especially for patients in whom the expected life span is not short.

Chronic pain

Chronic pain may originate in the body, or in the brain or spinal cord. It is often difficult to treat. Epidemiological studies have found that 8% - 11.2% of people in various countries have chronic widespread pain. Various non-opioid medicines are initially recommended to treat chronic pain, depending on whether the pain is due to tissue damage or is neuropathic. Psychological treatments including cognitive behavioral therapy and acceptance and commitment therapy may be effective for improving quality of life in those with chronic pain. Some people with chronic pain may benefit from opioid treatment while others can be harmed by it. People with non-cancer pain who have not been helped by non-opoid medicines might be recommended to try opioids if there is no history of substance use disorder and no current mental illness. If the chronic pain is not relieved, opioids should be discontinued.

The treatment of metastatic breast cancer in bone.

The author report clinical experience with 212 cases of mammary cancer metastatic to bone, in 186 of which radiotherapy was given, and in 26 steroid hormone therapy. At least 70 per cent of patients with bone metastasis from breast cancer were relieved of pain by adequate roentgen therapy, the relief lasting for most of the survival time in many instances. About 25 per cent of patients had recalcification or reossification of bony lesions with roentgen therapy; while dramatic, this is not always an indication that relief of pain will continue or that survival time will be lengthened. If and when adequate radiotherapy has not been effective or cannot be administered (for example, in a patient with extremely widespread metastasis, or one residing at a considerable distance from radiotherapeutic service) steroid hormone therapy in adequate dosage is frequently beneficial. From 40 per cent to 75 per cent of patients with bone metastases from breast cancer are relieved of pain by steroid hormone therapy. In about 15 per cent of cases recalcification of the lesion occurs. Effective roentgen therapy may usually be given in a relatively brief period of time (one to two weeks). Effective steroid hormone therapy usually requires from 12 to 24 weeks. Complications of steroid hormone therapy are numerous. Some patients are made considerably worse by such therapy. These complications may only be controlled by reduction or discontinuation of the hormones. For this reason, it is recommended that irradiation always be used as the initial method of palliation.

Combined application of diclofenac and celecoxib with an opioid yields superior efficacy in metastatic bone cancer pain: a randomized controlled trial.

Metastatic bone cancer pain is one of the most common clinical cancer pains and is caused by many factors. This study was conducted to explore the clinical efficacy of using two non-steroidal anti-inflammatory drugs (NSAIDs) along with an opioid in treating metastatic bone cancer pain. A total of 342 patients with a pain score of 7-10 on the visual analog scale (VAS) were recruited for 4 weeks of treatment and randomly assigned to three different groups-one group received two NSAIDs (diclofenac and celecoxib), one group received diclofenac, and one group received celecoxib. All patients received morphine sulfate 10 mg/12 h with a reduction of 50% or addition of 25% each time until the VAS score was <5. The VAS score, remission rate (RR), breakthrough pain (BTP), morphine sulfate dose and side-effects among the three groups were compared. After 4 weeks of treatment, we found that using two NSAIDs along with an opioid could yield a significantly lower VAS score (p = 0.006), higher RR (p = 0.0002) and fewer incidences of BTP (p = 0.011), compared to the use of only one NSAID. Furthermore, using two NSAIDS could significantly decrease the consumption of morphine sulfate compared to using each NSAID in isolation (p = 0.0031 in week 1; p = 0.020 in week 2; p = 0.0012 in week 4). Additionally, using two NSAIDs could produce fewer incidences of dizziness (p = 0.002), constipation (p < 0.0001) and drowsiness (p < 0.0001). Although limited by the relatively small samples, these results indicate that using two NSAIDs along with an opioid in treating metastatic bone cancer pain was more effective and acceptable, which is worthy of further clinical application.

Cancer pain

More than half of people with advanced cancer and pain will need strong opioids, and these in combination with non-opioid pain medicine can produce acceptable analgesia in 70–90 percent of cases. Morphine is effective in relieving cancer pain although oxycodone shows superior tolerability and anlgesic effect, though cost may limit its value in certain healthcare systems. Side effects of nausea and constipation are rarely severe enough to warrant stopping of treatment. Sedation and cognitive impairment usually occur with the initial dose or a significant increase in dosage of a strong opioid, but improve after a week or two of consistent dosage. Antiemetic and laxative treatment should be commenced concurrently with strong opioids, to counteract the usual nausea and constipation. Nausea normally resolves after two or three weeks of treatment but laxatives will need to be aggressively maintained. Buprenorphine is another opioid with some evidence of its efficacy but only low quality

[Effectiveness of Strontium-89 for Neuropathic Pain Caused by Bone Metastases from Breast Cancer: A Case Report].

The patient was a 47-year-old female with stage IV breast cancer and multiple bone metastases. She received various systemic therapies (hormone therapy and chemotherapy) and underwent mastectomy between 2013 and 2018; in the beginning of 2018, she started experiencing bone metastatic pain in the right hip joint and neural pain on the dorsal side of the left thigh. These symptoms worsened gradually, and nonsteroidal anti-inflammatory analgesics or narcotic analgesics were not effective for treating this pain. Strontium-89 (<sup89</supSr) treatment was administered in April 2018. The pain was relieved immediately after <sup89</supSr treatment. The patient's quality of life improved markedly. She spent her remaining life without using analgesic drugs, until she died in October 2018 due to exacerbation of the original disease. Although radiotherapy is believed to be less effective for neuropathic pain than for bone metastatic pain, it should be considered as a treatment option in patients with neuropathic pain.

Medication overuse headache

Headache treatment Opioids and butalbital are sometimes inappropriately used as treatment for migraine and headache and should be avoided in favor of more effective, migraine-specific treatments. Opioid and butalbital use can worsen headaches and cause MOH. When a patient fails to respond to other treatment or migraine specific treatment is unavailable, then opioids may be used. Regular use of over-the-counter drugs (OTC) such as paracetamol and NSAIDs can also be a cause of MOH. OTC medication for headache should be limited to use for not more than two days weekly. Concurrent with MOH, overuse of acetaminophen (known as paracetamol in some countries) for treating headaches risks causing liver damage and NSAID overuse can cause gastrointestinal bleeding.

Opioid-induced hyperalgesia

One general treatment option is to gradually reduce or discontinue the dose of opioid to see if OIH is improved, although this could induce withdrawal symptoms that may initially increase pain. Opioid switching, also called opioid rotation, is the replacement of the current opioid with another pharmacological agent such as morphine or methadone. It was effective in some studies, but can increase sensitivity to pain, requiring higher doses of the opioid-sparing drug. Opioid rotation is a safe and effective alternative to completely stopping opioid therapy. Methadone is also believed to show some efficacy in OIH, presumably due to its weak NMDA antagonist activity. Ketamine, an NMDA antagonist, has been shown to prevent the extended use of opioid in post-operative hyperalgesia when it is infused in a small amount perioperatively along with the opioid but there are also studies that show ketamine being ineffective in modulating hyperalgesia.

