We report herein improved methods for the safe and successful completion of endoscopic papillectomy (EP). Between January 2008 and November 2011, 12 patients underwent double-snare retracting papillectomy for the treatment of lesions of the major duodenal papilla. The main outcomes were en bloc resection rates, pathological findings, and adverse events. All of the patients (mean age, 60.1 years; range, 38 to 80 years) were diagnosed with ampullary adenoma by endoscopic forceps biopsies prior to endoscopic snare papillectomy. En bloc resection by double-snare retracting papillectomy was successfully performed for all lesions (median size, 12.3 mm), comprising six tubular adenomas, one tubulovillous adenoma, three cases of epithelial atypia, one hamartomatous polyp, and one case of duodenitis with regenerative change. Significant hemorrhage and pancreatitis were observed in one case after EP. Adenoma recurrence occurred in three patients during follow-up (median, 28.5 months) at a mean interval of 2 months postoperatively (range, 1 to 3 months). No serious adverse events were observed. Double-snare retracting papillectomy is effective and feasible for treating lesions of the major duodenal papilla. Further treatment experience, including a single-arm phase II study, needs to be accumulated before conducting a randomized controlled study.
Argon plasma coagulation; Endoscopic papillectomy; Endosonography; Intraductal ultrasonography; Tubular adenoma
An 83-year-old man underwent computed tomography during a routine check-up due to a history of surgical treatment for pancreatic cancer. Two tumors were detected in the anterior segment of the liver. A needle biopsy of the larger tumor was performed, and pathological examination showed that the tumor was a poorly differentiated hepatocellular carcinoma. Resection was not performed considering the patient’s poor physical condition. Thus, transcatheter arterial chemoembolization and radiofrequency ablation of the tumors were performed. Three months later, residual tumor of the larger lesion and multiple pulmonary metastases were detected. This time, continuous hepatic arterial infusion chemotherapy was performed. Although the pulmonary metastases markedly reduced, tumor thrombi appeared in the right portal vein on computed tomography. Finally, sorafenib was administered, which led to disappearance of the tumor thrombi and no other signs of recurrence 8 months after initiation of sorafenib on computed tomography. Although sorafenib administration has continued at reduced doses of 200 mg per day or less due to hypertension, complete response has persisted for the past 34 months. It is noteworthy that sorafenib has been given at reduced doses, but a long-term complete response is maintained in a patient who had portal tumor thrombi and distant metastasis. Herein, we present this rare case of advanced hepatocellular carcinoma controlled with reduced doses of sorafenib following multidisciplinary therapy, describe our single center experience with sorafenib use in patients with hepatocellular carcinoma, and review previous reports that focused on dose reduction of sorafenib.
Hepatocellular carcinoma; Tumor thrombi; Sorafenib; Reduced dose; Long-term complete response
We report two cases of cystic neoplasm of the liver with mucinous epithelium in which both ovarian-like stroma and bile duct communication were absent. The first case was a 41-year-old woman. She underwent right trisegmentectomy due to a multilocular cystic lesion, 15 cm in diameter, with papillary nodular components in the medial segment and right lobe. Histologically, arborizing papillae were seen in the papillary lesion. The constituent neoplastic cells had sufficient cytoarchitectural atypia to be classified as high-grade dysplasia. The second case was a 60-year-old woman. She underwent left lobectomy due to a unilocular cystic lesion, 17 cm in diameter, in the left lobe. Histologically, the cyst wall was lined by low columnar epithelia with slight cellular atypia. In both cases, neither ovarian-like stroma nor bile duct communications were found throughout the resected specimen. According to the most recent World Health Organization (WHO) classification in 2010, cystic tumors of the liver with mucinous epithelium are classified as mucinous cystic neoplasms when ovarian-like stromata are found, and as intraductal papillary neoplasm of bile duct when bile duct communication exists. Therefore, we diagnosed the cystic tumors as ‘biliary cystadenoma’ according to the past WHO classification scheme from 2000. We believe that the combined absence of both ovarian-like stroma and bile duct communication is possible in mucinous cystic tumors of the liver. Herein, we have described the clinicopathologic features of the two cases and reviewed past cases in the literature.
