Evidence-based clinical practice guidelines for cholelithiasis 2016.

Cholelithiasis is one of the commonest diseases in gastroenterology. Remarkable improvements in therapeutic modalities for cholelithiasis and its complications are evident. The Japanese Society of Gastroenterology has revised the evidence-based clinical practice guidelines for cholelithiasis. Forty-three clinical questions, for four categories-epidemiology and pathogenesis, diagnosis, treatments, and prognosis and complications-were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases for the period between 1983 and June 2012. The guidelines were developed with use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. This article preferentially describes the clinical management of cholelithiasis and its complications. Following description of the diagnosis performed stepwise through imaging modalities, treatments of cholecystolithiasis, choledocholithiasis, and hepatolithiasis are introduced along with a flowchart. Since there have been remarkable improvements in endoscopic treatments and surgical techniques, the guidelines ensure flexibility in choices according to the actual clinical environment. The revised clinical practice guidelines are appropriate for use by clinicians in their daily practice.

Long-term survival following extended hepatectomy with concomitant resection of all major hepatic veins for intrahepatic cholangiocarcinoma: report of a case.

Intrahepatic cholangiocarcinoma involving all major hepatic veins was diagnosed in a 62-year-old man. Multidetector-row computed tomography showed a massive tumor occupying segments 2-5, 7, and 8, with invasion of all major hepatic veins, although the inferior right hepatic vein, draining the venous flow of segment 6, was clearly visualized. Therefore, we planned an extended left trisectionectomy, involving resection of segments 1-5, 7, and 8, with extrahepatic bile duct resection and concomitant resection of all major hepatic veins. We performed portal vein embolization of the right anterior portal branch and the portal branch of segment 7 to identify the demarcation between segments 6 and 7 on the surface of the right lobe. We were able to divide the hepatic parenchyma between segments 6 and 7 and the planned surgery was accomplished, with repositioning of the confluence of the inferior right hepatic vein to prevent outflow blockage. The histological findings were pT3N0M0, Grade2, Stage III, and R0 resection, according to the UICC classification (seventh edition). Although remnant liver metastases were detected 75 months after surgery, the patient is still alive and being treated with chemotherapy, 88 months after surgery. We report this case to demonstrate how using portal vein embolization to identify the hepatic segment helps accomplish extended hepatectomy preserving only one segment and that R0 resection by extended hepatectomy with concomitant resection of all hepatic veins can achieve a satisfactory outcome.

Surgery for Recurrent Biliary Tract Cancer: A Single-center Experience With 74 Consecutive Resections.

OBJECTIVE: To review our experiences with surgery for recurrent biliary tract cancer (BTC). BACKGROUND: Few studies have reported on surgical procedures for recurrent BTC; therefore, it is unclear whether this surgery has survival benefit. METHODS: Between 1991 and 2010, 606 patients had recurrences after resection of BTC (gallbladder cancer, n = 135; cholangiocarcinoma, n = 471); 74 patients underwent resection for recurrence, whereas the remaining 532 did not. The medical records were retrospectively reviewed. RESULTS: Compared with the 532 patients without surgery for recurrence, the 74 patients with surgery had less advanced cancer, and their time to recurrence was significantly longer (1.4 vs 0.8 years; P < 0.001). A total of 89 surgical procedures for recurrence were performed in the 74 patients (1 time in 63 and ≥2 times in 11). Survival after recurrence was significantly better in the 74 patients with surgery than in the 532 without (32% vs 3% at 3 years; P < 0.001). Survival after surgery for recurrence was (1) similar between gallbladder cancer and cholangiocarcinoma; (2) significantly better in patients with initial disease-free interval of 2 or more years; (3) significantly worse in patients with chest or abdominal wall recurrences; and (4) significantly better in patients with pN0 disease in their primary cancer. Nodal status of the primary tumor and the site of initial recurrence were identified as independent prognostic factors after surgery for recurrence. CONCLUSIONS: Surgical resection for recurrent BTC can be performed safely and offers a better chance of long-term survival in selected patients.

Poor prognosis of common-type invasive ductal carcinomas that originate in the branching pancreatic duct.