Dexamethasone for the Prevention of a Pain Flare After Palliative Radiation Therapy for Painful Bone Metastases: The Multicenter Double-Blind Placebo-Controlled 3-Armed Randomized Dutch DEXA Study.

After radiation therapy for painful bone metastases, up to 44% of patients report a pain flare (PF). Our study compared 2 dose schedules of dexamethasone versus placebo to prevent PF. This double-blind, randomized, placebo-controlled trial allocated patients with painful bone metastases from solid tumors randomly to receive 8 mg dexamethasone before radiation therapy followed by 3 daily doses (group A), 8 mg dexamethasone followed by 3 doses of placebo (group B), or 4 doses of placebo (group C). Patients reported worst pain scores, study medication side effects, and opioid intake before treatment and thereafter daily for 14 days and on day 28. PF was defined as at least a 2-point increase on a 0 to 10 pain scale with no decrease in opioid intake or a 25% or greater increase in opioid intake with no decrease in pain score, followed by a return to baseline or lower. The primary analysis was by intention to treat with patients who had missing data classified as having a PF. From January 2012 to April 2016, 295 patients were randomized. PF incidence was 38% for group A, 27% for group B, and 39% for group C (P = .07). Although patients in group B had the lowest PF incidence, a relatively high percentage did not return to baseline pain levels, indicating pain progression. The mean duration of PF was 2.1 days for group A, 4.5 days for group B, and 3.3 days for group C (P = .0567). Dexamethasone postponed PF occurrence; in group A 52% occurred on days 2 to 5 versus 73% in group B and 99% in group C (P = .02). Patients in group A reported lower mean pain scores on days 2 to 5 than those in group B or C (P < .001). Side effects were similar. There was insufficient evidence that dexamethasone reduced the incidence of radiation-induced PF. However, dexamethasone postponed the occurrence of PF and led to lower mean pain scores on days 2 to 5.

Opioid-induced hyperalgesia

The use of an NSAID, especially some COX-2 inhibitors, or acetaminophen either as monotherapy or combination therapy is also suggested as a possible treatment option. Research needs It can be difficult to apply research into OIH to average patients, because some research focused on people taking very high doses or in methadone rehabilitation programs. Opioid-induced hyperalgesia has also been criticized as overdiagnosed among chronic pain patients, due to poor differential practice in distinguishing it from the much more common phenomenon of opioid tolerance. The misdiagnosis of common opioid tolerance (OT) as opioid-induced hyperalgesia (OIH) can be problematic as the clinical actions suggested by each condition can be contrary to each other. Patients misdiagnosed with OIH may have their opioid dose mistakenly decreased (in the attempt to counter OIH) at times when it is actually appropriate for their dose to be increased or rotated (as a counter to opioid tolerance).

Opioids for metastatic bone pain.

Metastatic bone pain is characteristic of cancer pain. Satisfactory analgesic effects are achieved in more than 70% of patients with cancer pain who receive a combination of nonsteroidal anti-inflammatory drugs and opioids, according to the WHO therapeutic guidelines. Morphine, oxycodone, and fentanyl are commonly administered opioids. We found that the mean dose of oxycodone to achieve analgesic effects was 55 mg, and at doses of <or=80 mg satisfactory analgesia was achieved in 80% of our patients. Palliative radiation was performed in 6 patients, resulting in pain relief in 4 and therefore the dose of opioids could be reduced. Bone metastasis should not be considered as the terminal stage, and decisions on the administration of drugs, in combination with radiation or orthopedic therapy, should be made at an early stage. Alleviation of pain and allowing a better quality of patient survival time, even if not for long, should be attempted.

Strontium chloride Sr 89 for treating pain from metastatic bone disease.

The role of strontium chloride Sr 89 in the palliative treatment of pain associated with metastatic bone disease is reviewed. Conventional therapies to relieve metastatic bone pain include nonopioid and opioid analgesics, hormonal therapy, external-beam irradiation, and chemotherapy. Limitations in the long-term safety and effectiveness of these treatments have increased interest in using systemic radioactive isotopes for palliation of pain. Strontium chloride Sr 89 is a relatively new bone-seeking radiopharmaceutical that has FDA-approved labeling for use in relieving pain associated with skeletal metastases. An analogue of calcium, strontium chloride Sr 89 is rapidly cleared from the blood after i.v. injection. The agent selectively irradiates metastatic sites while generally sparing normal soft-bone tissue. In clinical studies, a majority of patients with prostate or breast cancer obtained substantial relief from bone pain after receiving strontium chloride Sr 89 alone or in combination with external-beam irradiation. Adverse effects tend to be mild, but patients should be monitored for possible hematologic toxicity. Patients should discontinue any calcium-containing products before receiving the agent. The typical dose is 4 mCi (148 MBq) administered by slow i.v. push over one to two minutes; doses can be repeated at three-month intervals. Pain relief usually begins in 10-20 days and lasts up to six months. Radiation safety measures are necessary in handling strontium chloride Sr 89 and the wastes of patients. Strontium chloride Sr 89 is costly, but preliminary analysis indicates that it may reduce management expenditures overall.(ABSTRACT TRUNCATED AT 250 WORDS)

Opioid

Clinical studies have consistently associated medical and recreational opioid use with hypogonadism (low sex hormone levels) in different sexes. The effect is dose-dependent. Most studies suggest that the majority (perhaps as much as 90%) of chronic opioid users suffer from hypogonadism. Opioids can also interfere with menstruation in women by limiting the production of luteinizing hormone (LH). Opioid-induced hypogonadism likely causes the strong association of opioid use with osteoporosis and bone fracture, due to deficiency in estradiol. It also may increase pain and thereby interfere with the intended clinical effect of opioid treatment. Opioid-induced hypogonadism is likely caused by their agonism of opioid receptors in the hypothalamus and the pituitary gland. One study found that the depressed testosterone levels of heroin addicts returned to normal within one month of abstinence, suggesting that the effect is readily reversible and is not permanent. , the effect of low-dose or


Gestational trophoblastic disease should be followed up (regardless of whether the evacuation has been complete or not) and the patient should be advised not to become pregnant again until at least 6 months with negative BHCG titers. The risk of recurrence in another pregnancy is low (1/55) and 90% of cases progress satisfactorily without developing neoplasia.

A 24-year-old woman, primigestation, suffers a spontaneous abortion at 7 weeks of gestation. The anatomopathological study of the abortive remains indicates molar disease. We should inform you that:

The risk of a new molar gestation in a future pregnancy is 50%.

