Salivary gland tumors are rare. The majority of these tumors are benign and about 70% are pleomorphic adenomas (PA). Nasopharynx is an unusual site for the PA tumor. Only six cases are presented in the literature from 1990 to 2011. The diagnosis of this disease is linked to the sum of imaging tests, clinical and histological study of the mass of the above. The radiologic features of noninvasion of surrounding structures give the first clue to the benign lesion. From the review of the literature and our experience is identified as the gold standard in surgical treatment for this condition. Thanks to the endoscopic surgery, we can perform a complete resection of the lesion without damaging adjacent structures. We presented a case of pleomorphic adenoma of nasopharynx with literature review. Salivary gland tumors are rare, with less than 5% of all head and neck neoplasms forming in the salivary gland, commonly in the parotid .The majority of these tumors are benign and about 70% are pleomorphic adenomas (PA). It mainly occurs in the parotid gland and submandibular gland. If the tumor occurs in the minor salivary glands, the most common site is the palate,  but thisThe aim of this paper is to present a case of PA of the nasopharynx. Moreover, we report a literature review that reveals only six cases like the present one.A 51-year-old woman was referred to us with a progressive nasal obstruction associated left aural fullness and pain with a middle conductive hearing loss. The symptoms arose two years before. In home hospital, the patient has been already evaluated with a Magnetic Resonance.These imaging tests showed a mass connected to the lateral wall of nasopharynx space. The lesion does not infiltrate the adjacent tissue and had lobed margins. The radiologist retained that the images were assimilable to pleomorphic adenoma . The cheIn our hospital, on endoscopic examination the lesion appears as a soft whitish mass of 3 × 4 × 3 cm; it took up the entire nasopharynx.We performed a biopsy in order to obtain a definitive histological evaluations. The result confirmed the diagnosis of pleomorphic adenoma with mixture of myoepithelial elements and stromal areas of aspect mixocondoide Figures  and 3.We decided to perform a complete excision of the lesion, by endoscopic transnasal approach. The histological section is represented in After the surgery, we removed the whole lesion and the patient reported an improvement in symptoms and after 6 months the nasopharynx was disease-free.Nasopharynx is an unusual site for the PA tumor. Only six cases like the present one are described in international literature from 1990 to 2011.The diagnosis of PA is simple. But when the PA grows in unusual site like the pharyngeal cavity, it can be mistaken for malignant neoplasms. Furthermore, symptoms such as nasal obstruction, epistaxis, and ear pain are related to nasopharyngeal carcinoma. The PA induced only nasal obstruction. PA should be differentially diagnosed from various other tumors, such as angiofibroma, hamartoma, epidermoid cyst, hemangioma, vascular malformations, nasopharyngeal carcinoma, and nonepithelial tumors; therefore, an incisional biopsy is always a crucial step in the management of these lesions. Although histology is sometimes hard to evaluate, PA is characterized by epithelial tissue mixed with tissues of myxoid, mucoid, or chondroid appearance. Occasionally, pleomorphic adenomas are composed almost entirely of epithelial cells with few or no stromatic tissue. This can lead to misdiagnosis as a carcinoma.The PA is always treated by the surgical exeresis. Although PA of the nasopharynx is a highly curable disease, the surgical approach is not simple and there is the possibility of postoperative complications, such as dysfunctions of the Eustachian tube. For this reason the choice of surgical technique is essential to avoid postoperative complications, but at the same time it is able to dominate the mass in its entirety . VariousRoh et al. treated a similar case with surgical approach using the endoscope. Also Lee et al. used the endoscopic approach with excellent result. Thakur et al. were the only ones to utilize the FNAB for first and erroneous diagnosis of carcinoma. The nasopharynx “malignant tumor” was treated with a radiochemo therapy without any result. Then, an incisional biopsy was performed and was found to be suggestive of a pleomorphic adenoma. A surgical intervention was planned, and tumor was excised by transpalatal approach under general anesthesia.PA of the nasopharynx is a very rare disease. The diagnosis of this disease is linked to the sum of imaging tests, clinical and histological study of the mass of the above. The radiologic features of noninvasion of surrounding structures give the first clue to the benign lesion. The appearance of the lesion, not bleeding and multilobulated, gives us the second clue. Finally, histological examination gives us the final confirmation of the diagnosis.From the review of the literature and our experience is identified as the gold standard in surgical treatment for this condition. Thanks to the endoscopic surgery, we can perform a complete resection of the lesion without damaging adjacent structures. In some articles considering radiotherapy but in all concludes that this last do not have any action on the symptoms and the size of the lesion.


A 79-year-old female was referred to our Gynecologic Department presenting with a pelvic magnetic resonance imaging (MRI), showing an adnexal mass, later confirmed at the pelvic examination. The patient's routine laboratory tests were normal. A sonographic examination was performed with inconclusive results. Although the ultrasonography excluded the presence of vascularization and malignant degeneration, the adnexal localization appeared to be dubious. The laparoscopy and the subsequent histologic examination revealed the presence of a mucocele of the appendix. The following case report focuses the attention on a misdiagnosis of appendiceal mucocele. The misdiagnosis caused no negative impact on the treatment that in this case was adequate and successful. Mucocele of the appendix is a rare pathology with an incidence of approximately 0.2 to 0.3% of all appendicectomy specimens –4. MucocA 79 year-old woman was referred to our department with a magnetic resonance imaging (MRI) requested during her last gynecological examination, when a pelvic mass had been incidentally detected by office ultrasonography. The MRI showed a well capsulated cystic mass on the right ovary with a maximum diameter of 8 cm, homogeneous fluid content, and smooth regular walls without inner vegetations. The patient did not complain of any symptoms and her clinical history was characterized only by episodes of atrial fibrillation. No documentation of previous surgeries was reported. The pelvic examination was negative except for the presence of a palpable mass appreciated at the right vaginal fornix. Laboratory tests were all negative as well as tumor markers . The sonographic examination pointed out the presence, in the right adnexal region, of an oblong, well capsulated, uniloculated mass, characterized by dishomogeneous content, distal shadowing and not vascularized at power Doppler evaluation . The masThe clinical presentation of an appendiceal mucocele is not specific, with inconstant presence of abdominal and pelvic pain, nausea, and fever. Often, appendiceal mucoceles are asymptomatic –9. It maFinally, the preoperative diagnosis is the major component to prevent and to minimize intraoperative and postoperative complications, such as intussusception, bleeding, peritonitis, and pseudomyxoma peritonei , 10, 15.Regarding the treatment, in general, an appendicectomy is advised for mucosal hyperplasia and cystadenoma with intact appendiceal base; cecum resection is indicated for cystadenoma and right hemicolectomy in case of cystadenocarcinoma with or without lymphadenectomy , 24. An In conclusion, currently, the best surgical technique remains controversial and laparoscopic appendicectomy is not contraindicated in mucocele of appendix, if appropriate precautions can be taken intraoperatively to avoid rupture in the peritoneal cavity , 26, 27.In our patient the mucocele was incidentally reported to mimic an adnexal cyst by the MRI, while the ultrasonography failed to determine the origin of the mass. Our diagnostic error was due to three factors: the onion skin sign was not evident, probably because it was not properly investigated due to the fixity of mucocele; calcifications within the mass and the wall were the predominant sonographic marker; the right ovary was not recognized. The surgeon recognized this pathological entity at the time of surgery and performed a simple appendicectomy, without perforation and with no discharge into the peritoneum. No pathologic process at the basis of the appendix was found and the margins of resection were negative.Therefore, according to the literature, no long-term followup of the patient was necessary.


