Risk Factors for Progression in Patients Undergoing Surveillance for Pancreatic Cysts.

OBJECTIVE: To identify risk factors associated with the progression of pancreatic cysts in patients undergoing surveillance. BACKGROUND: Previous studies of intraductal papillary mucinous neoplasms (IPMNs) rely on surgical series to determine malignancy risk and have inconsistently identified characteristics associated with IPMN progression. METHODS: We conducted a retrospective review of 2197 patients presenting with imaging concerning for IPMN from 2010 to 2019 at a single institution. Cyst progression was defined as resection or pancreatic cancer development. RESULTS: The median follow-up time was 84 months from the presentation. The median age was 66 years, and 62% were female. Ten percent had a first-degree relative with pancreatic cancer, and 3.2% had a germline mutation or genetic syndrome associated with an increased risk of pancreatic ductal adenocarcinoma (PDAC). Cumulative incidence of progression was 17.8% and 20.0% at 12 and 60 months postpresentation, respectively. Surgical pathology for 417 resected cases showed noninvasive IPMN in 39% of cases and PDAC with or without associated IPMN in 20%. Only 18 patients developed PDAC after 6 months of surveillance (0.8%). On multivariable analysis, symptomatic disease [hazard ratio (HR)=1.58; 95% CI: 1.25-2.01], current smoker status (HR=1.58; 95% CI: 1.16-2.15), cyst size (HR=1.26; 95% CI: 1.20-1.33), main duct dilation (HR=3.17; 95% CI: 2.44-4.11), and solid components (HR=1.89; 95% CI: 1.34-2.66) were associated with progression. CONCLUSIONS: Worrisome features on imaging at presentation, current smoker status, and symptomatic presentation are associated with IPMN progression. Most patients progressed within the first year of presentation to Memorial Sloan Kettering Cancer Center (MSKCC). Further investigation is necessary to develop personalized cyst surveillance strategies.

Early-onset Colorectal Cancer Patients Do Not Require Shorter Intervals for Post-surgical Surveillance Colonoscopy.

BACKGROUND & AIMS: Early-onset colorectal cancer (EO-CRC), diagnosed before age 50, is rising in incidence worldwide. Although post-surgical colonoscopy surveillance strategies exist, appropriate intervals in EO-CRC remain elusive, as long-term surveillance outcomes remain scant. We sought to compare findings of surveillance colonoscopies of EO-CRC with patients with average onset colorectal cancer (AO-CRC) to help define surveillance outcomes in these groups. METHODS: Single-institution retrospective chart review identified EO-CRC and AO-CRC patients with colonoscopy and no evidence of disease. Surveillance intervals and time to development of advanced neoplasia (CRC and advanced polyps [adenoma/sessile serrated]) were examined. For each group, 3 serial surveillance colonoscopies were evaluated. Statistical analyses were performed utilizing log-ranked Kaplan-Meier method and Cox proportional hazards. RESULTS: A total of 1259 patients with CRC were identified, with 612 and 647 patients in the EO-CRC and AO-CRC groups, respectively. Compared with patients with AO-CRC, patients with EO-CRC had a 29% decreased risk of developing advanced neoplasia from time of initial surgery to first surveillance colonoscopy (hazard ratio, 0.71; 95% confidence interval, 0.52-1.0). Average follow-up time from surgical resection to first surveillance colonoscopy was 12.6 months for both cohorts. Overall surveillance findings differed between cohorts (P = .003), and patients with EO-CRC were found to have less advanced neoplasia compared with their counterparts with AO-CRC (12.4% vs 16.0%, respectively). Subsequent colonoscopies found that, while patients with EO-CRC returned for follow-up surveillance colonoscopy earlier than patients with AO-CRC, the EO-CRC cohort did not have more advanced neoplasia nor non-advanced adenomas. CONCLUSIONS: Patients with EO-CRC do not have an increased risk of advanced neoplasia compared with patients with AO-CRC and therefore do not require more frequent colonoscopy surveillance than current guidelines recommend.

Morbidity and mortality in patients with stage IV pancreatic adenocarcinoma and acute cholangitis: Outcomes and risk prognostication.

