Invasion Depth Measured in Millimeters is a Predictor of Survival in Patients with Distal Bile Duct Cancer: Decision Tree Approach.

BACKGROUND: AJCC staging system is unreliable for predicting survival in distal bile duct (DBD) cancer patients, due to inter-observer variation. Measured depth of invasion (DOI) is suggested to be more accurate to predict patients' clinical outcome in extra-hepatic cholangiocarcinomas, but its significance in DBD cancer and cutoff values are still debatable. This study aimed to identify the optimal cutoff value of DOI in relation to prognosis in DBD cancer patients. METHODS: Data of 179 patients with DBD adenocarcinoma treated in three institutions were investigated. Under microscopic review, DOI was measured. The relationships between the clinicopathological parameters and the groups based on DOI (≤3; 3-10; >10 mm) were evaluated, and the survival times of each group based on DOI and T classification were compared. RESULTS: Deeply invading tumors exhibited a greater tendency toward the infiltrative type, high histological grade, AJCC stage, and pancreatic, duodenal, lymphovascular and perineural invasion. The measured DOI was significantly correlated with worse relapse-free and overall survival (all p < 0.05). In multivariate analyses, the DOI remained as one of the prognostic factors (all p < 0.05), while T classification was not a significant prognostic factor. The new prognostic models (low, intermediate, and high risk) that applied DOI and nodal metastasis showed significant difference in recurrence and survival rate (all p < 0.05). CONCLUSIONS: On the basis of the proposed cutoff value, the DOI could be clear and meaningful, overcoming the vagueness of the T classification for predicting clinical outcomes in patients with DBD carcinoma.

Replaced common hepatic artery from the superior mesenteric artery: multidetector computed tomography (MDCT) classification focused on pancreatic penetration and the course of travel.

PURPOSE: We categorize the subtypes of the replaced common hepatic artery (RCHA) and evaluate the clinical implications. METHODS: Thirty-four cases of the RCHA were evaluated retrospectively using multidetector computed tomography. We categorized them into the three RCHA subtypes according to pancreatic penetration and the passing routes. The distance between the orifice of the superior mesenteric artery (SMA) and RCHA bifurcation (D SMA-RCHA) was measured using advanced 3D imaging software. Analysis of variance was used to evaluate the difference in D SMA-RCHA according to the RCHA subtype. RESULTS: Type A (n = 17, 50 %) referred to RCHA penetrating the pancreatic parenchyma, all crossing the dorsal aspect of the superior mesenteric vein (SMV). Among them, three cases were accompanied by the circumportal pancreas. Type B (n = 10, 29 %) referred to RCHA without penetration of the pancreatic parenchyma and crossing of the dorsal aspect of the main portal vein (MPV) or SMV. Type C (n = 7, 21 %) referred to RCHA without penetration of the pancreas parenchyma and crossing of the ventral aspect of the MPV or SMV. The mean D SMA-RCHA of each subtype was as follows: type A, 3.13 cm [95 % confidence interval (CI) 2.70-3.57]; type B, 2.04 cm [95 % CI 1.40-2.68]; and type C, 2.14 cm [95 % CI 2.23-2.92]. The D SMA-RCHA of the penetrating pancreatic parenchyma of the RCHA was significantly longer than that of the non-penetrating pancreatic parenchyma (P = 0.007). CONCLUSION: Half of RCHA show penetrating the pancreatic parenchyma, which was categorized as type A, and this type A takes off from the SMA more distally than RCHA without intrapancreatic penetration.

Distal appendiceal dilatation in equivocal appendicitis may be a useful sign for prediction of normal appendix.