Glomus tumors are benign neoplasms that arise from neuromyoarterial glomus bodies, with clinical manifestations that include acute pain, cold intolerance and tenderness. Glomus tumors may occur anywhere in the skin, soft tissue or gastrointestinal tract, but are most frequently encountered in the nail bed of the hands. The present study reports the case of a 30-year-old female with a history of shoulder pain caused by a cystic neoformation. Following surgery, a microscopic examination revealed nests of small cells of a rounded and regular shape. The tumor cells exhibited positive expression for CD34 and smooth muscle actin. This study supports and confirms the fact that a glomus tumor is a benign neoplasm that may occur in multiple locations. Therefore, the significance of a histological and immunohistochemical approach for a correct characterization of this lesion is required. Glomus tumors are neoplasms that arise from modified smooth muscle cells of the glomus body, which is a specialized form of an arteriovenous anastomosis that plays a significant role in the regulation of skin circulation ,2. GlomuGlomus tumors have been reported to account for 1–6% of all soft-tissue tumors and 1–5% of hand tumors . The tumClinical manifestations include paroxysms of pain, cold sensitivity and point tenderness. In certain patients the pain is accompanied by additional signs of hyperesthesia, muscle atrophy or osteoporosis of the affected area .Grossly, the tumor is a small purple nodule that varies between 2 and 20 mm in diameter, though tumors of >3 cm have been reported . HistoloThe present study reports a case of a glomus tumor of the shoulder and discusses the histological and immunohistochemical features.A 30-year-old female was referred to the Department of Thoracic Surgery  with a 1-year history of shoulder pain and paresthesia of the left arm. Upon physical examination, the range of motion of the left shoulder was normal.Ultrasonography of the supraclavicular area revealed a well-defined hypoechoic oval mass measuring ~3.5 cm. MRI of the shoulder confirmed the presence of a cystic neoformation measuring ~4 cm located between the trapezius and levator scapulae muscles .The patient was treated by a wide excision of the mass with a surgical incision in the neck, laterally to the sternocleidomastoid muscle. The patient did not undergo any further treatment following the excision and did not have any recurrence.Excised specimens were fixed in 10% neutral buffered formaldehyde and embedded in paraffin. Routine hematoxylin and eosin staining was performed on the microscopic section for histopathological examination.A paraffin block was chosen for immunohistochemical study. An immunohistochemical evaluation was performed using the avidin-biotin-peroxidase complex method. Antibodies were purchased from Ventana Medical Systems . The antibodies that were used were mouse monoclonal anti-smooth muscle actin, mouse monoclonal anti-CD34, rabbit monoclonal anti-CD31, polyclonal anti-factor VIII, mouse monoclonal anti-CK-Pan, mouse monoclonal anti-CD68, mouse monoclonal anti-S-100, mouse monoclonal anti-CD99, polyclonal anti-calretinin and mouse monoclonal anti-desmin. All the antibodies were pre-diluted.The analysis of the specimens was performed by two pathologists and the differential diagnosis was widely discussed.The specimens were obtained from a 30-year-old female who underwent an excision of a subcutaneous mass of the supraclavicular area.The gross appearance of the specimen was a grayish fragmented cystic lesion, measuring 4 cm at the maximum. The cut sections revealed firm tissue without hemorrhagic or necrotic areas.A microscopic examination showed multiple nests of typical glomus cells surrounded by fibrous tissue with focal myxoid changes. The glomus cells contained epithelioid elements with moderate amounts of clear to eosinophilic cytoplasm and round nuclei with fine chromatin. These cells were closely associated with small vascular channels and nerves. The cells demonstrated a low proliferative activity (Ki-67 <5%) and a low mitotic rate of <1 mitotic figure (MF)/50 high-power fields (HPFs). The lesion was well-circumscribed and there was no evidence of hemorrhage or necrosis.Immunohistochemical staining was positive for SMA and CD34 and negative for CD31, factor VIII, CK-Pan, CD68, S-100, CD99, calretinin and desmin .A glomus tumor is a hamartoma that develops from a neuromyoarterial glomus body and consists of dilated vascular channels surrounded by proliferating glomus and nerve cells. It accounts for 1–6% of all soft tissue tumors and 1–5% of hand tumors . Glomic Glomus tumors are usually located in the deep dermis of the extremities and in the subungual region of the hands. Other sites are the shoulder , thigh , knee 44 and gaset al. The surgical excision of the lesion resulted in a complete disappearance of the symptoms.In conclusion, glomus tumors of the shoulder are not as uncommon as previously believed. On this basis, in cases of unexplained pain in this area, a glomus tumor should be considered in the differential diagnosis.


Collecting duct carcinoma (CDC) of the kidney is a rare and aggressive malignant tumor arising from the distal collecting tubules which has been shown to have a poor response to several kinds of systemic therapy. We present a case of metastatic CDC that responded favorably to a multiple tyrosine kinase inhibitor, sunitinib, achieving a partial response in both lung and skeletal metastases. To our knowledge, this is the first report showing therapeutic activity of sunitinib against CDC. Considering these findings, it would be worthwhile prospectively investigating the role of multiple tyrosine kinase inhibitors, particularly sunitinib, in the management of metastatic CDC. Collecting duct carcinoma (CDC) of the kidney, also known as Bellini duct carcinoma, is a rare variant of renal cell carcinoma (RCC) arising from the epithelium of the distal collecting ducts; it accounts for 2% of all RCCs . ClinicaA 47-year-old man with a 14.1 cm left renal mass extending into the renal vein and metastases involving the bilateral lungs and retroperitoneal lymph nodes were referred to our institution.Radical left nephrectomy combined with lymphadenectomy was performed. Pathological examination resulted in diagnosis of this case as CDC with tubulopapillary architecture consisting of tumor cells with eosinophilic cytoplasm and high-grade nuclei Figure . In addiBecause CDC is an uncommon and aggressive disease with extremely poor prognosis, accumulated information about CDC is very limited. Therefore, no established therapy for CDC exists except for surgical resection of localized diseases. To date, however, there have been 14 reported cases of metastatic CDC showing response to systemic therapy, consisting 9, 2, 1, and 1 who were treated by gemcitabine plus cisplatin or carboplatin, paclitaxel plus carboplatin, gemcitabine plus doxorubicin, and interferon-a, respectively . ConsideIn the case presented, because of her poor performance status associated with skeletal metastases, it was judged to be difficult to perform intensive systemic chemotherapy. Accordingly, she was treated with sunitinib, which has been regarded as one of the most powerful agents against metastatic RCC , and shoAlthough the precise molecular mechanism involved in the antitumor activity of multiple tyrosine kinase inhibitors against CDC remains largely unknown, these findings suggest that the efficacy of these agents, for example sunitinib and sorafenib, against metastatic CDC needs to be prospectively evaluated.Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.EMT, IE, MFT and YA analyzed, interpreted the patient data regarding its oncological features, and has been involved in drafting the manuscript; HM and HE has given final approval of the version to be published. All authors read and approved the final manuscript.


Pelvic floor hernias pose a diagnostic and a treatment challange. Neurofibromatosis is a rare systemic disease, and urinary tract involvement is rare.Here we report a case of a 54-year-old female with multiple neurofibromatosis who presented with features of obstructed defecation and was found to have a large perineal hernia. At surgery, we found an unusual herniation of a large neuropathic bladder and rectum through a perineal defect. She underwent reduction cystoplasty and repair of the pelvic floor using a prolene mesh. Subsequent histopathological examination confirmed a large neurofibroma infiltrating the urinary bladder.Neurofibromatosis of the bladder is rare it should be considered as a differential diagnosis in patients presenting with symptoms of obstructed defecation. Perineal hernias are rare and to date, about 100 cases have been reported in the literature  and thatA 54 year old female presented with a history of a swelling in her right buttock of 6 years duration. Her main complaint was difficulty in defecation when sitting due to a large lump in the perineum Figure . She alsShe was a diagnosed patient with multiple neurofibromatosis type 1 since the age of 17 years and had undergone excision of neurofibromas adjacent to right knee joint and over the right buttock 7 years back. She did not have a family history of neurofibromatosis. She did not give a past history of hypertension or other comorbidities. On examination, she had multiple neurofibromas all over the body and one plexiform neurofibroma over left knee area. There was a non reducible lump of 25× 20 cm size over the right buttock. It had an expansile cough impulse and was non tender on palpation. Digital rectal examination was normal. Therefore, a clinical diagnosis of a secondary perineal hernia was made.Contrast enhanced computed tomography showed a large poorly enhancing mass in the region of right ischiorectal fossa suggestive of herniation of a large neuropathic bladder Figure  and rectThe patient was planned for a hernia repair by a combined surgery with participation of colorectal, urological and plastic surgical teams. The patient was positioned on Lloyd Davies position and the repair of her hernia was done using an abdominal approach with a lower mid line incision. There was a large hernia sac extending in to right buttock area which contained a large neuropathic urinary bladder Figure . A defecNF-1 is an autosomal dominant disorder characterized by multiple neurofibromas, multiple cutaneous café au lait spots, axillary freckling, optic nerve gliomas and skeletal abnormalities. It is one of the more common genetic disorders with a frequency of 1 in 3000 live births -6. It isImaging plays an important role in the diagnosis, evaluation and follow-up of patients with abdominal manifestations of NF1. Barium studies may demonstrate intraluminal mass lesions. Our patient’s barrium enema was suggestive of a displaced rectum and sigmoid colon with herniation of rectum through the pelvic floor. Anatomically, perineal hernias are classified as anterior or posterior, depending on the relationship to the transverse perineal muscle. The posterior is the less common variety and occurs through a defect in the levator ani muscle or between the levator ani and the coccygeus muscle ,14. Our Eventhough neurofibromatosis of the bladder is rare it should be considered as a differential diagnosis in patients presenting with symptoms of obstructed defecation specially with evidence of von Recklinghausen’s disease. According to the authors’ knowledge, this is the first report of neurofibromatosis involving the urinary bladder presenting as a buttock hernia causing obstructed defecation.Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.All authors contributed to management of the patient and contributed equally to drafting of the manuscript. DNS and DS provided overall supervision and edited the final version of the manuscript. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2482/14/21/prepub


Malignant spermatic cord tumor is rare. Spermatic cord metastasis is less common and the prognosis of these patients is poor. Here we report a case of unilateral spermatic cord metastasis from advanced gastric cancer. A 57-year-old male underwent total gastrectomy due to advanced gastric cancer. Three years later, a painless hard palpable mass in the left inguinal area developed and the pathology revealed a spermatic cord metastasis from stomach cancer. Malignant lesions of the spermatic cord, both primary and metastatic are extremely uncommon  and repoA 57-year-old male underwent total gastrectomy for an advanced gastric cancer (Borrmann type 2). The histology revealed poorly differentiated adenocarcinoma, penetration of the serosa and regional lymph node metastasis. The patient was followed for 3 years with no evidence of recurrence on computed tomography (CT) scans, endoscopy and PET-CT scans. Three years later, heterogeneous enhancement and thickening of the left spermatic cord was revealed on a follow-up CT scan . On physThe spermatic cord is an extremely rare site for distant metastasis from a malignant tumor. In adults, most spermatic cord tumors are malignant and have a sarcomatous origin , 2. A stThe most common primary origin of a spermatic cord metastasis is the gastrointestinal tract, followed by the pancreas, prostate and the kidneys , 4. The Our patient also demonstrated a hard palpable mass on the left inguinal area. In a previous case report, spermatic cord metastasis from lung cancer appeared on the ultrasonogram as a hypoechoic mass in the inguinal canal with an extension into the scrotum and as a solid mass with inner necrosis on CT scan . In our The prognosis for spermatic cord metastasis is poor. In a previous study, the average survival from the time of diagnosis was 9.1 months . The use


