Pancreatic Fistula Extending into the Thigh Caused by the Rupture of an Intraductal Papillary Mucinous Adenoma of the Pancreas.

We herein report the first case of a pancreatic fistula extending into the thigh caused by the rupture of an intraductal papillary mucinous neoplasm (IPMN) of the pancreas. An 80-year-old man was suspected to have necrotizing fasciitis because of right femoral pain. Computed tomography showed fluid retention from the pancreatic head to the right iliopsoas muscle and an IPMN at the pancreatic head. The findings of endoscopic retrograde pancreatography led to the suspicion of a minor leak and a pancreatic stent was placed. The patient died due to an uncontrollable infection. A pathological autopsy showed a pancreatic fistula extending into the thigh that had been caused by the rupture of the IPMN.

Clinical implications of doubling time of gastrointestinal submucosal tumors.

AIM: To evaluate the efficacy of doubling time (DT) of gastrointestinal submucosal tumors (GIST). METHODS: From April 1987 through November 2012, a total of 323 patients were given a final histopathological diagnosis of GISTs on surgical resection or endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in Kitasato University East Hospital or Kitasato University Hospital. We studied 53 of these patients (34 with resected tumors and 19 with unresected tumors) whose tumors could be measured on EUS on at least two successive occasions. The histopathological diagnosis was GIST in 34 patients, leiomyoma in 5, schwannoma in 3, ectopic pancreas in 1, hamartoma in 1, cyst in 1, Brunner's adenoma in 1, and spindle-cell tumor in 7. We retrospectively calculated the DT of GISTs on the basis of the time course of EUS findings to estimate the growth rate of such tumors. RESULTS: The DT was 17.2 mo for GIST, as compared with 231.2 mo for leiomyoma, 104.7 mo for schwannoma, 274.9 mo for ectopic pancreas, 61.2 mo for hamartoma, 49.0 mo for cyst, and 134.7 mo for Brunner's adenoma. The GISTs were divided into risk classes on the basis of tumor diameters and mitotic figures (Fletcher's classification). The classification was extremely low risk or low risk in 28 patients, intermediate risk in 3, and high risk in 3. DT of GIST according to risk was 24.0 mo for extremely low-risk plus low-risk GIST, 17.1 mo for intermediate-risk GIST, and 3.9 mo for high-risk GIST. DT of GIST was significantly shorter than that of leiomyoma plus schwannoma (P < 0.05), and DT of high-risk GIST was significantly shorter than that of extremely low-risk plus low-risk GIST (P < 0.05). CONCLUSION: For GIST, a higher risk grade was associated with a significantly shorter DT. Small SMTs should initially be followed up within 6 mo after detection.

A Patient with Pancreatic Castleman's Disease Arising around the Main Pancreatic Duct.

Castleman's disease of the pancreas is extremely rare. To the best of our knowledge, Castleman's disease arising around the main pancreatic duct has not been previously reported. The patient was a 74-year-old man. Abdominal ultrasonography performed at a health check-up revealed a dilated main pancreatic duct. Pancreatic cancer was strongly suspected on various imaging studies. However, the results of a cytological examination of the pancreatic juice were negative for malignancy. The patient did not want to undergo a histological diagnosis by endoscopic ultrasound-guided fine-needle aspiration, thus pylorus-preserving pancreatoduodenectomy was performed. Pancreatic Castleman's disease arising around the main pancreatic was diagnosed by the histopathological examination.

Phase I trial of combination chemotherapy with gemcitabine, cisplatin, and S-1 in patients with advanced biliary tract cancer.

AIM: To evaluate the dose-limiting toxicities (DLTs) and determine the maximum-tolerated dose (MTD) and recommended dose (RD) of combination chemotherapy with gemcitabine, cisplatin and S-1 which is an oral fluoropyrimidine pro-drug in patients with advanced biliary tract cancer. METHODS: Patients with histologically or cytologically confirmed unresectable or recurrent biliary tract cancer were enrolled. The planned dose levels of gemcitabine (mg/m(2)), cisplatin (mg/m(2)), and S-1 (mg/m(2) per day) were as follows: level -1, 800/20/60; level 0, 800/25/60; level 1, 1000/25/60; and level 2, 1000/25/80. In each cycle, gemcitabine and cisplatin were administered intravenously on days 1 and 15, and S-1 was administered orally twice daily on days 1 to 7 and days 15 to 21, every 4 wk. RESULTS: Twelve patients were enrolled, and level 0 was chosen as the starting dose. None of the first three patients had DLTs at level 0, and the dose was escalated to level 1. One of six patients had DLTs (grade 4 febrile neutropenia, leucopenia, and neutropenia; grade 3 thrombocytopenia) at level 1. We then proceeded to level 2. None of three patients had DLTs during the first cycle. Although the MTD was not determined, level 2 was designated at the RD for a subsequent phase II study. CONCLUSION: The RD was defined as gemcitabine 1000 mg/m(2) (days 1, 15), cisplatin 25 mg/m(2) (days 1, 15), and S-1 80 mg/m(2) per day (days 1-7, 15-21), every 4 weeks. A phase II study is planned to evaluate the effectiveness of combination chemotherapy with gemcitabine, cisplatin, and S-1 in advanced biliary tract cancer.