PURPOSE: To clarify the incidence, clinicopathological features and prognosis of pancreatic invasive ductal carcinomas (IDCs) with different tumor origin sites in the pancreatic duct. METHODS: Based on the relationship between the invasive cancer area (ICA) and the main pancreatic duct (MPD), IDCs less than 2 cm in diameter were classified into two groups: type I, in which the ICA and MPD were separated, and type II, in which the MPD passed through the ICA. The clinicopathological findings and prognosis of each type were compared in a total of 37 patients. RESULTS: The incidences of IDC types I and II were 18.9 and 81.1 %, respectively. Although there was no difference in local invasion, both node involvement and venous invasion tended to occur more frequently in type I IDC, and the three-year survival rate was significantly lower for type I (28.6 %) than type II (71.8 %) IDC. CONCLUSIONS: The prognosis of IDCs that originated in the branching pancreatic duct (BPD) distant from the MPD (type I) was worse than the prognosis of IDCs that originated in either the MPD or the BPD close to the MPD (type II). These data suggest that the progression and degree of malignancy of IDCs may vary depending on the site of tumor origin in the pancreatic duct.

Assessing resectability in cholangiocarcinoma.

Assessment of surgical resectability in cholangiocarcinoma is more complicated than other gastrointestinal malignancies and remains unestablished. According to the primary origin and tumor extent, the applied surgical procedure varies from extrahepatic bile duct resection to right or left trisectionectomy concomitant with pancreatoduodenectomy. Portal vein resection and reconstruction during hepatectomy has been feasible. Thanks to the availability of new microscopic surgical techniques, hepatic arterial resection and reconstruction have also come to be applied for locally advanced cholangiocarcinoma cases. These vascular surgical techniques can expand surgical indications for advanced cholangiocarcinoma. On the other hand, determination of the tumor extent or staging still remains difficult and imprecise. The endoscopic approach has come to play significant roles both for preoperative biliary drainage and tumor staging. Estimation of the functional reserve of future remnant liver in cholestatic patients still remains unresolved. Hepatobiliary surgeons should carefully estimate the safety of the surgical procedure in each individual patient requiring extensive hepatobiliary resection. Early establishment of the measurement methods of the functional capacity of future remnant liver is an important and urgent issue for assessing safer surgical resectablity of cholangiocarcinoma.

Isolated caudate lobectomy with pancreatoduodenectomy for a bile duct cancer.

BACKGROUND: In patients with distal bile duct cancer involving the hepatic hilus, a major hepatectomy concomitant with pancreatoduodenectomy (HPD) is sometimes ideal to obtain a cancer-free resection margin. However, the surgical invasiveness of HPD is considerable. PATIENTS AND METHODS: We present our treatment option for patients with distal bile duct cancer showing mucosal spreading to the hepatic hilum associated with impaired liver function. To minimize resection volume of the liver, an isolated caudate lobectomy (CL) with pancreatoduodenectomy (PD) using an anterior liver splitting approach is presented. Liver transection lines and bile duct resection points correspond complete with our standard right and left hemihepatectomies with CL for perihilar cholangiocarcinoma. RESULTS: Total operation time was 765 min, and pedicle occlusion time was 124 min, respectively. Although the proximal mucosal cancer extension was identified at both the right and the left hepatic ducts, all resection margins were negative for cancer. CONCLUSIONS: Isolated CL with PD is an alternative radical treatment option for bile duct cancer patients with impaired liver function.

Catastrophic head and neck injuries in judo players in Japan from 2003 to 2010.

