Clinicopathological features and surgical outcomes of neuroendocrine tumors of ampulla of Vater.

BACKGROUND: The study aims to investigate the clinicopathological features and surgical outcomes of neuroendocrine tumors of ampulla of Vater (NETAoVs) patients who underwent pancreaticoduodenectomy. METHODS: From January 2007 to December 2014, 45 patients underwent pancreaticoduodenectomy for malignant disease of the ampulla of Vater in our institution. Of those, 5 patients were diagnosed as neuroendocrine tumors. The data included age, sex, presenting symptoms, preoperative imaging, preoperative type of biopsy results, type of operation, pathologic findings and survival status. RESULTS: The patient's mean age was 55.2 ± 9.7 years. Endoscopic ultrasound guided biopsy was performed in 4 patients and gastroduodenoscopic biopsy was performed in one patient. All showed neuroendocrine tumor without mitosis. Mean tumor size was 1.9 ± 0.56 cm (range, 1.2-2.0 cm). Lymph node metastases were detected in two patients. All patients were synaptophysin-positive. Median periods of follow-up were 45 months (range, 43-78 months). Recurrence after operation occurred in two patients. 4 patients were alive at the last follow-up. CONCLUSIONS: Radical resection for NETAoVs can provide the information of status of lymph node metastasis after surgery. However, correlation between lymph node metastasis and overall survival is uncertain to date.

Outcomes for Patients with Recurrent Intrahepatic Cholangiocarcinoma After Surgery.

BACKGROUND: This study aimed to analyze the postoperative outcomes for patients with recurrent intrahepatic cholangiocarcinoma (ICC) and to determine the prognostic factors. In addition, this study investigated the effects of various treatment methods for patients with recurrent ICC. METHODS: This retrospective study analyzed the postoperative outcomes and prognostic factors of recurrent ICC that occurred for 81 of 128 patients who underwent hepatic resection for ICC between April 2001 and April 2013. In addition, the outcomes for a number of treatment methods were assessed for patients with recurrent ICC. RESULTS: After resection, the 128 patients with ICC had survival rates of 73 % at 1 year, 52 % at 3 years, and 43 % at 5 years. Recurrent ICC developed in 81 patients (56 men and 25 women) with a median age of 63 years. The median time from initial resection to recurrence was 9 months (range, 0-124 months), and the median survival time after recurrence was 8 months (range, 0-108 months). After recurrence, the overall survival rates were 47 % at 1 year, 23 % at 3 years, and 15 % at 5 years. Multivariate analysis showed disease-free survival time shorter than 1 year and bile duct invasion to be significant prognostic factors. Among the treatment methods, local management such as surgery, transarterial chemoembolization, and radiofrequency ablation were effective in select cases with localized intrahepatic and extrahepatic recurrence. CONCLUSION: Active local treatment (i.e., surgery, transarterial chemoembolization [TACE], and radiofrequency ablation [RFA]) may improve survival for patients with localized ICC recurrence.

Prognostic impact of immunohistochemical expression of CK7 and CK20 in curatively resected ampulla of Vater cancer.

BACKGROUND: In the consideration of ampullary adenocarcinoma, T stage, lymph node metastases, perineural invasion, tumor differentiation, pancraticobiliary type, and lymph node ratio are considered prognostic factors. The objectives of this study were to investigate surgical outcomes and the clinicopathological predictors affecting survival and recurrence, and to examine the prognostic roles of histopathological subtype and immunohistochemical markers. METHODS: From April 2006 to September 2012, 37 patients who underwent curative resection of ampullar of Vater adenocarcinoma were enrolled in this study. A retrospective review was performed based on medical records. Immunohistochemical expression, histopathological type and clinicopathologic factors were analyzed. RESULTS: The 5-year overall survival rates and disease-free survival rates after surgery were 77.4 and 75.7 %, respectively. Multivariate Cox regression analysis showed that advanced T stage (p = 0.019) and positive expression of Cytokeratin 7 (CK7) with negative expression of Cytokeratin 20 (CK20) (p = 0.046) were identified as significant independent factors related to survival, and poor differentiation (p = 0.031) significantly influenced disease-free survival in multivariate analysis. CONCLUSIONS: Advanced T stage is a significant prognostic factor affecting survival in ampullary adenocarcinoma. Also, positive expression of CK7 with negative expression of CK20 is an independent factor related to overall survival.

Coagulopathy-independent, bioinspired hemostatic materials: A full research story from preclinical models to a human clinical trial.

