The Clinical Significance of Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography in Patients with Occupational Cholangiocarcinoma

Objective: The present study aimed to identify the clinical significance of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in patients with occupational cholangiocarcinoma. Methods: This study included 10 men with occupational cholangiocarcinoma who were former or current workers at a printing company in Osaka, Japan. Of the 10 patients, 2 had 2 main tumors and 1 had 3 main tumors. Twelve FDG-PET imaging findings in the 10 patients could be analyzed. We evaluated the relationships between FDG-PET imaging parameters and clinicopathological findings of occupational cholangiocarcinoma. Results: Abnormal FDG uptake was observed in 8 of the 14 main tumors, with maximum standardized uptake values ranging from 2.9 to 11.0, and the sensitivity was 57.1%. Four patients had lymph node metastases, and abnormal marrow uptake was detected in all these patients. Although precancerous lesions, such as biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB) without any invasion, were not detected, abnormal FDG uptake was demonstrated in 2 of 4 patients with IPNB having an associated invasive carcinoma.Conclusions: Although FDG-PET may be useful for assessing tumor progression factors, such as lymph node metastasis, it cannot accurately detect precancerous lesions, such as BilIN and IPNB without invasive carcinoma.

A phase I study for adjuvant chemotherapy of gemcitabine plus S-1 in patients with biliary tract cancer undergoing curative resection without major hepatectomy (KHBO1202).

PURPOSE: To determine the recommended dose (RD) of gemcitabine (GEM) plus S-1 (GS) in curatively resected biliary tract cancer (BTC) patients without major hepatectomy. METHODS: A standard 3 + 3 dose-escalation design was used with planned dose levels (mg/m2) of GEM (administered intravenously on days 1 and 8) and S-1 (administered orally twice daily on days 1-14, with a 1-week rest, every 3 weeks for up to 24 weeks) of 1000/80 (Level 2), 1000/65 (Level 1), 800/65 (Level - 1), and 800/50 (Level - 2). RESULTS: Thirty-one patients (17 men and 14 women; median age, 70 years) were enrolled. Level 1 was chosen as the starting dose. Three of seven patients developed dose-limiting toxicities at Level 1 and the dose was de-escalated to Level - 1. Five of 12 patients developed Grade 4 neutropenia at Level - 1 and the dose was de-escalated to Level - 2. One patient developed Grade 4 neutropenia at Level - 2. Another patient was unable to receive the day 8 dose due to Grade 3 neutropenia at Level - 2. Level - 1 was confirmed as the maximum tolerated dose and Level - 2 the RD for this regimen. The 1- and 2-year recurrence-free survival rates were 77.0 and 54.0%, respectively. The recurrence-free survival rate of patients in the GS completion group was significantly higher than that of the GS discontinuation group. CONCLUSIONS: Level - 2 was confirmed as the RD (GEM 800 mg/m2 and S-1 50 mg/m2) for GS adjuvant chemotherapy in curatively resected BTC patients without major hepatectomy.

A clinical role of staging laparoscopy in patients with radiographically defined locally advanced pancreatic ductal adenocarcinoma.

BACKGROUND: The aim of current study is to verify usefulness of staging laparoscopy (stag-lap) for patient's selection and to find prognostic factors in patients with radiographically defined locally advanced (RD-LA) pancreatic ductal adenocarcinoma (PDAC). METHODS: The LA disease was defined as an unresectable disease without distant organ metastasis based on resectability status of NCCN guideline in this study. Stag-lap was performed in 67 patients with RD-LA (2007-2012) which were divided into 4 groups according to metastatic site: group CY (peritoneal fluid or washing cytology positive and without any distant organ metastasis); group P (peritoneal dissemination); group L (liver metastasis); group LA (peritoneal fluid or washing cytology negative and without any distant organ metastasis). Clinical backgrounds, survival curves, and prognostic factors were investigated. RESULTS: There were 16 patients in CY group (24%), 13 patients in P group (19%), 10 patients in L group (15%), and 28 patients in LA group (42%). Median survival time was 13 months in CY group and 11 months in LA group, which was significantly better than 7 months in P group, respectively (p<0.05). The rate of emergence of ascites in LA was significantly better than in CY or P groups (p<0.05). Multivariate analysis showed that the presence of partial response and administration of second-line chemotherapy were significantly independent prognostic factors. CONCLUSIONS: The majority of PDAC patients with RD-LA had occult distant organ metastasis. Clinical features and survival curves were different depending on the site of occult distant organ metastasis. Administration of second-line chemotherapy and responsiveness to chemotherapy were associated with favorable prognosis. Staging laparoscopy should be routinely performed in patients with RD-LA PDAC (UMIN000019936).