Despite many efforts to reduce unnecessary appendectomy for appendicitis, the negative appendectomy rate remains relatively high. Here, we investigated predisposing factors for normal appendix by analyzing the surgical outcomes for patients with equivocal appendicitis. Over a 3-year period, 1516 patients underwent treatment for appendicitis and 148 (10%) were prospectively diagnosed with equivocal appendicitis. We defined equivocal appendicitis as a right lower quadrant pain with tenderness and an apppendiceal diameter of 6 to 9 mm without appendicolith or severe adjacent inflammation as radiological findings. We investigated normal appendix rates in relation to clinical and radiological features. Of the 148 patients, 48 (32%) had a normal appendix and 100 had appendicitis. A higher normal appendix rate was found for low white blood cell count than for leukocytosis (41% vs 23%, odds ratio (OR) = 2.48), and laparoscopic treatment was then open (42% vs 21%, OR = 2.58). Distal appendiceal dilatation, as determined by radiological imaging, was associated with a higher normal appendix rate than whole dilatation (60% vs 27%, OR = 3.96). Low white blood cell count, laparoscopic treatment, and distal appendiceal dilatation were significant predisposing factors for normal appendix after surgery. Radiologically determined distal dilatation of the appendix may be a useful sign for predicting normal appendix.

Concurrent MET copy number gain and KRAS mutation is a poor prognostic factor in pancreatobiliary subtype ampullary cancers.

Hepatocyte growth factor (HGF) and MET are candidates of targeted therapies for cancer patients. Although MET and HGF are commonly expressed in biliary tract cancers, their expression and gene copy number status and their association with KRAS mutations have not been investigated in pancreatobiliary-type ampullary adenocarcinomas (A-ACs), one of the aggressive periampullary cancers. MET and HGF expressions and MET copy number status were examined by performing immunohistochemistry (IHC) and silver in situ hybridization (SISH) in 62 surgically resected, paraffin-embedded tumors, respectively. High MET and HGF protein expressions were detected in 24 (38.7%) and 15 (24.2%) tumors. High MET expression was associated with KRAS mutation. However, there were no associations of high MET/HGF expression alone with other clinicopathological feature or survival. MET SISH positivity was detected in 19 tumors (30.6%), where 84.2% were due to high trisomy or polysomy and only 3 cases (15.8%) were MET gene amplification. The overall MET protein overexpression was well correlated with MET SISH positivity. The concurrent MET SISH positivity and KRAS mutation, not each alone, was an independent poor prognostic factor of disease-free survival only in pancreatobiliary subtype of A-ACs, but not in intestinal subtype. Concurrent MET SISH positivity and KRAS mutation may predict a high risk of recurrence in pancreatobiliary subtype of A-ACs, indicating those markers could be potent candidates for a new therapeutic target in this cancer type. MET IHC can be used as a reliable tool screening for MET copy number status in ampullary cancers.

One-year experience with single incision laparoscopic cholecystectomy in a single center: without the use of inverse triangulation.

PURPOSE: Single incision laparoscopic cholecystectomy (SILC) is generally performed with the use of inverse triangulation. In this study, we performed 3-channel or 4-channel SILC without the use of inverse triangulation. We evaluated the adequacy and feasibility of SILC using our surgical method. METHODS: We retrospectively reviewed our series of 309 SILCs performed between March 2014 and February 2015. RESULTS: Among 309 SILCs, male were 148 and female were 161 patients, mean age was 48.7 ± 15.3 years old and mean body mass index was 24.8 ± 3.8 kg/m(2). Forty patients had previously undergone abdominal surgery including 6 cases of upper abdominal surgery. SILC after percutaneous transhepatic gallbladder (GB) drainage was completed in 8.7% of cases. There were 10 cases of emergency SILC. SILC was performed for noncomplicated GB including symptomatic GB stone and polyp in 66.7% of cases, acute cholecystitis in 33.3%. Overall, 96.8% of procedures were successfully completed without additional port. The reason for addition of an extra port or open conversion included technical difficulties due to severe adhesion and bleeding. The mean operating time was 60.7 ± 22.3 minutes. The overall complication rate was 4.8%: 9 patients of wound seroma, 1 case of bile leakage from GB bed, 4 cases of intra-abdominal abscess or fluid collection, and 1 case of incisional hernia were developed. There was no case of common bile duct injury. CONCLUSION: Our surgical method of SILC without the use of inverse triangulation is safe, feasible and effective technique.

Low incidence of KRAS, BRAF, and PIK3CA mutations in adenocarcinomas of the ampulla of Vater and their prognostic value.

