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Background & Aims. Postoperative weight loss is common following hepato-pancreato-biliary (HPB) surgical resections; however, the extent of weight loss and the association with poor outcomes have not been well described. We assessed the average percentage of weight loss and risk factors associated with sustained postoperative weight loss. Materials and Methods. We enrolled patients undergoing major HPB surgical resections from 2011–2016 at a single institution. We evaluated percent change in weight postoperatively, incidence of complications, and nutritional clinical markers at 1, 3, and 6 months postoperatively compared to preoperative baseline. We used multiple logistic regression to evaluate factors associated with significant weight loss (>10% from baseline) at 3 months from surgery. Results. Among 262 patients undergoing HPB surgery, liver surgery patients lost 2.5% of baseline weight at 3 months postoperatively but regained baseline weight by 6 months. Pancreatic surgery patients lost 7.7% at 3 months and were unable to recover their baseline weights at 6 months. Forty-three (16%) patients had major postoperative complications including abdominal abscess (5.3%) and anastomotic leak (3.8%). Patients who experienced major postoperative complications had a greater percentage weight loss at 3 months compared to those without major complications: median 11% (interquartile range (IQR): 7%–15%) vs 4% (IQR: 0%–8%), P < .001. In the multivariable analysis, major postoperative complications were associated with significant weight loss at 3 months (OR 3.39, 95% CI 1.38–8.33). Conclusions. Due to the association of weight loss and major postoperative complications, patients who experience significant weight loss (>10% from baseline) may benefit from nutritional assessment for dietary intervention.

IntroductionDespite use of operative and non-operative interventions to reduce blood loss during liver resection, 20%–40% of patients receive a perioperative blood transfusion. Extensive intraoperative blood loss is a major risk factor for postoperative morbidity and mortality and receipt of blood transfusion is associated with serious risks including an association with long-term cancer recurrence and overall survival. In addition, blood products are scarce and associated with appreciable expense; decreasing blood transfusion requirements would therefore have health system benefits. Tranexamic acid (TXA), an antifibrinolytic, has been shown to reduce the probability of receiving a blood transfusion by one-third for patients undergoing cardiac or orthopaedic surgery. However, its applicability in liver resection has not been widely researched.Methods and analysisThis protocol describes a prospective, blinded, randomised controlled trial being conducted at 10 sites in Canada and 1 in the USA. 1230 eligible and consenting participants will be randomised to one of two parallel groups: experimental (2 g of intravenous TXA) or placebo (saline) administered intraoperatively. The primary endpoint is receipt of blood transfusion within 7 days of surgery. Secondary outcomes include blood loss, postoperative complications, quality of life and 5-year disease-free and overall survival.Ethics and disseminationThis trial has been approved by the research ethics boards at participating centres and Health Canada (parent control number 177992) and is currently enrolling participants. All participants will provide written informed consent. Results will be distributed widely through local and international meetings, presentation, publication and ClinicalTrials.gov.Trial registration numberNCT02261415.

Simultaneous compared to staged resection of synchronous colorectal cancer liver metastases is considered safe. We aimed to determine their cost implications.Population-based cohort was generated by linking administrative healthcare datasets in Ontario, Canada (2006-2014). Resection of colorectal cancer and liver metastases within six months was considered synchronous. Cost analysis was performed from the perspective of a third-party payer. Median costs with range were estimated using the log-normal distribution of cost using t-test with a one-year time horizon.Among patients undergoing staged resection (n = 678), the estimated median cost was $54,321 CAD (IQR 45,472 to 68,475) and $41,286 CAD (IQR 31,633 to 58,958) for those undergoing simultaneous resection (n = 390), median difference: $13,035 CAD (p 0.001). Primary cost driver were all costs related to hospitalization for liver and colon resection, which was higher for the staged approach, median difference: $16,346 CAD (p 0.001). This was mainly due to a longer median length of hospital stay in the staged vs. simultaneous group (11 vs. 8 days, p 0.001 respectively), which was not attributable to differences in major postoperative complication rates (23% vs. 28%, p = 0.067 respectively). Other costs, including cost of chemotherapy within six months of surgery ($11,681 CAD vs. $8644 CAD, p = 0.074 respectively) and 90-day re-hospitalization cost ($2155 CAD vs. $2931 CAD, p = 0.454 respectively) were similar between groups.Cost of staged resection of synchronous colorectal cancer liver metastases is significantly higher compared to the simultaneous approach, mostly driven by a longer length of hospital stay despite similar postoperative complication rates.

We examined surgeon practice intentions and barriers to performing simultaneous resections for colorectal cancer with synchronous liver metastases.We electronically surveyed North American surgeons who provide colorectal cancer care with a pilot-tested questionnaire. Four clinical scenarios of increasing complexity were presented. Perceived outcomes of and barriers to simultaneous resection were assessed on a 7-point Likert scale. We compared results between general and hepatobiliary surgeons.Responses (rate 20%, 234/1166) included 50 general and 134 hepatobiliary surgeons. High likelihood scores for support of simultaneous resection among general and hepatobiliary surgeons, respectively, included the following for: minor liver and low complexity colon, 83% and 98% (p 0.001); minor liver and rectal resection, 57% and 73% (p = 0.042); complex liver and low complexity colon resection, 26% and 24% (p = 0.858); and, complex liver and rectal resection, 11% and 7.0% (p = 0.436). Among hepatobiliary surgeons, the most common barriers to simultaneous resections were patient comorbidities and lung metastases, whereas certain general surgeons additionally identified transfer of care.Surgeon support for simultaneous resection was high for cases with minor hepatectomy, and low for cases involving major hepatectomy. These results suggest that clinical trials should involve patients with limited disease to evaluate post-operative complications and cost.

Synchronous liver metastases from colorectal cancer may be resected simultaneously with the primary or as a second staged operation. We evaluated trends of resection for synchronous colorectal cancer liver metastases and associated patient outcomes.This is a retrospective cohort study that included patients undergoing resection for synchronous colorectal cancer liver metastases from 2006 to 2015 in the province of Ontario, Canada (population 13 million). Simultaneous resections occurred on the same admission, while staged resections occurred less than 6 months apart. Outcomes included postoperative complications, length of hospital stay, and overall survival. Kaplan Meier survival estimates, Cox proportional hazard models and logistic regression were used.Among 2,738 patients undergoing resection for colorectal cancer liver metastases, 1168 (42%) had synchronous disease. Of these, 442 resections were simultaneous (38%) and 776 were staged (62%). The proportion of synchronous disease among patients undergoing resection increased on average 3% per year (p = 0.02). For simultaneous versus staged resection, respectively, median length of hospital stay was shorter (8 vs. 11 days, p 0.001); rate of major liver resections was lower (17% vs. 65%, p 0.001), major postoperative complications were similar (28% vs. 23%, p = 0.067), and 90-day post-operative mortality was higher (6% vs. 1%, p 0.001). Chemotherapy was administered more commonly among patients undergoing staged resections (91% vs. 76%, p 0.001). Simultaneous resection was associated with a lower median overall survival (40 months, 95%CI 35-46 vs. 78 months, 95%CI 59-86). Risk factors for lower survival included higher comorbidities, right-sided primary and simultaneous resection.Simultaneous resection was associated with similar postoperative complications, higher postoperative mortality and poorer long-term survival. Prospective randomized trials can inform the role of simultaneous versus staged resection for synchronous colorectal cancer liver metastases.