BACKGROUND: Acute cholangitis (AC) is a common complication of pancreatic ductal adenocarcinoma (PDAC). Herein, we evaluated outcomes after the first AC episode and predictors of mortality and AC recurrence in patients with stage IV PDAC. METHODS: We conducted a single-center, retrospective observational study using institutional databases. Clinical data and outcomes for patients with stage IV PDAC and at least one documented episode of AC, were assessed. Overall survival (OS) was estimated using the Kaplan-Meier method, and Cox regression model was employed to identify predictors of AC recurrence and mortality. RESULTS: One hundred and twenty-four patients with stage IV PDAC and AC identified between January 01, 2014 and October 31, 2020 were included. Median OS after first episode of AC was 4.1 months (95 % CI, 4.0-5.5), and 30-day, 6, and 12-month survival was 86.2 % (95 % CI, 80.3-92.5), 37 % (95 % CI, 29.3-46.6 %) and 18.9 % (95 % CI, 13.1-27.3 %), respectively. Primary tumor in pancreatic body/tail (HR 2.29, 95 % CI: 1.26 to 4.18, p = 0.011), concomitant metastases to liver and other sites (HR 1.96, 95 % CI: 1.16 to 3.31, p = 0.003) and grade 3 AC (HR 2.26, 95 % CI: 1.45 to 3.52, p < 0.001), predicted worse outcomes. Intensive care unit admission, sepsis, systemic therapy, treatment regimen, and time to intervention did not predict survival or risk of recurrence of AC. CONCLUSIONS: AC confers significant morbidity and mortality in advanced PDAC. Worse outcomes are associated with higher grade AC, primary tumor location in pancreatic body/tail, and metastases to liver and other sites.

Feasibility of esophageal endoscopic submucosal dissection after radiofrequency ablation treatment in patients with Barrett's esophagus.

BACKGROUND AND AIMS: Radiofrequency ablation (RFA) is a well-established treatment for Barrett's esophagus (BE) in the United States. Similarly, endoscopic submucosal dissection (ESD) has been widely performed for early esophageal carcinoma. However, conducting ESD after RFA can be technically challenging. The aim of this study was to assess the feasibility and safety of ESD in patients with prior RFA. METHODS: This study was a single-center retrospective analysis of patients who underwent esophageal ESD after undergoing prior RFA treatment for BE. RESULTS: Of 44 esophageal ESD cases, 7 underwent prior RFA. In those 7 cases, the en bloc resection rate was 100%, and the R0 resection rate was 86%. No acute or delayed adverse events or rehospitalizations occurred in any patient. CONCLUSIONS: ESD may be a feasible and safe option for patients with a history of RFA. It could be considered for esophageal neoplasms in patients previously treated with RFA for BE.

Outcome of patients with perihilar cholangiocarcinoma and previous biliary instrumentation: an observational study.

BACKGROUND: To assess the outcome of previously untreated patients with perihilar cholangiocarcinoma who present to a cancer referral center with or without pre-existing trans-papillary biliary drainage. METHODS: Consecutive patients with a diagnosis of perihilar cholangiocarcinoma presenting between January 1, 2013, and December 31, 2017, were identified from a prospective surgical database and by a query of the institutional database. Of 237 patients identified, 106 met inclusion criteria and were reviewed. Clinical information was obtained from the Electronic Medical Record and imaging studies were reviewed in the Picture Archiving and Communication System. RESULTS: 73 of 106 patients (69%) presenting with a new diagnosis of perihilar cholangiocarcinoma underwent trans-papillary biliary drainage (65 endoscopic and 8 percutaneous) prior to presentation at our institution. 8 of the 73 patients with trans-papillary biliary drainage (11%) presented with and 5 developed cholangitis; all 13 (18%) required subsequent intervention; none of the patients without trans-papillary biliary drainage presented with or required drainage for cholangitis (p = 0.008). Requiring drainage for cholangitis was more likely to delay treatment (p = 0.012) and portended a poorer median overall survival (13.6 months, 95%CI [4.08, not reached)] vs. 20.6 months, 95%CI [18.34, 37.51] p = 0.043). CONCLUSION: Trans-papillary biliary drainage for perihilar cholangiocarcinoma carries a risk of cholangitis and should be avoided when possible. Clinical and imaging findings of perihilar cholangiocarcinoma should prompt evaluation at a cancer referral center before any intervention. This would mitigate development of cholangitis necessitating additional drainage procedures, delaying treatment and potentially compromising survival.

Patient metabolic profile defined by liver and muscle 18F-FDG PET avidity is independently associated with overall survival in gastric cancer.

