Updates in global oncology: Advancements and future directions.

Globally, cancer is the second leading cause of death, and low- and middle-income countries bear most of the disease burden. While cancer is increasingly recognized as a major global health issue, more work remains. Understanding the status of global cancer care will shape the next steps in ensuring equitable global access to cancer care. This article highlights ongoing initiatives in global oncology and the next steps in advancing the field.

Lending a hand for laparoscopic distal pancreatectomy: the optimal approach?

BACKGROUND: Both minimally invasive surgery (MIS) and open approaches for distal pancreatectomy are acceptable. MIS options include total laparoscopic/robotic (TLR) and hand-assist laparoscopy (HAL). When considering safety profile and specimen quality, the optimal approach is unknown. METHODS: Patients who underwent distal pancreatectomy from 2010-2018 at two major academic institutions were included. Converted procedures were categorized into final approach. Ninety-day perioperative/pathologic outcomes of MIS and open were compared. Subset analyses between TLR vs HAL and HAL vs open were performed. Intent-to-treat analysis was performed. RESULTS: Among 1006 patients, resection was performed by MIS in 35% (n = 352), open in 65% (n = 654). MIS had similar patient comorbidity profile as open but had increased operative time (183 vs 162 min; p < 0.01), lower estimated-blood-loss (EBL; 131 vs 341 mL; p < 0.01), fewer intraoperative blood transfusions (1.4 vs 5%; p < 0.01), shorter LOS (5.2 vs 7.2 days; p < 0.01). Tumor size was smaller (3.2 vs 4.4 cm; p < 0.01) with lower lymph node (LN) yield (14 vs 16; p < 0.01). When comparing HAL (n = 109) to TLR (n = 243), despite increased prior abdominal operations (60 vs 43%; p = 0.008), HAL had shorter operative time (167 vs 191 min; p < 0.01), similar length-of-stay (LOS; 5.4 vs 5.1 days; p = 0.27), and readmission rate (15 vs 13%; p = 0.47). When comparing HAL to open, the advantages of TLR approach persisted including lower EBL (171 vs 342 mL; p < 0.01), and shorter LOS (5.4 vs 7.2 days; p < 0.01). Although HAL had smaller tumors, it had a similar LN yield (16 vs 16; p = 0.80), and higher R0-rate (97 vs 83%; p < 0.01). CONCLUSION: Hand-assist laparoscopy is safe and feasible for distal pancreatectomy as operative time, complication profile, lymph node yield, and R0-rates are similar to open procedures, while maintaining the associated the advantages of a total laparoscopic/robotic approach with reduced blood loss and shorter length-of-stay.

A perioperative multidisciplinary care bundle reduces surgical site infections in patients undergoing synchronous colorectal and liver resection.

BACKGROUND: Surgical site infections (SSIs) are a major cause of morbidity, mortality, and healthcare costs, and patients undergoing simultaneous colorectal/liver resections are at an especially high SSI risk. METHODS: Data were collected on all patients undergoing synchronous colorectal/liver resection from 2011 to 2016 (n = 424). The intervention, implemented in 2013, included 13 multidisciplinary perioperative components. The primary endpoints were superficial/deep and organ space SSIs. Secondary endpoints were hospital length of stay (LOS) and 30-day readmission rate. To control for changes in SSI rates independent of the intervention, interrupted time series analysis was conducted. RESULTS: Overall, superficial/deep, and organ space SSIs decreased by 60.5% (p < 0.001), 80.6% (p < 0.001), and 47.6% (p = 0.008), respectively. In the pre-intervention cohort (n = 231), there were 79 (34.2%), 31 (13.4%), and 48 (20.8%) total, superficial/deep, and organs space SSIs, respectively. In the post-intervention cohort (n = 193), there were 26 (13.5%), 5 (2.6%), and 21 (10.9%) total, superficial/deep, and organs space SSIs, respectively. Median LOS decreased from 9 to 8 days (p < 0.001). Readmission rates did not change (p = 0.6). Interrupted time series analysis found no significant trends in SSI rate within the pre-intervention (p = 0.35) and post-intervention (p = 0.55) periods. CONCLUSION: In combined colorectal/liver resection patients, implementation of a multidisciplinary care bundle was associated with a 61% reduction in SSIs, with the greatest impact on superficial/deep SSI, and modest reduction in LOS. The absence of trends within each time period indicated that the intervention was likely responsible for SSI reduction. Future efforts should target further reduction in organ space SSI.

