Signet Histology Research Articles

SP3.3 - Real World Experience of 600+ Minimally Invasive Abdominoperineal Resections (APR) Done for Low Rectal Cancers in Tertiary Cancer Care Center

Abstract Introduction APR is standard of care surgery for low rectal cancers involving sphincter. Surgery is commonly done in minimally invasive way. Robotic surgery has recently gained popularity due to ease of procedure. Margin positivity and local recurrence still remain a challenge. Methods It is a retrospective study from prospectively maintained database from Aug 2013 to Aug 2023. Surgical and oncological outcome were analyzed using SPSS version 25 software. Results Total 657 minimally invasive APRs were done. All were done in supine lithotomy position. 570 were laparoscopic and 87 robotic. Mean age was 48.4 years. 6 cases were converted to open (5 lap and 1 robotic). Mean BMI was 22.3. Mean distance from anal verge was 3 cm. Majority patients were cT3 (74%). Median blood loss was 150 ml. Clavien Dindo grade III and beyond complications were seen in 11.2%. Mean hospital stay was 7 days. Mean nodes harvested were 13. Mean no of positive nodes were 1.22. Extended resections (extended TME) were 25% in lap and 42% in robotic. Poorly differentiated and signet histology was seen in 27%. CRM positivity was 6.9%. It increases to 15.5% in signet ring histology. Median follow up achieved was 46 months. Local recurrence was 5.5%. Distant recurrence was 20%. 3-year OS and DFS were 73% and 63% respectively. Conclusion In high volume minimally invasive surgery centre, MIS abdominoperineal resection - both laparoscopic and robotic has acceptable surgical and oncological outcomes.

Clinicopathologic Characteristics Influencing Overall Survival of Patients With Early- Versus Average-Onset Colorectal Cancer at a Tertiary Care Center in Indonesia.

There has been a global increase in early-onset colorectal cancer (EOCRC), yet there has been very limited exploration of its impact in Indonesia. This study aimed to determine the clinicopathologic characteristics and the overall survival (OS) of EOCRC compared with those of average-onset colorectal cancer (AOCRC). Medical records were retrospectively reviewed from all patients presenting with colorectal cancer (CRC) at Dr Sardjito General Hospital (Yogyakarta, Indonesia) between 2016 and 2019. Sociodemographic, clinicopathologic, and treatment variables were extracted. t Tests were used to compare characteristics of EOCRC and AOCRC patient groups. The Cox proportional hazards regression model was used to analyze age and other potential prognostic factors. The total population (N = 1,276) comprised EOCRC (n = 149; 11.7%) and AOCRC (n = 1,127; 88.3%) patients. EOCRC patients were more likely to have a higher education level, be single, have out-of-pocket insurance, be underweight, and have signet ring histology (all P values <.05), compared with AOCRC patients. EOCRC and AOCRC groups had a comparable estimated 5-year OS of 34.2% and 36.9%, respectively. In multivariable analyses, performance status (Eastern Cooperative Oncology Group), hemoglobin level, cancer stage, and treatment intention were independent prognostic factors for OS (all P values <.05). To our knowledge, this first major study of EOCRC in Indonesia highlights its role in the overall burden of CRC and its connection with social determinants of health. Patients with EOCRC are more commonly underweight and generally have a higher proportion of signet ring histology than AOCRC, yet OS in both groups is similar. Future research is required to identify risk factors to inform the content and focus of public health education activities, alongside delineating the biology and causes of early and average onset of the disease.

Impact of pCR after neoadjuvant chemotherapy and radical D2 dissection in locally advanced gastric cancers: Analysis of 1001 cases

BackgroundAdvances in perioperative chemotherapy have improved outcomes in patients with gastric cancers (GC). This strategy leads to tumour downstaging and may result in a pathologic complete response (pCR). The study aimed to evaluate the predictors of pCR and determine the impact of pCR on long-term survival. MethodsAt the Department of Gastrointestinal and HPB Oncology at the Tata Memorial Centre, Mumbai, 1001 consecutive patients with locally advanced GCs undergoing radical resection following neoadjuvant chemotherapy from January 2005 to June 2022 were included. ResultsAt a median follow-up of 61 months, the median OS was 53 months with a 5-year OS of 46.8 %. Ninety-five patients (9.49 %) realized pCR. Non-signet and well-differentiated histology were associated with pCR. pCR was significantly associated with improved OS, 5-year OS 79.2 % vs 43.2 % (HR 0.30, p < 0.001). On multivariable analysis, the realization of pCR and completion of adjuvant chemotherapy had superior OS. Whereas, signet-ring histology, linitis-like tumours, and high lymph node ratio had adverse outcomes. ConclusionTumour grade and signet-ring histology predict achievement of pCR in locally advanced GCs after neoadjuvant chemotherapy. Patients with pCR have significantly improved survival. Future neoadjuvant strategies should focus on enhancing pCR rates to improve overall outcomes.