Successful Multidisciplinary Therapy for Small Cell Carcinomas Arising from the Extrahepatic Bile Duct.

A 74-year-old man was diagnosed with small cell carcinoma arising from the extrahepatic bile duct according to a histological examination of the biopsy specimen obtained during endoscopic retrograde cholangiopancreatography. Additionally, bulky hilar lymphadenopathy was observed, and the patient was treated with the combination of radiation and chemotherapy (cisplatin and irinotecan). Post-therapy, he underwent pancreaticoduodenectomy. The histological examination of the resected specimen revealed no residual cancer cells in the bile duct wall and a small amount of cancer cells in only a single lymph node. Due to this multidisciplinary therapy, the patient showed no signs of recurrence 12 months postoperatively.

Antibiotic prophylaxis in laparoscopic cholecystectomy: a randomized controlled trial.

BACKGROUND: Recent meta-analyses concluded that antibiotic prophylaxis is not warranted in low-risk laparoscopic cholecystectomy. However, most trials in the meta-analyses had a relatively small sample size and were statistically underpowered. In addition, many of the trials mentioned potential cost savings owing to the elimination of prophylactic antibiotics. However, no trial has statistically estimated the cost effectiveness. To evaluate the results of meta-analyses, we conducted a randomized controlled trial on the role of prophylactic antibiotics in low-risk laparoscopic cholecystectomy with an adequate sample size. METHODS: From March 2007 to May 2013, at the Department of Surgery, Kansai Medical University, patients who were scheduled for elective laparoscopic cholecystectomy were randomly assigned to one of two arms: those who were and were not administered prophylactic antibiotics. The primary endpoint was the occurrence of postoperative infections and secondary endpoints were postoperative hospital stay and medical costs. FINDINGS: During the study period, 518 patients were assigned to the Antibiotics group and 519 to the No antibiotics group. Occurrences of surgical site infections, distant infections and overall infections were significantly lower in the Antibiotics group than in the No antibiotics group (0.8 vs. 3.7%, p = 0.001, OR: 0.205 (95%CI: 0.069 to 0.606); 0.4 vs. 3.1%, p = 0.0004, OR: 0.122 (95%CI: 0.028 to 0.533); 1.2 vs. 6.7%; p<0.0001, OR: 0.162 (95%CI: 0.068 to 0.389), respectively). The postoperative hospital stay was significantly shorter in the Antibiotics group (mean, SD: 3.69±1.56 vs. 4.07±3.00; p = 0.01) and the postoperative medical costs were significantly lower in the Antibiotics group (mean, SD: $766±341 vs. 832±670; p = 0.047). Multivariable analysis showed that independent risk factors for postoperative infectious complications were no prophylactic antibiotics (p<0.0001) and age 65 or older (p = 0.006). CONCLUSIONS: Perioperative administration of prophylactic antibiotics should be recommended in laparoscopic cholecystectomy to prevent postoperative infectious complications and to reduce medical costs. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000003749.

Phase I study of adjuvant gemcitabine or S-1 in patients with biliary tract cancers undergoing major hepatectomy: KHBO1003 study.