BACKGROUND: Few studies have documented catastrophic head and neck injuries in judo, but these injuries deserve greater attention. PURPOSE: To determine the features of catastrophic head and neck injuries in judo. STUDY DESIGN: Descriptive epidemiological study. METHODS: This study was based on the accident reports submitted to the All Japan Judo Federation's System for Compensation for Loss or Damage. A total of 72 judo injuries (30 head, 19 neck, and 23 other injuries) were reported between 2003 and 2010. The investigated parameters were mechanism of injury, age at time of injury, length of judo experience, diagnosis, and outcome. RESULTS: Among head injuries, 27 of 30 (90%) occurred in players younger than 20 years of age. The relationship between age, mechanism, and location of injury was more relevant when players younger than 20 years incurred head injury while being thrown (P = .0026). Among neck injuries, 13 of 19 (68%) occurred in players with more than 36 months of experience. The relationship between experience, mechanism, and location of injury was more relevant when experienced players incurred neck injury while executing an offensive maneuver (P = .0294). Acute subdural hematoma was diagnosed in 94% of head injuries. The outcomes of head injury were as follows: 15 players died; 5 were in a persistent vegetative state; 6 required assistance because of higher brain dysfunction, hemiplegia, or aphasia; and 4 had full recovery. Among neck injuries, 18 players were diagnosed with cervical spine injury, 11 of whom had fracture-dislocation of the cervical vertebra; there was also 1 case of atlantoaxial subluxation. The outcomes of neck injury were as follows: 7 players had complete paralysis, 7 had incomplete paralysis, and 5 had full recovery. CONCLUSION: Neck injuries were associated with having more experience and executing offensive maneuvers, whereas head injuries were associated with age younger than 20 years and with being thrown.

Assessment of nodal status for perihilar cholangiocarcinoma: location, number, or ratio of involved nodes.

OBJECTIVE: To analyze lymph node status in resected perihilar cholangiocarcinoma, to clarify which index (ie, location, number, or ratio of involved nodes) is better for staging, and to determine the minimum requirements for node examination. BACKGROUND: In the TNM classification for perihilar cholangiocarcinoma, the number or ratio of involved nodes is not considered for nodal staging. The minimum requirement for histologic examination of lymph nodes is arbitrary. METHODS: This study involved 320 patients with perihilar cholangiocarcinoma who underwent resection from January 2000 to December 2009 at Nagoya University Hospital. The relationship between lymph node status and patient survival was retrospectively analyzed. RESULTS: Total lymph node counts (TLNCs), ie, the number of lymph nodes examined histologically, averaged 12.9 ± 8.3 (range: 1-59). Lymph node metastasis was found in 146 (45.6%) patients and was an independent, powerful prognostic factor. The survival rates were not significantly different between patients with regional node metastasis alone and those with distant node metastasis (19.2% vs 11.5% at 5 years, P = 0.058). The survival for patients with multiple node metastases was significantly worse than that for patients with single metastasis (12.1% vs 27.6% at 5 years, P = 0.002), regardless of the presence or absence of distant lymph node metastasis. The survival for patients with lymph node ratios (LNRs) of 0.2 or less was significantly better than that for patients with LNRs greater than 0.2 (21.4% vs 13.5% at 5 years, P = 0.032). Upon multivariate analysis of the 146 patients with lymph node metastasis, the number of involved nodes (single vs multiple) was identified as an independent prognostic factor (RR of 1.61, P = 0.045), whereas the locations (regional alone vs distant) and ratios (LNR ≤ 0.2 vs LNR > 0.2) of involved nodes were not. When the 148 pN0-R0 patients were divided into 3 groups (ie, those with TLNC ≥ 8, with TLNC = 5, 6, or 7, and with TLNC ≤ 4), survivals were identical between the first and second groups, whereas they were largely different between the former two and the third. CONCLUSIONS: Lymph node metastasis is a powerful, independent prognostic factor in perihilar cholangiocarcinoma and is better classified based not on location but on the number of involved nodes. To adequately assess nodal status, histologic examination of 5 or more nodes is recommended.

Evolution of surgical treatment for perihilar cholangiocarcinoma: a single-center 34-year review of 574 consecutive resections.

