Feasibility and Colonoscopy Yield Using the Fecal Immunochemical Test (FIT)-Based Colorectal Cancer Screening in a Latin America Country.

BACKGROUND & AIMS: Organized colorectal cancer (CRC) screening is not widely practiced in Latin America and the results of regional studies may help overcome barriers for implementation of national screening programs. We aimed to describe the implementation and findings of a fecal immunochemical test (FIT)-based program in Brazil. METHODS: In a prospective population-based study, asymptomatic individuals (50-75 years old) from Sao Paulo city were invited to undergo FIT for CRC screening. Participants with positive FIT (≥10 µg Hb/g feces) were referred for colonoscopy. Subjects were classified into groups according to the presence of CRC, precursor lesions, and other benign findings, possibly related to bleeding. RESULTS: Of a total of 9881 subjects, 7.8% had positive FIT and colonoscopy compliance was 68.9% (n = 535). Boston scale was considered adequate in 99% and cecal intubation rate was 99.4%. CRC was diagnosed in 5.9% of the cases, adenoma in 63.2%, advanced adenoma in 31.4%, and advanced neoplasia in 33.0%. Age was positively associated with CRC (P = .03). Higher FIT concentrations were associated with increased detection of CRC (P < .008), advanced adenoma (P < .001), and advanced neoplasia (P < .001). CONCLUSIONS: Implementation of a FIT-based CRC screening program was feasible in a low-resource setting, and there was a high yield for neoplasia in individuals with a positive FIT. This approach could be used as a model to plan and disseminate organized CRC screening more broadly in Brazil and Latin America.

Evaluation of the endoscopic cure criteria in patients undergoing surgery for early gastric cancer.

BACKGROUND AND OBJECTIVES: Gastric cancer (GC) prognosis is influenced by the extent of the tumor, lymph node involvement (LNM), and metastasis. Endoscopic resection (ER) or gastrectomy with lymphadenectomy are standard treatments for early GC (EGC). This study evaluated LNM frequency according to eCura categories, clinicopathological characteristics, disease-free (DFS), and overall (OS) survival rates. METHODS: We included EGC patients who underwent curative gastrectomy between 2009 and 2020 from our single-center database. Anatomopathological and clinical reports were reviewed to analyze eCura categories. RESULTS: We included 160 EGC patients who underwent gastrectomy with eCura categories A, B, and C, comprising 26.3%, 13.8%, and 60%, respectively. Baseline clinical characteristics showed no intergroup disparities. LNM incidence for A, B, and C was 4.8%, 18.2%, and 19.8%. When evaluating the criteria for ER and its association with eCura categories, we found that 95.2% of eCura A and 100% of eCura B patients had classic or expanded criteria for ER. On the other hand, 97.9% of eCura C patients were referred to surgical resection. Multivariate analysis demonstrated that lymphatic (OR = 5.57, CI95% = 1.45-21.29, p = 0.012) and perineural (OR = 15.8, CI95% = 1.39-179.88, p = 0.026) invasions were associated with a higher risk of LNM. No significant differences in DFS or OS were found among eCura categories. CONCLUSION: The eCura categories were associated with the occurrence of LNM. In most patients, those with classic and expanded indication criteria for ER were classified as eCura A and B.

Impact of a Routine Colorectal Endoscopic Submucosal Dissection in the Surgical Management of Nonmalignant Colorectal Lesions Treated in a Referral Cancer Center.

