Number of positive lymph nodes and lymphatic invasion are significant prognostic factors after pancreaticoduodenectomy for distal cholangiocarcinoma.

Background: Early recurrence of distal cholangiocarcinoma (DCC) may result in a poorer prognosis. This study aimed to evaluate the clinicopathological factors that predict survival and recurrence in patients with DCC. Methods: Fifty-five patients with DCC who underwent pancreaticoduodenectomy between 2005 and 2015 were studied retrospectively. The following clinicopathological parameters were analyzed as predictors of disease-free survival (DFS) and overall survival (OS): sex, age, body mass index, presence of biliary tract decompression, macroscopic type, histological type, tumor size, TNM classification, lymph node metastasis ratio, number of positive lymph nodes (PLNs), lymphatic invasion, venous invasion, perineural invasion, proximal bile duct margin, dissected margin, portal system invasion, arterial system invasion, stage, and residual tumor. Results: Univariate analysis showed that contiguous extension of the primary tumor, PLN, lymphatic invasion, venous invasion, perineural invasion, and stage were significant prognostic factors for DFS and OS. Multivariate analysis revealed that PLN and lymphatic invasion were prognostic for DFS and OS (P<0.001). Significant differences in OS and DFS were found in analyses stratified by PLN (0, 1, 2 vs ≥3) and lymphatic invasion (0 vs 1, 2, 3). Conclusion: Among the clinicopathological parameters analyzed, PLN and lymphatic invasion were confirmed as prognostic factors for DCC.

Prognostic Factors Associated with Preoperative Clinicophysiological Outcomes of Distal Cholangiocarcinoma.

BACKGROUND/AIMS: Although biliary tract cancer is generally associated with a high mortality rate, patients with distal cholangiocarcinoma have better prognoses, compared to those with periampullary cancer. This study aimed to determine the preoperative clinicophysiological factors predictive of survival and recurrence in patients with distal cholangiocarcinoma. METHODS: Forty-five patients (34 men) with distal cholangiocarcinoma who underwent pancreaticoduodenectomy between 2005 and 2013 were examined retrospectively at our center and associated hospitals. Clinicophysiological parameters included predictors of overall survival (OS). Kaplan-Meier survival curves were generated and compared using log-rank tests, and Cox proportional hazard multivariate analyses were performed. RESULTS: The mean patient age was 68.8 years (range 54-81 years). Patients had a median OS duration of 43 months, and 1-, 3-, and 5-year OS rates of 91.1, 61.1, and 40.4%, respectively. Univariate analyses indicated that the body mass index, C-reactive protein (CRP) level, and carcinoembryonic antigen level were independent prognostic factors for OS; however, only the CRP level remained an independent prognostic factor in a multivariate analysis. CONCLUSIONS: A CRP level <0.3 mg/dL was predictive of a better outcome among patients with distal cholangiocarcinoma.

Efficacy and safety of oxaliplatin, bevacizumab and oral S-1 for advanced recurrent colorectal cancer.

The aim of this study was to evaluate the efficacy and safety of co-administration of oral S-1 and oxaliplatin (SOX) in combination with bevacizumab (bev) in patients with advanced recurrent colorectal cancer. A retrospective study of 36 patients with advanced recurrent colorectal cancer was performed, of whom 27 received first-line and 9 received second-line SOX+bev chemotherapy between 2010 and 2013 at the Hachioji Digestive Disease Hospital (Hachioji, Japan). The SOX+bev regimen consisted of administration of intravenous oxaliplatin (85 mg/m2) on days 1 and 14, bevacizumab (5 mg/kg) on day 1, and co-administration of oral S-1 twice daily on days 1-14. The drug regimen was repeated every 4 weeks. SOX+bev treatment was associated with a response rate of 45.2%, a disease control rate of 71%, and a median progression-free survival (PFS) and overall survival (OS) of 9.9 and 21.9 months, respectively. Patients who received first-line chemotherapy benefited from treatment in terms of prolonged PFS (13.8 months) and OS (28.2 months). Grade 3/4 adverse events were infrequent and included anaemia, thrombocytopenia, anorexia, diarrhea, sensory neuropathy, increased aspartate aminotransferase level and skin rash. In conclusion, SOX+bev therapy was found to be feasible and safe for patients with advanced and recurrent colorectal cancer.