OBJECTIVE: To review our 34-year experience with 574 consecutive resections for perihilar cholangiocarcinoma and to evaluate the progress made in surgical treatment of this disease. BACKGROUND: Few studies have reported improved surgical outcomes for perihilar cholangiocarcinoma; therefore, it is still unclear whether surgical treatment of this intractable disease has progressed. METHODS: Between April 1977 and December 2010, a total of 754 consecutive patients with perihilar cholangiocarcinoma were treated, of whom 574 (76.1%) underwent resection. The medical records of these resected patients were retrospectively reviewed. RESULTS: The incidence of major hepatectomies has increased, and limited resections, including central hepatectomies and bile duct resections, were rarely performed. Combined vascular resection was being used more often. Operative time has become shorter, and intraoperative blood loss has also decreased significantly. Because of refinements in surgical techniques and perioperative management, morbidity decreased significantly but was still high, with a rate of 43.1% in the last 5 years. Mortality rate has also decreased significantly (P < 0.001) from 11.1% (8/72) before 1990 to 1.4% (3/218) in the last 5 years. The ratio of advanced disease defined as pStage IVA and IVB has increased significantly from 49.4% before 2000 to 61.4% after 2001. The disease-specific survival for the 574 study patients (including all deaths) was 44.3% at year 3, 32.5% at year 5, and 19.9% at year 10. The survival was significantly better in the later period of 2001 to 2010 than in the earlier period of 1977 to 2000 (38.1% vs 23.1% at year 5, P < 0.001). For pM0, R0, and pN0 patients (n = 243), the survival in the later period was good with 67.1% at year 5, which was significantly better than that of the earlier period (P < 0.001). For pM0, R0, and pN1 patients (n = 142), however, the survival in the later period was similar to that of the earlier period (22.1% vs 14.6% at year 5, P = 0.647). Multivariate analysis revealed that lymph node metastasis was the strongest prognostic indicator. CONCLUSIONS: Surgical treatment of perihilar cholangiocarcinoma has been evolving steadily, with expanded surgical indication, decreased mortality, and increased survival. Survival for R0 and pN0 patients was satisfactory, whereas survival for pN1 patients was still poor, suggesting that establishment of effective adjuvant chemotherapy is needed.

Hepatopancreatoduodenectomy for cholangiocarcinoma: a single-center review of 85 consecutive patients.

OBJECTIVE: To outline our experience with hepatopancreatoduodenectomy (HPD) as a treatment for cholangiocarcinoma and to appraise the clinical significance of this challenging procedure. BACKGROUND: Cholangiocarcinomas often exhibit an extensive ductal spread invading from the hepatic hilus to the lower bile duct, and such tumors can be completely resected only by HPD. Early experiences with HPD were associated with high mortality and morbidity, leading to an underestimation of the survival benefit of HPD. METHODS: We retrospectively reviewed the medical records of 85 patients with cholangiocarcinoma who underwent HPD from 1992 to 2011. Major hepatectomy was performed in 79 patients (92.9%), and combined vascular resection was performed in 26 patients (30.6%). RESULTS: The operating time was 762 ± 141 minutes, and blood loss was 2696 ± 1970 mL. Liver failure was the most common abdominal complication (n = 64), followed by pancreatic fistula (n = 60), wound sepsis (n = 33), intra-abdominal abscess (n = 22), refractory ascites (n = 17), bacteremia (n = 16), bile leakage (n = 13), and delayed gastric emptying (n = 12). Re-laparotomy was necessary in 9 cases (11.1%). Overall, 19 patients (22.4%) exhibited Clavien grade 0 to II complications, 58 (68.2%) exhibited grade III, 6 (7.1%) exhibited grade IV, and 2 (2.4%) exhibited grade V (mortality). The overall survival rate for the 85 patients was 79.7% after 1 year, 48.5% after 3 years, 37.4% after 5 years, and 32.1% after 10 years; 9 (10.5%) patients survived for more than 5 years. The rate of survival for the 53 patients with pM0 disease who underwent R0 resection was the most favorable, with 5- and 10-year survival rates of 54.3% and 46.6%, respectively. CONCLUSIONS: HPD is technically demanding and is associated with high morbidity. However, this surgery can be performed with low mortality and offers a better probability of long-term survival in selected patients. As hepatobiliary surgeons, we should consider HPD to be a standard procedure for laterally advanced cholangiocarcinomas that are otherwise unresectable.

Chronic heavy metal exposure and gallbladder cancer risk in India, a comparative study with Japan.

