Early Versus Late Oral Refeeding After Pancreaticoduodenectomy for Malignancy: a Comparative Belgian-French Study in Two Tertiary Centers.

BACKGROUND: In the era of fast-track surgery, because pancreaticoduodenectomy (PD) carries a significant morbidity, surgeons hesitate to begin early oral feeding and achieve early discharge. We compared the outcome of two different approaches to the postoperative management of PD in two tertiary centers. METHODS: Of patients having undergone PD for malignancy from 2008 to 2017, 100 patients who received early postoperative oral feeding (group A) were compared to 100 patients from another center who received early enteral feeding and a delayed oral diet (group B). Surgical indication and approach and type of pancreatic anastomosis were similar between both groups. Postoperative outcomes were retrospectively reviewed. RESULTS: Patient characteristics were similar between both groups, except significantly more neoadjuvant treatment in group A (A = 20% vs. B = 9%, p < 0.01). Mortality rates were 3% and 4% in groups A and B, respectively (p = 0.71). The rate of severe postoperative morbidity was significantly lower in group A (13% vs. 26%, p = 0.02), resulting in a lower reoperation rate (p < 0.01). Delayed gastric emptying and clinically relevant pancreatic fistula were similar between both groups but chyle leaks were more frequent in group A (10% vs. 3%, p = 0.04). The median hospital stay was shorter in group A (16 vs. 20 days, p < 0.01). CONCLUSION: In the present study, early postoperative oral feeding after PD was associated with a shorter hospital stay and did not increase severe postoperative morbidity or the rate of pancreatic fistula. However, it resulted in more chyle leaks and did not prevent delayed gastric emptying.

Long-term results of secondary biliary repair for cholecystectomy-related bile duct injury: results of a tertiary referral center.

Background: Management of bile duct injury (BDI) after cholecystectomy is challenging. The authors analyzed their center's 49-year experience.Methods: From 1968 to 2016, 120 consecutive patients were managed in a tertiary HBP center, 105 referred from other centers (Group A), 15 from our center (Group B). Surgical strategies and long-term outcomes were retrospectively reviewed.Results: Primary cholecystectomy approach was open in 35% and laparoscopic in 65%. In Group A, intraoperative BDI diagnosis was made in 25/105 patients, including 13 via intraoperative cholangiography (IOC) which was used in 21% of cases. Median time from BDI to referral was 148 days (range 0-10,758), and 3 patients had BDI-related secondary cirrhosis. Ninety-four patients underwent secondary surgical repair, mostly a complex biliary procedure (97%). Postoperative overall and severe morbidity rates were 26% and 6%, respectively. One patient with biliary cirrhosis at referral died postoperatively from hepatic failure. Nine patients (9.6%) developed a secondary biliary stricture after a median of 54 months from repair (6-228 months). In Group B, IOC was performed in 14/15 in whom BDI were intraoperatively detected and immediately repaired. There were 13 minor and 2 major BDIs, all repaired by uncomplex procedures with uneventful postoperative course. One patient had a secondary biliary stricture after 5 months, successfully treated by temporary endoprosthesis.Conclusion: Late follow-up after primary or secondary repair of BDI is recommended to detect recurrent biliary stricture. Bile duct injuries may occur in a tertiary center, but are intraoperatively detected with routine IOC and immediately repaired resulting in satisfactory outcome.

Endoscopic management of common bile duct stones: European Society of Gastrointestinal Endoscopy (ESGE) guideline.

