DCLK1, a Putative Stem Cell Marker in Human Cholangiocarcinoma.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is a very aggressive cancer showing the presence of high cancer stem cells (CSCs). Doublecortin-like kinase1 (DCLK1) has been demonstrated as a CSC marker in different gastroenterological solid tumors. Our aim was to evaluate in vitro the expression and the biological function of DCLK1 in intrahepatic CCA (iCCA) and perihilar CCA (pCCA). APPROACH AND RESULTS: Specimens surgically resected of human CCA were enzymatically digested, submitted to immunosorting for specific CSC markers (LGR5 [leucine-rich repeat-containing G protein-coupled receptor], CD [clusters of differentiation] 90, EpCAM [epithelial cell adhesion molecule], CD133, and CD13), and primary cell cultures were prepared. DCLK1 expression was analyzed in CCA cell cultures by real-time quantitative PCR, western blot, and immunofluorescence. Functional studies have been performed by evaluating the effects of selective DCLK1 inhibitor (LRRK2-IN-1) on cell proliferation (MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay, cell population doubling time), apoptosis, and colony formation capacity. DCLK1 was investigated in situ by immunohistochemistry and real-time quantitative PCR. DCLK1 serum concentration was analyzed by enzyme-linked immunosorbent assay. We describe DCLK1 in CCA with an increased gene and protein DCLK1 expression in pCCALGR5+ and in iCCACD133+ cells compared with unsorted cells. LRRK2-IN-1 showed an anti-proliferative effect in a dose-dependent manner. LRRK2-IN-1 markedly impaired cell proliferation, induced apoptosis, and decreased colony formation capacity and colony size in both iCCA and pCCA compared with the untreated cells. In situ analysis confirmed that DCLK1 is present only in tumors, and not in healthy tissue. Interestingly, DCLK1 was detected in the human serum samples of patients with iCCA (high), pCCA (high), HCC (low), and cirrhosis (low), but it was almost undetectable in healthy controls. CONCLUSIONS: DCLK1 characterizes a specific CSC subpopulation of iCCACD133+ and pCCALGR5+ , and its inhibition exerts anti-neoplastic effects in primary CCA cell cultures. Human DCLK1 serum might represent a serum biomarker for the early CCA diagnosis.

Secondary Laparoscopic Cytoreduction in Recurrent Ovarian Cancer: A Large, Single-Institution Experience.

STUDY OBJECTIVE: To analyze the feasibility and safety of laparoscopic secondary cytoreductive surgery in a retrospective series of patients with platinum-sensitive recurrent ovarian cancer. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Catholic University of the Sacred Heart, Rome, Italy. PATIENTS: Between October 2010 and October 2016, 58 patients with recurrent ovarian cancer were selected for a retrospective analysis of data. INTERVENTIONS: All patients underwent a laparoscopic secondary cytoreduction with single or multiple procedures. RESULTS: The most frequent pattern of recurrence was peritoneal (48.3%); 6 patients (10.3%) experienced parenchymal disease (spleen, n = 5; liver, n = 1), and 24 patients (41.4%) had lymph node recurrence. Complete debulking was achieved in all patients. The median operative time was 204 minutes (range, 55-448 minutes), median estimated blood loss was 70 mL (range, 20-300 mL), and the median length of hospital stay was 4 days (range, 1-21 days). Four patients (6.8%) experienced intraoperative complications. Early postoperative complications were documented in 6 patients (10.3%), but only 1 G3 complication was noted. The median duration of follow-up since secondary cytoreduction was 24 months (range, 9-71 months). Twenty-one patients (36.2%) experienced a second disease relapse. The median progression-free survival (PFS) was 28 months, and the 2-year PFS was 58.7%. Five patients died (8.6%); the 2-year overall survival was 90.7%. CONCLUSIONS: For selected patients, laparoscopy is a feasible and safe approach to optimal cytoreduction for patients with recurrent ovarian cancer.

Hepatoceliac Lymph Node Involvement in Advanced Ovarian Cancer Patients: Prognostic Role and Clinical Considerations.

