A selective cyclooxygenase-2 inhibitor (Etodolac) prevents spontaneous biliary tumorigenesis in a hamster bilioenterostomy model.

BACKGROUND: Secondary biliary carcinomas are associated with persistent reflux cholangitis after bilioenterostomy. Cyclooxygenase-2 (COX-2) has been a target for cancer prevention. The aim of this study was to evaluate the chemopreventive efficacy of long-term treatment with a selective COX-2 inhibitor medication during the natural course after bilioenterostomy without chemical induction. METHODS: Syrian golden hamsters which underwent choledochojejunostomy were randomly divided into two groups: the control group (n = 31), which was fed a normal diet, and the etodolac group (n = 33), which was fed 0.01% etodolac (a selective COX-2 inhibitor) mixed in the meal. The hamsters were killed at the postoperative weeks 20-39, 40-59, 60-79, or 80-100. Biliary neoplasms, cholangitis, proliferating cell nuclear antigen labeling index (PCNA-LI) of the biliary epithelium, and prostaglandin E2 (PGE2) production were evaluated. RESULTS: The occurrence rates of biliary neoplasm were 43.8 and 15.2% in the control and etodolac groups, respectively (p < 0.05). The incidence of biliary neoplasm increased as time progressed in the control group, whereas it remained at a low level throughout the experimental period in the etodolac group. PGE2 products tended to be lower in the etodolac group, and PCNA-LI was significantly lower in the etodolac group (p < 0.01). These results suggest that the medication etodolac suppresses cell proliferation of the biliary epithelium, thereby preventing biliary carcinogenesis. CONCLUSIONS: Etodolac is expected to prevent secondary biliary carcinogenesis caused by persistent reflux cholangitis after bilioenterostomy.

Radical surgery for advanced pure squamous cell carcinoma of the gallbladder: report of a case.

Squamous cell carcinoma (SCC) of the gallbladder is frequently detected at an advanced stage because of its tendency to infiltrate adjacent organs. In addition, more rapid growth of this type of carcinoma compared to that of adenocarcinoma, the most frequent subtype of gallbladder carcinoma, has been reported. Although it is not rare to find squamous cell carcinoma components in cases other than the usual adenocarcinoma of the gallbladder, these cases must be distinguished from those of pure squamous cell carcinoma, as diagnosed in the present case. Pure squamous cell carcinoma is characterized by a well-localized growth, no visceral metastasis, and a rarity or lack of lymph node metastasis, even when the tumor has grown to a large size locally. Prognosis of SCC of the gallbladder has generally been considered poor. Nevertheless, long-term survival after curative resection in patients with SCC of the gallbladder has been sporadically reported. We performed extended right hemihepatectomy with portal vein resection after portal vein embolization for a 55-year-old woman with advanced SCC of the gallbladder. The patient has not developed any signs of recurrence 40 months after the surgery. Although such radical surgery remains challenging, it may lead to a favorable outcome in selected patients with advanced SCC of the gallbladder.

Limited pancreatectomy for metastatic pancreatic tumors from renal cell carcinoma.

BACKGROUND/AIMS: Metastasis of renal cell carcinoma (RCC) to distant organs occurs commonly, even after radical nephrectomy, but metastatic lesions are rarely detected in the pancreas. The present study aim was to improve the postoperative quality of life of a patient with pancreatic metastasis of RCC through limited resection of the pancreas. METHODOLOGY: Since therapeutic modalities including chemotherapy or radiation are ineffective for metastatic tumors, surgical intervention is a treatment of choice in selected patients. In patients with multiple pancreatic metastases, however, near-total or total pancreatectomy may result in a lower quality of life postoperatively due to endocrine and exocrine pancreatic insufficiency. RESULTS: We used limited resection of the pancreas combined with removal of the uncinate process and distal pancreatectomy for a 65-year-old woman with multifocal pancreatic metastases located in the uncinate process, body, and tail of the pancreas, which were detected 6 years after radical nephrectomy for RCC. This surgical procedure allowed preservation of about 40% of the pancreatic parenchyma, with complete excision of metastatic tumors in the pancreas. CONCLUSIONS: The patient has had an excellent quality of life with well-preserved pancreatic function and no evidence of tumor recurrence for 31 months after pancreatic surgery.

