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Neuroendocrine tumors (NETs) represent a heterogeneous group of tumors, with variable presentation based on the location of origin and degree of metastatic spread. There are no randomized control trials to guide surgical management; however, surgery remains the mainstay of treatment for most gastroenteropancreatic NETs based on retrospective studies. Metastatic disease is common at the time of presentation, particularly in the liver. There is a role for cytoreduction for improvement of both symptoms and survival. Robust prospective randomized data exists to support the use of medical therapies to improve progression-free and overall survival in patients with advanced, metastatic, and unresectable NETs.

Peritoneal metastases from colon cancer are a particularly challenging disease process given the limited response to systemic chemotherapy. In patients with isolated peritoneal metastases, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy offers a potential treatment option to these patients with limited peritoneal metastases as long as a complete cytoreduction is achieved. Decision about a patient's candidacy for this treatment modality should be undertaken by a multidisciplinary group at expert centers.

Context.— Claudin-18 is expressed in some gastric cancers. Clinical trials are evaluating it as a therapeutic target. Objectives.— To evaluate claudin-18 expression in intestinal metaplasia, dysplasia, and adenocarcinoma of the distal esophagus/gastroesophageal junction and stomach and to evaluate claudin-18 expression in gastric and nongastric neuroendocrine tumors as a marker of gastric origin. Design.— Samples included gastroesophageal junction with intestinal metaplasia (n = 40), dysplasia (n = 54), and adenocarcinoma (n = 20) and stomach with intestinal metaplasia (n = 79), dysplasia (n = 43), and adenocarcinoma (n = 25). Additionally, gastric (n = 40) and nongastric (n = 322) neuroendocrine tumors were included. Claudin-18 expression was evaluated for any staining as positive and by meeting clinical trial inclusion criteria (≥2+ intensity in ≥50% of tumor). Results.— Claudin-18 staining was not significantly different across dysplasia categories in the gastroesophageal junction (P = .11) or stomach (P = .12). The rate of positive staining was higher in gastroesophageal junction than stomach for intestinal metaplasia (37 of 40 [92.5%] versus 37 of 79 [46.8%]; P < .001) and high-grade dysplasia (33 of 38 [86.8%] versus 9 of 16 [56.3%]; P = .03). Intestinal metaplasia showed staining in 7 of 37 autoimmune gastritis samples (18.9%) compared with 30 of 42 samples without autoimmune gastritis (71.4%) (P < .001). Adenocarcinoma showed similar staining in gastroesophageal junction (15 of 20; 75.0%) and stomach (17 of 25; 68.0%) (P = .85). Eighty percent (32 of 40) of gastric neuroendocrine tumors were positive for claudin-18 expression, with 57.5% (23 of 40) meeting clinical trial inclusion criteria. Comparatively, 0.62% (2 of 322) of nongastric neuroendocrine tumors showed staining (P < .001). Conclusions.— Claudin-18 staining was similar in intestinal metaplasia, dysplasia, and adenocarcinoma. Claudin-18 was negative in most cases of intestinal metaplasia in autoimmune gastritis, indicating that intestinal metaplasia in this setting may differ from other forms. Claudin-18 was sensitive and specific for gastric origin in neuroendocrine tumors.

Introduction Adrenal myelolipomas (AMs) are rare, benign tumors without endocrine activity comprised of mature adipose and hematopoietic tissue. Surgical excision may be required for lesions which have associated symptoms, those that are growing, or have features concerning malignancy. Congenital adrenal hyperplasia (CAH) is often associated with adrenal masses such as AM. The majority of literature regarding AMs consists of case reports and case series with few describing giant AMs in the context of CAH. Case Presentation We present the case of a 50-year-old woman with CAH and surgical history relevant for left adrenalectomy who presented to the emergency department with abdominal pain. Computed tomography (CT) imaging led to a diagnosis of diverticulitis which was treated non-operatively. The scan also revealed a 20 × 13 × 23-cm right retroperitoneal mass causing mass effect on the duodenum, pancreas, right kidney, and inferior vena cava. CT-guided biopsy demonstrated adrenal and adipose tissue with hematolymphoid aggregates possibly representing myelolipoma but unable to rule out malignancy. Due to concern for retroperitoneal liposarcoma, the patient underwent an exploratory laparotomy with resection of > 40-cm right retroperitoneal mass, right nephrectomy, right adrenalectomy, and cholecystectomy. Final pathology demonstrated a myelolipoma with intra-tumoral ossification and hemorrhage as well as diffuse cortical hyperplasia with lymphoid aggregates. Due to acquired complete adrenal insufficiency, the patient required stress-dose steroids and steroid taper post-operatively. Conclusions Key points from this report include the occurrence of a giant AM in the context of CAH and special considerations in the diagnosis and operative approach of a giant retroperitoneal mass.