Background and objectives Despite quality evidence supporting postoperative extended venous thromboembolism prophylaxis (eVTEp) following abdominopelvic cancer surgery, baseline use of eVTEp at our institution was 3%. Our project aim was to improve the proportion of patients prescribed eVTEp following surgery for gynecologic, hepatobiliary, and colorectal cancers by a 30% absolute increase. Methods We performed an interrupted time series study using quality improvement methodology. Postoperative order sets, pre-printed prescriptions, process checklists, and multimodal education were introduced. Process and outcome data were collected and analyzed on statistical process control charts. Results We included 324 patients with gynecologic and hepatobiliary cancers. Despite efforts to include them, the colorectal team did not participate. The monthly mean order set-use was 58% (SD = 14%), by specialty: gynecology 79%, hepatobiliary 47%. The proportion of patients prescribed eVTEp increased from 3% to 70% (SD = 14%). The target goal was surpassed and sustained by both cohorts. Patient compliance was 73% (n = 117/160, SD = 16%). Of those who stopped eVTEp early, 45% (n = 14/31) objected because of the injectable nature. Bleeding events were infrequent (0.6%, n = 2/324). Conclusions Three process changes and multimodal education resulted in a significant increase in eVTEp use. Failure to identify improvement champions limited project expansion to colorectal patients. Patient compliance was largely limited by the injectable nature of the medication.

Staged resection is preferred to treat synchronous rectal cancer with liver metastases. Simultaneous resection of rectal cancer with synchronous liver metastases may potentially decrease postoperative complications, thereby improving quality of life, decreasing health care costs, and avoiding delays in postoperative chemotherapy administration. We evaluated the safety of simultaneous resection. We searched Medline, Embase, and PubMed for studies comparing simultaneous versus staged resection. Study selection, data abstraction, risk of bias (ROB), and quality of the evidence (QOE) assessment were performed in duplicate. The primary outcome was overall postoperative complications. The secondary outcome was postoperative complications in the intervention group. ROB and QOE were assessed using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). 4456 abstracts were retrieved; 18 retrospective cohort studies reported postoperative complications in the intervention arm, with six comparing intervention (288 patients) to control (287 patients). The odds ratio (OR) for overall complications was 0.93, 95% confidence interval (CI): 0.64–1.35, and for major complications was 0.77, 95%CI: 0.40–1.50. Proportion of complications (intervention arm): 41%, 95%CI: 33–50%. ROB was moderate. Simultaneous resection of synchronous rectal cancer with liver metastases carries a similar risk of overall and major complications compared to the staged approach. However, QOE is very low and a simultaneous approach ought to be pursued only in selected patients until better evidence is available.

Background Liver resection is commonly performed among patients at risk of being frail. Frailty can be used to assess perioperative risk. Thus, we evaluated frailty as a predictor of postoperative complications following liver resection using a validated modified frailty index (mFI). Methods A retrospective cohort of consecutive patients undergoing liver resection (2011-2018) were stratified according to the mFI and classified as the following: high (≥.27) and low mFI (Results Of 409 patients, 58 (14%) had high mFI. There were no differences in type of liver resection (laparoscopic: 57% vs 55%, P = .766), number of segments resected (3 vs 4, P = .417), or operative time (257 vs 293 minutes, P = .097) between the high and low mFI groups, respectively. High mFI patients had a longer median length of hospital stay (9.5 vs 5 days, P < .001) and higher proportion of postoperative complications (79% vs 46%, P < .001), including minor complications (69% vs 42%, P < .001), major complications (50% vs 13%, P < .001), and 90-day postoperative mortality (12% vs 3.4%, P = .04). On multivariable analysis, longer operating time (OR 1.15, 95% CI, 1.03 to 1.27), higher number of segments resected (OR 1.43, 95% CI, 1.12 to 1.82), and high mFI (OR 6.74, 95% CI, 2.76 to 16.51) were independent predictors of major postoperative complications. Discussion mFI predicts postoperative outcomes following liver resection and can be used as a risk stratification tool for patients being considered for surgery.

Background The detection of liver metastases is important for pancreatic cancer curative treatment eligibility. The data suggest that magnetic resonance imaging (MRI) is more sensitive than computed tomography (CT) for the diagnosis of pancreatic cancer liver metastases. However, MRI is not currently recommended in multiple published guidelines. Purpose To perform a comparative diagnostic test accuracy systematic review and meta-analysis comparing CT and MRI for pancreatic cancer liver metastases detection. Study type Systematic review and meta-analysis. Data sources MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and multiple radiology society meeting archives were searched until November 2018. Comparative design studies reporting on liver CT and MRI accuracy for detection of pancreatic cancer liver metastases in the same cohort were included. Field strength 1.5T or 3.0T. Assessment Demographic, methodologic, and diagnostic test accuracy data were extracted. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. Statistical tests Accuracy metrics were obtained using bivariate random-effects meta-analysis. The impact of different covariates on accuracy estimates was assessed using a meta-regression model. Covariates included modality, study design, tumor characteristics, risk of bias, and imaging protocols. Results Fourteen studies including 987 patients with pancreatic cancer (205 with liver metastases) were included. Sensitivity for CT and MRI was 45% (confidence intervals [95% CI] 21-71%) and 83% (95% CI 74-88%), respectively. Specificity for CT and MRI was 94% (95% CI 84-98%) and 96% (95% CI 93-97%), respectively. The greater observed sensitivity of MRI was preserved in the meta-regression model (P = 0.01), while no difference in specificity was detected (P = 0.16). CT sensitivity was highest for triphasic and quadriphasic examinations compared to single phase or biphasic protocols (P = 0.03). Most studies were at high risk of bias. Data conclusion MRI is more sensitive than CT for pancreatic cancer liver metastases detection, accounting for confounding variables. Consideration of this finding in clinical practice guidelines is recommended. Level of evidence 3 TECHNICAL EFFICACY STAGE: 3.