She should not become pregnant until she has undergone periodic controls and has spent one year with negative BHCG levels.

Subsequent controls are not necessary if the evacuation of the trophoblastic tissue was complete.

It is necessary to carry out periodic controls since 40% of the cases will develop a gestational trophoblastic neoplasia.

Gestational trophoblastic disease

In the past, it was seen as important not to get pregnant straight away after a GTD. Specialists recommended a waiting period of 6 months after the hCG levels become normal. Recently, this standpoint has been questioned. New medical data suggest that a significantly shorter waiting period after the hCG levels become normal is reasonable for approximately 97% of the patients with hydatidiform mole. Risk of a repeat GTD The risk of a repeat GTD is approximately 1 in 100, compared with approximately 1 in 1000 risk in the general population. Especially women whose hCG levels remain significantly elevated are at risk of developing a repeat GTD. Persistent trophoblastic disease The term «persistent trophoblastic disease» (PTD) is used when after treatment of a molar pregnancy, some molar tissue is left behind and again starts growing into a tumour. Although PTD can spread within the body like a malignant cancer, the overall cure rate is nearly 100%.

[Gestational trophoblastic tumors and recent clinical information].

Recent clinical advances in the field of gestational trophoblastic diseases are described. WHO modified its risk factor scoring system. This change was proposed to combine both the basic FIGO anatomic staging with the modified WHO risk factor scoring system. Patients who score as low-risk are treated with single agent chemotherapy, such as methotrexate (MTX), and patients refractory to MTX are treated with a combination chemotherapy, EMA/CO. Patients who score as high-risk are treated with EMA/CO, and patients refractory to the first line chemotherapy may be successfully treated with EP/EMA. Recent epidemiological data showed that women with complete hydatidiform moles could anticipate normal reproduction in the future. Studies found that pregnancies after treatment of molar pregnancy resulted in 69% full-term, live births; 8% premature deliveries; 1% ectopic pregnancies, and 0.5% stillbirths. First-trimester spontaneous abortions occurred in 17% of pregnancies, and major and minor malformations were detected in 0.4% of infants. Patients with hydatidiform mole were at increased risk of developing molar pregnancy in subsequent conceptions. After having one molar pregnancy, the risk of having molar disease in a future gestation was about 1%. The risk of persistent gestational trophoblastic tumors was increased by long-term oral contraceptive use before conception. In a large, multicenter, case-control study, the risk was shown to be increased in women who had ever used oral contraceptives, but was highest for women taking oral contraceptives during the cycle in which they became pregnant. Partial hydatidiform moles were never previously proven to transform into choriocarcinoma; however, a recent study with molecular techniques clearly showed that partial moles could transform into choriocarcinoma. All patients with suspected partial moles should be reviewed centrally and require hCG follow-up.

Placental site trophoblastic tumor arising from antecedent molar pregnancy.

Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic disease. Little is known about its pathogenesis and natural history. This report describes two cases that arose in patients with documented complete hydatidiform moles and summarizes the antecedent prenatal histories of PSTTs based on a detailed Medline literature analysis. A 28-year-old, G(2)P(2) female had a live, 12-week gestation fetus and a coexisting molar pregnancy. Her hCG levels dropped promptly from 1.5 million to 23,273 IU/ml after termination, but rose shortly thereafter together with the onset of recurrent vaginal bleeding. Curettage revealed persistent mole. Persistently elevated hCG led to hysterectomy disclosing a fundal PSTT. The second case was that of a 48-year-old, G(2) woman who presented with symptoms of preeclampsia, hyperthyroidism, and elevated hCG. Curettage yielded a complete hydatidiform mole. Although the hCG level decreased for a short period, it soon increased despite treatment with methotrexate. A second curettage revealed a PSTT. A Medline literature analysis of PSTT, which consists almost entirely of individual cases and several small series, disclosed that PSTT is preceded in 61% of cases by normal term pregnancy, 12% molar pregnancy, 9% spontaneous abortion, 8% therapeutic abortion, and 3% with ectopic pregnancy, stillbirths or preterm delivery. No information is known in 7%. This report describes two additional cases of PSTT preceded by complete molar pregnancy. PSTT is a well recognized, but uncommon form of gestational trophoblastic disease. Although little is known about its pathogenesis, it is preceded not uncommonly by an abnormal pregnancy, including a molar pregnancy.

[Studies on the viability of trophoblast after termination of various kinds of pregnancies (author's transl)].

Although normal value of hCG (LH level) does not necessarily indicate eradication of viable trophoblast, its confirmation has been demonstrated as a clinically useful guide for the probable prevention of choriocarcinoma after hydatidiform mole by Takeuchi et al. Choriocarcinoma preceded by other pregnancies than hydatidiform mole which has the highest risk for choriocarcinoma has drawn more attention than before in connection with the decrease of postmolar choriocarcinoma. So that I have studied the regression rate of urinary gonadotropin (hCG) after the termination of various kinds of pregnancies. In 2,433 cases of induced abortion, 695 cases of spontaneous abortion, 1,724 cases of term delivery and 43 cases of hydatidiform mole, their urinary hCG were determined to the level of physiological range of LH. The rate of hCG regression was in the order of term delivery, spontaneous abortion, induced abortion and hydatidiform mole. The younger was the gestational age of trophoblast, the slower was the regression of hCG. At one month after the termination of pregnancy, 80.1%, 11%, 0.3%, 8% and 4.1%, and at two month 55.8%, 1.6%, 0.5%, 4% and 0.5% for hydatidiform mole, induced abortion of less than 12 week of gestation, spontaneous abortion of less than 12 week of gestation, spontaneous abortion of between 13 and 20 week of gestation respectively still showed abnormal hCG value. One percent of induced abortion at 5 month, 4% of spontaneous abortion at 3 month, 0.3% of term delivery at 4 month still maintained abnormal titer. No malignant sequelae in patients under the investigation have ever been observed in the follow up period between 3 and 8 years.

Increased frequency of complete hydatidiform mole in women with repeated abortion.

The association between spontaneous abortion and gestational trophoblastic disease (GTD) has been investigated in a study based on 93 women with 2 consecutive (repeated) spontaneous abortions and 82 control subjects who delivered normal babies. Nine molar pregnancies were observed among 7 of the 93 cases of repeated abortion while no control reported previous GTD. This difference was statistically significant and was not explained by allowance for age and number of pregnancies between cases and controls (chi 2(1) = 4.20; P = 0.04). When the observed number (9) of hydatidiform mole in the 385 pregnancies of the women with repeated abortion was compared with the expected one (0.28) based on the regional frequency data, the estimated relative risk was 32.1 with a 95% confidence interval from 13.9 to 63.3. The present findings confirm the association between GTD and spontaneous abortion and indicate that the risk is larger in women with repeated abortions.