We report the case of an adult patient recently diagnosed with cirrhosis. The ultrasound evaluation described a multinodular inhomogeneous liver, requiring a magnetic resonance imaging scan for further characterization. The performed magnetic resonance imaging examination confirmed the diagnosis of cirrhosis associated with portal hypertension and detected a vascular left transdiaphragmatic hernia. Although various types of diaphragmatic hernias have been described - congenital or acquired - to the best of our knowledge, this type of pathology has never been reported. Diaphragmatic hernias appear secondary to structure or insertion abnormalities of the diaphragm and can be divided in two major categories - congenital and acquired hernias. They represent a permanent or temporary displacement of abdominal structures  into the thoracic cavity or a transdiaphragmatic extension of pathological entities, such as a pancreatic pseudocyst and mediastinal or retroperitoneal lipomas .Congenital hernias have a prevalence in the newborn population of one in 3,000  and can In our patient, the herniated structure was an anastomotic vessel connecting the left branch of his portal vein and the venous circulation of the left abdominal wall.We present the case of a 45-year-old white man, with a history of alcohol use , who was recently diagnosed with cirrhosis after an ultrasound examination. An echographic examination was performed prior to his admission to our clinic, which revealed a pseudonodular, inhomogeneous liver with fibrotic changes, an enlarged main portal vein with decreased velocity (7.3 cm/s) and multiple venous collateral circulations trajects . These findings were suggestive of cirrhosis with vascular decompensation. The spleen evaluation showed a normal size (11 cm) and multiple microcalcifications, interpreted as remnants of prior inflammatory lesions. No other pathological findings were reported.In order to exclude the presence of neoplastic lesions in the liver, additional investigations were required and the patient was referred to our clinic for further evaluation.During the clinical examination, the patient was conscious, cooperative, presenting a slightly decreased alveolar murmur in the pulmonary bases without abnormal breath sounds, abdominal discomfort on palpation in the right hypochondrium and a slightly enlarged liver, palpable in the epigastrium. Superficial lymph nodes were non-detectable. Collateral venous circulation was visible on both flanks.3); and normal range values for red blood cells (5.28 × 106/mm3), hemoglobin (13.8 g/dL), hematocrit (49.6 %), mean corpuscular volume (93.9 fL), mean corpuscular hemoglobin (31.8 pg) and red blood cell distribution width (12.5 %), unconjugated bilirubin (0.5 mg/dL), conjugated bilirubin (0.6 mg/dL), plasma total proteins (8.1 g/dL) and albumin (4.65 g/dL). He scored F3 in a FibroTest evaluation, with no inflammatory syndrome  and coagulation tests showed no alteration .A thorough blood work-up revealed the following: normal transaminases levels ; a slight increase in gamma-glutamyltranspeptidase (117 U/L) with alkaline phosphatase in the normal range (73 U/L); mild thrombocytopenia  scan was performed in order to assess the hepatic nodules described on the ultrasound examination, to exclude a possible hepatocarcinoma and to detect other possible associated pathologies.The MRI sequences showed the inhomogeneous structure of the liver, with a pseudonodular aspect, without signal abnormalities suggestive for neoplastic pathology as well as an irregular liver contour and increased dimensions of the left hepatic lobe and caudate segment. His spleen was normal size but with an inhomogeneous structure presenting small granular low signal images on both T1- and T2-weighted sequences, compatible with the microcalcifications described on ultrasound. Multiple collateral vascular trajects with perisplenic, periumbilical and perigastric topography were also observed, representing portosystemic collateral circulation.The interesting finding was an aberrant vein with its origin in the left hepatic portal branch, which follows a horizontal trajectory to the left, compressed between the enlarged left hepatic lobe and the inferior side of the left diaphragm; the vein herniated into the left thoracic cavity, described a loop and returned into the abdominal cavity Figure ; it passThe negative immunological tests corroborated with the imaging investigations  and the elevated level of gamma-glutamyltranspeptidase suggest liver cirrhosis with a possible alcohol use etiology.The manifestations of acquired diaphragmatic hernias are correlated with their size and content; they include circulatory and respiratory depression secondary to decreased function of the diaphragm and to compression of the lungs by the herniated abdominal structures. In the case of small diaphragmatic hernias, the symptoms are absent or mild , often ignored by the patients; the diagnosis is met when the size of the hernia increases and the symptomatology becomes more important or complications such as strangulation or dyspnea occurs.Hernias represent a weakness in the abdominal wall that can evolve into a localized defect, allowing abdominal structures covered with peritoneum to protrude: the protruding abdominal structure  can be observed in Figures In order to establish a positive diagnosis of diaphragmatic hernia, two main elements should be present: a diaphragmatic defect and an abdominal structure that passes through the defect into the thorax. When analyzing the vessel on the contrast enhanced images Figure , we can The relevance of this particular case is related to potential diagnostic problems, therapeutic implications and possible complications that may occur in the natural evolution of the disease, such as strangulation, thrombosis or rupture with secondary hemothorax, which are difficult to treat and diagnose if this diagnosis has not previously been considered.Pleural effusions are very common in patients with cirrhosis, especially in the late stages, and usually they have an insidious, asymptomatic evolution, correlated with the protein serum level. If the liquid quantity increases in a short time, another etiology  must be considered. In this pathological context, if specific pulmonary infectious findings are absent and the patient presents hypovolemic symptomatology, a rupture of the herniated collateral vein must be also considered. Another implication of this finding is related to common therapeutic practices - if a pleural effusion is to be evacuated by puncture in a patient with cirrhosis, the existence of a vascular hernia represents a contraindication due to the possible interception of the aberrant vessel and secondary hemothorax.The presence of a vascular diaphragmatic hernia also extends the differential diagnosis when analyzing a thoracic radiography, in cases of pulmonary opacities situated in the base of the lungs.et al. [D’Amico and Luca  have shoet al.  communicUsually the collateral vessels treated in cases of patients with cirrhosis are the gastro-esophageal varices; our case report adds another collateral vessel to the surgical indication list, in order to avoid possible complications.et al. [The standard evaluation for varices is represented by esogastro-duodenoscopy (EGD), which should be carried out for every patient at the time when cirrhosis is diagnosed. Garcia-Tsao et al.  recommenVascular transdiaphragmatic hernia, although a very rare pathological entity, may complicate the evolution of a cirrhotic patient. Such a possibility must be considered for a proper management of the disease.Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.CT: Computed tomography; EGD: Esogastro-duodenoscopy; EST: Endoscopic sclerotherapy; EVL: Band ligation of esophageal varices; MRI: Magnetic resonance imaging.The authors declare that they have no competing interests.ML was involved in data acquisition, analysis and interpretation, and in drafting the manuscript. DAI was involved in data analysis and in the critical revision of the manuscript. Both authors read and approved the final manuscript.