Highlights • Traditionally, synchronous colorectal cancer and CRLM are resected separately. • Many institutions have begun performing these procedures simultaneously. • Minimal data support simultaneous resection including major liver resection. • Complications will be investigated following simultaneous resection. • This protocol will be implemented in 5 high-volume tertiary care centres worldwide., Introduction The “traditional approach” to resect synchronous colorectal cancer with liver metastases (CRLM) is to perform staged resections. Many institutions perform simultaneous resection. Disadvantages to the simultaneous approach include longer operating room times, which may increase major postoperative complication rates. Data supporting simultaneous resection are limited to retrospective studies that are subject to selection bias. Therefore, we have proposed a single-arm prospective cohort pilot study to evaluate the postoperative complications following simultaneous resection of synchronous CRLM. Methods and analysis This single-arm study will be performed in five high-volume hepatobiliary centres to prospectively evaluate the following objectives: (1) To determine the 90-day postoperative complication rate of patients diagnosed with synchronous CRLM undergoing a simultaneous colorectal and liver resection, including major liver resections; (2) To determine the postoperative mortality rate at 90 days following index surgery; (3) To determine change in global health-related Quality of Life (QoL) following simultaneous resection at three months compared to baseline; and (4) To build a costing model for simultaneous resection, We will also evaluate the feasibility of performing combined resection in these patients by evaluating the number of eligible patients enrolled in the study and determining the reasons eligible patients were not enrolled. This protocol has been registered with ClinicalTrials.gov (NCT02954913). Ethics and dissemination This study has been provincially approved by the central research ethics board. Study results will inform the design a randomized controlled trial by providing information about the comprehensive complication index in this patient population used to calculate the sample size for the trial.

Surgical resection provides the best opportunity for cure for metastatic colorectal cancer. Whether addition of a biologic agent to chemotherapy improves the rate of conversion from unresectable to resectable disease remains uncertain. We carried out a systematic review of the literature and meta-analysis to define the impact of biologic agents on resection. We searched Medline, Embase, CENTRAL, and PubMed for randomized controlled trials published up until April 2017 comparing chemotherapy and biologics (intervention) vs. chemotherapy alone (control) in treatment-naive patients with unresectable metastatic colorectal cancer. Study selection, data abstraction, risk of bias, and quality of evidence assessment were performed in duplicate. Random-effects meta-analysis was used to estimate the pooled odds ratio (OR) for resection rate and corresponding confidence interval (CI). Nine studies, including a total of 4345 patients, were analyzed. Seven studies assessed epithelial growth factor receptor (EGFR)-directed monoclonal antibodies, and two used antiangiogenic agents. The addition of a biologic agent to chemotherapy was associated with higher resection rate (OR 1.47, 95% CI 1.07–2.02; resection rate 8.4 vs. 6.1%). Subgroup analysis based on mechanism of action of drugs showed benefit for resection rate only with EGFR-directed agents (OR 1.70, 95% CI 1.10–2.64). Heterogeneity among studies was low (I 2 = 34%). The addition of biologic agents to systemic chemotherapy in patients with initially unresectable metastatic colorectal cancer improved resection rate. The optimal biologic agent for this outcome cannot yet be determined.

To determine if CT texture analysis features are associated with hypovascular pancreas head adenocarcinoma (PHA) postoperative margin status, nodal status, grade, lymphovascular invasion (LVI), and perineural invasion (PNI). This Research Ethics Board–approved retrospective cohort study included 131 consecutive patients with resected PHA. Tumors were segmented on preoperative contrast-enhanced CT. Tumor diameter and texture analysis features including mean, minimum and maximum Hounsfield units, standard deviation, skewness, kurtosis, and entropy and gray-level co-occurrence matrix (GLCM) features correlation and dissimilarity were extracted. Two-sample t test and logistic regression were used to compare parameters for prediction of margin status, nodal status, grade, LVI, and PNI. Diagnostic accuracy was assessed using receiver operating characteristic curves and Youden method was used to establish cutpoints. Margin status was associated with GLCM correlation (p = 0.012) and dissimilarity (p = 0.003); nodal status was associated with standard deviation (p = 0.026) and entropy (p = 0.031); grade was associated with kurtosis (p = 0.031); LVI was associated with standard deviation (p = 0.047), entropy (p = 0.026), and GLCM correlation (p = 0.033) and dissimilarity (p = 0.011). No associations were found for PNI (p > 0.05). Logistic regression yielded an area under the curve of 0.70 for nodal disease, 0.70 for LVI, 0.68 for grade, and 0.65 for margin status. Optimal sensitivity/specificity was as follows: nodal disease 73%/72%, LVI 72%/65%, grade 55%/83%, and margin status 63%/66%. CT texture analysis features demonstrate fair diagnostic accuracy for assessment of hypovascular PHA nodal disease, LVI, grade, and postoperative margin status. Additional research is rapidly needed to identify these high-risk features with better accuracy. • CT texture analysis features are associated with pancreas head adenocarcinoma postoperative margin status which may help inform treatment decisions as a negative resection margin is required for cure. • CT texture analysis features are associated with pancreas head adenocarcinoma nodal disease, a poor prognostic feature. • Indicators of more aggressive pancreas head adenocarcinoma biology including tumor grade and LVI can be diagnosed using CT texture analysis with fair accuracy.

Background Abdominal surgery may increase the risk of splanchnic vein thrombosis (SVT). We determined the incidence of SVT after abdominal surgery and identified groups at highest risk. Materials and methods MEDLINE and Embase were searched for clinical studies evaluating the incidence of postoperative SVT after abdominopelvic surgery. Study selection, data abstraction, and risk of bias assessment were carried out independently by two reviewers. Clinical heterogeneity was explored by subgroup analyses (i.e., type of intra-abdominal procedure and organ group). Results Of 5549 abstracts screened, 48 were analyzed. Pooled incidence of SVT (n = 50,267) was 2.68% [95% confidence interval (CI), 2.24 to 3.11] (1347 events), I2 = 96%. Pooled incidence of SVT in high-risk procedures were splenectomy with devascularization (24%), hepatectomy in patients with cirrhosis (9%), and pancreatectomy with venous resection (5%). Pooled incidence of symptomatic and asymptomatic SVT was 1.02% (95% CI: 0.97% to 1.07%) and 0.98% (95% CI 0.88% to 1.07%), respectively. Most common causes of SVT-related mortality were irreversible thrombosis, bowel ischemia, liver failure, and gastrointestinal bleed. Most studies included were at a high risk of bias due to lack of prospective data collection and lack of SVT screening for all participants. Conclusions Incidence of SVT after abdominal surgery is low but remains a relevant complication. Patients undergoing procedures involving surgical manipulation of the venous system and splenectomy are at the highest risk. Given the life-threatening risks associated with SVT, there is a need for larger prospective studies on the incidence and impact of SVT after abdominal surgery.

