The Negative Impact of Body Mass Index on the Tumor Microenvironment in Colon Cancer: Results of a Prospective Trial.

BACKGROUND: The association between tumor mismatch repair status and obesity in colon cancer is not well understood. The authors of this study hypothesized that mismatch repair deficiency in colon cancer may be associated with a lower Body Mass Index (BMI) and improved patient outcome due to an enhanced tumor immune microenvironment. METHODS: For this study, 70 patients were randomly selected from a prospective trial evaluating nodal ultrastaging for colon cancer. The mismatch repair status of tumors and immunomarker expression were correlated with clinicopathologic characteristics and evaluated for disease-free survival. RESULTS: Patients with mismatch repair-deficient tumors (n = 11) had a lower mean BMI than those with mismatch repair-proficient tumors (n = 59) (22.16 vs. 26.30 kg/m2, respectively; p = 0.029).The findings showed that CD3+ T cells were inversely associated with mismatch repair proficiency (p = 0.048). Mismatch repair-proficient tumors in nonobese patients (BMI < 30 kg/m2) versus obese patients had a higher density of CD8+ (p = 0.008) and FOXP3+ (p = 0.005) T cells. Multivariable analysis linked CD4+ (hazard ratio [HR] 0.52; 95% confidence interval [CI] 0.35-0.76), CD8+ (HR 0.67; 95% CI 0.50-0.89), and number of tumor-positive lymph nodes (HR 1.19; 95% CI 1.03-1.36) to disease-free survival for patients with mismatch repair-proficient tumors. CONCLUSIONS: Tumor mismatch repair status and obesity are correlated in patients with colon cancer. Increased intratumoral T cells in nonobese patients suggests an unexplored link between tumor mismatch repair and immunoprofile.

Prospective randomized controlled trial comparing standard analgesia with combined intra-operative cystic plate and port-site local anesthesia for post-operative pain management in elective laparoscopic cholecystectomy.

BACKGROUND: Various mechanisms, including somatic and visceral nociceptive stimulation, have been suggested as a cause for pain after laparoscopic cholecystectomy (LC). We therefore conducted a prospective randomized controlled trial (PRCT) to evaluate whether somatovisceral pain blockade reduces pain after LC. HYPOTHESIS: Analgesic efficacy of multimodal analgesia is superior to standard analgesia for patients undergoing elective LC for symptomatic cholelithiasis. Specifically, topical cystic plate and port-site injection with 0.25 % bupivacaine significantly reduces pain after LC. DESIGN: This study was designed as single-blinded PRCT. SETTING: This study was conducted in an academic medical center. PATIENTS AND METHODS: Between February and May 2010 we randomly assigned 63 patients with symptomatic cholelithiasis in a 1:1 ratio to non-opioid/opioid analgesic combinations (Control Group, n = 32) and non-opioid/opioid analgesic combinations plus topical 0.25 % bupivacaine onto the cystic plate and local 0.25 % bupivacaine port-site injection, post-LC (Study Group, n = 31). Primary endpoint was patient-reported pain 1, 4, 6, 12, 24 h and 1 week post-LC using the Visual Analog Scale (VAS 0-10). RESULTS: Study groups were comparable clinicopathologically. There were no adverse events. A statistically significant reduction in mean pain score was apparent in Study Group patients in comparison with Control Group (mean VAS 4.83 ± 2.33 vs. 6.80 ± 1.87; p < 0.001) at all early (1-6 h) post-operative time points following LC. CONCLUSION: This PRCT shows significantly improved pain control with somatovisceral pain blockade over non-opioid/opioid analgesic combinations following LC for symptomatic cholelithiasis. For centers not utilizing adjunctive local anesthetic for LC, this topical use of bupivacaine may improve patient comfort during recovery. This trial was registered on www.ClinicalTrials.gov NCT# 01972620.