Persistence of gestational trophoblastic disease for longer than 1 year following evacuation of hydatidiform mole.

A spontaneous fall in the radioimmunoassay for the beta subunit of hCG to less than 2 mIU/mL documents regression of hydatidiform mole following evacuation of a molar pregnancy. Continued negative hCG levels for the year after evacuation indicates the absence of risk for persistent gestational trophoblastic disease. This report describes an unusual case of recurrent nonmetastatic gestational trophoblastic disease 16 months after initial evacuation. A 29-year-old woman presented at 19 weeks' gestation with severe preeclampsia and vaginal bleeding. Pelvic ultrasonography demonstrated a molar pregnancy. Pathology following uterine evacuation confirmed a hydatidiform mole. Serial hCG levels fell progressively to less than 2 mIU/mL over the following 25 weeks. She remained compliant with oral contraceptive pills despite having no sexual activity. Sixteen months after uterine evacuation, recurrence of gestational trophoblastic disease was documented by a rising beta-hCG, negative pelvic ultrasound, normal liver function tests, and normal computed tomography of the head. Endometrial curettage showed no chorionic villi or molar tissue. She was treated with five courses of actinomycin D and has remained disease-free for the following 5 years. This late recurrence of gestational trophoblastic disease suggests that those with a molar pregnancy may benefit from surveillance beyond 1 year after uterine evacuation.

Persistent gestational trophoblastic disease is rarely, if ever, derived from non-molar first-trimester miscarriage.

Traditional epidemiologic data suggest that persistent gestational trophoblastic disease (pGTD), may follow, and be derived from, either molar pregnancy, non-molar term pregnancy or first-trimester non-molar miscarriage. We examined a database of cases of possible or probable hydatidiform moles and proven pGTD derived from the Regional Trophoblastic Disease Unit, Charing Cross Hospital, London. There were 424 cases (6%), in whom the initial registered diagnosis was that of PHM or CHM but central histopathological review diagnosed a definite non-molar hydropic abortion (HA). In eight of the 424 (2%), although the histology of the most recent index pregnancy was that of non-molar miscarriage, there was a previous history of pregnancy affected by hydatidiform mole; two of these developed subsequent pGTD. Of a further 86 cases referred for a histopathological opinion prior to registration which demonstrated definite non-molar HA, none developed pGTD (zero of 510 (0%, 95% CI 0-0.7%)). During the same period there were 352 cases with pGTD requiring chemotherapy. In 31 cases, the only known pregnancy was the preceding apparent non-molar HA. However, of these, there were only three cases in whom the preceding histological products of conception had been centrally reviewed and were suggestive of non-molar pregnancy. However, in all three of these cases, the specimens were inadequate for definite exclusion of molar pregnancy. In one case in whom no material was available for review, molecular genetic analysis using restriction fragment length polymorphisms was carried out, and the choriocarcinoma was genetically derived from a previous molar pregnancy rather than the preceding HA. There were therefore no cases identified on the database of the trophoblastic disease unit of pGTD requiring treatment in whom the trophoblastic tumour could be genetically proven to have arisen from the preceding first trimester non-molar HA. We suggest that the risk of pGTD developing from a histologically confirmed non-molar HA is less than 1 in 50,000 and that the majority of pGTD cases previously reported to have been caused by a non-molar miscarriage probably represent disease due to an unrecognised early molar pregnancy.

Gestational Trophoblastic Disease -- Epidemiology

Risk factors for molar pregnancy include extremes of age, ethnicity, and a prior history of a HM, suggesting a genetic etiology. The risk of a complete mole is higher for women older than 35 years and younger than 21 years and 7.5 times higher for women older than 40 years. The risk of repeat molar pregnancy in women with a history of molar pregnancy is approximately 1% which is 10 to 20 times the risk in the general population. [1] Interestingly, a history of prior spontaneous abortion has been reported to confer a 2- to 3-fold increased risk of molar pregnancy compared to women without a history of spontaneous abortion. [3] Following 2 molar gestations, the risk of having a third mole is > 10%. [7] It is also important to note that malignant transformation such as choriocarcinoma or placental-site trophoblastic tumor can occur following any pregnancy.

Gestational trophoblastic disease

However, the incidence of rare diseases (such as GTD) is difficult to measure, because epidemiologic data on rare diseases is limited. Not all cases will be reported, and some cases will not be recognised. In addition, in GTD, this is especially difficult, because one would need to know all gestational events in the total population. Yet, it seems very likely that the estimated number of births that occur at home or outside of a hospital has been inflated in some reports. Terminology Gestational trophoblastic disease (GTD) may also be called gestational trophoblastic tumour (GTT). Hydatidiform mole (one type of GTD) may also be called molar pregnancy. Persistent disease; persistent GTD: If there is any evidence of persistence of GTD, usually defined as persistent elevation of beta hCG (see «Diagnosis» below), the condition may also be referred to as gestational trophoblastic neoplasia (GTN). See also Trophoblastic neoplasms References External links

Postevacuation hCG levels and risk of gestational trophoblastic neoplasia in women with complete molar pregnancy.

Women diagnosed with complete hydatidiform molar pregnancy are at 15% to 28% risk of developing persistent gestational trophoblastic neoplasia (GTN) requiring further management with chemotherapy. Our objective was to develop human chorionic gonadotropin (hCG) criteria that establish a patient's risk of developing persistent GTN or achieving remission from their baseline risk within a few weeks of molar evacuation. We used a database from the New England Trophoblastic Disease Center to analyze hCG levels from 1,029 women with complete molar pregnancies. We conducted a retrospective cohort study using data from 1973 to 2001. Women whose hCG level declined below 50 mIU/mL during their follow-up were found to be at no more than 1.1% risk for developing persistent GTN, irrespective of when this level was reached. Women whose hCG levels was below 200 mIU/mL in the fourth week after evacuation (59.8% of all women), or below 100 mIU/mL in the sixth week after evacuation (65.8% of all women), had a risk of persistence below 9%. hCG levels above 2,000 mIU/mL in the fourth week after evacuation (13.3% of women) were associated with a 63.8% risk of developing persistent disease. These data may allow clinicians to evaluate the risk of persistence that their patients with complete molar pregnancy have based on early hCG results after molar evacuation. In the fourth week after molar evacuation, 59.8% of women may be counseled that their risk of developing persistent GTN is substantially reduced from their baseline, whereas 13.3% of women may be warned that their risk of developing persistent GTN is greater than 50%. II-2.