Neurofibroma is an autosomal dominant disorder which has major criteria such as hyperpigmentation (cafe-au lait spots), cutaneous and subcutaneous tumors and bone deformities. In this report, a case of multifocal intraosseous neurofibroma in a 16-year-old male with right facial asymmetry, multiple unerupted maxillary posterior teeth and a previous history of infratemporal and orbital neurofibroma is presented. The majority of reported cases occurred in the posterior portion of the mandible and a limited number in the maxilla. Cone beam CT (CBCT) was performed for better evaluation of the extension and form of the maxillary and mandibular lesions. This report presents a rare situation of simultaneous peripheral neurofibromatosis (NF) and multifocal intraosseous NF in the mandible, maxilla and orbits and also focuses on advanced imaging findings of bony and soft tissue neurofibroma. Neurofibroma (NF) is an autosomal dominant disorder in 50 percent of cases and in the other fifty percent, there is no negative familial trait. This group has the highest mutation rate among genetic diseases 2]..2].The two major classifications are NF-1, a generalized form, and NF-2, a central form.The majoMore common radiographic findings of the jaw bones are enlargement of the mandibular foramen and the inferior alveolar canal, an elongated coronoid process, a deep sigmoid notch, unerupted teeth and a cystic lesion. Neurofibroma of the orbit as an isolated entity  and alsoMore than 40 cases of solitary neurofibroma have been reported until 2006 . The majThe patient, a 16-year-old male, was referred with right facial asymmetry and multiple unerupted maxillary posterior teeth. There was no history of pain. The palatal enlargement was observed on the right side of the maxilla. The overlying soft tissue on the palatal side of the right posterior portion of the maxilla was soft and fluctuant without gingival ulceration and inflammation. In clinical examination, several cutaneous nodular masses and hyperpigmentations were observed. Periauricular soft tissue swelling on the left side with extension to the posterior portion of the auricle and also external auditory meatus were observed. Hypoglobus and proptosis of the left eye were detected.In the panoramic view, a deep sigmoid notch, an elongated left coronoid process and separated pericoronal radiolucency were found. Impaction of the right maxillary molar teeth and destruction of the overlying bone were also observed .CBCT was carried out for better evaluation of the extension and form of the maxillary and mandibular lesions . Axial vDeformity of the zygomatic bone and lateral bowing and thinning of the ramus were observed. Due to preauricular soft tissue swelling and a previous history of soft tissue mass in the left infratemporal fossa, MRI was performed for re-evaluation of the left infratemporal fossa. In MRI, a huge sized tumor was seen adjacent to the parotid gland which involved the infratemporal fossa .In the evaluation of the patient’s past medical history, we found that he was a known case of intraorbital neurofibroma when he was 3 years old. Multislice CT without contrast enhancement revealed proptosis of the left eye, thick optic nerve, preseptal soft tissue density with swelling of the upper and lower eyelids and bony defect of the greater wing of the sphenoid bone .Incisional biopsy of the maxillary lesion was performed. In the histopathological examination, a neoplastic structure was found in the connective tissue of the gingival mucosa, composed of spindle and ovoid cells in the fairly loose stroma and some of them had wavy nuclei . MethyleIntraosseous neurofibroma is relatively rare in the head and neck, with the most common site being in the mandible. Neurofibroma has been reported infrequently in the maxilla. In this case, involvement of the maxilla accompanying the mandible is the prominent point. The higher occurrence of this lesion in the mandible may be related to the long thick bundle of the inferior alveolar nerve . In addiIn the mandible, neurofibroma is accompanied with fusiform enlargement of the foramen and the inferior canal, a branched mandibular canal, a deep sigmoid notch, a decreased mandibular angle, a deformed condyle, non-eruption of the teeth and a cyst like lesion 11]12][[12][11][[[12][11]In the differential diagnosis of neurofibroma, shwannoma, hemangioma, lymphangioma and rhabdomyosarcoma should be considered. Orbital neurofibroma must be discriminated from optic sheath meningioma, orbital pseudotumor and granulomatous disease .The simultaneous occurrence of neurofibroma and in tratumor bleeding may happen which is the result of vessel hyperplasia and aneurysm 16]..16].Low platelet sensitivity to collagen fibers in cases with neurofibroma is the rational explanation for intratumor hemorrhage and excessive bleeding during surgery 16]17][[17][16][[[17][16]Totally, concurrent involvement of the mandible, maxilla and orbit is not common. In this case, CBCT is required to evaluate the exact extension of the maxillary lesion and the pattern of tooth impaction in the lesion site. As a result of extension of this lesion to the posterior portion of the maxilla, exact evaluation of the pterygomaxillary fissure in order to rule out its involvement is necessary.


Opercular syndrome, also known as Foix-Chavany-Marie syndrome, is a paralysis of the facial, pharyngeal, masticatory, tongue, laryngeal, and brachial muscles. It is a rare cortical form of pseudobulbar palsies caused by vascular insults to bilateral operculum. Its clinical presentations include anarthria, weakness of voluntary muscles involving face, tongue, pharynx, larynx, and masticatory muscles. However, autonomic reflexes and emotional activities of these structures are preserved. In the present case, an 81-year-old male presented with acute onset of anarthria with difficulties in chewing, speaking, and swallowing that was diagnosed with opercular syndrome. Opercular syndrome (OPS) is a rarely seen cortical type of pseudobulbar palsy that is characterized by paralysis of facial, lingual, pharyngeal, and masticatory voluntary muscles with preservation of autonomic, involuntary, and reflexive functions . OPS, faHerein, we report an 81-year-old male presenting with acute onset of aphonia, and facio-labio-glosso-pharyngo-laryngeal paralysis with preservation of involuntary and emotional activities. An 81-year-old right-handed male presented with acute onset of sound volume loss, inability to swallow and speak, inability to move tongue, and difficulties in chewing the foods. The past medical history was remarkable for diabetes mellitus, hypertension, coronary artery disease, and benign prostate hypertrophy. His first cerebral vascular event presenting with right-sided arm and leg weakness was observed about 4 years ago and his weakness was recovered completely. However, he has not used suggested antiplatelet treatment up to now. The family history was unremarkable. In neurological assessment, he was aphonic, but his verbal and reading perception was normal. He was able to answer the questions with signs and writing. The pupillary, corneal reflexes, and extraocular movements were intact. The left nasolabial sulcus disappeared. He was not able to open the mouth, protrude the tongue, show the teeth, whistle, chew, and swallow. The tongue was on the midline and immobile. No tongue atrophy, fibrillation, and deviation were observed. The taste sensation was intact. Palatal, laryngeal, blink, and gag reflexes, spontaneous smiling, and yawning were protected. The upper and lower limbs muscles strengths were 5/5. Deep tendon reflex was normoactive. Babinski response was absent. Extrapyramidal, coordination, and sensory examinations were normal. No vocal cord paralysis was detected on the laryngoscopic examination. The laboratory investigation including liver and kidney function, complete cell count, urinalysis, and erythrocyte sedimentation rate was normal. A transthoracic echocardiogram showed biatrial dilatation, mild calcification of mitral and aortic valves, and mild aortic and mitral valves insufficiency. A doppler ultrasonography of carotid and vertebral arteries was unremarkable. The magnetic resonance imaging (MRI) of brain indicated right frontal opercular acute infarct with 3.3 × 2.6 cm on dimensions  and bilaOPS is characterized by anarthria and paralysis of the facial, pharyngeal, masticatory, tongue, laryngeal, and brachial voluntary muscles. Operculum refers to the brain cortex covering the insula, inferior frontal, pre- and postcentral, supramarginal, angular , and superior temporal gyrus. OPS is particularly originated from the damages that are located in posterior part of the inferior frontal gyrus and inferior part of precentral gyrus . There aThe voluntary muscle controls of the face, tongue, and pharynx are provided by primary motor cortex and pyramidal tract, whereas the spontaneous and emotional controls are provided by thalamus, hypothalamus, and extrapyramidal tract . The selThe etiologic factors of OPS include thrombotic or embolic multiple strokes, head trauma, tumor, developmental perisylvian dysplasia, multiple sclerosis, acute disseminated encephalomyelitis, moyamoya disease, vasculitis, and neurodegenerative disease . IschemiPseudobulbar paralysis in OPS is clinically distinguished from bulbar paralysis, disorders of the cranial nerves and neuromuscular junction  by normal eye movements, preserved or hyperactive brainstem reflexes , the dissociation of automatic and volitional movements of the bulbar muscles with preservation of automatic movements, and the absence of atrophy and fasciculations of the lower motor neuron-innervated muscles .The treatment and prognosis of OPB is related to underlying etiological factors. However, clinical improvement is usually poor. Chewing, swallowing, and speech functions do not usually recover completely. Patients with OPS have a significant risk for aspiration pneumonia. Therefore, during acute treatment and rehabilitation process, speech dysfunction and feeding are two most important issues. In our case, no improvement in speech, swallowing, and chewing functions was observed. He could produce nonsense sounds and open the mouth at the end of the 3rd weeks. Preserving patients from OPS can be possible via preventive treatment of repetitive stroke.


The knowledge of the vascular anatomy of the concerned region is an important prerequisite for planning surgical intervention. The awareness of the existing vascular anomalies enhances the insight regarding that region. We report a patient undergoing preoperative evaluation with CTA finding of Superior Mesenteric Artery (SMA) originating from the celiac artery. This celiac-mesenteric trunk is rare (<1%). A 74-year-old woman was referred by her gastroenterologist with painless jaundice. She presented with several months of decreased appetite and a three week history of light colored stool with dark urine. An endoscopic ultrasound was performed and revealed a hypoechoic, irregular, 3.4 cm mass in the head of the pancreas. The common bile duct and pancreatic duct were obstructed from the mass. No vascular invasion, celiac or peri-celiac lymph nodes were noted. Two biliary stents were placed and no biopsies were taken during the procedure.Prior to considering the patient a candidate for surgery, a high resolution computed tomography (CT) scan was performed with pancreatic protocol in non-contrast, arterial and venous phase to determine resectablity. CT scan was consistent with a double duct sign with markedly dilated pancreatic and common bile duct and intrahepatic biliary dilation secondary to mass on the pancreatic head. An interesting variant in anatomy was also identified, which was important for proper surgical planning. The superior mesenteric artery was found to be originating from the celiac axis. Figure , 2, 3Pancreaticoduodenectomy is utilized selectively in the management of patients with neoplastic lesions of the pancreas and periampullary region. In these patients, the role of CT angiography (CTA) is important in determining tumor respectability and it allows one to evaluate for variant arterial anatomy. Preoperative knowledge of variant anatomy can assist in selection of treatment options and facilitate in surgical dissection and avoid iatrogenic injury.The celiac artery supplies the liver, spleen, pancreas, and some of the stomach and duodenum. The superior mesenteric artery (SMA) supplies the small intestine, ascending colon, and a large portion of the transverse colon. Variation of arterial anatomy is common and occurs in nearly half of the population ).We report a patient undergoing preoperative evaluation with CTA finding of Superior Mesenteric Artery (SMA) originating from the celiac artery. This celiac-mesenteric trunk is rare (<1%), however has been described .In the embryo, the three paired arteries of the trunk originate from the aorta. Posterior arteries are parietal, lateral arteries are urogenital, and anterior arteries are intestinal. In human embryos the primitive intestinal arteries (vitelline arteries) are connected by a Tandler's anterior longitudinal anastomosis . When thIn our patient the CTA also demonstrated a subtotal occlusion of the origin of the celiac axis. There was significantly enlarged inferior mesenteric artery, which is likely due to the retrograde perfusion of SMA and celiac arteries.It is important to understand the vascular anatomy of a region in planning a surgical intervention. When performing a pancreaticoduodenectomy, an awareness of the vasculature is necessary in case vasculature reconstruction needs to be performed because of tumor involvement of the vessels. Knowing the existing vascular anomalies enhances the insight regarding that area and helps to prevent mistakes due to a lack of awareness. Our patient underwent a pancreaticoduodenectomy. There was no vessel involvement found during the case. The patient tolerated the procedure well and was discharged in a timely fashion, without complication.Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.MW-lead author and primary surgeon for the patient. RN-assisted in writing the paper. SV-gathered and edited all the images. AC-assistant surgeon and edited the final paper. All authors read and approved the final manuscript.