Efficacy of non-stented pancreaticojejunostomy demonstrated in the hard pancreas.

BACKGROUND/AIMS: The aim of this study was to compare hard and soft pancreas for short-term complications of pancreaticoduodenectomy performed with a duct-to-mucosa anastomosis of pancreaticojejunostomy without a stenting tube. METHODOLOGY: We investigated 156 patients with pancreaticojejunostomy who were classified into two groups of hard pancreas (group A: 79) and soft pancreas (group B: 77). Outcomes, including complications and operative procedures, are reported. RESULTS: There were no differences between groups A and B for median age, gender, performance status. Biliary drainage ratio and disease classification of Groups A and B were statistically different. In preoperative status, there were no differences in Body Mass Index, total bilirubin, albumin, hemoglobin, creatinine, and PFD. Group B had lower HbA1C levels than group A. In operative procedures, there were no differences in operative times and blood loss, but group B had longer postoperative hospital days than group A. On operative results, there were no differences in mortality, delayed gastric emptying, biliary fistula, hemorrhage, cholangitis, lymph leakage, and others. There were significant differences between groups A and B in morbidity (12.7% vs. 35.1%), pancreatic fistula (0% vs. 9.1%), intra-abdominal abscess (1.3% vs. 9.1%). CONCLUSION: Efficacy of pancreaticojejunostomy without a stenting tube for hard pancreas was demonstrated.

Adjuvant chemotherapy using gemcitabine for resected distal bile duct and ampullary cancers.

BACKGROUND/AIMS: This retrospective study aimed to evaluate adjuvant chemotherapy using gemcitabine for resected distal bile duct and ampullary cancers. METHODOLOGY: Thirty-seven patients who had curative surgery for distal bile duct and ampullary cancers were classified into two groups: A, 19, surgery alone, and B, 18, surgery plus gemcitabine adjuvant chemotherapy between 2004 and 2010. Outcomes, including backgrounds, overall survival (OS), disease free survival (DFS), and adverse events are reported. RESULTS: There were no differences in characteristics between patients of groups A and B for age, gender, location of tumor, UICC stage, UICC pT factor, UICC pN factor, curability, and operative procedures. For all stages, except stage II, there was no difference between groups A and B for OS and DFS. For stage II however, groups A and B showed significant differences in median survival times for OS and DFS. Grade 3 or 4 adverse events included 5.6% with leucopenia. CONCLUSIONS: Adjuvant chemotherapy using gemcitabine showed the potential of contributing to prolonged OS and DFS in stage II resected distal bile duct and ampullary cancers. However, a large cohort will be needed to confirm the overall efficacy in all stages of resected BTC's.

Retrospective study of gemcitabine plus S-1 versus gemcitabine alone in cases with unresectable advanced pancreatic cancer.

BACKGROUND/AIMS: The aim of this study was to compare gemcitabine plus S-1 (GS) combination chemotherapy to gemcitabine (GEM) monotherapy in cases with unresectable advanced pancreatic cancer. METHODS: We retrospectively reviewed 107 consecutive patients with unresectable advanced pancreatic cancer who received GEM monotherapy or GS combination chemotherapy between 2004 and 2010. In 73 patients, GEM (1000 mg/m2) was administered intravenously on days 1, 8 and 15, repeated every four weeks. The GS regimen received by 34 patients consisted of intravenous GEM (1000 mg/m2) on days 1 and 8, combined with oral S-1 (40 mg/m2) twice daily on days 1-14, repeated every four weeks. RESULTS: Response rates in the GEM and GS groups (6.8% versus 32.4%) varied significantly, as did disease control rates (28.8% versus 61.8%, respectively). There was a significant difference in median overall survival (206 versus 258 days) and median progression-free survival (86 versus 123 days) between the GEM and GS groups. Grade 3/4 toxicities in both groups were neutropenia (16.4% in GEM, 17.6% in GS), thrombocytopenia (1.3%, 2.9%), anorexia (1.3%, 0%), and diarrhea (1.3%, 0%). CONCLUSIONS: Retrospectively, GS combination therapy is feasible more effective than GEM monotherapy, and therefore should be considered in cases with unresectable advanced pancreatic cancer.