BACKGROUND: PET-CT-based patient metabolic profiling is a novel concept to incorporate patient-specific metabolism into gastric cancer care. METHODS: Staging PET-CTs, demographics, and clinicopathologic variables of gastric cancer patients were obtained from a prospectively maintained institutional database. PET-CT avidity was measured in tumor, liver, spleen, four paired muscles, and two paired fat areas in each patient. The liver to rectus femoris (LRF) ratio was defined as the ratio of SUVmean of liver to the average SUVmean of the bilateral rectus femoris muscles. Kaplan-Meier and Cox-proportional hazards models were used to identify the impact of LRF ratio on OS. RESULTS: Two hundred and one patients with distal gastroesophageal (48%) or gastric (52%) adenocarcinoma were included. Median age was 65 years, and 146 (73%) were male. On univariate analysis, rectus femoris PET-CT avidity and LRF ratio were significantly associated with overall survival (p < 0.05). LRF ratio was significantly higher in males, early-stage cancer, patients with an ECOG 0 or 1 performance status, patients with albumin > 3.5 mg/dL, and those with moderately differentiated tumor histology. In multivariable regression, gastric cancer stage, albumin, and LRF ratio were significant independent predictors of overall survival (LRF ratio HR = 0.73 (0.56-0.96); p = 0.024). Survival curves showed that the prognostic impact of LRF was associated with metastatic gastric cancer (p = 0.009). CONCLUSIONS: Elevated LRF ratio, a patient-specific PET-CT-based metabolic parameter, was independently associated with an improvement in OS in patients with metastatic gastric cancer. With prospective validation, LRF ratio may be a useful, host-specific metabolic parameter for prognostication in gastric cancer.

First-line regorafenib with nivolumab and chemotherapy in advanced oesophageal, gastric, or gastro-oesophageal junction cancer in the USA: a single-arm, single-centre, phase 2 trial.

BACKGROUND: The addition of nivolumab to chemotherapy improves survival in patients with advanced oesophagogastric (oesophageal, gastric, or gastro-oesophageal junction) adenocarcinoma; however, outcomes remain poor. We assessed the safety and activity of regorafenib in combination with nivolumab and chemotherapy in the first-line treatment of advanced oesophagogastric adenocarcinoma. METHODS: This investigator-initiated, single-arm, phase 2 trial in adult patients (aged ≥18 years) with previously untreated, HER2-negative, metastatic oesophagogastric adenocarcinoma was done at the Memorial Sloan Kettering Cancer Center (New York, NY, USA). Eligible patients had measurable disease or non-measurable disease that was evaluable (defined by Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1) and Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received FOLFOX chemotherapy (fluorouracil [400 mg/m2 bolus followed by 2400 mg/m2 over 48 h], leucovorin [400 mg/m2], and oxaliplatin [85 mg/m2]) and nivolumab (240 mg) intravenously on days 1 and 15, and oral regorafenib (80 mg) on days 1-21 of a 28-day cycle. Treatment was continued until disease progression (defined by RECIST version 1.1), unacceptable toxicity, or withdrawal of consent. The primary endpoint was 6-month progression-free survival in the per-protocol population (ie, all participants who received a dose of all study treatments). The regimen would be considered worthy of further investigation if at least 24 of 35 patients were progression free at 6 months. Safety was assessed in all participants who received at least one dose of any study treatment. This trial is registered with ClinicalTrials.gov, NCT04757363, and is now complete. FINDINGS: Between Feb 11, 2021, and May 4, 2022, 39 patients were enrolled, received at least one dose of study drug, and were included in safety analyses. 35 patients were evaluable for 6-month progression-free survival. Median age was 57 years (IQR 52-66), nine (26%) patients were women, 26 (74%) were men, 28 (80%) were White, and seven (20%) were Asian. At data cutoff (March 3, 2023), median follow-up was 18·1 months (IQR 12·7-20·4). The primary endpoint was reached, with 25 (71%; 95% CI 54-85) of 35 patients progression free at 6 months. Nine (26%) of 35 patients had disease progression and one (3%) patient died; the death was unrelated to treatment. The most common adverse event of any grade was fatigue (36 [92%] of 39). The most common grade 3 or 4 adverse events were decreased neutrophil count (18 [46%]), hypertension (six [15%]), dry skin, pruritus, or rash (five [13%]), and anaemia (four [10%]). Serious treatment-related adverse events occurred in ten (26%) patients, which were acute kidney injury (three [8%]), hepatotoxicity (two [5%]), sepsis (two [5%]), dry skin, pruritus, or rash (one [3%]), nausea (one [3%]), and gastric perforation (one [3%]). There were no treatment-related deaths. INTERPRETATION: Regorafenib can be safely combined with nivolumab and chemotherapy and showed promising activity in HER2-negative metastatic oesophagogastric cancer. A randomised, phase 3 clinical trial is planned. FUNDING: Bristol Myers Squibb, Bayer and National Institutes of Health/National Cancer Institute.