Could Microplastics Be a Driver for Early Onset Colorectal Cancer?

Introduction: The incidence of colorectal cancer in those under 50 years of age (early onset colorectal cancer (EOCRC)) is increasing throughout the world. This has predominantly been an increase in distal colonic and rectal cancers, which are biologically similar to late onset colorectal cancer (LOCRC) but with higher rates of mucinous or signet ring histology, or poorly differentiated cancers. The epidemiology of this change suggests that it is a cohort effect since 1960, and is most likely driven by an environmental cause. We explore the possible role of microplastics as a driver for this change. Review: The development of sporadic colorectal cancer is likely facilitated by the interaction of gut bacteria and the intestinal wall. Normally, a complex layer of luminal mucus provides colonocytes with a level of protection from the effects of these bacteria and their toxins. Plastics were first developed in the early 1900s. After 1945 they became more widely used, with a resultant dramatic increase in plastic pollution and their breakdown to microplastics. Microplastics (MPs) are consumed by humans from an early age and in increasingly large quantities. As MPs pass through the gastrointestinal tract they interact with the normal physiological mechanism of the body, particularly in the colon and rectum, where they may interact with the protective colonic mucus layer. We describe several possible mechanisms of how microplastics may disrupt this mucus layer, thus reducing its protective effect and increasing the likelihood of colorectal cancer. Conclusions: The epidemiology of increase in EOCRC suggests an environmental driver. This increase in EOCRC matches the time sequence in which we could expect to see an effect of rapid increase of MPs in the environment and, as such, we have explored possible mechanisms for this effect. We suggest that it is possible that the MPs damage the barrier integrity of the colonic mucus layer, thus reducing its protective effect. MPs in CRC pathogenesis warrants further investigation. Future directions: Further clarification needs to be sought regarding the interaction between MPs, gut microbiota and the mucus layer. This will need to be modelled in long-term animal studies to better understand how chronic consumption of environmentally-acquired MPs may contribute to an increased risk of colorectal carcinogenesis.

Outcomes of peritoneal metastases in mismatch repair deficient (dMMR) cancers treated with immune checkpoint inhibitors and variables associated with response.

e14576 Background: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of many solid malignancies. ICI appears particularly effective when tumors exhibit high microsatellite instability (MSI-H) and/or mismatch repair deficient (dMMR) status. Although the response is typically quite good in this setting, there are scenarios where benefit is less than anticipated. In this study, we aimed to explore the efficacy of ICIs in patients with MSI-H/dMMR cancers with peritoneal metastasis (PM). Methods: We conducted a retrospective chart review to identify patients (pts) with PM from primary MSI-H/dMMR cancers treated with immunotherapy between 2010 and 2022 at Mayo Clinic. Data was collected to include pt demographics, tumor characteristics, pathology, tumor markers, imaging, mutational profile, and previous and subsequent treatments. The primary endpoint was disease control rate (DCR), defined as objective response rate (RECIST v1.1 criteria) or stable disease. Results: Forty-six pts with MSI-H/dMMR and PM treated with ICIs. Most of our cohort were female (61%) with a median age at diagnosis of 61 years. Colorectal cancer was the most common primary site (69.6%), followed by endometrial (6.5%). Most pts received treatment with PD-1 antibodies as second-line therapy following systemic chemotherapy. DCR of the PM was 71.6 % (n= 13 PR, 9 CR, and 9 SD), with a median duration of response of 12.6 months. Thirteen pts (28.4%) had progressive peritoneal disease on ICI with a median PFS of 2.2 months. Ascites was a poor prognosticator and predicted a lack of benefit from ICI (HR 6.6, 95% CI=2.24-19.9, p= 0.006). Mucinous and signet ring histology were common in pts with peritoneal progression (61.5%); however, this was not statistically significant (HR=1.6; 95%CI= 0.4383 to 3.899, p 0.5). Multivariate analysis for the presence or absence of BRAF and/or RAS mutations was not statistically significant in predicting response. Neither was the specific MMR gene mutation(i.e., MLH1 or PMS2). Interestingly, discordant responses between the peritoneum and other sites of metastasis to immunotherapy were seen in 13 pts (28.4%), primarily as primary peritoneal progression compared to other tumor sites. Conclusions: In our cohort, the DCR of metastatic peritoneal disease in MSI-H/dMMR tumors was approximately 71%. The presence of ascites was identified as a poor prognosticator in this setting and was associated with a lack of response/benefit from ICIs. Histologic subtype (i.e., mucinous/signet ring) did not show statistical significance in predicting ICI response. The subpopulation with discordant response to ICI suggests that peritoneal immunobiology may differ from other sites. Further research on immunotherapy response in the peritoneum is needed for this special subset of pts.

