Uncovered versus covered metallic stents for the management of unresectable malignant distal biliary obstruction: a randomized multicenter trial.

OBJECTIVE: The treatment result of the uncovered metallic stent (uncovered MS) and covered metallic stent (covered MS) for unresectable malignant distal biliary obstruction is controversial. This time, we conducted this study to compare the efficacies and complication rates of uncovered MS and covered MS in unresectable malignant distal biliary obstructions at a prospective randomized multicenter trial. MATERIALS AND METHODS: From April 2014 to September 2018, patients with unresectable malignant distal biliary obstruction were randomly assigned to 2 groups: the uncovered MS group and the covered MS group. RESULTS: 92 treatment results patients were discussed. 48 patients were assigned to the uncovered MS group and 44 cases were assigned to the covered MS group. Both groups showed a drainage effect. No significant difference was found in the drainage effect between the 2 groups. The number of stent occlusion was significantly greater (p = .0467) in uncovered MS (43.8%) comparing with those in covered MS (22.7%). As the cause of stent occlusion, tumor ingrowth was significantly greater (p < .001) in the uncovered MS group (35.4%) than in the covered MS group (2.3%). The median stent patency period was significantly longer (p = .0112) in the covered MS group (455 days) than that of the uncovered MS group (301 days). A significant difference in the median survival period was not found between the 2 groups. CONCLUSIONS: Covered MS showed the possibility of extending the stent patency period by suppressing tumor ingrowth more than uncovered MS does. The UMIN Clinical Trial Registry number is UMIN000015093.

Multicenter study of endoscopic preoperative biliary drainage for malignant hilar biliary obstruction: E-POD hilar study.

BACKGROUND AND AIM: Endoscopic nasobiliary drainage (ENBD) is often recommended in preoperative biliary drainage (PBD) for hilar malignant biliary obstruction (MBO), but endoscopic biliary stent (EBS) is also used in the clinical practice. We conducted this large-scale multicenter study to compare ENBD and EBS in this setting. METHODS: A total of 374 cases undergoing PBD including 281 ENBD and 76 EBS for hilar MBO in 29 centers were retrospectively studied. RESULTS: Extrahepatic cholangiocarcinoma (ECC) accounted for 69.8% and Bismuth-Corlette classification was III or more in 58.8% of the study population. Endoscopic PBD was technically successful in 94.6%, and adverse event rate was 21.9%. The rate of post-endoscopic retrograde cholangiopancreatography pancreatitis was 16.0%, and non-endoscopic sphincterotomy was the only risk factor (odds ratio [OR] 2.51). Preoperative re-intervention was performed in 61.5%: planned re-interventions in 48.4% and unplanned re-interventions in 31.0%. Percutaneous transhepatic biliary drainage was placed in 6.4% at the time of surgery. The risk factors for unplanned procedures were ECC (OR 2.64) and total bilirubin ≥ 10 mg/dL (OR 2.18). In surgically resected cases, prognostic factors were ECC (hazard ratio [HR] 0.57), predraiange magnetic resonance cholangiopancreatography (HR 1.62) and unplanned re-interventions (HR 1.81). EBS was not associated with increased adverse events, unplanned re-interventions, or a poor prognosis. CONCLUSIONS: Our retrospective analysis did not demonstrate the advantage of ENBD over EBS as the initial PBD for resectable hilar MBO. Although the technical success rate of endoscopic PBD was high, its re-intervention rate was not negligible, and unplanned re-intervention was associated with a poor prognosis in resected hilar MBO.

Nectin-1 expression in cancer-associated fibroblasts is a predictor of poor prognosis for pancreatic ductal adenocarcinoma.

PURPOSE: Nectin-1 is a cell adhesion molecule that regulates the formation of adherens junctions and tight junctions. We measured the expression of nectin-1 in cancer-associated fibroblasts (CAFs) in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Nectin-1 expression was measured via immunohistochemistry using tissue microarray blocks constructed from resected PDAC tissue from 258 patients. We screened for associations between nectin-1 expression and clinicopathological parameters. According to the percentage of CAFs stained, expression was classified as negative at ≤ 30% and positive at > 30%. RESULTS: Nectin-1 expression was confirmed in CAFs from 64 patients (24.8%), and was associated with lymph node metastasis (p = 0.016), advanced Union for International Cancer Control stage (p = 0.016), perineural invasion (p = 0.022), pancreatic head tumors (p = 0.023), and shorter overall survival (p = 0.003). Multivariate analysis revealed that nectin-1 expression in CAFs was an independent prognostic factor (p = 0.038). CONCLUSIONS: Diffuse nectin-1 expression in the CAFs of PDAC patients is associated with invasion, metastasis, and shorter survival.