Risk of Lymph Node Metastasis in T1b Gastric Cancer: An International Comprehensive Analysis from the Global Gastric Group (G3) Alliance.

OBJECTIVE: We sought to define criteria associated with low lymph node metastasis risk in patients with submucosal (pT1b) gastric cancer from 3 Western and 3 Eastern countries. SUMMARY BACKGROUND DATA: Accurate prediction of lymph node metastasis risk is essential when determining the need for gastrectomy with lymph node dissection following endoscopic resection. Under present guidelines, endoscopic resection is considered definitive treatment if submucosal invasion is only superficial, but this is not routinely assessed. METHODS: Lymph node metastasis rates were determined for patient groups defined according to tumor pathological characteristics. Clinicopathological predictors of lymph node metastasis were determined by multivariable logistic regression and used to develop a nomogram in a randomly selected subset that was validated in the remainder. Overall survival was compared between Eastern and Western countries. RESULTS: Lymph node metastasis was found in 701 of 3166 (22.1%) Eastern and 153 of 560 (27.3%) Western patients. Independent predictors of lymph node metastasis were female sex, tumor size, distal stomach location, lymphovascular invasion, and moderate or poor differentiation. Patients fulfilling the National Comprehensive Cancer Network guideline criteria, excluding the requirement that invasion not extend beyond the superficial submucosa, had a lymph node metastasis rate of 8.9% (53/594). Excluding moderately differentiated tumors lowered the rate to 3.4% (10/296). The nomogram's area under the curve was 0.690. Regardless of lymph node status, overall survival was better in Eastern patients. CONCLUSIONS: The lymph node metastasis rate was lowest in patients with well differentiated tumors that were ≤3 cm and lacked lymphovascular invasion. These criteria may be useful in decisions regarding endoscopic resection as definitive treatment for pT1b gastric cancer.

Factors associated with detection of hereditary diffuse gastric cancer on endoscopy in individuals with germline CDH1 mutations.

BACKGROUND AND AIMS: Individuals with germline pathogenic CDH1 variants have a high risk of hereditary diffuse gastric cancer. The sensitivity of EGD in detecting signet ring cell carcinoma (SRCC) in this population is low. We aimed to identify endoscopic findings and biopsy practices associated with detection of SRCC. METHODS: This retrospective cohort included individuals with a germline pathogenic/likely pathogenic CDH1 variant undergoing at least 1 EGD at Memorial Sloan Kettering Cancer Center between January 1, 2006, and March 25, 2022. The primary outcome was detection of SRCC on EGD. Findings on gastrectomy were also assessed. The study included periods before and after implementation of the Cambridge protocol for endoscopic surveillance, allowing for assessment of a spectrum of biopsy practices. RESULTS: Ninety-eight CDH1 patients underwent at least 1 EGD at our institution. SRCC was detected in 20 (20%) individuals on EGD overall and in 50 (86%) of the 58 patients undergoing gastrectomy. Most SRCC foci were detected in the gastric cardia/fundus (EGD, 50%; gastrectomy, 62%) and body/transition zone (EGD, 60%; gastrectomy, 62%). Biopsy results of gastric pale mucosal areas were associated with detection of SRCC (P < .01). The total number of biopsy samples taken on EGD was associated with increased detection of SRCC (P = .01), with 43% detected when ≥40 samples were taken. CONCLUSIONS: Targeted biopsy sampling of gastric pale mucosal areas and increasing number of biopsy samples taken on EGD were associated with detection of SRCC. SRCC foci were mostly detected in the proximal stomach, supporting updated endoscopic surveillance guidelines. Further studies are needed to refine endoscopic protocols to improve SRCC detection in this high-risk population.

Endoscopic and Surgical Management of Non-Metastatic Ampullary Neuroendocrine Neoplasia: A Multi-Institutional Pancreas2000/EPC Study.

