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61 Background: It is difficult to know when the best timing is to transfer terminally ill cancer patients from hospitals to palliative hospice home care for their quality of life to death. This study aimed to articulate the best time for medical teams working in hospitals to refer their terminally ill cancer patients to palliative home care. Methods: A statistical analysis of a survey was conducted with 1,055 surviving families whose members had died with palliative home care from 1995 to 2014. The questionnaire included the following 8 contents: 1. transfer timing from hospitalization to the home care; A. appropriate, B. too late, C. too early; and the contextual items ware, 2. peacefulness of patient at dying, 3. peacefulness of patient all through the care, 4. physical pain, 5. mental pain, 6. spiritual pain, 7. alleviation of family sufferings, 8. satisfaction of family as care-givers. The response rate is 31% (311 persons). However, we excluded responses without names on the questionnaire, of non-cancer patients, with death location out of home, and without answer to question 1, resulting in 166 responses for analysis. Results: Focusing on the question 1, number of responders are A; 113 (68%), B; 52 (31%), C; 1 (0.6%). The medians of home care days to death are A; 66, B; 23, C; analysis impossible. Comparison of respondents’ satisfaction according to number of days of palliative home care revealed that 89.4% people with two months or more before their patients’ death were satisfied (A), while 10.6% of those who had less than two month were unsatisfied (B+C). Conclusions: Most surviving families were satisfied if they had two months or more for palliative home care. This survey suggests the relevancy to start preparation for discharge that enables the patients to stay home with their family members for two months or more. [Table: see text]

We conducted this study to evaluate the optimal hepatic resection for pT2 and pT3 advanced carcinoma of the gallbladder without invasion of the hepatoduodenal ligament. We conducted a questionnaire survey regarding 4,243 cases of carcinoma of the gallbladder treated during the recent 10-year period at 112 institutions belonging to the Japanese Society of Biliary Surgery. The questionnaires included questions on preoperative-diagnosis, complications, treatment, and surgical treatment, procedures of resection, surgical result, path histological findings, mode, and site of recurrence, additional post-operative treatment. They included 293 pT2 and 192 pT3 R0 cases, which were negative for hepatoduodenal ligament invasion, and the cumulative survival rates and sites of postoperative recurrence in the form of liver metastasis, were retrospectively analyzed in these 485 cases. There were no significant differences in survival rate or recurrence rates in the form of liver metastasis between the groups that underwent resection of the gallbladder bed, the group that underwent segmentectomy 4a+5, and the group that underwent hepatectomy in patients with of both pT2 or pT3 gallbladder cancers. Our results also did not show that liver metastasis to segment 4a5 alone was particularly common. For gallbladder cancer, neither with hepatoduodenal ligament invasion nor hepatic invasion, resection of the gallbladder bed is more preferable for surgical hepatic procedure. For gallbladder cancer that invades any hepatic sites, a hepatic surgical procedure that could eliminate surgical margins would be desirable.

The recurrence rate after surgery in patients with hepatocellular carcinoma (HCC) is very high, while prognosis is quite poor. However, there is no standard treatment to prevent recurrence of HCC after a curative operation. In this study, we investigated the clinical utilization of an autologous tumor lysate-pulsed dendritic cell vaccine plus ex vivo activated T cell transfer (ATVAC) in an adjuvant setting for postoperative HCC as a non-randomized controlled trial. Ninety-four patients with invasive HCC received informed consent information regarding the study, and 42 opted to have the ATVAC after surgery. Their recurrence-free survival (RFS) and overall survival (OS) were measured after 5 years and compared with those of 52 patients who selected to have the curative operation alone. The median RFS and OS were 24.5 months and 97.7 months in the patients receiving adjuvant ATVAC and 12.6 months and 41.0 months in the group receiving surgery alone (P = 0.011 and 0.029). In the treated group, patients with positive delayed-type hypersensitivity (DTH) had a better prognosis (RFS P = 0.019, OS P = 0.025). No adverse events of grade 3 or more were observed. A postoperative dendritic cell vaccine plus activated T cell transfer would be a feasible and effective treatment for preventing recurrence in HCC patients and achieving long-term survival especially in DTH positive patients.

Purpose: The prognosis of patients with advanced biliary tract cancer (BTC) is extremely poor and there are only a few standard treatments. We conducted a phase I trial to investigate the safety, immune response, and antitumor effect of vaccination with four peptides derived from cancer-testis antigens, with a focus on their fluctuations during long-term vaccination until the disease had progressed. Experimental Design: Nine patients with advanced BTC who had unresectable tumors and were refractory to standard chemotherapy were enrolled. HLA-A*2402–restricted epitope peptides, lymphocyte antigen 6 complex locus K, TTK protein kinase, insulin-like growth factor-II mRNA-binding protein 3, and DEP domain containing 1 were vaccinated subcutaneously once a week at doses of 0.5, 1, or 2 mg and continued until disease progression. The adverse events were assessed by Common Terminology Criteria for Adverse Events and the immune response was monitored by an enzyme-linked immunospot assay or by flow cytometry. The clinical effects observed were tumor response, progression-free survival (PFS), and overall survival (OS). Results: Four-peptide vaccination was well tolerated. No grade 3 or 4 adverse events were observed. Peptide-specific T-cell immune responses were observed in seven of nine patients and clinical responses were observed in six of nine patients. The median PFS and OS were 156 and 380 days. The injection site reaction and CTL induction seemed to be prognostic factors of both PFS and OS. Conclusions: Four-peptide vaccination was well tolerated and seemed to provide some clinical benefit to some patients. These immunologic and clinical responses were maintained over the long term through continuous vaccinations. Clin Cancer Res; 19(8); 2224–31. ©2013 AACR.