BACKGROUND: Standardized adjuvant therapy is not performed after major hepatectomy for biliary tract cancer (BTC) because of frequent adverse events, which may be caused by insufficient liver function. Therefore, the aim of this multicenter study (KHBO1003) was to determine the safety protocol for adjuvant chemotherapy after major hepatectomy. METHODS: Within 12 weeks of R0 or R1 major hepatectomy (hemihepatectomy or trisectionectomy) for BTC, the following adjuvant chemotherapy was performed for 6 months: 800-1,000 mg/m(2) gemcitabine on days 1, 8, and 15 and then every 3-4 weeks or 40-80 mg/m(2)/day S-1 on days 1-28 and every 3-6 weeks. Major dose-limited toxicity (DLT) was defined as grade 4 hematotoxicity, grade 3/4 febrile neutropenia, grade 3/4 non-hematotoxicity, skipped gemcitabine on days 8 and 15, or halting the course at or after 14 days. Dose-escalation and de-escalation decisions were based on the continual reassessment method. Every three patients were alternately assigned to each arm. RESULTS: Thirty-three patients (14 intrahepatic bile duct, 1 gall bladder, 18 extrahepatic bile duct) were enrolled in this study from February 2011 to July 2012 (n = 18 gemcitabine, n = 15 S-1). At 10% of DLT, the recommended dose was 1,000 mg/m(2) gemcitabine biweekly and 80 mg/m(2)/day S-1 on days 1-28 and every 6 weeks. Major DLT and adverse drug reactions were neutropenia. No grade 3 or 4 non-hematological adverse events were noted. CONCLUSION: We determined RDs for gemcitabine and S-1 adjuvant chemotherapy after major hepatectomy with a DLT that does not exceed 10%.

Role of adjuvant surgery in initially unresectable pancreatic cancer after long-term chemotherapy or chemoradiation therapy: survival benefit?

BACKGROUND: The purpose of the present study was to analyze the survival benefit and safety of adjuvant surgery in patients with initially unresectable pancreatic cancer following chemo(radio)therapy. METHODS: The 130 patients with unresectable pancreatic cancer treated during 2006 to 2013 were divided into a study group (15 patients) with planned adjuvant surgery, and a control group (115 patients with locally advanced disease) without adjuvant surgery. RESULTS: The study group of 15 patients had shrunken tumor, decreased tumor marker, and maintained performance status after 9 months (range 5-18 months) of chemo(radio)therapy. Thirteen patients had curative resection and two patients were not resected. The remaining controls of 115 patients did not undergo surgical resection due to poor response to chemo(radio)therapy or performance status. The median survival time in the study group was better than in the control group (36 vs. 9 months, P < 0.001). The mortality and morbidity rates in the study group were 0% and 46% respectively, in spite of concomitant organ resections in 77%. CONCLUSION: Patients who had adjuvant surgery had significant improvement of survival without increase in morbidity and mortality, relative to patients with locally advanced disease. Thus, adjuvant surgery may provide the promising results in this group who responded favorably to initial chemo(radio)therapy in unresectable pancreatic cancer.

Antitumor effect of angiotensin II type 1 receptor blocker losartan for orthotopic rat pancreatic adenocarcinoma.

OBJECTIVE: The aim of this study was to investigate the synergistic inhibitory effects of gemcitabine and losartan, angiotensin II type 1 (AT1) receptor blockers, on an orthotopic rat pancreatic cancer model. METHODS: The rat orthotopic pancreatic cancer model was prepared using DSL-6A/C cells, a rat ductal pancreatic adenocarcinoma cell line. The rats were treated with gemcitabine alone (100 mg/kg per week), losartan alone (100 mg/kg per day), or gemcitabine plus losartan. RESULTS: Survival was significantly improved by treatment with gemcitabine (89.6 ± 21.8 days) or losartan (76.9 ± 18.7 days) alone compared with that in the control group (59.6 ± 13.4 days; P < 0.05). Treatment with gemcitabine plus losartan further prolonged the survival time to 102.6 ± 16.5 days compared with that in the control group (P < 0.0001). Gemcitabine or losartan significantly and dose-dependently reduced the proliferation of DSL-6A/C cells in vitro. Both drugs inhibited pancreatic vascular endothelial growth factor expression compared with that in the control group (P < 0.05). CONCLUSIONS: The results of this study indicate that combined treatment with gemcitabine and losartan significantly improved the survival of rats with orthotopic pancreatic cancer by inhibiting vascular endothelial growth factor synthesis and suppressing cancer cell proliferation via AT1 receptor blockade. Thus, an AT1 receptor blocker in combination with gemcitabine might improve the clinical outcomes of patients with advanced pancreatic cancer.