Background The burden of gastric cancer involving Hispanic patients in the United States is growing as both the population and the incidence of gastric cancer in this group increases. This burden is compounded by presentation with advanced disease and socioeconomic challenges shaping cancer care. We sought to describe the demographics, socioeconomic factors, treatment, and survival experience of Hispanic patients with gastric adenocarcinoma. Methods Patients with gastric adenocarcinoma diagnosed between 2004 and 2015 (n=90,737) in the National Cancer Database were retrospectively identified. Patients of Hispanic ethnicity were compared against non-Hispanic white patients. Surgical cohort was further analyzed, and 1:1 propensity score matching was used to balance covariates between Hispanic and non-Hispanic white surgical patients. Survival was compared using Kaplan-Meier method. Cox regression was used to determine prognostic factors for survival. Results Compared to non-Hispanic white patients, Hispanic patients are more likely to be younger, female, and healthier. They were more likely to be uninsured, reside in poorer neighborhoods and reside in areas with lower rates of education. Hispanic patients were more likely to live in a metropolitan area, travel shorter distances for healthcare, and receive treatment at an academic and high volume centers. Hispanic patients were more likely to have higher stage disease presentation, higher grade tumors, lymphovascular invasion, and poorly cohesive adenocarcinoma. Hispanic patients were more likely to receive surgery, but less likely to receive adjuvant therapy. In Cox regression of all patients, unmatched surgical patients, and matched surgical patients, Hispanic ethnicity was an independent prognostic factor of improved survival. Conclusions Hispanic patients with gastric adenocarcinoma present with several unfavorable clinicopathologic and socioeconomic factors. Paradoxically, these patients demonstrate improved survival. Further study is warranted to characterize disease biology in this population.

Colon cancer with high microsatellite instability is characterized by a high tumor mutational burden and responds well to immunotherapy. Mutations in polymerase ɛ, a DNA polymerase involved in DNA replication and repair, are also associated with an ultra-mutated phenotype. We describe a case where a patient with POLE-mutated and hypermutated recurrent colon cancer was treated with pembrolizumab. Treatment with immunotherapy in this patient also led to the clearance of circulating tumor DNA (ctDNA). ctDNA is beginning to emerge as a marker for minimal residual disease in many solid malignancies, including colon cancer. Its clearance with treatment suggests that the selection of pembrolizumab on the basis of identifying a POLE mutation on next-generation sequencing may increase disease-free survival in this patient.

INTRODUCTION: Neuroendocrine tumors are becoming increasingly prevalent with many patients presenting with or developing metastatic disease to the liver. METHODS: In this landmark series paper, we highlight the critical studies that have defined the surgical management of neuroendocrine tumor liver metastases, as well as several randomized control trials which have investigated strategies for systemic control of metastatic disease. RESULTS: Liver-directed surgical approaches and locally ablative procedures are recommended for patients with limited, resectable and in some cases, nonresectable tumor burden. Angiographic liver-directed techniques, such as transarterial embolization, chemoembolization, and radioembolization, offer another approach for management in patients with liver-predominant disease. Peptide receptor radionuclide therapy is a promising therapy for patients with hepatic and/or extrahepatic metastases. Various systemic medical therapies are also available as adjunct or definitive therapy for patients with metastatic disease. CONCLUSION: This article will review the current data regarding management of neuroendocrine liver metastases and highlight areas for future study.

Management of metastatic midgut neuroendocrine tumors (MNET) remains controversial. The benefits of resecting the primary tumor are not clear and advocated only for select patients. This study aimed to determine whether resection of the primary MNET in patients with untreated liver-only metastases has an impact on survival. This retrospective study reviewed data of the National Cancer Database from 2004 to 2015 for patients with liver-only metastatic MNETs and compared those who received resection of their primary MNET with those who did not. Patient demographics, tumor characteristics, and clinical outcomes were compared between the groups. The primary outcome was overall survival (OS) after adjustment for patient, demographic, and tumor-related factors. The study identified 1952 patients with a median age of 63 years (range, 18–90 years). The median primary tumor size was 2.4 cm (range, 0.1–20 cm). Of these patients, 1295 (66%) underwent resection of the primary tumor and 667 (34%) did not. The patients who underwent resection were younger (median age, 63 vs 65 years; p

The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of desmoplastic small round cell tumor, breast, and gastrointestinal stromal tumor specifically related to peritoneal surface malignancy. These guidelines are developed with input from leading experts including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

The Chicago Consensus Working Group provides multidisciplinary recommendations for palliative care specifically related to peritoneal surface malignancies. These guidelines are developed with input from leading experts including surgical oncologists, medical oncologists, gynecologic oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of neuroendocrine tumors specifically related to the management of peritoneal surface malignancy. These guidelines are developed with input from leading experts, including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