BACKGROUND: High incidence of gallbladder cancer (GBC) is reported from North India, with elevated concentrations of heavy metals in water and soil. This Indo-Japan collaborative study compared presence of heavy metals in gallbladder tissues. METHODS: Heavy metal concentrations were estimated in Indian GBC and cholecystitis tissues and compared with Japanese GBC and cholecystitis tissues. Spectrophotometry was done for 13 Indian gallbladder tissues (8 GBC, 5 cholecystitis) and 9 Japanese (5 GBC, 4 cholecystitis). Transmission electron microscopy (TEM) thin foil element analysis was done in 10 Indian samples (6 GBC, 4 cholecystitis). RESULTS: Chromium, lead, arsenic and zinc were significantly high in Indian GBC compared with Japanese GBC. Chromium, lead and arsenic were significantly high in the Indian cholecystitis tissues compared to the Japanese. TEM of Indian tissues demonstrated electron dense deposits in GBC. CONCLUSION: Heavy metals- chromium, lead, arsenic and zinc are potential carcinogens in Indian GBC from endemic areas. This preliminary study links presence of heavy metals in gallbladder cancer tissues in endemic areas.

Effect of biliary drainage on chemotherapy in patients with biliary tract cancer: an exploratory analysis of the BT22 study.

BACKGROUND/PURPOSE: Complications from biliary drainage in biliary tract cancer (BTC) may influence the relative dose intensity of chemotherapy or increase adverse events during chemotherapy. BT22 was a randomized phase II trial, the results of which were consistent with those of a phase III trial in non-Japanese that demonstrated the effectiveness of gemcitabine plus cisplatin combination therapy (GC) in BTC. The purpose of this exploratory analysis of the BT22 study was to identify the possible effects of biliary drainage on the efficacy and safety of GC or gemcitabine monotherapy (G). PATIENTS AND METHODS: The 83 BTC patients who received GC or G in BT22 were retrospectively analysed in two subgroups dependent upon whether biliary drainage was performed before study entry. Efficacy and safety of treatment (GC vs. G) were compared in these two groups. RESULTS: The GC arm had a higher 1-year survival rate and longer median survival time (MST) than the G arm independent of prior biliary drainage. Patients in the drainage subgroup developed cholangitis more frequently, however, the frequency of grade 3/4 adverse events did not differ between the treatment regimens with/without drainage. CONCLUSIONS: Biliary drainage before chemotherapy did not affect the therapeutic efficacy or tolerability of chemotherapy using G or GC.

Standard versus extended lymphadenectomy in radical pancreatoduodenectomy for ductal adenocarcinoma of the head of the pancreas: long-term results of a Japanese multicenter randomized controlled trial.

BACKGROUND: The value of pancreatoduodenectomy (PD) with extended lymphadenectomy for pancreatic cancer has been evaluated by many retrospective studies and 3 randomized controlled trials (RCT). However, the protocols used and the results found in the 3 RCTs were diverse. Therefore, a multicenter RCT was proposed in 1998 to evaluate the primary end point of long-term survival and the secondary end points of morbidity, mortality and quality of life of patients undergoing standard versus extended lymphadenectomy in radical PD for pancreatic cancer. METHODS: From March 2000 to May 2003, 112 patients with potentially curable pancreatic head cancer were enrolled and intraoperatively randomized to a standard or extended lymphadenectomy group. No resected patients received any adjuvant treatments. RESULTS: A hundred and one eligible patients were analyzed. Demographic and histopathological characteristics of the two groups were similar. The mean operating time, intraoperative blood loss and number of retrieved lymph nodes were greater in the extended group, but the other operative results were comparable. CONCLUSIONS: Although this multicenter RCT was conducted in a strict setting, extended lymphadenectomy in radical PD did not benefit long-term survival in patients with resectable pancreatic head cancer and led to levels of morbidity, mortality and quality of life comparable to those found after standard lymphadenectomy.

[Severe head injuries during Judo practice].