Postoperative complications and overall survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

INTRODUCTION: Pancreaticoduodenectomy (PD) performed for pancreatic ductal adenocarcinoma (PDA) has a postoperative morbidity of 40-50%. In this study, we analyzed the impact of high grade complications after PD for PDA on overall survival. METHODS: A total of 596 patients that underwent PD for PDA between 2001 and 2009 were identified from a prospective database. Complications were defined and graded (1-5) as per our Institutional Surgical Secondary Events Program. High grade complications were defined as ≥grade 3. Postoperative mortality (≤90 days) was excluded. Univariate and multivariate analyses were performed to identify factors associated with overall survival. RESULTS: Median survival was 24 months. Overall complication rate was 51% (301/596). Low grade complications were recorded in 266 patients (45%) and high grade complications in 22% (n = 129). Our 90 day mortality was 3.7% (n = 22). Anastomotic fistula/leak/abscess rate was 14% (n = 82). Multivariate Cox-Regression analysis identified node positivity, estimated blood loss (EBL) >600 ml, length of stay (LOS) >10 days, margin positivity, and vascular procedures as predictors of decreased overall survival (P < 0.05). High grade complications were not associated with overall survival (P = 0.948). CONCLUSION: In this study, the occurrence of high grade postoperative complications was not associated with overall survival.

Value of primary tumor gene signatures in colon cancer when national quality standards are adhered to: preliminary results of an international prospective multicenter trial.

BACKGROUND: The purpose of this study was to determine if gene signatures are informative in colon cancer (CC) when National Quality Standards (NQS) are adhered to. Several studies have demonstrated the prognostic potential of gene signatures in primary CC. This has never been evaluated prospectively with adherence to NQS. METHODS: This was a prospective, international, multicenter trial. Eligibility criteria were: no distant metastasis, ≥12 lymph nodes (LNs), and no adjuvant chemotherapy for LN-negative CC. RNA from frozen tumor samples was considered reliable if RNA Integrity Number >9. Using an Agilent whole human genome array, 44,000 genes were analyzed in primary tumors for differential gene expression (DGE). ANOVA applied at 2-fold expression level was performed in at least 8 experiments to obtain the DGEs. RESULTS: Molecular analysis was completed in 113 of 128 patients. With median follow-up of 27 months, 11.5 % recurred within 3 years after surgery. Significant DGE was identified in recurrent tumors reflected by upregulation (UR) in cellular proliferation and by downregulation (DR) in prodifferentiating panel of 9 genes, independent of T or N classification. By multivariate analysis 3-year disease-free survival was 12.5 % in the UR/DR group versus 93.4 % in the non-UR/DR group (p < .0001; HR = 24.2; 95 % CI 4.8-120.4). CONCLUSIONS: This is the first prospective trial to evaluate gene signatures in CC with adherence to a 12-node minimum quality standard. Certain molecular pathways may be prognostically relevant if both surgery and pathology are standardized, regardless of T or N classification. Careful consideration should be made to include surgical quality measures when planning clinical trials to evaluate the true effect of molecular markers in CC.

Clinical decision support and individualized prediction of survival in colon cancer: bayesian belief network model.

BACKGROUND: We used a large population-based data set to create a clinical decision support system (CDSS) for real-time estimation of overall survival (OS) among colon cancer (CC) patients. Patients with CC diagnosed between 1969 and 2006 were identified from the Surveillance Epidemiology and End Results (SEER) registry. Low- and high-risk cohorts were defined. The tenfold cross-validation assessed predictive utility of the machine-learned Bayesian belief network (ml-BBN) model for clinical decision support (CDS). METHODS: A data set consisting of 146,248 records was analyzed using ml-BBN models to provide CDS in estimating OS based on prognostic factors at 12-, 24-, 36-, and 60-month post-treatment follow-up. RESULTS: Independent prognostic factors in the ml-BBN model included age, race; primary tumor histology, grade and location; Number of primaries, AJCC T stage, N stage, and M stage. The ml-BBN model accurately estimated OS with area under the receiver-operating-characteristic curve of 0.85, thereby improving significantly upon existing AJCC stage-specific OS estimates. Significant differences in OS were found between low- and high-risk cohorts (odds ratios for mortality: 17.1, 16.3, 13.9, and 8.8 for 12-, 24-, 36-, and 60-month cohorts, respectively). CONCLUSIONS: A CDSS was developed to provide individualized estimates of survival in CC. This ml-BBN model provides insights as to how disease-specific factors influence outcome. Time-dependent, individualized mortality risk assessments may inform treatment decisions and facilitate clinical trial design.

