Akimasa Nakao

Prognostic factors for survival after extended pancreatectomy for pancreatic head cancer: influence of resection margin status on survival.

Objectives: Although a positive resection margin has been reported to be a strong prognostic factor after resection for pancreatic cancer, several studies indicated that resection status did not independently affect survival. The aim of this study was to examine the influence of resection margin status on survival after extended radical resection for pancreatic head cancer. Methods: One hundred thirty-eight cases of pancreatoduodenectomy and 38 cases of pylorus-preserving pancreatoduodenectomy for invasive ductal carcinoma of the pancreas were retrospectively analyzed. Results: The resection margins were negative (R0) in 115 patients (65.3%), microscopically positive (R1) in 38 patients (21.6%), and grossly positive (R2) in 23 patients (13.1%). Patients with R1 resection survived significantly shorter (median survival time [MST], 9.4 months) than R0 resection patients (MST, 15.2 months) but survived longer than R2 resection patients (MST, 6.2 months). By multivariate analysis, R2 resection, together with lymph node metastasis, portal venous system, and extrapancreatic nerve plexus invasions, independently affected the overall survival, but R1 resection was not significantly influential. Conclusions: R2 resection was an independent predictor of poor prognosis after pancreatoduodenectomy/pylorus-preserving pancreatoduodenectomy, whereas R1 resection did not independently affect the survival.

Pancreatic cancer with paraaortic lymph node metastasis: a contraindication for radical surgery?

Objectives: The purpose of this study was to determine the operative indications for pancreatic cancer with paraaortic lymph node metastases (No. 16 [+]). Methods: Between July 1981 and March 2007, 335 patients with pancreatic cancer including 45 No. 16 (+) patients underwent extended radical surgery at the Department of Surgery II, Nagoya University. The overall survival rates and clinicopathological parameters were analyzed using univariate and multivariate analyses. Results: Although there was no significant difference in survival between the No. 16 (+) patients and the unresectable cases, there were some long-term survivors among the No. 16 (+) patients. Multivariate analysis of the No. 16 (+) patients identified age (59 years or younger), tumor size (>4 cm), and pathologically confirmed portal invasion (pPV[+]) as independent prognostic factors. The survival of No. 16 (+) patients without these factors was significantly better than the unresectable cases. The survival of patients with only 1 metastatic paraaortic lymph node also was significantly better than the unresectable cases, and tended to be better than those with more than 2 metastatic nodes. Conclusions: No. 16 (+) pancreatic cancer patients with age 60 years or older, tumor size 4 cm or less, and pPV(−) may benefit from resection.

A phase II study of radical surgery followed by postoperative chemotherapy with S-1 for gastric carcinoma with free cancer cells in the peritoneal cavity (CCOG0301 study)

BACKGROUNDnPatients with gastric cancer who have positive cytologic results for cancer cells in peritoneal washings (CY1) have poor outcomes, even in the absence of other distant metastases. A standard treatment for such patients remains to be established.nnnMETHODSnWe conducted a phase II trial with the 2-year survival rate as the primary endpoint. Patients who had gastric cancer with CY1 status but no other residual disease received postoperative chemotherapy with S-1 (1M tegafur-0.4M gimestat-1M otastat potassium) at a daily dose of 80mg/m(2) for 4 weeks, followed by 2 weeks of rest. This cycle was continued until disease progression or intolerable adverse events. D2 dissection was the recommended surgical procedure; splenectomy could be omitted at the discretion of the surgeon. Accrual of 50 patients was planned, and a 2-year survival rate of more than 36% was needed to exceed the historical control.nnnRESULTSnForty-eight patients were enrolled, among whom 47 were assessable for survival and 46 for adverse reactions. Median overall survival was 705 days, and progression-free survival was 376 days. The 2-year survival rate was 47%. Median time to treatment failure was 288 days. Neutropenia was the commonest > or = grade 3 toxicity (6 patients), and anorexia was the most frequent > or = grade 2 non-hematologic toxicity (10 patients).nnnCONCLUSIONSnGastrectomy followed by S-1 monotherapy resulted in survival that surpassed historical data and can serve as an active control treatment for future trials in patients who have gastric cancer with CY1 status in the Far East.

Nonfunctioning neuroendocrine pancreatic tumors: our experience and management

BACKGROUND AND PURPOSEnWe present our experience in the treatment of nonfunctioning neuroendocrine pancreatic tumors (NFNPTs) to define the clinical and pathological characteristics and to suggest proper management.nnnMETHODSnThe records of 17 patients with NFNPTs operated on between 1998 and 2008 were retrospectively reviewed, and all tumors were classified clinicopathologically as benign, uncertain, and malignant, based on the World Health Organization (WHO) classification of neuroendocrine tumors.nnnRESULTSnThere were four benign, six uncertain, and seven malignant NFNPTs. The most frequent symptoms were abdominal pain (five patients) and obstructive jaundice (one patient). Most of these symptomatic patients had malignant tumors. Mean tumor size of benign, uncertain, and malignant tumors were 1.0 +/- 0.3, 3.2 +/- 1.6, and 5.3 +/- 2.4 cm, respectively. Metastatic lesions of malignant tumors were lymph node (six patients), liver (four patients), and adrenal gland (one patient). Six of seven patients with malignant tumors underwent curative rejection. There were recurrences in four of six patients with curatively rejected malignant tumors. Two patients underwent more rejection, three patients received systemic chemotherapy, and two patients underwent radiofrequency ablation and transcatheter arterial chemoembolization for liver metastases. Survival of patients with malignant tumors was significantly shorter than that of patients with benign and uncertain tumors. However, three patients with malignant tumors had long survival of more than 3 years, even with metastases or recurrences.nnnCONCLUSIONSnAggressive surgical resection should be performed in patients with resectable NFNPTs, even with metastases. Even when a tumor was unresectable or there were recurrences, long-time palliation could be achieved by a multidisciplinary approach.