Placement of a plastic biliary stent tube with primary closure of the common bile duct after laparoscopic common bile duct exploration.

Laparoscopic common bile duct exploration (LCBDE) is one of the standard surgical procedures for treating choledocholithiasis. Several methods of biliary drainage following LCBDE have been advocated to prevent bile leakage. We report herein a surgical procedure using a plastic biliary stent tube following LCBDE for biliary drainage. Our method is technically simple, feasible and an ideal procedure for biliary drainage with LCBDE.

Dynamic contrast-enhanced magnetic resonance imaging to predict pancreatic fistula after distal pancreatectomy.

BACKGROUND/AIMS: This study hopes to identify risk factors for postoperative pancreatic fistulae in patients undergoing distal pancreatectomy. METHODS: The study group was composed of 39 patients who had undergone distal pancreatectomy between January 2000 and June 2008. Fourteen presumed risk factors were retrospectively reviewed. RESULTS: Pancreatic fistula developed in 10 patients (25.6%). Pancreatic fibrosis estimated by dynamic contrast-enhanced magnetic resonance imaging (MRI) was the only predictor of pancreatic fistula formation after distal pancreatectomy (p = 0.037). CONCLUSIONS: The preoperative evaluation of pancreatic fibrosis by dynamic MRI can provide reliable and objective information for predicting the risk of postoperative pancreatic fistula after distal pancreatectomy.

Utility of preoperative dynamic magnetic resonance imaging of the pancreas in diagnosing tumor-forming pancreatitis that mimics pancreatic cancer: report of a case.

The differential diagnosis of pancreatic carcinoma and tumor-forming pancreatitis remains difficult, and this situation can cause serious problems because the management and prognosis of these two focal pancreatic masses are entirely different. We herein report a case of tumor-forming pancreatitis that mimics pancreatic carcinoma in an 80-year-old woman. Computed tomography showed a solid mass in the head of the pancreas, and endoscopic retrograde cholangiopancreatography showed a complete obstruction of the main pancreatic duct in the head of the pancreas. Dynamic contrastenhanced magnetic resonance imaging (MRI) demonstrated a time-signal intensity curve (TIC) with a slow rise to a peak (1 min after the administration of the contrast material), followed by a slow decline at the pancreatic mass, indicating a fibrotic pancreas. Under the diagnosis of tumor-forming pancreatitis, the patient underwent a segmental pancreatectomy instead of a pancreaticoduodenectomy. The histopathology of the pancreatic mass was chronic pancreatitis without malignancy. The pancreatic TIC obtained from dynamiccontrast MRI can be helpful to differentiate tumor-forming pancreatitis from pancreatic carcinoma and to avoid any unnecessary major pancreatic surgery.

Monitoring fibrosis of the pancreatic remnant after a pancreaticoduodenectomy with dynamic MRI.