BACKGROUND: The study aimed too investigate the rate of hepatoceliac lymph node (HCLN) involvement, as well as its association with clinicopathologic features, together with morbidity of HCLN resection and the prognostic impact of metastatic HCLN status on patients with advanced ovarian cancer (OC) undergoing cytoreductive surgery. METHODS: All consecutive patients with stages 3c to 4 epithelial OC who underwent HCLN surgery from January 2010 to September 2016 were analyzed for surgical procedures, pathology, and oncologic outcomes. RESULTS: During the study period, 85 patients underwent HCLN resection. Absence of visible tumor at the end of surgery was documented for 73 of the patients (85.9%). The median number of HCLNs removed was 6 (range 1-18). Histopathologic evaluation was able to identify HCLN metastasis in 45 (52.9%) of the 85 cases. No difference in the rate of surgical morbidity according to pathologic status of HCLN was observed. As of December 2016, the median follow-up period was 36 months (range 6-54 months). Recurrence of disease was observed in 35 (41.2%) of the 85 cases. Relapse of disease most frequently occurred for the patients with metastatic HCLN involvement (65.7%) compared with the patients who had no HCLN involvement (34.3%) (p = 0.048). The median progression-free survival values were 16 months (95% confidence interval [CI], 12-19 months) for the patients with metastatic HCLNs and 22 months (95% CI, 12-19 months) for the patients with no HCLN involvement (p = 0.035). CONCLUSIONS: The study confirmed that HCLN surgery is feasible with acceptable morbidities for patients with advanced OC. Metastatic HCLNs are a marker of disease severity associated with worst oncologic outcome.

Evaluation of the economic impact of the robotic approach in major and postero-superior segment liver resections: a multicenter retrospective analysis.

Background: Economic impact of robotic liver surgery (RLS) is still a debated issue due to the heterogeneity of liver resections considered and the lack of a rigorous methodology. Therefore, the aim of this study is to perform a time-driven activity-based costing (TD-ABC) comparing the costs of RLS, laparoscopic liver surgery (LLS) and open liver surgery (OLS) in the context of complex liver resections and to compare short term perioperative outcomes. Methods: The institutional databases of two Italian high volume hepatobiliary centres were retrospectively reviewed from February 2021 to April 2022. Patients submitted to major hepatectomies or postero-superior liver resections were selected and divided into three groups according to the approach scheduled (RLS, LLS and OLS) and compared. Major contributors of perioperative expenses were calculated using the TD-ABC model and accurately quantifying each unit resource consumed per patient and the time spent performing each activity. A primary intention-to-treat analysis (ITT-A) including conversions in the RLS and LLS groups was performed. Results: Forty-seven RLS, 101 LLS and 124 OLS were collected. LLS and RLS showed reduced blood loss, morbidity, mortality and hospital stay compared with open. A trend towards reduced conversion rate in RLS compared to LLS was registered. Total costs associated with RLS were estimated at €10,637 vs. €9,543 for LLS and vs. €13,960 for OLS. The higher intraoperative costs associated with RLS (+153.3% vs. OLS and +148.2% vs. LLS, P<0.001), primarily related to surgical equipment expenses, were slightly offset by the postoperative savings (-56.0% vs. OLS and -29.4% vs. LLS, P<0.001) resulting from significantly reduced hospital stays. Conclusions: RLS offers economic advantages over OLS, as initial higher costs are offset by better perioperative outcomes. The evolving robotic marketplace is expected to drive down RLS costs, promoting widespread adoption in minimally invasive procedures. Despite its higher costs than LLS, RLS's ability to enhance minimally invasive feasibility makes it a preferred choice for complex cases, reducing the need for conversions.

Pancreatico-Jejunostomy On Isolated Loop After Pancreatico-Duodenectomy: Is It Worthwhile?