ESGE recommends offering stone extraction to all patients with common bile duct stones, symptomatic or not, who are fit enough to tolerate the intervention.Strong recommendation, low quality evidence.ESGE recommends liver function tests and abdominal ultrasonography as the initial diagnostic steps for suspected common bile duct stones. Combining these tests defines the probability of having common bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends endoscopic ultrasonography or magnetic resonance cholangiopancreatography to diagnose common bile duct stones in patients with persistent clinical suspicion but insufficient evidence of stones on abdominal ultrasonography.Strong recommendation, moderate quality evidence.ESGE recommends the following timing for biliary drainage, preferably endoscopic, in patients with acute cholangitis, classified according to the 2018 revision of the Tokyo Guidelines:- severe, as soon as possible and within 12 hours for patients with septic shock- moderate, within 48 - 72 hours- mild, elective.Strong recommendation, low quality evidence.ESGE recommends endoscopic placement of a temporary biliary plastic stent in patients with irretrievable biliary stones that warrant biliary drainage.Strong recommendation, moderate quality of evidence.ESGE recommends limited sphincterotomy combined with endoscopic papillary large-balloon dilation as the first-line approach to remove difficult common bile duct stones. Strong recommendation, high quality evidence.ESGE recommends the use of cholangioscopy-assisted intraluminal lithotripsy (electrohydraulic or laser) as an effective and safe treatment of difficult bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends performing a laparoscopic cholecystectomy within 2 weeks from ERCP for patients treated for choledocholithiasis to reduce the conversion rate and the risk of recurrent biliary events. Strong recommendation, moderate quality evidence.

The Link between the Multiverse of Immune Microenvironments in Metastases and the Survival of Colorectal Cancer Patients.

Treatment of metastatic colorectal cancer is based upon the assumption that metastases are homogeneous within a patient. We quantified immune cell types of 603 whole-slide metastases and primary colorectal tumors from 222 patients. Primary lesions, and synchronous and metachronous metastases, had a heterogeneous immune infiltrate and mutational diversity. Small metastases had frequently a low Immunoscore and T and B cell score, while a high Immunoscore was associated with a lower number of metastases. Anti-epidermal growth factor receptor treatment modified immune gene expression and significantly increased T cell densities in the metastasis core. The predictive accuracy of the Immunoscore from a single biopsy was superior to the one of programmed cell death ligand 1 (PD-L1). The immune phenotype of the least-infiltrated metastasis had a stronger association with patient outcome than other metastases.

Impact of biological agents on the prevalence of chemotherapy associated liver injury (CALI): Multicentric study of patients operated for colorectal liver metastases.

BACKGROUND: The prevalence of chemotherapy associated liver injuries (CALI), especially SOS (sinusoidal obstruction syndrome) and NRH (nodular regenerative hyperplasia) might be reduced since the introduction of routine use of biological agents with chemotherapy in colorectal liver metastases (CRLM). METHODS: One hundred patients with CRLM having undergone at least one liver segment resection were prospectively included, and chemotherapy data recorded. Specimens were reviewed by a single pathologist and CALI were described. Prevalence of CALI was compared to our previous experience published in 2013. NRH diagnosis was performed on reticulin special stain, by contrast to our previous study. Postoperative outcome was analysed. RESULTS: Bevacizumab was more frequently administrated in patients of the present study: 53/100 (53%) compared to 20/151 (13%), p < 0.0001. Overall, in the present series, SOS was only observed in 28/100 (28%) patients compared to 116/151 (77%) in 2013 (p < 0.001). When looking specifically to patients receiving Bevacizumab with Folfox, we observed a reduced SOS prevalence compared to Folfox alone (p = 0.008). A higher prevalence of NRH was found in the present study, related to increased detection accuracy, but in patients receiving Bevacizumab in association with Folfox, this prevalence was also reduced compared to Folfox alone (p = 0.03). Both SOS and NRH were associated with severe complications (p = 0.008 and p = 0.005, respectively) and postoperative liver insufficiency (p < 0.001 and p < 0.01, respectively). CONCLUSIONS: The routine use of Bevacizumab in association with Folfox significantly reduced CALI prevalence, in turn linked to severe postoperative complications.

Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival.