Although posture distortion is a common problem in elderly patients, spinal deformity caused by a thymoma has not been previously reported. Thymomas are slowly growing tumors that predominantly cause respiratory symptoms.We report the case of an 83-year-old woman who was admitted with a giant mediastinal mass that had caused progressive spinal distortion and weight loss to our department. The clinical and laboratory investigations that followed revealed one of the largest thymomas ever reported in the medical literature, presenting as a mass lesion placed at the left hemithorax. She underwent complete surgical excision of the tumor via a median sternotomy. Two years after the operation, she showed significant improvement in her posture, no pulmonary discomfort, and a gain of 20 kg; she remains disease free based on radiographic investigations.In this case, a chronic asymmetric load on the spine resulted in an abnormal vertebral curvature deformity that presented as kyphosis. Thymomas are rare neoplasms with a largely indolent growth pattern and various clinical symptoms . The sucAn 83-year-old Caucasian woman was admitted to the Department of Orthopedics with a chief complaint of progressive kyphosis, which had worsened over the previous six months. The patient complained of a progressive dysphagia and had lost approximately 20 kg over the previous six months. Posteroanterior and lateral chest radiographs Figures  and 1b dA physical examination revealed marked prominence of the left hemithorax. This region was dull to percussion and did not move with respiration. The intercostal spaces were bulging, and no breath sounds were heard on the left. The right hemithorax was clear and moved well with respiration. The remainder of the physical examination was unremarkable. Her general condition was good. Physical examination of the heart as well as an electrocardiogram (ECG) revealed no abnormal findings. Routine laboratory tests were within normal limits. Liver and renal function was very good.The presence of a giant tumor was confirmed by computed tomography (CT) Figure   largely depends on complete surgical resection, if possible . If an iAlthough thymomas are responsive to both chemotherapy and radiation, the mainstay of treatment is surgical resection . PatientKyphosis in an adult with no previous history of any spinal curvature deformity should be considered as a possible symptom of an intrathoracic tumor. Imaging is an essential part of the investigation needed prior to surgical excision. CT-guided fine-needle aspiration biopsy is necessary for a definitive diagnosis and patient management. In the case of thymomas, complete surgical resection should be planned. Thymoma recurrence has been reported as late as 32 years after initial surgery . As a reWritten informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.ES analyzed and interpreted the patient's files, wrote the paper, assisted at the operation and looked after the patient postoperatively. TK and PT were the surgeons responsible for the patient, performed the operation and critically revised the manuscript. PK and GKa contributed to the writing. GKo is the supervising professor. All authors read and approved the final manuscript.


Introduction. De novo pleomorphic adenomas in the parapharyngeal space are rare and cause difficulties in its surgical management. We report the largest de novo pleomorphic adenoma arising from the parapharyngeal space and discuss its surgical management. Presentation of Case. A 34-year-old male presented with a giant de novo pleomorphic adenoma arising from the parapharyngeal space, which was initially misdiagnosed as an impacted wisdom tooth. Measuring 8.4 × 6.5 × 3.9 cm in size and weighing 87.3 g, this is the largest primary salivary gland tumour arising de novo from the parapharyngeal space reported in the literature, presenting challenges in its surgical management. Discussion. Parapharyngeal space tumours cause nonspecific symptoms and may be difficult to diagnose, which can allow the tumours to become very large and cause obstructive and compressive symptoms in an anatomically difficult area. A combined trans-cervical and trans-oral approach can be used to safely perform an en bloc resection. Conclusion. We report the diagnosis and surgical management of the largest pleomorphic adenoma arising de novo from the parapharyngeal space reported in the literature. The parapharyngeal space is found anterior to the cervical column, posterior to the infratemporal fossa, and laterally to the nasopharynx. It forms an inverted pyramid with the skull base superiorly and the apex at the joint between the posterior belly of the digastric muscle and the greater cornu of the hyoid bone .de novo in the parapharyngeal space are very rare and present challenges in achieving en bloc excision without spilling the contents of the tumour [de novo from the parapharyngeal space and discuss its management.Tumours arising e tumour . We descA 34-year-old male presented to our multidisciplinary head and neck clinic with a 3-year history of recurrent discomfort in his right retromolar trigone. These episodes were initially diagnosed by a dentist as an impacted wisdom tooth with subclinical infection and were treated with oral antibiotics with minor improvement in symptoms. One year prior to presentation, the patient noticed a prominence on the right side of his oropharynx but this was not reviewed by a medical professional.Over the last 2 years, the patient had worsening obstructive symptoms, including snoring, episodes of sleep apnoea, nasal speech, and a sensation of decreased hearing in his right ear. The patient also reported 7 kg of weight loss and lethargy in the preceding 3 months before presentation. There was no relevant past medical or family history and the patient took no regular medications. He was a lifelong nonsmoker with occasional consumption of alcohol.Physical examination revealed a submucosal mass arising from the lateral wall of the right oropharynx, displacing the soft palate and the right anterior tonsillar pillar anteromedially . The masMagnetic resonance imaging (MRI) demonstrated a well demarcated but lobulated homogenous mass with little contrast enhancement, separate from the deep lobe of the parotid . There wen bloc  methods to surgically access and perform an extracapsular dissection of parapharyngeal space tumours , 4. In len bloc, maintaining oncological planes and minimizing the risk of spillage of the contents of the tumour.In this case, a combined trans-cervical and trans-oral approach was used to dissect out the tumour, which was delivered through the cervical incision. This is an effective way of excising giant parapharyngeal space tumours de novo from the parapharyngeal space. The combined trans-cervical and trans-oral surgical approach was successfully used in this anatomically difficult area and may be considered for excision of such giant tumours in the parapharyngeal space.In summary, we report a giant pleomorphic adenoma arising


A 68-year-old female presented with inflammatory lumbalgia and cruralgia. Physical examination revealed a lumbar stiffness without neurological deficit. Secondarily, paraplegia and urinary retention appeared. Magnetic resonance imaging showed a vertebral compaction of L3 vertebra with medullar compression. Emergent surgery revealed an epidural tumor involving largely the L3 vertebral body. Histology found schwannoma with positive protein S100 on the immunohistochemical study. Metastasis screening revealed bilateral nodular lesions of the lungs and a trochanter high scintigraphic signal. It was a malignant schwannoma. The patient underwent radiotherapy in addition to the total tumor resection. Schwannomas are nerve tumors that might be benign or transformed to a malignant peripheral nerve sheath tumor (MPNST). Schwannomas present almost third of primary spinal tumors. Intraosseous localization is rare, reported as case reports. We report a new case of malignant spinal intraosseous schwannoma.A 68-year-old female, with no previous medical problems, presented with inflammatory lumbalgia and cruralgia which are progressively increasing since three months. She had no genital or sphincter dysfunction. Physical examination revealed a lumbar stiffness without neurological deficit. During hospitalization, paraplegia and urinary retention appeared. Magnetic resonance imaging showed a vertebral compaction of L3 vertebra with decline of the posterior vertebral wall and compression of the dural sac Figures , and 3. Spinal schwannomas account for 30% of primitive spinal tumors . They arSchwannomas seem to appear between the third and the sixth decades . The meaSymptoms of spinal schwannoma are various including lumbar and root pain, motor deficit of variable degree, and genitosphincter dysfunction. Magnetic resonance is an excellent imaging exam in schwannomas. It usually finds high signs on T2 weighted images and shows possible osseous destructions and extraosseous progression , 13. IntIntraosseous schwannoma is a rare curable nerve tumor. Magnetic resonance is the best indicated imaging. The diagnosis confirmation is histological and immunohistochemical. Other localizations or familiar cases must be searched in order to diagnosis schwannomatosis. Total surgical removal is the treatment. The outcome is good in benign forms but malignant forms have low outcome despite surgery and chemotherapy or radiotherapy.