The goal of this study is to elucidate the characteristic features of Judo head injuries and to propose safety measures and a reaction manual on how to prevent and to deal with such accidents in Japan. Thirty cases of severe head injuries suffered during Judo practice were enrolled in this study. They have made insurance claims for damage compensation and inquiries about Judo accidents attributed to the All Japan Judo Federation, from 2003 to 2010. The average age of the patients was 16.5 year old. The incidence of injury showed 2 peaks in different academic grade levels; one is in the first year of junior high-school (30.0%, n=9) and the other is in senior high school (26.7%, n=8). Around half of them were beginners. Four cases (13.3%) had past history of head trauma or headache and dizziness before a catastrophic accident, suggesting the presence of a second impact. Lucid interval was observed in 25 cases (83.3%). Most patients (93.3%) suffered acute subdural hematoma associated with avulsion of a cerebral bridging vein. Of patients who underwent emergency removal of the hematoma, 15 patients (50%) died and 7 patients (23.3%) entered a persistent vegetative state. Based on these findings, we propose an emergency manual with safety measures for effectively preventing and treating Judo head injuries in an appropriate manner. To reduce the disastrous head injuries in Judo, the safety measures and an optimal action manual should be reconsidered and widely spread and accepted by society.

Post-hepatectomy haemorrhage: a definition and grading by the International Study Group of Liver Surgery (ISGLS).

BACKGROUND: A standardized definition of post-hepatectomy haemorrhage (PHH) has not yet been established. METHODS: An international study group of hepatobiliary surgeons from high-volume centres was convened and a definition of PHH was developed together with a grading of severity considering the impact on patients' clinical management. RESULTS: The definition of PHH varies strongly within the hepatic surgery literature. PHH is defined as a drop in haemoglobin level > 3 g/dl post-operatively compared with the post-operative baseline level and/or any post-operative transfusion of packed red blood cells (PRBC) for a falling haemoglobin and/or the need for radiological intervention (such as embolization) and/or re-laparotomy to stop bleeding. Evidence of intra-abdominal bleeding should be obtained by imaging or blood loss via the abdominal drains if present. Transfusion of up to two units of PRBC is considered as being Grade A PHH. Grade B PHH requires transfusion of more than two units of PRBC, whereas the need for invasive re-intervention such as embolization and/ or re-laparotomy defines Grade C PHH. CONCLUSION: The proposed definition and grading of severity of PHH enables valid comparisons of results from different studies. It is easily applicable in clinical routine and should be applied in future trials to standardize reporting of complications.

New staging system and a registry for perihilar cholangiocarcinoma.

Perihilar cholangiocarcinoma is one of the most challenging diseases with poor overall survival. The major problem for anyone trying to convincingly compare studies among centers or over time is the lack of a reliable staging system. The most commonly used system is the Bismuth-Corlette classification of bile duct involvement, which, however, does not include crucial information such as vascular encasement and distant metastases. Other systems are rarely used because they do not provide several key pieces of information guiding therapy. Therefore, we have designed a new system reporting the size of the tumor, the extent of the disease in the biliary system, the involvement of the hepatic artery and portal vein, the involvement of lymph nodes, distant metastases, and the volume of the putative remnant liver after resection. The aim of this system is the standardization of the reporting of perihilar cholangiocarcinoma so that relevant information regarding resectability, indications for liver transplantation, and prognosis can be provided. With this tool, we have created a new registry enabling every center to prospectively enter data on their patients with hilar cholangiocarcinoma (www.cholangioca.org). The availability of such standardized and multicenter data will enable us to identify the critical criteria guiding therapy.

Dramatic tumor response to everolimus for malignant epithelioid angiomyolipoma.

Malignant epithelioid variant of angiomyolipoma has aggressive characteristics, against which conventional cytotoxic agents have been reported to be disappointingly inactive, and the prognosis of unresectable or recurrent disease is dismal poor. A 52-year-old man with a history of left nephrectomy for epithelioid angiomyolipoma was referred to our institution. The computed tomographic scan showed a soft tissue dense mass around the Rex's recess and behind the spleen, and a large pelvic mass. Specimens obtained by percutaneous needle biopsy confirmed the recurrence of malignant epithelioid angiomyolipoma. Everolimus was initiated at 10 mg per day for recurrent disease. Computed tomographic scans 2 months later showed the tumors to be markedly decreased in size. The patient has continued with this treatment on an outpatient basis without signs of disease progression over 7 months, as of February 2011. In this case, treatment with everolimus resulted in dramatic tumor response for the malignant epithelioid variant of angiomyolipoma.

Bile leakage after hepatobiliary and pancreatic surgery: a definition and grading of severity by the International Study Group of Liver Surgery.