Background: This study assesses how the metastatic immune landscape is impacting the response to treatment and the outcome of colorectal cancer (CRC) patients. Methods: Complete curative resection of metastases (n = 441) was performed for two patient cohorts (n = 153). Immune densities were quantified in the center and invasive margin of all metastases. Immunoscore and T and B cell (TB) score were analyzed in relation to radiological and pathological responses and patient's disease-free (DFS) and overall survival (OS) using multivariable Cox proportional hazards models. All statistical tests were two-sided. Results: The spatial distribution of immune cells within metastases was nonuniform. Patients, as well as metastases of the same patient, had variable immune infiltrates and response to therapy. A beneficial response was statistically significantly associated with increased immune densities. Among all metastases, Immunoscore (I) and TB score evaluated in the least immune-infiltrated metastases were the strongest predictors for DFS and OS (five-year follow-up, Immunoscore: I 3-4: DFS rate = 27.9%, 95% CI = 15.2 to 51.3; vs I 0-1-2: DFS rate = 12.3%, 95% CI = 4.9 to 30.6; HR = 0.45, 95% CI = 0.28 to 0.70, P = .02; I 3-4: OS rate = 64.6%, 95% CI = 46.6 to 89.6; vs I 0-1-2: OS rate = 32.5%, 95% CI = 17.2 to 61.4; HR = 0.32, 95% CI = 0.15 to 0.66, P = .001, C-index = 65.9%; five-year follow-up, TB score: TB 3-4: DFS rate = 25.7%, 95% CI = 14.2 to 46.6; vs TB 0-1-2: DFS rate = 5.0%, 95% CI = 0.8 to 32.4; HR = 0.36, 95% CI = 0.22 to 0.57, P < .001; TB 3-4: OS rate = 63.7%, 95% CI = 46.4 to 87.5; vs TB 0-1-2: OS rate: 21.4%, 95% CI = 9.2 to 49.8; HR = 0.25, 95% CI = 0.12 to 0.51, P < .001, C-index = 67.8%). High TB score and Immunoscore patients had a median survival of 70.5 months, while low patients survived only 25.1 to 38.3 months. Nonresponding patients with high-immune infiltrates had prolonged DFS (HR = 0.28, 95% CI = 0.15 to 0.52, P = .001) and OS (HR = 0.25, 95% CI = 0.1 to 0.62, P = .001). The immune parameters remained the only statistically significant prognostic factor associated with DFS and OS in multivariable analysis (P < .001), while response to treatment was not. Conclusions: Response to treatment and prolonged survival of metastatic CRC patients were statistically significantly associated with high-immune densities quantified into the least immune-infiltrated metastasis.

Pancreaticobiliary Maljunctions in European Patients with Bile Duct Cysts: Results of the Multicenter Study of the French Surgical Association (AFC).

BACKGROUND: Pancreaticobiliary maljunctions (PBMs) are congenital anomalies of the junction between pancreatic and bile ducts, frequently associated with bile duct cyst (BDC). BDC is congenital biliary tree diseases that are characterized by distinctive dilatation types of the extra- and/or intrahepatic bile ducts. Todani's types I and IVa, in which dilatation involves principally the main bile duct, are the most frequent. PBM induces pancreatic juice reflux into the biliary tract that is supposed to be one of the main factors of biliary cancer degeneration, although the diagnostic criteria of PBM that can be either morphological and/or functional are not well defined especially in Western series. OBJECTIVE: The aim of this study was to assess the relative prevalence of PBM in BDC in a large European multicenter study, to analyze the characteristics of PBM and try to propose diagnostic criteria of PBMs based on morphological and/or functional criteria and define the positive, negative predictive values, sensibility and specificity of either criteria. RESULTS: From 1975 to 2012, 263 patients with BDC were analyzed. Among them, 190 (72.2 %) were considered to present PBM. Types I and IVa had a similar rate of PBM association. According to the "AFC classification," 57.2 % had a C-P type, 34.5 % a P-C type and 8.3 % a complex type ("anse-de-seau"). The median length of the common channel in patients with PBM was 15.8 ± 6.8 mm (range 5-40 mm). The median intrabiliary amylase and lipase levels were 65,249 and 172,104 UI/L, respectively. For the diagnostic of PBM, a common channel length of more than 8 mm and an intrabiliary amylase level superior to 8000 UI/L were associated with a predictive positive value and a specificity of more than 90 %. Synchronous biliary cancer had an incidence of 8.7 % in all patients with BDC and PBM 11.1 % in adults. Compared to type IV, the type I BDC was associated with statistically more cancer patients in the presence of PBM. CONCLUSIONS: Characteristics of PBM associated with BDC in Western population are quite close to reported Eastern series. The results suggest considering both the intrabiliary value of amylase >8000 UI/L and a length of a common channel >8 mm as appropriate values for positive diagnosis of PBM.