Gestational trophoblastic disease

The use of a reliable contraception method is very important during the entire follow up period, as patients are strongly advised against pregnancy at that time. If a reliable contraception method is not used during the follow-up, it could be initially unclear to clinicians as to whether a rising hCG level is caused by the patient becoming pregnant again, or by the continued presence of GTD. In women who have a malignant form of GTD, hCG concentrations stay the same (plateau) or they rise. Persistent elevation of serum hCG levels after a non molar pregnancy (i.e., normal pregnancy [term pregnancy], or preterm pregnancy, or ectopic pregnancy [pregnancy taking place in the wrong place, usually in the fallopian tube], or abortion) always indicate persistent GTD (very frequently due to choriocarcinoma or placental site trophoblastic tumour), but this is not common, because treatment mostly is successful.

Gestational trophoblastic disease

All five closely related tumours develop in the placenta. All five tumours arise from trophoblastic cells. The trophoblast is the membrane that forms the wall of the blastocyst in the early development of the fetus. In a normal pregnancy, trophoblastic cells aid the implantation of the fertilised egg into the uterine wall. But in GTD, they develop into tumour cells. Cause Two main risk factors increase the likelihood for the development of GTD: 1) The woman being under 20 years of age, or over 35 years of age, and 2) previous GTD. Although molar pregnancies affect women of all ages, women under 16 and over 45 years of age have an increased risk of developing a molar pregnancy.Being from Asia/of Asian ethnicity is an important risk factor. Hydatidiform moles are abnormal conceptions with excessive placental development. Conception takes place, but placental tissue grows very fast, rather than supporting the growth of a fetus.

Gestational trophoblastic disease

In this scoring system, women with a score of 7 or greater are considered at high risk. It is very important for malignant forms of GTD to be discovered in time. In Western countries, women with molar pregnancies are followed carefully; for instance, in the UK, all women who have had a molar pregnancy are registered at the National Trophoblastic Screening Centre. There are efforts in this direction in the developing countries too, and there have been improvements in these countries in the early detection of choriocarcinoma, thereby significantly reducing the mortality rate also in developing countries. Becoming pregnant again Most women with GTD can become pregnant again and can have children again. The risk of a further molar pregnancy is low. More than 98% of women who become pregnant following a molar pregnancy will not have a further hydatidiform mole or be at increased risk of complications.

Trophoblastic neoplasm

Management of GTN requires pathology review, treatment options and monitoring of hCG. Therefore, it can be treated with curettage, hysterectomy and single agent or multi agent chemotherapy. Although this group of diseases are highly susceptible to chemotherapy, prognosis depends on the type of GTN and whether the tumor has spread to other areas of the body. Cause and Risk factors The exact cause of gestational trophoblastic neoplasia (GTN) is unknown. GTN often arises after molar pregnancies but can also occur after any gestation including miscarriages and term pregnancies. Although risk factors may impact on the development of the tumor, most do not directly cause of disease. According to the some studies, the risk of complete molar pregnancy is highest in women over age 35 and younger than 20. The risk is even higher for women over age 45. Signs and Symptoms The symptoms of GTN will vary from person to person. People with the same disease may not have all the symptoms listed.

[Reservation of fertility for seventeen patients with placental site trophoblastic tumor].

To approach the efficiency and feasibility of preserving the fertility for patients with placental site trophoblastic tumor (PSTT). Totally 2 086 cases of gestational trophoblastic neoplasm (GTN) patients registered in Peking Union Medical College Hospital between 1998 and 2013. Fifty-seven of them were PSTT patients, 40 cases of which suffered hysterectomy, the rest 17 PSTT patients who preserved their fertility were analyzed retrospectively. The computerized database of clinical and pathological reports was reviewed in this cohort. The clinical manifestation of PSTT was not specific compared to other types of GTN. The average age of the 17 patients was 29.5 years old (range 22-39 years). The most common antecedent pregnancy was term birth (8 cases), the others were spontaneous abortion in 4 case, artificial abortion in 3 cases and molar pregnancy in 2 cases. The baseline serum β-hCG was slightly elevated and 12 patients (12/15) were less than 1 000 U/L. In this cohort, nine of the patients were in stage I, while the other eight cases were in stage III . The patients suffered conservative surgery, including dilation and curettage of uterus in 7 cases, open abdomen uterine lesion excision in 4 cases, laparoscopic uterine lesion excision in 3 cases, hysteroscopic uterine lesion excision in 1 case, and pulmonary lobectomy in 2 cases. Two of the patients didn't received chemotherapy, while the other 15 cases suffered combination chemotherapy. Compared with 40 patients who suffered hysterectomy during the same interval, fertility preservation group did not result in poor outcomes or high risk of relapse rate. Six subsequent pregnancies happened after the therapy, two of them were during their second-trimester, while four patients had healthy babies by vaginal delivery in two and cesarean section in two. The scar of the uterus was fairly well during the cesarean sections. Reservation of fertility therapy could be considered in highly-selected patients for young women who strongly desired to preserve their fertility and with localized lesion. Exactitude follow-up after therapy should be recommended. Contraception should also be recommended for at least one year after the chemotherapy. Vaginal delivery could be an option for the future pregnancies.

Low risk of relapse after achieving undetectable HCG levels in women with complete molar pregnancy.

Complete hydatidiform molar pregnancies occur in approximately 1 of 1,000 conceptions. After uterine evacuation of the trophoblastic tissue, women are followed up with serial serum human chorionic gonadotropin (hCG) measurements. Patients are considered to have attained remission when their hCG level spontaneously declines to an undetectable level and remains there during a 6-month follow-up period. This standard effectively detects all disease recurrence; however, it is resource intensive, delays child bearing, and is subject to significant noncompliance. Our objective was to determine the risk of disease recurrence after hCG spontaneously declines to undetectable levels. We used a database from the New England Trophoblastic Disease Center to analyze hCG levels in patients with complete molar pregnancies. Among 1,029 women with complete molar pregnancy and complete data, 15% developed persistent gestational trophoblastic neoplasia. The rate of persistent neoplasm among those whose hCG level fell spontaneously to undetectable levels was 0.2% (2/876, 95% confidence interval 0-0.8%). No women developed persistent gestational trophoblastic neoplasia after their hCG level fell to undetectable levels using an assay with a sensitivity of 5 mIU/mL (n = 82, 95% confidence interval 0-4.5%). Based on our experience with women with complete hydatidiform molar pregnancies whose hCG values spontaneously fell to undetectable levels after molar evacuation, we conclude that the risk of recurrent neoplasm after hCG levels fall to less than 5 mIU/mL approaches zero.

Gestational trophoblastic neoplasia: A 6 year retrospective study.