Passive-bending, short-type single-balloon enteroscope for endoscopic retrograde cholangiopancreatography in Roux-en-Y anastomosis patients.

AIM: To evaluate short-type-single-balloon enteroscope (SBE) with passive-bending, high-force transmission functions for endoscopic retrograde cholangiopancreatography (ERCP) in patients with Roux-en-Y anastomosis. METHODS: Short-type SBE with this technology (SIF-Y0004-V01; working length, 1520 mm; channel diameter, 3.2 mm) was used to perform 50 ERCP procedures in 37 patients with Roux-en-Y anastomosis. The rate of reaching the blind end, time required to reach the blind end, diagnostic and therapeutic success rates, and procedure time and complications were studied retrospectively and compared with the results of 34 sessions of ERCP performed using a short-type SBE without this technology (SIF-Y0004; working length, 1520 mm; channel diameter, 3.2 mm) in 25 patients. RESULTS: The rate of reaching the blind end was 90% with SIF-Y0004-V01 and 91% with SIF-Y0004 (P = 0.59). The median time required to reach the papilla was significantly shorter with SIF-Y0004-V01 than with SIF-Y0004 (16 min vs 24 min, P = 0.04). The diagnostic success rate was 93% with SIF-Y0004-V01 and 84% with SIF-Y0004 (P = 0.17). The therapeutic success rate was 95% with SIF-Y0004-V01 and 96% with SIF-Y0004 (P = 0.68). The median procedure time was 40 min with SIF-Y0004-V01 and 36 min with SIF-Y0004 (P = 0.50). The incidence of hyperamylasemia was 6.0% in the SIF-Y0004-V01 group and 14.7% in the SIF-Y0004 group (P = 0.723). The incidence of pancreatitis was 0% in the SIF-Y0004-V01 group and 5.9% in the SIF-Y0004 group (P > 0.999). The incidence of gastrointestinal perforation was 2.0% (1/50) in the SIF-Y0004-V01 group and 2.9% (1/34) in the SIF-Y0004 group (P > 0.999). CONCLUSION: SIF-Y0004-V01 is useful for ERCP in patients with Roux-en-Y anastomosis and may reduce the time required to reach the blind end.

First case of IgG4-related sclerosing cholangitis associated with autoimmune hemolytic anemia.

To our knowledge, patients with immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) associated with autoimmune hemolytic anemia (AIHA) have not been reported previously. Many patients with IgG4-SC have autoimmune pancreatitis (AIP) and respond to steroid treatment. However, isolated cases of IgG4-SC are difficult to diagnose. We describe our experience with a patient who had IgG4-SC without AIP in whom the presence of AIHA led to diagnosis. The patient was a 73-year-old man who was being treated for dementia. Liver dysfunction was diagnosed on blood tests at another hospital. Imaging studies suggested the presence of carcinoma of the hepatic hilus and primary sclerosing cholangitis, but a rapidly progressing anemia developed simultaneously. After the diagnosis of AIHA, steroid treatment was begun, and the biliary stricture improved. IgG4-SC without AIP was thus diagnosed.

A resected perivascular epithelioid cell tumor (PEComa) of the pancreas diagnosed using endoscopic ultrasound-guided fine-needle aspiration.

Primary perivascular epithelioid cell tumors (PEComas) of the pancreas are extremely rare. We herein report our experience with a patient who had a primary PEComa of the pancreas that was diagnosed by the preoperative histopathological examination of a biopsy specimen obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The patient was a 43-year-old woman whose chief complaint was abdominal pain. Imaging studies revealed a pancreatic tumor. Gastrointestinal stromal tumor (GIST), solid pseudopapillary tumor and neuroendocrine tumor were considered in the differential diagnosis. A histopathological examination of a specimen of the tumor obtained using EUS-FNA showed spindle-shaped tumor cells with enlarged nuclei and eosinophilic cytoplasm. The tumor cells proliferated in a sheet-like fashion and stained positive for the melanoma-associated antigen HMB-45. A PEComa was thus diagnosed. If an adequate tumor specimen can be obtained using EUS-FNA, immunostaining may facilitate the diagnosis of extremely rare diseases and therefore assist in deciding the treatment policy.