Phase I study of adjuvant chemotherapy with gemcitabine plus cisplatin in patients with biliary tract cancer undergoing curative resection without major hepatectomy (KHBO1004).

PURPOSE: We conducted a phase I study to determine the maximum tolerated dose and recommended dose (RD) of this gemcitabine plus cisplatin (GC) combination in the adjuvant setting for biliary tract cancer (BTC). GC has become a standard chemotherapy regimen for patients with locally advanced or metastatic BTC; however, the benefit of adjuvant therapy for BTC is unclear. METHODS: Patients with BTC were eligible if they met the following criteria: Stage IB or higher; and undergoing resection without major hepatectomy. The starting dose matched the standard dose of gemcitabine (1,000 mg/m(2)) and cisplatin (25 mg/m(2)) on days 1 and 8, every 3 weeks for up to 24 weeks. The dose limiting toxicities (DLTs) were determined during the first 6 weeks, and a 3+3 dose finding design with cohorts of 3-6 patients was used. Further cohort expansion took place. RESULTS: One DLT, namely grade 4 neutropenia, was observed among six patients at the starting dosages. Then, we expanded the cohort with a total of eighteen patients to evaluate RD and no further DLTs were observed. During the entire study, the most common grade 3/4 adverse events were neutropenia (94 %) and leucopenia (56 %). Non-hematological toxicities were manageable. CONCLUSIONS: We defined the standard dose of GC as the RD for adjuvant chemotherapy for BTC treated by curative resection without major hepatectomy. Further study is warranted to clarify the safety and efficacy of this regimen for all patients.

Case series of 17 patients with cholangiocarcinoma among young adult workers of a printing company in Japan.

BACKGROUND: An outbreak of cholangiocarcinoma occurred among workers in the offset color proof-printing department at a printing company in Japan. The aim of this study was to clarify the characteristics of the patients with cholangiocarcinoma. METHODS: This was a retrospective study conducted in 13 Japanese hospitals between 1996 to 2013. The clinicopathological findings of cholangiocarcinoma developed in 17 of 111 former or current workers in the department were investigated. Most workers were relatively young. RESULTS: The cholangiocarcinoma was diagnosed at 25-45 years old. They were exposed to chemicals, including dichloromethane and 1,2-dichloropropane. The serum γ-glutamyl transpeptidase activity was elevated in all patients. Dilated intrahepatic bile ducts without tumor-induced obstruction were observed in five patients. The cholangiocarcinomas arose from the large bile ducts. The precancerous or early cancerous lesions, such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile ducts, as well as non-specific bile duct injuries, such as fibrosis, were observed in various sites of the bile ducts in all eight patients for whom operative specimens were available. CONCLUSIONS: The present results showed that cholangiocarcinomas occurred at a high incidence in relatively young workers of a printing company, who were exposed to chemicals including chlorinated organic solvents.

Clinical impact of preoperative cholangitis after biliary drainage in patients who undergo pancreaticoduodenectomy on postoperative pancreatic fistula.

The objective of this study was to examine whether the development of cholangitis after preoperative biliary drainage (PBD) can increase the incidence of postoperative pancreatic fistula (POPF). The study population included 185 consecutive patients who underwent pancreaticoduodenectomy from April 2006 to March 2011. All patients were divided into two groups, which consisted of a "no PBD" group (73 patients) and a PBD group (112 patients). Moreover, the PBD group was divided into a "cholangitis" group (21 patients) and a "no cholangitis" group (91 patients). Clinical background, clinical outcome, and postoperative complications were compared between groups. All patients received prophylactic antibiotics using cefmetazole until 1 or 2 days postoperatively. There was no difference between noncholangitis and non-PBD groups except the frequency of overall POPF. Clinically relevant POPF and drain infection occurred in the cholangitis group significantly more than in the noncholangitis group (P < 0.05). Univariate and multivariate analyses showed that development of preoperative cholangitis after preoperative biliary drainage and small pancreatic duct (less than 3 mm diameter) were independent risk factors for clinically relevant POPF. The frequency of clinically relevant POPF was 8 per cent (eight of 99) in patients without two risk factors, 19 per cent (15 of 80) in patients with one risk factor, and 50 per cent (three of six) in patients with both risk factors. The development of preoperative cholangitis after PBD was closely associated with the development of clinically relevant POPF under the limited use of prophylactic antibiotics.