BACKGROUND: Postoperative morbidity remains a significant problem after pancreatico-duodenectomy. The management of pancreatic stump continues to be a challenge, and many technical solutions have been developed over the years. In this study, we report the results obtained with the use of an isolated loop for pancreatico-jejunostomy in patients with soft pancreas and small pancreatic duct diameter. METHODS: Clinical data of patients submitted to pancreatico-duodenectomy in a period of sixteen years (2005-2020) were extracted from a prospective database. Patients with soft pancreas, main duct diameter < 2 mm and reconstruction by pancreatico-jejunostomy on single loop or isolated loop were selected. Primary end-point was the incidence of clinically relevant fistulas in the two groups of patients. Secondary endpoint was the length of postoperative hospital stay. A propensity score matching analysis was used for the statistics. RESULTS: Two hundred and twenty-one patients with the above characteristics were found in the database. One hundred and twelve of these received a single-loop reconstruction and 109 an isolated loop reconstruction. Incidence of clinically relevant fistulas was higher in the first group (41% vs 27%; p = 0.023). Postoperative hospital stay was significantly shorter in the second group (21 days vs 15; p < 0.001). These results were confirmed at the propensity score matching. CONCLUSION: In patients with soft pancreatic texture and small main duct diameter, pancreatico-jejunostomy on isolated loop is associated with a lower incidence of clinically relevant fistulas than after classic reconstruction. The duration of postoperative hospital stay was significantly reduced, with consequent reduction of cost.

Survival by Number and Sites of Resections of Recurrence after First Curative Resection of Colorectal Liver Metastases.

BACKGROUND: Recurrence after curative hepatectomy for colorectal liver metastases (CRLM) is common. We sought to determine if number and sites of resections of recurrence after hepatectomy for CRLM impact survival. METHODS: The study included patients who underwent resection of recurrence following complete curative-intent resection of CRLM during 1998-2016 at two academic medical centers in Houston, USA, and Rome, Italy. The survival impacts of number and sites of resections of recurrence were evaluated. Patients with synchronous extrahepatic disease at curative CRLM resection were excluded. RESULTS: Among 2163 patients who underwent curative hepatectomy, 1456 (67.3%) developed a recurrence. Four hundred seventy-eight patients underwent one (322/478; 67.4%) or two or more (156/478; 32.6%) resections of recurrence. The 5-year overall survival (OS) rate was higher in patients with resected than unresected recurrence (70.2% vs. 24.0%; p < 0.001). In patients who underwent only one resection of recurrence, the 5-year OS rate differed by location (lung, 81.6%; liver, 64.3%; other, 54.1%). In patients who underwent two or more resections of recurrence, the 5-year OS rate was similar for liver-only resection (87.5%) and resection of liver and other sites (66.1%) (p = 0.223) and for liver-only resection and other-sites-only resection (80.7%) (p = 0.258); 5-year OS rate by site of first resection of recurrence did not differ between liver (78.5%) and lung (81.8%) (p = 0.502) but was worse for other sites (61.1%) than for lung (p = 0.045). CONCLUSION: When recurrence after initial CRLM resection is resectable, the ability to undergo resection was associated with improved survival and can be considered as an option regardless of the number of recurrence and resection. Sites of resection of recurrence impact survival and should be considered.

The Italian Consensus on minimally invasive simultaneous resections for synchronous liver metastasis and primary colorectal cancer: A Delphi methodology.

At the time of diagnosis synchronous colorectal cancer, liver metastases (SCRLM) account for 15-25% of patients. If primary tumour and synchronous liver metastases are resectable, good results may be achieved performing surgical treatment incorporated into the chemotherapy regimen. So far, the possibility of simultaneous minimally invasive (MI) surgery for SCRLM has not been extensively investigated. The Italian surgical community has captured the need and undertaken the effort to establish a National Consensus on this topic. Four main areas of interest have been analysed: patients' selection, procedures, techniques, and implementations. To establish consensus, an adapted Delphi method was used through as many reiterative rounds were needed. Systematic literature reviews were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses instructions. The Consensus took place between February 2019 and July 2020. Twenty-six Italian centres participated. Eighteen clinically relevant items were identified. After a total of three Delphi rounds, 30-tree recommendations reached expert consensus establishing the herein presented guidelines. The Italian Consensus on MI surgery for SCRLM indicates possible pathways to optimise the treatment for these patients as consensus papers express a trend that is likely to become shortly a standard procedure for clinical pictures still on debate. As matter of fact, no RCT or relevant case series on simultaneous treatment of SCRLM are available in the literature to suggest guidelines. It remains to be investigated whether the MI technique for the simultaneous treatment of SCRLM maintain the already documented benefit of the two separate surgeries.

