Tsutomu Tanaka

Cisplatin and Etoposide as First-line Chemotherapy for Poorly Differentiated Neuroendocrine Carcinoma of the Hepatobiliary Tract and Pancreas

OBJECTIVEnThe combination chemotherapy consisting of cisplatin and etoposide, one of the standard regimens for small cell lung cancer, has been widely used to treat extrapulmonary poorly differentiated neuroendocrine carcinomas. However, there were no prior reports limited to the hepatobiliary tract and pancreas as the primary sites.nnnMETHODSnWe reviewed the cases in our database from October 1995 to January 2009 and retrospectively examined the clinical data of patients, with unresectable or recurrent poorly differentiated neuroendocrine carcinoma arising from the hepatobiliary tract and pancreas, who received combination chemotherapy with cisplatin and etoposide as the first-line treatment. The chemotherapy regimen consisted of cisplatin 80 mg/m(2) given intravenously on day 1 and etoposide 100 mg/m(2) intravenously on days 1-3, repeated every 3-4 weeks.nnnRESULTSnTwenty-one patients were treated with the above regimen of cisplatin and etoposide combination chemotherapy. The primary tumor site was the liver in 2 patients, gallbladder in 8 patients, pancreas in 10 patients and ampulla of Vater in 1 patient. Although no complete responses were obtained, three patients had partial responses, resulting in an overall response rate of 14%. Median progression-free survival was 1.8 months, and median overall survival was 5.8 months. The major adverse events were myelosuppression and gastrointestinal toxicities, with Grade 3 or 4 neutropenia (90%), nausea (33%) and anorexia (24%).nnnCONCLUSIONSnCisplatin and etoposide combination as the first-line chemotherapy for hepatobiliary or pancreatic poorly differentiated neuroendocrine carcinoma had only marginal antitumor activity and relatively severe toxicity compared with previous studies on extrapulmonary poorly differentiated neuroendocrine carcinoma treated with the same regimen.

Diagnostic ability and factors affecting accuracy of endoscopic ultrasound-guided fine needle aspiration for pancreatic solid lesions: Japanese large single center experience.

BackgroundSeveral studies have investigated the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for pancreatic lesions, but they have included only limited patient populations. This study aimed to clarify the diagnostic accuracy of EUS-FNA in a large number of pancreatic lesions, and to describe the factors that influence it.MethodsFrom March 1997 to May 2010, 944 consecutive patients who had undergone EUS-FNA for pancreatic solid lesions were evaluated retrospectively. Factors affecting EUS-FNA accuracy were then analyzed.ResultsA total of 996 solid pancreatic lesions were sampled by EUS-FNA. The overall sampling adequacy and diagnostic accuracy of these lesions were 99.3xa0% (989/996) and 91.8xa0% (918/996), respectively. The sensitivity and specificity for differentiating malignant from benign lesions were 91.5xa0% (793/867) and 97.7xa0% (126/129), respectively. The diagnostic performance was significantly higher when both cytological and cell-block examinations were carried out than with only cytological examination. In multivariate analysis, final diagnosis, location of lesion, lesion size, availability of on-site cytopathological evaluation, and experience of EUS-FNA procedure were independent factors affecting the accuracy of EUS-FNA. On-site cytopathological evaluation and lesion size were found to be the most weighted factors affecting diagnostic accuracy.ConclusionsEUS-FNA for pancreatic solid lesions yielded a high accuracy and low complication rate. Both cytological and cell-block preparations and on-site cytopathological evaluation contributed to improve the accuracy. The diagnostic ability of EUS-FNA was less for smaller lesions, and repeated procedures may be needed if malignancy is suspected.