BACKGROUND: Recent data show an increasing number of abdominal surgeries being performed for the treatment of nonmalignant colorectal polyps in the West but in settings in which colorectal endoscopic submucosal dissection is not routinely performed. This study evaluated the number of nonmalignant colorectal lesions referred to surgical treatment in a tertiary cancer center that incorporated magnification chromoendoscopy and endoscopic submucosal dissection as part of the standard management of complex colorectal polyps. OBJECTIVE: The study aimed to estimate the number of patients with nonmalignant colorectal lesions referred to surgical resection at our institution after the standardization of routine endoscopic submucosal dissection and to describe outcomes for patients undergoing colorectal endoscopic submucosal dissection. DESIGN: Single-center retrospective study from a prospectively collected database of endoscopic submucosal dissections and colorectal surgeries performed between January 2016 and December 2019. SETTING: Reference cancer center. PATIENTS: Consecutive adult patients with complex nonmalignant colorectal polyps were included. INTERVENTIONS: Patients with nonmalignant colorectal polyps were treated by endoscopic submucosal dissection or surgery (elective colectomy, rectosigmoidectomy, low anterior resection, or proctocolectomy). MAIN OUTCOMES MEASURES: The primary outcome measure was the percentage of patients referred to colorectal surgery for nonmalignant lesions. RESULTS: In the study period, 1.1% of 825 colorectal surgeries were performed for nonmalignant lesions, and 97 complex polyps were endoscopically removed by endoscopic submucosal dissection. The en bloc, R0, and curative resection rates of endoscopic submucosal dissection were 91.7%, 83.5%, and 81.4%, respectively. The mean tumor size was 59 (SD 37.8) mm. Perforations during endoscopic submucosal dissection occurred in 3 cases, all treated with clipping. One patient presented with a delayed perforation 2 days after the endoscopic resection and underwent surgery. The mean follow-up period was 3 years, with no tumor recurrence in this cohort. LIMITATIONS: Single-center retrospective study. CONCLUSIONS: A workflow that includes assessment of the lesions with magnification chromoendoscopy and resection through endoscopic submucosal dissection can lead to a very low rate of abdominal surgery for nonmalignant colorectal lesions. See Video Abstract at http://links.lww.com/DCR/C123 . IMPACTO DE LA DISECCIN SUBMUCOSA ENDOSCPICA COLORRECTAL DE RUTINA EN EL MANEJO QUIRRGICO DE LESIONES COLORRECTALES NO MALIGNAS TRATADAS EN UN CENTRO ONCOLGICO DE REFERENCIA: ANTECEDENTES:Datos recientes muestran un número cada vez mayor de cirugías abdominales realizadas para el tratamiento de pólipos colorrectales no malignos en Occidente, pero no en los entornos donde la disección submucosa endoscópica colorrectal se realiza de forma rutinaria. El estudio evaluó el número de lesiones colorrectales no malignas referidas a tratamiento quirúrgico en un centro oncológico terciario, que incorporó cromoendoscopia de aumento y disección submucosa endoscópica como parte del manejo estándar de pólipos colorrectales complejos.OBJETIVO:Estimar el número de pacientes con lesiones colorrectales no malignas referidos para resección quirúrgica en nuestra institución, después de la estandarización de la disección submucosa endoscópica de rutina y describir los resultados para los pacientes sometidos a disección submucosa endoscópica colorrectal.DISEÑO:Estudio retrospectivo de un solo centro, a partir de una base de datos recolectada prospectivamente de disecciones submucosas endoscópicas y cirugías colorrectales realizadas entre enero de 2016 y diciembre de 2019.AJUSTE:Centro oncológico de referencia.PACIENTES:Pacientes adultos consecutivos con pólipos colorrectales no malignos complejos.INTERVENCIONES:Pacientes con pólipos colorrectales no malignos tratados mediante disección submucosa endoscópica o cirugía (colectomía electiva, rectosigmoidectomía, resección anterior baja o proctocolectomía).PRINCIPALES MEDIDAS DE RESULTADO:La medida de resultado primario fue el porcentaje de pacientes remitidos a cirugía colorrectal por lesiones no malignas.RESULTADOS:En el período, 1,1% de 825 cirugías colorrectales fueron realizadas por lesiones no malignas y 97 pólipos complejos fueron extirpados por. disección submucosa endoscópica. Las tasas de resección en bloque, R0 y curativa de disección submucosa endoscópica fueron 91,7%, 83,5% y 81,4%, respectivamente. El tamaño tumoral medio fue de 59 (DE 37,8) mm. Se produjeron perforaciones durante la disección submucosa endoscópica en 3 casos, todos tratados con clipaje. Un paciente presentó una perforación diferida 2 días después de la resección endoscópica y fue intervenido quirúrgicamente. El seguimiento medio fue de 3 años, sin recurrencia tumoral en esta cohorte.LIMITACIONES:Estudio retrospectivo de un solo centro.CONCLUSIONES:Un flujo de trabajo que incluye la evaluación de las lesiones con cromoendoscopia de aumento y resección a través de disección submucosa endoscópica, puede conducir a una tasa muy baja de cirugía abdominal para lesiones colorrectales no malignas. Consulte Video Resumen en http://links.lww.com/DCR/C123 . (Traducción-Dr. Fidel Ruiz Healy ).