Impact of previous cyst-enterostomy on patients' outcome following resection of bile duct cysts.

AIM: To analyze the impact of previous cyst-enterostomy of patients underwent congenital bile duct cysts (BDC) resection. METHODS: A multicenter European retrospective study between 1974 and 2011 were conducted by the French Surgical Association. Only Todani subtypes I and IVb were included. Diagnostic imaging studies and operative and pathology reports underwent central revision. Patients with and without a previous history of cyst-enterostomy (CE) were compared. RESULTS: Among 243 patients with Todani types I and IVb BDC, 16 had undergone previous CE (6.5%). Patients with a prior history of CE experienced a greater incidence of preoperative cholangitis (75% vs 22.9%, P < 0.0001), had more complicated presentations (75% vs 40.5%, P = 0.007), and were more likely to have synchronous biliary cancer (31.3% vs 6.2%, P = 0.004) than patients without a prior CE. Overall morbidity (75% vs 33.5%; P < 0.0008), severe complications (43.8% vs 11.9%; P = 0.0026) and reoperation rates (37.5% vs 8.8%; P = 0.0032) were also significantly greater in patients with previous CE, and their Mayo Risk Score, during a median follow-up of 37.5 mo (range: 4-372 mo) indicated significantly more patients with fair and poor results (46.1% vs 15.6%; P = 0.0136). CONCLUSION: This is the large series to show that previous CE is associated with poorer short- and long-term results after Todani types I and IVb BDC resection.

Congenital bile duct cyst (BDC) is a more indolent disease in children compared to adults, except for Todani type IV-A BDC: results of the European multicenter study of the French Surgical Association.

AIM: To compare clinical presentation, operative management and short- and long-term outcomes of congenital bile duct cysts (BDC) in adults with children. METHODS: Retrospective multi-institutional Association Francaise de Chirurgie study of Todani types I+IVB and IVA BDC. RESULTS: During the 37-year period to 2011, 33 centers included 314 patients (98 children; 216 adults). The adult population included more high-risk patients, with more active, more frequent prior treatment (47.7% vs 11.2%; p < 0.0001), more complicated presentation (50.5% vs 35.7%; p = 0.015), more synchronous biliary cancer (11.6% vs 0%; p = 0.0118) and more major surgery (23.6% vs 2%; p < 0.0001), but this latter feature was only true for type I+IVB BDC. Compared to children, the postoperative morbidity (48.1% vs 20.4%; p < 0.0001), the need for repeat procedures and the status at follow-up were worse in adults (27% vs 8.8%; p = 0.0009). However, severe postoperative morbidity and fair or poor status at follow-up were not statistically different for type IVA BDC, irrespective of patients' age. Synchronous cancer, prior HBP surgery and Todani type IVA BDC were independent predictive factors of poor or fair long-term outcome. CONCLUSION: BDC is a more indolent disease in children compared to adults, except for Todani type IV-A BDC.

Impact of Intraoperative Pancreatoscopy with Intraductal Biopsies on Surgical Management of Intraductal Papillary Mucinous Neoplasm of the Pancreas.