To study the clinical presentations of gestational trophoblastic neoplasia and its response to chemotherapy. This is a retrospective study of 28 women of gestational trophoblastic neoplasia evaluated over a period of 6 years from January 2004 to December 2009. Patients were evaluated on the basis of their age, number of deliveries, history of abortion or molar pregnancy, and the treatment received. All patients were scored on the basis of WHO scoring system. Patients with low risk (score </=6) received single agent chemotherapy with methotrexate or actinomycin D. Patients with high risk (score >/=7) received multiple agent chemotherapy with EMACO regimen. After completion of chemotherapy patients were followed for a minimum of 2 years. The response to treatment was evaluated during follow-up by clinical examination, beta hCG levels and imaging as and when required. Out of 28 women only 27 could be evaluated, because 1 patient was lost to follow-up. Out of 27 patients, 18 patients (66.67%) achieved complete remission with the first-line chemotherapy and additional 25.92% (7/27) achieved complete remission with second line chemotherapy resulting in complete remission of 92.5% (25/27). Gestational trophoblastic neoplasia is curable if patient is properly evaluated and scored. It shows good response to chemotherapy.

Placental site trophoblastic tumor

Placental site trophoblastic tumor is a form of gestational trophoblastic disease, which is thought to arise from intermediate trophoblast. It may secrete human placental lactogen (human chorionic somatomammotropin), and result in a false-positive pregnancy test. Placental site trophoblastic tumor is a monophasic neoplasm of the implantation site intermediate trophoblast, and usually a benign lesion, which comprises less than 2% of all gestational trophoblastic proliferations. Preceding conditions include molar pregnancy (5%). Compared to choriocarcinoma or invasive mole, hemorrhage is less conspicuous and serum β-HCG level is low, making early diagnosis difficult. Immunohistochemistry: Often stains with hPL, keratin, Mel-CAM, EGFR. Treatment Because chemotherapy is ineffective; the patient should undergo hysterectomy. Prognosis 10–20% of cases metastasize leading to death. References External links Health issues in pregnancy Germ cell neoplasia

Gestational trophoblastic disease: is intensive follow up essential in all women?

To determine the timescale of the registration process for gestational trophoblastic disease and its impact on hCG level at registration and subsequent need for chemotherapy. A prospective observational study using a standardised protocol for registration, assessment and treatment for molar pregnancy. A supra-regional tertiary referral centre for gestational trophoblastic disease. A total of 2046 consecutive women registered between January 1994 and December 1998 with a diagnosis of molar pregnancy. Data at and after registration, collected prospectively on a computerised database, were statistically analysed (by multiple logistic regression and ANOVA). Relationship between length of time to and hCG value at registration; also the subsequent need for chemotherapy. A total of 2046 women with a diagnosis of molar pregnancy were registered in the study period. The mean time interval between first evacuation and registration at the referral centre was 47 days (median 37, range 0-594). One hundred and five out of 2046 (5.1%) women needed chemotherapy. Sixty-three precent of the women (1296 out of 2046) had a normal level of urinary hCG (less than 40 IU/24 hours) at the time of registration and only one (0.08%) needed chemotherapy. Binary logistic regression analysis showed a statistically significant relationship between time to registration, hCG value, histology, pretreatment risk score and decision to administer chemotherapy. Women with gestational trophoblastic disease who were registered late were significantly more likely to have normal levels of hCG and were less likely to need chemotherapy. A less intensive follow up may be justified in women with gestational trophoblastic disease who are registered with a normal hCG level.

Molar pregnancy

Etymology The etymology is derived from hydatisia (Greek "a drop of water"), referring to the watery contents of the cysts, and mole (from Latin mola = millstone/false conception). The term, however, comes from the similar appearance of the cyst to a hydatid cyst in an Echinococcosis. See also Gestational trophoblastic disease References External links Humpath #3186 (Pathology images) Clinically reviewed molar pregnancy and choriocarcinoma information for patients from Cancer Research UK MyMolarPregnancy.com: Resource for those diagnosed with molar pregnancy. Links, personal stories, and support groups. Germ cell neoplasia Pregnancy with abortive outcome

Postmolar gestational trophoblastic neoplasia: beyond the traditional risk factors.

To investigate the slope of linear regression of postevacuation serum hCG as an independent risk factor for postmolar gestational trophoblastic neoplasia (GTN). Multicenter retrospective cohort study. Academic referral health care centers. All subjects with confirmed hydatidiform mole and at least four measurements of β-hCG titer. None. Type and magnitude of the relationship between the slope of linear regression of β-hCG as a new risk factor and GTN using Bayesian logistic regression with penalized log-likelihood estimation. Among the high-risk and low-risk molar pregnancy cases, 11 (18.6%) and 19 cases (13.3%) had GTN, respectively. No significant relationship was found between the components of a high-risk pregnancy and GTN. The β-hCG return slope was higher in the spontaneous cure group. However, the initial level of this hormone in the first measurement was higher in the GTN group compared with in the spontaneous recovery group. The average time for diagnosing GTN in the high-risk molar pregnancy group was 2 weeks less than that of the low-risk molar pregnancy group. In addition to slope of linear regression of β-hCG (odds ratio [OR], 12.74, confidence interval [CI], 5.42-29.2), abortion history (OR, 2.53; 95% CI, 1.27-5.04) and large uterine height for gestational age (OR, 1.26; CI, 1.04-1.54) had the maximum effects on GTN outcome, respectively. The slope of linear regression of β-hCG was introduced as an independent risk factor, which could be used for clinical decision making based on records of β-hCG titer and subsequent prevention program.

Gestational Trophoblastic Neoplasia After Human Chorionic Gonadotropin Normalization Following Molar Pregnancy: A Systematic Review and Meta-analysis.

To estimate the incidence of gestational trophoblastic neoplasia following complete and partial molar pregnancy after reaching normal human chorionic gonadotropin (hCG) levels to guide evidence-based follow-up recommendations. MEDLINE, EMBASE, Web of Science, POPLINE, Cochrane, and ClinicalTrials.gov were searched from inception to November 2018, using the intersection of "gestational trophoblastic disease," "molar pregnancy," and "human chorionic gonadotropin" themes. Search results were screened to identify cohort studies of molar pregnancy reporting gestational trophoblastic neoplasia development, with at least 6 months of intended normal hCG follow-up. Two reviewers independently identified articles for inclusion. Data were extracted using a standardized form. For meta-analysis, cumulative incidence of gestational trophoblastic neoplasia, with CIs by the Agresti-Coull method, and pooled risk ratios (RRs) comparing complete and partial mole were calculated. Among the 19 eligible studies that reported adequate data for inclusion in the primary meta-analysis, we found low incidence of gestational trophoblastic neoplasia after normal hCG level following both complete mole (64/18,357, 0.35%, 95% CI 0.27-0.45%), and partial mole (5/14,864, 0.03%, 95% CI 0.01-0.08%). There was a significantly higher risk of gestational trophoblastic neoplasia after complete compared with partial molar pregnancy (RR 4.72, 95% CI 1.81-12.3, P=.002). Among gestational trophoblastic neoplasia cases after normal hCG level following complete mole, 89.6% occurred when the time from evacuation to normalization was 56 days or longer, and 60.7% were diagnosed beyond the commonly recommended 6-month surveillance interval. Sensitivity analyses, including those limiting to studies at low risk of bias, did not significantly affect results. We found an overall incidence of gestational trophoblastic neoplasia of 15.7% for complete mole (1,354/8,611, 95% CI 15.0-16.5%) and 3.95% for partial mole (221/5,593, 95% CI 3.47-4.50%). Gestational trophoblastic neoplasia development after normal hCG level following molar pregnancy is rare. Recommendations for frequency and duration of hCG follow-up can be minimized to lessen burden on patients and informed by the type of molar pregnancy and time interval from uterine evacuation to hCG normalization. PROSPERO, CRD42019116414.