Ampullary adenocarcinomas (A-ACs) are rare malignancies with considerable importance because of their high curable resection rate and improved survival rate among periampullary cancers. The RAS-RAF-MAPK pathway is involved in the development of A-ACs and is a potential therapeutic target. However, molecular profiles of A-ACs and their prognostic impact are poorly understood. Peptide nucleic acid-mediated polymerase chain reaction clamping and Mutyper were used to detect KRAS, BRAF, and PIK3CA mutations in 62 paraffinized samples of A-ACs. Of 62 A-ACs, 30.6% had KRAS mutations, but no BRAF mutations and low frequency (1.6%) of PIK3CA mutation were detected. KRAS mutation was correlated with poor tumor differentiation and was a predictor of shorter recurrence-free survival period in overall A-ACs, whereas the prognosis according to the histologic subtypes was not affected by KRAS mutation. Lymph node metastasis was an independent prognostic factor of poor overall survival. Intestinal- and pancreatobiliary-type A-ACs had similar prognosis. Intestinal- and pancreatobiliary-type A-ACs had different prognostic factors; tumor differentiation and lymph node metastasis strongly predicted overall survival and recurrence-free survival in pancreatobiliary-type tumors, respectively, whereas no independent prognostic factors were demonstrated for intestinal-type tumors. Low incidence of KRAS mutations and their strong prognostic value in A-ACs may suggest the potential of survival benefit depending on the epidermal growth factor receptor-targeted therapy. Much lower frequencies of BRAF and PIK3CA mutations may suggest that they do not play a major role in the tumorigenesis of A-ACs. Different therapeutic protocols should be considered for treating pancreatobiliary- and intestinal-type A-ACs.

Low frequency of KRAS mutation in pancreatic ductal adenocarcinomas in Korean patients and its prognostic value.

OBJECTIVES: Low prevalence and prognostic relevance of KRAS mutations in Korean pancreatic ductal adenocarcinomas (PDACs) need to be validated with sensitive detection method. METHODS: Peptide nucleic acid (PNA)-mediated polymerase chain reaction (PCR) clamping was used to precisely detect KRAS mutation in 72 paraffinized tumor samples and was validated by pancreatic cell lines to compare the efficiency of direct sequencing. RESULTS: The PNA-mediated PCR clamping detected mutant allele proportions of as low as 0.5% against a background of wild-type DNA and was 20-fold more sensitive than direct sequencing through the validation of pancreatic cell lines. Peptide nucleic acid-mediated PCR clamping detected KRAS mutations in 47.2% of 72 PDACs. Low tumor cellularity and low PCR amplification efficiency led to be undetected or failed by direct sequencing in pancreatic paraffinized samples.KRAS mutations were an independent worse prognostic factor predicting a reduced progression-free survival rate in the postoperative chemotherapy group. CONCLUSIONS: Peptide nucleic acid clamp real-time PCR was a sensitive method for detecting KRAS status in paraffinized PDAC samples. We identified a low KRAS mutation rate among the Korean PDAC patients using PNA clamp real-time PCR, potentially implicating epidemiological characteristics. The low KRAS mutation rate and its prognostic role may suggest the further survival benefit in Korean PDAC patients.

Phase II study of gemcitabine and S-1 combination chemotherapy in patients with metastatic biliary tract cancer.