High dose image-guided, intensity modulated radiation therapy (IG-IMRT) for chordomas of the sacrum, mobile spine and skull base: preliminary outcomes.

PURPOSE: To report preliminary outcomes of high dose image-guided intensity modulated radiotherapy (IG-IMRT) in the treatment of chordomas of the sacrum, mobile spine and skull base. METHODS: Retrospective analysis of chordoma patients treated with surgery and/or radiotherapy (RT) in a single tertiary cancer center. Initial treatment was categorized as (A) Adjuvant or definitive high-dose RT (78 Gy/39fx or 24 Gy/1fx) vs (B) surgery-only or low dose RT. The primary endpoint was the cumulative incidence of local failure. RESULTS: A total of 31 patients were treated from 2010 through 2020. Median age was 55 years, tumor location was 64% sacrum, 13% lumbar, 16% cervical and 6% clivus. Median tumor volume was 148 cc (8.3 cm in largest diameter), 42% of patients received curative-intent surgery and 65% received primary RT (adjuvant or definitive). 5-year cumulative incidence of local failure was 48% in group A vs 83% in group B (p = 0.041). Tumor size > 330 cc was associated with local failure (SHR 2.2, 95% CI 1.12 to 7.45; p = 0.028). Eight patients developed distant metastases, with a median metastases-free survival of 56.1 months. 5-year survival for patients that received high dose RT was 72% vs 76% in patients that received no or low dose RT (p = 0.63). CONCLUSION: Our study suggests high-dose photon IG-IMRT improves local control in the initial management of chordomas. Health systems should promote reference centers with clinical expertise and technical capabilities to improve outcomes for this complex disease.

Long-term outcomes of endoscopic submucosal dissection and transanal endoscopic microsurgery for the treatment of rectal tumors.

BACKGROUND AND AIM: Endoscopic submucosal dissection and transanal endoscopic microsurgery are good options for the treatment of rectal adenomas and early rectal carcinomas, but whether long-term outcomes of these procedures are comparable is not known. The aim of this study was to address this question. METHODS: A retrospective single-center study evaluating 98 consecutive procedures between June 2008 and December 2017 was performed in a tertiary cancer center. Consecutive patients who had undergone either endoscopic submucosal resection or transanal endoscopic microsurgery for rectal adenomas and early rectal carcinomas were evaluated, and long-term recurrence and complication rates were compared. RESULTS: Both groups were similar regarding sex, age, preoperative surgical risk, and en bloc resection rate (95.7% in the endoscopic and 100% in the surgical group, P = 0.81). Mean follow-up period was 37.6 months. Lesions resected endoscopically were significantly larger (68.5 mm) than those resected by transanal resection (44.5 mm), P = 0.003. Curative resections occurred in 97.2% of endoscopic resections and 85.2% of the surgical ones (P = 0.04). Comparing resections that fulfilled histologic curative criteria, there were no recurrences in the endoscopic group (out of 69 cases) and two recurrences in the transanal group (8.3% of 24 cases), P = 0.06. Late complications occurred in 12.7% of endoscopic procedures and 25.9% of surgical procedures (P = 0.13). CONCLUSIONS: In our experience, endoscopic submucosal resection seems to have advantages over transanal endoscopic microsurgery, with similar en bloc resection rate and lower rate of late complications and recurrences. Multicenter randomized controlled trials are needed to support our findings.