INTRODUCTION: Ampullary neuroendocrine neoplasia (NEN) is rare and evidence regarding their management is scarce. This study aimed to describe clinicopathological features, management, and prognosis of ampullary NEN according to their endoscopic or surgical management. METHODS: From a multi-institutional international database, patients treated with either endoscopic papillectomy (EP), transduodenal surgical ampullectomy (TSA), or pancreaticoduodenectomy (PD) for ampullary NEN were included. Clinical features, post-procedure complications, and recurrences were assessed. RESULTS: 65 patients were included, 20 (30.8%) treated with EP, 19 (29.2%) with TSA, and 26 (40%) with PD. Patients were mostly asymptomatic (n = 46; 70.8%). Median tumor size was 17 mm (12-22), tumors were mostly grade 1 (70.8%) and pT2 (55.4%). Two (10%) EP resulted in severe American Society for Gastrointestinal Enterology (ASGE) adverse post-procedure complications and 10 (50%) were R0. Clavien 3-5 complications did not occur after TSA and in 4, including 1 postoperative death (15.4%) of patients after PD, with 17 (89.5%) and 26 R0 resection (100%), respectively. The pN1/2 rate was 51.9% (n = 14) after PD. Tumor size larger than 1 cm (i.e., pT stage >1) was a predictor for R1 resection (p < 0.001). Three-year overall survival and disease-free survival after EP, TSA, and PD were 92%, 68%, 92% and 92%, 85%, 73%, respectively. CONCLUSION: Management of ampullary NEN is challenging. EP should not be performed in lesions larger than 1 cm or with a endoscopic ultrasonography T stage beyond T1. Local resection by TSA seems safe and feasible for lesions without nodal involvement. PD should be preferred for larger ampullary NEN at risk of nodal metastasis.

A Novel Microbiome Signature in Gastric Cancer: A Two Independent Cohort Retrospective Analysis.

OBJECTIVE: The microbiome is hypothesized to have a significant impact on cancer development. In gastric cancer (GC), Helicobacter pylori is an established class I carcinogen. However, additional organisms in the intratumoral microbiome play an important role in GC pathogenesis and progression. In this study, we characterize the full spectrum of the microbes present within GC and identify distinctions among molecular subtypes. METHODS: A microbiome bioinformatics pipeline that is generalizable across multiple next-generation sequencing platforms was developed. Microbial profiles for alpha diversity and enrichment were generated for 2 large, demographically distinct cohorts: (1) internal Memorial Sloan Kettering Cancer Center (MSKCC) and (2) The Cancer Genome Atlas (TCGA) cohorts. A total of 520 GC samples were compared with select tumor-adjacent nonmalignant samples. Microbiome differences among the GC molecular subtypes were identified. RESULTS: Compared with nonmalignant samples, GC had significantly decreased microbial diversity in both MSKCC and TCGA cohorts ( P <0.05). Helicobacter , Lactobacillus , Streptococcus , Prevotella , and Bacteroides were significantly more enriched in GC samples when compared with nonmalignant tissue ( P <0.05). Microsatellite instability-high GC had distinct microbial enrichment compared with other GC molecular subtypes. CONCLUSION: Distinct patterns of microbial diversity and species enrichment were identified in patients with GC. Given the varied spectrum of disease progression and treatment response of GC, understanding unique microbial signatures will provide the landscape to explore key microbial targets for therapy.

Multiinstitutional Validation Study of Cyst Fluid Protein Biomarkers in Patients With Cystic Lesions of the Pancreas.

OBJECTIVE: Prospective evaluation of 2 clinical-molecular models in patients with unknown pathology who underwent endoscopic ultrasound with fine-needle aspiration (EUS-FNA) for a cystic lesion of the pancreas. SUMMARY OF BACKGROUND DATA: Preoperative prediction of histologic subtype (mucinous vs nonmucinous) and grade of dysplasia in patients with pancreatic cystic neoplasms is challenging. Our group has previously published 2 clinical-molecular nomograms for intraductal papillary mucinous neoplasms (IPMN) that incorporated both clinical/radiographic features and cyst fluid protein markers (sFASL, CA72-4, MMP9, IL-4). METHODS: This multiinstitutional study enrolled patients who underwent EUS-FNA for a cystic lesion of the pancreas. Treatment recommendations regarding resection were based on standard clinical, radiographic, and endoscopic features. Predicted probabilities of high-risk IPMN (high-grade dysplasia/invasive cancer) were calculated using the previously developed clinical-molecular nomograms. RESULTS: Cyst fluid was obtained from 100 patients who underwent diagnostic EUS-FNA. Within this group there were 35 patients who underwent resection, and 65 were monitored radiographically. Within the group that underwent resection, 26 had low-risk IPMN or benign non-IPMN lesions, and 9 had high-risk IPMN. Within the surveillance group, no patient progressed to resection or developed cancer after a median follow-up of 12months (range: 0.5-38). Using the clinical/radiographic nomogram alone, 2 out of 9 patients with high-risk IPMN had a predicted probability >0.5. In the clinical-molecular models, 6 of 9 patients in model 1, and 6 of 9 in model 2, had scores >0.5. CONCLUSIONS: This prospective study of patients with unknown cyst pathology further demonstrates the importance of cyst fluid protein analysis in the preoperative identification of patients with high-risk IPMN. Longer follow-up is necessary to determine if this model will be useful in clinical practice.