Congenital choledochal cyst with pancreaticobiliary maljunction (PBM) is known as a high-risk factor for various complications such as cholangitis, pancreatitis, and carcinogenesis of the biliary system by mutual refluxes of bile and pancreatic juice. Furthermore, it is not rare to suffer from postoperative complications if the wrong operative procedure is chosen. Therefore, we sought to review the relationship between operative procedure for types I and IV-A (Todani's classification) congenital choledochal cyst with PBM, and long-term treatment outcome.A retrospective review was carried out of 144 patients who underwent flow diversion surgery in our institution during the 40-year period from 1968 to 2008 and who did not have a coexisting malignant tumor at the time of surgery.Of these 144 patients, 137 underwent complete cyst excision and 7 underwent pancreas head resection as flow diversion surgery. The follow-up periods ranged from 1 to 345 months and from 1 to 271 months (average, 100.2 and 94.1) in patients with type I and type IV-A cysts, respectively. Regarding surgical treatment outcome, postoperative progress was good in 130 (90.3%) of the 144 patients. Fourteen patients required hospitalization for long-term postoperative complications such as cholangitis, pancreatitis, intrahepatic calculi, pancreatic calculus, and carcinogenesis during postoperative follow-up. Of these, 2 patients who underwent surgery for type IV-A cysts died because of secondary biliary cirrhosis with liver failure and advanced intrahepatic cholangiocarcinoma, respectively.The present study shows that flow diversion surgery for congenital choledochal cysts with PBM significantly reduces the risk of subsequent development of malignancy in the biliary tract, and it is vital to choose the appropriate operative procedure to prevent occurrence of these postoperative complications.

We assessed the significance of an extra bile duct resection by comparing the survival of patients with advanced gallbladder carcinoma who had resected bile ducts with those who had preserved bile ducts. A radical cholecystectomy that includes extra bile duct resections has been performed without any clear evidence of whether an extra bile duct resection is preventive or curative.We conducted a questionnaire survey among clinicians who belonged to the 114 member institutions of the Japanese Society of Biliary Surgery. The questionnaires included questions on the preoperative diagnosis, complications, treatment, and surgical treatment, resection procedures, surgical results, pathological and histological findings, mode and site of recurrence, and the need for additional postoperative treatment. A total of 4243 patients who had gallbladder carcinoma and were treated from January 1, 1994 to December 31, 2003 were identified. The 838 R0 patients with pT2, pT3, and pT4 advanced carcinoma of the gallbladder for which there was no cancer invasion to the hepatoduodenal ligament or cystic duct in the final analysis.The 5-year cumulative survival, postoperative complications, postoperative lymph node metastasis, and local recurrence along the hepatoduodenal ligament were not substantially different between the resected bile duct and the preserved bile duct groups.Our retrospective questionnaire survey showed that an extrahepatic bile duct resection had no preventive value in some patients with advanced gallbladder carcinoma in comparison to similar patients who had no such bile duct resection. An extrahepatic bile duct resection may therefore be unnecessary in advanced gallbladder carcinoma without a direct infiltration of the hepatoduodenal ligament and the cystic duct.

The prognosis of patients with advanced biliary tract cancer (BTC) is extremely poor and only a few standard treatments are available for this condition. We performed a phase I trial to investigate the safety, immune response and anti-tumor effect of vaccination with three peptides derived from cancer-testis antigens. This study was conducted as a phase I trial. Nine patients with advanced BTC who had unresectable tumors and were refractory to standard chemotherapy were enrolled. Three HLA-A*2402 restricted epitope peptides-cell division cycle associated 1 (CDCA1), cadherin 3 (CDH3) and kinesin family member 20A (KIF20A)-were administered subcutaneously, and the adverse events and immune response were assessed. The clinical effects observed were the tumor response, progression-free survival (PFS) and overall survival (OS). The three-peptide vaccination was well-tolerated up to a dose of 3 mg per peptide (9 mg total). No grade 3 or 4 adverse events were observed after vaccination. Peptide-specific T cell immune responses were observed in all patients and stable disease was observed in 5 of 9 patients. The median PFS and OS were 3.4 and 9.7 months. The Grade 2 injection site reaction and continuous vaccination after PD judgment appeared to be prognostic of OS. Multiple-peptide vaccination was well tolerated and induced peptide-specific T-cell responses. This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN- CTR000003229 ).