A 25-year-old male was referred to the Radiology Department with new onset of right upper quadrant and epigastric abdominal pain. He had no past medical or surgical history. Physical exam was unremarkable. The patient underwent computed tomography (CT), fluoroscopic upper gastrointestinal (GI) evaluation, endoscopic ultrasound (EUS), and positron emission tomography (PET) evaluation, revealing the presence of a heterogeneous esophageal mass. In light of imaging findings and clinical workup, the patient was ultimately referred for thorascopic surgery. Surgical findings and histology confirmed the diagnosis of esophageal heterotopic pancreas. Heterotopic pancreas is defined as histologically proven normal pancreatic tissue that lacks anatomic, vascular, and ductal continuity with the orthotopic pancreas. Other common names for this entity include ectopic, aberrant, or accessory pancreas . HeterotA 25-year-old male with no significant past medical or surgical history presented with 2 weeks of moderate to severe right upper quadrant and epigastric abdominal pain. His pain was occasionally associated with heavy exercise and meals. Physical exam and clinical laboratory findings were unremarkable.Initial radiographic evaluation demonstrated abnormal frontal and lateral chest images Figures . FollowiGiven the vague right upper quadrant and epigastric symptoms, a right upper quadrant ultrasound (US) was performed. However, the exam was noncontributory. Continued suspicion for a mass prompted further evaluation with computed tomography (CT) Figures . A 4.4 ×An upper gastrointestinal (UGI) double contrast fluoroscopic exam was performed to further characterize the subepithelial mass and to investigate the apparent fistulas. Upright frontal and left anterior oblique low-dose fluoroscopic images demonstrated classic UGI findings of a subepithelial mass: a smooth-surfaced, hemispheric lesion forming obtuse angles with the adjacent luminal contour  Figures. InteresDespite extensive imaging and numerous biopsy attempts, the differential diagnosis remained broad and included both benign and malignant processes. Considering the possibility of malignancy, a positron emission tomography (PET) scan was performed utilizing fluorine-18 fluorodeoxyglucose (F-18 FDG). The mass demonstrated increased FDG avidity, with a standardized uptake value average of 6.0 and maximally of 10.0 Figures . The remIn the absence of a tissue diagnosis or diagnostic imaging, optimal management remained unclear. In order to obtain definitive tissue diagnosis, left-sided video-assisted thoracic surgery was performed which revealed a soft, mobile, cyst-like structure upon direct visualization. Pathologic analysis demonstrated presence of pancreatic heterotopia with overlying unremarkable squamoglandular mucosa Figures . The patManagement of this entity has varied from observation to radical surgery, such as Ivor-Lewis esophagectomy. As evidenced by our case, preoperative diagnosis is often difficult and is usually determined once the specimen is removed in its entirety. After weighing the severity of symptoms and the possibility for malignant potential, surgical resection of heterotopic pancreas is often the preferred management . While tThe patient had an uneventful surgical recovery. A swallow study performed on postoperative day three showed no evidence of contrast extravasation (images not shown). He had an uneventful hospital course, and the patient returned for two-month clinic follow-up without surgical complications and self-reported resolution of the epigastric pain.Heterotopic pancreas, in any location, is found in 0.6% to 13.6% of autopsies and 0.2% to 0.5% of abdominal operations [Our case demonstrated a classic presentation of subepithelial mass on UGI fluoroscopic evaluation. Subepithelial masses, previously termed “submucosal” masses, are defined as masses covered with normal appearing submucosa. “Subepithelial” is the preferred term because these masses can arise from any layer of the gastrointestinal (GI) wall . In addition, other intra-abdominal structures and masses  can produce extrinsic impressions visible on imaging . The PETAlthough typically asymptomatic, esophageal heterotopic pancreas has been associated with epigastric pain, dysphagia, obstruction, and upper gastrointestinal bleeding . As a noThe normal pancreas arises from fusion of the ventral and dorsal outpouchings of the foregut . Althoug


A 71 years old Italian man had type 3 gastric cancer of the greater curvature. Total gastrectomy with splenectomy and D2 lymph node dissection were performed. After discharge chemotherapy ELF regimen was administred for 6 months. After 16 months from the operation a local recurrence was discovered by CT scan. Surgical en-bloc resection was performed removing pancreatic tail, splenic colic flexure and a portion of left diaphragm. Histological examination confirmed local recurrence of gastric adenocarcinoma infiltrating pancreas, colon and diaphragm with lymph node metastasis. In Western countries gastric cancer still represents a disabling disease: unfortunately late diagnosis is common and loco-regional recurrence rate after surgery alone is high especially in patients with advanced stage disease at the time of diagnosis . Local recurrence may occur also in those patient which had R0 resection: management of these cases is extremely difficult for the involvement of regional structures resulting in poor surgical chances. Therefore multidisciplinary therapeutic approach is necessary to achieve better results. The aim of this report is to refer about an unusual presentation of local relapse in an old patient submitted to a total gastrectomy in which surgical approach permitted a good control of the disease.th post-operative day after X-ray control with hydro-soluble contrast. Hospital stay was prolonged by left basal pneumonia associated to pleural effusion; discharge occurred after one month. Histological examination demonstrated an adenocarcinoma  extended to all layers of gastric wall and metastasis to greater curvature lymph-nodes (station 4 of JGCA) [th post-operative day; after resolution of this complication patient was discharged. Histological examination resulted in poor differentiated gastric carcinoma infiltrating colic wall and pancreas with metastasis in one of nine peri-colic lymph-nodes examinated.Male, 71 years old; on July 27, 2004, he was submitted to total gastrectomy with splenectomy and lymph-node dissection (D2) for an ulcerated adenocarcinoma of the greater curvature of the upper third of the stomach. Roux-en-Y stapled esofago-jejunoanastomosis was performed and oral food intake resumed in 7Loco-regional recurrence and distant metastases are common events after surgery for gastric adenocarcinoma. Abdominal extraluminal recurrence of gastric cancer is a disarmimg condition because of poor therapeutic chances. Generally it is a matter of peritoneal carcinosis or multiple liver metastasis; in these cases surgery has little opportunities to be useful. Literature reports rare cases of single localization in abdominal cavity that may be resected. Menzel  reportedOur case is unusual in its presentation: an isolated bulk involving neighbouring organs suitable for surgical resection. The result after the en-bloc resection is very amazing. Considering the primary surgical specimen we may suppose the modalities of the local relapse: the spleen and local lymph-nodes were radically removed, but in spite of that, local contamination during the first operation remains the most reasonable interpretation. All risk factors suggested by Yoo and Colleagues  were preThe authors declare that they have no competing interests.BM, CM and RL have studied the patient and performed the surgical operation. FC performed the endoscopic preoperative study of the patient and contributed to the literature review. CT contributed to the discussion of medico-legal issues and to the writing of the paper. BA and CM gave their contribution to the analysis of the data and contributed to the writing of the paper. All the authors read and approved the final manuscript.


Echinococcus granulosus. It has serious impact on health and economy especially in countries where it is endemic. It occurs frequently in liver and lung. The disease is chronic and cyst can localize in different organs. A hydatid cyst occurrence in the head and neck is extremely rare. To know the distribution of disease can help in its control and prevention. We report a case of primary cervical hydatid cyst in 20 year old female. A high index of suspicion is required to diagnose hydatid cyst in rare locations like this. Hydatid cyst should be considered in differential diagnosis of benign swellings of head and neck region, so that it can be managed during surgery to prevent acute anaphylaxis.Hydatid disease, a parasitic infection is caused by http://www.diagnosticpathology.diagnomx.eu/vs/4915595218376646The virtual slides’ for this article can be found here:  Ecchinococcus granulosus[Taenia echinococcus requires two distinct mammalian hosts. Dogs, wolves and foxes are the definitive host. Intermediate hosts are herbivores like sheep, cattle, horses and rarely human [Hydatid disease is caused by the cestode parasite (tapeworm) ranulosus. It is franulosus. Life cyly human . Humans ly human . The eggly human -8. Involly human ,10. TherA 20-year-old female came to neurosurgery department of northwest general hospital with one year history of a slowly growing occipitocervical mass that was painless and without fever. Clinical examination revealed 7x7x4cm round swelling to be cystic and fluctuant with no local inflammatory response or spasm of the cervical muscles. Physical and neurological examinations revealed no abnormalities. Magnetic resonance imaging (MRI) showed a cyst in the muscular plane of upper posterior cervical region, exhibiting low signal on T1W1 with high signal on T2W1 measuring 6.5x6.1 x3.1 cm in size (volume 64 ml)  of the abdomen with computed tomography (CT) scan of the thorax was done, to know status of other visceral organs but it did not reveal any other organ involvement by the disease process. Patient was given medical treatment with albendazole (800 mg/d) for six weeks.The outcome was good, with no recurrence after 3months.Hydatid cyst at unusual sites have been reported around the world including the spleen, kidney, heart, bones, muscles and cranium, but soft tissue hydatid disease represents less than 3% of all hydatid disease . HydatidHydatid disease may affect humans especially in endemic areas where sheep, dogs and man live in close contact such as Mediterranean countries, the Middle East, South America, New Zealand, Australia, and Southeast Asia and many parts of china ,12,13. UPatients having echinococcosis in any part of the body must undergo thorough systemic investigation as most of the larvae become adult cysts in liver and lung. Multiorgan involvement is seen in 20% to 30% of the cases with involvement of liver in all cases . Our patEchinococcus infection mainly depends on the clinical history of the patient, diagnostic radiological findings and serologic tests. ELISA, Casoni skin tests, latex agglutination, immunoelectrophoresis and direct hemagglutination are serological methods, used for the diagnosis of hydatid disease. Sensitivity of serology is high (80-100%) for liver cysts, but low for lung (50-56%) and other organs (25-56%). Importance of these tests lies mainly in the follow up of treated patients. An increase in titer indicates recurrence of disease and a decrease in titer indicates resolution [In non endemic areas because of clinician’s lack of experience and rarity of the disease, it is at times difficult to diagnose a hydatid cyst located in the head and neck region. The diagnosis of solution ,14,17. Isolution .No serological test was done in our case because hydatid cyst was not in the clinical differentials. MRI done was not able to do exact characterization and the report was suggestive of benign cyst. The differential diagnosis therefore includes branchial cleft cyst, bronchogenic, thymic, parathyroid, thoracic duct, and foregut-derived  cysts, pseudocysts or benign tumor that is congenital and acquired cystic lesions of the neck .For the evaluation of mass lesions in the cervical region, fine-needle aspiration cytology (FNAC) is beneficial however due to possibility of an anaphylactic reaction, dissemination of disease and recurrence as result of spillage of cyst contents, it is not recommended in the routine evaluation of suspected hydatid cysts ,20,21. FSurgical removal is the most effective treatment of hydatid cyst ,20. SurgThe diagnosis of hydatid cyst is confirmed by histology . HistopaOur case also demonstrates histopathologically, scolices, an acellular, thick, lamellar cyst wall. The surrounding host reaction, which is composed of the inflammatory fibrous tissue, forms a dense pseudocapsule around the cyst confirms the diagnosis.The case is a reminder that although rare in head and neck, clinicians has to bear in mind Hydatid cyst in the differential diagnosis of cervical masses especially in countries where echinococcus infestation is endemic. Imaging techniques, though sensitive sometimes cannot pin-point the exact etiology of cystic lesion. During surgical removal of cysts in which no definite etiology has been made preoperatively, great care must be taken to avoid spilling of the cystic contents.Written informed consent was obtained from the patient of this case report and accompanying images. A copy of the written consent is available for review by the Editor –In-Chief of this journal.The authors declare that they have no competing interests.NS and WS participate by conceiving the idea and write the manuscript.TK and ZK performed surgical removal. TM performs radiological interpretation. NS, WS and SY do the pathological exploration. All authors read and approved the final manuscript.