Prognostic Factors in Japanese Patients with Advanced Pancreatic Cancer Treated with Single-agent Gemcitabine as First-line Therapy

OBJECTIVEnThe purpose of the retrospective analysis is to elucidate the treatment efficacy and toxicity as well as to identify prognostic factors in Japanese patients with advanced pancreatic cancer treated with gemcitabine.nnnMETHODSnTwo hundred and sixty-four patients with pathologically confirmed locally advanced or metastatic pancreatic cancer, who had received gemcitabine monotherapy as first-line chemotherapy for pancreatic cancer, were analyzed. A dose of 1000 mg/m(2) gemcitabine was administered intravenously for 30 min on Days 1, 8 and 15 of a 28-day cycle.nnnRESULTSnOne patient achieved a complete response (0.3%) and 27 patients showed a partial response (10.2%), with an overall response rate of 10.6% (95% confidence interval: 6.9-14.3%). The main grade 3/4 toxicities were neutropenia in 94 patients (35.6%) and leukocytopenia in 52 patients (19.7%). The median survival time, 1-year survival proportion and median progression-free survival time were 6.8 months, 21.6% and 3.7 months, respectively. A multivariate analysis using the Cox proportional hazards model demonstrated that a Karnofsky performance status > or = 90 (P = 0.01), Stage III (P = 0.01), serum carbohydrate antigen 19-9 level <10,000 U/ml (P = 0.02), serum hemoglobin level > or = 10 g/dl (P = 0.01) and serum C-reactive protein level <5.0 mg/dl (P < 0.01) were the independent favorable prognostic factors.nnnCONCLUSIONSnThe treatment efficacy, toxicity and prognostic factors of single-agent gemcitabine in Japanese patients with advanced pancreatic cancer are comparable to those that have been reported in Western patients. These results may be useful as reference data in determining treatments strategies and planning for further clinical trials in Japanese patients with advanced pancreatic cancer.

Does the WHO 2010 classification of pancreatic neuroendocrine neoplasms accurately characterize pancreatic neuroendocrine carcinomas

BackgroundThe WHO classified pancreatic neuroendocrine neoplasms in 2010 as G1, G2, and neuroendocrine carcinoma (NEC), according to the Ki67 labeling index (LI). However, the clinical behavior of NEC is still not fully studied. We aimed to clarify the clinicopathological and molecular characteristics of NECs.MethodsWe retrospectively evaluated the clinicopathological characteristics, KRAS mutation status, treatment response, and the overall survival of eleven pNEC patients diagnosed between 2001 and 2014 according to the WHO 2010. We subclassified WHO-NECs into well-differentiated NEC (WDNEC) and poorly differentiated NEC (PDNEC). The latter was further subdivided into large-cell and small-cell subtypes.ResultsThe median Ki67 LI was 69.1xa0% (range 40–95xa0%). Eleven WHO-NECs were subclassified into 4 WDNECs and 7 PDNECs. The latter was further separated into 3 large-cell and 4 small-cell subtypes. Comparisons of WDNEC vs. PDNEC revealed the following traits: hypervascularity on CT, 50xa0% (2/4) vs. 0xa0% (0/7) (Pxa0=xa00.109); median Ki67 LI, 46.3xa0% (40–53xa0%) vs. 85xa0% (54–95xa0%) (Pxa0=xa00.001); Rb immunopositivity, 100xa0% (4/4) vs. 14xa0% (1/7) (Pxa0=xa00.015); KRAS mutations, 0xa0% (0/4) vs. 86xa0% (6/7) (Pxa0=xa00.015); response rates to platinum-based chemotherapy, 0xa0% (0/2) vs. 100xa0% (4/4) (Pxa0=xa00.067), and median survival, 227 vs. 186xa0days (Pxa0=xa00.227).ConclusionsThe WHO-NEC category may be composed of heterogeneous disease entities, namely WDNEC and PDNEC. These subgroups tended to exhibit differing profiles of Ki67 LI, Rb immunopositivity and KRAS mutation, and distinct response to chemotherapy. Further studies for the reevaluation of the current WHO 2010 classification are warranted.

Nodal cytotoxic molecule (CM)-positive Epstein-Barr virus (EBV)-associated peripheral T cell lymphoma (PTCL): a clinicopathological study of 26 cases.