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his is the most common type of trophoblastic neoplasm to follow a term pregnancy or a miscarriage, and only a third of TABLE 20-4. International Federation of Gynecology and Obstetrics (FIGO) Staging and Diagnostic Scoring System for Gestational Trophoblastic Neoplasia Age (years) <40 :::40 Antecedent pregnancy Mole Abortion Term <103 largest tumor size (including uterus) <3 cm 3-4 cm :::5 cm Site of metastases Spleen, kidney GI Liver, brain Number of metastases Previous failed chemotherapy drugs :::2 aAdapted by FIGO. blow risk = WHO score of 0 to 6; high risk = WHO score ofs:::7. J-hCG = beta human chorionic gonadotropin; GI = gastrointestinal; GTN = gestational trophoblastic neoplasia. Adapted with permission from FIGO Committee on Gynecologic Oncology: Current FIGO staging for cancer of the vagina, fallopian tube, ovary, and gestational trophoblastic neoplasia, Int J Gynaecol Obstet 2009 Apr;l 05(1 )j3-4. 4-6 7-12 >12 103 to 104 104 to 105 :::105

Gestational trophoblastic disease

Gestational trophoblastic disease (GTD) is a term used for a group of pregnancy-related tumours. These tumours are rare, and they appear when cells in the womb start to proliferate uncontrollably. The cells that form gestational trophoblastic tumours are called trophoblasts and come from tissue that grows to form the placenta during pregnancy. There are several different types of GTD. Hydatidiform moles are benign in most cases, but sometimes may develop into invasive moles, or, in rare cases, into choriocarcinoma, which is likely to spread quickly, but which is very sensitive to chemotherapy, and has a very good prognosis. Gestational trophoblasts are of particular interest to cell biologists because, like cancer, these cells invade tissue (the uterus), but unlike cancer, they sometimes "know" when to stop.

Gestational trophoblastic disease.

To provide standards for the diagnosis and treatment of patients with hydatidiform mole and gestational trophoblastic tumours (GTT). Prognostic factors useful for treatment decisions in GTT are defined with patients classified as low-, medium-, and high-risk groups. Improved mortality and morbidity. Evidence was gathered using Medline for relevant studies and articles from 1980 to 2001 with specific reference to diagnosis, treatment options, and outcomes. The quality of evidence of Recommendations has been described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on the Periodic Health Exam. 1. Suction curettage is the preferred method of evacuation of the hydatidiform mole (III-C). Post-operative surveillance with hCG assays is essential (II-3B). 2. Low-risk patients with both non-metastatic and metastatic disease should be treated with single-agent chemotherapy, either methotrexate or dactinomycin (II-3B). 3. Medium-risk patients should usually be treated with multi-agent chemotherapy, either MAC or EMA (III-C); single-agent chemotherapy may also be used (III-C). 4. High-risk patients should be treated with multi-agent chemotherapy EMA/CO, with selective use of surgery and radiotherapy (II-3B). Salvage chemotherapy with EP/EMA and surgery should be employed in resistant disease (III-C). 5. Placental site trophoblastic tumour that is non-metastatic should be treated with hysterectomy (III-C). Metastatic disease should be treated with chemotherapy, most commonly EMA/CO (III-C).6. Women should be advised to avoid pregnancy until hCG levels have been normal for six months following evacuation of a molar pregnancy and for one year following chemotherapy for gestational trophoblastic tumour. The combined oral contraceptive pill is safe for use by women with GTT (III-C). These guidelines have been reviewed and approved by the Policy and Practice Guidelines Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC), the Gynaecologic Oncologists of Canada (GOC), the Society of Canadian Colposcopists (SCC), and by Executive and Council of the SOGC. The Society of Obstetricians and Gynaecologists of Canada.

Gestational trophoblastic disease

Women who undergo chemotherapy are advised not to conceive for one year after completion of treatment. These women also are likely to have an earlier menopause. It has been estimated by the Royal College of Obstetricians and Gynaecologists that the age at menopause for women who receive single agent chemotherapy is advanced by 1 year, and by 3 years for women who receive multi agent chemotherapy. Follow up Follow up is necessary in all women with gestational trophoblastic disease, because of the possibility of persistent disease, or because of the risk of developing malignant uterine invasion or malignant metastatic disease even after treatment in some women with certain risk factors.

[Gestational trophoblastic disease: the epidemiological analysis of 342 cases].

Between 1987-1996 dates were collected to assess frequency and risk factors for gestational trophoblastic disease in a case-control study of 342 women with trophoblastic tumors and 342 pregnant women admitted for deliveries or spontaneous abortion to University Hospitals in Poznan, Poland. Were analyzed the age of women obstetric history, place of live and repeat appearance of hydatidiform mole. The risk of trophoblastic disease increased with increase in maternal age and above third pregnancy. The risk independent of living in town or in the country. The second and more incident of hydatidiform mole was associated with greater risk of malignant sequele. The study of the pregnancy of gestational trophoblastic disease was led in Great Poland in the support on the date from all pathologic centres in this region and public demographic office. The frequently of hydatidiform mole was between 1987-1996 2.32 per 100,000 women, and 0.76 for 1000 live birth (1 HM for 1315 live birth). The frequently of choriocarcinoma was 0.08 per 100,000 women (and 0.38 per 10,000 live birth (1 CHA per 26,315 live birth).

PP120. Hydatidiform mole as a cause of eclampsia in the first trimester: A case report.