BACKGROUND: The time-signal intensity curve (TIC) of the pancreas obtained from dynamic contrast-enhanced magnetic resonance imaging closely reflects the histological degree of pancreatic fibrosis. MATERIALS AND METHODS: Seventy-six patients who had undergone a pancreatic TIC analysis prior to receiving a pancreaticoduodenectomy for various reasons were subjected to a yearly monitoring with pancreatic TIC for the pancreatic remnants. The pancreatic TIC profiles were classified into 3 types: type I, indicating a normal pancreas without fibrosis; and types II and III indicating fibrotic pancreas. RESULTS: The preoperative pancreatic TICs were type-I in 51 patients, type-II in 20, and type-III in 5, and the corresponding pancreatic fibrosis ratios were proved histologically to be 4.1%, 13.3%, and 21.2%, respectively. The mean postoperative follow-up period was 40.2 mo. A type-I changed to type-II in 16 patients, by 32.3 mo after surgery. In these patients, the exocrine remnant pancreatic function was preserved at the time of TIC conversion, but it significantly deteriorated thereafter. Pancreatic anastomotic leakage was found to be a significant risk factor predisposing a patient to undergo postoperative TIC conversion. In contrast, a preoperative type-II or III showed a postoperative conversion to type-I or II in 6 patients. In this group, the exocrine pancreatic function was noted to show a good recovery. In 35 patients who had a type-I TIC throughout the study, the remnant pancreatic function was well maintained. CONCLUSIONS: Pancreatic TIC analysis has the ability to detect an early fibrotic change that precedes a functional deterioration of the pancreatic remnant after a pancreaticoduodenectomy. Following a pancreaticoduodenectomy, some patients show an improvement in pancreatic fibrosis, but they may also experience remnant pancreatic fibrosis when pancreatic anastomotic leakage occurs after surgery.

Interleukin-6 expression on the biliary epithelia during inflammation-associated biliary carcinogenesis in bilioenterostomized hamsters.

BACKGROUND: Chronic inflammatory conditions of the biliary tree strongly predispose patients to biliary carcinoma. The aim of this study was to evaluate the role of interleukin-6 (IL-6) expression during biliary carcinogenesis in bilioenterostomized hamsters. MATERIALS AND METHODS: Syrian hamsters were subjected to either a choledochoduodenostomy (CD, n=11) or a simple laparotomy (SL, n=10) and then received N-nitrosobis(2-oxopropyl)amine (BOP) treatment. The animals were sacrificed 20 wk after surgery and the development of biliary carcinoma, the presence and degree of cholangitis, and IL-6 expression on the biliary epithelia were examined histologically. RESULTS: In the CD group, eight hamsters (73%) demonstrated persistent cholangitis and six (55%) of them developed intrahepatic biliary carcinoma, while no hamster without cholangitis showed any biliary carcinoma. In the SL group, cholangitis was recognized in four hamsters (40%) and no development of biliary carcinoma was identified. A significantly high incidence of tumor development (P=0.024) and a close correlation between the presence of cholangitis and the occurrence of biliary carcinoma (P =0.013) were thus evident in the CD group. Moreover, the degree of cholangitis was significantly higher in the CD hamsters (P=0.041) and an IL-6 overexpression was identified in five hamsters that had undergone a CD, with a scattered expression on the intra- and extrahepatic biliary epithelia. Despite the fact that the induced biliary carcinomas showed a multicentric occurrence in the liver, these tumors originated from within the restricted area where IL-6 was expressed. CONCLUSIONS: A deregulated IL-6 overexpression on the biliary epithelia may therefore be involved in inflammation-associated biliary carcinogenesis in hamsters that have undergone a bilioenterostomy.

Rib-lifting method for retraction of the low-lying costal arch in laparoscopic cholecystectomy of gallbladder torsion with kyphoscoliosis.

Gallbladder torsion is a rare entity. Recently, laparoscopic cholecystectomy has become accepted as a standard operation for gallbladder torsion. Unfortunately, kyphoscoliosis is a risk factor of gallbladder torsion, and kyphoscoliosis results in a low-lying costal arch and disturbs the laparoscopic view. The present paper reports a new surgical procedure, a "rib-lifting method" for retracting the low-lying costal arch at laparoscopic cholecystectomy of gallbladder torsion with kyphoscoliosis.

Chemopreventative effect of an inducible nitric oxide synthase inhibitor, ONO-1714, on inflammation-associated biliary carcinogenesis in hamsters.