Intraoperative fluid management and complications following pancreatectomy.

BACKGROUND: Considerable debate exists as to appropriate perioperative fluid management. Data from several studies suggest that the amount of fluid administered perioperatively influences surgical outcome. Pancreatic resection is a major procedure in which complications are common. We examined 1,030 sequential patients who had undergone pancreatic resection at Memorial Sloan-Kettering Cancer Center. We documented the prevalence and nature of their complications, and then correlated complications to intraoperative fluid administration. METHODS: We retrospectively examined 1,030 pancreatic resections performed at Memorial Sloan-Kettering Cancer Center between May 2004 and December 2009 from our pancreatic database. Intraoperative administration of colloid and crystalloid was obtained from anesthesia records, and complication data from our institutional database. RESULTS: The overall in-hospital mortality was 1.7%. Operative mortality was due predominantly to intraabdominal infection. Sixty percent of the mortality resulted from intraabdominal complications related to the procedure. We did not demonstrate a clinically significant relationship between intraoperative fluid administration and complications, although minor statistical significance was suggested. CONCLUSIONS: In this retrospective review of intraoperative fluid administration we were not able to demonstrate a clinically significant association between postoperative complications and intraoperative crystalloid and colloid fluid administration. A randomized controlled trial has been initiated to address this question.

EORTC 1409 GITCG/ESSO 01 - A prospective colorectal liver metastasis database for borderline or initially unresectable diseases (CLIMB): Lessons learnt from real life. From paradigm to unmet need.

AIM: Multidisciplinary management of metastatic colorectal liver metastases (CRLM) is still challenging. To assess postoperative complications in initially unresectable or borderline resectable CRLM, the prospective EORTC-1409 ESSO 01-CLIMB trial capturing 'real-life data' of European centres specialized in liver surgery was initiated. MATERIAL AND METHODS: A total of 219 patients were registered between May 2015 and January 2019 from 15 centres in nine countries. Eligible patients had borderline or initially unresectable CRLM assessed by pre-operative multidisciplinary team discussion (MDT). Primary endpoints were postoperative complications, 30-day and 90-days mortality post-surgery, and quality indicators. We report the final results of the 151 eligible patients that underwent at least one liver surgery. RESULTS: Perioperative chemotherapy with or without targeted treatment were administered in 100 patients (69.4%). One stage resection (OSR) was performed in 119 patients (78.8%). Two stage resections (TSR, incl. Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy (ALPPS)) were completed in 24 out of 32 patients (75%). Postoperative complications were reported in 55.5% (95% CI: 46.1-64.6%), 64.0% (95% CI: 42.5-82%), and 100% (95% CI: 59-100%) of the patients in OSR, TSR and ALPPS, respectively. Post-hepatectomy liver failure occurred in 6.7%, 20.0%, and 28.6% in OSR, TSR, and ALPPS, respectively. In total, four patients (2.6%) died after surgery. CONCLUSION: Across nine countries, OSR was more often performed than TSR and tended to result in less postoperative complications. Despite many efforts to register patients across Europe, it is still challenging to set up a prospective CRLM database.

United States Military Cancer Institute Clinical Trials Group (USMCI GI-01) randomized controlled trial comparing targeted nodal assessment and ultrastaging with standard pathological evaluation for colon cancer.

