Preoperative Frailty and Malnutrition in Surgical Oncology Patients Predicts Higher Postoperative Adverse Events and Worse Survival: Results of a Blinded, Prospective Trial.

BACKGROUND: Frailty, a multidimensional state leading to reduced physiologic reserve, is associated with worse postoperative outcomes. Despite the availability of various frailty tools, surgeons often make subjective assessments of patients' ability to tolerate surgery. The Risk Analysis Index (RAI) is a validated preoperative frailty assessment tool that has not been studied in cancer patients with plans for curative-intent surgery. METHODS: In this prospective, surgeon-blinded study, patients who had abdominal malignancy with plans for resection underwent preoperative frailty assessment with the RAI and nutrition assessment by measurement of albumin, prealbumin, and C-reactive protein (CRP). Postoperative outcomes and survival were assessed. RESULTS: The study included 220 patients, 158 (72%) of whom were considered frail (RAI ≥21). Frail patients were more likely to be readmitted within 30 and 90 days, (16% vs. 3% [P = 0.006] and 16% vs. 5% [P = 0.025], respectively). Patients with abnormal CRP, prealbumin, and albumin experienced higher rates of unplanned intensive care unit admission (CRP [27% vs. 8%; P < 0.001], albumin [30% vs. 10%; P < 0.001], prealbumin [29% vs. 9%; P < 0.001]) and increased postoperative mortality at 90 and 180 days. Survival was similar for frail and non-frail patients. In the multivariate analysis, frailty remained an independent risk factor for readmission (hazard ratio, 5.58; 95% confidence interval, 1.39-22.15; P = 0.015). In the post hoc analysis using the pre-cancer RAI score, the postoperative outcomes did not differ between the frail and non-frail patients. CONCLUSION: In conjunction with preoperative markers of nutrition, the RAI may be used to identify patients who may benefit from additional preoperative risk stratification and increased postoperative follow-up evaluation.

Stereotactic Body Radiation Therapy versus Surgical Resection for Stage I/II Hepatocellular Carcinoma.

SBRT is an emerging locoregional treatment modality for hepatocellular carcinoma (HCC). Although local tumor control rates seem encouraging, large-scale survival data comparing SBRT to surgical resection are lacking. We identified patients with stage I/II HCC from the National Cancer Database amenable for potential surgical resection. Patients undergoing hepatectomy were matched by propensity score (1:2) with patients who underwent SBRT as primary treatment. A total of 3787 (91%) and 366 (9%) patients underwent surgical resection or SBRT between 2004 and 2015, respectively. After propensity matching, the 5-year overall survival was 24% (95% CI 19-30%) in the SBRT group versus 48% (95% CI 43-53%) in the surgery group (p < 0.001). The association of surgery with overall survival was consistent in all subgroups. In patients treated with SBRT, a biologic effective dose (BED) of ≥100 Gy (31%, 95% CI 22%-40%) compared with BED < 100 Gy (13%, 95% CI 8-22%) was associated with a higher 5-year overall survival rate (hazard ratio of mortality of 0.58, 95% CI 0.43-0.77; p < 0.001). Surgical resection may be associated with prolonged overall survival compared with SBRT in patients with stage I/II HCC.

Outcomes after primary tumor resection of metastatic pancreatic neuroendocrine tumors: An analysis of the National Cancer Database.

INTRODUCTION: There is no consensus regarding the role of primary tumor resection for patients with metastatic pancreatic neuroendocrine tumors (panNET). We assessed surgical treatment patterns and evaluated the survival impact of primary tumor resection in patients with metastatic panNET. METHODS: Patients with synchronous metastatic nonfunctional panNET in the National Cancer Database (2004-2016) were categorized based on whether they underwent primary tumor resection. We used logistic regressions to assess associations with primary tumor resection. We performed survival analyses with Kaplan-Meier survival functions, log-rank test, and Cox proportional hazard regression within a propensity score matched cohort. RESULTS: In the overall cohort of 2613 patients, 68% (n = 839) underwent primary tumor resection. The proportion of patients who underwent primary tumor resection decreased over time from 36% (2004) to 16% (2016, p < 0.001). After propensity score matching on age at diagnosis, median income quartile, tumor grade, size, liver metastasis, and hospital type, primary tumor resection was associated with longer median overall survival (OS) (65 vs. 24 months; p < 0.001) and was associated with lower hazard of mortality (HR: 0.39, p < 0.001). CONCLUSION: Primary tumor resection was significantly associated with improved OS, suggesting that, if feasible, surgical resection can be considered for well-selected patients with panNET and synchronous metastasis.