Since the first report of underwater adhesive proteins of marine mussels in 1981, numerous studies have reported mussel-inspired synthetic adhesive polymers. However, none of them have developed up to human-level translational studies. Here, we report a sticky polysaccharide that effectively promotes hemostasis from animal bleeding models to first-in-human hepatectomy. We found that the hemostatic material instantly generates a barrier layer that seals hemorrhaging sites. The barrier is created within a few seconds by in situ interactions with abundant plasma proteins. Therefore, as long as patient blood contains proper levels of plasma proteins, hemostasis should always occur even in coagulopathic conditions. To date, insufficient tools have been developed to arrest coagulopathic bleedings originated from genetic disorders, chronic diseases, or surgical settings such as organ transplantations. Mussel-inspired adhesion chemistry described here provides a useful alternative to the use of fibrin glues up to a human-level biomedical application.

A multicenter, prospective, randomized clinical trial of marine mussel-inspired adhesive hemostatic materials, InnoSEAL Plus.

PURPOSE: InnoSEAL Plus is an adhesive, coagulant-free hemostatic material that mimics the adhesion mechanism of marine mussels. This study reports on the safety and efficacy of InnoSEAL Plus for patients with hemorrhage after hepatectomy despite first-line hemostasis treatments. METHODS: This is a multicenter, prospective, single-blinded, randomized clinical trial involving 96 hepatectomy patients. TachoSil was used as a comparator group. Three-minute and 10-minute hemostatic success rates were monitored. Rebleeding rates were also observed. Safety was assessed by recording all novel undesirable symptoms. RESULTS: InnoSEAL Plus showed a 3-minute hemostasis rate of 100%, while TachoSil had a rate of 98.0% (48 of 49 patients), demonstrating that the 2 had similar hemostatic efficacies. The difference in efficacy between the test and comparator group was 2.04%, and the lower limit of the one-sided 97.5% confidence interval was -1.92%; as this is greater than the noninferiority limit of -23.9%, the 2 treatments were equivalent. Meanwhile, the 10-minute hemostatic success rate was the same in both groups (100%). No rebleeding occurred in either group. In the safety evaluation, 89 patients experienced adverse events (45 in the test group and 44 in the comparator group). The difference between the 2 groups was not significant. No death occurred after application of the test or comparator group product. CONCLUSION: Given that InnoSEAL Plus is a coagulation factor-free product, the hemostasis results are encouraging, especially considering that TachoSil contains a coagulation factor. InnoSEAL Plus was found to be a safe and effective hemostatic material for control of bleeding in hepatectomy patients.

Use of Neoveil or TachoSil to prevent pancreatic fistula following pancreaticoduodenectomy: A retrospective study.

The aim of this study was to evaluate the effectiveness of using Neoveil and TachoSil sponges at the pancreaticojejunostomy anastomosis site in reducing the rate and severity of postoperative pancreatic fistula (POPF).In this study, we retrospectively evaluated data that were prospectively collected on pancreaticoduodenectomy (PD) procedures. Patients were divided into 3 groups: no patch application, Neoveil patch application, and TachoSil patch application. Demographic and surgical data were analyzed.Around 165 patients with PD were enrolled in this study and were divided into 3 groups. In the standard group (n = 43), no patch was applied, while in the Neoveil and TachoSil groups (n = 84 and n = 38, respectively), the pancreaticojejunostomy anastomosis site was covered with Neoveil and TachoSil patches, respectively. POPF grade B or above occurred in 37.2% (16/43), 14.3% (12/84), and 18.8% (6/38) of patients in the standard, Neoveil and TachoSil groups, respectively, with a significant difference between patients with and without patch application (P = .004). On multivariate logistic analysis of predictive factors for POPF, male sex, patch application, and hospital day were found to be the significant independent predictors of POPF grade B or above.Significant independent predictors of POPF were male sex and patch application. This study demonstrated that the use of Neoveil or TachoSil patches may reduce the incidence of POPF after PD.

Clinical aspects of bile culture in patients undergoing laparoscopic cholecystectomy.