Inguinal hernia repair is commonly performed operation in surgical practice. Thirty-five years old female patient was operated with the diagnosis of inguinal hernia. The inguinal defect was misdiagnosed as femoral vein aneurysm in surgical exploration. The postoperative diagnostic imaging revealed that the inguinal defect had been confused as femoral vein aneurysm due to intra-abdominal hemorrhogical fluid after an ovarian cyst rupture. Inguinal hernia repair is one of the most commonly performed operation in surgical practice. Sometimes, challenging cases may be encountered. An inguinal hernia can mimic many pathologies and become a surgical dilemma, even for the skilled surgeon . The corWe reported a patient who had been explorated with the diagnosis of inguinal hernia. The defect was diagnosed as femoral vein aneurysm in surgical exploration. The postoperative diagnostic imaging revealed that the inguinal defect had been confused as femoral vein aneurysm due to intra-abdominal hemorrhogical fluid after an ovarian cyst rupture. We concluded that an inguinal mass can be a diagnostic dilemma with treatment problems.Thirty-five years old female patient presented with pain and swelling in her left inguinal region. She was very thin in appreance. On physical examination, an inguinal mass, bulging with coughing about 3 × 4 cm in diameter was palpated. She had been operated for left ovarian cyst rupture about 8 years ago. She was diagnosed as inguinal hernia and prepared for elective inguinal hernia repair. The routine preoperative laboratory tests were within normal limits.The inguinal canal was explorated in operation. A lump, bluish-purple in color, about 3 × 4 cm in diameter was detected Figure . It was We performed pelvic ultrasonography (USG) and pelvic Magnetic Resonance Imaging (MRI) postoperatively. Two ovarian cysts about 2.5 × 3.5 cm and 3 × 2.5 cm in diameter were detected in left ovary. There was also free hemorrhogic fluid in lower abdominal quadrants (Figure Many surgical pathologies may present as inguinal swelling such as hernia, lymphadenopathy, varices, and endometriosis ,3 SometiA venous aneurysm is usually defined as a venous dilation which comminicates with a main venous structure by a channel. It may cause serious complications such as deep vein thrombosis and pulmonary emboli . Venous The postoperative diagnostic evaluation was performed. The arterial and venous system was imaged with MRI angiography and color doppler ultrasonography. There were no aneurysm in both femoral artery or vein. The only detected pathology was ovarian cysts with intra-abdominal hemorrhogic fluid in pelvic MRI. Marcucci G recommended doppler USG for venous aneurysms in inguinal region and lower extremities . The bulIt is also important to conclude that although it is very rare, an inguinal defect with an intra abdominal bleeding can mimic a vascular lesion like venous aneurysm. The definitive diagnosis of inguinal mass is mandatory for proper treatment. Radiological evaluation of inguinal mass before surgery can gain clinical importance.The authors declare that they have no competing interests.BK, OB, NE, KM were involved in the direct care of the patient. In addition, BK was responsible for drafting the manuscript and OB, NE and KM helped to draft the manuscript. All authors have read and approved the final manuscript.Written informed consent was obtained from the patients for publication of this case report and accompanying images. A copy of the written consents is available for review by the Editor-in-Chief of this journal.


Here, we report a new case of botryoid Wilms’ tumor, a 4-year-old boy, who was referred to us with a chief complaint of dysuria and gross hematuria. The computed tomography and radical nephroureterectomy showed that a botryoid sarcoma-like appearance occupied the right renal pelvis and extended into the bladder. Histologic examination further confirmed this case was a mixed type of Wilms’ tumor. In a word, we demonstrated a rare case of botryoid Wilms’ tumor, which extended from the renal pelvis into the ureter and bladder, then some degenerative and necrotic tissue with calcification discharged from urethra. Postoperative adjuvant chemotherapy was executed. At 24-month follow-up, there was no evidence of recurrence. Wilms’ tumor is the most common renal neoplasm in children. Wilms’ tumor usually originates from the renal parenchyma and expands into the surrounding tissue. Botryoid Wilms’ tumor is a great rarity. The differential diagnosis might be challenging; it may depend on the gender, regional difference, and environmental exposure of the patient. Based on the case of a 4-year-old boy, we discuss the pathogenesis, diagnosis,treatment of this rare entity, and present a review of the still scarce published literature on the subject.+ 143 mmol/L, K + 5 mmol/L, ALT 6 u/L, AST 46 u/L, Cr 62.8 umol/L, BUN 9.1 mmol/L). An ultrasonography examination revealed that the right kidney, right ureter, and bladder were filled with heterogeneous-hypoechoic appearance, which indicated that the tumor had occupied right renal pelvis, ureter, and extended into the bladder. There was also left hydronephrosis and ureter dilated according to the ultrasonography examination. Abdominal computed tomography (CT) scan examination showed a right enlarged inhomogeneous renal mass  count was 11,770/mm3  and C-reactive protein level was 6.0 mg/dL. His hemoglobin level was 11.7 mg/dL . Urinalysis results showed numerous red blood cells per high-power field and white blood cells were negative. Renal and hepatic function, electrolytes examinations were normal .In this paper, we presented our experience of diagnosis and treatment in Wilms’ tumor based on a special case in our hospital. In our opinion, the treatment and prognosis of botryoid Wilms’ tumor should be no different from ordinary Wilms’ tumor of similar stage and grade. The patients should receive chemotherapy referring to the regimen of the National Wilms’ Tumor Study Group 5 (NWTS-5). Whereafter, we summarized that gender, regional difference, and environmental factor may be important pathogenic elements of botryoid Wilms’ tumor by reviewing literatures.Written informed consent was obtained from the patient for publication of this case report and the accompanying images. Copies of the written consent are available for review upon request.The authors declare that there is no conflict of interest referring to this article.GX and JH wrote the initial draft. YW and MX performed the surgery. YX performed the pathological examination. All authors read and approved the final manuscript.