The Impact of Primary Tumor Location on Long-Term Survival in Patients Undergoing Hepatic Resection for Metastatic Colon Cancer.

BACKGROUND: The impact of primary tumor location on overall survival (OS), recurrence-free survival (RFS), and long-term outcomes has not been well established in patients undergoing potentially curative resection of colorectal liver metastases (CRLM). METHODS: A single-institution database was queried for initial resections for CRLM 1992-2004. Primary tumor location determined by chart review (right = cecum to transverse; left = splenic flexure to sigmoid). Rectal cancer (distal 16 cm), multiple primaries, and unknown location were excluded. Kaplan-Meier and Cox regression methods were used. Cure was defined as actual 10-year survival with either no recurrence or resected recurrence with at least 3 years of disease-free follow-up. RESULTS: A total of 907 patients were included with a median follow-up of 11 years; 578 patients (64%) had left-sided and 329 (36%) right-sided primaries. Median OS for patients with a left-sided primary was 5.2 years (95% confidence interval [CI] 4.6-6.0) versus 3.6 years (95% CI 3.2-4.2) for right-sided (p = 0.004). On multivariable analysis, the hazard ratio for right-sided tumors was 1.22 (95% CI 1.02-1.45, p = 0.028) after adjusting for common clinicopathologic factors. Median RFS was marginally different stratified by primary location (1.3 vs. 1.7 years; p = 0.065). On multivariable analysis, location of primary was not significantly associated with RFS (p = 0.105). Observed cure rates were 22% for left-sided and 20% for right-sided tumors. CONCLUSIONS: Among patients undergoing resection of CRLM, left-sided primary tumors were associated with improved median OS. However, long-term survival and recurrence-free survival were not significantly different stratified by primary location. Patients with left-sided primary tumors displayed a prolonged clinical course suggestive of more indolent biology.

Recurrence After Partial Hepatectomy for Metastatic Colorectal Cancer: Potentially Curative Role of Salvage Repeat Resection.

PURPOSE: Patients with recurrence after complete resection of colorectal liver metastases (CLM) are considered for repeat resection as a potential salvage therapy (PST). However, outcomes for this approach are not well defined. We sought to analyze the natural history of recurrence and PST in a large cohort of patients with long-term follow-up. METHODS: Recurrence patterns, treatments, and outcomes in consecutive patients undergoing resection for colorectal liver metastases were analyzed retrospectively. PST was defined as repeat resection of all recurrent disease and effective salvage therapy (EST) as free of disease for 36 months after last PST. Factors associated with PST, EST, and outcomes were analyzed. RESULTS: Of 952 patients who underwent resection, 594 (62 %) experienced recurrence (median interval = 13 months). Initial recurrences involved liver (n = 157,26 %), lung (n = 167,28 %), multiple sites (n = 171,29 %), and other single sites (n = 99,17 %). PST was performed in 160 (27 %) of 594, most commonly with a single site of recurrence (n = 149). Young age (p = 0.01), negative initial resection margin (p = 0.003), initial tumor size <5 cm (p = 0.006), and recurrence pattern (p < 0.001) were independently associated with PST. Thirty-six patients experienced EST (25 % of PSTs). Overall median survival was 61 and 43 months in those with recurrence. Median survival of patients undergoing PST was 87 months compared to 34 months for those who did not. CONCLUSIONS: Recurrence is common after CLM resection, but 27 % of patients were able to undergo PST. Approximately one-quarter of these experienced EST and may be cured. PST is associated with long-term survival and possible cure, and therefore active surveillance after CLM resection is justified.

Readmission after pancreatic resection: causes and causality pattern.

BACKGROUND: Readmission rates have been targeted for cost/reimbursement control. Our goal was to identify causes for readmission and delineate the pattern of early and late readmission. METHODS: Between 2011 and 2012, a total of 490 patients underwent pancreaticoduodenectomy, distal pancreatectomy or central pancreatectomy. Logistic regression was used to identify predictors of readmission. K-medoids clustering was performed to identify the major readmission subgroups. RESULTS: Median postoperative length of stay (LOS) was 7 days, and the 30- and 90-day readmission rates were 23 and 29 %, respectively. The most common cause for 30-day readmissions was procedure-related infections (58 %), while the most common cause for 31-90-day readmissions was failure to thrive and chemotherapy-related symptoms (38 %). Independent predictors of 30-day readmissions were central pancreatectomy, discharge with a drain, pancreatic duct <3 mm, previous abdominal surgery, and postoperative LOS. Independent predictors for 31-90-day readmissions were age and preoperative serum carcinoembryonic antigen. Cancer-related covariates were more common in the 31-90-day readmission group. Postoperative carbohydrate antigen 19-9 levels were twofold higher in the 31-90-day readmission group compared with the no readmission group (p = 0.03). K-medoids clustering identified a subgroup where 74 % of readmissions occur at a median of 7 days after discharge. CONCLUSIONS: Readmissions after pancreatic operations are procedure-related in the first 30 days, but those after this period are influenced by the natural history of the underlying diagnosis. The readmission penalty policy should account for the timing of readmission and the natural history of the underlying disease and procedure. Early follow-up for patients at high risk for readmission may minimize early readmissions.