Molecular alterations in sporadic pancreatic neuroendocrine microadenomas.

BACKGROUND: Pancreatic neuroendocrine microadenomas (pNEMAs) are neuroendocrine tumors measuring <5 mm in diameter. They are considered the precursor of pancreatic neuroendocrine tumors (pNETs). The aim of this study was to investigate the immunohistochemical differences between pNEMA, pNET, and hyperplasia of pancreatic islet cells (HPIL) in patients with non-familial syndromes. METHODS: We evaluated 21 pNEMAs, 19 HPILs, and 21 non-functional pNETs (10 G1 and 11 G2 cases) in patients with non-familial syndromes. Immunohistochemistry for tumor-associated markers death domain-associated protein (DAXX), alpha thalassemia/mental retardation X-linked (ATRX), cytokeratin 19 (CK19), bcl-2, and CD99 was performed. RESULTS: DAXX was expressed in 95%, 71%, and 71% of HPIL, pNEMA, and pNET samples, respectively; the differences were not significant. ATRX expression in pNEMA and pNET was significantly lower than that in HPIL, whereas there was no significant difference between pNEMA and pNET (HPIL: 95%, pNEMA: 43%, and pNET: 52%). All HPIL and pNEMA cases were negative for bcl-2 and positive for CD99, whereas 29% of pNETs were positive for bcl-2 and 24% were negative for CD99. CK19 expression in HPIL was significantly lower than in pNEMA and pNET, although no significant difference was observed between pNEMA and pNET (HPIL: 5%, pNEMA: 57%, and pNET: 43%). Among G1 and G2 pNETs, CD99 was expressed in 50% of G1 pNETs but not in any G2 pNET cases. CONCLUSION: Non-familial HPIL, pNEMA, and pNET patients exhibit distinct ATRX, CD99, CK19, and bcl-2 molecular profiles.

Bone morphogenetic protein-2 expression in an intraductal papillary mucinous neoplasm with marked ossification: A case report.

Intratumoral ossification has been reported in a number of epithelial tumors, but its presence in intraductal papillary mucinous neoplasms (IPMNs) is very rare. Herein, we present a rare case of IPMN with marked ossification. A 56-year-old Japanese man was under follow-up for a previously diagnosed IPMN. Seven years later, he was found to have dilatation of the main pancreatic duct and an enlarged solid mass, for which pancreaticoduodenectomy was performed. Macroscopically, multiple and cystically dilated pancreatic branch ducts, as well as a dilated main pancreatic duct, were identified. There was a solid, polypoid hard mass measuring 15 × 12 mm in the cystically dilated branch of the duct in the pancreatic head. Histological examination revealed papillary proliferation of atypical cuboidal or columnar epithelial cells in the dilated main and branch pancreatic ducts. The solid mass included an invasive adenocarcinoma component with a tubular or trabecular structure that showed pronounced ossification. We diagnosed the patient with invasive IPMN accompanied by marked ossification. Immunohistochemically, tumor cells in both the non-invasive and invasive lesions expressed bone morphogenetic protein-2 (BMP-2). While the mechanism of intratumoral ossification is unclear, it may have involved BMP-2 in the present case.

Relationship between pain and plasma amino acid levels in chronic pancreatitis.

OBJECTIVE: Our aim was to investigate the relationship between imbalances of plasma amino acids and pain in chronic pancreatitis (CP). METHODS: Thirty patients with alcoholic CP in an exocrine-insufficient state were examined. We divided them between diet and control group. Diet group ingested 80 g/300 kcal of the elemental diet "Elental®". This diet of 300 kcal/day was administered for two months. Selected clinical and laboratory values were compared between both groups before and after diet. Pain was observed and compared using a visual analog scale (VAS). RESULTS: There was no significant difference in the BMI between both groups before and after diet. The serum albumin level in diet group after diet was significantly higher than in control group (P=0.036). There was no significant difference in HbA1c between both groups before and after diet. The total amino acid concentration was significantly higher in diet group after diet than in control group (P=0.033). The concentrations of serum histidine and methionine in diet group after diet were significantly higher than in control group (histidine, P=0.022; methionine, P=0.026). The concentration of serum glutamate in diet group after diet was significantly lower than in control group (P=0.027). The balance of amino acids in diet group was normalized after the Elental® was ingested. The VAS score was significantly lower in diet group after diet than in control group (P=0.018). CONCLUSION: These amino acid levels and pancreatic pain were improved by the elemental diet. The pancreatic pain may be related to these amino acid imbalances.