BACKGROUND: Despite the potentially severe impact of bile leakage on patients' perioperative and long-term outcome, a commonly used definition of this complication after hepatobiliary and pancreatic operations has not yet been established. The aim of the present article is to propose a uniform definition and severity grading of bile leakage after hepatobiliary and pancreatic operative therapy. METHODS: An international study group of hepatobiliary and pancreatic surgeons was convened. A consensus definition of bile leakage after hepatobiliary and pancreatic operative therapy was developed based on the postoperative course of bilirubin concentrations in patients' serum and drain fluid. RESULTS: After evaluation of the postoperative course of bilirubin levels in the drain fluid of patients who underwent hepatobiliary and pancreatic operations, bile leakage was defined as bilirubin concentration in the drain fluid at least 3 times the serum bilirubin concentration on or after postoperative day 3 or as the need for radiologic or operative intervention resulting from biliary collections or bile peritonitis. Using this criterion severity of bile leakage was classified according to its impact on patients' clinical management. Grade A bile leakage causes no change in patients' clinical management. A Grade B bile leakage requires active therapeutic intervention but is manageable without relaparotomy, whereas in Grade C, bile leakage relaparotomy is required. CONCLUSION: We propose a simple definition and severity grading of bile leakage after hepatobiliary and pancreatic operative therapy. The application of the present proposal will enable a standardized comparison of the results of different clinical trials and may facilitate an objective evaluation of diagnostic and therapeutic modalities in the field of hepatobiliary and pancreatic operative therapy.

Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS).

BACKGROUND: Posthepatectomy liver failure is a feared complication after hepatic resection and a major cause of perioperative mortality. There is currently no standardized definition of posthepatectomy liver failure that allows valid comparison of results from different studies and institutions. The aim of the current article was to propose a definition and grading of severity of posthepatectomy liver failure. METHODS: A literature search on posthepatectomy liver failure after hepatic resection was conducted. Based on the normal course of biochemical liver function tests after hepatic resection, a simple and easily applicable definition of posthepatectomy liver failure was developed by the International Study Group of Liver Surgery. Furthermore, a grading of severity is proposed based on the impact on patients' clinical management. RESULTS: No uniform definition of posthepatectomy liver failure has been established in the literature addressing hepatic surgery. Considering the normal postoperative course of serum bilirubin concentration and International Normalized Ratio, we propose defining posthepatectomy liver failure as the impaired ability of the liver to maintain its synthetic, excretory, and detoxifying functions, which are characterized by an increased international normalized ratio and concomitant hyperbilirubinemia (according to the normal limits of the local laboratory) on or after postoperative day 5. The severity of posthepatectomy liver failure should be graded based on its impact on clinical management. Grade A posthepatectomy liver failure requires no change of the patient's clinical management. The clinical management of patients with grade B posthepatectomy liver failure deviates from the regular course but does not require invasive therapy. The need for invasive treatment defines grade C posthepatectomy liver failure. CONCLUSION: The current definition of posthepatectomy liver failure is simple and easily applicable in clinical routine. This definition can be used in future studies to allow objective and accurate comparisons of operative interventions in the field of hepatic surgery.

Pathological complete response of colorectal liver metastases following chemotherapy with S-1 and oxaliplatin (SOX) in combination with bevacizumab: A case report.

Pathological complete response to systemic chemotherapy is associated with more favorable survival in patients with colorectal cancer liver metastases. We present a case of a 63-year-old man with multiple liver metastases from descending colon cancer. Following surgical resection of the primary tumor, the patient received systemic chemotherapy with S-1 and oxaliplatin in combination with bevacizumab. On achievement of a markedly favorable response to chemotherapy, surgical treatment of liver metastases was performed, and the liver tumors were successfully resected without any macroscopic residue. Histopathological analyses showed necrotic tissue in the complete absence of residual viable tumor cells. This is the first reported case of a patient with multiple liver metastases from descending colorectal cancer to achieve a pathological complete response following systemic chemotherapy with S-1 and oxaliplatin in combination with bevacizumab. This regimen is a systemic chemotherapy option to 'cure' liver metastasis from colorectal cancer.