[Primary intrahepatic lithiasis: indications and results of liver resection]. / La calcolosi intraepatica primaria: indicazioni e risultati del trattamento chirurgico resettivo.

The aim of this study was to review a series of patients submitted to hepatectomy for primary intrahepatic lithiasis to evaluate early and late results with an assessment of indications, methods and long-term outcomes. From January 1992 to December 2007, 40 patients (25 males and 15 females with a mean age of 51 years) underwent surgery for primary intrahepatic lithiasis in our Hepato-biliary Surgery Unit. Left hepatectomy (20 patients) and left lateral segmentectomy (12 patients) were the most common procedures performed. A cholangiocarcinoma was found in 4 patients (10%) and only two of these underwent liver resection, while an exploratory laparotomy was performed in the remaining two patients for an unresectable tumour, unexpected before surgery. There was no postoperative mortality. The morbidity rate was 22.5% with a prevalence of infectious complications related to bile leakage. Long-term results, assessed in 30 patients with a follow-up longer than 12 months, were good or fair in 28 patients (93.3%). Primary intrahepatic lithiasis is diagnosed increasingly in Western countries as a result of the improvement in imaging techniques. The stones originate inside the liver at the level of dilatations of the bile ducts above congenital strictures of the main hilar ducts. Biliary pain and cholangitis are the most common presenting symptoms, whereas cholangiocarcinoma represents the unfavourable complication of the disease. In the majority of cases, a single liver lobe or segment is involved and liver resection allows definitive treatment of the disease and prevention of cancer.

Prognostic factors value of germline and somatic brca in patients undergoing surgery for recurrent ovarian cancer with liver metastases.

OBJECTIVE: To describe accurately the oncological outcomes after hepatic resection (HR) in recurrent ovarian carcinoma (ROC) evaluating clinic-pathological variables and mutational status of BRCA1/2. Although HR is considered a challenging situation in ROC patients, assessment of BRCA1/2 mutational status seems to have a relevant clinical value to guide surgical therapy. METHODS: Patients who underwent HR for ROC at the Catholic University of Rome, between June 2012 and October 2017 were included. Exclusion criteria were represented by extra-abdominal disease and presence of diffuse peritoneal carcinomatosis requiring more than 2 bowel resections. Details relative to HR were collected and BRCA analysis was performed. Predictive factors of post-HR progression free survival (PHR-PFS) were assessed by univariate analyses using Cox-proportional hazard regression models. RESULTS: Thirty-four patients undewent HR within secondary cytoreductive surgery (SCS). Six patients (17.6%) presented with hepatic relapse only, while the remaining 28 patients (82.4%) had concomitant extra-hepatic disease. In the whole series, the 3-yr PHR-PFS was 49.1% and the 3-yr post-HR overall survival was 72.9%. Univariate analysis of variables conditioning PHR-PFS showed that only BRCA mutational status played a statistically significant favourable role: the 3-yr PHR-PFS rate was 81.0% in BRCA mutated patient compared to 15.2% in wild type ones (p value: 0.001). CONCLUSIONS: Our clinical analyses suggest that in ROC patients with liver disease the assessment of germline and somatic BRCA mutational status can help to select patients elegible for SCS.

The Mucocele of the Gallbladder.

The gallbladder polyps are a common finding during ultrasonography but only in rare cases they may be a cancer. When a polyp is greater than 1 cm, the cholecystectomy is usually performed. In these images, a polyp of 4 cm corresponding to a collection of mucus (mucocele) is reported. This unusual polyp of the gallbladder was caused by heterotopic intestinal mucosa.