OBJECTIVE: Our randomized controlled trial previously demonstrated improved staging accuracy with targeted nodal assessment and ultrastaging (TNA-us) in colon cancer (CC). Our objective was to test the hypothesis that TNA-us improves disease-free survival (DFS) in CC. METHODS: In this randomized trial, targeted nodal assessment and ultrastaging resulted in enhanced lymph node diagnostic yield associated with improved staging accuracy, which was further associated with improved disease-free survival in early colon cancer. RESULTS: Clinical parameters of the control (n = 94) and TNA-us (n = 98) groups were comparable. Median (interquartile range) lymph node yield was higher in the TNA-us arm: 16 (12-22) versus 13 (10-18); P = 0.002. Median follow-up was 46 (29-70) months. Overall 5-year DFS was 61% in the control arm and 71% in the TNA-us arm (P = 0.11). Clinical parameters of node-negative patients in the control (n = 51) and TNA-us (n = 55) groups were comparable. Lymph node yield was higher in the TNA-us arm: 15 (12-21) versus 13 (8-18); P = 0.03. Five-year DFS differed significantly between groups with node-negative CC (control 71% vs TNA-us 86%; P = 0.04). Survival among stage II CC alone was higher in the TNA-us group, 83% versus 65%; P = 0.03. Adjuvant chemotherapy use was nearly identical between groups. TNA-us stratified CC prognosis; DFS differed significantly between ultrastaged and conventionally staged node-negative patients [control pN0 72% vs TNA-us pN0(i-) 87%; P = 0.03]. Survival varied according to lymph node yield in patients with node-negative CC [5-year DFS: <12 lymph nodes = 57% vs 12+ lymph nodes = 85%; P = 0.011] but not in stage III CC. CONCLUSIONS: TNA-us is associated with improved nodal diagnostic yield and enhanced staging accuracy (stage migration), which is further associated with improved DFS in early CC. This study is registered at clinicaltrials.gov under the registration number: NCT01623258.

Time-dependent trends in lymph node yield and impact on adjuvant therapy decisions in colon cancer surgery: an international multi-institutional study.

BACKGROUND: Lymph node yield (LNY) and accuracy of nodal assessment are critical to staging and treatment planning in colon cancer (CC). A nationally agreed upon 12-node minimum is a quality standard in CC. The impact of this quality measure on LNY and impact on therapeutic decisions are evaluated in two international, multi-center, prospective trials comprising a well-characterized cohort assembled over 8 years (2001-2009) with long-term follow-up. HYPOTHESIS: Quality adherence through increased LNY improves staging accuracy and impacts adjuvant therapy decisions. METHODS: Retrospective analysis of prospective data to assess time-dependent LNY, the dependent variable in multivariate linear regression analysis adjusted for age, gender, body-mass-index (BMI), tumor size/stage/grade, anatomic location and surgery date. RESULTS: Two-hundred-forty-five patients with non-metastatic CC, median age 70 years, BMI 26 kg/m(2), tumor size 4.0 cm, and LNY 17 nodes were studied. Seventy-two percent had T3 (70 %)/T4 (2 %) tumors. Adherence to the 12-node minimum was 70 %(2001-2002), 81 % (2003-2004), 90 % (2005-2006), 94 % (2007-2008). LNY significantly increased over time (Median LNY: 2001-2004 = 15 vs. 2005-2008 = 17; P < 0.001) on multivariate analysis controlling for tumor size (P < 0.001), and right-sided tumor location (P < 0.001). Adjuvant therapy administration and indication for chemotherapy according to LNY (<12 vs. 12 + LNs = 33 % vs. 39 %; P = 0.48) and time period (2001-2004 vs. 2005-2008 = 39 % vs. 37 %; P = 0.89) remained unchanged. CONCLUSIONS: Despite the independent predictors of nodal yield (tumor location and size), year of study still had a significant impact on nodal yield. Despite increased quality adherence and LNY over time, there appears to be a delayed impact on adjuvant therapy decisions once quality standard adherence takes effect.

The Clinical Benefit of Percutaneous Transhepatic Biliary Drainage for Malignant Biliary Tract Obstruction.