PURPOSE: A phase II study was conducted to evaluate the efficacy and safety of gemcitabine and S-1 combination chemotherapy in patients with metastatic biliary tract cancer (BTC). METHODS: Patients with pathologically confirmed, unresectable, recurrent, or metastatic adenocarcinoma that originated from the intrahepatic or extrahepatic biliary ducts or gallbladder were assessed for eligibility. The primary end point was the overall response rate (ORR). The treatment consisted of 1,000 mg/m(2) intravenous gemcitabine administered over 30 min on days 1 and 8, and 80 mg/m(2) oral S-1 on days 1-14 of each cycle. The treatment was repeated every 3 weeks. RESULTS: Thirty-eight patients were enrolled between November 2005 and 2010. All patients had metastatic disease, and the primary sites of cancer were as follows: gallbladder in 12 (31.6%), intrahepatic and extrahepatic bile ducts in 23 (60.5%), and the ampulla of Vater in 3 (7.9%) patients. One patient achieved a complete response, and six experienced a partial response. The ORR was 20.6% (95% CI 8.5-36.7] in the per-protocol (PP) population, and 18.4% (95%CI 6.1-30.7) in the intention-to-treat (ITT) population; the median response duration was 10.8 months. Nineteen patients had stable disease, and the disease control rate was 76.5% (95%CI 60.6-87.6) in the PP population. The median progression-free survival was 4.4 months (95%CI 1.8-6.9), and the median overall survival was 9.0 months (95%CI 4.0-13.9) with a 1-year survival rate of 44.7% (95%CI 29.0-61.5) in the ITT population. Grade 3/4 hematologic toxicities, neutropenia, anemia, and thrombocytopenia were observed in 13 (37.1%), 9 (25.7%), 2 (5.7%), and 2 (5.7%) patients, respectively. One patient experienced a grade 3 febrile neutropenia without any documented infection. The grade 3/4 non-hematologic toxicities were hepatic toxicity (11.4%), anorexia (2.9%), and renal toxicity (2.9%). CONCLUSION: Gemcitabine and S-1 combination chemotherapy showed acceptable efficacy and favorable toxicity profiles. Therefore, it might offer an alternative therapeutic strategy in patients with BTC.

Laparoscopic treatment for post-cholecystectomy Mirizzi syndrome.

The remnant cystic duct or gallbladder neck calculus may rarely result in post-cholecystectomy Mirizzi syndrome. Various managements have been proposed for the treatment of post-cholecystectomy Mirizzi syndrome. Some previous cases of post-cholecystectomy Mirizzi syndrome have been managed with open cholecystectomy and endoscopically. We report a case of a laparoscopic stone removal of post-cholecystectomy Mirizzi syndrome that developed 7 months after laparoscopic cholecystectomy. To our knowledge, this is the first case of laparoscopic management of post-cholecystectomy Mirizzi syndrome. The mechanism, diagnosis and treatment of post-cholecystectomy Mirizzi syndrome are discussed.

Phase II trial of gemcitabine and S-1 for patients with advanced pancreatic cancer.

PURPOSE: To evaluate the efficacy and safety of combined gemcitabine and S-1 as first-line chemotherapy for patients with locally advanced or metastatic pancreatic cancer. METHODS: This study included patients who had been diagnosed with unresectable, locally advanced or metastatic adenocarcinoma arising from the pancreas, which was histologically or cytologically confirmed and involved at least 1 unidimensionally measurable lesion. The regimen consisted of intravenous 1,000 mg/m(2) gemcitabine on day 1 and 8 combined with oral S-1 on days 1-14 every 21 days. The dosage of S-1 was based on the body surface area (BSA) as follows: 40 mg bid (total 80 mg/day) for a BSA of <1.25, 50 mg bid (total 100 mg/day) for a BSA of ≥1.25 but <1.5, and 60 mg bid (total 120 mg/day) for a BSA of ≥1.5. Treatment consisted of at least 2 courses unless rapid disease progression was noted. The primary end points were the response and disease control rates, and the secondary end points were toxicity and survival. RESULTS: Thirty-seven patients were enrolled between August 2005 and December 2010. The median number of chemotherapy cycles was 4 (range 1-28 cycles). Response to treatment could be evaluated in 31 patients. None of the patients showed complete response, but 5 achieved partial response. The response rate was thus 13.5 % [95 % confidence interval (CI) 2.7-24.3 %] in the intent-to-treat population. Sixteen patients (43.2 %; 95 % CI 27-59.5 %) showed stable disease, and the overall disease control rate was 56.8 % (95 % CI 40.6-72.9 %). For all 37 patients, the median progression-free survival was 4.6 months (95 % CI 1.8-7.6 month), and the median overall survival was 9.4 month (95 % CI 5.8-12.6 month). Chemotherapy-related grade 3/4 hematological toxicities were neutropenia (36.1 %), leucopenia (22.2 %), and anemia (13.9 %). The non-hematological toxicities were generally mild. CONCLUSIONS: Combination chemotherapy with gemcitabine and S-1 was effective, convenient, and safe in patients with advanced pancreatic cancer.