Metabolic consequences of the occlusion of the main pancreatic duct with acrylic glue after pancreaticoduodenectomy.

BACKGROUND: Pancreaticoduodenectomy represents the major treatment for pancreatic and periampullary neoplasms. Complications related to pancreaticojejunostomy are still the leading cause of morbidity and mortality. A solution proposed by some surgeons is the occlusion of main pancreatic duct by acrylic glue, avoiding pancreaticojejunostomy. Nevertheless, the consequences of this procedure on glucose metabolism are not well-defined. METHODS: We retrospectively analyzed a cohort of 50 patients who underwent pancreaticoduodenectomy and had metabolic assessments available. The metabolic evaluation included the following: body composition and clinical evaluation, an oral glucose tolerance test, and an hyperinsulinemic euglycemic clamp procedure. RESULTS: Twenty-three patients underwent pancreatic duct occlusion and were compared with 27 patients, well-matched controls, who underwent pancreaticojejunostomy. Pancreatic duct occlusion leads to a greater impairment in insulin secretion compared with classic pancreaticojeunostomy. CONCLUSION: Pancreatic duct occlusion is associated with a greater reduction in insulin secretion but does not lead to meaningful differences in the management of patients with diabetes.

Sensitivity of Human Intrahepatic Cholangiocarcinoma Subtypes to Chemotherapeutics and Molecular Targeted Agents: A Study on Primary Cell Cultures.

We investigated the sensitivity of intrahepatic cholangiocarcinoma (IHCCA) subtypes to chemotherapeutics and molecular targeted agents. Primary cultures of mucin- and mixed-IHCCA were prepared from surgical specimens (N. 18 IHCCA patients) and evaluated for cell proliferation (MTS assay) and apoptosis (Caspase 3) after incubation (72 hours) with increasing concentrations of different drugs. In vivo, subcutaneous human tumor xenografts were evaluated. Primary cultures of mucin- and mixed-IHCCA were characterized by a different pattern of expression of cancer stem cell markers, and by a different drug sensitivity. Gemcitabine and the Gemcitabine-Cisplatin combination were more active in inhibiting cell proliferation in mixed-IHCCA while Cisplatin or Abraxane were more effective against mucin-IHCCA, where Abraxane also enhances apoptosis. 5-Fluoracil showed a slight inhibitory effect on cell proliferation that was more significant in mixed- than mucin-IHCCA primary cultures and, induced apoptosis only in mucin-IHCCA. Among Hg inhibitors, LY2940680 and Vismodegib showed slight effects on proliferation of both IHCCA subtypes. The tyrosine kinase inhibitors, Imatinib Mesylate and Sorafenib showed significant inhibitory effects on proliferation of both mucin- and mixed-IHCCA. The MEK 1/2 inhibitor, Selumetinib, inhibited proliferation of only mucin-IHCCA while the aminopeptidase-N inhibitor, Bestatin was more active against mixed-IHCCA. The c-erbB2 blocking antibody was more active against mixed-IHCCA while, the Wnt inhibitor, LGK974, similarly inhibited proliferation of mucin- and mixed-IHCCA. Either mucin- or mixed-IHCCA showed high sensitivity to nanomolar concentrations of the dual PI3-kinase/mTOR inhibitor, NVP-BEZ235. In vivo, in subcutaneous xenografts, either NVP-BEZ235 or Abraxane, blocked tumor growth. In conclusion, mucin- and mixed-IHCCA are characterized by a different drug sensitivity. Cisplatin, Abraxane and the MEK 1/2 inhibitor, Selumetinib were more active against mucin-IHCCA while, Gemcitabine, Gemcitabine-Cisplatin combination, the c-erbB2 blocking antibody and bestatin worked better against mixed-IHCCA. Remarkably, we identified a dual PI3-kinase/mTOR inhibitor that both in vitro and in vivo, exerts dramatic antiproliferative effects against both mucin- and mixed-IHCCA.