The Image-to-Physical Liver Registration Sparse Data Challenge: comparison of state-of-the-art using a common dataset.

Purpose: Computational methods for image-to-physical registration during surgical guidance frequently rely on sparse point clouds obtained over a limited region of the organ surface. However, soft tissue deformations complicate the ability to accurately infer anatomical alignments from sparse descriptors of the organ surface. The Image-to-Physical Liver Registration Sparse Data Challenge introduced at SPIE Medical Imaging 2019 seeks to characterize the performance of sparse data registration methods on a common dataset to benchmark and identify effective tactics and limitations that will continue to inform the evolution of image-to-physical registration algorithms. Approach: Three rigid and five deformable registration methods were contributed to the challenge. The deformable approaches consisted of two deep learning and three biomechanical boundary condition reconstruction methods. These algorithms were compared on a common dataset of 112 registration scenarios derived from a tissue-mimicking phantom with 159 subsurface validation targets. Target registration errors (TRE) were evaluated under varying conditions of data extent, target location, and measurement noise. Jacobian determinants and strain magnitudes were compared to assess displacement field consistency. Results: Rigid registration algorithms produced significant differences in TRE ranging from 3.8±2.4 mm to 7.7±4.5 mm, depending on the choice of technique. Two biomechanical methods yielded TRE of 3.1±1.8 mm and 3.3±1.9 mm, which outperformed optimal rigid registration of targets. These methods demonstrated good performance under varying degrees of surface data coverage and across all anatomical segments of the liver. Deep learning methods exhibited TRE ranging from 4.3±3.3 mm to 7.6±5.3 mm but are likely to improve with continued development. TRE was weakly correlated among methods, with greatest agreement and field consistency observed among the biomechanical approaches. Conclusions: The choice of registration algorithm significantly impacts registration accuracy and variability of deformation fields. Among current sparse data driven image-to-physical registration algorithms, biomechanical simulations that incorporate task-specific insight into boundary conditions seem to offer best performance.

Risk of occult irresectable disease at liver resection for hepatic colorectal cancer metastases: a contemporary analysis.

INTRODUCTION: Traditionally, rates of irresectable disease at laparotomy for colorectal liver metastases (CRLM) have ranged from 15 to 70%. Diagnostic laparoscopy has been shown to be effective at preventing nontherapeutic laparotomy in selected patients. The purpose of this study was to analyze the resectability rate and role of diagnostic laparoscopy in a contemporary cohort. METHODS: Using a prospectively maintained database, we identified patients who were explored for presumed resectable CRLM. Clinical and pathologic data associated with the finding of irresectable disease were analyzed. RESULTS: From 2008-2010, 455 patients were explored. Of these, 35 (7.7%) did not undergo a resection and/or ablation. Of the 35 patients with irresectable disease, 15 (43%) had disease limited to the liver, 17 (49%) had extrahepatic disease (EHD), and 3 (9%) had other reasons precluding resection. Of the whole cohort, 45 patients (9.9%) were found to have EHD, and 27 of these (60%) underwent complete resection or ablation. The only factor associated with irresectable disease was a prior history of EHD, which was present in 29% of those found irresectable versus 13% of those resected (p = 0.022). Diagnostic laparoscopy was performed in 55 patients. Four of these patients had irresectable disease, and three were spared unnecessary laparotomy. Therefore, the yield was 5% and the sensitivity 75%. CONCLUSIONS: The finding of irresectable disease is a rare event with modern radiologic assessment and the expansion of indications for resection. Diagnostic laparoscopy has a low yield and should be considered if there is a history of EHD or suspicious findings on preoperative imaging.