BackgroundChemotherapy has long been shown to confer a survival benefit in patients with metastatic esophageal cancer. However, not all patients with metastatic disease receive chemotherapy.AimTo evaluate a large cancer database of metastatic esophageal cancer cases to identify predictors of receipt to chemotherapy and survival.MethodsWe interrogated the National Cancer Database (NCDB) between 2004-2015 and included patients with M1 disease who had received or did not receive chemotherapy. A logistic regression model was used to examine the associations between chemotherapy and potential confounders and a Cox proportional hazards model was employed to examine the effect of chemotherapy on overall survival (OS). Propensity score analyses were further performed to balance measurable confounders between patients treated with and without chemotherapy.ResultsA total of 29182 patients met criteria for inclusion in this analysis, with 21911 (75%) receiving chemotherapy and 7271 (25%) not receiving chemotherapy. The median follow-up was 69.45 mo. The median OS for patients receiving chemotherapy was 9.53 mo (9.33-9.72) vs 2.43 mo (2.27-2.60) with no chemotherapy. Year of diagnosis 2010-2014 [odds ratio (OR): 1.29, 95% confidence interval (CI): 1.17-1.43, P value < 0.001], median income > $46000 (OR: 1.49, 95%CI: 1.27-1.75, P value < 0.001), and node-positivity (OR: 1.35, 95%CI: 1.20-1.52, P < 0.001) were independent predictors of receiving chemotherapy, while female gender (OR: 0.86, 95%CI: 0.76-0.98, P = 0.019), black race (OR: 0.76, 95%CI: 0.67-0.93, P = 0.005), uninsured status (OR: 0.41, 95%CI: 0.33-0.52, P < 0.001), and high Charlson Comorbidity Index (CCI) (OR for CCI ≥ 2: 0.61, 95%CI: 0.50-0.74, P < 0.001) predicted for lower odds of receiving chemotherapy. Modeling the effect of chemotherapy on OS using a time-dependent coefficient showed that chemotherapy was associated with improved OS up to 10 mo, after which there is no significant effect on OS. Moreover, uninsured status [hazard ratio (HR): 1.20, 95%CI: 1.09-1.31, P < 0.001], being from the geographic Midwest (HR: 1.07, 95%CI: 1.01-1.14, P = 0.032), high CCI (HR for CCI ≥ 2: 1.16, 95%CI: 1.07-1.26, P < 0.001), and higher tumor grade (HR for grade 3 vs grade 1: 1.28, 95%CI: 1.14-1.44, P < 0.001) and higher T stage (HR for T1 vs T4: 0.89, 95%CI: 0.84-0.95, P < 0.001) were independent predictors of worse OS on multivariable analyses.ConclusionIn this large, retrospective NCDB analysis, we identified several socioeconomic and clinicopathologic predictors for receiving chemotherapy and OS in patients with metastatic esophageal cancer. The benefit of chemotherapy on OS is time-dependent and favors early initiation. Focused outreach in lower income and underinsured patients is critical as receipt of chemotherapy is associated with improved OS.

Circulating tumor DNA (ctDNA) is increasingly being investigated as a tool to detect minimal residual disease in resected, stage I-III colorectal cancer. Recent ctDNA studies have indicated that detection of ctDNA following surgery for resectable colorectal cancer confers a significantly higher risk of recurrence than those with negative ctDNA postoperatively. In those with postoperative ctDNA positivity, clearance of minimal residual disease with adjuvant chemotherapy is a positive prognostic indicator. Lastly, ctDNA has demonstrated superior sensitivity to the conventional blood tumor marker carcinoembryonic antigen (CEA) and can offer median lead times of up to 11 months for radiographic detection of recurrence during the surveillance of resected, stage I-III colorectal cancer. In metastatic colorectal cancer (mCRC), there is growing evidence to suggest that plasma ctDNA can be used to monitor tumor response to conventional chemotherapy as well. The present case series demonstrated that plasma ctDNA is a predictor of tumor response to immunotherapy in patients with mCRC that are microsatellite stable or microsatellite instability high. Plasma ctDNA could serve as a dynamic marker of immunotherapy response even in colorectal tumors that were CEA non-producers. Overall, these findings add to ongoing efforts to establish the role of plasma ctDNA in monitoring response to immunotherapy in CRC.

181 Background: KRAS mutations have been widely characterized as markers of poor prognosis in CRC. In stage IV CRC, KRAS mutations are predictive of benefit to anti-EGFR therapy. ctDNA has increasingly been recognized as a prognostic biomarker in CRC as well. We evaluated the association between plasma metabolites and KRAS mutation or ctDNA status in a longitudinal, observational cohort of patients with stage I-IV CRC. Methods: This was a retrospective analysis of prospectively collected blood samples from a single-institute cohort of patients with stage I-IV CRC. All blood samples were collected at pre-chemotherapy baseline. A modified Epi proColon 2.0 CE (Epigenomics AG) assay was used for plasma ctDNA testing on the methylated SEPTIN9 gene (mSEPT9). ctDNA positivity was defined as a mSEPT9 percentage of methylation reference (PMR) value greater than zero. Up to 150 metabolites of central carbon metabolism were analyzed by mass spectrometry and high-performance liquid chromatography. Analytes were compared by relative area under the curve (AUC) and differences evaluated by ANOVA. The mean AUC was used in patients with metabolites measured from > 1 timepoint of collection. Patients were stratified by ctDNA status (positive or negative) and KRAS mutant (MT) or wildtype (WT) status. Results: A total of 32 patients were included with median age 65 years (range 20-90). The majority were female (53%) and had stage IV disease (78%). Of 25 patients with stage IV CRC, 88% had pre-chemotherapy blood samples collected in the first-line setting. Most patients were KRAS MT (44%) compared to KRAS WT (37%) or unknown KRAS status (19%). The most common KRAS MT subtypes were G12D (29%), G12V (29%), G13D (21%), and G12C (14%). The mean overall survival in this cohort was 27.4 months while the mean mSEPT9 PMR value was 2553.6. When stratified by ctDNA status, ctDNA positivity was associated with decreased levels of essential amino acids (lysine, methionine, threonine) and the non-essential amino acid arginine (all p < 0.05). Compared to KRAS WT tumors, KRAS MT tumors were associated with increased levels of proline, phenylalanine, and intermediates of glycolysis (lactate), MTA cycle (SAM, 5-Methioadenosine), and O-GlcNAcylation (GlcNac, all p < 0.05). Conclusions: We are the first to demonstrate the feasibility of associating central carbon metabolites with ctDNA and KRAS mutation status. As ctDNA positivity and KRAS MT status have evolving prognostic potential in CRC, associated metabolic signatures may identify metabolic pathways for novel biomarker development. Our findings also show that KRAS MT CRC appears to be enriched in intermediates of glycolytic, methyl donor, and O-GlcNAcylation pathways.