Investigating the synergistic interaction of diabetes, tobacco smoking, alcohol consumption, and hypercholesterolemia on the risk of pancreatic cancer: a case-control study in Italy.

The aims of the present research are to investigate the possible predictors of pancreatic cancer, in particular smoking status, alcohol consumption, hypercholesterolemia, and diabetes mellitus, in patients with histologically confirmed pancreatic carcinoma and to examine the synergism between risk factors. A case-control study (80 patients and 392 controls) was conducted at the Teaching Hospital "Agostino Gemelli" in Rome. A conditional logistic regression was used for the statistical analysis and results were presented as odds ratio (OR) and 95% confidence intervals (95% CI). We also investigated the possible interactions between risk factors and calculated the synergism index (SI). The multivariate analysis revealed that hypercholesterolemia and alcohol consumption resulted in important risk factors for pancreatic cancer even after the adjustment for all variables (OR: 5.05, 95% CI: 2.94-8.66; OR: 2.25, 95% CI: 1.30-3.89, resp.). Interestingly, important synergistic interactions between risk factors were found, especially between ever smoking status and alcohol consumptions (SI = 17.61) as well as alcohol consumption and diabetes (SI = 17.77). In conclusion, the study confirms that hypercholesterolemia and alcohol consumption represent significant and independent risk factors for pancreatic cancer. Moreover, there is evidence of synergistic interaction between diabetes and lifestyle factors (drinking alcohol and eating fatty foods).

Clinical characteristics and survival of European patients with resectable large hepatocellular carcinomas.

PURPOSE: Large hepatocellular carcinoma (HCC) presents on cirrhosis or in the absence of cirrhosis. Prognostic factors include both tumor and liver factors. Evaluate clinical and tumor characteristics of a group of large resected HCC in European patients. METHODS: Data for patients with HCC >7 cm who underwent liver resection between 1992 and 2011 were analyzed. Patients were dichotomized into those with tumor diameters of 7-10 cm or >10 cm and their characteristics and outcomes were compared. RESULTS: A total of 65 hepatectomies for HCC ≥7 cm were performed. Severe fibrosis or cirrhosis was present in 41.5 % of patients. Thirty-seven (56.9 %) patients had HCC ≥10 cm. Mortality and morbidity rates were 1.5 % and 37.5 %, respectively. Preoperative blood platelet levels and serum alkaline phosphatase (ALKP) levels showed significant differences between the groups. The 3-year survival was 43.5 % and 17.4 % for patients with tumors 7-10 and ≥10 cm, respectively. CONCLUSIONS: Patients with large size HCC and preserved liver function can be resected with low operative risk. ALKP levels and platelet counts were higher in the larger tumors. Given these patterns of clinical and biochemical characteristics, this group of tumors may be a selected subset of large HCCs and might potentially benefit from surgical resection.

Prognostic significance of tumor doubling time in mass-forming type cholangiocarcinoma.

OBJECTIVE: The aim of this study was to determine the prognostic significance of the preoperatively assessed tumor doubling time (DT) in patients undergoing liver resection for mass-forming intrahepatic cholangiocarcinoma (IHC). METHODS: We evaluated 79 patients who underwent curative resection for IHC, and in whom the same imaging technique was preoperatively available in two consecutive occasions, to allow the calculation of the DT. The influence of DT and other clinical and pathological variables on tumor recurrence and patient survival was determined by the Kaplan-Meier method and uni- and multivariate analysis. RESULTS: Median overall survival was 40 months; 1-, 3-, and 5-year survival rates were 86.1, 55.1, and 35.1 %, respectively. Median disease-free survival was 17 months; 1-, 3-, and 5-year disease-free survival rates were 62.0, 29.1, and 23.3 %, respectively. At univariate analysis, DT <70 days (p < 0.001) and advanced tumor stage (p = 0.024) were associated with worse overall survival and maintained significance at multivariate analysis. CONCLUSIONS: DT is a clinically useful parameter to estimate the prognosis of "mass-forming" IHC in patients undergoing liver resection.

Parenteral nutrition in liver resection.