The value of cellular components of blood in the setting of trimodal therapy for esophageal cancer.

BACKGROUND: Inflammation status plays an important role in the natural history of malignancy. Consequently, hematological markers of systemic inflammation may predict prognosis in neoplasms. This study evaluated the value of cellular blood components changes during neoadjuvant chemoradiotherapy followed by esophagectomy for cancer in predicting prognosis. METHODS: A cohort of 149 patients was analyzed. Cellular components of blood were assessed before neoadjuvant therapy (A); before surgery (B); and 3 to 5 months after surgery (C); for the following outcomes: pathological response, overall survival (OS), and disease-free survival (DFS). Univariate and multivariate Cox regression models were applied to evaluate the independent prognostic significance of blood count variables. RESULTS: Low hematocrit (Ht) (C) (HR, 0.85; 95% CI, 0.79-0.92) and high neutrophil-to-lymphocyte ratio (NLR) (C) (HR, 1.07; 95% CI, 1.07-1.10) were related to poor OS. Low Hb (C) (HR, 0.72; 95% CI, 0.58-0.88), red cell distribution width (RDW) (C-A) (HR, 1.16; 95% CI, 1.02-1.31), and NLR (C-A) (1.06; 95% CI, 1.03-1.09) were related to poor DFS. RDW (B-A) (HR, 1.15; 95% CI, 1.08-1.22), RDW (C) (HR, 1.12; 95% CI, 1.04-1.2), NLR (C) (HR, 1.12; 95% CI, 1.08-1.17) were related to systemic recurrence. CONCLUSION: Variables of routine blood count are easily assessable and their changes throughout trimodal therapy for esophageal carcinoma provide important information for cancer patient's prognosis.

Role of Magnification Chromoendoscopy in the Management of Colorectal Neoplastic Lesions Suspicious for Submucosal Invasion.

BACKGROUND: Correctly predicting the depth of tumor invasion in the colorectal wall is crucial for successful endoscopic resection of superficial colorectal neoplasms. OBJECTIVE: The aim of this study was to assess the accuracy of magnifying chromoendoscopy in a Western medical center to predict the depth of invasion by the pit pattern classification in patients with colorectal neoplasms with a high risk of submucosal invasion. DESIGN: This single-center retrospective study, from a prospectively collected database, was conducted between April 2009 and June 2015. SETTINGS: The study was conducted at a single academic center. PATIENTS: Consecutive patients with colorectal neoplasms with high risk of submucosal invasion were included. These tumors were defined by large (≥20 mm) sessile polyps (nonpedunculated), laterally spreading tumors, or depressed lesions of any size. INTERVENTIONS: Patients underwent magnifying chromoendoscopy and were classified according to the Kudo pit pattern. The therapeutic decision, endoscopic or surgery, was defined by the magnification assessment. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values of magnifying chromoendoscopy for assessment of these lesions were determined. RESULTS: A total of 123 lesions were included, with a mean size of 54.0 ± 37.1 mm. Preoperative magnifying chromoendoscopy with pit pattern classification had 73.3% sensitivity, 100% specificity, 100% positive predictive value, 96.4% negative predictive value, and 96.7% accuracy to predict depth of invasion and consequently to guide the appropriate treatment. Thirty-three rectal lesions were also examined by MRI, and 31 were diagnosed as T2 lesions. Twenty two (70.1%) of these lesions were diagnosed as noninvasive by magnifying colonoscopy, were treated by endoscopic resection, and met the curative criteria. LIMITATIONS: This was a single-center retrospective study with a single expert endoscopist experience. CONCLUSIONS: Magnifying chromoendoscopy is highly accurate for assessing colorectal neoplasms suspicious for submucosal invasion and can help to select the most appropriate treatment. See Video Abstract at http://links.lww.com/DCR/A920.