BACKGROUND: Because of its known malignant potential, precise histologic diagnosis of intraductal papillary mucinous neoplasm of the pancreas (IPMN) during intraoperative pancreatoscopy (IOP) is essential for complete surgical resection. The impact of IOP on perioperative IPMN patient management was reviewed over 20 years of practice at Cliniques universitaires Saint-Luc, Brussels, Belgium. STUDY DESIGN: Among 86 IPMN patients treated by pancreatectomy between 1991 and 2013, 21 patients had a dilated main pancreatic duct enabling IOP and were retrospectively reviewed. The IOP was performed using an ultrathin flexible endoscope and biopsy forceps, and specimens of all suspicious lesions underwent frozen section examination. RESULTS: Complete IOP with intraductal biopsies was easily and safely performed in 21 patients, revealing 8 occult IPMN lesions. In 5 cases (23.8%), initially planned surgical resection was modified secondary to IOP: 3 for carcinoma in situ and 2 for invasive carcinoma. The postoperative morbidity rate at 3 months was 25.0% (5 of 20); 1 patient died from septic shock postoperatively and was excluded. Median follow-up was 93 months (range 13 to 248 months). Nineteen of 21 patients were still alive and free of disease at last follow-up (90.5%); there was 1 patient with invasive carcinoma at initial pathology (pT3 N1) who died of pulmonary recurrence 21 months after surgery. CONCLUSIONS: Intraoperative pancreatoscopy of the main pancreatic duct combined with intraductal biopsies plays a significant role in the surgical management of IPMN patients and should be used in all patients presenting a sufficiently dilated main pancreatic duct.

Early hyperlactatemia predicts pancreatic fistula after surgery.

BACKGROUND: Postoperative pancreatic fistula (POPF) is a major complication after pancreatic surgery and results from an impaired healing of the pancreatic enteric anastomosis. Whether perioperative hemodynamic fluid management aiming to provide an adequate tissue perfusion could influence the occurrence of POPF is unknown. Serum lactate level is a well-recognized marker of decreased tissue perfusion and is known to be associated with higher morbidity and mortality in various postoperative settings. We aimed to determine in a retrospective high-volume center's cohort whether postoperative hyperlactatemia could predict POPF occurrence. METHOD: We conducted a retrospective analysis of 96 consecutive patients admitted in the intensive care unit (ICU) after pancreaticoduodenectomy or distal pancreatectomy. Univariate analysis was conducted to compare lactate levels at 6 h between patients evolving with versus without POPF. A logistic regression model was developed and included potential confounding factors. RESULTS: POPF occurred in 28 patients (29 %). Serum lactate level 6 h after admission was significantly higher in the POPF group (2.8 mmol/L [95 % confidence interval (CI): 2.1-3.5] versus 1.8 mmol/L [95 % CI: 1.8-2.4], p-value = 0.04) whereas it did not differ at ICU admission or at 12 h. Despite similar cumulative fluid balance, fluid intake and vasopressor use, hyperlactatemia > 2.5 mmol/L (Odds ratio (OR): 3.58; 95 % CI: 1.22-10.48; p-value = 0.020) and red blood cells transfusion (OR: 1.24; 95 % CI: 1.03-1.49; p-value = 0.022) were found to be independent predictive factors of POPF occurrence. CONCLUSION: In patients undergoing partial pancreatectomy, hyperlactatemia measured 6 h after ICU admission is a predictive factor for the occurrence of POPF. Inflammatory changes after surgery may account for this observation and should be further evaluated.

Does the site of platelet sequestration predict the response to splenectomy in adult patients with immune thrombocytopenic purpura?

Splenectomy is the only potentially curative treatment for chronic immune thrombocytopenic purpura (ITP) in adults. However, one-third of the patients relapse without predictive factors identified. We evaluate the predictive value of the site of platelet sequestration on the response to splenectomy in patients with ITP. Eighty-two consecutive patients with ITP treated by splenectomy between 1992 and 2013 were retrospectively reviewed. Platelet sequestration site was studied by (111)Indium-oxinate-labeled platelets in 93% of patients. Response to splenectomy was defined at last follow-up as: complete response (CR) for platelet count (PC) ≥100 × 10(9)/L, response (R) for PC≥30 × 10(9)/L and <100 × 10(9)/L with absence of bleeding, no response (NR) for PC<30 × 10(3)/L or significant bleeding. Laparoscopic splenectomy was performed in 81 patients (conversion rate of 16%), and open approach in one patient. Median follow-up was 57 months (range, 1-235). Platelet sequestration study was performed in 93% of patients: 50 patients (61%) exhibited splenic sequestration, 9 (11%) hepatic sequestration and 14 patients (17%) mixed sequestration. CR was obtained in 72% of patients, R in 25% and NR in 4% (two with splenic sequestration, one with hepatic sequestration). Preoperative PC, age at diagnosis, hepatic sequestration and male gender were significant for predicting CR in univariate analysis, but only age (HR = 1.025 by one-year increase, 95% CI [1.004-1.047], p = 0.020) and pre-operative PC (HR = 0.112 for > 100 versus <=100, 95% CI [0.025-0.493], p = 0.004) were significant predictors of recurrence-free survival in multivariate analysis. Response to splenectomy was independent of the site of platelet sequestration in patients with ITP. Pre-operative platelet sequestration study in these patients cannot be recommended.