Kato S, Takahashi E, Asano N, Tanaka T, Megahed N, Kinoshita T & Nakamura S u2028(2012) Histopathology 61, 186–199

Retrospective analysis of primary gastric diffuse large B cell lymphoma in the rituximab era: a multicenter study of 95 patients in Japan

Primary gastric diffuse large B cell lymphoma (PG-DLBCL) is common subtype of extranodal non-Hodgkin lymphoma. The optimal treatment strategy for PG-DLBCL in the rituximab era still remains unknown. To evaluate clinical outcomes of PG-DLBCL in the rituximab era, we conducted a retrospective, multicenter analysis of 95 patients with PG-DLBCL. In 58 patients with localized disease, 3-year progression-free survival (PFS) and overall survival (OS) were 91% and 91% for patients with six cycles of rituximab plus CHOP (R-CHOP) and 92% and 95% for patients with three to four cycles of R-CHOP plus radiotherapy (Log-rank test, Pu2009=u20090.595 and Pu2009=u20090.278, respectively). In 37 patients with advanced disease, 3-year PFS and 3-year OS were 43% and 64% for patients with R-CHOP chemotherapy with or without radiotherapy. On multivariate analysis, advanced stage and elevated serum LDH levels were independent predictors of survival in patients with PG-DLBCL. One patient with localized disease relapsed in lymph node, and eight patients with advanced disease relapsed in lymph node (nu2009=u20093), stomach (nu2009=u20092), central nervous system (CNS; nu2009=u20092), and duodenum (nu2009=u20091). Intriguingly, CNS relapse developed within 6xa0months after initial series of treatment (4.9 and 5.8xa0months, respectively), and stomach relapse developed in later phase (27.2 and 32.9xa0months, respectively). Clinical outcomes of PG-DLBCL were extremely favorable for localized-stage patients in the rituximab era, although these might be poor for advanced-stage patients even in the rituximab era. Further prospective analyses are warranted.

Diagnostic performance and factors influencing the accuracy of EUS-FNA of pancreatic neuroendocrine neoplasms.

BackgroundMultiple studies have investigated sampling adequacy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for pancreatic neuroendocrine neoplasms (pNENs). However, none have described the diagnostic performance of EUS-FNA for pNENs, or the influencing factors. The aim of this study was to evaluate the diagnostic accuracy of EUS-FNA, with post-operative pathological diagnosis as the gold standard, and factors predictive of inadequate EUS sampling.MethodsFrom 1998 to 2014, a total of 698 patients underwent pancreatic resection and 1455 patients underwent EUS-FNA sampling for pancreatic lesions. A total of 410 cases underwent both surgical resection and preceding EUS-FNA. Of these, 60 cases (49 true pNEN, nine non-diagnostic, two misdiagnoses) were included. We studied diagnostic performance of EUS-FNA and factors that were associated with failed diagnosis.ResultsOf the 60 cases, EUS-FNA yield was 49 true-positive cases, two misdiagnoses, and nine non-diagnostic cases (including six suggestive cases). Sensitivity, specificity, and accuracy were 84.5, 99.4, and 97.3xa0%, respectively; including the six suggestive cases, diagnostic values were 94.8xa0% sensitivity (55/58), 99.4xa0% specificity (350/352), and 98.7xa0% accuracy (405/410). In multivariate analysis, sampling adequacy rates were significantly lower when lesions were located in the pancreatic head [odds ratio (OR)xa0=xa010.0] and in tumor-rich stromal fibrosis (ORxa0=xa010.45). Tumor size, needle type, tumor grading, presence of cystic component, and time period were not significant factors.ConclusionsEUS-FNA offers high accuracy for pNEN. However, location of the tumor in the pancreatic head and presence of rich stromal fibrosis negatively impacts sampling adequacy.