Clinicopathologic characteristics of pancreatic neuroendocrine tumors and relation of somatostatin receptor type 2A to outcomes.

BACKGROUND: The impact of somatostatin receptor type 2 (SSTR-2a) expression levels on outcomes in patients with pancreatic neuroendocrine tumors (PNETs) has not been evaluated. METHODS: Correlations between clinicopathologic characteristics, including SSTR-2a expression and outcomes, were retrospectively studied in 79 patients with pancreatic neuroendocrine tumors (PNETs). RESULTS: The SSTR-2a score was 0 in 27% of patients, 1 in 24% of patients, 3 in 30% of patients, and 4 in 18% of patients. The overall survival rate was 87% at 1 year, 77% at 3 years, and 71% at 5 years. On univariate analysis, a pancreatic tumor that measured ≥ 20 mm in greatest dimension, stage IV disease, vascular invasion, neuroendocrine carcinoma (NEC), and an SSTR-2a score of 0 were associated significantly with poor outcomes. On multivariate analysis, NEC (P = .000; hazard ratio, 28.8; 95% confidence interval, 7.502-111.240) and an SSTR-2a score of 0 (P = .001; hazard ratio, 3.611; 95% confidence interval, 1.344-9.702) were related independently to poor outcomes. CONCLUSIONS: The current analysis of prognostic factors in patients with PNETs demonstrated that NEC and an SSTR-2a score of 0 both were significant independent predictors of poor outcomes. The results suggest that the assessment of SSTR-2a may facilitate the selection of treatment regimens and the prediction of outcomes. Because a considerable proportion of patients with NEC have SSTR-2a-positive tumors, further analyses of the usefulness of somatostatin analogues are warranted in patients who have SSTR-2a-positive NEC.

Short-type single balloon enteroscope for endoscopic retrograde cholangiopancreatography with altered gastrointestinal anatomy.

AIM: To evaluate the effectiveness of a short-type single-balloon-enteroscope (SBE) for endoscopic retrograde cholangiopancreatography (ERCP) in patients with a reconstructed intestine. METHODS: Short-type SBE was developed to perform ERCP in postoperative patients with a reconstructed intestine. Short-type SBE is a direct-viewing endoscope with the following specifications: working length, 1520 mm; total length, 1840 mm; channel diameter, 3.2 mm. In addition, short-type SBE has a water-jet channel. The study group comprised 22 patients who underwent 31 sessions of short-type SBE-assisted ERCP from June 2011 through May 2012. Reconstruction was performed by Billroth-II (B-II) gastrectomy in 6 patients (8 sessions), Roux-en-Y (R-Y) gastrectomy in 14 patients (21 sessions), and R-Y hepaticojejunostomy in 2 patients (2 sessions). We retrospectively studied the rate of reaching the blind end (papilla of Vater or choledochojejunal anastomosis), mean time required to reach the blind end, diagnostic success rate (defined as the rate of successfully imaging the bile and pancreatic ducts), therapeutic success rate (defined as the rate of successfully completing endoscopic treatment), mean procedure time, and complications. RESULTS: Among the 31 sessions of ERCP, the rate of reaching the blind end was 88% in B-II gastrectomy, 91% in R-Y gastrectomy, and 100% in R-Y hepaticojejunostomy. The mean time required to reach the papilla was 18.3 min in B-II gastrectomy, 21.1 min in R-Y gastrectomy, and 32.5 min in R-Y hepaticojejunostomy. The diagnostic success rates in all patients and those with an intact papilla were respectively 86% and 86% in B-II gastrectomy, 90% and 87% in R-Y gastrectomy, and 100% in R-Y hepaticojejunostomy. The therapeutic success rates in all patients and those with an intact papilla were respectively 100% and 100% in B-II gastrectomy, 94% and 92% in R-Y gastrectomy, and 100% in R-Y hepaticojejunostomy. Because the channel diameter was 3.2 mm, stone extraction could be performed with a wire-guided basket in 12 sessions, and wire-guided intraductal ultrasonography could be performed in 8 sessions. As for complications, hyperamylasemia (defined as a rise in serum amylase levels to more than 3 times the upper limit of normal) occurred in 1 patient (7 sessions) with a B-II gastrectomy and 4 patients (19 sessions) with an R-Y gastrectomy. After ERCP in patients with an R-Y gastrectomy, 2 patients (19 sessions) had pancreatitis, 1 patient (21 sessions) had gastrointestinal perforation, and 1 patient (19 sessions) had papillary bleeding. Pancreatitis and bleeding were both mild. Gastrointestinal perforation improved after conservative treatment. CONCLUSION: Short-type SBE is effective for ERCP in patients with a reconstructed intestine and allows most conventional ERCP devices to be used.