Percutaneous transhepatic biliary drainage (PTBD) is a decompression procedure for malignant proximal biliary obstruction. In this research, over a six-year period, 89 patients underwent PTBD procedure for jaundice caused by malignant disease to restart chemotherapy or for palliative intent. Clinical outcomes after PTBD procedure in the two groups of patients, according to the adequate bilirubin decline (ABD) needed for subsequent chemotherapy, are presented in this paper. Survival and logistic regression were plotted and compared using Kaplan−Meier survival multivariate analysis with a long-range test. Results were processed by MEDCALC software. In the series, 58.4% (52/89) of patients were in good performance status (ECOG 0/1), and PTBD was performed with the intention to (re)start chemotherapy. The normalization of the bilirubin level was seen in 23.0% (12/52), but only 15.4% (8/52) received chemotherapy. The median survival time after PTBD was 9 weeks. In patients with ABD that received chemotherapy, the median survival time was 64 weeks, with 30-day mortality of 27.7%, and 6.4% of death within 7 days. The best outcome was in patients with good performance status (ECOG 0−1), low bilirubin (<120 µmol/L) and LDH (<300 µmol/L) levels and elevated leukocytes at the time of the procedures. PTBD is considered in ABD patients who are candidates for chemotherapy.

Prospective Non-Randomized Study of Intraoperative Assessment of Surgical Resection Margin of Colo-Rectal Liver Metastases.

Introduction: More than 50% of patients with colorectal cancer (CRC) develop liver metastases during the natural course of disease. Surgical resection is currently the most potentially curative method in the treatment of colorectal liver metastases (CRLM). The goal of surgery is to achieve a negative resection margin (RM) of at least 1 mm, which provides the best prognosis for patients. The RM can be assessed by the pathologist of the resected liver specimen (RLS) and by the surgeon intraoperatively. The aim of this research paper is to determine the degree of agreement on intraoperative assessment of the RM by the surgeon and histopathological RM assessment by the pathologist. Material and methods: This prospective non-randomized double-blind study was approved by the Ethics Committee of the Oncology Institute of Vojvodina and registered on ClinicalTrials.gov #NCT04634526. The study was conducted at the Oncology Institute of Vojvodina, Sremska Kamenica, Serbia. An experienced hepatobiliary surgeon assessed RM for every specimen intra-operatively, immediately after CRLM resection. Resected CRLM lesions were analyzed by two experienced pathologists. These data were compared with pathological RM assessment as a "gold standard". RM of 1 mm or more was rated as negative RM (RM-). Disease-free survival (DFS) and recurrence rate was calculated by RM status defined by surgeon and by pathologist. Results: From 01 January 2015 to 31 August 2019, 98 patients were enrolled in the study. There were 219 RLS with 245 CRLM. The surgeon registered positive RM (RM+) of <1mm in 41 (18.7%) RLS. Taking the result of the histopathological assessment (HPA) as the "gold standard", it was determined that RM was true positive in 32 (14.6%) cases. False positive RM was found in 9 (4.1%) cases. False negative RM was found in 20 (9.1%) cases. True negative RM was found in 158 (72.2%) cases. Sensitivity of surgical assessment (SA) of RM+ was 61.5% (32/52). Specificity of SA of RM+ was 94.6% (158/167). The positive predictive value (PPV) was 78.0% (32/41), while the negative predictive value (NPV) was 88.8% (158/178). The overall accuracy of the RM+ SA was 86.8% (190/219). There was no statistically significant difference in the assessment of RM+ per RLS by surgeon and pathologists (p=0.061), but it was significant when analyses per patients was performed (p=0.017). Recurrence rate for RM+ patients was 48.1% (13/27, p=0.05) for SA and 35.0% (14/40, p=0.17) for HPA. Three year DFS for RM- and RM+ was 66.5% and 27.9% (p=0.04), respectively, by SA, and 64.8% and 42.1% (p=0.106), respectively, by HPA. Conclusion: Intraoperative assessment of RM- by surgeon of RLS is clinically meaningful. There is not a statistically significant difference in the assessment of RM+ by surgeon and pathologists per RLS, but it was statically significant on a per patient basis. RM determined by surgeon has better prognostic impact on recurrence rate and 1- and 3-year DFS than standard histopathological assessment.

Predictive model of outcome of targeted nodal assessment in colorectal cancer.