Sex differences in immunohistochemical expression and capillary density in pancreatic solid pseudopapillary neoplasm.

Solid pseudopapillary neoplasm (SPN) is a rare and low-grade malignant pancreatic neoplasm. Solid pseudopapillary neoplasm is rare in men, and most SPN cases are in young women. This study aimed to investigate sex differences in SPN clinical histopathology including capillary density and expression of immunochemical markers, including glypican 3. A total of 22 resected tumors from pancreatic SPN patients, including 16 women (73%) and 6 men (27%), were analyzed histopathologically and immunohistochemically for synaptophysin, ß-catenin, estrogen receptor, progesterone receptor, Ki-67, CD10, CD31, and glypican 3. The median age was 52.5 years in men and 24 years in women (P = .046). The median tumor size was 22.5 mm in men and 40 mm in women (P = .337). In 11 of the 16 women (69%), but in none of the men, tumors showed complete or incomplete fibrous cap`sules (P = .006). Cholesterol clefts were observed in tumors from 10 women (63%) but in none from the men (P = .012). No significant sex differences were noted in tumor characteristics, including size, macroscopic cystic degeneration, necrosis, lymphovascular involvement, and perineural invasion. The SPNs were weakly positive for glypican 3, although there was no significant difference between sexes. Capillary density tended to be lower in tumors from men than in those from women, but not significantly. Thus, except for the fibrous capsule and cholesterol clefts often found in tumors and the younger age of the women, there were no significant sex differences in histopathologic or immunohistochemical features of SPN, despite its markedly higher occurrence in women.

Therapeutic Outcome of Multidisciplinary Treatment in Unresectable Biliary Tract Cancer: A Multicenter Retrospective Analysis.

Background: There is little established evidence regarding treatment strategies for unresectable biliary tract cancer (BTC). This study aimed to clarify the situation of multidisciplinary treatment for unresectable BTC in the 2000s when there was no international standard first-line therapy. Methods: We retrospectively reviewed 315 consecutive patients with unresectable BTC who had been treated at seven tertiary institutions in Kanagawa Prefecture, Japan between 1999 and 2008. Results: The unresectable factors were as follows: locally advanced, 101 cases (32.1%); hematogenous metastases, 80 cases (25.4%); and peritoneal dissemination, 30 cases (9.5%). Chemotherapy or radiation therapy was administered to 218 patients (69.2%). The best supportive care was provided in 97 cases (30.8%). The most common regimen was gemcitabine monotherapy, followed by gemcitabine combination therapy and S-1 monotherapy. The 1- and 2-year survival rates of all patients were 34.6% and 12.2%, respectively. The median survival time (MST) was 8 months in all patients. The 1-year survival rate was 65%, and the MST was 12 months among the locally advanced patients, whereas patients with peritoneal dissemination had the worst outcome; the 1-year survival rate was 7%, and the MST was 5 months. Among treated 90 cases of perihilar cholangiocarcinoma, patients who received chemoradiotherapy (n = 24) had a significantly better outcome than those who received chemotherapy alone (MST: 20 vs. 11 months, P < 0.001). Conclusions: Unresectable BTC has heterogeneous treatment outcomes depending on the mode of tumor extension and location. Multidisciplinary treatment seems useful for patients with locally advanced BTC, whereas patients with metastatic disease still have a poor prognosis.

Alterations in plasma amino acid levels in alcoholic chronic pancreatitis in Japanese.

