Hiroki Sumiyoshi

Clinical outcomes for 14 consecutive patients with solid pseudopapillary neoplasms who underwent laparoscopic distal pancreatectomy

The postoperative results of laparoscopic distal pancreatectomy for solid pseudopapillary neoplasm of the pancreas (SPN), including the effects of spleen‐preserving resection, are still to be elucidated.

Laparoscopic distal pancreatectomy: Educating surgeons about advanced laparoscopic surgery

Laparoscopic distal pancreatectomy (Lap‐DP) has been recognized worldwide as a feasible and highly beneficial procedure. The aim of this study is to investigate whether Lap‐DP techniques are being implemented safely by surgeons training to perform this procedure.

Mitotic index and multipolar mitosis in routine histologic sections as prognostic markers of pancreatic cancers: A clinicopathological study

OBJECTIVES Pancreatic cancer is characterized by genomic complexity and chromosomal instability, and atypical mitotic figures are morphological features of this phenotype. In the present study, we determined the frequency and the clinicopathological and prognostic significance of mitotic figures in pancreatic cancers. METHODS We surveyed the mitotic figures of the normal ductal epithelium, acinar cells, pancreatic intraepithelial neoplasias, and pancreatic cancers on hematoxylin-and-eosin-stained tissue specimens (n = 121). RESULTS Pancreatic cancer cells showed significantly higher mitotic indices as compared with the ductal cells, acinar cells, and pancreatic intraepithelial neoplasias. Both normal and atypical mitosis were significantly elevated only in pancreatic cancers. In pancreatic cancers, approximately 30% of total mitosis was atypical including multipolar, lag-type, ring and asymmetrical mitosis, and anaphase bridges. The Kaplan-Meier curves in pancreatic cancers showed significant correlations between total mitosis and disease free survival. Furthermore, the cases with multipolar mitosis showed poorer prognosis than those without. Lymph node metastasis and multipolar mitosis were independent prognostic factors for overall survival of patients with pancreatic cancer. In addition, lymph node metastasis and total mitosis were independent factors for disease free survival. CONCLUSION These findings suggest that routinely obtained pathological specimens, even small biopsy or cytological specimens, can provide valuable information concerning the prognosis of pancreatic cancers.

Suppression of STAT5b in pancreatic cancer cells leads to attenuated gemcitabine chemoresistance, adhesion and invasion

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid malignancies, and there is an urgent need for new therapeutic strategies based on the molecular biology of PDAC. Signal transducers and activators of transcription 5 (STAT5) are known to be activated in a variety of malignancies and involved in tumor proliferation, apoptosis, and invasion, whereas the expression and biological role of STAT5b in PDAC are less clearly defined. In the present study, we examined the expression and role of STAT5b in human pancreatic cancer cell lines. Expressions of STAT5b mRNA and protein were detected in eight kinds of pancreatic cancer cells. Confocal microscopy and western blot analysis indicated that STAT5b is localized in both cytoplasm and nuclei. Immunoprecipitation analysis revealed tyrosine phosphorylation of STAT5b in pancreatic cancer cells. These results indicate that STAT5b in pancreatic cancer cells is constitutively activated. STAT5b shRNA clones in PANC-1 cells, which express relatively high levels of STAT5b, exhibited reduced chemoresistance against gemcitabine, adhesion and invasion compared to sham. On the other hand, AsPC-1 and BxPC3 cells, which express relatively low levels of STAT5b, exhibited reduced chemoresistance compared to PANC-1 cells. Moreover, STAT5b overexpression clones in AsPC-1 cells exhibited increased chemoresistance compared to sham. STAT5b shRNA clones in PANC-1 cells were more sensitive to the proapoptotic actions of gemcitabine, as evidenced by PARP and cleaved caspase-3 activation. Gemcitabine also significantly reduced Bcl-xL levels in the STAT5b shRNA-expressing cells. We also investigated the clinicopathological characteristics of STAT5b expression of PDAC. Although a significant correlation between STAT5b expression and overall survival rates was not observed, a significant correlation with main pancreatic duct invasion was observed. These findings suggest that STAT5b confers gemcitabine chemoresistance and promotes cell adherence and invasiveness in pancreatic cancer cells. Targeting STAT5b may lead to novel therapeutic strategies for PDAC.

Clinical outcomes of 15 consecutive patients who underwent laparoscopic insulinoma resection: The usefulness of monitoring intraoperative blood insulin during laparoscopic pancreatectomy

Insulinoma is a very serious functional tumor. Surgeons should confirm complete resection of insulinomas before completing the operation, even in laparoscopic surgery.