Frequency of CDH1 germline variants and contribution of dietary habits in early age onset gastric cancer patients in Brazil.

INTRODUCTION: The contribution of CDH1 germline variants to gastric cancer burden among young adults is unknown in Brazil. We aimed to evaluate the frequency of CDH1 germline variants and the diet/lifestyle habits in early age onset gastric cancer (EOGC, ≤ 55 years old) patients. METHODOLOGY: From 2013 to 2015, a total of 88 unrelated and consecutive patients diagnosed with EOGC were enrolled. All CDH1 exons and intronic boundaries were sequenced, and large genomic rearrangements were screened by MLPA. CDH1 transcription analysis was performed for variants that could potentially induce an effect on splicing. The diet and lifestyle habits of EOGC patients were compared to Brazilian population diet and lifestyle, obtained from governmental databases. RESULTS: Of 88 patients, the mean age at EOGC diagnosis was 39 years and 55% fulfilled the criteria for hereditary diffuse gastric cancer. The majority of the tumors were diffuse (74%) and poorly differentiated (80%). In total, 4 novel missense variants of uncertain significance (VUS) were identified: c.313T>A, c.387G>T, c.1676G>A, and c.1806C>A. The MLPA results revealed no rearrangements and CDH1 transcription analysis for variants of interest were inconclusive. EOGC patients had a higher red (OR:2.6, 95%CI:1.4-4.9) and processed (OR:3.1, 95%CI:1.6-6.0) meat intake and higher fruit consumption (OR:0.4, 95%IC:0.3-0.7) compared to eating habits of the Brazilian population. CONCLUSIONS: No unequivocal pathogenic germline CDH1 variants were identified in Brazilian EOGC patients. Dietary habits may be associated with the EOGC development.

Adverse events of self-expandable esophageal metallic stents in patients with long-term survival from advanced malignant disease.

BACKGROUND AND AIMS: Self-expandable metallic stents are considered the best palliative treatment of dysphagia for patients with advanced esophageal cancer. Adverse events (AEs) are a major concern, especially in patients with better prognosis and longer survival. The present study aimed to evaluate the AEs of patients who survived longer than 6 months with esophageal stents in place. METHODS: This is a retrospective analysis of a prospectively collected database including all patients submitted to esophageal stent placement for the palliation of malignant diseases during the period from February 2009 to February 2014 at a tertiary care academic center who had stents longer than 6 months. RESULTS: Sixty-three patients were included. Mean follow-up was 10.7 months. Clinical success was achieved in all patients, and the median stent patency was 7.1 months. AEs occurred in 40 patients (63.5%), totaling 62 AEs (mean, 1.5 AEs per patient). Endoscopic management of AEs was successful in 84.5% of cases, with a mean of 1.6 reinterventions per patient. The univariate analysis revealed that performance status, age, and post-stent radiotherapy presented a trend to higher risk of AEs. The multivariate analysis revealed that only performance status was associated with AEs (P = .025; hazard ratio, 4.1). CONCLUSIONS: AEs are common in patients with long-term esophageal stenting for malignancy. However, AEs were not related to higher mortality rate, and most AEs could be successfully managed by endoscopy. Only performance status was a risk factor for AEs. Our data suggest that metallic stenting is a valid option for the treatment of malignant esophageal conditions, even when survival longer than 6 months is expected.

Efficacy of 3-Dimensional Endorectal Ultrasound for Staging Early Extraperitoneal Rectal Neoplasms.