PMC6682346; Pexastimogene devacirepvec (Pexa-Vec) is a vaccinia virus-based oncolytic immunotherapy designed to preferentially replicate in and destroy tumor cells while stimulating anti-tumor immunity by expressing GM-CSF. An earlier randomized Phase IIa trial in predominantly sorafenib-naive hepatocellular carcinoma (HCC) demonstrated an overall survival (OS) benefit. This randomized, open-label Phase IIb trial investigated whether Pexa-Vec plus Best Supportive Care (BSC) improved OS over BSC alone in HCC patients who failed sorafenib therapy (TRAVERSE). 129 patients were randomly assigned 2:1 to Pexa-Vec plus BSC vs. BSC alone. Pexa-Vec was given as a single intravenous (IV) infusion followed by up to 5 IT injections. The primary endpoint was OS. Secondary endpoints included overall response rate (RR), time to progression (TTP) and safety. A high drop-out rate in the control arm (63%) confounded assessment of response-based endpoints. Median OS (ITT) for Pexa-Vec plus BSC vs. BSC alone was 4.2 and 4.4 months, respectively (HR, 1.19, 95% CI: 0.78-1.80; p = .428). There was no difference between the two treatment arms in RR or TTP. Pexa-Vec was generally well-tolerated. The most frequent Grade 3 included pyrexia (8%) and hypotension (8%). Induction of immune responses to vaccinia antigens and HCC associated antigens were observed. Despite a tolerable safety profile and induction of T cell responses, Pexa-Vec did not improve OS as second-line therapy after sorafenib failure. The true potential of oncolytic viruses may lie in the treatment of patients with earlier disease stages which should be addressed in future studies. ClinicalTrials.gov: NCT01387555.

Perioperative carbohydrate loading, increased protein intake, and immunonutrition may decrease postoperative complications. Studies on the topic have led to controversial results. We searched Medline, EMBASE, and CENTRAL up to August 2018 for randomized trials comparing the effect of perioperative nutritional supplements (intervention) versus control on postoperative complications in patients undergoing gastrointestinal cancer surgery. Secondary outcomes included infectious complications and length of hospital stay (LOS). Random effects model was used to estimate the pooled risk ratio (RR) of treatment effects. Pooled mean difference (MD) was used to compare LOS. Heterogeneity was assessed using I2. Sources of heterogeneity were explored through subgroup analysis by nutritional supplementation protocol, type of surgery, and type of nutritional supplement. Risk of bias and quality of the evidence were assessed. Of 3951 articles, we identified 56 trials (n = 6370). Perioperative nutrition was associated with a lower risk of postoperative complications (RR 0.74, 95% confidence interval (CI) 0.69–0.80); postoperative infections (RR 0.71, 95% CI 0.64–0.79, n = 4582); and postoperative non-infectious complications (RR 0.79, 95% CI 0.71–0.87, n = 4883). There were no significant heterogeneity outcomes analyzed (I2 = 14%, 1%, and 7%, respectively). LOS was shorter for the intervention group, MD − 1.58 days; 95% CI − 1.83 to − 1.32; I2 = 89%). Subgroup analysis did not identify sources of heterogeneity. The quality of evidence for postoperative complications was high and for LOS was moderate. Perioperative nutritional optimization decreases the risk of postoperative infectious and non-infectious complications. It also decreases LOS in patients undergoing gastrointestinal cancer surgery, but these findings should be taken with caution given the high heterogeneity.

Complications frequently occur after pancreaticoduodenectomy. Patients undergoing pancreaticoduodenectomy tend to be older; age and postoperative complication may be associated. To clarify this association, we compared postoperative outcomes in patients undergoing pancreaticoduodenectomy based on age group. We aimed to determine whether we could identify an age cutoff where the incidence and cost of postoperative complications starts increasing and potentially outweigh the potential benefits of pancreaticoduodenectomy.We built a retrospective cohort of consecutive patients undergoing pancreaticoduodenectomy at one institution from 2011 to 2017. Demographics, operative data and costs were obtained from hospital and administrative databases. A restricted cubic spline regression analysis was performed to graphically identify the age in which the comprehensive complication index (CCI) substantially increased. Cost analysis was undertaken from the perspective of a third-party payer. Differences in costs between age groups were tested using t-test.Among 440 patients, the CCI became significantly higher at the age cutoff of 72 (median 21 in the older vs. 12 in the younger group, P = 0.014). Postoperative complications (74% vs. 64%, P = 0.038), and mortality (8% vs. 3%, P = 0.016) were also significantly higher in the older age group; mostly driven by pneumonia (11% vs. 6%, P = 0.097), myocardial infarction (12% vs. 4%, P 0.002) and urinary tract infection (18% vs. 5%, P = 0.003). Median length of hospital stay was also longer for the older age group (10 vs. 8 days, P = 0.002). Total mean cost was significantly higher in the older age group ($38,225 CAD vs. $29,771 CAD).In our cohort of patients, after age 72, pancreaticoduodenectomy is associated with significantly more postoperative complications and deaths which translated in longer hospital stay and higher costs. This information may help patients and surgeons make informed decisions.

511 Background: Neoadjuvant immunotherapy with anti-programmed cell death protein-1 (PD-1) or anti-programmed cell death ligand-1 (PD-L1) and tyrosine kinase inhibitor (TKI) therapy is currently being used to treat certain solid tumours prior to surgery. Neoadjuvant therapy may cause delays to resection potentially losing a window of opportunity. We explored the pooled proportion of patients with solid tumours receiving neoadjuvant therapy who completed planned surgical resection. Methods: Medline, CENTRAL and Embase databases were searched for single arm or randomized controlled trials studying neoadjuvant PD-1/PD-L1 immunotherapy or TKI therapy. Random-effects model was used to estimate the pooled proportion of patients undergoing planned resection, and weights were estimated using inverse variance method. Statistical heterogeneity was calculated using the I2 and chi-squared test. Results: From 368 relevant articles, eleven studies with a total of 382 patients receiving neoadjuvant PD-1 immunotherapy (n = 234) or neoadjuvant TKI therapy (n = 148) were analyzed. The types of tumours included hepatocellular carcinoma (1 study), renal cell carcinoma (8 studies), bladder carcinoma (1 study) or non-small cell lung cancer (1 study). The pooled proportion of patients who completed planned surgery after neoadjuvant therapy was 95% (95% CI 0.92 to 0.99). The overall partial response rate prior to surgery was 12% (95% CI 0.07 to 0.16) in the PD-1 therapy group and 46% (95% CI -0.12 to 1.03) in the TKI group. The pooled serious adverse events rate was 17% (95% CI 0.02 to 0.32) in the PD-1 therapy group and 29% (95% CI -0.10 to 0.68) in the TKI group. For all patients receiving neoadjuvant therapy, the pooled median overall survival was 23.41 months (95% CI 16.21 to 30.62) and median progression free survival was 7.46 months (95% CI 4.41 to 10.51). Conclusions: Neoadjuvant PD-1 or TKI therapy prior to surgery for solid tumours is safe, does not delay surgical resection and can result in a partial radiological response prior to surgery.