Pancreaticoduodenectomy can be safely performed in the elderly.

BACKGROUND: Although pancreaticoduodenectomy has been recognized in the past for its severe complications, improvements in operative methods and perioperative management have made it a safe procedure. Therefore, pancreaticoduodenectomy can be performed in elderly patients, and our experience and outcomes are described in this report. METHODS: We retrospectively investigated 142 patients in whom pancreaticoduodenectomy was performed without stenting tubes during pancreaticojejunostomy. The patients were classified into two groups: (A) those older and (B) younger than 75 years. The outcomes, including preoperative characteristics, intraoperative characteristics, postoperative complications and mortality, are herein reported. Continuous variables were compared using Student's t test and the Chi-square test. RESULTS: There were no differences between groups A and B in terms of sex, operative time, amount of blood loss, performance status, soft pancreas rate, disease distribution and operative procedure. Comorbidities in groups A and B were statistically different. Regarding the preoperative status, the elderly patients exhibited lower serum albumin and hemoglobin levels than the younger patients. There were no differences in mortality (0 vs. 0 %), morbidity (24.3 vs. 29.5 %, p = 0.362), postoperative hospital days or major complications such as pancreatic fistula development, delayed gastric emptying, intra-abdominal abscess development, biliary fistula formation and postpancreatectomy hemorrhage. CONCLUSIONS: Pancreaticoduodenectomy can be safely performed in elderly as well as younger patients.

[A case of bile duct cancer with positive surgical margin obtaining long-term survival after S-1 monotherapy].

We report a case of bile duct cancer with a positive surgical margin obtaining long-term survival after S-1 monotherapy. A 79-year-old male with fever and liver dysfunction was admitted to our hospital. After a series of examinations he was diagnosed as hilar cholangiocarcinoma, which was treated with bile duct resection and biliary reconstruction for adhesion and pulmonary dysfunction of tuberculosis. Histopathological findings revealed that both surgical margins of the bile duct were positive. After operation, the patient received S-1 oral monotherapy(100mg/day for 28 days, followed by 14 days of rest)for 3 years. The patient has been alive for 5 years without recurrence.

[Effectiveness of adjuvant chemotherapy using gemcitabine for resected pancreatic cancer].

BACKGROUND: The aim was to evaluate the adjuvant chemotherapy using gemcitabine (GEM) for resected pancreatic cancer. METHODS: We investigated 69 patients who had undergone curative operations for pancreatic cancer. They were classified into two groups of patients using GEM (group A: 37) and patients with surgery alone (group B: 32) between 2009 and 1998. Outcomes, including disease-free survival (DFS), median survival time (MST), and adverse events were reported retrospectively. Patients assigned to the gemcitabine group received GEM at a dose of 800 mg/m² on days 1, 8 and 15, every 4 weeks for 5 cycles. RESULTS: DFS and MST did not differ significantly between group A and group B (DFS; group A: 10. 4 vs group B 8. 0 months, MST; group A: 21. 7 vs group B 16. 3 months). The estimated overall survival rates at 3 and 5 years were 40% and 25. 7%, respectively, in group A, and 12. 9% and 12. 9% in group B. Grade 3 or 4 toxicity revealed 8.1%with leucopenia, 2. 7% with thrombocytopenia, and 2. 7% with nausea. RESULTS: Adjuvant chemotherapy using gemcitabine for resected pancreatic cancer contributes to prolonged DFS, MST, and estimated overall survival.

Pancreaticoduodenectomies with a duct-to-mucosa pancreaticojejunostomy anastomosis with and without a stenting tube showed no differences in long-term follow-up.