Pancreaticogastrostomy following distal pancreatectomy prevents pancreatic fistula-related complications.

BACKGROUND: The most common postoperative complication after distal pancreatectomy (DP) is still postoperative pancreatic fistula (POPF), which is closely associated with other major complications and remains an unsolved problem. METHODS: This retrospective study included 47 consecutive patients who underwent a distal pancreatectomy with (DP-PG group, n = 21) or without (DP group, n = 26) duct-to-mucosa pancreaticogastrostomy from June 2010 to May 2012. Clinical data including POPF-related complications (POPF, fluid collection, intra-abdominal abscess, bleeding and delayed gastric emptying) as a primary endpoint were compared between the two groups. RESULTS: The frequencies of POPF-related complications as well as overall POPF and complications in the DP-PG group were lower than in the DP group (P = 0.037, P < 0.001, respectively). The 30 days morbidity after hospital discharge in the DP-PG group was less than in the DP group (P = 0.014). In both groups median hospital stay was similar. Although additional time needed for pancreaticogastrostomy was 35 (20-55) min, there was no difference in operative times. Patients in the DP group had a higher medical cost for hospitalization than the DP-PG group (P = 0.048). CONCLUSION: Pancreaticogastrostomy as an additional procedure following distal pancreatectomy was associated with a reduced rate of POPF-related complications that resulted in relatively lower medical cost for hospitalization.

Less morbidity after introduction of a new departmental policy for patients who undergo open distal pancreatectomy.

BACKGROUND: The aim of this study was to retrospectively compare morbidity and mortality before and after introduction of a new departmental policy for patients who undergo distal pancreatectomy. METHODS: We have introduced the use of an ultrasonically-activated device in distal pancreatectomy, an "early removal of drains" policy and perioperative management using a clinical pathway since May 2006. Group A consisted of 52 consecutive patients from 2000 to February 2006. Group B consisted of 57 consecutive patients from May 2006 to 2010. RESULTS: Although there was no difference in the fluid collection rate within 30 postoperative days (Group A, 44% vs. Group B, 35%), the rates of intra-abdominal abscess (A, 19% vs. B, 4%) and grade 3/4 of the Clavien classification (A, 23% vs. B, 9%) in Group B were significantly lower than in Group A (P < 0.05). Time of drain removal (median 3 days vs. 8 days) and length of in-hospital stay (median 8 days vs. 17 days) in Group B were significantly shorter than in Group A (P < 0.001). CONCLUSION: The implementation of new departmental guidelines for distal pancreatectomy was closely associated with a low frequency of intra-abdominal abscess and grade 3/4 Clavien score, resulting in a shorter in-hospital stay.

Comparative outcomes of elderly and non-elderly patients receiving first-line palliative chemotherapy for advanced biliary tract cancer.

BACKGROUND AND AIM: Few studies have reported the efficacy and safety of palliative chemotherapy in elderly patients with advanced biliary tract cancer. We aimed to investigate the clinical outcomes of palliative chemotherapy for advanced biliary tract cancer in elderly patients. METHODS: We retrospectively evaluated 403 consecutive patients who received palliative chemotherapy between April 2006 and March 2009 for pathologically confirmed unresectable or recurrent biliary tract cancer. Clinical outcomes of the elderly group (≥ 75 years old; n = 94) were compared with those of the non-elderly group (< 75 years old; n = 309). RESULTS: Except for the extent of disease, patient baseline characteristics were well balanced between both groups. The median overall survival was 10.4 months in the elderly group and 11.5 months in the non-elderly group (hazard ratio, 1.14; 95% confidence interval, 0.89-1.45; P = 0.31). Although the frequency of adverse events between both groups was similar, interstitial pneumonitis was significantly more frequent in the elderly group than in the non-elderly group (4.3% vs 0%, P < 0.01). CONCLUSIONS: In advanced biliary tract cancer, overall survival of elderly patients receiving palliative chemotherapy is comparable with that of non-elderly patients. To our knowledge, this is one of the largest studies that have reported the clinical outcomes of elderly patients following palliative chemotherapy.