BACKGROUND: Adequate oncologic staging of rectal neoplasia is important for treatment and prognostic evaluation of the disease. Diagnostic methods such as endorectal ultrasound can assess rectal wall invasion and lymph node involvement. OBJECTIVE: The purpose of this study was to correlate findings of 3-dimensional endorectal ultrasound and pathologic diagnosis of extraperitoneal rectal tumors with regard to depth of rectal wall invasion, lymph node involvement, percentage of rectal circumference involvement, and tumor extension. DESIGN: Consecutive patients with extraperitoneal rectal tumors were prospectively assessed by 3-dimensional endorectal ultrasound blind to other staging methods and pathologic diagnosis. PATIENTS: Patients who underwent endorectal ultrasound followed by surgery were included in the study. SETTINGS: The study was conducted at a single academic institution. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values, area under curve, and κ coefficient between 3-dimensional endorectal ultrasound and pathologic diagnosis were determined. Intraclass correlation coefficient was calculated for tumor extension and percentage of rectal wall involvement. RESULTS: Forty-four patients (27 women; mean age = 63.5 years) were evaluated between September 2010 and June 2014. Most lesions were malignant (72.7%). For depth of submucosal invasion, 3-dimensional endorectal ultrasound showed sensitivity of 77.3%, specificity of 86.4%, positive predictive value of 85.0%, a negative predictive value of 79.2%, and an area under curve of 0.82. The weighted κ coefficient for depth of rectal wall invasion staging was 0.67, and there was no agreement between 3-dimensional endorectal ultrasound and pathologic diagnosis for lymph node involvement (κ = -0.164). Intraclass correlation coefficient for lesion extension and percentage of rectal circumference involvement were 0.45 and 0.66. A better correlation between 3-dimensional endorectal ultrasound and pathologic diagnosis was observed in tumors <5 cm and with <50% of rectal wall involvement. LIMITATIONS: The relatively small sample size of patients with early rectal lesions referred directly for surgery could represent a potential selection bias. CONCLUSIONS: Three-dimensional endorectal ultrasound was effective for determining rectal wall invasion and lesion extension in tumors <5 cm and with <50% of rectal wall invasion but was limited for detecting lymph node involvement in early rectal lesions.

Lymphoepithelioma-like gastric carcinoma: clinicopathological characteristics and infection status.

BACKGROUND: Lymphoepithelioma-like gastric carcinoma (LLGC) is a rare subtype of gastric carcinoma (GC) characterized by prominent lymphocytic infiltration. LLGC may be associated with latent Epstein-Barr virus (EBV) infection or microsatellite instability (MSI). This study aims to assess the clinicopathological characteristics, EBV infection, and MSI status in LLGC. METHODS: A retrospective analysis of GC patients submitted to potentially curative resection between 2009 and 2014 was performed. The LLGC subtype specimens were examined for EBV by in situ hybridization and MSI by immunohistochemical analysis. The LLGC profile was analyzed accordingly to clinicopathological parameters. RESULTS: From 255 patients, seven were identified on the pathological report as LLGC. Six cases were EBV-positive and one had MSI, showing loss of MLH1 and PMS2 expression. LLGC was more frequently seen in men, and the mean age was 69 years. When compared to non-LLGC, LLGC cases were larger (∼5.8 cm) poorly differentiated tumors and had lower incidence of lymph node metastasis (P = 0.045). Mean number of lymph nodes dissected in the LLGC group was 39.5, and only one patient had a single positive lymph node. In addition, two patients presented associated lesions. LLGC was not associated with HER-2, chromogranin and synaptophysin positivity or Helicobacter pylori infection. CONCLUSIONS: Distinct pathological aspects and clinical behavior of LLGC reinforce the need for proper recognition of this histological subtype to choose better therapeutic approaches.

Carnoy's solution increases the number of examined lymph nodes following gastrectomy for adenocarcinoma: a randomized trial.