Outcomes of extended total mesorectal excision in patients with locally advanced rectal cancer.

Extended total mesorectal excision (eTME) is a complex procedure involving en bloc resection of the structures surrounding the various quadrants of the rectum. This study, presenting the largest series so far of patients undergoing eTME, aimed to assess the surgical and survival outcomes of patients following treatment with eTME and to compare these outcomes with historical data on pelvic exenteration. The study is a retrospective review of all patients with locally advanced rectal cancer requiring an eTME (2014-2020). The database includes the demographic profile, operative details, histopathological features and follow-up. One hundred and sixty three patients who underwent eTME were analysed. The overall Clavien-Dindo complication rate of > IIIa was 21.1%. The anterior quadrant was the most common anatomical site resected (68.5%). The R1 resection rate was 10.4%. After a median follow-up of 28 months, there were 51 recurrences in the study and twenty two deaths were recorded. The local recurrence rate was 7.3% among the study population. The disease-free survival (DFS) and overall survival were 66.7% and 80.4%, respectively, at 3 years. The majority of the recurrences were distant metastasis (84.3%). In univariate analysis, the quadrant involved did not affect survival. In multivariate analysis, signet ring histology, metastatic presentation, inadequate tumour response and R1 resection affected DFS. The recurrence pattern, R1 resection rate and survival outcomes of patients in the present study were comparable with those for patients undergoing an exenteration. Therefore, eTME is probably a safe alternative to pelvic exenterations when R0 resection is achievable and when the procedure is performed in high-volume specialist tertiary care centres.

MicroRNA‑153 may act as a potential biomarker and prognostic indicator of patients with gastric cancer.

MicroRNA (miR/miRNA)-153, as a novel tumor-related miRNA, has been found to be aberrantly expressed in different types of cancer; however, to the best of our knowledge, the role of miR-153 in gastric cancer (GC) remains unclear. The present study demonstrated that miR-153 expression was markedly decreased in GC, including GC cell lines and culture medium, GC tissues, and serum samples, based on reverse transcription-quantitative PCR, and this was further confirmed by fluorescence in situ hybridization. Transfection with miR-153 mimics inhibited proliferation and migration, and promoted apoptosis in GC cells. The serum expression levels of miR-153 were decreased in 59 patients with GC compared with those of 9 healthy controls, and more decreased in advanced GC compared with early-stage GC, suggesting that miR-153 was associated with tumor progression. Furthermore, serum miR-153 was expressed at significantly lower levels in patients with GC with larger tumor size (≥4 cm; P=0.013), poor differentiation and signet histology (P=0.013), lymph node metastasis (P=0.025) and advanced tumor stage (TNM stage III and IV; P=0.048) compared with patients with a smaller tumor size (<4 cm), well and moderate differentiation, no lymph node metastasis, and TNM stage I and II, respectively. In conclusion, the present study revealed that low miR-153 expression was associated with poor prognosis in GC and miR-153 may potentially act as a tumor biomarker and therapeutic target in GC.

Modified FOLFIRINOX (mFOLFIRINOX) as neoadjuvant therapy and 'salvage' in patients with high risk locally advanced rectal cancers - tolerance and early outcomes.

There is limited data with regard to the use of modified 5-fluoroural-leucovorin-irinotecan-oxaliplatin (mFOLFIRINOX) in terms of tolerance and enabling total mesorectal excision (TME) of locally advanced rectal adenocarcinomas (LARC) with high-risk characteristics (T4b status, signet ring histology etc) post standard neoadjuvant long course chemoradiation (NACTRT) or short course radiation (SCRT) and chemotherapy. Patients with LARC from January 2018 to December 2020 receiving mFOLFIRINOX post NACTRT/SCRT to facilitate TME were evaluated. The primary endpoint was assessment of grade 3 and grade 4 treatment related toxicity and TME rates. Event free survival (EFS), where event was defined as disease progression or recurrence post resection after mFOLFIRINOX, was calculated by Kaplan Meier method. Forty-seven patients were evaluated with a median age of 33 years (Range:18-59), 45% T4b status, 96% radiological circumferential margin (CRM) involved (79% CRM positive post NACTRT/SCRT), 43% extramural venous invasion (n=33) and 36% signet ring histology. 62% had received prior NACTRT and 38% had received SCRT with chemotherapy before receiving mFOLFIRINOX. The most common grade 3 and grade 4 treatment related side effects included diarrhoea (7%), anaemia (4%) and infections (4%). Intended duration of mFOLFIRINOX or beyond was completed in 94% of patients. 60% of patients underwent curative local resection with R0 resection rates of 100% (n=28) and pathological complete response rates of 21%. The most common surgeries done were exenterations and abdominoperineal in 22% and 17% patients respectively. With a median follow up of 19 months, 24 patients had recurred or progressed for a median EFS of 20 months [95% confidence interval (CI): 15-24]. Locally advanced rectal cancers with high-risk characteristics are a niche group of cancers with less-than-optimal outcomes post standard neoadjuvant strategies. mFOLFIRINOX appears to be well tolerated and enables TME in a significant proportion of these patients.