Surveillance after resection of non-invasive intraductal papillary mucinous neoplasms (IPMN). A systematic review.

BACKGROUND: The ideal surveillance strategy after partial pancreatectomy for non-invasive IPMN remains undefined and existing guidelines provide conflicting recommendations. The present study was developed in anticipation of the joint meeting of the International Association of Pancreatology (IAP) and the Japan Pancreas Society (JPS) held in Kyoto in July 2022. METHODS: An international team of experts developed the four clinical questions (CQ) to operationalize issues pertaining to surveillance of patients in this context. A systematic review was designed following the PRISMA guidelines and registered in PROSPERO. The search strategy was executed in PubMed/Medline (Ovid), Embase, the Cochrane Library and Web of Science databases. Four investigators individually extracted data from the selected studies and drafted recommendations for each CQ. These were subsequently discussed and agreed upon that the IAP/JPS meeting. RESULTS: From a total of 1098 studies identified through the initial search, 41 studies were included in the review and informed the recommendations. No studies providing level one data were identified in this systematic review, all studies included were cohort or case-control studies. CONCLUSIONS: There is a lack of level 1 data addressing the issue of surveillance of patients following partial pancreatectomy for non-invasive IPMN. The definition of remnant pancreatic lesion in this setting is largely heterogeneous across all studies evaluated. Herein we propose an inclusive definition of remnant pancreatic lesions to guide future prospective efforts for reporting the natural history and long-term outcomes of these patients.

Time to Curative-Intent Surgery in Gastric Cancer Shows a Bimodal Relationship with Overall Survival.

BACKGROUND: Time to treatment (TTT) varies widely for patients with gastric cancer. We aimed to evaluate relationships between time to treatment, overall survival (OS), and other surgical outcomes in patients with stage I-III gastric cancer. METHODS: We identified patients with clinical stage I-III gastric cancer who underwent curative-intent gastrectomy within the National Cancer Database (2006-2015) and grouped them by treatment sequence: neoadjuvant chemotherapy or surgery upfront. We defined TTT as weeks from diagnosis to treatment initiation (neoadjuvant chemotherapy or definitive surgical procedure, respectively). Survival differences were assessed by Kaplan-Meier estimate, Cox proportional hazard regression, and log rank test. RESULTS: Among the 22,846 patients with stage I-III gastric cancer, most (56%) received surgery upfront. Median TTT was 5 weeks (IQR 4-7) and 6 weeks (IQR 3-9) for patients in the neoadjuvant and surgery upfront groups, respectively. In the neoadjuvant group, increasing TTT was significantly associated with increasing median OS up to TTT of 5 weeks, with no change in median OS when TTT was > 5 weeks. In the surgery group, increasing TTT was significantly associated with increasing median OS up to 6 weeks; however, increasing TTT between 14 and 21 weeks was associated with decreasing median OS. CONCLUSIONS: The relationship between time to treatment and survival outcomes is non-linear. Among patients who underwent surgery upfront, the relationship between time to treatment and OS was bimodal, suggesting that deferring definitive surgery, up to 14 weeks, is not associated with worse OS or oncologic outcomes. The relationship between time to treatment and overall survival among patients was bimodal, suggesting that deferring definitive surgery up to 14 weeks is not associated with worse OS.

Natural History of Stage IV Pancreatic Cancer. Identifying Survival Benchmarks for Curative-intent Resection in Patients With Synchronous Liver-only Metastases.

