Chandrakanth Are

Effect of postoperative morbidity on long-term survival after hepatic resection for metastatic colorectal cancer.

Purpose:Resection is the most effective treatment for metastatic colorectal cancer (MCRC) to the liver. However, postoperative morbidity is common and its impact on long-term oncological outcome is unclear. The objective of this study was to evaluate the impact of postoperative morbidity on the long-term outcome after liver resection for MCRC. Methods:Medical records of patients who underwent liver resection for MCRC with curative intent between 1991 and 2002 were reviewed. Patients who died of postoperative complications were excluded; operative and perioperative data, including morbidity and clinicopathological variables, were analyzed. Patients were stratified by disease extent and risk of recurrence using a clinical risk scoring system. Results:A total of 1067 patients were included in the study and the median follow-up period was 41 months. The overall morbidity rate was 42%; the 5-year disease-specific survival (DSS) and overall disease-free survival (DFS) rates of patients who had complications were 41% and 25%, respectively, compared with 48% and 33%, respectively, for patients who did not have complications (P = 0.0059 for DSS, P = 0.0053 for DFS). On multivariate analysis, morbidity was not an independent predictor of either DSS or DFS; however, in a subgroup of patients with low clinical risk scores, morbidity was associated with a significant reduction in both DSS and DFS. Conclusions:Postoperative morbidity adversely affects long-term outcome after hepatic resection for MCRC in patients at lower risk for recurrence. Efforts aimed at reducing perioperative morbidity will not only reduce usage of resources but will likely further enhance the therapeutic benefit of resection for such patients.

Laparoscopic versus Open Liver Resection: A Matched-Pair Case Control Study

BackgroundLaparoscopic liver resection (LLR) has become an increasingly popular operation; however, its theoretical benefits remain unproven. The aim of this study was to conduct a comparative outcome study between LLR and matched-pair open liver resections (OLR).MethodsSixty five patients underwent attempted LLR from 1998 through 2008; 52 of which were completed laparoscopically. Patients who underwent OLR prior to 1998 were matched to laparoscopic cases for demographics, comorbidities, diagnosis, tumor characteristics, procedure, and background liver. Perioperative and oncologic outcomes were compared between the two groups. Analyses were performed excluding and including conversion cases.ResultsCharacteristics were comparable between both groups. LLR was associated with significant reductions in estimated blood loss, frequency of transfusion, frequency of Pringle maneuver, postoperative morbidity, time to recovery, length of hospital stay, and incidence of incisional hernia. For patients with malignant tumors, there were no positive surgical margins or local recurrence in either group and the overall pattern of recurrence was similar.ConclusionFor well-selected patients, LLR is a feasible operation that does not compromise operative or oncologic outcomes. While LLR was associated with some benefits, these can only be definitively proven in a randomized controlled trial.

Histological Aggressiveness of Fluorodeoxyglucose Positron-Emission Tomogram (FDG-PET)-Detected Incidental Thyroid Carcinomas

BackgroundWe previously reported a high incidence of primary thyroid cancer in fluorodeoxyglucose positron-emission tomogram (FDG-PET)-detected incidental thyroid abnormalities. The aim of our study was to determine if these FDG-PET-detected thyroid malignancies represent a more-aggressive variant of primary thyroid carcinoma.Materials and methodsAll patients that underwent operative intervention for FDG-PET-detected incidental thyroid abnormalities were identified (June 2003 to April 2006). Patients with a diagnosis of primary thyroid carcinoma on final histopathology were included in the study. The patient demographics and histopathological findings were analyzed to identify adverse prognostic features.ResultsIn 11,500 patients, 17,250 FDG-PET scans were performed; 377 of these patients (3.2% of patients and 2.1% of FDG-PET scans) had findings positive for thyroid abnormality. Of the 32 patients that underwent operative intervention, 22 patients with a final diagnosis of primary thyroid malignancy were included in the study. A greater number of patients [12 patients, (54%)] were noted to harbor poor prognostic variants of primary thyroid carcinoma on final histopathology [tall-cell variant: 11 patients (50%) and poorly differentiated thyroid carcinoma: 1 patient (4%)]. Extra-thyroidal extension (ETE) was noted in the majority of patients [14 patients (63%)]. In patients with tall cell variant on final histopathology, the rate of ETE was even higher [10 patients (90%)].ConclusionThyroid malignancies incidentally detected on FDG-PET scan harbor a high rate of unfavorable prognostic features and may represent a more-aggressive variant of primary thyroid carcinoma. These patients need to be subjected to further investigation with a view to possible operative intervention.