Diagnostic and prognostic value of immunohistochemical expression of S100P and IMP3 in transpapillary biliary forceps biopsy samples of extrahepatic bile duct carcinoma

BackgroundBecause the biopsy specimen of extrahepatic bile duct carcinoma (EHBDC) is small and shows reactive changes, the histological distinction between malignant and benign tissue can be difficult. Recent studies reported that S100P and insulin-like growth factor II mRNA-binding protein 3 (IMP3) were not only diagnostic molecules but also prognostic biomarkers in several organs. The objective of this study is to clarify the diagnostic and prognostic value of immunohistochemical expression of S100P and IMP3 in transpapillary biliary forceps biopsy (TBFB) samples.MethodsThe TBFB samples were collected from 80 patients (EHBDC, 68 patients; benign, 12 patients), retrospectively.ResultsWhen using cytoplasmic-positive staining for IMP3 as a marker of malignancy, the sensitivity and specificity reached 79.4 and 91.7xa0%, respectively. The sensitivity, specificity and accuracy achieved 89.7, 91.7 and 90.0xa0%, respectively, when using positive staining for IMP3 and/or positive histology as a maker of malignancy. While univariate (Pxa0=xa00.033) and multivariate (Pxa0=xa00.039) analysis revealed that S100P-positive EHBDC patients showed significantly shorter survival.ConclusionsThe results of this study suggest that immunohistochemical staining for IMP3 is useful in the diagnosis of EHBDC and that of S100P is useful as a prognostic marker for EHBDC.

Diagnostic yield of endoscopic retrograde cholangiography and of EUS-guided fine needle aspiration sampling in gallbladder carcinomas

BackgroundObtaining histological evidence of gallbladder carcinoma (GBC) is difficult due to its extraductal nature, and pathological confirmation remains challenging. We compared the diagnostic value and safety of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with endoscopic retrograde cholangiography (ERC) in patients with suspected GBC.PatientsEighty-three patients with GBC were evaluated. Prior to definitive management, pathological evidence of GBC was obtained through either ERC cytopathologic sampling (nxa0=xa033), EUS-FNA (nxa0=xa024) or both (nxa0=xa026).ResultsAmong the 83 patients, 59 (71.0%) with biliary obstruction were sampled using ERC with 47.4% (28/59) sensitivity. In 19 of the remaining 31 cases, EUS-FNA sampling had 100% diagnostic sensitivity. Likewise, 50 (60.2%) of the 83 patients with suspected GBC underwent EUS-FNA of regional lymph nodes or the gallbladder (GB) mass itself with 94.8% sensitivity. The overall diagnostic sensitivity rates of ERC and EUS-FNA were 47.4 and 96%, respectively (Pxa0<xa00.001). Post-procedural complications were seen in 6.7% of the ERC group (4/59, all were mild pancreatitis), and in none of the EUS-FNA group (Pxa0=xa00.10).ConclusionsGallbladder carcinoma sampling using ERC and EUS-FNA should be incorporated into the diagnostic workup of GB lesions as complementary tools, and EUS-FNA should be applied in the setting of failed or not indicated ERC.

Can endoscopic ultrasound-guided fine needle aspiration offer clinical benefit for tumors of the ampulla of vater? -An initial study

Objective: No previous studies have described endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) only for intra-ampullary lesions of the papilla of Vater. We aimed to examine whether EUS-FNA can be used to diagnose such lesions. Methods: This study included a subset of 10 consecutive patients in whom EUS-FNA targeted the ampulla of Vater. All the patients underwent biopsy and/or brushing cytology under endoscopic retrograde cholangiopancreatography (ERCP) prior to EUS-FNA. The final diagnosis was based on pathological examinations of specimens obtained by surgical resection or clinical follow-up more than 1 year in case of evidence of benign lesions. Results: Tissues from the ampulla of Vater could be obtained by EUS-FNA for all 10 patients. The final diagnosis was papillitis (n = 7) and intra-ampullary carcinoma (n = 3). Carcinoma of the ampulla of Vater showed neither exposure on the duodenal mucosal surface nor invasion to the pancreas. The diagnostic accuracy of surface biopsy with duodenoscopy, and intra-ampullary biopsy and/or brush cytology with ERCP and/or intra-ampullary biopsy after endoscopic sphincterotomy (EST) in distinguishing between benign and malignancy was 70%. The diagnostic accuracy of EUS-FNA was 100%. No complications associated with EUS-FNA were encountered in this study. Conclusion: EUS-FNA for ampulla of Vater may be safely and accurately performed, and should be considered as a diagnostic modality before EST.