Background Adjuvant therapy for early-stage colorectal cancer improves survival. Biologic agents have shown promise as adjuncts to chemotherapy in metastatic colon cancer, but the effect on earlier stage cancer remains unclear. Materials and methods We conducted a systematic review and meta-analysis of the additive effect of biologic agents to adjuvant chemotherapy on survival in colorectal cancer (all comers and subpopulations defined by microsatellite instability, BRAF and KRAS status, and stage). Only randomized controlled trials published between 2002 and 2017 in MEDLINE, EMBASE, and CENTRAL were included. The control arm: chemotherapy alone, the intervention arm: chemotherapy with biologic agents. Outcomes: overall survival (OS) and disease-free survival. Results Six trials including 10,754 patients were included. OS (hazard ratio [HR] 2.55, 95% confidence interval [CI] 2.15-3.03) and disease-free survival (HR 2.54, 95% CI 2.25-2.87) were significantly worse in the intervention arm. High heterogeneity was explained by subgroup analysis of different biologic agents (bevacizumab versus others); however, results still showed harm in the intervention arm across subgroups. Bevacizumab was associated with improved OS in patients with microsatellite instability (HR 0.58, 95% CI 0.36-0.92); this was the only indication of benefit for a biomarker-defined subpopulation. Analyses by tumor stage failed to demonstrate advantage with use of a biologic agent; however, it explained heterogeneity. Conclusions The addition of biologic agents to adjuvant chemotherapy in the treatment of high-risk stage II and III colorectal cancer is associated with worse survival outcomes. The only subgroup of patients that may benefit from the addition of bevacizumab to adjuvant chemotherapy is those with microsatellite unstable tumors.

BACKGROUND Postoperative morbidity following gastrointestinal tract major surgery ranges between 40% and 60%. Malnutrition, poor protein intake, and surgery-related impairment of the immune system and its function have been associated with postoperative infections. Supplemental perioperative nutrition may improve nutrition by increasing protein intake to influence cell-mediated immunity, thereby reducing the rate of postoperative infectious complications. OBJECTIVE The primary objective of our trial is to determine the proportion of eligible patients randomized in an 18-month period. The primary feasibility outcome will be to (1) stop, main study not feasible: estimated proportion of randomized patients METHODS This is a double-blind randomized placebo-controlled feasibility trial. The intervention comprises three nutritional supplements: a protein isolate powder (ISOlution); immunomodulation (INergy-FLD), formulated liquid diet; and carbohydrate loading (PreCovery). Patients will consume 1 serving of the protein supplement per day from the randomization time up to 6 days before surgery (30 days in total). The immunomodulation, a solution that contains arginine, protein isolate, omega-6 fatty acids, and RNA, aims to attenuate excessive inflammatory responses and to replenish nutrients. This solution will be consumed as 3 doses per day for 5 days before and after surgery. Carbohydrate loading helps to reduce the stress from surgery by decreasing insulin resistance. Patients will have 2 servings the evening before surgery and 1 serving 2-3 hours before surgery. To be eligible, patients must have a resectable gastrointestinal cancer for which an elective operation is planned. Patients will be stratified according to nutritional status. The operation should occur within 4 weeks from enrollment. RESULTS We expect to screen 165 eligible patients; 60.6% (100/165) of them will be randomized to either intervention or placebo. Assuming a two-sided alpha of .05, this will give us a 95% CI around the estimate of 53%-68%. A sample size of 50 per group will enable us to estimate the treatment effect and corresponding variance of the complication rate and QoL measures with adequate precision. The success is defined as the proportion of eligible patients randomized as ≥60.0% (60/100). Patients’ compliance is defined as an intake of at least 70% (41/58) sachets of the intervention volume. CONCLUSIONS The results will help to determine the feasibility of a larger randomized controlled trial to implement a perioperative nutritional supplement program for patients undergoing gastrointestinal surgery for cancer. CLINICALTRIAL ClinicalTrials.gov NCT03445260; https://clinicaltrials.gov/ct2/show/NCT03445260 (Archived by WebCite at http://www.webcitation.org/72CAmMzgP) INTERNATIONAL REGISTERED REPOR PRR1-10.2196/10491

The aim of this study was to evaluate the incidence and risk factors for post-hospital discharge venous thromboembolism (VTE) following abdominal cancer surgery without post-discharge prophylaxis. This was a single-center, prospective cohort study. Patients were evaluated at 1, 3, and 6 months from surgery for the presence of proximal deep vein thrombosis (DVT; screening ultrasound at 1 month and questionnaire at each visit). Cumulative VTE incidence with 95% confidence interval (CI) was estimated using Kaplan–Meier methods, and multivariable analysis was performed using a Cox proportional hazards model. Of 284 patients enrolled, 79 (28%) underwent colorectal laparotomy, 97 (34%) underwent hepatobiliary laparotomy, 100 (35%) underwent gynecological laparotomy, and 8 (3%) underwent exploratory laparotomy without resection. All patients received pre- and postoperative inpatient prophylaxis. The cumulative incidence of VTE at 1 month was 0.35% (95% CI 0.05–2.48), 2.5% at 3 months (95% CI 1.19–5.15), and 7.2% at 6 months (95% CI 4.72–10.97). Screening ultrasound performed 4 weeks after surgery in 50% of patients was negative for thrombosis in all cases. Event distribution was similar according to the type of surgery (open/laparoscopic) and type of cancer. Seventeen (6.6%) patients died (95% CI 3.5–9.4) (two had a VTE-related death). Postoperative chemotherapy and Caprini score were significantly associated with VTE [hazard ratios 3.77 (95% CI 1.56–9.12) and 1.17 (95% CI 1.02–1.34), respectively]. The incidence of post-hospital discharge proximal DVT and/or symptomatic VTE following abdominal and pelvic cancer surgery appears to be low. The cumulative number of events increased at 6 months, but this was likely due to additional risk factors that were not related to surgery. Postoperative chemotherapy increases the risk of VTE.