An Expert, Multidisciplinary Perspective on Best Practices in Biomarker Testing in Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is a rare and aggressive malignancy that arises from the intrahepatic biliary tree and is associated with a poor prognosis. Until recently, the treatment landscape of advanced/metastatic iCCA has been limited primarily to chemotherapy. In recent years, the advent of biomarker testing has identified actionable genetic alterations in 40%-50% of patients with iCCA, heralding an era of precision medicine for these patients. Biomarker testing using next-generation sequencing (NGS) has since become increasingly relevant in iCCA; however, several challenges and gaps in standard image-guided liver biopsy and processing have been identified. These include variability in tissue acquisition relating to the imaging modality used for biopsy guidance, the biopsy method used, number of passes, needle choice, specimen preparation methods, the desmoplastic nature of the tumor, as well as the lack of communication among the multidisciplinary team. Recognizing these challenges and the lack of evidence-based guidelines for biomarker testing in iCCA, a multidisciplinary team of experts including interventional oncologists, a gastroenterologist, medical oncologists, and pathologists suggest best practices for optimizing tissue collection and biomarker testing in iCCA.

Technical feasibility of salvage endoscopic submucosal dissection after chemoradiation for locally advanced rectal adenocarcinoma.

BACKGROUND AND AIMS: The standard treatment of locally advanced rectal cancer is chemoradiation (CRT) followed by proctectomy and adjuvant chemotherapy. However, there is an emerging role for nonsurgical management after CRT or total neoadjuvant therapy (TNT) consisting of CRT and neoadjuvant chemotherapy. Endoscopic submucosal dissection (ESD) after CRT or TNT for rectal cancer, termed "salvage ESD," may be a viable nonsurgical option for carefully selected patients. We aimed to evaluate the feasibility and safety of salvage ESD. METHODS: A retrospective chart review of cases of salvage ESD for locally advanced rectal cancer and standard ESD for rectal tumors without prior CRT from July 2018 to August 2020 at our institution was performed. Clinical factors and imaging, procedural, and pathology results were collected and compared. RESULTS: Twelve salvage ESD cases were compared with 27 standard ESD cases. Before CRT, 83.3% of lesions in the salvage ESD group were initially clinically staged as T3. The en-bloc resection rates were 92.7% and 91.7% (P = 1.00) and R0 resection rates 66.7% and 75.0% (P = .55) for the standard and salvage groups, respectively. In the salvage ESD group, no adverse events were observed, and 75.0% of the adenocarcinomas in the salvage ESD group had morphologically changed to hyperplasia or adenoma after CRT, with no identifiable lesions greater than T1 tumor depth. CONCLUSIONS: Salvage ESD for locally advanced rectal cancer is technically feasible with low adverse event rates. There may be a diagnostic role in salvage ESD in assessing pathologic response to CRT and a possible therapeutic role in resection of residual lesions with the potential to avoid surgery.

Effectiveness of a surveillance program of upper endoscopy for upper gastrointestinal cancers in Lynch syndrome patients.

BACKGROUND AND AIMS: Lynch syndrome (LS) is the most common cause of hereditary colorectal cancer and is associated with an increased lifetime risk of gastric and duodenal cancers of 8-16% and 7%, respectively; therefore, we aim to describe an esophagogastroduodenoscopy (EGD) surveillance program for upper gastrointestinal (GI) precursor lesions and cancer in LS patients. METHODS: Patients who either had positive genetic testing or met clinical criteria for LS who had a surveillance EGD at our institution from 1996 to 2017 were identified. Patients were included if they had at least two EGDs or an upper GI cancer detected on the first surveillance EGD. EGD and pathology reports were extracted manually. RESULTS: Our cohort included 247 patients with a mean age of 47.1 years (SD 12.6) at first EGD. Patients had a mean of 3.5 EGDs (range 1-16). Mean duration of follow-up was 5.7 years. Average interval between EGDs was 2.3 years. Surveillance EGD detected precursor lesions in 8 (3.2%) patients, two (0.8%) gastric cancers and two (0.8%) duodenal cancers. Two interval cancers were diagnosed: a duodenal adenocarcinoma was detected 2 years, 8 months after prior EGD and a jejunal adenocarcinoma was detected 1 year, 9 months after prior EGD. CONCLUSIONS: Our data suggest that surveillance EGD is a useful tool to help detect precancerous and cancerous upper GI lesions in LS patients. To our knowledge, this is the first study to examine a program of surveillance EGDs in LS patients. More data are needed to determine the appropriate surveillance interval.