OBJECTIVE: To evaluate long-term oncologic outcomes of patients with stage IV pancreatic ductal adenocarcinoma and to identify survival benchmarks for comparison when considering resection in these patients. BACKGROUND: Highly selected cohorts of patients with liver-oligometastatic pancreas cancer have reported prolonged survival after resection. The long-term impact of surgery in this setting remains undefined because of a lack of appropriate control groups. METHODS: We identified patients with clinical stage IV pancreatic ductal adenocarcinoma with synchronous liver metastases within our cancer registry. We estimated overall survival (OS) among various patient subgroups using the Kaplan-Meier method. To mitigate immortal time bias, we analyzed long-term outcomes of patients who survived beyond 12 months (landmark time) from diagnosis. RESULTS: We identified 241 patients. Median OS was 7 months (95% CI, 5-9), both overall and for patients with liver-only metastasis (n=144). Ninety patients (38% of liver only; 40% of whole cohort) survived at least 12 months; those who received chemotherapy in this subgroup had a median OS of 26 months (95% CI, 17-39). Of these patients, those with resectable or borderline resectable primary tumors and resectable liver-only metastasis (n=9, 4%) had a median OS of 39 months (95% CI, 13-NR). CONCLUSIONS: The 4% of our cohort that were potentially eligible for surgery experienced a prolonged survival compared with all-comers with stage IV disease. Oncologic outcomes of patients undergoing resection of metastatic pancreas cancer should be assessed in the context of the expected survival of patients potentially eligible for surgery and not relative to all patients with stage IV disease.

Regional Patterns of Hospital-Level Guideline Adherence in Gastric Cancer: An Analysis of the National Cancer Database.

BACKGROUND: Adherence to evidence-based guidelines for gastric cancer is low, particularly at the hospital level, despite a strong association with improved overall survival (OS). We aimed to evaluate patterns of hospital and regional adherence to National Comprehensive Cancer Network guidelines for gastric cancer. METHODS: Using the National Cancer Database (2004-2015), we identified patients with stage I-III gastric cancer. Hospital-level guideline adherence was calculated by dividing the patients who received guideline adherent care by the total patients treated at that hospital. OS was estimated for each hospital. Associations between adherence, region, and survival were compared using mixed-effects, hierarchical regression. RESULTS: Among 576 hospitals, the median hospital guideline adherence rate was 25% (range 0-76%) and varied significantly by region (p = 0.001). Adherence was highest in the Middle Atlantic (29%) and lowest in the East South Central region (19%); hospitals in the New England, Middle Atlantic, and East North Central regions were more likely to be guideline adherent than those in the East South Central region (all p < 0.05), after adjusting for patient and hospital mix. Most (35%) of the adherence variation was attributable to the hospital. Median 2-year OS varied significantly by region. After adjusting for hospital and patient mix, hazard of mortality was 17% lower in the Middle Atlantic (hazard ratio 0.82, 95% confidence interval 0.74-0.90) relative to the East South Central region, with most of the variation (54%) attributable to patient-level factors. CONCLUSIONS: Hospital-level guideline adherence for gastric cancer demonstrated significant regional variation and was associated with longer OS, suggesting that efforts to improve guideline adherence should be directed toward lower-performing hospitals.

Outcomes After Surgical Palliation of Patients With Gastric Cancer.

INTRODUCTION: Surgery is an option for symptom palliation in patients with metastatic gastric cancer. Operative outcomes after palliative interventions are largely unknown. Herein, we assess the trends of surgical palliation use for patients with gastric cancer and describe outcomes of patients undergoing surgical palliation compared to nonsurgical palliation. METHODS: Patients with clinical Stage IV gastric cancer in the National Cancer Database (2004-2015) who received surgical or nonsurgical palliation were selected. We identified factors associated with palliative surgery. Survival differences were assessed by Kaplan-Meier estimate, Cox proportional hazard regression, and log rank test. RESULTS: Six thousand eight hundred twenty nine patients received palliative care for gastric cancer. Most patients (87%, n = 5944) received nonsurgical palliation: 29% radiation therapy, 57% systemic treatment, and 14% pain management. The number of patients receiving palliative care increased between 2004 and 2015; however, use of surgical palliation declined significantly (22% in 2004, 8% in 2015; P < 0.001). Median overall survival (OS) for the cohort was 5.65 mo (95% confidence interval 5.45-5.85); 1-year and 2-year OS were 24% and 9%, respectively. Older age at diagnosis and diagnosis between 2004 and 2006 were significantly associated with undergoing surgical palliation. Patients who underwent surgical palliation had significantly shorter median OS and a 20% higher hazard of mortality than those who received nonsurgical palliation. CONCLUSIONS: Patients with metastatic gastric cancer experience very short survival. While palliative surgery is used infrequently, the observed association with shorter median OS underscores the importance of careful patient selection. Palliative surgery should be offered judiciously and expectations about outcomes clearly established.