Gastroenterological Surgery: Pancreas

■ Explanation No study has compared the outcomes of LDP with that of open distal pancreatectomy (ODP) for the treatment of benign or low-grade lesions. With regard to the treatment of malignant disease, a meta-analysis shows no significant difference in the percentage of positive margin along the resection line between LDP and ODP (1). Another study of patients with benign to low-grade lesions as well as malignant disease also shows no significant difference between LDP and ODP with respect to positive margin, although the evidence level is low (2). Regarding intraoperative measures, two meta-analyses show LDP results in significantly less blood loss than ODP, with no significant difference in surgical time (1,3). These meta-analyses also show that LDP has a significantly lower incidence of all complications and a significantly shorter length of hospitalization than ODP (1,3). These intraoperative and postoperative findings suggest LDP may reduce total operative expense compared to ODP; this is corroborated by a low evidencelevel study suggesting the cost-saving potential of LDP over ODP (4). The same meta-analyses also show no significant difference in the reoperation or operational death rate between LDP and ODP (1,3). 1-2 Is postoperative recovery earlier after laparoscopic surgery than after laparotomy? Laparoscopic surgery is likely to lead to earlier resolution of wound pain, but there is no robust evidence supporting the lower invasiveness of laparoscopic pancreatectomy compared to open pancreatectomy.

Laparoscopic Pancreatectomy for Pancreatic Cancer

Introduction: The recent advances of surgical techniques and technology allow minimally invasive surgery to be applied in patients with benign and malignant diseases of the pancreas. About malignancy, we still have concerns regarding the oncologic adequacy of laparoscopic pancreatectomy, with fewer studies reporting oncologic outcomes. We describe the surgical technique to improve the curability of laparoscopic pancreatectomy in the treatment of Pancreatic Adenocarcinoma (PDAC) and focuse on the oncologic outcomes and long-term outcomes of laparoscopic surgery for PDAC patients. Methods: From January 2004, patients who had been diagnosed with the tumor in the pancreas without suspicion for vascular involvement were eligible for laparoscopic pancreatectomy at Nippon Medical School. In Lap- PD for PDAC patients, we apply laparoscopic left mesenteric approach, which enables both accurate laparoscopic lymph node retrieval and complete pancreatic nerve plexuses dissection to achieve R0 resection. In Lap-DP for PDAC patients, we perform retroperitoneal tissue dissection, which often includes adrenalectomy. Results: We have experienced laparoscopic pancreatectomies in 148 patients including 25 PDAC patients. In the 25 patients with PDAC, the mean number of lymph nodes dissected was 22.4 ± 12.6 (6–57). Metastasis to the lymph nodes was observed in 8 of the 25 patients (32%). R0 resection was performed in 22 patients (88%). The median follow-up period for the PDAC patients undergoing laparoscopic pancreatectomy was 16 months (1–71 months). Six of the 25 patients died, at 2.5 months (stage IV), 15 months (stage IA), 29 months (stage IIB), 33 months (stage IIB), 24 months (stage IIA), and 18 months (stage IIB). Surviving 19 patients had no recurrence. Conclusion: Laparoscopic pancreatectomy for pancreatic cancer seems to achieve similar oncologic and longterm outcomes to open approach.

A Pilot Study- Neoadjuvant Chemotherapy with Gemcitabine and S1 in Patients with Resectable and Borderline Resectable Pancreatic Cancer

Introduction: Combination chemotherapy with gemcitabine and S-1 (GS) in metastatic advanced pancreatic cancer patients is superior to gemcitabine alone in response rate and progression free survival. We investigated this combination chemotherapy as neoadjuvant therapy for resectable and borderline resectable pancreatic cancer. Methods: Eleven patients with resectable or borderline resectable pancreatic cancer were administered to neoadjuvant chemotherapy with GS (NeoGS) from June 2011 to March 2013 at Nippon Medical School, and shortterm outcome was evaluated. Results: The median age was 69.1 years. According to NCCN criteria, 6 patients were resectable diseases and 5 were borderline resectable diseases. All patients received Neo GS with a median cycle of 3.5 (range: 2-11). No serious adverse events including death or life-threatening complications happened. Grade 3 or 4 chemotherapyrelated toxicities included neutropenia (81.8%), anemia (18.2%), thrombocytopenia (18.2%), and febrile neutropenia (9.1%). Other non-hematological toxicities with grade 1 or 2 were anorexia (36.4%), constipation (36%), nausea (27.3%), diarrhea (18.2%), dysgeusia (9.1%), and stomatitis (9.1%). Radiologically, partial response was documented in 3 patients (27.3%), and the remaining 8 patients (72.7%) had stable disease. All patients underwent pancreatic resection with lymphadenectomy. An R0 resection was achieved in 10 of 11 (90.9%), and negative nodal involvement (N0) was found in 6 (54.5%). Pathologically, all specimens showed at least Evans grade I, while eight of eleven (72.7%) had Evans grade IIa. There was no mortality and severe morbidity including clinically relevant pancreatic fistula. All patients received adjuvant chemotherapy with either gemcitabine or S1. Conclusion: This pilot study suggests NeoGS is feasible in patients with resectable and borderline resectable pancreatic cancer and may be associated with a high R0 resection rate and a low lymph node metastasis rate, suggesting that further phase 2 and 3 trials are warranted.