The present study was designed to investigate whether an inducible nitric oxide synthase (iNOS)-specific inhibitor, ONO-1714 [(1S, 5S, 6R, 7R)-7-chloro-3-imino-5-methyl-2-azabicyclo[4.1.0] heptane], could prevent inflammation-associated biliary carcinogenesis in bilioenterostomized hamsters. Syrian golden hamsters underwent choledochojejunostomy and then received subcutaneous injections of the chemical carcinogen N-nitrosobis(2-oxopropyl)amine every 2 weeks at a dose of 10 mg/kg body wt, starting 4 weeks after surgery and continuing for 18 weeks. The hamsters were divided into two groups according to their oral intake of either a standard pelleted diet containing ONO-1714 at 100 p.p.m. for 18 weeks (ONO group, n = 15) or an ordinary diet alone (control group, n = 15). The animals were killed 22 weeks after surgery, and the development of biliary tumors was examined histologically. The presence and degree of cholangitis, cell kinetic status of the biliary epithelium and iNOS expression were evaluated. Intrahepatic biliary adenomas developed in all control animals, whereas they developed in only seven (47%) hamsters treated with ONO-1714 (P < 0.05). Intrahepatic biliary carcinomas were present in 13 (87%) hamsters in the control group and in only 6 (40%) hamsters in the ONO groups (P < 0.05). Histological and immunohistochemical examinations demonstrated a significant decrease in the degree of cholangitis, biliary epithelial cell kinetics and the expression of iNOS in the biliary epithelium in the ONO group in comparison with the control (P < 0.05). These results indicate that ONO-1714 represses N-nitrosobis(2-oxopropyl)amine-induced biliary carcinogenesis in bilioenterostomized hamsters and inhibits iNOS expression in the biliary epithelium. ONO-1714 may therefore be a promising agent for the prevention of biliary carcinoma in various inflammation-associated biliary disorders.

Anatomy-specific pancreatic stump management to reduce the risk of pancreatic fistula after pancreatic head resection.

BACKGROUND: The anatomical status of the pancreatic remnant after a pancreatic head resection varies greatly among patients. The aim of the present study was to improve management of the pancreatic remnant for reducing pancreatic fistula after pancreatic head resection. METHODS: Ninety-five consecutive patients who underwent an end-to-side, duct-to-mucosa pancreaticojejunostomy after pancreatic head resection were included in the study. To approximate the pancreatic stump to the jejunum, the transfixing and interrupted suture techniques were used in 51 and 44 patients, respectively. We modified the interrupted suture technique according to the anatomical status of the pancreatic remnant, i.e., the shape of the pancreatic stump and the location of the pancreatic duct. RESULTS: There was no operative mortality in this study. Overall, 14 patients (15%) developed a clinically relevant pancreatic fistula. Certain anatomical features, including a small pancreatic duct, a soft, nonfibrotic pancreatic gland, and a pancreatic duct adjacent to the posterior cut edge, were significantly associated with pancreatic fistula. The fistula rate in the interrupted suture group was 7%, lower than that (22%) in the transfixing suture group (P = 0.036), and it was not influenced by pancreatic anatomy. Multivariate analysis identified a nonfibrotic pancreas (versus fibrotic pancreas; odds ratio [OR] 12.58, 95% CI 1.2-23.9; P = 0.001), a soft pancreas (versus hard pancreas; OR 4.67, CI 1.2-51.1; P = 0.006), and the transfixing suture technique (versus interrupted suture technique; OR 9.91, CI 1.7-57.5; P = 0.003) as significant predictors of clinically relevant pancreatic fistula. CONCLUSIONS: Pancreatic anastomosis modified according to the pancreatic anatomy is effective in reducing the risk of pancreatic fistula formation with end-to-side, duct-to-mucosa pancreaticojejunostomy after pancreatic head resection.

Gastric wall-covering method prevents pancreatic fistula after distal pancreatectomy.