Cystic neoplasm; Liver; Ovarian-like stroma; Bile duct communication; Mucinous cystic neoplasm; Intraductal papillary neoplasm of bile duct
Metastatic pancreatic cancer is rare, accounting for approximately 2% of all pancreatic malignancies, and most cases arise from renal cell carcinoma. We report the case of a 63-year-old woman, who presented with a pancreatic tumor detected during her annual health examination. She had undergone left nephrectomy 13 years previously for renal cell carcinoma. Computed tomography (CT) revealed two tumors in the head and body of the pancreas, a hypervascular tumor and a hypovascular tumor with an enhanced rim, respectively. She underwent pylorus-preserving pancreaticoduodenectomy, and metastatic pancreatic tumors arising from the kidney with clustered clear cell carcinoma immunohistochemically positive for CD10 were diagnosed. This report presents the different enhancement features of different lesions on CT scans. Because the enhancement features of lesions have been reported to vary according to the size of the metastatic tumor, a knowledge of the history of renal cell carcinoma is crucial for diagnosis.
Pancreatic metastasis; Surgery; Renal cell carcinoma; Imaging; Radiological characteristics
We report a rare case of lymphoepithelioma-like hepatocellular carcinoma. A 79-year-old Japanese man had undergone curative resection of extrahepatic bile ducts because of bile duct cancer 9 years prior. The bile duct cancer was diagnosed as mucosal adenocarcinoma, and the patient had been followed up every 6 months for the last 9 years. A recent computed tomography examination revealed a tumor, 4.2 cm in size, in the lateral segment of the liver. Based on the imaging findings, the tumor was diagnosed as hepatocellular carcinoma. Serology tests were negative for hepatitis B and C viruses. Chest and abdominal image analyses showed no evidence of metastasis, but a swollen lymph node was noted around the abdominal aorta. The patient subsequently underwent extended lateral segmentectomy and resection of the swollen lymph node. Microscopically, the tumor had the characteristic appearance of poorly differentiated hepatocellular carcinoma. Moreover, an abundant infiltration of inflammatory cells was observed in the tumor. Therefore, we diagnosed the tumor as lymphoepithelioma-like hepatocellular carcinoma. The resected para-aortic lymph node also had a carcinoma with features similar to those of the main tumor. The patient has been alive for 20 months since performance of the surgery. Since the first report of lymphoepithelioma-like hepatocellular carcinoma in 2000, only nine cases have been reported in the medical literature, and the clinicopathological features of the disease have not been well documented. Herein, we describe the clinicopathological features of this case for further understanding of the disease and review past cases in the literature.
Lymphoepithelioma; Lymphoepithelioma-like carcinoma; Hepatocellular carcinoma
We report a case of concomitant pancreatic endocrine neoplasm (PEN) and intraductal papillary mucinous neoplasm (IPMN). A 74-year-old man had been followed-up for mixed-type IPMN for 10 years. Recent magnetic resonance images revealed an increase in size of the branch duct IPMN in the pancreas head, while the dilation of the main pancreatic duct showed minimal change. Although contrast-enhanced computed tomography and magnetic resonance imaging did not reveal any nodules in the branch duct IPMN, endoscopic ultrasound indicated a suspected nodule in the IPMN. A malignancy in the branch duct IPMN was suspected and we performed pylorus-preserving pancreatoduodenectomy with lymphadenectomy. The resected specimen contained a cystic lesion, 10 x 10 mm in diameter, in the head of the pancreas. Histological examination revealed that the dilated main pancreatic duct and the branch ducts were composed of intraductal papillary mucinous adenoma with mild atypia. No evidence of carcinoma was detected in the specimen. Incidentally, a 3-mm nodule consisting of small neuroendocrine cells was found in the main pancreatic duct. The cells demonstrated positive staining for chromogranin A, synaptophysin, and glucagon but negative staining for insulin and somatostatin. Therefore, the 3-mm nodule was diagnosed as a PEN. Since the mitotic count per 10 high-power fields was less than 2 and the Ki-67 index was less than 2%, the PEN was pathologically classified as low-grade (G1) according to the 2010 World Health Organization (WHO) criteria. Herein, we review the case and relevant studies in the literature and discuss issues related to the synchronous occurrence of the relatively rare tumors, PEN and IPMN.