Diagnostic laparoscopy is underutilized in the staging of gastric adenocarcinoma regardless of hospital type: An US safety net collaborative analysis.

BACKGROUND: Diagnostic laparoscopy (DL) is a key component of staging for locally advanced gastric adenocarcinoma (GA). We hypothesized that utilization of DL varied between safety net (SNH) and affiliated tertiary referral centers (TRCs). METHODS: Patients diagnosed with primary GA eligible for DL were identified from the US Safety Net Collaborative database (2012-2014). Clinicopathologic factors were analyzed for association with use of DL and findings on DL. Overall survival (OS) was analyzed by Kaplan-Meier method. RESULTS: Among 233 eligible patients, 69 (30%) received DL, of which 24 (35%) were positive for metastatic disease. Forty percent of eligible SNH patients underwent DL compared to 21.5% at TRCs. Lack of insurance was significantly associated with decreased use of DL (OR 0.48, p < 0.01), while African American (OR 6.87, p = 0.02) and Asian race (OR 3.12, p ≤ 0.01), signet ring cells on biopsy (OR 3.14, p < 0.01), and distal tumors (OR 1.62, p < 0.01) were associated with increased use. Median OS of patients with a negative DL was better than those without DL or a positive DL (not reached vs. 32 vs. 12 months, p < 0.005, Figure 1). CONCLUSIONS: Results from DL are a strong predictor of OS in GA; however, the procedure is underutilized. Patients from racial minority groups were more likely to undergo DL, which likely accounts for higher DL rates among SNH patients.

Systemic therapy for duodenal adenocarcinoma: An analysis of the National Cancer Database (NCDB).

BACKGROUND: National Comprehensive Cancer Network guidelines recommend resection and adjuvant chemotherapy for patients with locally advanced duodenal adenocarcinoma. Outcomes after systemic treatment in this rare malignancy have not been well studied. We examined utilization patterns of systemic treatment and compared overall survival of patients receiving neoadjuvant therapy, surgery alone, and adjuvant therapy. METHODS: Patients with stage 0 to III duodenal adenocarcinoma undergoing curative-intent surgery were identified within the National Cancer Database from 2006 to 2015. Outcomes, including median overall survival and 30- and 90-day mortality, were compared based on treatment sequence (neoadjuvant, adjuvant, or surgery alone). Propensity score matching on likelihood of receiving systemic treatment and landmark analysis were performed to mitigate bias. RESULTS: Of the 2,956 patients meeting inclusion criteria, most patients with known clinical stage had locally advanced disease (72%), of which 53% received systemic therapy (8% neoadjuvant, 45% adjuvant). After landmark analysis on the propensity matched cohort, patients with locally advanced disease who received systemic treatment had longer median overall survival compared to patients who underwent surgery alone (49 vs 40 months, P = .018) and a 20% lower hazard of mortality (hazard ratio 0.80, 95% confidence interval 0.69-0.93, P = .003). Patients who received neoadjuvant and adjuvant therapy had similar survival outcomes. CONCLUSION: Adjuvant therapy was underutilized in patients with National Comprehensive Cancer Network guideline indications, despite an association with longer median overall survival and decreased hazard of mortality. Neoadjuvant therapy, although rarely used, had similar survival to adjuvant therapy. Given its other potential benefits, systemic treatment in the neoadjuvant setting may be a reasonable option in adequately selected patients with clinically advanced duodenal adenocarcinoma.

Adherence to guidelines at the patient- and hospital-levels is associated with improved overall survival in patients with gastric cancer.