BACKGROUND: Improvement in staging accuracy is the principal aim of targeted nodal assessment in colorectal carcinoma. Technical factors independently predictive of false negative (FN) sentinel lymph node (SLN) mapping should be identified to facilitate operative decision making. PURPOSE: To define independent predictors of FN SLN mapping and to develop a predictive model that could support surgical decisions. PATIENTS AND METHODS: Data was analyzed from 2 completed prospective clinical trials involving 278 patients with colorectal carcinoma undergoing SLN mapping. Clinical outcome of interest was FN SLN(s), defined as one(s) with no apparent tumor cells in the presence of non-SLN metastases. To assess the independent predictive effect of a covariate for a nominal response (FN SLN), a logistic regression model was constructed and parameters estimated using maximum likelihood. A probabilistic Bayesian model was also trained and cross validated using 10-fold train-and-test sets to predict FN SLN mapping. Area under the curve (AUC) from receiver operating characteristics curves of these predictions was calculated to determine the predictive value of the model. RESULTS: Number of SLNs (<3; P = 0.03) and tumor-replaced nodes (P < 0.01) independently predicted FN SLN. Cross validation of the model created with Bayesian Network Analysis effectively predicted FN SLN (area under the curve = 0.84-0.86). The positive and negative predictive values of the model are 83% and 97%, respectively. CONCLUSION: This study supports a minimum threshold of 3 nodes for targeted nodal assessment in colorectal cancer, and establishes sufficient basis to conclude that SLN mapping and biopsy cannot be justified in the presence of clinically apparent tumor-replaced nodes.

Surgical quality and nodal ultrastaging is associated with long-term disease-free survival in early colorectal cancer: an analysis of 2 international multicenter prospective trials.

BACKGROUND: The National Quality Forum has endorsed a minimum of 12 lymph node (LN) as a surrogate measure of quality in colorectal cancer (CRC). The prognostic value of ultrastaging hematoxylin and eosin (H&E) negative LNs (N0) using pan-cytokeratin immunohistochemistry (pan-CK-IHC) is unknown. PURPOSE: To assess the effect on survival of surgical quality and focused pathologic analysis. PATIENTS AND METHODS: Between 2001 and 2007, 253 evaluable patients with resectable CRC were enrolled. Multiple sectioning and pan-CK-IHC were performed on N0 LNs (American Joint Commission on Cancer Stage II). Follow-up was performed at 6-month intervals with a 4-year disease-free survival (DFS) primary end-point. RESULTS: There were 253 patients, 177 N0 and 76 N1/N2 patients, staged conventionally. Thirty-six (20%) N0 patients were upstaged using ultrastaging (N0-->N0i+ [n = 27] and N0-->N1mi [n = 9]). At a mean follow-up of 3.4 +/- 1.6 years, 38 (15%) have recurred. Only 3% (3/108) of patients with > or =12 LNs, negative by H&E and pan-CK-IHC (N0i-), compared with 18% (6/33) with <12 LNs/N0i- (6/33; P = 0.0015) have recurred. Four-year DFS differed significantly according to surgical quality (<12 vs. > or =12 LNs) among Stage II patients only (DFS, <12 vs. > or =12 LNs: Stage I, 90.5% vs. 97.7%, P = 0.22; Stage II, 67.5% vs. 94.7%, P = 0.0036; Stage III, 61% vs. 61%, P = 0.61). CONCLUSION: This represents the first prospective report demonstrating that both surgical quality and nodal ultrastaging impacts survival in Stage II CRC. Patients with Stage II CRC having > or =12 LNs negative for micrometastases (N0i-) are likely cured by surgery alone. Both surgical and pathologic quality measures are imperative in early CRC to improve patient selection for adjuvant chemotherapy.

Building a collaboration to improve surgical research through EORTC/ESSO 1409-CLIMB study: A prospective liver metastasis database with an integrated quality assurance program.