Todani Type II Congenital Bile Duct Cyst: European Multicenter Study of the French Surgical Association and Literature Review.

OBJECTIVE: The purpose of the study was to analyze clinical presentation, surgical management, and long-term outcome of patients suffering from biliary diverticulum, namely Todani type II congenital bile duct cyst (BDC). BACKGROUND: The disease incidence ranges between 0.8% and 5% of all reported BDC cases with a lack of information about clinical presentation, management, and outcome. METHODS: A multicenter European retrospective study was conducted by the French Surgical Association. The patients' medical records were included in a Web site database. Diagnostic imaging studies, operative and pathology reports underwent central revision. RESULTS: Among 350 patients with congenital BDC, 19 type II were identified (5.4%), 17 in adults (89.5%) and 2 in children. The biliary diverticulum was located at the upper, middle, and lower part of the extrahepatic biliary tree in 11, 4, and 4 patients (58%, 21%, and 21%, respectively). Complicated presentation occurred in 6 patients (31.6%), including one case of synchronous carcinoma. Surgical techniques included diverticulum excision in all patients. Associated resection of the extrahepatic biliary tree was required in 11 cases (58%) and could be predicted by the presence of complicated clinical presentation. There was no mortality. Long-term outcome was excellent in 89.5% of patients (median follow-uptime: 52 months). CONCLUSIONS: According to the present largest Western series of Todani type II BDC, the type of clinical presentation rather than BDC location, was able to guide the extent of biliary resection. Excellent long-term outcome can be achieved in expert centers.

Tumour size over 3 cm predicts poor short-term outcomes after major liver resection for hilar cholangiocarcinoma. By the HC-AFC-2009 group.

INTRODUCTION: As mortality and morbidity after a curative resection remains high, it is essential to identify pre-operative factors associated with an early death after a major resection. METHODS: Between 1998 and 2008, we selected a population of 331 patients having undergone a major hepatectomy including segment I with a lymphadenectomy and a common bile duct resection for a proven hilar cholangiocarcinoma in 21 tertiary centres. The study's objective was to identify pre-operative predictors of early death (<12 months) after a resection. RESULTS: The study cohort consisted of 221 men and 110 women, with a median age of 61 years (range: 24-85). The post-operative mortality and morbidity rates were 8.2% and 61%, respectively. The 1-, 3- and 5-year overall survival rates were 85%, 64% and 53%, respectively. The median tumour size was 23 mm on pathology, ranging from 8 to 40. A tumour size >30 mm [odds ratio (OR) 2.471 (95% confidence interval (CI) 1.136-7.339), P = 0.001] and major post-operative complication [OR 3.369 (95% CI 1.038-10.938), P = 0.004] were independently associated with death <12 months in a multivariate analysis. CONCLUSION: The present analysis of a series of 331 patients with hilar cholangiocarcinoma showed that tumour size >30 mm was independently associated with death <12 months.

Surgical management of liver hydatid disease: subadventitial cystectomy versus resection of the protruding dome.