Albeit a very large number of experiments have assessed the impact of various substrates on liver regeneration after partial hepatectomy, a limited number of clinical studies have evaluated artificial nutrition in liver resection patients. This is a peculiar topic because many patients do not need artificial nutrition, while several patients need it because of malnutrition and/or prolonged inability to feeding caused by complications. The optimal nutritional regimen to support liver regeneration, within other postoperative problems or complications, is not yet exactly defined. This short review addresses relevant aspects and potential developments in the issue of postoperative parenteral nutrition after liver resection.

Unexpected gallbladder cancer after laparoscopic cholecystectomy for acute cholecystitis: a worrisome picture.

OBJECTIVE: The objective of this study is to assess the prognosis of unexpected gallbladder cancer diagnosed after laparoscopic cholecystectomy for acute cholecystitis. METHODS: Data of all patients treated for unexpected gallbladder cancer after laparoscopic cholecystectomy at a tertiary care surgical center between January 1998 and December 2009 were reviewed. Demographics and clinical and pathological data of patients submitted to adjunctive revisional surgery were analyzed. Survival was calculated by the Kaplan-Meier method, and log-rank test was used to compare the survival curves. The Cox proportional hazard model was used to determine the effect on survival of urgent surgery for acute cholecystitis and of the other common factors such as age, gender, tumor grading, pT stage, nodal involvement, residual disease at re-exploration, and American Joint Committee on Cancer stage. RESULTS: In the considered period, 34 patients with pT1b, pT2, or pT3 unexpected gallbladder cancer underwent a second standard revisional procedure including resection of liver segments 4b and 5, lymphadenectomy, and port-sites excision. Thirteen patients had previously undergone urgent surgery for acute cholecystitis; 21 had undergone a routine operation. The 5-year overall survival was 63.3 %. At multivariate analysis, G3 tumor grading (hazard ratio, 12.261; p = 0.002), residual disease at re-exploration [hazard ratios (HR) = 7.760, p = 0.004], and urgent surgery for acute cholecystitis (HR = 5.436, p = 0.012) were independent predictors of poor prognosis. CONCLUSIONS: The prognosis of unexpected gallbladder cancer is worsened when laparoscopic cholecystectomy is performed for acute cholecystitits. The unfavorable impact of emergency surgery on prognosis might be related to intraoperative gallbladder emptying with bile spillage and cancer dissemination.

Intrahepatic cholangiocarcinoma: prognostic factors after liver resection.

Liver resection may represent the only hope of cure for patients with intrahepatic cholangiocarcinoma (IHC) but long-term results are still far from satisfactory and the impact of prognostic factors is still controversial. Fifty-five patients underwent hepatectomy for IHC between 1997 and 2008 in our unit. Features of the patients and the tumors, operations, postoperative and long-term results were retrospectively assessed. Twenty-one patients had HBV/HCV infection, four had congenital biliary dilatation. Thirty-two patients had increased CA 19-9; 12 had multiple (≥ 4) tumors. Operations included 43 major resections, with 9 resections of biliary confluence, 40 regional lymphadenectomies. Operative mortality and morbidity were 0 and 27.3%, respectively. There were 44 R0-resections (80.0%). Lymphadenectomy yielded lymph node metastases in 14 cases (14/40; 35.0%). Five-year overall and disease-free survival rates were 30.2 and 27.5%, respectively. At multivariate analysis the strongest poor prognostic factor for overall survival was tumor stage. This factor, with multiplicity of lesions (≥ 4) and tumor grading > 2, was significant predictor of recurrence. CA19-9 > 100 IU/mL and tumor grading > 2 were found to be significantly related with early multinodular hepatic recurrence. Patients with lymph node metastases had significantly lower overall and disease-free survival but patients who underwent lymph node dissection with negative lymph nodes at final pathology showed significantly higher 5-year disease-free survival than patients who did not underwent lymphadenectomy. In conclusion, these results support the role of hepatectomy with regional lymphadenectomy as the best available treatment for IHC. Prognosis after liver resection correlates with clinical stage and multiplicity of lesions.