Perioperative Modified FLOT Versus EOX in Locally Advanced Resectable Gastric and Gastro-Oesophageal Junction Adenocarcinoma: Results of a Matched-Pair Analysis.

There is limited real-world data on the efficacy of 2-weekly cycles of docetaxel, oxaliplatin, leucovorin, and fluorouracil (FLOT) compared to epirubicin, oxaliplatin, and capecitabine (EOX) as perioperative therapy in esophagogastric adenocarcinomas (EGAC). The data of 611 patients with EGAC treated with perioperative chemotherapy and planned for curative resection between January 2013 and December 2019 were retrieved. Patients receiving EOX and a dose-modified version of FLOT (mFLOT) were evaluated. A 1:1 matching, using age, tumour location, signet ring histology, and Eastern Cooperative Oncology Group performance status, without replacement was performed by using nearest neighbour matching method. The primary endpoint of the study was 3-year event-free survival (EFS). A total of 593 patients (261 with EOX and 332 with mFLOT) were matched. One hundred and nighty-eight patients (76%) and 285 patients (86%) in the EOX and mFLOT cohorts underwent curative resection, respectively (p = 0.002). With a median follow-up of 35 and 53months, respectively, the primary outcome of 3-year EFS was statistically superior in patients receiving mFLOT as compared to the EOX regimen (60% vs. 39%; p < 0.001). There was a greater incidence of grade 3 and grade 4 neutropenia (neoadjuvant: 18% vs. 2%; p < 0.001, adjuvant: 18% vs. 1%; p = 0.001) and febrile neutropenia (neoadjuvant: 8% vs. 1.1%; p < 0.001, adjuvant: 6% vs. 0; p = 0.001) with mFLOT. mFLOT is associated with improved resection rates and survival in comparison to EOX as perioperative therapy in gastric adenocarcinomas in this large real-world cohort, with manageable increase in clinically relevant toxicities such as grade 3 and grade 4 febrile neutropenia and neutropenia.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in Young Patients With Peritoneal Metastasis of Colorectal Cancer—An Asian Experience

IntroductionCytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are accepted treatment options for patients with cancers associated with the abdominal region. Currently, there are insufficient data that evaluate the effectiveness of these therapeutic options in young patients who have peritoneal metastasis (PM) originating from colorectal cancer. MethodsIn this investigation, we evaluated perioperative data, clinicopathological manifestations, and survival consequences in 46 younger (≤50 y) patients who underwent CRS and HIPEC therapy between 2017 June and 2019 June and then compared these data with 94 older patients (aged >50 y). ResultsCompared with older patients, younger patients had a higher synchronous PM incidence (78.3% versus 51.1%, P < 0.001) and were more likely to exhibit signet ring histology and mucinous (29.8% versus 60.9%; P < 0.001). The cancer-specific survival rates after CRS and HIPEC treatment were similar in both age sets. Multivariate Cox regression revealed that mucinous/signet adenocarcinoma (hazard ratio 2.20, 95% confidence interval 1.02-4.74; P = 0.044) and rectal origin (hazard ratio 2.51, 95% confidence interval 1.11-5.67; P = 0.027) were independent risk factors for a lower cancer-specific survival rate. ConclusionsYounger (age ≤50 y) patients who have PM of colorectal cancer origin often present synchronous PM, which is less commonly observed in older patients. Tumors in younger patients are more aggressive; however, post-CRS and HIPEC treatment, the benefits are similar to those observed in older cohorts.

Treatment of Metastatic Colorectal Cancers in Resource-Constrained Low- and Middle-Income Countries (LMICS) Scenario-Outcomes, Practice Patterns, and Commentary on Treatment Costs.