Bile is aseptic; under conditions of no external influx, there is a less than 30% chance of isolating bacteria even in acute cholecystitis. This study was conducted to evaluate the incidence of biliary microflora and most common biliary microflora and resistance to antibiotics in patients with cholecystitis, as well as predict situations that do not require the use of prophylactic antibiotics.Bile samples were collected for culture using standard methods during all cholecystectomies performed from January 2015 to December 2015 in the Department of Surgery, Pusan National University Hospital. A total of 366 laparoscopic cholecystectomies were performed during the study period. In 215 patients, bile culture was performed and cultures were positive in 54 cases. Prophylactic antibiotics with 2nd-generation cephalosporin were administered once 30 minutes before surgery. According to the results of bile culture, patients were divided into 2 groups, culture-negative and culture-positive groups. Preoperative, intraoperative, and postoperative factors were compared between groups.The culture positive group was older (P = .000). The number of patients with performance of endoscopic retrograde cholangiopancreatography (ERCP), performance of percutaneous transhepatic gallbladder drainage (PTGBD), presence of symptoms, presence of operative complications, and hospital stay was significantly higher in the culture-positive group than in culture-negative group. In multivariate analysis of factors associated with positive culture, age, ERCP, and symptoms were independent factors affecting positive bile culture. Eighty-five bacteria were identified in 54 patients. Escherichia coli and Klebsiella were common in gram-negative bacteria. Enterococcus was the most common in gram-positive bacteria. Less than 5% resistance was observed against carbapenem, beta-lactam antibiotics, glycopeptide antibiotics, and linezolid.The bile of patients with laparoscopic cholecystectomy may contain microorganisms, particularly elderly patients, those with symptoms, and those who undergo preoperative ERCP. When ERCP was performed, multiple bacteria culture-positive results were more likely to be found. Although carbapenem, beta-lactam antibiotics, glycopeptide antibiotics, and linezolid may be suitable prophylactic antibiotics, additional studies of the clinical aspects of culture-positive bile is needed to determine the importance of bacterial growth in bile.

Prevalence and risk factors of nonalcoholic fatty liver disease in breast cancer patients.

AIMS AND BACKGROUND: We aimed to evaluate the prevalence of nonalcoholic fatty liver disease (NAFLD) in breast cancer patients using liver magnetic resonance imaging (MRI), and to investigate factors associated with NAFLD. METHODS: We evaluated 104 patients surgically treated for breast cancer at our hospital between September and November 2013. None of the patients had any other causes of secondary hepatic fat accumulation (such as significant alcohol consumption, use of steatogenic medication or inborn disorders). Hepatic fat accumulation was measured using liver MRI perfomed in all patients before surgical treatment. RESULTS: Based on the fat signal percentage from liver MRIs, 19 of 104 breast cancer patients were diagnosed with NAFLD, so the prevalence of NAFLD was 18.3%. In univariate analysis, factors associated with NAFLD were older age, high body mass index, type 2 diabetes mellitus (DM), hypertension, elevated aspartate aminotransferase, elevated alanine aminotransferase and elevated triglycerides (TG). In multivariate analysis, factors associated with NAFLD were high body mass index (BMI) (odds ratio [OR] 1.403; 95% confidence interval [CI] 1.111-1.771; p = 0.005), type 2 DM (OR 11.872; 95% CI 1.065-132.373; p = 0.044), and an elevated TG level (OR 50.267; 95% CI 4.409-573.030; p = 0.002). CONCLUSIONS: The prevalence of NAFLD in breast cancer patients was not different from that of the general population. High BMI, type 2 DM and an elevated serum TG level were factors associated with NAFLD.

Does the pancreatic volume reduction rate using serial computed tomographic volumetry predict new onset diabetes after pancreaticoduodenectomy?

Volume reduction of the pancreatic tissues following a pancreatectomy can lead to the deterioration of glucose homeostasis. This is defined as pancreatogenic diabetes mellitus (DM). The objective of this study was to investigate the occurrence of new-onset DM (NODM) and evaluate the risk factors, including the pancreas volume reduction rate in patients undergoing pancreaticoduodenectomy (PD).Sixty-six patients without preoperative DM underwent PD for periampullary tumors between August 2007 and December 2012 and were included in this analysis. These patients underwent follow-up tests and abdominal computed tomography (CT) scan 7 days, 6 months, 12 months, 24 months, and 36 months after the operation. The pancreas volume reduction rate was calculated by CT volumetry. The patients were divided into 2 groups according to the postoperative development of DM.After PD, newly diagnosed DM occurred in 16 patients (24.2%). The incidence of DM was highest among patients with carcinomas with an advanced T stage. The pancreatic volume reduction rate after 6 and 12 months in the NODM group was significantly higher than the normal glucose group in the univariate analysis. In the multivariate analysis, the pancreatic volume reduction rate 6 months after PD was the only significant predictive factor for the development of NODM (P = 0.002).This study suggests that the pancreatic volume reduction rate 6 months after PD was the only significant predictive factor for the development of NODM. CT volumetry of the pancreas may be useful as a predictor of NODM after PD.

Do hepatic-sided tumors require more extensive resection than peritoneal-sided tumors in patients with T2 gallbladder cancer? Results of a retrospective multicenter study.