BACKGROUND/PURPOSE: The aim of this study was to evaluate the long-term complications of pancreaticoduodenectomy with a duct-to-mucosa pancreaticojejunostomy anastomosis without a stenting tube. METHODS: Patients were followed for at least 3 years after pancreaticoduodenectomy. They were classified into two groups: duct-to-mucosa pancreaticojejunostomy anastomosis with a stenting tube (group A: 24) and without a stenting tube (group B: 21). Outcomes, including complications and dilatation of the pancreatic duct, were reported retrospectively. RESULTS: The following complication rates were found for group A: morbidity 29.1%, cholangitis 12.5%, nonalcoholic steatohepatitis 4.2%, liver abscess 4.2%, intrahepatic stones 4.2%, abnormal glucose tolerance (progression of diabetes) 20.8%, and dilatation of the pancreatic duct 20.8%. In group B, the rates for morbidity (14.3%) and abnormal glucose tolerance (19%), and dilatation of the pancreatic duct (4.8%) were lower than those in group A, but all results lacked statistical significance. CONCLUSIONS: Pancreaticoduodenectomy with a duct-to-mucosa anastomosis of pancreaticojejunostomy with or without a stenting tube showed no difference in long-term follow-up.

Pancreatic schwannoma: a case report and literature review with special reference to imaging features.

CONTEXT: We report the imaging features of pancreatic schwannomas, a rare benign type of pancreatic tumor. CASE REPORT: A 66-year-old woman was admitted to our hospital with a pancreatic tumor indicated in medical examinations. Computed tomography (CT), magnetic resonance imaging (MRI) and endoscopic ultrasonography (EUS) revealed a solid and cystic tumor, 3 cm in diameter, within the body of the pancreas. Contrast-enhanced CT, MRI and ultrasonography showed partial enhancement in the solid component. Endoscopic retrograde cholangiopancreatography (ERCP) and angiography showed no abnormal findings. A distal pancreatectomy together with a splenectomy and lymph node dissection were performed with a tentative diagnosis of mucinous cystic neoplasm of the pancreas. The cut surface of the resected pancreas showed a well-demarcated, pale yellow, solid tumor within the pancreas parenchyma. Histopathological examination of the tumor revealed proliferation of the spindle cells showing interlacing and palisading patterns. Immunohistochemically, these spindle cells were positive for S-100 protein and vimentin, and negative for alpha-smooth muscle actin, CD34, and cytokeratin. Thus the tumor was diagnosed as a pancreatic schwannoma. CONCLUSION: CT and US can detect pancreatic schwannomas as solid and cystic masses, and MRI shows a relatively characteristic feature. Imaging procedures such as CT, MRI and US are able to differentiate a pancreatic tumor, such as a pancreatic schwannoma.

[A case of pathologic complete response of primary esophageal carcinoma treated with 5-FU/CDDP as neoadjuvant chemotherapy].

A 77-year-old man with advanced esophageal carcinoma and lymph node swelling of abdomen and mediastinum, underwent neoadjuvant chemotherapy (NAC) with 5-FU/CDDP. Adverse reactions were general fatigue and nausea of grade 3 and stomatitis of grade 2. Primary tumor and lymph node swelling revealed remarkable effectiveness after 1 course of NAC, so 2 courses of NAC were given. The esophageal carcinoma was not found by endoscopy, and a biopsy specimen revealed inflammatory granulation. Lymph node on CT examination disappeared in the abdomen and reduced in the mediastinum. Because of retention of lymph node swelling, radical resection of the esophageal carcinoma was performed. Pathologic examination of the resected specimen revealed no malignant cells in the esophagus, and 3 lymph node metastases (pStage III). He had no recurrence in 15 months after the operation. Because NAC was markedly effective for primary tumor and lymph node of esophageal carcinoma, a radical operation was performed.

Pancreaticojejunostomy of duct to mucosa anastomosis can be performed more safely without than with a stenting tube.