AIMS: Our aim was to investigate plasma amino acid levels in chronic pancreatitis (CP) patients and examine their relationship with exocrine insufficiency. METHODS: Thirty-nine patients with alcoholic CP and 20 healthy controls were examined. CP patients were divided into an exocrine normal group (n = 28) and an exocrine insufficiency group (n = 11). Selected clinical and laboratory values were compared among the three groups, and the effect of an elemental diet was observed in 6 patients of the exocrine insufficiency group. RESULTS: Total amino acid concentration was significantly higher in the control group than in the exocrine normal group and exocrine insufficiency group (p = 0.032, p = 0.020). In the exocrine insufficiency group, significant reductions in the concentrations of serum histidine and methionine were found compared with the control group and exocrine normal group (histidine: p = 0.032, p = 0.045; methionine: p = 0.043, p = 0.049). In the exocrine normal group and exocrine insufficiency group, significant elevation in the concentration of serum glutamate was found compared with the control group (p = 0.036, p = 0.029). Elemental diet improved these amino acid concentrations. CONCLUSION: Patients with CP exhibit alterations in the levels of several amino acids, such as histidine, methionine, and glutamate. These amino acid deficiencies seem to correlate with exocrine insufficiency and be improved by an elemental diet.

Efficacy and Safety of Endoscopic Removal for Asymptomatic Common Bile Duct Stones in Comparison with Symptomatic Stones.

OBJECTIVE: Endoscopic removal is recommended for common bile duct stones (CBDs). However, in patients with asymptomatic CBDs, follow-up without treatment may be recommended because of the increased complication risks associated with asymptomatic CBDs removal. The objective of our study was to investigate the efficacy and safety of CBDs removal in asymptomatic patients. METHODS: Consecutive patients with naive papilla who underwent endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of CBDs from April 2016 to August 2020 were retrospectively analyzed. We compared the efficacy and safety of CBDs removal in asymptomatic and symptomatic patients. RESULTS: We enrolled 300 patients, 53 asymptomatic and 247 symptomatic patients. Endoscopic CBDs removal was successful in all patients, except one symptomatic patient. However, the complete stone removal rate in a single session was significantly higher in the asymptomatic group than that in the symptomatic group. ERCP-related complications did not differ between the asymptomatic and symptomatic patients. The incidence of post-ERCP pancreatitis was similar and liver cirrhosis was the only significant risk factor for pancreatitis. CONCLUSION: Complication risks associated with endoscopic CBDs removal was not significantly different between asymptomatic and symptomatic patients. Liver cirrhosis was a significant risk factor of ERCP-related pancreatitis.

Perivascular epithelioid cell tumor (PEComa) of the pancreas: immunoelectron microscopy and review of the literature.

A perivascular epithelioid tumor (PEComa) is a rare tumor probably arising from the perivascular epithelioid cells. Only three cases of pancreatic PEComa have been reported in the English-language literature. The present report describes an extremely rare case of pancreatic PEComa. A 47-year-old Japanese woman complained of lower abdominal pain and a well-demarcated solid tumor was found in the pancreatic head. There was no history of tuberous sclerosis complexes. Pylorus-preserving pancreaticoduodenectomy was thus performed. There was a well-demarcated, solid tumor measuring 17 mm in the pancreatic head. The tumor was composed of a diffuse proliferation of epithelioid tumor cells with many blood vessels but no adipose tissue. The tumor cells expressed HMB45 and alpha-smooth muscle actin. Ultrastructurally, the tumor cells possessed many membrane-bound granules that were positive for HMB45 on immunoelectron microscopy. The results of immunoelectron microscopy show that some PEComas possess not only typical melanosomes or premelanosomes but also aberrant melanosomes.

Endometrial adenocarcinoma without myometrial invasion metastasizing to the pancreas and masquerading as primary pancreatic neoplasm.

Reported herein is a case of endometrial adenocarcinoma without myometrial invasion that metastasized to the pancreas in a 69-year-old Japanese woman who had a history of hysterectomy. Although systemic radiography could not detect any metastasis in the whole body before hysterectomy, imaging performed 2 months after the hysterectomy consisting of CT, magnetic resonance imaging, gallium scintigraphy and positron emission tomography identified a solitary pancreatic tumor. Imaging demonstrated an intracystic papillary growth in the pancreas, suggesting intraductal papillary mucinous neoplasm or mucinous cystic neoplasm. Excised in distal pancreatectomy, the tumor was diagnosed as a pancreatic primary, an invasive papillary adenocarcinoma at first, but both the endometrial tumor and the pancreatic tumor demonstrated similar morphology and immunohistochemistry. Furthermore, the identical nucleotide mutation of TP53 gene was observed from both the endometrial and pancreatic tumors. The pancreatic tumor was therefore confirmed to be a metastasis from the primary endometrial adenocarcinoma. Metastasis to the pancreas from endometrial carcinoma is extremely rare but must be considered even if the previous cancer was treated at an early stage. Histopathological comparison study and genetic analysis are important for the correct diagnosis of metastasis.