BACKGROUND: Tumor location is a prognostic factor for survival in patients with T2 gallbladder cancer. However, the optimal extent of resection according to tumor location remains unclear. METHODS: We reviewed the records of 192 patients with T2 gallbladder cancer who underwent R0 or R1 resection at 6 institutions. Perioperative and oncologic outcomes were compared according to the extent of resection between hepatic-sided (n = 93) and peritoneal-sided (n = 99) tumors. RESULTS: After a median follow-up of 30 months, the 5-year overall survival (84.9% vs 71.8%, P = .048) and recurrence-free survival (74.6% vs 62.2%, P = .060) were greater in peritoneal-sided T2 patients than in hepatic-sided T2 patients. Among hepatic-sided T2 patients, the 5-year overall survival was greater in patients who underwent radical cholecystectomy including lymph node dissection with liver resection than in patients who underwent lymph node dissection without liver resection (80.3% vs 30.0%, P = .032), and the extent of liver resection was not associated with overall survival (P = .526). Lymph node dissection without liver resection was an independent prognostic factor for overall survival in hepatic-sided T2 gallbladder cancer (hazard ratio 5.009, 95% confidence interval 1.512-16.596, P = .008). In peritoneal-sided T2 patients, the 5-year overall survival was not significantly different between the lymph node dissection with liver resection and the lymph node dissection without liver resection subgroups (70.5% vs 54.8%, P = .111) and the extent of lymph node dissection was not associated with overall survival (P = .395). CONCLUSION: In peritoneal-sided T2 gallbladder cancer, radical cholecystectomy including lymph node dissection without liver resection is a reasonable operative option. Radical cholecystectomy including lymph node dissection with liver resection is suitable for hepatic-sided T2 gallbladder cancer.

Necrotizing soft tissue infection: analysis of the factors related to mortality in 30 cases of a single institution for 5 years.

PURPOSE: Necrotizing soft tissue infection is the infection of the soft tissue with necrotic changes. It is rare, but results in high mortality. We analyzed the characteristics of patients, prognosis, and mortality factors after reviewing 30 cases of a single hospital for 5 years. METHODS: From January 2009 to December 2013, 30 patients diagnosed with necrotizing fasciitis or Fournier's gangrene in Pusan National University Hospital were enrolled for this study. The following parameters were analyzed retrospectively: demographics, infection site, initial laboratory finding, initial antibiotics, isolated microorganisms, number of surgeries, time to first operation, length of intensive care unit, and total hospital stays. RESULTS: The overall mortality rate was 23.3%. Mean body mass index (BMI) of the survival group (24.7 ± 5.0 kg/m(2)) was significantly higher than the nonsurvival group (22.0 ± 1.4 kg/m(2), P = 0.029). When BMI was less than 23 kg/m(2), the mortality rate was significantly higher (P = 0.025). Two patients (6.7%) with chronic kidney disease requiring hemodialysis died (P = 0.048). Initial WBC count (>13×10(3)/µL), CRP (>26.5 mg/dL), and platelet (PLT) count (<148×10(3)/µL) were found to have negative impact on the prognosis of necrotizing soft tissue infection. Factors such as potassium level, blood urea nitrogen (>27.6 mg/dL), serum creatinine (>1.2 mg/dL) that reflected kidney function were significant mortality factors. CONCLUSION: Patients with low BMI or abnormal values of WBC count, CRP, and PLT count reflecting the degree of infection or abnormal renal function will need more intensive care.

Clinical outcomes of small cell neuroendocrine carcinoma and adenocarcinoma of the gallbladder.

AIM: To compare the demographics and survival rates between gallbladder adenocarcinoma (GB-adenocarcinoma) and small cell neuroendocrine carcinoma of the gallbladder (GB-NEC-SCC). METHODS: From March 2007 to September 2012, patients who underwent resection of tumor stage T2/T3 GB cancer were enrolled for this study. Forty-two patients were included in this study, including 38 diagnosed with GB-adenocarcinoma and four diagnosed with GB-NEC-SCC. In the GB-adenocarcinoma group, a radical operation was performed in 28 patients, and ten patients underwent simple cholecystectomy. In the GB-NEC-SCC group, a radical operation was performed in three patients, and one patient underwent simple cholecystectomy. Comparative analysis of the two groups was performed, including clinicopathologic features and survival rates. RESULTS: The median age of the patients was 68 y (range: 35-83 years) and females comprised 26/42 of the patients. GB-adenocarcinoma patients were significantly older than GB-NEC-SCC patients (67.89 ± 11.15 vs 55.75 ± 10.31 years; P = 0.029). The median tumor size in GB-adenocarcinoma patients was 2.56 ± 1.75 cm and 3.98 ± 3.74 cm in GB-NEC-SCC patients; however, there was no significant difference between the two groups. For tumors > 2 cm, T stage (T2 vs T3), lymphovascular invasion, perineural invasion, lymph node metastasis and lymph node ratio showed no significant differences between the two groups. The overall survival rate of the 42 patients at five years was 77.0%. In the GB-adenocarcinoma group, the overall five-year survival rate was 74.8%, and survival in the GB-NEC-SCC group was 100%, which was not significantly different between the two groups. CONCLUSION: The strategy for treating patients with GB-NEC-SCC should be similar to that used for treating GB-adenocarcinoma, including radical cholecystectomy and liver resection.