Anant RamaswamyIntroduction The overall survival (OS) of metastatic colorectal cancers (mCRCs) in clinical practice and resource-constrained low- and middle-income countries (LMICS) like India is not known. Materials and Methods Data of patients with mCRC treated between January 2013 and August 2017 were accessed from a prospectively maintained database. Demographics, disease characteristics, chemotherapeutic regimens, use of monoclonal antibodies, and survival outcomes in treated patients were collected and analyzed. Costs of treatment options as off 2017 were also interpreted. Results The data of 403 patients satisfied prespecified inclusion criteria and were included for analysis. The median age of the cohort was 48 years (range: 17-86) with a predominance of rectal cancers (63.3%), liver alone metastases (47.1%), and resected primary (69.7%). Signet ring histology was present in 82 patients (20.3%). The most commonly used first-line regimen (CT1) was modified capecitabine-oxaliplatin (53.3%). Two hundred and nineteen patients (54.3%) received second-line systemic therapy (CT2). Patients received a median of two lines of therapy (range: 1-6). MoAbs were used by 48 patients (13.4%) with CT1 and 34 patients (15.5%) with CT2. Median OS of the entire cohort was 17.61 months (95% confidence interval: 15.48-19.74), which was within the predicted range, as per investigator hypothesis. The presence of signet ring histology ( p <0.001), raised carcinoembryonic antigen at baseline ( p =0.017), and the absence of a resected primary ( p <0.001) predicted inferior median OS. Conclusions Survival of patients with mCRC in a resource-constrained LMIC scenario like India is approximately 12 to 15 months lower than published trial data. Limited access to targeted therapy and newer expensive treatment options due to financial constraints may contribute to this disparity.

Molecular profiles of gastric adenocarcinoma among Hispanic patients at a safety-net healthcare system.

e16067 Background: Hispanic patients with gastric cancer are more likely to have advanced stage at diagnosis, signet ring histology, and worse survival outcomes than non-Hispanic patients. Although socioeconomic factors may contribute to these disparities, the molecular biology of gastric cancer in Hispanic patients has not been well characterized. Hispanic patients comprise &lt; 0.05% of gastric adenocarcinoma cases in The Cancer Genome Atlas (TCGA). Methods: We conducted a retrospective study of patients with gastric adenocarcinoma diagnosed between January 2019 to January 2022 at a safety net hospital in Houston, Texas. The hospital serves a patient population of which 91% are racial/ethnic minorities and 57% are Hispanic. Next generation sequencing data was obtained via Tempus|xT tissue assay (DNA sequencing of 648 genes in tumor and matched normal samples at 500x depth) and/or Tempus|xF liquid biopsy assay (ctDNA sequencing of 105 genes in peripheral blood samples at 5,000x depth) for germline and/or somatic mutations. We compared mutation findings in Hispanic vs non-Hispanic patients. Results: Among 56 patients with gastric adenocarcinoma, 45 (80%) were Hispanic, 11 (20%) were non-Hispanic White, Black, or other, 30 (54%) were male, median age was 54±13, and 14 (25%) were younger than 50 years old. The majority were metastatic (65%), and 6 (11%) were signet ring cell subtype. The most common pathogenic somatic variants across the entire cohort included: TP53 (55%) , CDH1 (34%) , ARID1A (25%) , LRP1B (20%) , RHOA (16%) , SMAD4 (16%) , ERBB2 (14%) , KRAS (14%) , CDKN2A (12%), and PIK3CA (12%). Microsatellite instability was found in 1 (0.02%) patient. Somatic CDH1 mutations were present in 15 (33%) Hispanic patients, of whom 7 were younger than 50 years old, and 2 (18%) non-Hispanic patients. Germline CDH1 mutations was identified in 1 Hispanic patient. TP53 mutations occurred in 14 (31%) Hispanic patients and 6 (55%) non-Hispanic patients. Conclusions: CDH1 mutations, which are associated with familial gastric cancers and more aggressive disease, were present in 33% of Hispanic patients with gastric adenocarcinoma in our study. Nearly half of these identified patients were younger than 50 years old. The high frequency of CDH1 mutations may contribute to the unique pathogenesis of gastric cancers in Hispanic patients.

Modified FOLFIRINOX (mFOLFIRINOX) in high risk locally advanced rectal adenocarcinomas.