BACKGROUND/AIMS: Pancreatic fistula is the most common complication after distal pancreatectomy. The aim of this study was to evaluate retrospectively the usefulness of a new surgical technique, the gastric wall-covering method, after distal pancreatectomy. METHODOLOGY: The study group consisted of 53 patients who underwent distal pancreatectomy. The management of the stump of the remnant pancreas was accomplished by the gastric wall-covering method (GWC group, n=20) or by conventional surgery (CS group, n=33). In the gastric wall-covering method, the cut surface of the pancreas is fixed to the posterior wall of the gastric body. RESULTS: There were no significant differences in operating time, intraoperative blood loss, or texture of the remnant stump between the two groups. Postoperative pancreatic fistula was diagnosed in 1 patient (5.0%) in the GWC group and in 12 patients (36.4%) in the CS group (P=0.01). CONCLUSIONS: The gastric wall-covering method for the management of the pancreatic stump after distal pancreatectomy reduces the incidence of postoperative pancreatic fistula.

Intraoperative pancreatography using an endoscopic naso-pancreatic drainage tube for the prevention of pancreatic fistula after local pancreatic resection.

BACKGROUND/AIMS: Local pancreatic resections can avoid the unnecessary resection of the normal pancreatic parenchyma in comparison with standard pancreatic resection. However, the incidence of pancreatic fistula after local pancreatic resection is high, and still responsible for most morbidity and mortality. METHODOLOGY: We reviewed 6 patients who underwent intraoperative pancreatography using an endoscopic naso-pancreatic drainage (ENPD) tube during local pancreatic resection for the prevention of postoperative pancreatic fistula. RESULTS: One patient had injury to the main pancreatic duct during surgery, and transient pancreatic fistula of grade B occurred. In this patient, ENPD tube was left in place for the management the pancreatic fistula, resulted in a favorable outcome. Other 5 patients showed no postoperative complications including pancreatic fistula. CONCLUSIONS: Intraoperative pancreatography using ENPD tube is a simple technique and useful for the prevention of pancreatic fistula after local pancreatic resection.

Intraductal papillary mucinous neoplasm of the pancreas with a bifid pancreatic duct.

A bifid pancreatic duct presenting a major bifurcation in the main pancreatic duct is one of the anatomical variations of the pancreatic ducts. We encountered a 71-year-old female with a 5-cm-diameter branch duct intraductal papillary mucinous neoplasm of the pancreas in whom preoperative endoscopic retrograde pancreatography demonstrated an anomalous bifurcation of the main pancreatic duct at the body of the pancreas. We performed a distal pancreatectomy, instead of a middle pancreatectomy, with a cutting line at the downstream pancreas to the duct bifurcation point. Intraoperative ultrasonography was useful to confirm the exact location of the pancreatic duct bifurcation as well as the tumor extension. The procedure resulted in a favorable outcome without any postoperative complications. Although a bifid pancreatic duct is an unusual anomalous condition, this case should alert surgeons to be aware of such anatomical variants when performing pancreatic resection, otherwise, incurable pancreatic complications may occur postoperatively.

Chemopreventative effect of hochu-ekki-to (TJ-41) on chemically induced biliary carcinogenesis in hamsters.