Comparison between Endoscopic Treatment and Surgical Drainage of the Pancreatic Duct in Chronic Pancreatitis.

BACKGROUND: Treatment of recurrent chronic obstructive pancreatitis is pancreatic duct decompression with endoscopic drainage (endoscopic pancreatic stenting [EPS] with extracorporeal shockwave lithotripsy [ESWL]) or surgical drainage. Despite the recent popularization of endoscopic drainage, treatment or stent removal is difficult in many patients. We compared the efficacy, safety, and medical cost of endoscopic and surgical treatments. PATIENTS AND METHODS: We retrospectively compared the treatment course and medical cost of hospitalization between 41 patients who had undergone pancreatic stenting between 2006 and 2010 (EPS group) and 10 patients who had undergone surgery for poor control of pancreatitis between 2001 and 2005 (surgical drainage group). RESULTS: No intergroup differences were observed in causes, symptoms, disease duration, smoking history, or endocrine and exocrine functions. The technical success rate was 100% in both groups, and pain had improved in all of the patients in both groups. The incidences of complications did not differ significantly, and the mortality rate was 0% in both groups. The rehospitalization rate was significantly higher in the EPS group (78%) than that in the surgical drainage group (20%; P<0.01). This was considered attributable to rehospitalization for stent replacement. The effects to improve endocrine and exocrine functions were not different between the two groups before and after treatment, and the current condition was maintained in 80% or more of the patients. For the entire EPS group, the mean hospitalization period was 18 days and the mean medical cost of hospitalization was 2,133,330 yen. For the entire surgical drainage group, the mean hospitalization period was 23 days and the mean medical cost of hospitalization was 2,246,548 yen, thus indicating no significant differences between the two groups. CONCLUSIONS: Although both endoscopic and surgical treatments achieved high symptom control and safety rates, re-hospitalization is required for stent replacement, which leads to poor cost-effectiveness, particularly in patients in whom stent removal is difficult. Endoscopic treatment for severe pancreatic duct stenosis will need to be advanced and evaluated in the future.

Sevelamer hydrochloride improves hyperphosphatemia in hemodialysis patients with low bone turnover rate and low intact parathyroid hormone levels.

Sevelamer improves hyperphosphatemia without increasing the calcium load. However, it remains unknown whether sevelamer restores bone metabolism in hemodialysis patients with low bone turnover osteodystrophy and hypoparathyroidism. We investigated the changes in serum intact parathyroid hormone (iPTH) and bone metabolic marker levels after replacing calcium carbonate with sevelamer in these patients. We also conducted stratified analysis based on patient background and multivariate analysis to determine the factors affecting these parameters. During sevelamer replacement therapy, serum calcium and phosphate concentrations, and the calcium phosphate product were measured at 0, 1, 3, and 6 months. Serum iPTH, bone alkaline phosphatase and osteocalcin concentrations were measured at 0 and 6 months. In hemodialysis patients (71 men and 46 women, 63 +/- 12 years old) serum calcium levels and the calcium phosphate product decreased significantly at 1 month. Serum iPTH, bone alkaline phosphatase and osteocalcin levels increased significantly at 6 months. Increases in serum iPTH concentrations were observed in all stratified groups. Significant increases in serum bone alkaline phosphatase and osteocalcin concentrations were found only in the relative hypoparathyroidism group (iPTH levels > or =51.5 pg/mL, the median pretreatment level). Multivariate analysis showed that the factors affecting change in serum iPTH level are baseline serum iPTH, baseline calcium level (> or =9.5 mg/dL), and dialysis duration of 10 years or longer. Sevelamer appears useful for the treatment of hyperphosphatemia in these patients. Particularly, in the relative hypoparathyroidism group, the iPTH secretory response is probably enhanced and bone turnover may have been improved as a result of reducing the calcium load.

Clinicopathological significance of Necl-4 expression in pancreatic ductal adenocarcinoma.