108 Background: There is limited data with regard to the use of modified 5-fluoroural-leucovorin-irinotecan-oxaliplatin (mFOLFIRINOX) in enabling resection and increasing survival of locally advanced rectal adenocarcinomas (LARC) with high-risk characteristics (T4b status, signet ring histology, etc.) post standard neoadjuvant long course chemoradiation (NACTRT) or short course radiation (SCRT) and chemotherapy. Methods: Patients with LARC from January 2018 to December 2020 receiving mFOLFIRINOX (5-Fluorouracil - 1800mg/m2 over 46 hours, Leucovorin 300mg, Irinotecan 135mg/m2, oxaliplatin 65mg/m2) post NACTRT/SCRT to facilitate curative local resection were evaluated. The primary endpoint was event free survival (EFS), where event was defined as disease progression or recurrence post resection after mFOLFIRINOX. Survivals were calculated using Kaplan-Meier analysis. Results: Forty-seven patients were evaluated with a median age of 33 years (Range:18-59), 45% T4b status, 94% radiological circumferential margin (CRM) involved (79% CRM positive post NACTRT/SCRT), 43% extramural venous invasion (n=33) and 36% signet ring histology. 62% had received prior NACTRT and 38% had received SCRT with chemotherapy before receiving mFOLFIRINOX. The most common grade 3 and grade 4 treatment related side effects included diarrhoea (7%), anaemia (4%) and infections (4%). Intended duration of mFOLFIRINOX or beyond was completed in 94% of patients. 60% of patients underwent curative local resection with R0 resection rates of 100% (n=28) and pathological complete response rates of 21%. The most common surgeries done were exenterations and abdominoperineal resections in 22% and 17% patients respectively. With a median follow up of 19 months, 25 patients had recurred or progressed for a median EFS of 20 months [95% confidence interval (CI): 15-24] while median overall survival was 55 months (95% CI: 24-86). Conclusions: Locally advanced rectal cancers with high-risk characteristics are a niche group of cancers with less-than-optimal outcomes post standard neoadjuvant strategies. mFOLFIRINOX appears to be well tolerated in this cohort of patients and enables conversion to curative local resection and potentially improves survival as well.

Patterns of gastric cancer metastasis in the United States

BackgroundLiterature on the epidemiology of gastric cancer metastasis is limited, although outcomes are known to be poor. We describe patterns of gastric cancer metastasis and treatment in the United States. MethodsPatients with metastatic gastric adenocarcinoma were identified in the NCDB from 2004 to 2016. We describe univariate associations between sites of metastasis and clinicopathologic characteristics and treatment modalities, using chi-square and Kruskal-Wallis tests. Overall survival was calculated using Kaplan-Meier estimation. Results43% (n = 2028) of patients presented with peritoneal metastases, 26% (n = 1228) with liver metastases, 20% (n = 941) with distant nodes, and 11% (n = 552) with bone, brain or lung metastases. Compared to liver metastases, peritoneal metastases were more likely from an antral primary site (28% v. 16%); associated with signet ring histology (34% v. 6%); tumor grade of III/IV (85% vs. 60%) (p < 0.0001 for all). Isolated metastasis to distant lymph nodes had the longest median overall survival (7.6 months, p < 0.0001). ConclusionsMost patients with metastatic gastric cancer in the USA present with peritoneal disease. Predictors for peritoneal metastases include primary antral site, signet ring histology and higher tumor grades.

Treatment of Anastomotic Recurrence After Esophagectomy

BackgroundIsolated local recurrence after curative esophagectomy for esophageal cancer is a rare event. Although it is potentially curable, management can be challenging. MethodsWe retrospectively reviewed all patients undergoing esophagectomy for esophageal adenocarcinoma (EAC) from 2000 to 2019. Date of recurrence was defined as the date at which the initial abnormal surveillance study result or symptomatic presentation led to further workup and subsequent pathologic diagnosis of recurrence. Overall survival after recurrence was estimated using Kaplan-Meier methods and compared between treatment groups using the log-rank test. ResultsOf the 1370 patients with EAC who underwent esophagectomy in our cohort, 531 (39%) developed recurrence of their disease. The 5-year cumulative incidence of recurrence was 2.7% (95% CI, 2.0%-3.6%) for local, 6.3% (95% CI, 5.2%-7.8%) for regional, and 22.0% (95% CI, 20.0%-24.4%) for distant recurrences. On univariable and multivariable competing-risk regression analysis, advanced pT stage, signet ring histology, and serious complication were independently associated with local recurrence. Patients with local recurrence treated with definitive therapy had a median survival after recurrence of 19.1 months (95% CI, 11.4-33.2 months) compared with 10.6 months (95% CI, 8.5-14.2 months) for chemotherapy or radiotherapy alone and 1.73 months (95% CI, 0.23-15.6 months) for no treatment (P < .001). ConclusionsIsolated local recurrence occurred in only 3% of patients. Advanced T stage, signet cell histology, and serious complication were risk factors for recurrence. Although complex surgical resection is required, in very select cases, more aggressive treatment may be warranted.