Simple Summary Circulating tumor DNA, or ctDNA, are fragments of tumor DNA that can be detected in the blood of patients with colorectal cancer. Measuring ctDNA levels in the blood has shown the potential to provide important information that can be helpful in the clinical care of patients with colorectal cancer. For example, in patients with colon cancer that has been removed by surgery, measuring ctDNA in the blood can predict the likelihood of cancer recurrence, while in those with metastatic colorectal cancer, measuring ctDNA can inform the clinician whether chemotherapy is effective at earlier timepoints than currently available tests. In this review, we discuss the results from ongoing studies describing the utility of ctDNA measurements across all stages of colorectal cancer. We also discuss the various clinical scenarios that ctDNA may have the most immediate impact in colorectal cancer management. Abstract Emerging data suggest that circulating tumor DNA (ctDNA) can detect colorectal cancer (CRC)-specific signals across both non-metastatic and metastatic settings. With the development of multiple platforms, including tumor-informed and tumor-agnostic ctDNA assays and demonstration of their provocative analytic performance to detect minimal residual disease, there are now ongoing, phase III randomized clinical trials to evaluate their role in the management paradigm of CRC. In this review, we highlight landmark studies that have formed the basis for ongoing studies on the clinically applicability of plasma ctDNA assays in resected, stage I–III CRC and metastatic CRC. We discuss clinical settings by which ctDNA may have the most immediate impact in routine clinical practice. These include the potential for ctDNA to (1) guide surveillance and intensification or de-intensification strategies of adjuvant therapy in resected, stage I–III CRC, (2) predict treatment response to neoadjuvant therapy in locally advanced rectal cancer inclusive of total neoadjuvant therapy (TNT), and (3) predict response to systemic and surgical therapies in metastatic disease. We end by considering clinical variables that can influence our ability to reliably interpret ctDNA dynamics in the clinic.

Immunotherapy has been established as a standard in select molecular subgroups of treatment-refractory advanced gastric cancer. However, its role in resectable gastric cancer where perioperative systemic therapy is the standard remains unclear. We present a case of a man who was diagnosed with resectable gastric cancer that was microsatellite stable but programmed death-ligand 1 (PD-L1) and Epstein-Barr Virus (EBV)-positive. Given extenuating circumstances of the SARS-CoV-2 pandemic, preferences to limit exposure to the healthcare setting, and the unique tumor molecular features, neoadjuvant pembrolizumab and capecitabine was pursued after multidisciplinary discussion. He was able to achieve a complete response to this neoadjuvant regimen with no further signs of radiographic or pathologic disease on follow-up. We highlight a dramatic response to this novel approach that represents among the first cases to support a potentially viable neoadjuvant chemoimmunotherapy strategy to resectable gastric cancer. In select patients, perioperative immunotherapy-based therapy may constitute a promising strategy in resectable gastric cancer and warrants further investigation.

Early-onset colorectal cancer has been on the rise in Western populations. Here, we compare patient characteristics between those with early- (&lt, 50 years) vs. late-onset (≥50 years) disease in a large multinational cohort of colorectal cancer patients (n = 2193). We calculated descriptive statistics and assessed associations of clinicodemographic factors with age of onset using mutually-adjusted logistic regression models. Patients were on average 60 years old, with BMI of 29 kg/m2, 52% colon cancers, 21% early-onset, and presented with stage II or III (60%) disease. Early-onset patients presented with more advanced disease (stages III–IV: 63% vs. 51%, respectively), and received more neo and adjuvant treatment compared to late-onset patients, after controlling for stage (odds ratio (OR) (95% confidence interval (CI)) = 2.30 (1.82–3.83) and 2.00 (1.43–2.81), respectively). Early-onset rectal cancer patients across all stages more commonly received neoadjuvant treatment, even when not indicated as the standard of care, e.g., during stage I disease. The odds of early-onset disease were higher among never smokers and lower among overweight patients (1.55 (1.21–1.98) and 0.56 (0.41–0.76), respectively). Patients with early-onset colorectal cancer were more likely to be diagnosed with advanced stage disease, to have received systemic treatments regardless of stage at diagnosis, and were less likely to be ever smokers or overweight.