BACKGROUND: The aim of this study was to compare postoperative outcome and long-term results after management of liver hydatid cysts (LHC) by subadventitial cystectomy (SC) and resection of the protruding dome (RPD) in two tertiary liver surgery centers. METHODS: Medical records of 52 patients who underwent SC in one center, and 27 patients who underwent RPD in another center between 1991 and 2011 were reviewed. Patients underwent long-term follow-up, including serology tests and morphological examinations. RESULTS: Postoperative mortality was nil. The rate of severe morbidity was 7.7 and 22% (p = 0.082), while the rate of serological clearing-up was 20 and 13.3% after SC and RPD, respectively (p = 1.000). After a mean follow-up of 41 months (1-197), four patients developed a long-term cavity-related complication (LTCRC) after RPD (including one recurrence) and none after SC (p = 0.012). All LTCRCs occurred in patients with hydatid cysts located at the liver dome; three required an invasive procedure by either puncture aspiration injection re-aspiration (N = 1) or repeat surgery (N = 2). CONCLUSIONS: RPD exposes to specific LTCRC, especially when hydatid cysts are located at the liver dome, while SC allows ad integrum restoration of the operated liver. Therefore, SC should be considered as the standard surgical treatment for LHC in experienced hepato-pancreato-biliary centers.

Genomic profiling of intrahepatic cholangiocarcinoma: refining prognosis and identifying therapeutic targets.

BACKGROUND: The molecular alterations that drive tumorigenesis in intrahepatic cholangiocarcinoma (ICC) remain poorly defined. We sought to determine the incidence and prognostic significance of mutations associated with ICC among patients undergoing surgical resection. METHODS: Multiplexed mutational profiling was performed using nucleic acids that were extracted from 200 resected ICC tumor specimens from 7 centers. The frequency of mutations was ascertained and the effect on outcome was determined. RESULTS: The majority of patients (61.5 %) had no genetic mutation identified. Among the 77 patients (38.5 %) with a genetic mutation, only a small number of gene mutations were identified with a frequency of >5 %: IDH1 (15.5 %) and KRAS (8.6 %). Other genetic mutations were identified in very low frequency: BRAF (4.9 %), IDH2 (4.5 %), PIK3CA (4.3 %), NRAS (3.1 %), TP53 (2.5 %), MAP2K1 (1.9 %), CTNNB1 (0.6 %), and PTEN (0.6 %). Among patients with an IDH1-mutant tumor, approximately 7 % were associated with a concurrent PIK3CA gene mutation or a mutation in MAP2K1 (4 %). No concurrent mutations in IDH1 and KRAS were noted. Compared with ICC tumors that had no identified mutation, IDH1-mutant tumors were more often bilateral (odds ratio 2.75), while KRAS-mutant tumors were more likely to be associated with R1 margin (odds ratio 6.51) (both P < 0.05). Although clinicopathological features such as tumor number and nodal status were associated with survival, no specific mutation was associated with prognosis. CONCLUSIONS: Most somatic mutations in resected ICC tissue are found at low frequency, supporting a need for broad-based mutational profiling in these patients. IDH1 and KRAS were the most common mutations noted. Although certain mutations were associated with ICC clinicopathological features, mutational status did not seemingly affect long-term prognosis.

Vascular resection during radical resection of pancreatic adenocarcinomas: evolution over the past 15 years.

This literature review aimed to critically analyze oncological results of vascular resection during pancreatectomy for adenocarcinoma in the light of the concept evolution of locally advanced tumors and microscopic complete resection. The literature search was conducted in PubMed and Medline for the period June 1994 to December 2012, retaining English as the language of publication. The review of 12 publications indicated that mortality and morbidity rates were not significantly different for pancreatectomy with or without venous resection (VR). Six comparative studies showed worse long-term survival in the VR group, though one meta-analysis, albeit with a significant population heterogeneity, demonstrated that the overall survival between VR and the control group was similar (12% vs. 17%). The compilation of 13 comparative studies showed a significantly lower rate of complete microscopic resection in the VR patient group compared to controls (63% vs. 77%; P = 0.001). Concerning pancreatectomy combined to arterial resection, the literature review indicated a significantly greater mortality and morbidity rate and a lower survival rate compared to pancreatic resection alone. Conflicting results concerning the long-term outcome of VR was due to the heterogeneity of the patient population. Since the only chance to cure patients of pancreatic adenocarcinoma is to obtain free resection margins, VR is a valid therapeutic option. But combined arterial resection to pancreatic resection does not appear to be recommended.