Clinicopathological Features of Gastric Cancer in a Cohort of Gulf Council Countries’ Patients: A Cross-Sectional Study of 96 Cases

Objective: This cross-sectional study aims to report the clinicopathological features of Gulf Cooperation Council (GCC) patients with Gastric Cancer (GC). Patients and Methods: This cross-sectional study evaluated patients from GCC countries presenting with GC, treated at the University of Texas MD Anderson Cancer Center, Houston, Texas from 1981 to 2015. After obtaining an Institutional Review Board (IRB) approval to conduct this cross-sectional study, the data were collected from the charts of 96 consecutive GCC patients diagnosed with GC according to electronic and paper medical records (for cases prior to the implementation of the electronic medical records): The charts were reviewed for demographic data, clinical data, diagnostic tools, endoscopic location of the tumour and clinicopathological features of the GC. Statistical analyses were performed by using SPSS version 20. Numerical data were presented as mean +/- standard deviation (SD) (For normally distributed data); median and range (For not normally distributed data). Nominal data were expressed by percentages. Results: 96 patients identified with histologically confirmed gastric carcinoma from Saudi Arabia (KSA) (40%), UAE (26%), Qatar (16%) Kuwait (10%), Oman (3%) and Bahrain (2%). The median age was 54.5 years and 40 patients (42%) were less than 50 years of age. 61% of the patients were of male gender and 39% were female. Intestinal type was the most common histological type in 61% of cases, 30% had signet cell histology. The aggressive signet ring histology is the most common (71.4%) in younger patients (Age &lt; 50) in this cohort. Out of those 28 patients tested for HER-2 amplification, 6 (20%) were found to be amplified. Finally, 76% of the patients presented with stage IV disease. Conclusion: GC tends to present in advanced stages in GCC population with median duration from first symptoms to diagnosis was 9.3 months (2 to 18 months). GC in patients from GCC countries is diagnosed at 10 years earlier than in Western population. Intestinal‐type histology is most common similar to the western population, yet aggressive histology (signet ring) is high in younger population. HER-2 amplification rate is similar to Western populations. This is the first study to report these findings in GCC population with gastric cancer. Further collaboration and research are needed across the GCC countries to better characterize GC in this region and to understand the early onset pattern of GC observed in this report.

Colorectal cancer with microsatellite instability: Right-sided location and signet ring cell histology are associated with nodal metastases, and extranodal extension influences disease-free survival

Colorectal cancer (CRC) with microsatellite instability (MSI) accounts for 15–18 % of all CRCs and represents the category with the best prognosis. This study aimed at determining any possible clinical/pathological features associated with a higher risk of nodal metastasization in MSI-CRC, and at defining any possible prognostic moderators in this setting. All surgically resected CRCs of the last 20 years (mono-institutional series) with a PCR-based diagnosis of MSI, with and without nodal metastasis, have been retrieved for histological review, which was performed following WHO guidelines. Furthermore, the most important prognostic moderators have been investigated with a survival analysis. The study of 33 cases of MSI-CRCs with nodal metastasis highlighted a high fidelity of histology maintenance between primary tumors and matched nodal metastases. At survival analysis, the strongest prognostic variable in MSI-CRCs with nodal metastasis was the extranodal extension (multivariate analysis, HR: 14.4, 95 %CI: 1.46−140.9, p = 0.022). Furthermore, through a comparison between nodal positive (33 cases) and nodal negative (71 cases) MSI-CRCs, right-sided location (p < 0.0001), pT4 stage (p = 0.0004) and signet-ring histology (p = 0.0089) emerged as parameters more commonly associated with nodal metastasization. These findings shed new light on the biology of MSI-CRC and can be of help for the prognostic stratification of MSI-CRC patients.

Clinical and molecular characteristics of early-onset versus average-onset esophagogastric cancer.

250 Background: While the rate of esophagogastric (EG) cancer is declining, early onset (EO) gastric cancer prior to age 50 is rising. It is unknown whether EO-EG cancer represents a distinct entity. This study investigates the clinical and molecular characteristics of EO compared with average onset (AO)-EG cancers. Methods: We reviewed clinical and molecular features of gastric (G), esophageal (E) and gastroesophageal junction (GEJ) cancer in patients treated at MSKCC between 2005 and 2018. We defined early onset as age &lt; 49, based on the age cutoff for urgent endoscopy referral. Clinical symptoms at diagnosis, primary tumor location, histology, HER2 and MSI status and molecular alterations were compared using Fisher’s exact test. Benjamini-Hochberg method was used to decrease the false discovery rate. Results: We analyzed 738 pts with EG cancer (age &lt; 49 n=151; age &gt;50 n=587). Race and sex were different with more Asian (19% vs. 9%), fewer Caucasian (62% vs. 81%) ( P&lt;0.001) and more female patients (40% vs. 29%, P=0.014) in the EO group. Time from symptom onset to diagnosis was longer in the EO group (median (IQR) 144 d (66-276) vs. 75 d (34-136), P=0.009), though stage did not differ ( P=0.49). Patients with EO-EG cancer had less weight loss ( P&lt;0.001), but no other distinct presenting symptoms. Primary disease site was different with more gastric in the EO group (66% vs. 55%, P=0.04). Signet-ring histology was more common in the EO group (11% vs. 3%; P=0.0009). ERBB2 amp and MSI-H were similar, with a trend toward more MSI-H in the AO group (ERBB2 amp P=0.88, Q=0.830; MSI-H P=0.0157, Q=0.056). The most frequent somatic alterations were similar in EO vs. AO pts, including TP53 (68% vs. 70%, P=0.370, Q=0.825), CDH1 (15% vs. 11%, P=0.139, Q=0.825), RHOA (6% vs. 5%, P=0.395, Q=0.825). There was a trend toward more ARID1A (19% vs. 7%, P&lt;0.01, Q=0.250) and FBWX7 (5% vs. 2%, P=139, Q=0.825) mutations in the AO group. Conclusions: Presenting symptoms, stage, histology, HER2 and MSI status are similar in patients with EO vs. AO-EG cancer. There is a trend in EO toward longer time to diagnosis, gastric primary site of disease, signet-ring histology and fewer ARID1A and FBWX7 mutations. Expanded clinical and molecular data will be presented. [Table: see text]