BACKGROUND AND OBJECTIVES: Adherence to evidence-based guidelines in gastric cancer is low. We aimed to evaluate adherence to National Comprehensive Cancer Network (NCCN) Guidelines for gastric cancer at both patient- and hospital-levels and examine associations between guideline adherence and treatment outcomes, including overall survival (OS). METHODS: We applied stage-specific, annual NCCN Guidelines (2004-2015) to patients with gastric cancer treated with curative-intent within the National Cancer Database and compared characteristics of patients who did and did not receive guideline-adherent care. Hospitals were evaluated by guideline adherence rate. We identified associations with OS through multivariable Cox regression. RESULTS: Of 37 659 patients included, 32% received NCCN Guideline-adherent treatment. OS was significantly associated with both guideline adherence (51 months for patients receiving guideline-adherent treatment vs. 22 for patients receiving nonadherent treatment, p < 0.001). Treatment at a hospital with higher adherence was associated with longer OS (21 months for patients treated at lowest adherence quartile hospitals vs. 37 months at highest adherence quartile hospitals, p < 0.001), regardless of type of treatment received. CONCLUSIONS: Guideline-adherent treatment was strongly associated with longer median OS. Guideline adherence should be used as a benchmark for focused quality improvement for physicians taking care of patients with gastric cancer and institutions at large.

Surgical Treatment of Patients with Poorly Differentiated Pancreatic Neuroendocrine Carcinoma: An NCDB Analysis.

BACKGROUND: Consensus guidelines discourage resection of poorly differentiated pancreatic neuroendocrine carcinoma (panNEC) given its association with poor long-term survival. This study assessed treatment patterns and outcomes for this rare malignancy using the National Cancer Database (NCDB). METHODS: Patients with non-functional pancreatic neuroendocrine tumors in the NCDB (2004-2016) were categorized based on pathologic differentiation. Logistic and Cox proportional hazard regressions identified associations with resection and overall survival (OS). Survival was compared using Kaplan-Meier and log-rank tests. RESULTS: Most patients (83%) in the cohort of 8560 patients had well-differentiated tumors (panNET). The median OS was 47 months (panNET, 63 months vs panNEC, 17 months; p < 0.001). Surgery was less likely for older patients (odds ratio [OR], 0.97), patients with panNEC (OR, 0.27), and patients with metastasis at diagnosis (OR, 0.08) (all p < 0.001). After propensity score-matching of these factors, surgical resection was associated with longer OS (82 vs 29 months; p < 0.001) and a decreased hazard of mortality (hazard ratio [HR], 0.37; p < 0.001). Surgery remained associated with longer OS when stratified by differentiation (98 vs 41 months for patients with panNET and 36 vs 8 months for patients with panNEC). Overall survival did not differ between patients with panNEC who underwent surgery and patients with panNET who did not (both 39 months; p = 0.294). CONCLUSIONS: Poorly differentiated panNEC exhibits poorer survival than well-differentiated panNET. In the current cohort, surgical resection was strongly and independently associated with improved OS, suggesting that patients with panNEC who are suitable operative candidates should be considered for multimodality therapy, including surgery.

Minimally Invasive versus Open Liver Resection for Stage I/II Hepatocellular Carcinoma.

Minimally invasive liver resection (MILR) is increasingly used as a surgical treatment for patients with hepatocellular carcinoma (HCC). However, there is no large scale data to compare the effectiveness of MILR in comparison to open liver resection (OLR). We identified patients with stage I or II HCC from the National Cancer Database using propensity score matching techniques. Overall, 1931 (66%) and 995 (34%) patients underwent OLR or MILR between 2010 and 2015. After propensity matching, 5-year OS was similar in the MILR and OLR group (51.7% vs. 52.8%, p = 0.766). MILR was associated with lower 90-day mortality (5% vs. 7%, p = 0.041) and shorter length of stay (4 days vs. 5 days, p < 0.001), but higher rates of positive margins (6% vs. 4%, p = 0.001). An operation at an academic institution was identified as an independent preventive factor for a positive resection margin (OR 0.64: 95% CI 0.43-0.97) and 90-day mortality (OR 0.61; 95% CI 0.41-0.91). MILR for HCC is associated with similar overall survival to OLR, with the benefit of improved short term postoperative outcomes. The increased rate of positive margins after MILR requires further investigation, as do the differences in perioperative outcomes between academic and nonacademic institutions.

Clinical Presentation Patterns and Survival Outcomes of Hispanic Patients With Gastric Cancer.