Effects of pancrelipase on nonalcoholic fatty liver disease after pancreaticoduodenectomy.

BACKGROUND: Postoperative nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD) has recently become recognized. However, the pathoetiology of postoperative NAFLD is largely unknown. Furthermore, the optimal treatment has not been established. The aim of this prospective study was to clarify whether pancrelipase, which contains digestive pancreatic enzymes, could reverse NAFLD. METHODS: A collaborative clinical trial has been conducted (UMIN000006841). A total of 30 patients who developed NAFLD after PD were prospectively treated with pancrelipase. NAFLD was defined and evaluated by the liver-to-spleen attenuation ratio on computed tomography (CT). Clinical symptoms and laboratory findings were also assessed. RESULTS: The mean liver-to-spleen CT ratio before surgery in 30 patients was 1.233. It declined to 0.453 at diagnosis of NAFLD. It was significantly improved by the treatment and the CT ratios at 1, 3 and 6 months after treatment were 0.762, 0.958 and 0.904, respectively (vs. pretreatment, P < 0.001). The mild liver dysfunction was also improved. Total protein, albumin and total cholesterol levels were significantly improved by the treatment. Importantly, relatively severe diarrhea seen in 11 patients was also ameliorated. CONCLUSIONS: Pancrelipase has a significant beneficial impact on NAFLD after PD. Maldigestion after pancreatic surgery may be a main cause for the development of postoperative NAFLD.

Patients with recurrent biliary tract cancer have a better prognosis than those with unresectable disease: retrospective analysis of a multi-institutional experience with patients of advanced biliary tract cancer who received palliative chemotherapy.

BACKGROUND: Prognostic factors for patients with advanced biliary tract cancer (BTC) who received palliative chemotherapy have not been fully established. Especially, the status of unresectable/recurrent disease has not been well studied because of a small number of patients with recurrent BTC in previous studies. METHODS: This multicenter retrospective study was conducted in 18 institutions in Japan. We retrospectively reviewed data regarding 403 patients with pathologically proven BTC who received palliative chemotherapy between April 2006 and March 2009. One hundred and ninety-two patients with recurrent BTC were included. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: The median overall survival was significantly longer in the recurrent BTC patients than in the unresectable BTC patients (398 days vs. 323 days, P = 0.004). After adjustment using multivariate analysis, the status of recurrent/unresectable disease remained an independent prognostic factor (hazard ratio 1.33, 95% confidence interval 1.04-1.70, P = 0.022) in addition to performance status, extent of disease, carbohydrate antigen 19-9 levels, and carcinoembryonic antigen levels. CONCLUSIONS: The status of unresectable/recurrent disease was shown as an independent prognostic factor in the BTC patients. This result may help to predict life expectancy of BTC patients and design future clinical trials evaluating palliative chemotherapy in BTC.

Laparoscopic distal pancreatectomy for a pancreatic lymphoepithelial cyst: case report and review of literature.

CONTEXT: Lymphoepithelial cysts of the pancreas are a rare disease of true pancreatic cysts, the cause of which is unknown. The differential diagnosis is broad and includes many benign and malignant cystic lesions of the pancreas and surrounding organs. A combination of imaging modalities and fine needle aspiration might narrow the differential diagnosis. However, the final diagnosis can only be achieved with certainty after resection of the cyst. CASE REPORT: The present case report is a lymphoepithelial cyst of the pancreas that was resected laparoscopically. A 53-year-old man was incidentally found to have a cystic tumor in the tail of the pancreas after undergoing an abdominal ultrasound, which showed a 41x33 mm cystic mass in the pancreatic tail. He had no abdominal symptoms. Laparoscopic distal pancreatectomy and splenectomy were performed. Histologic examination revealed a lymphoepithelial cyst. CONCLUSION: Herein, we discuss the diagnostic difficulties and management decisions that face surgeons treating pancreatic cysts.