AIMS: The loss, or decreased expression, of nectin-like molecule 4 (Necl-4; an immunoglobulin-like cell adhesion molecule) is reported to be associated with the development and progression of certain types of cancer. We investigated the clinicopathological significance of Necl-4 expression in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Immunohistochemical analyses of Necl-4 (n=258) and E-cadherin (n=256) expression were performed using tissue microarray blocks of PDAC samples. Necl-4 expression of 38 pancreatic intraepithelial neoplasia (PanIN) lesions included in tissue microarray cores was also evaluated. Necl-4 and E-cadherin expression was considered positive if >30% of cells were stained, and negative if ≤30% of cells were stained. RESULTS: Necl-4 expression was positive in 45.7% (n=118) and negative in 54.3% (n=140) of PDAC cases. Necl-4 staining was positive in 96.7% (n=29) and negative in 3.3% (n=1) of low-grade PanIN cases, and positive in 62.5% (n=5) and negative in 37.5% (n=3) of high-grade PanIN cases. The number of cases with positive Necl-4 expression decreased in the order low-grade PanIN>high-grade PanIN>PDAC (p<0.001). Negative Necl-4 expression was significantly associated with a larger tumour size of >30 mm, perineural invasion, lymphatic involvement, lymph node metastasis (pN1), an advanced TNM (tumour, node, metastases) stage (stage IIB-IV), an advanced histological grade (G2/3), and shorter overall survival. E-cadherin staining was positive in 46.1% (n=118) and negative in 53.9% (n=138) of PDAC cases. Necl-4 expression correlated positively with E-cadherin expression (r=0.405, p<0.001). CONCLUSIONS: The results suggest that Necl-4 is associated with carcinogenesis and aggressiveness of PDAC.

An Intra-Abdominal Desmoid Tumor, Embedded in the Pancreas, Preoperatively Diagnosed as an Extragastric Growing Gastrointestinal Stromal Tumor.

A 45-year-old woman was found to have a pancreatic tumor by abdominal ultrasound performed for a medical check-up. Abdominal contrast-enhanced computed tomography showed a hypovascular tumor measuring 30 mm in diameter in the pancreatic tail. Endoscopic ultrasound-guided fine needle aspiration was performed. An extragastric growing gastrointestinal stromal tumor was thereby diagnosed preoperatively, and surgical resection was planned. Laparoscopic surgery was attempted but conversion to open surgery was necessitated by extensive adhesions, and distal pancreatectomy, splenectomy, and partial gastrectomy were performed. The histological diagnosis was an intra-abdominal desmoid tumor. A desmoid tumor is a fibrous soft tissue tumor arising in the fascia and musculoaponeurotic tissues. It usually occurs in the extremities and abdominal wall, and only rarely in the abdominal cavity. We experienced a case with an intra-abdominal desmoid tumor that was histologically diagnosed after laparotomy, which had been preoperatively diagnosed as an extragastric growing gastrointestinal stromal tumor. Although rare, desmoid tumors should be considered in the differential diagnosis of intra-abdominal tumors. Herein, we report this case with a literature review.

Epidermoid cysts are a characteristic feature of intrapancreatic but not of extrapancreatic accessory spleens.

Accessory spleens (ASs), ectopic splenic tissue at intrapancreatic and extrapancreatic sites, rarely contain epidermoid cysts. Our aim was to analyze the incidence of epidermoid cysts in ASs and perform an immunohistochemical analysis of its epithelial lining. We included in the study 148 ASs from 135 patients, for which pathological data were available. Eleven were intrapancreatic ASs (IPASs) and 137 were extrapancreatic ASs (EPASs). Six of the eleven (55%) IPASs contained epidermoid cysts, but they were not detected in EPASs. Immunohistochemical analysis showed that both the superficial/luminal and basal layer of the epithelial lining of epidermoid cysts in IPASs are negative for MUC2, MUC5AC, MUC6, WT-1, calretinin, thrombomodulin, uroplakin-II, and uroplakin-III. The superficial/luminal layer was positive for MUC4, CK7, and CA19-9 in all cases (100%), for CEA and HBME-1 in three cases (50%), and for MUC1, CK5/6, and CK20 in two cases (33%). The superficial/luminal layer was negative for p63 and D2-40 in all cases. The basal layer was positive for MUC1, CK5/6, p63, and HBME-1 in all six cases (100%), for CK7 and D2-40 in two cases (33%), and for CEA in one case (17%). The basal layer was negative for MUC4, CK20, and CA19-9 in all cases. Epidermoid cysts are a characteristic feature of IPASs but not of EPASs. Immunohistochemical analysis showed that the epithelial lining of epidermoid cysts in IPASs has a mixed character of glandular, squamous, mesothelial, and urothelial epithelium.