Identification of urinary biomarkers of colorectal cancer: Towards the development of a colorectal screening test in limited resource settings.

BACKGROUND: African colorectal cancer (CRC) rates are rising rapidly. A low-cost CRC screening approach is needed to identify CRC from non-CRC patients who should be sent for colonoscopy (a scarcity in Africa). OBJECTIVE: To identify urinary metabolite biomarkers that, combined with easy-to-measure clinical variables, would identify patients that should be further screened for CRC by colonoscopy. Ideal metabolites would be water-soluble and easily translated into a sensitive, low-cost point-of-care (POC) test. METHODS: Liquid-chromatography mass spectrometry (LC-MS/MS) was used to quantify 142 metabolites in spot urine samples from 514 Nigerian CRC patients and healthy controls. Metabolite concentration data and clinical characteristics were used to determine optimal sets of biomarkers for identifying CRC from non-CRC subjects. RESULTS: Our statistical analysis identified N1, N12-diacetylspermine, hippurate, p-hydroxyhippurate, and glutamate as the best metabolites to discriminate CRC patients via POC screening. Logistic regression modeling using these metabolites plus clinical data achieved an area under the receiver-operator characteristic (AUCs) curves of 89.2% for the discovery set, and 89.7% for a separate validation set. CONCLUSIONS: Effective urinary biomarkers for CRC screening do exist. These results could be transferred into a simple, POC urinary test for screening CRC patients in Africa.

Laparoscopic Liver Resection Difficulty Score-a Validation Study.

OBJECTIVE(S): The technical complexity of laparoscopic liver resection (LLR) poses unique challenges distinct from open surgery. An objective scoring system was developed that preoperatively quantifies the difficulty of LRR to help guide surgeon decision-making regarding the feasibility and safety of minimally invasive approaches. The aim of this multiinstitutional study was to externally validate this scoring system. METHODS: Patients who underwent LLR at two institutions were reviewed. LLR difficulty score (LDS) was calculated based on patient, tumor, and anatomic characteristics by two independent, blinded hepatobiliary surgeons. Surrogates of case complexity (e.g., conversion rate, operative time) were used for validation of this index. RESULTS: From 2006 to 2016, 444 LLR were scored as low (n = 94), intermediate (n = 98), and high difficulty (n = 152) with respective conversion rates of 5.3%, 15.7%, and 25%. Cases of higher LDS correlated with larger mean blood loss (203 ml vs. 331 ml vs. 635 ml). Mean operative and Pringle maneuver used were associated with increasing LDS (155 min vs. 202 min vs. 315 min and 14.4% vs. 29.7% vs. 45.1% respectively). These operative surrogates of difficulty correlated significantly with the LDS (all p < 0.0001). CONCLUSIONS: This comprehensive external validation of the LDS is robust and applicable in diverse patient populations. This LDS serves as a useful objective predictor of technical difficulty for LLR to help surgeons in selecting patients according to their individual operative experience and is valuable for preoperative risk estimation and stratification in randomized trials.

Predicting Residual Disease in Incidental Gallbladder Cancer: Risk Stratification for Modified Treatment Strategies.

INTRODUCTION: Re-operation is advised for patients with T1b or greater incidental gallbladder cancer (GBCA). The presence of residual disease (RD) impacts resectability, chemotherapy, and survival. This study created a preoperative model to predict RD at re-operation. METHODS: Patients with re-operation for incidental GBCA from 1992-2015 were included. The relationship between pathology data from initial cholecystectomy and RD at re-operation was assessed with logistic regression and classification and regression tree (CART) analysis. RESULTS: Two hundred fifty-four patients were included and 188 underwent definitive re-resection (74.0%). Distant RD was identified in 69 (27.2%) patients and locoregional only RD in 82 (32.3%). On multivariate analysis, T3 (OR 22.7, 95% CI 5.5-94.4) and poorly differentiated tumors (OR 4.3, 95% CI 1.4-13.3) were associated with RD (p < 0.001-0.012). AUC of multivariate model was 0.78 (95% CI 0.72-0.83). CART analysis split patients into groups based on percentage with RD: 87% RD with T3, 67% RD with T1b/T2 and poorly differentiated, and 35% RD with T1b/T2 and well/moderate differentiated tumors. CONCLUSION: Based on T stage and grade from cholecystectomy, this study developed a model for predicting RD at re-operation in incidental GBCA. This model delineates patient groups with variable percentages of RD and could be used to stratify high-risk patients for prospective trials.