662 Background: Decision to proceed with simultaneous or staged resection in synchronous colorectal cancer liver metastases (CRLM) varies and is usually left to the individual surgeon. We examined practice intentions and barriers to performing simultaneous resection. Methods: We developed and pilot-tested a tailored questionnaire. Members of the Society of Surgical Oncology and the College of Physicians and Surgeons of Ontario operating colorectal cancer were surveyed electronically. Four clinical scenarios of synchronous CRLM determined practice intentions for varying degrees of complexity. Perceived barriers were assessed on a 7-point Likert scale. We compared general and hepatobiliary surgeons’ responses with Mann-Whitney U test for continuous variables and Chi-square test for categorical variables. Results: There were 184/1,335 surgeons (14% response rate), including 50 general and 134 hepatobiliary surgeons. Both were supportive of simultaneous resection, though hepatobiliary surgeons were more so; for minor liver and low complexity colorectal resections (Likert ≥5-7: 83% vs. 98% p

Highlights • Rectal prolapse occurs particularly in elderly females. • Complications include incarceration, strangulation, and, rarely, perforation with evisceration of other viscera requiring urgent operation. • Such complications can be prevented by a strict bowel regimen and avoidance of activities that increase intra-abdominal pressure. • Prompt surgical consult is warranted if any signs or symptoms suggestive of complications from prolapse are present., Introduction Rectal prolapse occurs particularly in elder females and presentation can sometimes lead to complications such as strangulation and evisceration of other organs through the necrotic mucosa. Presentation of case This is a case of a 61 year-old female with rectal prolapse complicated by rectal perforation through which a segment of sigmoid colon eviscerated and became strangulated. This patient initially presented with sepsis requiring ICU admission, but fully recovered following a Hartmann’s procedure with a sacral rectopexy. Discussion Complications of rectal prolapse include incarceration, strangulation, and rarely, perforation with evisceration of other viscera requiring urgent operation. This report provides a brief overview of complications associated with rectal prolapse, reviews similar cases of transrectal evisceration, and discusses the management of chronic rectal prolapse. Conclusion Prompt surgical consult is warranted if any signs or symptoms suggestive of complications from prolapse are present.

Oncolytic viruses and active immunotherapeutics have complementary mechanisms of action (MOA) that are both self amplifying in tumors, yet the impact of dose on subject outcome is unclear. JX-594 (Pexa-Vec) is an oncolytic and immunotherapeutic vaccinia virus. To determine the optimal JX-594 dose in subjects with advanced hepatocellular carcinoma (HCC), we conducted a randomized phase 2 dose-finding trial (n 5 30). Radiologists infused low-or high-dose JX-594 into liver tumors (days 1, 15 and 29); infusions resulted in acute detectable intravascular JX-594 genomes. Objective intrahepatic Modified Response Evaluation Criteria in Solid Tumors (mRECIST) (15%) and Choi (62%) response rates and intrahepatic disease control (50%) were equivalent in injected and distant noninjected tumors at both doses. JX-594 replication and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression preceded the induction of anticancer immunity. In contrast to tumor response rate and immune endpoints, subject survival duration was significantly related to dose (median survival of 14.1 months compared to 6.7 months on the high and low dose, respectively; hazard ratio 0.39; P = 0.020). JX-594 demonstrated oncolytic and immunotherapy MOA, tumor responses and dose-related survival in individuals with HCC.

To determine if the degree of blood loss during resection of hepatocellular carcinoma (HCC) is predictive of recurrence and long-term survival.Several studies have addressed the impact of blood transfusion on survival and recurrence after liver resection for HCC. However, the independent effect of intraoperative estimated blood loss (EBL) on oncologic outcome is unclear.From our prospective database, we identified 192 patients who had a partial hepatectomy for HCC from 1985 to 2002. Clinicopathologic predictors of EBL were identified using logistic regression. Overall survival (OS), disease-specific survival (DSS), and recurrence free survival (RFS) were assessed using the Kaplan-Meier and Cox regression methods.The median patient age was 64 (range, 19-86) and 66% were men. All patients had histologically proven HCC. The median follow-up time was 34 months (range, 1-297). Factors associated with increased EBL on multivariate analysis were male gender, vascular invasion, extent of hepatectomy, and operative time (P0.01). EBL and vascular invasion were independent predictors of OS and DSS. Only EBL was significantly associated with RFS on multivariate analysis (P = 0.02). Additionally, we found a significant inverse correlation between increasing levels of EBL and length of DSS (P = 0.01).The magnitude of EBL during HCC resection is related to biologic characteristics of the tumor as well as the extent of surgery. Increased intraoperative blood loss during HCC resection is an independent prognostic factor for tumor recurrence and death.

Purpose After preoperative chemoradiotherapy of rectal cancer, the number of retrievable and metastatic lymph nodes is decreased. The current TNM classification is based on number and not location of lymph node metastases and may understage disease after chemoradiotherapy. The aim of this study was to examine the prognostic significance of location of involved lymph nodes in rectal cancer patients after preoperative chemoradiotherapy. Patients and Methods We prospectively examined whole-mount specimens from 121 patients with uT3-4 and/or N+ rectal cancer who received preoperative chemoradiotherapy followed by resection. Location of involved lymph nodes was compared with median number of lymph nodes involved as well as presence of distant metastasis at presentation. Results Lymph node metastases were detected in 37 patients (31%). Thirteen patients with lymph node involvement along major supplying vessels (proximal lymph node metastases) had a significantly higher rate of distant metastatic disease at time of surgery than patients without proximal lymph node involvement (P < .001); median number of lymph nodes involved was two for patients with proximal lymph node metastases and 1.5 for patients with mesorectal lymph node involvement alone. Conclusion Our data suggest that, after preoperative chemoradiotherapy, proximal lymph node involvement is associated with a high incidence of metastatic disease at time of surgery. Because the median number of involved lymph nodes is low after preoperative chemoradiotherapy, the TNM staging system may not provide an accurate assessment of metastatic disease. Therefore, the ypTNM staging system should incorporate distribution as well as number of lymph node metastases after preoperative chemoradiotherapy for rectal cancer.

Compared with surgery alone, preoperative radiotherapy and 5-fluorouracil-based chemotherapy (combined-modality therapy; CMT) improves outcomes in patients with locally advanced rectal cancer. Although numerous studies have focused on identifying molecular markers of prognosis in the primary rectal cancer before CMT, our aim was to identify markers of prognosis in residual rectal cancer after preoperative CMT.Sixty-seven patients with locally advanced (T3-4 and/or N1) rectal cancer were treated with preoperative radiotherapy (median, 5040 cGy) with or without 5-fluorouracil-based chemotherapy. Residual tumor in the resected specimen, available for 52 patients, was analyzed for tumor-node-metastasis stage, lymphovascular and/or perineural invasion, and immunohistochemical expression of p27, p21, p53, Ki-67, retinoblastoma gene, cyclin D1, and bcl-2. Recurrence-free survival (RFS) was determined by the Kaplan-Meier method and compared by the log-rank test.With a median follow-up of 69 months, the overall 5-year RFS was 74%. RFS was significantly worse for patients with positive p27 expression (P = .005), T3-4 tumors (P = .02), and positive lymph nodes (P = .04) in the irradiated specimen. On multivariate analysis, positive p27 expression remained an independent negative prognostic factor for RFS (P = .04). None of the other proteins was significantly associated with RFS.Our results indicate that positive p27 expression in rectal cancer after preoperative chemoradiation is an independent negative predictor of RFS. Expression of p27 in the residual rectal cancer may therefore identify patients with disease likely to be refractory to standard therapy and for whom investigational approaches should be strongly considered.