Pancreatic endocrine neoplasm; Intraductal papillary mucinous neoplasm
We report a case of multiple primary hepatic cancers exhibiting different pathologic features coexisting in a patient with chronic hepatitis C. Computed tomography showed 2 tumors in segment 8, 20 mm (S8-A) and 5 mm (S8-B) in diameter, and a 10-mm tumor in segment 6 (S6). Based on the images, the S8-A lesion was diagnosed as cholangiocellular carcinoma or combined hepatocellular carcinoma and cholangiocarcinoma (combined HCC-CC). The other 2 tumors were diagnosed as HCC. The patient underwent partial resections of segments 6 and 8. We found 2 more tumors (S8-C was 6 mm in diameter and S8-D was 4 mm) in the resected segment 8 specimen. Histopathologic examination revealed that the S8-A and S8-C tumors were combined HCC-CC, the S8-B and S6 lesions were scirrhous HCC, and the S8-D tumor was an early HCC. This is a very rare case in which different hepatic cancers with multiple pathologic features coexisted.
Multicentric hepatocellular carcinoma; Combined hepatocellular carcinoma and cholangiocarcinoma; Scirrhous type of hepatocellular carcinoma; Early hepatocellular carcinoma; Multiple pathologic features; Hepatitis C virus; Chronic hepatitis
Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome that is commonly associated with a germline mutation in the tumor suppressor gene p53. Loss of p53 results in increased expression of CD44, a cancer stem cell (CSC) marker, which is involved in the scavenging of reactive oxygen species (ROS). Here, we report a change in the expression of a CD44 variant isoform (CD44v8-10) in an 8-year-old female LFS patient with osteosarcoma and atypical liver cancer after chemotherapy.
The patient visited a clinic with a chief complaint of chronic pain in a bruise on her right knee. Magnetic resonance imaging (MRI) raised the possibility of a bone malignancy. Biochemical testing also revealed significantly elevated levels of AFP, which strongly suggested the existence of a primary malignancy in the liver. MRI imaging showed the simultaneous development of osteosarcoma and liver cancer, both of which were confirmed upon biopsy. Combined therapy with surgical resection after chemotherapy was successful in this patient. Regardless of the absence of a familial history of hereditary cancer, a germline mutation in p53 was identified (a missense mutation defined as c.722 C>T, p.Ser241Phe). To better understand the cancer progression and response to treatment, immunohistochemical (IHC) analysis of biopsy specimens obtained before and after chemotherapy was performed using a specific antibody against CD44v8-10.
This case demonstrates the ectopic up-regulation of CD44v8-10 in a biopsy sample obtained after cytotoxic chemotherapy, which confers high levels of oxidative stress on cancer cells. Because the alternative splicing of CD44 is tightly regulated epigenetically, it is possible that micro-environmental stress resulting from chemotherapy caused the ectopic induction of CD44v8-10 in vivo.
Li-Fraumeni syndrome (LFS); cancer stem cells (CSCs); CD44 variant isoforms
Limited resection is reserved for patients with high operative risk or benign adenomas. We aimed to define indications for limited resection of early ampulla of Vater carcinoma with curative intent through detailed preoperative examinations and histopathological evaluations.
We performed a retrospective cohort study of all consecutive Japanese patients who underwent resection for ampulla of Vater neoplasms at our hospital from 1986 to 2010.
A total of 75 patients were identified. Moderately/poorly differentiated histology, lympho-vascular/perineural invasion, and duodenal/pancreatic invasion were significant risk factors for lymph node metastases. Macroscopically, non-exposed protruded- or ulcerative-type disease did not correlate directly with lymph node metastases; however, these tumor types were associated with other invasive features. In a subset of early carcinomas fulfilling the conditions of exposed protruded adenoma or papillary/well-differentiated adenocarcinoma determined by endoscopic biopsy, negative duodenal invasion determined by endoscopic ultrasonography, no tumor infiltration into the pancreatic duct determined by intraductal ultrasound, and diameter of the pancreatic duct ≤3 mm determined by endoscopic retrograde cholangiopancreatography (N = 11), the incidence of lymph node metastasis and tumor infiltration into the pancreatic duct was 0%.
Strictly selected patients with early ampulla of Vater carcinomas may benefit from limited resection if the resected specimen is evaluated to confirm all histopathological criteria.
Ampulla of Vater carcinoma; Limited resection; Local resection; Indication; Criteria