The tumor suppressor NPRL2 in hepatocellular carcinoma plays an important role in progression and can be served as an independent prognostic factor

Hepatocarcinogenesis is a multifactorial, multistep process that involves the activation of oncogenes or the inactivation of tumor suppressor genes throughout the different stages of hepatocellular carcinoma (HCC) progression. NPRL2 is one of the candidate tumor suppressor genes identified on chromosome 3p21.3, a region which frequently contains genetic abnormalities found in the early stages of the development of various human cancers. In the current study, we aimed to evaluate NPRL2 expression in HCC and to explore the prognostic significance of NPRL2.

Radical Surgery for Gastric Carcinoma: It is Not an Issue of Whether to Perform D1 or D2. Dissect as Many Lymph Nodes as Possible and You Will Be Rewarded

Abstract In the current review article, evidences on radical surgery for gastric cancer reported in the literature are highlighted. The authors conclude that extended lymphadenectomy offers a statistically significant survival benefit. This benefit is only evident if the operative mortality is less than 2%, as obtained in centers of excellence with a high-volume experience of resection of gastric cancer. Lymphadenectomy should no longer be considered only as a tool for cancer-staging, but also as a beneficial therapeutic measure.

Serial measurement of Doppler hepatic hemodynamic parameters for the diagnosis of acute rejection after live donor liver transplantation

To elucidate the role of Doppler hepatic hemodynamic parameters as surrogate markers of acute rejection (AR) after live donor liver transplantation (LDLT), serial Doppler measurements were prospectively performed during the first 2 weeks after LDLT to compare the longitudinal hepatic hemodynamic changes between patients with histologically proven AR and patients without histologically proven AR. Forty‐six patients that had undergone adult‐to‐adult LDLT using a right lobe graft were enrolled in this study. The portal venous maximum velocity (PVV; cm/second), portal venous flow volume, hepatic arterial peak systolic velocity, hepatic arterial pulsatility index, hepatic venous maximum velocity, hepatic venous pulsatility index, and splenic arterial pulsatility index were measured. Fourteen patients were diagnosed by biopsy to have clinically relevant AR. Markedly increased PVV was seen soon after surgery and gradually decreased in both patients with clinically relevant AR and patients without clinically relevant AR. This serial change of decreasing PVV was significantly greater in patients with clinically relevant AR (P < 0.0001). After postoperative day 6, the PVV in patients with clinically relevant AR was significantly lower than that in patients without clinically relevant AR (PVV on postoperative day 6: 35.6 ± 21.3 versus 58.3 ± 27.1 cm/second, respectively, P = 0.0080). A PVV cutoff value of 20.2 cm/second demonstrated the best accuracy for predicting clinically relevant AR. The sensitivity and specificity for predicting clinically relevant AR were 92.9% and 87.1%, respectively. The area under the curve was 0.94. In conclusion, serial Doppler measurement of hepatic parameters in LDLT is useful for the diagnosis of clinically relevant AR. Clinically relevant AR should therefore be suspected when a marked unexpected decrease in the PVV is observed. Liver Transpl 15:1119–1125, 2009.

Considerations for intravascular administration of oncolytic herpes virus for the treatment of multiple liver metastases

PurposeOncolytic viral therapy is a newly developed modality for treating tumors. Many clinical trials using oncolytic virus have been performed worldwide, but most of them have used local injection in the tumor. Determination of the effect and safety of intravascular virus injection instead of local injection is necessary for clinical use against multiple liver metastases and systemic metastases.MethodsTo evaluate the efficacy and safety of intravascular virus therapy, mice bearing multiple liver metastases were treated by intraportal or intravenous administration of the herpes simplex virus type 1 (HSV-1) mutant, hrR3. Mice treated with hrR3 were killed and organs were harvested for lacZ staining and PCR analysis. Inactivation of oncolytic virus in bloodstream was assessed by neutralization assay in vitro. Infectious activity of hrR3 with vascular endothelial cells was evaluated by replication and cytotoxicity assay.ResultsThe survival rate of animals treated by hrR3 was significantly improved compared with the untreated group. lacZ staining and PCR analysis demonstrated detectable virus in the tumor but not in normal tissue or other organs except for the adrenal glands. We also showed that vascular endothelial cells allowed virus replication, while normal hepatocytes did not, and human anti-HSV antibody revealed attenuation of the infectious activity of hrR3.ConclusionsIntravascular delivery of hrR3 is effective in treating multiple liver metastases, however, several points must be kept in mind at the time of human clinical trials using intravascular virus administration in order to avoid critical side effects.