Background. In this single-institution study, we applied the current (eighth edition) American Joint Committee on Cancer pathologic staging criteria to 64 low-grade mucinous neoplasms of the appendix (LAMNs), examined their histopathologic features, and studied the patients’ clinical outcomes. Design. Sixty-four LAMNs, with a median follow-up of 52 months, were reviewed. Results. The distribution of pathologic stages was pTis (n = 39), pT3 (n = 1), pT4a (n = 5), pT4aM1a (n = 8), and pT4aM1b (n = 11). Recurrence was observed in only 2 patients (both with pT4aM1b disease), one of whom died of disease. All remaining patients were disease-free after a median clinical follow-up of 60 months. Conclusions. Our study confirms that pTis LAMNs have an excellent prognosis and suggests that pT4a and pT4aM1a LAMNs may also have a low risk of developing progressive disease.

e16270 Background: PDAC is the third most fatal cancer, where most patients present with metastases at diagnosis. Previous studies, including a retrospective analysis from our single-center experience, suggests survival rates are significantly higher for those with lung-only metastases (mets) when compared to liver metastasis or other sites of metastases (liver+other). The objective of this analysis is to explore this difference based on sites and metastasis and the impact of chemotherapy from a national cohort. Methods: We identified PDAC patients (>18years) from with metastases to either 1) lung-only; 2) liver+other sites in the National Cancer Database diagnosed between 2010 and 2015.We analyzed patient characteristics, demographics, type of chemotherapy, and survival outcomes. Kaplan Meir survival curves were generated, and Cox proportional hazard models adjusted for age and sex were fit to evaluate associations between met site and survival. Survival was calculated from time of diagnosis to death and compared across mets site, receipt of chemotherapy, and treatment and type (single versus multi-agent). Results: 15359 PDAC patients were included in the analysis [51.6% male 48.4% female, mean age 69 years] of which 4512 (29.4%) patients had lung only mets and 10847 (70.6%) had liver + other mets. Median survival was 5.72 and 2.37 months for lung only vs. liver+other mets, respectively (log rank p

Appendiceal primary peritoneal surface malignancies are rare and include a broad spectrum of pathologies ranging from indolent disease to aggressive disease. As such, the data that drive the management of appendiceal peritoneal surface malignancies is generally not based on prospective clinical trial data, but rather consists of level 1 data based on retrospective studies and high-volume institutional experiences. Complete surgical debulking typically offers the best chance for long-term survival. This review highlights the landmark articles on which management of primary appendiceal peritoneal surface malignancies are based.

Background Multi-visceral resection often is used in the treatment of retroperitoneal sarcoma (RPS). The morbidity after distal pancreatectomy for primary pancreatic cancer is well-documented, but the outcomes after distal pancreatectomy for primary RPS are not. This study aimed to evaluate morbidity and oncologic outcomes after distal pancreatectomy for primary RPS. Methods In this study, 26 sarcoma centers that are members of the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) retrospectively identified consecutive patients who underwent distal pancreatectomy for primary RPS from 2008 to 2017. The outcomes measured were 90-day severe complications (Clavien-Dindo >= 3), postoperative pancreatic fistula (POPF) rate, and oncologic outcomes. Results Between 2008 and 2017, 280 patients underwent distal pancreatectomy for primary RPS. The median tumor size was 25 cm, and the median number of organs resected, including the pancreas, was three. In 96% of the operations, R0/R1 resection was achieved. The 90-day severe complication rate was 40 %. The grades B and C POPF complication rates were respectively 19% and 5% and not associated with worse overall survival. Administration of preoperative radiation and factors to mitigate POPF did not have an impact on the risk for the development of a POPF. The RPS invaded the pancreas in 38% of the patients, and local recurrence was doubled for the patients who had a microscopic, positive pancreas margin (hazard ratio, 2.0; p = 0.042). Conclusion Distal pancreatectomy for primary RPS has acceptable morbidity and oncologic outcomes and is a reasonable approach to facilitate complete tumor resection.

BRCA1 or 2 mutations result in higher cancer risk for breast cancer (BC) and epithelial ovarian cancer (EOC) for carriers than exists in the general population. Optimal breast imaging surveillance in these patients has not been well defined. An Institutional Review Board-approved, multi-institutional retrospective chart review was performed. Patients diagnosed with BRCA-associated EOC between 1990-2015 were identified; demographic and clinical data were collected and analyzed. 192 BRCA mutation–positive patients with EOC were identified. 16/192 (8.3%) women were diagnosed with BC following EOC, at a median of 50 (range 5-327) months following EOC diagnosis and median age 59.5 (45-84) years. Breast cancer was most commonly detected on mammogram 7/16 (44%) or clinical exam 7/16 (44%). 2/16 (12.5%) had occult BC found during risk-reducing mastectomy. 14 (88%) had early-stage (0-2) disease. At mean follow-up of 8.1 years, 6 (37.5%) patients with BC following EOC had died due to EOC. The risk of BC diagnosis following EOC in BRCA mutation carriers is low; most of these BCs are early stage and diagnosed with mammography or physical exam. Overall, survival in BRCA mutation carriers is dominated by EOC-related mortality. Breast cancer surveillance in BRCA mutation carriers following EOC should prioritize nonsurgical strategies.