The challenges of conducting surgical oncology trials have resulted to low quantity and poor quality research [1,2]. Considering the definitive role of surgery to offer cure, immediate response to improve surgical research is needed [3]. The European Organization for Research and Treatment of Cancer (EORTC) and the European Society of Surgical Oncology (ESSO) share the vision to achieve excellent surgical research and care for cancer patients. Building on their complimentary expertise, they embarked on a pilot project to map out challenges and initiate a sustainable collaboration to advance cancer surgery research in Europe. This pilot project is EORTC-ESSO 1409 GITCG/ ESSO-01: A Prospective Colorectal Liver Metastasis Database with an Integrated Quality Assurance Program (CLIMB). This article will describe the challenges, milestones and vision of both organizations in setting up this collaboration.

Preoperative predictors for complications after pancreaticoduodenectomy: impact of BMI and body fat distribution.

BACKGROUND: The purpose of this study was to examine the preoperative patient and radiographic factors that are associated with operative morbidity after pancreaticoduodenectomy. MATERIAL AND METHODS: Patient characteristics and preoperative radiographic findings and their association with postoperative complications after pancreaticoduodenectomy were analyzed for 356 patients with pancreatic adenocarcinoma who underwent resection between 2000 and 2005. RESULTS: Postoperative complications developed in 135 patients (38%). The most common complications were pancreatic fistula/abscess (15%), wound infection (14%), and delayed gastric emptying (4%). On multivariate analysis, the only preoperative radiographic factors associated with having any postoperative complication were the absence of pancreatic atrophy and the extent of central obesity determined by the thickness of retrorenal visceral fat (VF). Complications occurred in 51% of patients with VF > or = 2 cm, compared to 31% of patients with VF < 2 cm, p < 0.001. Postoperatively, pancreatic fistula developed in 24% of patients with VF > or = 2 cm and in only 10% of patients with VF < 2 cm, p = 0.01. Wound infections occurred in 21% of the patients with body mass index greater than or equal to 30 kg/m(2) compared to 12% of the nonobese patients, p = 0.03. CONCLUSIONS: Generalized obesity is associated with postoperative wound infections after pancreaticoduodenectomy. The degree of visceral fat on preoperative cross-sectional imaging is associated with significantly higher rates of overall complications and pancreatic fistula.

Both the intratumoral immune and microbial microenvironment are linked to recurrence in human colon cancer: results from a prospective, multicenter nodal ultrastaging trial.

Colon cancer (CC) is the third most common cancer diagnosed in the United States and the incidence has been rising among young adults. We and others have shown a relationship between the immune infiltrate and prognosis, with improved disease-free survival (DFS) being associated with a higher expression of CD8+ T cells. We hypothesized that a microbial signature might be associated with intratumoral immune cells as well as DFS. We found that the relative abundance of one Operational Taxonomic Unit (OTU), OTU_104, was significantly associated with recurrence even after applying false discovery correction (HR 1.21, CI 1.08 to 1.36). The final multivariable model showed that DFS was influenced by three parameters: N-stage, CD8+ labeling, as well as this OTU_104 belonging to the order Clostridiales. Not only were CD8+ labeling and OTU_104 significant contributors in the final DFS model, but they were also inversely correlated to each other (p=0.022). Interestingly, CD8+ was also significantly associated with the microbiota composition in the tumor: CD8+ T cells was inversely correlated with alpha diversity (p=0.027) and significantly associated with the beta diversity. This study is the first to demonstrate an association among the intratumoral microbiome, CD8+ T cells, and recurrence in CC. An increased relative abundance of a specific OTU_104 was inversely associated with CD8+ T cells and directly associated with CC recurrence. The link between this microbe, CD8+ T cells, and DFS has not been previously shown.

Sex-Specific Differences in Colon Cancer when Quality Measures Are Adhered to: Results from International, Prospective, Multicenter Clinical Trials.