Heterotopic pancreas of the gallbladder associated with segmental adenomyomatosis of the gallbladder.

Heterotopic pancreas in the gallbladder is extremely rare and usually incidentally discovered at the pathologic examination followed by cholecystectomy for symptomatic gallbladder disease. Up to the presents, only about 30 cases have been reported. We report the case of a 36-year-old female who presented with symptoms of cholecystitis. The histological analysis followed by cholecystectomy revealed heterotopic pancreas of the cystic duct.

Long-term follow-up may be needed for pancreaticobiliary reflux in healthy adults.

PURPOSE: The reflux of pancreatic enzymes into the biliary tract is associated with chronic inflammation and increases cellular proliferation of the biliary epithelium, leading to biliary carcinoma. The aim of this study is to detect the incidence of occult pancreaticobiliary reflux (OPBR) in patients who underwent elective cholecystectomy. METHODS: Forty-seven patients with symptomatic gallstones who underwent cholecystectomy were recruited for this study. The gallbladder bile samples were obtained from the specimen of gallbladder and the amylase level was measured. The immunohistochemistry of p53, SMAD4 and Ki-67 were performed for the detection of metaplasia and dysplasia. RESULTS: Biliary amylase was higher than the serum amylase in 10 patients (group A, 15,402.66 ± 33,592.43 IU/L; group B, 13.06 ± 18.12 IU/L). The mean age was 67.2 years in group A and 51.2 in group B (P < 0.01). The ratio of male to female was 1:2.3 and 1:1.8 in group A and B, respectively (P = 0.297). Eight patients in group A and thirteen patients in group B had inflammation (P = 0.014). The positive results of the Ki-67 test were exhibited in five cases in each group (P = 0.024). CONCLUSION: Results from the study indicate that the age was older, degree of inflammation and positive rate of Ki-67 were higher when OPBR was suspected. In conclusion, the patients with OPBR would need long-term follow-up, because the OPBR can cause dysplasia and the reflux of pancreatic juice may be considered as a risk factor for extrahepatic bile duct carcinoma.

Primary leiomyosarcoma of gallbladder.

Malignant mesenchymalneoplasms of the gallbladder are extremely rare with only 105 cases of primary gallbladder sarcoma having been described. It has a very aggressive behavior and is usually diagnosed at advanced stages. Therefore, curative surgical management may not be possible. We performed a radical cholecystectomy (S4b + S5 segmentectomy), omentectomy and small bowel resection in a 54-year-old patient with locally invasive leiomyosarcoma of the gallbladder. Further studies are needed to confirm the benefit of aggressive treatment for patients with leiomyosarcoma of the gallbladder.

Complication analysis of distal pancreatectomy based on early personal experience.

BACKGROUNDS/AIMS: The objective of this study was to evaluate the relationship between initial personal experiences with distal pancreatectomy and perioperative risk factors, outcomes, and management of pancreatic fistulas. METHODS: Between May, 2007 and May, 2010, a total of 28 patients who had undergone elective distal pancreatectomy were evaluated for this study. Perioperative factors and the occurrence of pancreatic fistula were analyzed on the basis of International Study Group of Pancreatic Fistula (ISGPF) criteria. RESULTS: There were sixteen cases of benign neoplasms and twelve cases of malignant tumors. The remnant pancreas was manually sutured with ligation of the pancreatic duct (n=14), auto-suture stapling along with manual sutures (n=12), or stapling alone (n=2). According to the ISGPF classification, morbidity and mortality associated with pancreatic fistulas was 42.9% (n=12) and 0%, respectively. These pancreatic fistulae were classified as grade A in 8 cases (28.6%), grade B in 3 cases (10.7%), and grade C in one case (3.6%). All patients with pancreatic fistula were treated conservatively. CONCLUSIONS: Perioperative factors do not affect the risk of pancreatic fistula. Adequate drainage is the most effective method for management of a pancreatic fistula after distal pancreatectomy.