Small bowel neuroendocrine tumors (SB NETs) are increasing in frequency and becoming more common in surgical practice. It is often difficult to make the diagnosis of a SB NET at an early stage, as the primary tumor tends to be small and patients are asymptomatic until there is regional or distant metastasis, when they develop abdominal pain, partial obstruction, or bleeding and/or develop carcinoid syndrome. Despite this advanced presentation at the time of diagnosis, patients with metastatic SB NETs, as compared to other gastrointestinal malignancies, have favorable survival, which can be improved by appropriate surgical interventions. With the lack of randomized studies, there is reasonable controversy surrounding the optimal management of patients with SB NETs. As such, treatment of these patients is driven primarily by physician experience and available data based predominantly on retrospective studies. Based on this, current recommendations advocate for patients with SB NETs (localized or metastatic) to be managed at experienced centers by a multidisciplinary team. Eligible patients should undergo surgical resection of primary and regional disease as outlined in this article. Additionally, patients with metastatic disease should be evaluated on a case by case basis to evaluate surgical options that may mitigate bowel symptoms (i.e., pain, intestinal angina, obstruction) and carcinoid symptoms (flushing, diarrhea, hemodynamic instability) and prolong survival. Unlike other gastrointestinal malignancies, aggressive surgical management of these patients, even in the context of unresectable metastatic disease, can improve patients' symptoms and long-term survival. The principles outlined in this article are geared to guide appropriate management of SB NET patients with improvement in quality of life and overall survival outcomes.

Studies have reported worse overall survival (OS) for adenosquamous carcinoma (ASC) compared to adenocarcinoma (AC) of the colon, but none have analyzed a national dataset for over 30 years.The National Cancer Database was queried from 2004 to 2016 for patients with ASC and AC of the colon. Kaplan-Meier survival analysis was performed to assess OS. Descriptive variables were evaluated using independent T-test and Chi-square analyses.332 ASC patients were compared to 496,950 AC patients. AC patients were older than ASC patients (68.6 vs. 64.4 years); p 0.001. Most ASC cancers presented with stage IV (41.3%) and poorly-differentiated disease (57.5%) compared to AC (22.4% and 17.7%). OS of the ASC cohort was 13.9 months. Median OS for stage IV AC versus stage IV ASC was significantly better (14.1 vs. 8.0 months); p 0.0001.This is the largest national database study to compare ASC with AC. Our findings confirm that unlike AC, ASC most frequently presents late stage, as poorly-differentiated lesions, and have worse OS.

The role of palliative surgery in the management of acute complications in patients with disseminated malignancy remains controversial given the complexity of assessing acute surgical risk and long-term oncologic outcome. With the emergence of checkpoint blockade immunotherapy, there appears to be an increasing role for historically palliative procedures as a bridge to systemic immunotherapy. This is especially evident in advanced microsatellite instability-high (MSI-H) colorectal cancer where malignant obstruction and fistula formation are more common and where immunotherapy with checkpoint blockade (anti-PD-1/PD-L1, anti-CTLA-4) has a high response rate with potential for favorable oncologic outcomes. We present a series of three patients with MSI-H metastatic colorectal cancer complicated by malignant bowel obstruction and fistula formation, who having progressed on standard chemotherapy, underwent palliative intervention as a bridge to immune checkpoint blockade with durable and clinically meaningful anti-cancer responses. These cases highlight the need to re-evaluate the role of historically palliative operations in the setting of disease progression for immunotherapy-responsive tumors.

In this chapter, we highlight the human factors approach to care in the cancer patient population. We review the impact of human factors in patients undergoing surgery for cancer and focus on ways to prevent any adverse consequences of these elements from significantly affecting outcomes.

Small bowel neuroendocrine tumors (SBNETs) are often indolent, but occasionally, patients present with acute symptoms requiring emergent operative intervention. Our aim was to determine whether emergency surgery for SBNETs affects long-term outcomes. An institutional database was reviewed to identify patients with SBNET diagnosed between 1990 and 2015. Need for emergency resection (ER) was compared with elective resection (ELR). One hundred and thirty-four patients met inclusion criteria. Median age was 59 years (range, 21–91), and median tumor size was 1.5 cm (range, 0.1–5). Median follow-up time was 5.5 years. One hundred (74.6%) patients had ELR, whereas 34 (25.4%) required ER. ELR had a higher number of lymph nodes resected (median 12.5 vs 8 ER, P = 0.04); however, there was no difference in the number of positive nodes (median 3 vs 2, P = 0.85). There were 45 (33.6%) recurrences (31 [31.0%] ELR vs 14 [41.7%] ER, P = 0.29) and 13 (9.7%) deaths (7 [7.0%] ELR; 6 [17.6%] ER). There was no significant difference in 5-year disease-free survival (ELR 72.6% vs ER 77.9%, P = 0.71) or overall survival (ELR 97.2% vs ER 96.6%, P = 0.81). Although patients undergoing ER have significantly fewer lymph nodes resected, they have comparable recurrence rates and long-term outcomes with those patients undergoing ER.

