Satoshi Shiba

Characteristics of 18 patients with hepatocellular carcinoma who obtained a complete response after treatment with sorafenib

Sorafenib, a multi‐targeted tyrosine kinase inhibitor, is a first‐line systemic treatment for advanced hepatocellular carcinoma (HCC). However, possible predictors of the efficacy of sorafenib treatment in HCC patients remain unclear.

Pancreatic neuroendocrine tumors: a single-center 20-year experience with 100 patients

BACKGROUND/OBJECTIVES Pancreatic neuroendocrine neoplasms (NENs) are rare tumors, exhibiting several morphological, functional, and behavioral characteristics. However, only few reports have evaluated large case series of pancreatic NEN. METHODS We conducted a retrospective review of 100 consecutive patients with pancreatic NEN diagnosed pathologically and treated at the National Cancer Center Hospital between 1991 and 2010. RESULTS The study included 48 males and 52 females (median age: 55 years). Fourteen patients had clinical symptoms caused by excess hormone secretion at diagnosis. Twelve patients were diagnosed with neuroendocrine tumor (NET) G1, 54 with NET G2, and 32 with neuroendocrine carcinoma (NEC) as per the 2010 World Health Organization classification. Distant metastases were observed in 25%, 43%, and 84% of the patients with NET G1, NET G2, and NEC, respectively. Serum levels of neuron-specific enolase and lactate dehydrogenase significantly increased in patients with NEC compared with those in patients with NET G1/G2. The 5-year survival rates of patients with NET G1, NET G2, and NEC were 91%, 69%, and 10%, respectively. Good performance status (PS), lower stage, and histopathological grade were identified as independent favorable prognostic factors. CONCLUSIONS Patients with NET G1/G2 treated with surgical resection had a good prognosis. Most patients with NEC exhibited distant metastases and had a poor prognosis. Staging classification and the WHO 2010 grading are important factors for selecting the appropriate treatment strategy and predicting prognosis for patients with pancreatic NEN.

Hepatitis B Virus Reactivation during Treatment with Multi-Tyrosine Kinase Inhibitor for Hepatocellular Carcinoma

Hepatitis B virus (HBV) reactivation is well documented in individuals with cancer who receive certain cytotoxic or immunosuppressive therapies including rituximab treatment. As a general rule, the risk is greatest upon withdrawal of chemotherapy. The risk ranges from approximately 20 to 50% among HBsAg-positive carriers. A 67-year-old man was diagnosed with inoperable multiple hepatocellular carcinoma accompanied by an increase in alpha-fetoprotein and protein induced by vitamin K absence or antagonist II level. Eighteen weeks after starting on the oral multi-tyrosine kinase inhibitor TSU-68, laboratory investigations showed a substantial increase in serum transaminase levels (AST: 302 IU/l; ALT: 324 IU/l) and an elevation of the HBV-DNA level (6.9 log copies/ml). The diagnosis was that the cause of the acute hepatitis was HBV reactivation and we immediately administered entecavir. Two months after the initiation of daily entecavir treatment, laboratory findings showed that the serum levels of transaminases and ALP had improved (AST: 18 IU/l; ALT: 10 IU/l; ALP: 197 U/l). When the HBV markers were examined 4 months later, they were altered: HBeAg was negative and HBeAb was positive. Entecavir treatment was discontinued after 6 months. Although reactivation with rituximab has been reported, reactivation with a tyrosine kinase inhibitor is extremely unusual in a patient who is HBsAg negative but anti-HBc positive. This is the first report describing HBV reactivation with an increasing HBV-DNA level in a HBsAg-negative/HBcAb-positive/HBsAb-positive patient who was treated with TSU-68 for hepatocellular carcinoma.

Multicenter retrospective analysis of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma.

We conducted a multicenter retrospective analysis to evaluate the efficacy of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma. We enrolled 36 patients with pathologically proven, unresectable combined hepatocellular and cholangiocarcinoma treated with systemic chemotherapy. The log‐rank test determined the significance of each prognostic factor. Elevated alpha‐fetoprotein, carcinoembryonic antigen and carbohydrate antigen 19‐9 levels were observed in 58.3%, 16.7% and 38.9% of patients, respectively. First‐line chemotherapy included platinum‐containing regimens consisting of gemcitabine/cisplatin (n = 12) and fluorouracil/cisplatin (n = 11), sorafenib (n = 5) and others (n = 8). The median overall and progression‐free survival times were 8.9 and 2.8 months, respectively, with an overall response rate of 5.6%. Prognostic factors associated with negative outcomes included poor performance status, no prior primary tumor resection, a Child‐Pugh class of B, and elevated carcinoembryonic antigen levels with a hazard ratio of 2.25, 2.48, 3.25 and 2.84 by univariate analysis, respectively. The median overall survival times of the gemcitabine/cisplatin, fluorouracil/cisplatin, sorafenib and other groups were 11.9, 10.2, 3.5 and 8.1 months, respectively. Multivariate analysis revealed that the overall survival of patients within the sorafenib monotherapy group was poor compared with platinum‐containing regimens (HR: 15.83 [95% CI: 2.25‐111.43], P = .006). All 7 patients in the sorafenib group had progressive disease, including 2 patients with second‐line therapy. In conclusion, the platinum‐containing regimens such as gemcitabine/cisplatin were associated with more favorable outcomes than sorafenib monotherapy for unresectable combined hepatocellular and cholangiocarcinoma.