Background We have previously demonstrated that fluorodeoxyglucose-positron emission tomography (FDG-PET) can assess extent of pathologic response of primary rectal cancer to preoperative chemoradiation. Our goal was to determine the prognostic significance of FDG-PET assessment of rectal cancer response to preoperative chemoradiation. Study design Fifteen patients with locally advanced primary rectal cancer (clinically bulky or tethered, or ultrasound evidence of T3–4 disease, N1 disease, or both) deemed eligible for preoperative radiation and 5-FU-based chemotherapy (5,040 cGy to the pelvis and 2 cycles of bolus 5-FU/leucovorin) were prospectively enrolled from May 1997 to September 1998. FDG-PET was performed before and 4 to 5 weeks after completion of preoperative chemoradiation. FDG-PET parameters included maximum standard uptake value (SUV max ), total lesion glycolysis (TLG), and visual response score. Patients were prospectively followed after operation, and disease status was determined. Results All patients demonstrated some degree of response to preoperative therapy based on pathologic examination. At a median followup of 42 months (range 23 to 54 months), 11 patients had no evidence of disease and 4 had died of disease. The mean percentage decrease in SUV max (ΔSUV max ) was 69% for patients free from recurrence and 37% for patients with recurrence (p = 0.004). ΔSUV max ≥ 62.5 and δTLG ≥ 69.5 were the best predictors of no-evidence-of-disease status and freedom from recurrence. Patients with ΔSUV max ≥ 62.5 and δTLG ≥ 69.5 had significantly improved disease-specific and recurrence-free survival (p = 0.08, 0.02 and p=0.03, 0.01, respectively). Conclusions Our results indicate that FDG-PET assessment of locally-advanced rectal cancer response to preoperative chemoradiation may predict longterm outcomes.

Preoperative radiation (RT) and chemotherapy improve outcome in patients with locally advanced rectal adenocarcinoma and, therefore, have been used increasingly in patient management. The histopathologic alterations in postirradiated rectal adenocarcinoma and their prognostic significance have not been fully characterized. In this study, detailed analyses of morphologic alterations of stromal and tumor cells were performed in a series of 66 posttreatment rectal carcinomas, and the pathologic findings were correlated with long-term outcome. All tumors were locally advanced, with a bulky and/or tethered tumor or endorectal ultrasound or magnetic resonance imaging evidence of T3-4 and / or N1 disease. All patients were treated at one institution with preoperative RT to the pelvis (at least 4500 cGy) with or without concurrent 5-fluorouracil (5-FU)-based chemotherapy 4 to 7 weeks prior to surgical resection. Pathologic assessment showed some treatment response in all patients. Nine patients (13.4%) had complete response, and 8 (11.9%) had near-complete response (95% of the tumor replaced by fibroinflammatory tissue). Salient morphologic features included marked fibrosis with or without prominent inflammatory cells replacing neoplastic glands; lack of active tumor necrosis; increased mucin production and mucin pools; marked cytoplasmic eosinophilia, often in combination with marked nuclear atypia but without active mitoses in tumor cells showing treatment effect; endocrine tumor phenotype; and retention of mucosal adenoma in the presence of tumor regression within the bowel wall. With a median follow-up of 69 months, the estimated 5-year recurrence-free survival (RFS) for the entire group was 79%. By univariate analysis, the residual tumor stage (P0.05) and reduction of pretreatment T stage (P = 0.002) significantly correlated with RFS, as did pN stage (P = 0.002) and lymphovascular invasion (P = 0.008). The extent of treatment response did not correlate with RFS (P = 0.4). However, patients with a treatment responseor = 95% seemed to fare better than those with a treatment response95% (marginally significant difference in RFS, P = 0.057). Univariate and multivariate analyses identified the following morphologic patterns that were significantly associated with a reduced RFS independent of other risk factors: a fibrotic-type stromal response with minimal inflammatory infiltrates (P = 0.001) and absence of surface ulceration (P = 0.026). Our study represents the first detailed morphologic assessment of rectal carcinomas that have been subjected to long course preoperative RT and chemotherapy. Our results demonstrate distinct morphologic features in treated rectal carcinomas that are prognostically relevant.

Hepatocellular carcinoma (HCC) is the fifth-leading cause of cancer in the world.1,2 In the United States, there will be 20,200 new cases of HCC this year, which is a 75% increase over the past decade and reflects the increased prevalence of chronic hepatitis infection.3 Three million people have chronic hepatitis C, and 1.2 million have chronic hepatitis B in the United States. These patients are estimated to develop HCC at a rate of 5% per year for chronic hepatitis C and 0.5% per year for hepatitis B.4,5 It is predicted that the number of deaths from HCC will rise dramatically over the next 10-15 years in this country.2,6,7 Partial hepatectomy has been the standard therapy for patients with HCC and good hepatic reserve when complete tumor resection is feasible. Five-year survival rates after resection have ranged from approximately 30 to 40%.8-14 Unfortunately, the majority of patients subsequently develop recurrent cancer in the liver remnant after resection.12,15 Adjuvant therapy has not been proven to be effective.16,17 In an attempt to achieve better results, surgeons have used liver transplantation for patients with HCC. The initial experience, in which transplantation was used liberally for patients with all stages of HCC, was discouraging, with 5-year survival rates ranging from 20-36%.18-22 It was noted, however, that patients with incidentally discovered HCC in the explanted liver and those with small tumors had similar survival comparable with patients undergoing liver transplantation for benign disease.23 Soon thereafter, the eligibility criteria for transplantation in patients with HCC were restricted. Mazzaferro et al24 published one of the first series to propose the currently accepted criteria for transplantation: a solitary tumor ≤ 5 cm, 2 or 3 tumors ≤ 3 cm in size, and the absence of vascular invasion. Four-year survival was reported at 75%, and 4 year recurrence free survival was 83%. Several other studies have confirmed these findings.20-23,25-28 Some authors have found the results to be so convincing that they are using liver transplantation as a first line treatment of patients with HCC and cirrhosis, regardless of the degree of liver dysfunction.29 However, the seemingly better results with transplantation versus partial hepatectomy may simply reflect the more stringent selection of patients with earlier stage HCC. In an attempt to determine whether partial hepatectomy or transplantation is a better treatment of early HCC, we examined the outcome of patients with early HCC treated with partial hepatectomy who would have been candidates for transplantation.