Clinical practice guideline for post-ERCP pancreatitis.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERPC) is used for the diagnosis and treatment of pancreatic and biliary diseases. Post-ERCP pancreatitis (PEP) is a complication which needs special care and clinical practice guideline for this morbidity is also needed. METHODS: The key clinical issues of diagnosis and treatment of PEP were listed and checked, and then the clinical questions were formulated. PubMed (MEDLINE) and Ichushi-web (Japanese medical literature) were used as databases. For the study of diagnostic test accuracy, items similar to QUADAS-2, i.e., random selection from a population to which the diagnostic test is applied, blinding of index tests and reference tests, completeness of reference standard, completeness of test implementations, the same timing of tests, and missing data were assessed as well as the indirectness of the study subjects, index tests, reference standard, and outcomes. Grading of recommendations was determined as strong or weak. In clinical practice, the judgment of attending doctors should be more important than recommendations described in clinical practice guidelines. Gastroenterologists are the target users of this clinical practice guideline. General practitioners or general citizens are not supposed to use this guideline. The guideline committee has decided to include wide clinical issues such as etiological information, techniques of ERCP, the diagnosis, treatments, and monitoring of PEP in this guideline. RESULTS: In this concise report, we described ten clinical questions, recommendations, and explanations pertaining to risk factors, diagnosis, prognostic factors, treatments, and preventive interventions in the medical practice for PEP. CONCLUSIONS: We reported here the essence of the clinical practice guideline for PEP.

Undifferentiated carcinoma of the ampulla of Vater.

Undifferentiated carcinoma of the ampulla of Vater is a rare disease with unclear and clinical characteristics and prognosis. Here, we report the case of a 61-year-old man with undifferentiated carcinoma of the ampulla of Vater. He presented to our hospital with an increase in hepatobiliary system enzymes that was detected during a health check-up. Imaging and endoscopy demonstrated a tumor with ulcer in the ampulla of Vater, which was diagnosed as a carcinoma by biopsy. No distant metastasis was observed. Subtotal stomach-preserving pancreaticoduodenectomy was performed. Undifferentiated carcinoma was confirmed based on the presence of small round atypical cells with the formation of a solid alveolar lesion on histopathological examination and immunohistochemical staining that was positive for CAM 5.2 but negative for chromogranin A and synaptophysin. The tumor infiltrated the duodenum, but not the pancreas; no lymph node metastasis was observed. However, liver metastases were detected 2 months postoperatively. Chemotherapy was performed, and the tumor size temporality decreased; however, it grew in size again, and the patients subsequently died of the primary disease 15 months postoperatively. Undifferentiated carcinoma of the ampulla of Vater is a very rare histological type. More number of cases is necessary to clarify optimal treatment.

A Serous Cystic Neoplasm of the Pancreas Coexisting with High-Grade Pancreatic Intraepithelial Neoplasia Mimicking an Intraepithelial Papillary Mucinous Neoplasm: A Case Report.

Serous cystic neoplasms of the pancreas are rare exocrine pancreatic neoplasms, most of which are benign and do not communicate with the pancreatic duct. Pancreatic intraepithelial neoplasm (PanIN) is considered a precursor of ductal adenocarcinoma that is microscopically recognized in pancreatic ducts. A 67-year-old Japanese woman presented with a 10-mm multilocular cystic lesion at the pancreatic body. Magnetic resonance pancreatography showed stenosis of the main pancreatic duct at the pancreatic body and dilatation of the distal side of the main pancreatic duct. Furthermore, communication between the cystic lesion and the main pancreatic duct was suspected based on magnetic resonance pancreatography findings. Distal pancreatectomy was performed under the preoperative diagnosis of intraductal papillary mucinous neoplasm. Histologically, the cystic lesion was lined with a non-atypical cuboidal or flat epithelium with clear cytoplasm and was thus diagnosed as a serous cystic neoplasm. High-grade PanIN lesions with stromal fibrosis were observed at the main and branch pancreatic ducts. Histological examination revealed no communication between the serous cystic neoplasm and the pancreatic ducts. Immunohistochemically, the epithelium of the serous cystic neoplasm showed positive anti-von Hippel-Lindau antibody staining, whereas the epithelium of the PanIN showed negative staining. A serous cystic neoplasm coexisting with another pancreatic neoplasm is rare. When dilatation of the main or branch pancreatic ducts coexists with a serous cystic neoplasm, as in this case, the lesion clinically mimics an intraductal papillary mucinous neoplasm.