A review of global cancer burden: trends, challenges, strategies, and a role for surgeons.

Cancer is one of the leading causes of death worldwide. The global cancer burden (GCB) is expected to rise significantly and will disproportionately affect the less developed world (LDW). The aim of this review is to analyze the trends in GCB and describe the types, estimates, and causes of new cancer cases. The challenges and strategies associated with tackling this rising GCB are described in which surgeons can play a vital role. J. Surg. Oncol. 2013;107:221–226.

MicroRNA-192 suppresses liver metastasis of colon cancer

Metastasis causes most deaths from colon cancer yet mechanistic understanding and therapeutic options remain limited. Here we show that expression of microRNA (miR)-192 is inversely correlated with metastatic potential of colon cancer cells. Ectopic expression of miR-192 sensitizes colon cancer cells to growth factor deprivation stress-induced apoptosis, whereas inhibition of miR-192 confers resistance. Overexpression of miR-192 inhibits metastatic colonization to the liver in an orthotopic mouse model of colon cancer. Alterations associated with the metastatic phenotype in the primary tumors include increased apoptosis, decreased proliferation and angiogenesis. Further studies indicate that miR-192 downregulates expression of Bcl-2, Zeb2 and VEGFA in vitro and in vivo, which is responsible for enhanced apoptosis, increased expression of E-cadherin and decreased angiogenesis in vivo, respectively. Finally, studies performed on human colonic adenocarcinoma show that expression of miR-192 is significantly reduced in neoplastic cells as compared with normal colonic epithelium. Importantly, there is a significant decrease in miR-192 expression in stage IV tumors when compared with stage I or II lesions. These findings indicate that miR-192 has an important role in colon cancer development and progression. Our studies underscore the clinical relevance and prognostic significance of miR-192 expression in colon cancer. Therefore, a major implication of our studies is that restoration of miR-192 expression or antagonism of its target genes (Bcl-2, Zeb2 or VEGFA) may have considerable therapeutic potential for anti-metastatic therapy in patients with colon cancer.

Influence of margins on overall survival after hepatic resection for colorectal metastasis: A meta-analysis

Objective: The aim of our study was to conduct a meta-analysis of reports published on hepatic resection for colorectal liver metastasis (CRLM) and determine whether a negative margin of 1 cm or more confers a survival advantage over subcentimeter negative margins. Background: Surgical margin is an important prognostic factor in patients undergoing hepatic resection for CRLM. Although there is a consensus that positive margins portend a worse outcome than negative margins, the extent of negative margins remains controversial. Methods: A PubMed search was conducted to identify articles on hepatic resection for CRLM. The 357 initially located articles were screened to identify 90 articles of interest. The texts of these 90 articles were completely reviewed to finalize 18 articles for inclusion in the study on the basis of absolute and relative inclusion criteria. Patients with positive margins were excluded from the meta-analysis. Meta-analysis was performed using STATA 9.2 statistical software. Results: A total of 4821 patients with negative margins from the 18 studies were included in the meta-analysis. The overall 5-year survival for all patients was 41% [95% confidence interval (CI), 40%-43%]. The overall 5-year survival for the ≥1 cm negative margin subgroup was 46% (95% CI, 44%-48%) when compared with 38% (95% CI, 36%-40%) for less than 1 cm negative margin subgroup. The odds ratio for 1-cm or more negative margins was found to be 0.773 (95% CI, 0.638-0.938; P = 0.009) when compared with less than 1 cm negative margins. Conclusions: The results of this meta-analysis demonstrate that in patients undergoing hepatic resection for CRLM, a negative margin of 1 cm or more confers a survival advantage when compared with subcentimeter negative margins.