Clinical features of young onset colorectal cancer patients from a large cohort at a single cancer center.

PURPOSE: The aim of this study is to describe the demographics and clinical features of patients with young onset (YO) CRC. METHODS: A retrospective review of patients with CRC diagnosed between ages 20 and 49 years was evaluated at the Memorial Sloan Kettering Cancer Center from 1/2004 to 6/2019. We excluded those with a hereditary CRC syndrome, inflammatory bowel disease, or prior CRC diagnosis. Patient demographics; presenting symptoms; medical, surgical, and smoking history; family history of cancer; tumor characteristics; and pathology were obtained from the electronic medical record. RESULTS: We identified 3856 YO CRC patients (median age CRC diagnosis 43; 52.5% male). A total of 59.1% were overweight or obese (32.2% and 26.9%, respectively). Most (90.1%) had no family history of CRC in a first-degree relative; 56.3% of patients reported being never smokers; 5.2% had diabetes. The most common presenting symptoms were rectal bleeding (47.7%), abdominal pain/bloating (33.1%), and change in bowel habits (24.7%). The majority presented with left-sided cancers (77.3%), at late-stage disease (68.4% at stages 3 or 4). CONCLUSION: Most YO CRC patients presented with rectal bleeding or abdominal pain, left-sided cancers, and later-stage disease and had no family history of CRC in a first-degree relative. Over half were overweight and obese and were more likely to have never smoked. More data are needed to better understand YO CRC risk factors and to help identify high-risk populations who may benefit from earlier screening.

Robotic Gastrectomy for Gastric Adenocarcinoma in the USA: Insights and Oncologic Outcomes in 220 Patients.

BACKGROUND: While multiple Asian and a few Western retrospective series have demonstrated the feasibility and safety of robotic-assisted gastrectomy for gastric cancer, its reliability for thorough resection, especially for locoregional disease, has not yet been firmly established, and reported learning curves vary widely. To support wider implementation of robotic gastrectomy, we evaluated the learning curve for this approach, assessed its oncologic feasibility, and created a selection model predicting the likelihood of conversion to open surgery in a US patient population. PATIENTS AND METHODS: We retrospectively reviewed data on all consecutive patients who underwent robotic gastrectomy at a high-volume institution between May 2012 and March 2019. RESULTS: Of the 220 patients with gastric cancer selected to undergo curative-intent robotic gastrectomy, surgery was completed using robotics in 159 (72.3%). The median number of removed lymph nodes was 28, and ≥ 15 lymph nodes were removed in 94% of procedures. Surgical time decreased steadily over the first 60-80 cases. Complications were generally minor: 7% of patients experienced complications of grade 3 or higher, with an anastomotic leak rate of 2% and mortality rate 0.9%. Factors predicting conversion to open surgery included neoadjuvant chemotherapy, BMI ≥ 31 kg/m2, and tumor size ≥ 6 cm. CONCLUSIONS: These findings support the safety and oncologic feasibility of robotic gastrectomy for selected patients with gastric cancer. Proficiency can be achieved by 20 cases and mastery by 60-80 cases. Ideal candidates for this approach are patients with few comorbidities, BMI < 31 kg/m2, and tumors < 6 cm.

Longitudinal Analysis of Quality-of-Life Recovery After Gastrectomy for Cancer.