BACKGROUND: The aim of this study was to evaluate the safety of performing a pancreaticojejunostomy with a duct-to-mucosa anastomosis without a stenting tube. METHODS: One hundred twenty-one patients with pancreaticojejunostomy, classified into 2 groups of those with duct-to-mucosa anastomoses with stenting tubes (group A; n = 49) and without stenting tubes (group B; n = 72), were investigated. Outcomes, including complications and survival rates, are reported. RESULTS: In group A, morbidity was 32.7%, 6.7% had pancreatic fistulas, 14.3% had delayed gastric emptying, 6.1% had remnant pancreatitis, 2% had intra-abdominal abscesses, 2% had intra-abdominal bleeding, and mortality was 2%. In group B, morbidity (15.3%) and delayed gastric emptying (2.8%) showed significant differences from group A. Other results were nonsignificant. In the normal soft pancreas, pancreatic fistulas in group B (3.3%) were less frequent than in group A (12.5%). CONCLUSION: Pancreaticojejunostomy of a duct-to-mucosa anastomosis could be performed more safely without than with a stenting tube to obtain a definitive anastomosis and transection of the pancreas.

Nonmyeloablative chemotherapy followed by T-cell adoptive transfer and dendritic cell-based vaccination results in rejection of established melanoma.

We demonstrated previously that dendritic cell (DC)-based vaccines could mediate a specific and long-lasting antitumor immune response during early lymphoid reconstitution after lethal irradiation and bone marrow transplant. The purpose of this current study was to examine the potential therapeutic efficacy of DC-based vaccines in combination with sublethal lymphodepletion and T-cell transfer. In an aggressive model of melanoma, treatment with the combination of 200 mg/kg cyclophosphamide (Cy) and 100 mg/kg fludarabine (Flu) led to a lymphopenic state lasting approximately 14 days, but had no effect on the growth of an established M05 melanoma. Addition of ovalbumin (OVA) peptide-pulsed DC-based immunization resulted in a delay in tumor growth but did not enhance overall survival in this model. To improve treatment, adoptively transferred naive T cells were added. After induction of lymphopenia with Cy and Flu, transferred T cells demonstrated an activated memory phenotype including high expression of CD44 and low expression of CD62L. Induction of lymphopenia with Cy and Flu in combination with adoptive transfer of naive T cells and OVA peptide-pulsed DCs immunization led to an enhancement in the number of OVA specific, CD8 T cells that demonstrated specific cytotoxic activity, proliferation, and interferon-gamma production in response to the OVA expressing M05 melanoma. This combination therapy also led to tumor regression and enhanced survival in mice bearing M05 melanoma.

Malignant glucagonoma of the pancreas diagnoses through anemia and diabetes mellitus.

Glucagonoma of the pancreas is a rare tumor with distinct clinical manifestations, such as necrolytic migratory erythema,weight loss, anemia, diabetes mellitus, and hypoamino-acidemia. We report the case of a 68-year-old Japanese man who underwent curative resection for malignant glucagonoma of the pancreas diagnosed through anemia and diabetes mellitus. The patient had had diabetes mellitus for 20 years. Anemia was diagnosed in 1998. On admission, the hemoglobin level was 8.3g/dl, but the levels of serum iron, vitamin B12, and erythropoietin and, the number of reticulocytes were within normal limits. The levels of carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, and DUPAN-2 were also within normal limits, and exocrine function of the pancreas (PFD, 75%) was normal. Ultrasonography (US) revealed a hypoechoic tumor in the distal pancreas. Computed tomography (CT) demonstrated a high-density area 4 cm in diameter with calcification. The serum glucagon level was very high (2360 pg/ml), but the levels of other hormones such as somatostatin or gastrin were within normal limits, while insulin was low. Glucagonoma of the pancreas was diagnosed, and distal pancreatectomy with splenectomy was performed. Histological examination revealed a malignant endocrine tumor,which was immunohistochemically positive for chromogranin A and glucagon. Two months after the operation, the serum glucagon level had decreased to within normal limits and the hemoglobin level had increased to 10.4 g/dl. The case of glucagonoma reported here was found through diagnostic examinations of anemia and treated by surgical resection, by which the patient's anemia was largely alleviated. Therefore, we recommend checking patients who have diabetes mellitus and anemia in order to diagnose and treat glucagonoma in its early stage.