The occurrence of preeclampsia before the 20th week of gestation is rare and it has been associated with hydatidiform molar pregnancy. We describe a case of first trimester eclampsia which occurred in a patient with hydatidiform mole. Case report. A 16-year-old woman came to emergency service for abdominal pain and vaginal bleeding. She had been suffering of vomiting after meals and complaining for abdominal mass for 2months, without consulting her physician. The last reported period was 1month before; the patient told her periods were regular and the only disease she reported was chronic HBV hepatitis. Vital parameters were all normal. Urine pregnancy test resulted always negative. The gynecological exam reported an increased uterus and a little bleeding, so serum bhCG was performed because of the exam findings and resulted 110,5317UI/L. The transvaginal ultrasound showed images consistent with gestational trophoblastic disease. Computed tomography (CT) scan revealed the presence of an uterine mass and three lung nodules, reported as possibly metastatic. A few days later, the patient underwent dilation and curettage (D&C). Second grade hydatiform mole was diagnosed by histology. After D&C, the serum bhCG was 202,511UI/L. The day after, the patient presented bilateral acute blindness, followed by incoming general seizures, concurrent hypertension and tachycardia. Intravenous diazepam, levetiracetam and mannitol controlled the seizures, but the conscious state of the patient remained critical. Temperature reached 40°C, with concurrent leukocytosis. Then, a lumbar puncture was performed but it resulted negative for inflammatory/infective processes. A head CT was performed the same day and showed a posterior reversible encephalopathy syndrome (PRES). Intravenous methylprednisolone was started. Long term therapy with methylprednisolone and levetiracetam was effective and the patient's status improved and stabilized. A subsequent chemotherapy with EMA/CO regimen (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine/oncovine) was performed for six cycles, until serum bhCG resulted negative and the abdomen/pelvis ultrasound, head NMR and chest X-ray resulted normal. Preeclampsia and eclampsia are regarded as common causes of PRES, which is considered to be the result of vasogenic brain edema. Clinical and imaging findings are usually reversible. Early diagnosis and elimination of possible causes are important in order to avoid permanent visual or brain injury. Imaging (especially MRI) should be carried out in eclamptic patients with visual disturbance in order to exclude other causes of blindness. Molar pregnancy is a rare but important cause of eclampsia, and it has always to be considered in case of early manifestations.

Gestational trophoblastic disease

Differential diagnosis These are not GTD, and they are not tumours Exaggerated placental site Placental site nodule Both are composed of intermediate trophoblast, but their morphological features and clinical presentation can differ significantly. Exaggerated placental site is a benign, non cancerous lesion with an increased number of implantation site intermediate trophoblastic cells that infiltrate the endometrium and the underlying myometrium. An exaggerated placental site may occur with normal pregnancy, or after an abortion. No specific treatment or follow up is necessary. Placental site nodules are lesions of chorionic type intermediate trophoblast, usually small. 40 to 50% of placental site nodules are found in the cervix. They almost always are incidental findings after a surgical procedure. No specific treatment or follow up is necessary. Treatment Treatment is always necessary.

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Cormano ], Mackay G, Holschneider C: Gestational trophoblastic disease diagnosis delayed by the hook efect. Obstet GynecoIo126(4):811, 2015 Dantas PRS, Maesd. I, Filho ]R, et al: Does hormonal contraception during molar pregnancy follow-up influence the risk and clinical aggressiveness of gestational trophoblastic neoplasia after controlling for risk factors? Gynecol Oncol September 16, 2017 [Epub ahead of print] Davis MR, Howitt BE, Quade B], et al: Epithelioid trophoblastic tumor: a single institution case series at the New England Trophoblastic Disease Center. Gynecol Oncol 137(3):456,o20o15 Delmis ], Pfeifer 0, Ivanisecvic M, et al: Sudden death from trophoblastic embolism in pregnancy. Euro] Obstet Gynecol Reprod Bioi 92:225, 2000 de Medeiros SF, Norman RJ: Human chorionic gonadotrophin protein core and sugar branches heterogeneity: basic and clinical insights. Hum Reprod Update 15(1):69,o2009

Estrogen and progesterone receptors and telomerase enzyme immunohistochemical detection in gestational trophoblastic tumors.

The purpose of this study is to evaluate the immunohistochemical detection of telomerase enzyme and estrogen receptor (ER) and progesterone receptor (PGR) in gestational trophoblastic neoplasia (GTN) and its clinical significance. Formalin-fixed paraffin blocks for 30 patients (24 with molar pregnancy, 3 with choriocarcinoma, and 3 with placental site trophoblastic tumor) as cases and six products of conception samples from patients with incomplete abortion as controls were included in the study. Immunohistochemical detection of the telomerase catalytic protein and ER and PGR was carried out using streptavidin-biotin-peroxidase method. All control tissues were negative for telomerase and ER expression, while five of six were PGR positive. Significant positive telomerase expression was detected in all gestational trophoblastic tumors (three of six partial moles, 12 of 18 complete moles, three of three choriocarcinomas, and two of three placental site trophoblastic tumors). Nine of 24 molar pregnancies were followed by GTN. Molar pregnancies followed by GTN were associated with higher serum beta-hCG (human chorionic gonadotrophic hormone), larger uterine size for gestational age, negative ER expression, negative PGR expression, and positive telomerase expression. All patients with molar pregnancy with negative telomerase expression (9 of 24) showed spontaneous regression after evacuation. Positive telomerase expression and its immunohistochemical detection are associated with the development of GTN. Negative telomerase expression is highly predictive of postmolar spontaneous regression. Patients with molar pregnancies with negative telomerase expression can be saved the long-term follow-up. ER and PGR expression do not show a significantly different pattern in molar tissues, while negative expression is associated with developing GTN. Cautions on the use of postmolar hormonal contraception may be unjustified.

Pregnancy outcomes of patients who conceived within 1 year after chemotherapy for gestational trophoblastic tumor: a clinical report of 22 patients.

The aim of this study was to explore the risk of pregnancy of patients who conceived within 1 year after successful chemotherapy for gestational trophoblastic tumor (GTT). From 1966 to 1996, 22 patients who conceived within 1 year after chemotherapy were followed up and analyzed retrospectively. Among 22 patients, 9 had term deliveries and 1 had a premature birth, 6 had induced abortion at the patient's request, and 6 had therapeutic abortion because of various indications such as repeated hydatidiform mole (1 case), intrauterine death (1 case), inevitable abortion (1 case), and threatened abortion (3 cases). The fetal loss rate was 27.1% (6/22). The incidence rate of gestational trophoblastic disease (GTD) was 9.1% (2/22). The incidence rate of GTT was 4.5% (1/22). The average interval between completion of chemotherapy and pregnancy was 10.25 months in the group of term pregnancies and 5.86 months in that of fetal loss (P < 0.05), indicating that the longer the interval, the lesser the risk of GTD. The results suggest that contraception for 1 year is necessary in patients with GTT after successful chemotherapy. However, in the case of a patient who conceives within 1 year, it is not necessary to terminate pregnancy, but the pregnancy must be carefully watched.