An unusual case of cutaneous angiosarcoma clinically mimicking eczema is described. A 98-year-old Caucasian male presented with a 6-month history of a flesh-colored, subcutaneous nodule on his left forehead with contralateral facial erythema and scaling that had been previously diagnosed as eczema. Despite treatments with topical steroids and moisturizers, the condition did not resolve. At our clinic, excisional biopsy of the forehead lesion and scouting biopsies from the contralateral cheek were performed which revealed cutaneous angiosarcoma. The described case illustrates that dermatitis-like features should be considered as a rare clinical manifestation of cutaneous angiosarcoma. It also demonstrates that these lesions may respond well to radiotherapy as a single modality. Angiosarcoma is a highly invasive tumor of vascular endothelial origin with poor prognosis and high rates of recurrences; therefore, early detection is essential to its treatment. The following case is reported because of the unusual clinical presentation of the malignant tumor in an elderly patient.In early 2012, a 98-year-old robust Caucasian male presented to our clinic with a 6-month history of an enlarging flesh-colored nodule on his forehead. Following the development of this lesion, mildly pruritic red, scaly patches appeared on the right side of his face. A clinical diagnosis of eczema was rendered by an outside physician. For his presumed dermatitis, a course of therapy including topical hydrocortisone and moisturizers was prescribed. While he complied with the outlined regimen, his symptoms did not improve.On clinical examination, the patient was found to have a flesh-colored subcutaneous nodule measuring 1.5 × 0.9 cm in diameter on his left forehead and poorly demarcated red, scaly patches which were most prominent on the right contralateral cheek . An exciBecause of the pervasive nature of this tumor, two scouting biopsies were taken from the right cheek, which were also consistent with angiosarcoma . ResultsGiven the extensive involvement of the tumor in the scalp and face, complete resection was not feasible, and the patient was referred for evaluation by oncology and radiation oncology. The oncologist did not recommend administration of systemic therapy due to the patient's history of resected renal cell carcinoma, chronic renal failure with baseline creatinine >2 mg/dL, and cardiovascular disease significant for placement of multiple stents. After this multidisciplinary review, radiotherapy was recommended to treat the facial and scalp lesions. While the patient was waiting to begin radiation, one treatment of modified laser photodynamic therapy was administered but did not show any significant effect.Enterobacter cloacae on the left forehead, which was resolved with topical garamycin  , 3. In mWhile angiosarcoma may occur virtually anywhere in the body, it commonly presents on the head and neck. Retrospective analysis of a series of 47 patients with CA without lymphedema revealed that lesions most commonly presented on the scalp (49%) followed by the cheek (19%) . AltogetIn the clinical setting, the appearance of CA can be variable. Typical manifestations of CA have been described as raised purplish-red papules , rosaceaUnder the microscope, the most common histological patterns include atypical and pleomorphic  endothelial cells exhibiting a diffuse epithelioid or spindle cell proliferation , 6, 10. Prognosis of CA is poor with a reported 5-year survival rate ranging from 12 to 34% . DependiWhile the prognosis of patients with metastatic CA is significantly worse, the influence of other prognostic factors such as histological grade and size of the tumor is less clear. In one multivariate analysis, high mitotic counts were associated with worse outcomes . In otheGiven the rarity of angiosarcoma, the optimal treatment has yet to be delineated. Current guidelines are mainly based on retrospective data. Single therapeutic modality  is frequently employed; however, the high frequency of local recurrence has been disappointing –14, 21. Although the combination of surgery and radiotherapy has been effective in local control of CA, patients are still at risk for the development of distant metastases , 5. ThisFor unresectable and regionally metastatic tumors, radiotherapy is a rational therapeutic approach due to the wide regional spread that can be treated while sparing the underlying tissue. Radiotherapy appears to improve local control and possibly overall survival based on retrospective series , 14, 23.Due to the invasive nature of CA, another therapeutic option is chemotherapy. Doxorubicin-based chemotherapy remains the treatment of choice in metastatic soft tissue sarcomas. However, it is becoming clear that histologic subtypes differ in their susceptibility to chemotherapy and that treatment strategies should therefore be tailored according to histologic subtypes. Angiosarcomas appear to be particularly responsive to taxanes , 28, likRecently, photodynamic therapy (PDT) has been suggested as an alternative modality for the treatment of CA. The photosensitizer (5-amino levulinic acid) used in this therapy becomes activated when photoirradiated by the proper wavelength. This technology has been shown to be effective for the control of primary CA tumors and the spontaneous remission of untreated metastases . In the Cutaneous angiosarcoma is a very aggressive tumor with poor prognosis and high rates of recurrences; therefore, early detection is essential to its treatment . Optimal


Cardiac myxoma is the most common primary cardiac tumour, but infected cardiac myxoma is relatively rare. Infected cardiac myxoma is very fragile, and has a potential to lead to catastrophic disorder with systemic bacteremia, systemic mycotic embolism, and disseminated intravascular coagulation (DIC).We present here the successful surgical treatment of a case of infected left atrial myxoma with septic shock, DIC and cerebral infarction without hemorrahage. Collective review of 58 reported cases with infected cardiac myxoma revealed that surgical treatment for it were still challenging and its result was poor. Until date, only one successful surgical treatment for a case complicated by DIC and cerebral infarctions has been reported, and our report describes second such case of successful resection. Even though this report is limited to a case, only aggressive and prompt surgical intervention could relieve the intractable conditions in such a patient with extremely high risk. Cardiac myxoma is the most common primary cardiac tumour, but infected cardiac myxoma is relatively rare. To the best of our knowledge, 57 previous cases of infected cardiac myxoma have been reported in the English literature -6. InfecA 52-year-old man had fever and was diagnosed with an influenza-B virus infection two weeks before admission to our hospital. Despite receiving treatment for the influenza virus, he did not recover and his temperature was elevated at 40°C. A blood culture was positive for gram-positive coccus, and echocardiography showed a large left atrial tumour, which was considered to be atrial myxoma with mobile vegetation. He was referred to our hospital for an emergent operation.3 and a C-reactive protein level of 30.0 mg/dl. His platelet count was only 1.0 × 104/mm3 and D-dimer was 12.72 μg/ml, which indicated severe DIC. Echocardiography showed a large mass (60 × 35 mm in diameter) with a stem attached to the septum of the atrial wall, which prolapsed into the left ventricle during the diastolic phase with trivial mitral regurgitation  showed multiple small infarctions but fortunately no haemorrhage was detected. Laboratory data revealed a white blood cell count of 13000/mmAn urgent operation was performed using tepid hypothermic cardiopulmonary bypass (CPB) and the usual dose of systemic heparinization. The tumor was completely excised with the attached atrial septum via a trans-septal approach. A small amount of vegetation was observed in the posterior mitral chordae, which was carefully excised without injuring the mitral structure. The gross pathological findings were a very fragile myxoid tumor with the red thrombus Figure . The plaStaphylococcus aureus. He was still in septic septic shock soon after the operation, but after intravenous immunogloburin and intravenous antibiotic therapy with ampicillin, his general condition was getting better and was extubated at the second postoperative day. The antibiotic therapy with ampicillin was totally administered for six weeks. Histological examination showed that the mass was an infected atrial myxoma, and gram staining of the infected portion revealed the presence of gram-positive coccal bacteria  than those reported from uninfected myxoma (33% of cases) or uncomplicated endocarditis (40% of cases) . In our S. aureus. Five cases combined with DIC have been reported, and all five cases were infected by S. aureus [Including our case, 47 of 58 cases (81.0%) were caused by gram-positive cocci, and 14 of them were caused by . aureus . DIC cauOur case, which presented with both a bacterial cerebral infarction and DIC, is the second successful case reported. Even though this report is limited to a case, only aggressive and prompt surgical intervention could relieve the intractable conditions in such a patient with extremely high risk.In infected cardiac myxoma patients with severe complications, only aggressive and prompt surgical treatment have to be performed for salvage of these patients.The authors confirm that written consent has been obtained from patient in order to publish photographs and relevant clinical information included in the submitted manuscript.The authors declare that they have no competing interests.DY is responsible for acquisition of data and writing the original manuscript. TT, TI and TH are responsible for conception and design as well as critical revision of the manuscript. All authors approved the final version submitted.


The authors report a clinical case of a primary sternal chondrosarcoma, presented as a mass in the anterior mediastinum. The patient was treated with subtotal sternectomy and sternal transplantation followed by radiotherapy. Twelve months after surgery, the patient is in good clinical condition, without any sign of tumor relapse and with normal respiratory mechanics.Primary malignant tumors of the sternum are uncommon and a presentation mimicking thymoma is rare and unreported. The stermal replacement with a cryopreserved allograft sternum is an innovative technique that overcomes the problems related to the prosthetic biocompatibility or to the bone autograft. Primary malignant tumors of the chest wall are uncommon; nevertheless, chondrosarcoma is the most common malignant tumor of the bony thorax and the single most common malignancy of the sternum. The authors report a successful surgery for primary sternal chondrosarcoma, which was treated with subtotal sternectomy and sternal transplantation.A 71-year-old female was referred to our Unit for anterior thoracic pain associated with a mass of the anterior mediastinum. The CT-scan detected a calcified shadow measuring 10 × 7 cm that suggested a thymoma . The chest wall stability was excellent and the postoperative course was uneventful Figure . Final hPrimary malignant tumors of the sternum are really rare, and account approximately for 0.5% of primary bone tumors. The chondrosarcoma is the most common primary malignant tumor of the sternum. This tumor generally occurs in young adult men; the patient is usually presented with a gradually growing, painful, hard and fixed mass of the sternum. On chest radiograph, chondrosarcoma commonly appears as a lobulated mass originating from the medullary portion of the bone, the margin is not well defined and the destruction of cortex is common. The chondrosarcoma is generally radiolucent but stippled, ring-like or arc-like calcifications are usually present .To the authors’ knowledge, their case is the first report of a chondrosarcoma originating from the posterior face of the sternum, integrally preserving the cortex and growing in the anterior mediastinum like a thymoma.Wide excision remains the key for good local control; total sternectomy must be carried out if the sternum is entirely involved, but a subtotal resection, if possible, is recommended in order to partially preserve the chest wall stability . When a Following the theory of regenerative medicine, we believe bone graft is the best substitute for the resected sternum; the graft could act as a scaffold for new bone formation, mesenchymal cells could migrate into the graft and a differentiation into osteoblastic elements has been demonstrated . In the From a practical point of view, the cryopreserved sternum is easily manipulated and tailored: a perfect fitting of the osteochondral graft into the defect could be achieved in a few minutes. Time consuming is the fixation of the graft by screws and plates, notwithstanding, the final impression is a satisfactory picture of a solid and biocompatible work.The sternal replacement with a cryopreserved allograft is a new procedure needing validation; our report follows the first by the Padua group , but conWritten informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of written consent is avaiable for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.MN, LR and LS performed surgical operation, designed research and analyzed data. PM, DT and AP performed research and collected data. AP analyzed data and results. MN wrote the article. All Authors read and approved the final manuscript.