The clinical role of critical pathway implementation for pancreaticoduodenectomy in 179 patients.

BACKGROUND/PURPOSE: In June 2004, a critical pathway for patients undergoing pancreaticoduodenectomy (PD) was introduced. The objective of this study was to determine the clinical value of critical pathway implementation. METHODS: 256 consecutive patients who underwent PD between 2000 and 2010 were divided into 4 groups by date of operation as follows; group A (n = 77), the pre-pathway group; group B (n = 51), the CP implementation group who were managed according to departmental guidelines; group C (n = 78), the group who had no stenting in the reconstruction of PD; and group D (n = 50), the group who had reinforcement of the pancreaticojejunostomy. The success rates of clinical outcomes and post-operative morbidity were compared between each group, year by year and every 50 patients. RESULTS: The success rates of clinical outcomes, including the timings of nasogastric tube removal, discontinuation of prophylactic anti-microbial agent, drain removal, starting oral intake, and patient discharge, were significantly improved in group B relative to group A, and in group C relative to group B. There were no significant differences in mortality and morbidity between any of the groups. All clinical outcomes reached a plateau at 2-3 years or 100-150 patients' operations after critical pathway implementation. CONCLUSIONS: Long-term use of a critical pathway is associated with improved clinical outcomes. A certain period of time or volume of patients is needed for this improvement in clinical outcomes to reach a plateau, which indicates achieving standardization of peri-operative management.

Activation of alpha-smooth muscle actin-positive myofibroblast-like cells after chemotherapy with gemcitabine in a rat orthotopic pancreatic cancer model.

BACKGROUND: To investigate the behavior of activated pancreatic stellate cells (PSCs), which express alpha-smooth muscle actin (α-SMA), and pancreatic cancer cells in vivo, we examined the expression of α-SMA-positive myofibroblast-like cells in pancreatic cancer tissue after treatment with gemcitabine (GEM) using a Lewis orthotopic rat pancreatic cancer model. METHODS: The effect of GEM on DSL-6A/C1 cell proliferation was determined by cell counting method. The orthotopic pancreatic cancer animals were prepared with DSL-6A/C cells, and treated with GEM (100 mg/kg/weekly, for 3 weeks). At the end of treatment, α-SMA expression, fibrosis, transforming growth factor (TGF)-ß1 and vascular endothelial growth factor (VEGF) were evaluated by histopathological and Western blot analyses. RESULTS: DSL-6A/C1 cell proliferation was significantly reduced by co-culturing with GEM in vitro. Survival time of pancreatic cancer animals (59.6 ± 13.4 days) was significantly improved by treatment with GEM (89.6 ± 21.8 days; p = 0.0005). Alpha-SMA expression in pancreatic cancer tissue was significantly reduced after treatment with GEM (p = 0.03), however, there was no significant difference in Sirius-red expression. Expression of VEGF was significantly reduced by GEM treatment, but the expression of TGF-ß1 was not inhibited. CONCLUSION: GEM may suppress not only the tumor cell proliferation but also suppress PSCs activation through VEGF reduction.

Absence of cystic duct leakage using locking clips in 1017 cases of laparoscopic cholecystectomy.

Cystic duct leakage with metal clips persists after laparoscopic cholecystectomy (LC). The aim of the study is to evaluate the preventive effect of locking clips on leaks from the cystic duct stump after LC as an alternative to metal clips. Locking clips were routinely used to close the cystic duct in LC. A total of 1101 patients who underwent LC were retrospectively assessed from a database of the surgical department at our university hospital. A main outcome measurement is bile leakage after LC. From January 2006 to April 2011, 1053 LCs were performed. Of these, the cystic duct was closed with locking clips in 1017 cases, and no bile leaks from the cystic duct were observed in any of these 1017 cases. Locking clips should be routinely used to close the cystic duct in preference to metallic clips to reduce postoperative bile leaks after LC.