Recent advances of biliary stent management.

Recent progress in chemotherapy has prolonged the survival of patients with malignant biliary strictures, leading to increased rates of stent occlusion. Even we employed metallic stents which contributed to higher rates and longer durations of patency, and occlusion of covered metallic stents now occurs in about half of all patients during their survival. We investigated the complication and patency rate for the removal of covered metallic stents, and found that the durations were similar for initial stent placement and re-intervention. In order to preserve patient quality of life, we currently recommend the use of covered metallic stents for patients with malignant biliary obstruction because of their removability and longest patency duration, even though uncovered metallic stents have similar patency durations.

Comparison of diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration with 22- and 25-gauge needles in the same patients.

BACKGROUND: Various factors, such as the optimal number of passes, aspiration pressure, and the use of 19-gauge and Trucut biopsy needles, have been studied to improve the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). We retrospectively compared the diagnostic accuracy of EUS-FNA between 25- and 22-gauge needles, which have been widely used recently. SUBJECTS AND METHODS: The study group comprised 47 consecutive patients who underwent EUS-FNA with both 22- and 25-gauge needles from October 2007 through March 2010. Their underlying diseases were pancreatic cancer in 24 patients, submucosal tumors in 11, other pancreatic tumors in 4, chronic pancreatitis in 4, enlarged lymph nodes in 3, and gall bladder cancer in 1. Tissue specimens, which were pushed out of the puncture needle, were placed into physiological saline solution. Gray-whitish, worm-like specimens were used for histologic diagnosis. The remaining specimen was centrifuged, and the sediment was plated on slides and examined by a cytopathologist to obtain the cytologic diagnosis. RESULTS: A total of 75 punctures (mean, 1.6) were performed with 25-gauge needles, and 69 punctures (mean, 1.4) were performed with 22-gauge needles. The overall tissue-sampling rate for cytology was 100% (47/47), which was significantly (p=0.01) superior to 83% (39/47) for histology. The overall diagnostic accuracy on the cytologic and histologic examinations was 79% (37/47) and 85% (33/39) (p=0.48). According to needle type, the tissue-sampling rate for cytology and histology on each puncture was 97% (73/75) and 56% (42/75) with 25-guage needles, and was 97% (67/69) and 58% (40/69) with 22-guage needles, the accuracy of cytologic diagnosis on each puncture was 73% (53/73) with 25-gauge needles and 66% (44/67) with 22-gauge needles (p=0.37); the accuracy of histologic diagnosis on each puncture was 60% (25/42) and 75% (30/40) (p=0.14), respectively. No patient had complications. CONCLUSIONS: The tissue-sampling rate and diagnostic accuracy did not differ significantly between 22- and 25-gauge needles in patients with pancreatic or gastrointestinal diseases who underwent EUS-FNA.

Diagnostic findings of ultrasound-guided fine-needle aspiration cytology for gastrointestinal stromal tumors: proposal of a combined cytology with newly defined features and histology diagnosis.

Recently, endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) has been applied for diagnosis of gastrointestinal submucosal tumors. There have been no definite criteria, however, for the adequate cytological diagnosis of gastrointestinal stromal tumor (GIST) in practice. To facilitate this a novel method is proposed that combines cytology and histology. For 49 cases of submucosal tumor of gastrointestinal tract, EUS-FNA was performed. The aspirated materials were processed for cytology and histology. Both cytological and histological findings were examined on immunocytochemical and immunohistochemical staining of c-kit. Of 49 cases, 40 (81.6%) proved adequate for cytological and/or histological examination. On cytology, cluster types were classified into type A (piled clusters with high cellularity showing a fascicular pattern), type B (thin layered clusters with high cellularity showing a fascicular pattern), and type C (mono-layered clusters or scattered cells). Types A and B were strongly associated with histological diagnosis of GIST. Type C clusters needed confirmation on c-kit positivity and histology. Thus, the combined cytology with newly defined features, and classification and histological diagnostic method for EUS-FNA materials can contribute to improved routine diagnosis for GIST.