Comparative Study of Colorectal Cancer Based on Tumor Location in Adolescent and Young Adult Population in Nepal

Introduction: Colorectal cancer in the Adolescent and Young Adult population are increasing and are characterized by a more advanced stage at diagnosis, poorer cell differentiation, higher signet ring histology, and left-sided colon location of the primary tumor. This study aims to compare colorectal cancer data in the Adolescent and Young Adult population-based on tumor location.Materials and Methods: This is a retrospective cross-sectional study of colorectal cancer in the Adolescent and Young Adult population from April 2017 to September 2020 in Shree Birendra Hospital. Data were collected for age, sex, clinical features, histology, TNM stage, colonoscopy finding, radiologic features, treatment, and follow-up status based on tumor location. Data were analyzed using Excel 2010 and SPSS v 17.Results: The total number of patients was 61 with the mean age of 32.36 ± 6.24 years. There was a male preponderance of 63.93%. Right-sided colorectal cancer was 24.59% while left-sided colorectal cancer was 75.41%. For right-sided colorectal cancers, the most common symptoms were pain abdomen (73.3%) and diarrhea (53.3%) while for left-sided colorectal cancers, it was pain abdomen (80.4%) and bleeding per rectum (45.7%). The most common histology was adenocarcinoma (95.08%) with moderately differentiated being most common in both locations. Surgery, radiation and chemotherapy for right-sided and left-sided colorectal cancer were 86.66%, 0.0%, 86.66% and 58.67%, 28.26%, 89.13% respectively.Conclusions: Left-sided colorectal cancer was more common in the Adolescent and Young Adult population in our study. There were signifi cant differences in the clinical presentation of colorectal cancer as per the tumor location.

High Rate of Positive Circumferential Resection Margin in Colon Cancer: A National Appraisal and Call for Action.

To identify rates of positive circumferential resection margin (CRM) for colon cancer surgery in the US. CRM is one of the most important determinants of local control in colorectal cancers. The extent to which CRM involvement exists after colon cancer surgery is unknown. Colon cancer cases with resection 2010 to 2015 were identified from the National Cancer Data Base. Adjusting for patient and tumor characteristics, comparisons were made between cases with CRM > 1 mm (negative margin) and those with margin involved with tumor or ≤ 1 mm (positive margin, CRM+). Hospital-level analysis was performed, examining observed-to-expected CRM+ rates. In total, 170,022 cases were identified: 150,291 CRM- and 19,731 CRM+ (11.6%). Pathologic T-category was the greatest predictor of CRM+, with higher rates in pT4(25.8%), pT4A(24.7%), and pT4B(31.5%) versus pT1(4.5%), pT2(6.3%) and pT3 (10.9%, P < 0.001). Within pT4 patients, predictors of CRM+ included signet-ring histology (38.1% vs 26.7% nonmucinous, and 26.9% mucinous adenocarcinoma, P < 0.001), removing < 12 lymph nodes (36.5% vs 26.1% >12, P < 0.001), community facilities (32.7%) versus academic/research (23.6%, P < 0.001), year (30.1% 2010 vs 22.6% 2015, P < 0.001), and hospital volume (24.5% highest quartile vs 32.7% lowest, P < 0.001). Across 1288 hospitals, observed-to-expected ratios for CRM+ ranged from 0 to 7.899; 429 facilities had higher than expected rates. Overall rate of CRM+ in US colon cancer cases is high. Variation exists across hospitals, with higher than expected rates in many facilities. Although biology is a major influencing factor, CRM+ rates represent an area for multidisciplinary improvement in quality of colon cancer care.