Relationship between the risk of bile duct injury during laparoscopic cholecystectomy and the types of preoperative magnetic resonance cholangiopancreatiocography (MRCP).

BACKGROUNDS/AIMS: Bile duct injury is one of the potential severe complications that can occur during laparoscopic cholecystectomy, which can be cause by anatomic variations in the confluence of the bile duct. Recently magnetic resonance cholangiopancreatiocography (MRCP) has become a helpful tool to detect bile duct variation on a preoperative basis and to prevent bile duct injury during laparoscopic cholecystectomy, as well other hepatic surgeries. This study aimed to clarify the types of bile duct on MRCP and to search for a method of avoiding injury during laparoscopic cholecystectomy. METHODS: Between January 2009 and December 2010, 277 patients underwent laparoscopic cholecystectomy with preoperative MRCP in our institution. On a retrospective basis, the bile ducts were categorized into 5 types according to the Couinaud classification system. RESULTS: The proportion of types was revealed type A (70.4%), type B (8.7%), type C (19.5%), type D (0.7%), type E (0%), and type F (0.7%), respectively. Bile duct injury occurred in 4 cases (1.4%) during laparoscopic cholecystectomy. In particular, the possibility of aberrant extrahepatic confluence (Type C and F) represented the highest risk of duct injury (OR=11.89 [CI: 1.21-116.53]). CONCLUSIONS: Preoperative evaluation of the bile duct anatomy is important to avoid injury of duct during laparoscopic cholecystectomy. Specific types of bile duct variation should be considered as a high risk group for bile duct injury.

Percutaneous transhepatic gallbladder drainage changes emergency laparoscopic cholecystectomy to an elective operation in patients with acute cholecystitis.

Many surgeons have found it difficult to decide whether to apply percutaneous transhepatic gallbladder drainage (PTGBD) in patients with acute cholecystitis that is not responsive to initial medical management (IMMx), because the indications of PTGBD are ambiguous. The aim of this study was to evaluate the appropriate treatment for acute cholecystitis that is not responsive to IMMx. Specifically, we focused on differences in surgical outcomes between elective and emergency laparoscopic surgeries. Between March 2006 and February 2009, 738 patients with acute cholecystitis who had undergone laparoscopic cholecystectomy (LC) at our institution were retrospectively studied. We divided them into 3 groups. Group I included 494 patients who underwent elective LC without pre-operative PTGBD, group II included 97 patients who intended to undergo elective LC after preoperative PTGBD, and group III included 147 patients who underwent emergency LC without preoperative PTGBD. We compared age, sex, symptom duration, body temperature, leukocyte counts, and American Society of Anesthesiologists (ASA) class on admission as clinical characteristics. We compared the time interval from symptom development and admission to surgery, operative time, the conversion rate to open surgery, postoperative complications, the total length of stay, and the postoperative length of stay as perioperative surgical outcomes. For patients with ASA 2 and 3, the conversion rate to open surgery in group II was significantly less than that in group III (P<.05, P<.01, respectively). We recommend PTGBD as the first choice for acute cholecystitis in patients who show no improvement after IMMx, to allow the patient to undergo an elective LC rather than emergency surgery for patients with ASA 2 and 3.

Predictable factors for lymph node metastasis in early gastric cancer-analysis of single institutional experience.

INTRODUCTION: Prediction of lymph node metastasis in early gastric cancer (EGC) is very important to decide treatment strategies preoperatively. The aim of this study was to evaluate factors that predict the presence of lymph node metastasis and to identify the differences between mucosal and submucosal gastric cancers. METHODS: A total of 376 patients with EGC who underwent gastrectomy from March 1999 through December 2007 were retrospectively identified. The clinopathological factors and biological markers (p53, Ki67) were analyzed. RESULTS: The rate of lymph node metastasis was 9.6% (mucosal cancer 2.8%, submucosal cancer 18.4%). Tumor size, depth of invasion, macroscopic type, and lymphovascular invasion were related to lymph node metastasis in EGC. When the carcinomas were confined to the mucosal layer, tumor size and lymphovascular invasion showed significant correlation with lymph node metastasis. On the other side, macroscopic type and lymphovascular invasion were association with lymph node metastasis in submucosal carcinoma. CONCLUSION: The risk factors for lymph node metastasis in EGC are quite different depending on depth of tumor invasion. To predict lymph node metastasis in EGC, it is recommended that distinct assessment according to individual situation should be clearly established.