OBJECTIVE: The purpose of this study was to identify factors associated with quality-of-life recovery after gastrectomy. METHODS: Patients anticipated to undergo gastric cancer resection were invited to complete the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and STO22 surveys in the preoperative setting and at 0-1.5 months (early), > 1.5-6 months (intermediate), and > 6-18 months (late) following resection. Quality-of-life recovery was measured as paired differences between pre- and postoperative results. Multivariable linear regression identified factors associated with preoperative quality of life and degree of change following resection. RESULTS: Across 393 participants, response rates at the intermediate and late postoperative time points were 58% (n = 228) and 71% (n = 277), respectively. Relative to baseline, median global health scale decreased in the early (- 15.1 pts, p < 0.001) and intermediate (- 3.6 pts, p = 0.02) time points, but recovered by the late time point (+ 1.2 pts, p = 0.411). Relative to distal/subtotal gastrectomy, proximal/total gastrectomy was associated with worse recovery in both the early and late time points. Surgical complications were associated with worse early recovery. Patients who presented with locally advanced tumors (T3-T4) had lower preoperative quality-of-life scores, and more readily recovered to baseline after surgery. A minimally invasive approach was not associated with postoperative recovery. CONCLUSIONS: Most patients recover to baseline within 1 year following major gastrectomy, and recovery is easier with more limited resections. Patients with locally advanced tumors tend to have poorer baseline quality of life, which may improve following resection.

Comparison of Long- and Short-term Outcomes in 845 Open and Minimally Invasive Gastrectomies for Gastric Cancer in the United States.

BACKGROUND: Few Western studies have evaluated the long-term oncologic outcomes of minimally invasive surgery (MIS) approaches to gastrectomy for gastric cancer. This study aimed to compare the outcomes between minimally invasive and open gastrectomies and between laparoscopic and robotic gastrectomies at a high-volume cancer center in the United States. METHODS: The study analyzed data for all patients undergoing curative gastrectomy for gastric adenocarcinoma from January 2007 to June 2017. Postoperative complications and disease-specific survival (DSS) were compared between surgical approaches. RESULTS: The median follow-up period for the 845 patients in this study was 38.5 months. The stage-stratified 5-year DSS did not differ significantly between open surgery (n = 534) and MIS (n = 311). The MIS approach resulted in significantly fewer complications, as confirmed by adjusted comparison (odds ratio [OR], 0.70; range, 0.49-1.00; p = 0.049). After adjustment, the two groups did not differ in terms of DSS (hazard ratio [HR], 0.83; range, 0.55-1.25; p = 0.362). The robotic operations (n = 190) had fewer conversions to open procedure (p = 0.010), a shorter operative time (212 vs 240 min; p < 0.001), more dissected nodes (27 vs 22; p < 0.001), fewer Clavien-Dindo grade ≥3 complications (5.8% vs 13.2%; p = 0.023), and a shorter postoperative stay (5 vs 6 days; p = 0.045) than the laparoscopic operations (n = 121). The DSS rate did not differ between the laparoscopic and robotic groups. CONCLUSION: The study findings demonstrated the long-term survival and oncologic equivalency of MIS gastrectomy and the open approach in a Western cohort, supporting the use of MIS at centers that have adequate experience with appropriately selected patients.

Bevacizumab does not increase risk of perforation in patients undergoing percutaneous endoscopic gastrostomy or jejunostomy placement.

INTRODUCTION: Bevacizumab is a humanized anti-vascular endothelial growth factor monoclonal antibody used in the treatment of cervical cancer, ovarian cancer, colorectal cancer, lung cancer, renal cell cancer, and recurrent glioblastomas. Its approval by US FDA was issued with a black box warning that its use has been associated with a risk of gastrointestinal (GI) tract perforation and that it should be discontinued in patients who have experienced such. The reported incidence of GI perforation in those receiving bevacizumab is as high as 3%. However, the incidence of GI perforation in those receiving bevacizumab undergoing GI endoscopic procedures has not been well studied. METHODS: A retrospective, single-center observational study was conducted at Memorial Sloan Kettering Cancer Center (MSKCC) between 2011 and 2018. All patients who underwent upper GI endoscopy with percutaneous endoscopic gastrostomy (PEG) or percutaneous endoscopic jejunostomy (PEJ) tube placement and received bevacizumab within 6 months of their endoscopic procedure were included. RESULTS: We identified 176 patients who underwent PEG or PEJ tube placement and received bevacizumab within 6 months. Eighty-one percent of patients were female (n = 144) and the median age was 61 years. Prior to endoscopic procedures, patients received a median of seven doses of bevacizumab. Patients received bevacizumab from 170 days before to 170 days after their endoscopic procedures (median 44 days). No GI perforations were observed during or after the time of the endoscopic procedures. CONCLUSION: Our study demonstrated that receiving bevacizumab within 6 months prior to their endoscopic procedure was not associated with an increased risk of GI tract perforation and thus not an absolute contraindication to proceeding with PEG and PEJ tube placement in these patients.