Surgical resection of primary colorectal cancer (CRC) in patients with stage IV disease at initial presentation remains controversial. Although bowel resection to manage symptoms such as bleeding, perforation, or obstruction has been advocated, management of asymptomatic patients has not been well defined. Patient-dependent factors (performance status, comorbid disease) and extent of distant metastases are among the considerations that impact on the decision to proceed with surgical management in asymptomatic stage IV CRC patients. We postulated that selected patients might benefit from elective resection of the asymptomatic primary CRC. The extent of distant metastases was objectively measured by several methods to identify potential prognostic variables that may help guide patient selection in this population.We reviewed hospital and colorectal service databases for the years 1996 to 1999. Stage IV patients who had colorectal resections with gross residual metastatic disease were identified (n = 209). Among these 209 patients, 82 patients operated on for symptoms (obstruction, perforation, bleeding, or pain) were excluded, leaving 127 patients who underwent elective resection of their asymptomatic primary CRC. Over the same time period, 103 stage IV patients who did not undergo resection were identified. Data on patient characteristics and clinical management were collected. A radiologist performed an independent review of available CT scans to assess extent of liver disease. The chi-square test was used for analysis of categoric data and Student's t-test for continuous variables. Survival was determined by the Kaplan-Meier method and distributions compared by the log rank test. Multivariate analysis was performed using Cox regression.The resected group could be easily distinguished from the nonresected group by a higher frequency of right colon cancers (p = 0.03) and metastatic disease restricted to the liver (p = 0.02) or one other site apart from the primary tumor (p = 0.02). Resected patients had prolonged median (16 versus 9 months, p0.001) and 2-year (25% versus 6%, p0.001) survival compared with patients never resected. Univariate analysis identified three significant prognostic variables (number of distant sites involved, metastases to liver only, and volume of hepatic replacement by tumor) in the resected group. Volume of hepatic replacement was also a significant predictor of survival in Cox multivariate regression analysis (p = 0.01). Subsequent to resection of asymptomatic primary CRC, 26 patients (20%) developed postoperative complications. Median hospital stay was 6 days. Two patients (1.6%) died within 30 days of surgery.Stage IV patients selected for elective palliative resection of asymptomatic primary colorectal cancers had substantial postoperative survival that was significantly better than those never having resection. Limited metastatic tumor burden and less extensive liver involvement were associated with better survival and a higher likelihood of benefit from elective bowel resection in asymptomatic patients with incurable stage IV CRC.

Adenomatous polyps and adenocarcinomas of the periampullary region are the most common upper gastrointestinal neoplasms encountered in familial adenomatous polyposis (FAP) patients. Tumors arising from the liver, biliary tract, and pancreas have also been reported. The purpose of this study was to review the clinical outcome of FAP patients after pancreaticoduodenal surgery for periampullary neoplasms. Of the 61 individuals participating in our prospective FAP registry, 8 underwent surgical resection of periampullary neoplasms between 1987 and 1998. The charts of these individuals were reviewed for clinical indications, type of pancreaticoduodenal surgery, postoperative complications, and outcome. Of the 8 patients identified, 7 had pancreaticoduodenectomy and 1 had duodenotomy with ampullectomy. The indications for surgery were periampullary cancer (3), severe dysplasia within a duodenal villous tumor (4), and solid-pseudopapillary tumor of the pancreas (1). At the time of pancreaticoduodenal surgery, patients ranged in age from 29-65 years, and all but one had undergone colorectal surgery, on average 16 years beforehand. Pancreatic ascites after a pylorus-sparing pancreaticoduodenectomy was the only surgical complication. At a median follow-up of 70.5 months (range 37-162), 2 patients had died, neither from their periampullary neoplasm. The patient treated by local excision subsequently developed gastric cancer arising from a polyp and went on to gastrectomy. Another patient developed confluent benign jejunal adenomas just beyond the gastroenteric anastomosis almost 12 years after pancreaticoduodenectomy for severe dysplasia of a duodenal villous adenoma. Pancreaticoduodenectomy is a safe and appropriate surgical option for FAP patients with duodenal villous tumors containing severe dysplasia or carcinoma. Postoperative morbidity was minimal and there was no perioperative mortality. Good long-term prognosis can be expected in completely resected patients although subsequent proliferative and/or neoplastic lesions may still be detected in the gastrointestinal tract with prolonged follow-up.

To determine whether selected clinicopathologic factors, including the extent of pathologic response to preoperative radiation and chemotherapy (RT +/- chemo), have an impact on long-term recurrence-free survival (RFS) in patients with locally advanced primary rectal cancer after optimal multimodality therapy.Although complete pathologic response to preoperative RT +/- chemo has been detected in up to 30% of rectal cancers, its significance on long-term outcome has not been widely reported. Previous retrospective studies evaluating clinical outcome in patients with complete or near-complete pathologic response documented good prognosis in this population but were limited by median follow-up in the range of 2 to 3 years.Sixty-nine patients with locally advanced (T(3-4) and/or N1) primary rectal cancer were prospectively identified. All were treated at one institution with preoperative RT to the pelvis (at least 4,500 cGy). Forty patients received concurrent preoperative 5-fluorouracil-based chemotherapy and 27 received both pre- and postoperative chemotherapy. Patients underwent resection 4 to 7 weeks after completion of RT. TNM stage, angiolymphatic or perineural invasion, and extent of response to preoperative RT +/- chemo were determined by pathologic evaluation. Adverse pathologic features were defined as the presence of angiolymphatic and/or perineural invasion. RFS at 5 years was determined by the Kaplan-Meier method.With a median follow-up of 69 months, 5-year RFS was 79%. RFS was significantly worse for patients with aggressive pathologic features and positive nodal status identified in the postirradiated surgical specimen. Risk ratios for RFS were 3.68 for the presence of aggressive pathologic features and 4.64 for node-positive rectal cancers. In patients with greater than 95% rectal cancer response to preoperative RT +/- chemo, only one patient has died as a consequence of cancer, another has died of an unrelated cause, and the remainder were free of disease with a minimum follow-up of 47 months.These data suggest that a marked response to preoperative RT +/- chemo may be associated with good long-term outcome but was not predictive of RFS. The presence of poor histopathologic features and positive nodal status are the most important prognostic indicators after neoadjuvant therapy.

Before the second half of this century, treatment approaches to breast cancer were radical and disfiguring. In the past four decades, however, multiple prospective randomized trials have made highly significant advances in the management of patients with this disease. These trials have established, in select patients, breast conservation therapy as a primary therapeutic procedure, and radiation therapy as a means to improve local control and survival. This article provides an overview of some of these trials.