A review and update of treatment options and controversies in the management of hepatocellular carcinoma

Objective:To review the current management, outline recent advances and address controversies in the management of hepatocellular carcinoma (HCC). Summary of Background data:The treatment of HCC is multidisciplinary involving hepatologists, surgeons, medical oncologists, radiation oncologists, radiologists, interventional radiologists, and other disciplines. Each of these disciplines brings its unique perspective and differing opinions that add to controversies in the management of HCC. Methods:A focused literature review was performed to identify recent studies on the management of HCC and thereby summarize relevant information on the various therapeutic modalities and controversies involved in the treatment of HCC. Results:The main treatment algorithms continue to rely on hepatic resection or transplantation with controversies involving patients harboring early stage disease and borderline hepatic function. The other treatment strategies include locoregional therapies, radiation, and systemic therapy used alone or in combination with other treatment modalities. Recent advances in locoregional therapies, radiation, and systemic therapies have provided better therapeutic options with curative intent potential for some locoregional therapies. Further refinements in combination therapies such as algorithms consisting of locoregional therapies and systemic or radiation therapies are likely to add additional options and improve survival. Conclusions:The management of HCC has witnessed significant strides with advances in existing options and introduction of several new treatment modalities of various combinations. Further refinements in these treatment options combined with enrollment in clinical trials are essential to improve the management and outcomes of patients with HCC.

Preoperative Nomogram to Predict Risk of Perioperative Mortality Following Pancreatic Resections for Malignancy

IntroductionThe majority of pancreatic resections for malignancy are performed in older patients with major comorbidities. The aim of this study was to develop a preoperative nomogram based on the presence of comorbidities to predict risk of perioperative mortality.Materials and MethodsThe National Inpatient Sample database was queried to identify patients that underwent pancreatectomy for malignancy. The preoperative comorbidities identified as predictors were used, and a nomogram was created. Sample A (2000–2004) was utilized to develop the model, and sample B (2005) was utilized to validate this model.ResultsThe overall actual observed perioperative mortality rate for samples A and B was 6.3% and 5.2%, respectively. The mean total points calculated for sample A by the nomogram was 131.7 that translates to a nomogram-predicted mortality rate of 4.9%, which is similar to the actual mortality. The mean total points for sample B was 128.1, which translates to a nomogram-predicted mortality rate of 4.6%. The similarity of mortality rates as predicted by the nomogram and a concordance index of 0.76 shows good agreement between the data and the nomogram.ConclusionThis preoperative nomogram has been shown to accurately predict the risk of perioperative mortality following pancreatectomy for malignancy.

Factors Associated With General Surgery Residents’ Desire to Leave Residency Programs: A Multi-institutional Study

IMPORTANCE General surgical residency continues to experience attrition. To date, work hour amendments have not changed the annual rate of attrition. OBJECTIVE To determine how often categorical general surgery residents seriously consider leaving residency. DESIGN, SETTING, AND PARTICIPANTS At 13 residency programs, an anonymous survey of 371 categorical general surgery residents and 10-year attrition rates for each program. Responses from those who seriously considered leaving surgical residency were compared with those who did not. MAIN OUTCOMES AND MEASURES Factors associated with the desire to leave residency. RESULTS The survey response rate was 77.6%. Overall, 58.0% seriously considered leaving training. The most frequent reasons for wanting to leave were sleep deprivation on a specific rotation (50.0%), an undesirable future lifestyle (47.0%), and excessive work hours on a specific rotation (41.4%). Factors most often cited that kept residents from leaving were support from family or significant others (65.0%), support from other residents (63.5%), and perception of being better rested (58.9%). On univariate analysis, older age, female sex, postgraduate year, training in a university program, the presence of a faculty mentor, and lack of Alpha Omega Alpha status were associated with serious thoughts of leaving surgical residency. On multivariate analysis, only female sex was significantly associated with serious thoughts of leaving residency (odds ratio, 1.2; 95% CI, 1.1-1.3; P = .003). Eighty-six respondents were from historically high-attrition programs, and 202 respondents were from historically low-attrition programs (27.8% vs 8.4% 10-year attrition rate, P = .04). Residents from high-attrition programs were more likely to seriously consider leaving residency (odds ratio, 1.8; 95% CI, 1.0-3.0; P = .03). CONCLUSIONS AND RELEVANCE A majority of categorical general surgery residents seriously consider leaving residency. Female residents are more likely to consider leaving. Thoughts of leaving seem to be associated with work conditions on specific rotations rather than with overall work hours and are more prevalent among programs with historically high attrition rates.

Hepatobiliary cancers, version 1.2017 featured updates to the NCCN guidelines

The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panels discussion and most recent recommendations regarding locoregional therapy for treatment of patients with hepatocellular carcinoma.