The incidence of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is rising. While the risk factors for HCC are well established with potential for early detection, most cases of ICC occur in patients without the presence of identifiable risk factors, leading to delayed diagnosis. The only treatment option that offers potential cure for both types of cancer is resection, but most patients are not candidates for surgery at presentation. In unresectable HCC and ICC, various locoregional therapies can be used to provide some degree of tumor control and improve overall survival. Options for locoregional therapy, outcomes, and current clinical recommendations for HCC and ICC will be discussed.

This comparative effectiveness study assesses the association of various neoadjuvant and adjuvant treatments for resectable gastric cancer with pathologic complete response, surgical margin status, and overall survival., Key Points Question Which treatment modality for gastric cancer is associated with the greatest effectiveness? Findings In this comparative effectiveness study of 3064 patients with resectable gastric cancer, which compared various treatment regimens of gastric cancer through a modality-by-modality approach, neoadjuvant chemoradiation had the highest pathologic complete response rate, while chemotherapy with timing unknown had the highest survival rate. Meaning These findings suggest that neoadjuvant chemoradiation may be superior to alternative treatment modalities for achieving pathologic complete response and that receipt of any chemotherapy may be associated with the greatest survival benefit for patients with resectable gastric cancer., Importance Treatment of resectable gastric cancer (RGC) uses a multimodal approach, including surgical treatment and chemotherapy with or without radiation therapy, and the optimal treatment strategy and timing of each of these modalities is unknown. Objective To investigate the association of various neoadjuvant and adjuvant treatment modalities with pathologic complete response (pCR), surgical margin status (SMS), and overall survival (OS) in RGC. Design, Setting, and Participants For this comparative effectiveness study, the National Cancer Database was interrogated to identify patients with RGC diagnosed from 2004 to 2015. Patients with gastric adenocarcinoma that was cT2-T4b, any N, and M0 and who underwent definitive surgical treatment were included. Main Outcomes and Measures The association of 9 treatment groups (ie, neoadjuvant chemoradiation only [nCRT], neoadjuvant chemotherapy only, adjuvant chemotherapy only [aCT], adjuvant chemoradiation only [aCRT], neoadjuvant chemotherapy and adjuvant radiation, chemotherapy with timing unknown [CTTU], chemoradiation therapy with timing unknown, radiation therapy with timing unknown (RTTU), and no perioperative therapy [NT]) with 3 end points (ie, pCR, SMS, and OS) was analyzed. The analysis was done using logistic regression and Cox proportional hazards models with adjustment for baseline characteristics. Data were analyzed from September 2019 through February 2020. Results Among 183 204 patients with RGC who were screened, 3064 patients were included in the analysis (median [IQR] age, 68 [57-77] years; 1764 [57.6%] men). There were 1584 tumors (51.7%) located in the antrum and 1539 stage 2 tumors (50.2%). On multivariable analyses among 1939 patients (owing to 137 patients with missing data for pCR and the exclusion of 988 patients with aCT and aCRT from pCR analysis), nCRT was associated with increased odds of pCR compared with NT, with the greatest odds ratio (OR) among all treatments (OR, 59.55; 95% CI, 10.63-333.56; P

Neuroendocrine tumors (NETs) account for 30% of small bowel (SB) neoplasms. The objectives of this study were to evaluate the incidence of multifocality in primary small bowel neuroendocrine tumors (SBNETs) and to examine the associated outcomes. Patients with multifocal SBNET were compared to those with a solitary lesion. Only patients who underwent diagnostic workup and surgical intervention at our institution were included in this study. The primary aim of our study was surgical outcomes and mortality and recurrence. The second aim of our study was to evaluate the utility of double-balloon enteroscopy (DBE) and capsule endoscopy. Of 178 patients with SBNETs during the study period, 85 met inclusion criteria. The mean age was 61.0 ± 12.6 years and 44.7% were male. The ileum was the primary tumor site for 66 patients (77.7%). Of DBE patients, 28 (62.2%) had additional lesions identified, of which 23 (82.1%) had NET confirmed on pathology. Average tumor size was 1.8 cm and most were well differentiated (89.9%), with Ki-67 of ≥ 2% (65.8%); 74.4% had nodal metastases and 51% of patients had stage IV disease. Forty-six patients (54.1%) had multifocal disease, of whom 37 (80.5%) had an ileal primary. No differences in survival or recurrence were seen for multifocal versus solitary disease. SBNETs have a high incidence of multifocality. DBE can be used in the preoperative assessment to detect multifocal NET. Multifocality has no impact on survival or recurrence outcomes.