Management of endoscopic retrograde cholangiopancreatography-related perforations.

PURPOSE: The purpose of this study is to analyze the treatment strategies of patients with endoscopic retrograde cholangiopancreatography (ERCP)-related perforations. This is a retrospective study. METHODS: We experienced 13 perforations associated with ERCP. We reviewed the medical recordsand classified ERCP-related perforations according to mechanism of injury in terms of perforating device. Injury by endoscopic tip or insertion tube was classified as type I, injury by cannulation catheter or sphincterotomy knife as type II, and injury by guidewire as type III. RESULTS: Of four type I injuries, one case was managed by conservative management after primary closure with a hemoclip during ERCP. The other three patients underwent surgical treatments such as primary closure orpancreatico-duodenectomy. Of five type II injuries, two patients underwent conservative management and the other three cases were managed by surgical treatment such as duodenojejunostomy, duodenal diverticulization and pancreatico-duodenectomy. Of four type III injuries, three patients were managed conservatively and the remaining patient was managed by T-tube choledochostomy. CONCLUSION: Type I injuries require immediate surgical management after EPCP or immediate endoscopic closure during ERCP whenever possible. Type II injuries require surgical or conservative treatment according to intra- and retro-peritoneal dirty fluid collection findings following radiologic evaluation. Type III injuries almost always improve after conservative treatment with endoscopic nasobilliary drainage.

Cavo-caval intervention stent insertion after deceased-donor liver transplantation using side-to-side piggyback technique: report of a case.

Liver transplantation with preservation of the recipient vena cava (piggyback technique) has been performed as an alternative to the conventional method. Outflow disturbance or obstruction of the vena cava in the early period after liver transplantation is associated with high morbidity and mortality. We used side-to-side cavo-caval anastomosis (modified piggyback technique) in a deceased-donor liver transplantation (DDLT) for venous outflow reconstruction. On postoperative day 9, the patient developed abdominal discomfort, and abnormal liver function showing serum total bilirubin of 6.2 mg/dl and serum AST/ALT of 297/597 IU/L. Doppler ultrasound showed mono-phasic wave forms of the hepatic vein. Computed tomography showed focal narrowing of 9.5 mm×12 mm in diameter at the cavo-caval anastomosis site. Liver biopsy was showed that there was no evidence of acute allograft rejection. Direct venogram showed stenosis of the cavo-caval anastomosis with a pressure gradient of 12 mmHg. An interventional stent was inserted in the stenotic site of the inferior vena cava, and the pressure gradient decreased to 2 mmHg. He was discharged from hospital on postoperative day 23 without any other complications. Herein we report a case of deceased-donor liver transplantation using the modified piggyback technique, who received an inferior vena cava stent due to stricture of the reconstructed orifice of the vena cava.

Totally laparoscopic left hemihepatectomy using ventral hilum exposure (VHE) for intrahepatic bile duct stone.

The unique technique of ventral hilum exposure (VHE) was reported that it had excellent surgical outcomes in patients with intrahepatic bile duct stone. The basis of this surgical technique is that all the openings of the 2nd-order bile duct branches are exposed fully. In this article, we describe laparoscopic hemihepatectomy from using the VHE method in a patient with intrahepatic bile duct stone. Our patient was a 70-year-old female who had been diagnosed with an intrahepatic duct stone 30 years prior. Multiple intrahepatic bile duct stones in the left lateral section of the liver were revealed by abdominal computed tomography and magnetic resonance cholangiopancreatography. The patient resumed her oral intake on postoperative day 6. The patient had hyperbilirubinemia (10.3 mg/100 mL) on postoperative day 10. However, her serum bilirubin level decreased to 2.7 mg/100 mL on postoperative day 28. She was discharged without any serious complications on postoperative day 31. Totally laparoscopic left hemihepatectomy, using the VHE method, can be one option of surgical procedure in the near future, although a larger series of cases should be necessary to prove the feasibility of laparoscopic VHE.