BACKGROUND: There is no consensus on the relationship between patient sex and the location, stage, and oncologic outcome of colon cancer (CC). We hypothesized that there is a sex-specific difference in the biology and management of CC. STUDY DESIGN: Our cohort was drawn from a database of patients enrolled in international trials of nodal ultrastaging for nonmetastatic CC. These trials required strict adherence to surgical and pathologic quality measures. Postoperative follow-up included colonoscopy at 1 and 4 years and annual CT scans. Sex-specific differences in tumor biology, location, stage, and recurrence were evaluated by chi-square, Fischer's exact, and independent t-tests. RESULTS: The cohort included 435 males (median age 69 years) and 423 females (median age 70 years). Females had more right-sided (p = 0.03) and earlier T stage (p = 0.05) tumors, but there was no sex-based difference in pathologic grade, total lymph nodes retrieved, nodal positivity (p = 0.47) or lymphovascular invasion (p = 0.45). The overall 4-year disease-free survival (DFS) was comparable in females and males (77.9% and 77.5%, respectively). By multivariate analysis, only nodal positivity and cancer recurrence affected overall survival (OS) (p = 0.008). Neither sex nor primary tumor affected DFS or OS. CONCLUSIONS: This is the first prospective study to demonstrate sex-specific differences in location and T stage of CC when surgical and pathologic management adhered to strict quality standards. The predominance of right-sided CC in females suggests that flexible sigmoidoscopy may be inadequate for screening and surveillance. Interestingly, earlier stage and right-sided location did not confer a DFS or OS advantage for women. Additional studies are needed to determine why females have a higher propensity for right-sided lesions and a potential difference in CC biology.

Prognostic Effect of Ultra-Staging Node-Negative Colon Cancer Without Adjuvant Chemotherapy: A Prospective National Cancer Institute-Sponsored Clinical Trial.

BACKGROUND: We recently reported, in a prospective randomized trial, that ultra-staging of patients with colon cancer is associated with significantly improved disease-free survival (DFS) compared with conventional staging. That trial did not control for lymph node (LN) number or adjuvant chemotherapy use. STUDY DESIGN: The current international prospective multicenter cooperative group trial (ClinicalTrials.gov identifier NCT00949312; "Ultra-staging in Early Colon Cancer") evaluates the 12-LN quality measure and nodal ultra-staging impact on DFS in patients not receiving adjuvant chemotherapy. Eligibility criteria included biopsy-proven colon adenocarcinoma; absence of metastatic disease; >12 LNs staged pathologically; pan-cytokeratin immunohistochemistry (IHC) of hematoxylin and eosin (H&E)-negative LNs; and no adjuvant chemotherapy. RESULTS: Of 445 patients screened, 203 patients were eligible. The majority of patients had intermediate grade (57.7%) and T3 tumors (64.9%). At a mean follow-up of 36.8 ± 22.1 months (range 0 to 97 months), 94.3% remain disease free. Recurrence was least likely in patients with ≥12 LNs, H&E-negative LNs, and IHC-negative LNs (pN0i-): 2.6% vs 16.7% in the pN0i+ group (p < 0.0001). CONCLUSIONS: This is the first prospective report to demonstrate that patients with optimally staged node-negative colon cancer (≥12 LNs, pN0i-) are unlikely to benefit from adjuvant chemotherapy; 97% remain disease free after primary tumor resection. Both surgical and pathologic quality measures are imperative in planning clinical trials in nonmetastatic colon cancer.

Dysfunctional ectopic thyroid gland: a case report.

INTRODUCTION: Lingual thyroid gland is a rare anomaly of thyroid gland development, occurring more frequently in females. If it causes local symptomatology such as dysphagia, dysphonia or dyspnea it is diagnosed in childhood, however, if it is asymptomatic it is usually diagnosed in adulthood. CASE OUTLINE: We present a 23-year-old female patient in whom we diagnosed lingual thyroid gland coincidentally during diagnostic procedures of a concomitant disease. The application of 131I scintigraphy showed an oval field of intensive accumulation of radio markers in the zone of medial face line, around tongue base, with the absence of thyroid gland in its physiological position. Functional testing proved primary hypothyroidism and we started the application of substitution therapy. The application of levothyroxine resulted in reaching euthyroid state and the reduction of thyroid gland size. CONCLUSION: We present a very rare anomaly of the thyroid gland, and so far there have been no clear attitudes about further treatment. The general condition of the patient, age, the size of ectopic thyroid gland and the existence of local symptomatology or complications represent the factors that have influence on the choice of treatment method.