Background: This study’s objective was to evaluate the change in sarcopenia score following neoadjuvant chemotherapy (NAC) and to correlate both sarcopenia and change in score with perioperative outcomes in patients with advanced resected gastric cancer. Methods: Multi-institutional analysis of patients with gastric cancer who underwent NAC and resection from 2000–2015 was performed. Demographic and perioperative data were included. Sarcopenia score was defined as CT measurement of total psoas muscle at L3, stratified by height (m). Sarcopenia was defined as a score Results: Of 36 patients, 19% were sarcopenic prior to NAC. Following NAC, 31% were sarcopenic, with 14% developing sarcopenia during NAC. One patient (3%) became non-sarcopenic. There were no significant differences in patient, disease, or surgery characteristics between patients who were sarcopenic vs. not. Patients with sarcopenia were more likely to have post-operative complications (P=0.05). There was no significant difference in hospital stay (P=0.7402) or survival (P=0.2317). Conclusions: A significant number of patients with gastric cancer become sarcopenic during NAC. Although patients with sarcopenia were nearly twice as likely to develop post-operative complications, this did not appear to impact length of stay (LOS) or survival.

Young women with breast cancer (BC) have an increased risk of contralateral breast cancer (CBC) compared with older women. This may contribute to the rising rates of bilateral mastectomy (BM), but it is unclear if BM leads to improved outcomes. A prospectively maintained database was reviewed. Patient and tumor characteristics, survival, and rate of CBC were compared in women age ≤40 years treated for unilateral Stage 1–3 BC from January 2000 through December 2013. Patients ranged in age from 20 to 40 (mean 36) years. Of the 446 women, 188 had breast conservation surgery (BCS), 78 had unilateral mastectomy (UM), and 183 had BM. UM, BCS, and BM groups did not differ in mean age, tumor type, hormone receptor status, or Her2 status. Patients in the BCS and BM group had smaller, fewer node-positive (p = 0.02) and lower grade tumors (p

Talimogene laherparepvec (T-VEC, IMLYGIC) is an oncolytic herpes virus type I used as intralesional therapy for the treatment of unresectable metastatic melanoma in a cutaneous, subcutaneous, or nodal location. Talimogene laherparepvec selectively replicates within and lyses tumor cells while producing granulocyte macrophage colony-stimulating factor (GM-CSF), which may promote an immune mediated antitumor response. Areas covered: The US Food and Drug Administration approved Talimogene laherparepvec in late 2015 following the completion of phase I, II and III trials that demonstrated safety and efficacy. Current NCCN practice guidelines have added Talimogene laherparepvec as a primary treatment for stage IIIB/C and stage IVM1a melanoma patients with evidence of good durable response rates, and this article sets out to review the use and safety and efficacy of T-VEC Expert opinion: Treatment options for locally advanced and metastatic melanoma are expanding with new developments in immunotherapy and immune checkpoint inhibitors. The ideal treatment of metastatic melanoma continues to be multimodal, combining systemic treatments, intralesional and regional therapies, surgery and radiotherapy to achieve optimal outcomes. Use of talimogene laherparepvec as intrelsional therapy has demonstrated promising effects in select patients with advanced melanoma. Future directions for Talimogene laherparepvec include combination therapies with other systemic immunotherapies such as anti-CTLA-4 antibody and anti-PD-1 drugs.

Management of metastatic midgut neuroendocrine tumors (MNET) remains controversial. The benefits of resecting the primary tumor are not clear and advocated only for select patients. This study aimed to determine whether resection of the primary MNET in patients with untreated liver-only metastases has an impact on survival.This retrospective study reviewed data of the National Cancer Database from 2004 to 2015 for patients with liver-only metastatic MNETs and compared those who received resection of their primary MNET with those who did not. Patient demographics, tumor characteristics, and clinical outcomes were compared between the groups. The primary outcome was overall survival (OS) after adjustment for patient, demographic, and tumor-related factors.The study identified 1952 patients with a median age of 63 years (range, 18-90 years). The median primary tumor size was 2.4 cm (range, 0.1-20 cm). Of these patients, 1295 (66%) underwent resection of the primary tumor and 667 (34%) did not. The patients who underwent resection were younger (median age, 63 vs 65 years; p 0.001) and had smaller primary tumors (median, 2.3 vs 3.0 cm; p 0.001). The patients with clinical T1 or T2 tumors were significantly less likely to undergo resection than those with stage T3 or T4 tumors (58.5% vs 89.7%; p 0.001). The median follow-up period was 43 months (range, 1-83 months). In the entire cohort, 483 deaths occurred, with a 5-year OS of 61%. The 5-year OS rate was 49% for the patients who underwent resection and 66% for those who did not (p 0.001). When the patients were grouped according to T stage, no OS difference between resection and no resection for stages T1 (p = 0.07) and T2 (p = 0.40) was identified. However, the 5-year OS rate was significantly better for the resected patient cohort with T3 (67.5% vs 37.2%; p 0.001) or T4 (59.8% vs 21.5%; p 0.001) tumors.The patients with treatment-naïve liver-only metastatic MNET had improved OS when the primary tumor was resected, particularly those with clinical stage T3 or T4 tumors. These patients may benefit from surgical resection of their primary tumor.