Efficacy of an educational program for patients with pancreatic and biliary cancers, and their caregivers.

e18221Background: We first introduced an educational program delivered in a classroom environment for patients with pancreatic and biliary cancers and their caregivers in 2007. Physicians, pharmaci...

Efficacy of radiotherapy for primary tumor in patients with unresectable pancreatic neuroendocrine tumors

Background Detailed information regarding the clinical efficacy of radiotherapy (RT) for primary tumor in patients with unresectable pancreatic neuroendocrine tumors (pNETs) is unknown. We therefore performed a retrospective study to evaluate the efficacy and safety of RT for primary pancreatic tumors in patients with pNETs. Methods We investigated 11 patients with pNETs who received RT to the primary site between January 1997 and June 2015. Seven patients had Grade 2 neuroendocrine tumors (NET-G2) and four had neuroendocrine carcinoma (NEC) according to the 2010 WHO histopathological classification. Results The tumor response and control rates were 27.2% and 100%, respectively (3: partial response, 8: stable disease). Among patients with NET-G2 tumors, the response rate was 28.5% (2/7 patients) and symptomatic improvement was noted in 33.3% of the patients (1/3 patients). The response rate for patients with NEC were 25% (1/4), one NEC patients with symptoms exhibited symptomatic improvement. The median overall survival and median progression-free survival were 35.9 months and 5.5 months, respectively. Grade 3 diarrhea as an acute toxicity and Grade 3 gastrointestinal hemorrhage as a late toxicity were observed. Conclusions RT to the primary cancer site in patients with pNETs was an effective modality for local disease control and the treated patients had good outcomes. If metastatic tumors are under control, RT to the primary site may be beneficial for patients with pNETs.

Pancreatic neuroendocrine tumors: Twenty years’ experience of 100 patients at a single center.

179 Background: Pancreatic neuroendocrine tumors (NETs) are rare neoplasms that exhibit a variety of diverse morphological, functional and behavioral characteristics. However, only a few reports have evaluated large case series of pancreatic endocrine tumors. METHODS We conducted a retrospective review of 100 consecutive patients with pancreatic NETs diagnosed pathologically and treated at the National Cancer Center Hospital between 1991 and 2010. RESULTS The characteristics of the 100 patients were as follows: male, 49; female, 51; median age, 55 years. Fourteen patients gave a history of endocrine symptoms at the time of diagnosis. The primary tumors arose in the head, body and tail of the pancreas in 54, 25 and 21 patients, respectively. According to the 2010 grading classification of the World Health Organization, 11 patients were classified as having NET G1, 44 as having NET G2 and 29 as having NEC. The five-year survival rates of the patients with NET G1, NET G2 and NEC were 91%, 78% and 12%, respectively. The five-year survival rates of the patients with stage I, II and III, and IV disease classified according to the American Joint Committee on Cancer (AJCC) were 100%, 68% and 9%, respectively. Distant metastases occurred in 18% percent of the NET G1 patients, 39% of the NET G2 patients and 83% of the NEC patients. Treatment was undertaken by surgical resection in 82%, 59% and 24% of patients with NET G1, NET G2 and NEC, respectively. The five-year survival rates of the patients with NET G1, NET G2 and NEC after radical surgery were 100%, 91% and 36%, respectively. Among the 33 patients treated by systemic chemotherapy, the median survival period was 22.9 months in the patients with NET G1/G2 and 6.6 months in those with NEC. A multivariate analysis identified lower age, good performance status (PS) and lower histopathologic grade as independent favorable prognostic factors. CONCLUSIONS Patients with NET G1, G2 treated by surgical resection had a good prognosis. Most patients with NEC exhibited distant metastases and had a poor prognosis. Histopathologic grade is an important factor for selecting the appropriate treatment strategy and predicting the prognosis in patients with pancreatic NETs.