BACKGROUND: Hispanic patients have a higher incidence of gastric cancer when compared to non-Hispanics. Outlining clinicodemographic characteristics and assessing the impact of ethnicity on stage-specific survival may identify opportunities to improve gastric cancer care for this population. METHODS: Patients with gastric cancer in the US Safety Net Collaborative (2012-2014) were retrospectively reviewed. Demographics, clinicopathologic characteristics, operative details, and outcomes were compared between Hispanic and non-Hispanic patients. Early onset gastric cancer was defined as age <50 years. Kaplan-Meier and Cox proportional-hazards models were used to identify the impact of ethnicity on disease-specific survival (DSS). RESULTS: Seven hundred and ninety-seven patients were included, of which 219 (28%) were Hispanic. Hispanic patients were more likely to seek care at safety-net hospitals (66 vs 39%) and be uninsured (36 vs 17%), and less likely to have a primary care provider (PCP) (46 vs 75%; all P<0.05). Hispanic patients were twice as likely to present with early onset gastric cancer (28 vs 15%) and were more frequently diagnosed in the emergency room (54 vs 37%) with both abdominal pain and weight loss (44 vs 31%; all P <0.05). Treatment paradigms, operative outcomes, and DSS were similar between Hispanic and non-Hispanic patients when accounting for cancer stage. Cancer stage, pathologically positive nodes, and negative surgical margins were independently associated with DSS. CONCLUSIONS: A diagnosis of gastric cancer must be considered in previously healthy Hispanic patients who present to the emergency room with both abdominal pain and weight loss. Fewer than 50% of Hispanic patients have a PCP, indicating poor outpatient support. Efforts to improve outpatient support and screening may improve gastric cancer outcomes in this vulnerable population.

Surgical resection of early stage hepatocellular carcinoma improves patient survival at safety net hospitals.

BACKGROUND AND OBJECTIVES: Surgical resection is indicated for hepatocellular carcinoma (HCC) patients with Child A cirrhosis. We hypothesize that surgical intervention and survival are limited by advanced HCC presentation at safety net hospitals (SNHs) versus academic medical centers (AMCs). METHODS: Patients with HCC and Child A cirrhosis in the US Safety Net Collaborative (2012-2014) were evaluated. Demographics, clinicopathologic features, operative characteristics, and outcomes were compared between SNHs and AMCs. Liver transplantation was excluded. Kaplan-Meier and Cox proportional-hazards models were used to identify the effect of surgery on overall (OS). RESULTS: A total of 689 Child A patients with HCC were identified. SNH patients frequently presented with T3/T4 stage (35% vs. 24%) and metastases (17% vs. 8%; p < .05). SNH patients were as likely to undergo surgery as AMC patients (17% vs. 18%); however, SNH patients were younger (56 vs. 64 years), underwent minor hepatectomy (65% vs. 38%), and frequently harbored well-differentiated tumors (23% vs. 2%; p < .05). On multivariate analysis, surgical resection and stage, but not hospital type, were associated with improved OS. CONCLUSIONS: Although SNH patients present with advanced HCC, survival outcomes for early stage HCC are similar at SNHs and AMCs. Identifying barriers to early diagnosis at SNH may increase surgical candidacy and improve outcomes.

Invasive central venous monitoring during hepatic resection: unnecessary for most patients.

BACKGROUND: Low central venous pressure (LCVP) anesthesia reduces blood loss during hepatic resection and historically has required a central venous catheter (CVC) for intra-operative monitoring. The aim of this study was to assess the effect of an evolution of practice to CVP monitoring without CVC on the perioperative outcomes after liver resection. METHODS: A retrospective study of partial hepatectomy patients from 2007 to 2016 who were over 18 years of age was performed. RESULTS: Of 3903 patients having partial hepatectomy, 2445 (62%) met inclusion criteria, and 404 (16%) had a CVC. Overall morbidity (33% non-CVC vs 38% CVC P = 0.076), major morbidity (16% vs 20% P = 0.067), and infective complications (superficial wound infection) 3% vs 4% P = 0.429; deep wound infection (5% vs 6% P = 0.720) did not differ between the two groups. In multivariate analysis, superficial wound infection, deep wound infection, and major complications were not associated with the presence of a CVC. All-cause mortality at 90 days was associated with CVC presence (OR 3.45, CI 1.74-6.85, P = 0.001) and age (OR 1.05, CI 1.02-1.08, P < 0.001). CONCLUSION: Since the adoption of non-invasive CVP monitoring, there has been no increase in adverse peri-operative outcomes.