BACKGROUND: Bilioenterostomy is a common surgical technique that is widely used. Recently, clinical studies have revealed that biliary carcinomas can occur after bilioenterostomy. The present study was designed to evaluate whether hochu-ekki-to (TJ-41), a Japanese herbal drug, could prevent chemically induced biliary carcinomas in bilioenterostomized hamsters. MATERIALS AND METHODS: Syrian golden hamsters were subjected to choledochojejunostomy and then received subcutaneous injections of N-nitrosobis(2-oxopropyl) amine every 2 weeks at a dose of 10 mg/kg. N-nitrosobis(2-oxopropyl) amine administration was started 4 weeks after surgery. The animals were simultaneously p.o. administered TJ-41 in water every day at a dose of 1000 mg/kg (TJ-41 group). The control hamsters were administered water alone. The hamsters were sacrificed 22 weeks after surgery, and the development of biliary carcinomas, the presence and degree of cholangitis, and the cell kinetic status of the biliary epithelium were evaluated histologically. RESULTS: Intrahepatic bile duct carcinomas developed in 15/17 (88%) hamsters in the control group and in only 8/17 (47%) hamsters in the TJ-41 group (P < 0.05). The degree of cholangitis was not different between the two groups. However, the proliferating cell nuclear antigen labeling index of the biliary epithelium in the TJ-41 group (6.46%) was significantly lower than the controls (9.67%) (P < 0.05). These findings indicated that TJ-41 reduced accelerated biliary epithelial cell kinetics after bilioenterostomy, resulting in the prevention of carcinogenesis. CONCLUSION: TJ-41 has a preventive effect on chemically induced carcinoma of the biliary tract after bilioenterostomy.

Clinical images. Gallbladder torsion showing a "whirl sign" on a multidetector computed tomography scan.

An 82-year-old woman presented with a 5-day history of right upper quadrant pain. A physical examination showed a palpable tender mass in the right upper quadrant with Murphy's sign. The contrast-enhanced multidetector computed tomography (MDCT) scan clearly showed the twisted pedicle of the cystic duct and gallbladder mesentery on the right side of the gallbladder, thus showing a "whirl sign," and a definitive diagnosis of gallbladder torsion was made. The patient underwent a cholecystectomy, resulting in a favorable outcome. Therefore, the whirl sign on MDCT imaging can be a key to making a definitive diagnosis of gallbladder torsion.

Combined pancreatic resection and pancreatic duct-navigation surgery for multiple lesions of the pancreas: intraductal papillary mucinous neoplasm of the pancreas concomitant with ductal carcinoma of the pancreas.

When a branch-type IPMN of the uncinate process is concomitant with ductal carcinoma of the body of the pancreas, total pancreatectomy may be recommended. However, a decrease in quality of life becomes a serious problem after total pancreatectomy because of the abolition of endocrine and exocrine pancreatic function. We proposed the combined resection, which consists of resection of the uncinate process of the pancreas with distal pancreatectomy. This surgical procedure of combined resection is most suitable for preservation of the pancreatic functions. In addition, we recommend the pancreatic duct-navigation surgery to enable us to prevent injury to the main pancreatic duct, and to dissect at the optimal cutting point of the pancreatic branch duct.

A jejunal wall-covering method following central pancreatectomy for prevention of a pancreatic fistula: a novel technique.

To preserve pancreatic endocrine and exocrine function, various types of pancreatic resection, including central pancreatectomy, have been introduced as less invasive surgeries. However, postoperative pancreatic leakage has been demonstrated to be the most frequent complication following pancreas-preserving surgery. The authors' new surgical technique, a jejunal wall-covering method, helps to prevent pancreatic leakage following central pancreatectomy.

Multifocal branch-duct pancreatic intraductal papillary mucinous neoplasms.

The appropriate management for patients with multifocal branch-duct intraductal papillary mucinous neoplasms (IPMNs) of the pancreas involving the entire pancreatic gland remains unclear. We present a 66-year-old woman who underwent pylorus-preserving pancreaticoduodenectomy for a branch-duct intraductal papillary mucinous carcinoma demonstrating a grape-like multilocular cyst, 35 mm in diameter, in the head of the pancreas along with numerous number of small branch-duct IPMNs in the whole pancreas. Histologically, the multifocal cystic lesions were lined by a single row of columnar mucin-containing epithelial cells without atypia. The patient has been doing well without any recurrence during 9-year follow-up after surgery. Surgical removal of the prominent lesions suspicious of malignancy and a close observation of the remaining lesions in the remnant pancreas may be a reasonable treatment plan for patients with multifocal branch-duct IPMNs involving the entire pancreatic gland.