Tumor size predicts vascular invasion and histologic grade among patients undergoing resection of intrahepatic cholangiocarcinoma.

The association between tumor size and survival in patients with intrahepatic cholangiocarcinoma (ICC) undergoing surgical resection is controversial. We sought to define the incidence of major and microscopic vascular invasion relative to ICC tumor size, and identify predictors of microscopic vascular invasion in patients with ICC ≥5 cm. A total of 443 patients undergoing surgical resection for ICC between 1973 and 2011 at one of 11 participating institutions were identified. Clinical and pathologic data were evaluated using uni- and multivariate analyses. As tumor sized increased, the incidence of microscopic vascular invasion increased: <3 cm, 3.6 %; 3-5 cm, 24.7 %; 5-7 cm, 38.3 %; 7-15 cm, 32.9 %, ≥15 cm, 55.6 %; (p < 0.001). Increasing tumor size was also found to be associated with worsening tumor grade. The incidence of poorly differentiated tumors increased with increasing ICC tumor size: <3 cm, 9.7 %; 3-5 cm, 19.8 %; 5-7 cm, 24.2 %; 7-15 cm, 21.1 %; >15 cm, 31.6 % (p = 0.04). The presence of perineural invasion (odds ratio [OR] = 2.98) and regional lymph node metastasis (OR = 4.43) were independently associated with an increased risk of microscopic vascular invasion in tumors ≥5 cm (both p < 0.05). Risk of microscopic vascular invasion and worse tumor grade increased with tumor size. Large tumors likely harbor worse pathologic features; this information should be considered when determining therapy and prognosis of patients with large ICC.

A nomogram to predict long-term survival after resection for intrahepatic cholangiocarcinoma: an Eastern and Western experience.

IMPORTANCE: Intrahepatic cholangiocarcinoma (ICC) is a primary cancer of the liver that is increasing in incidence, and the prognostic factors associated with outcome after surgery remain poorly defined. OBJECTIVE: To combine clinicopathologic variables associated with overall survival after resection of ICC into a prediction nomogram. DESIGN, SETTING, AND PARTICIPANTS: We performed an international multicenter study of 514 patients who underwent resection for ICC at 13 major hepatobiliary centers in the United States, Europe, and Asia from May 1, 1990, through December 31, 2011. Multivariate Cox proportional hazards regression modeling with backward selection using the Akaike information criteria was used to select variables for construction of the nomogram. Discrimination and calibration were performed using Kaplan-Meier curves and calibration plots. INTERVENTIONS: Surgical resection of ICC at a participating hospital. MAIN OUTCOMES AND MEASURES: Long-term survival, effect of potential prognostic factors, and performance of proposed nomogram. RESULTS: Median patient age was 59.2 years, and 53.1% of the patients were male. Most patients (74.7%) had a solitary tumor, and median tumor size was 6.0 cm. Patients were treated with an extended hepatectomy (202 [39.3%]), a hemihepatectomy (180 [35.0%]), or a minor liver resection (<3 segments) (132 [25.7%]). Most patients underwent R0 resection (87.9%), and 35.7% of patients had N1 disease. Using the backward selection of clinically relevant variables, we found that age at diagnosis (hazard ratio [HR], 1.31; P < .001), tumor size (HR, 1.50; P < .001), multiple tumors (HR, 1.58; P < .001), cirrhosis (HR, 1.51; P = .08), lymph node metastasis (HR, 1.78; P = .01), and macrovascular invasion (HR, 2.10; P < .001) were selected as factors predictive of survival. On the basis of these factors, a nomogram was created to predict survival of ICC after resection. Discrimination using Kaplan-Meier curves, calibration curves, and bootstrap cross-validation revealed good predictive abilities (C index, 0.692). CONCLUSIONS AND RELEVANCE: On the basis of an Eastern and Western experience, a nomogram was developed to predict overall survival after resection for ICC. Validation revealed good discrimination and calibration, suggesting clinical utility to improve individualized predictions of survival for patients undergoing resection of ICC.