BACKGROUND: Pathological examination of a minimum of 16 lymph nodes is recommended following surgery for gastric adenocarcinoma, despite this a longer survival is expected when 30 or more lymph nodes are examined. Small lymph nodes are difficult to identify, and fat-clearing solutions have been proposed to improve this, but there is no evidence of their clinical benefit. METHODS: Fifty D2 subtotal gastrectomy specimens were randomized for fixation in Carnoy's solution (CS) or 10% neutral buffered formalin (NBF), with subsequent fat dissection. After dissection, the residual fat from the NBF group, instead of being discarded, was immersed in CS and dissected again. Data from 25 D2 subtotal gastrectomies performed before the study were also analyzed. RESULTS: The mean number of examined lymph nodes was 50.4 and 34.8 for CS and NBF, respectively (p < 0.001). Missing lymph nodes were found in all cases from the residual fat group (mean of 16.9), and in eight of them (32%) metastatic lymph nodes were present; this allowed the upstaging of two patients. Lymph nodes in the CS group were smaller than those in the NBF group (p = 0.01). The number of retrieved lymph nodes was similar among the NBF and Retrospective groups (p = 0.802). CONCLUSIONS: Compared with NBF, CS increases lymph node detection following gastrectomy and allows a more accurate pathological staging. No influence of the research protocol on the number of examined lymph nodes was observed.

A REVIEW TO HONOR THE HISTORICAL CONTRIBUTIONS OF PAULINE GROSS, ALDRED WARTHIN, AND HENRY LYNCH IN THE DESCRIPTION AND RECOGNITION OF INHERITANCE IN COLORECTAL CANCER.

The present manuscript aimed to review the historical development and most important contributions regarding Lynch Syndrome since its first description, more than a century ago. In 1895, a reputed pathologist from Michigan University, Dr. Aldred Scott Warthin, got intrigued by the family history of a local seamstress called Pauline Gross. According to her prevision, she would present an early death due to cancer, which actually happened (from the uterus). Historically, her family was designated "Family G", comprising a group recognized as the longest and most detailed cancer genealogy that has ever been studied. Warthin concluded that its members had genetic susceptibility for cancer, and they are, nowadays, considered the first reported Lynch Syndrome family. At that time, however, the medical cancer community was far less receptive to the association between heredity and cancer, despite the description of other families with similar heredograms. Unfortunately, this historical fact remained somewhat dormant until another investigator inaugurated a new era in the understanding of family cancer clusters. After reports and studies from this family and many others, the condition initially called Cancer Family Syndrome was changed to the eponym Lynch Syndrome. This was a recognition of the extensive and dedicated work developed by Dr. Henry Lynch in describing various characteristics of the disease, and his efforts to establish the correct recommendations for its diagnosis and treatment. Although the future announces there is still far to go for a complete understanding of Lynch Syndrome, the remarkable contributions of Pauline's intuition, Warthin's perseverance, and Lynch's work consistency must never be forgotten by those who already have or will still benefit from this knowledge.

THE VALUE OF PREOPERATIVE PROGNOSTIC NUTRITIONAL INDEX IN GASTRIC CANCER AFTER CURATIVE RESECTION.

BACKGROUND: Predicting short- and long-term outcomes of oncological therapies is crucial for developing effective treatment strategies. Malnutrition and the host immune status significantly affect outcomes in major surgeries. AIMS: To assess the value of preoperative prognostic nutritional index (PNI) in predicting outcomes in gastric cancer patients. METHODS: A retrospective cohort analysis was conducted on patients undergoing curative-intent surgery for gastric adenocarcinoma between 2009 and 2020. PNI was calculated as follows: PNI=(10 x albumin [g/dL])+(0.005 x lymphocytes [nº/mm3]). The optimal cutoff value was determined by the receiver operating characteristic curve (PNI cutoff=52), and patients were grouped into low and high PNI. RESULTS: Of the 529 patients included, 315 (59.5%) were classified as a low-PNI group (PNI<52) and 214 (40.5%) as a high-PNI group (PNI≥52). Older age (p=0.050), male sex (p=0.003), American Society of Anesthesiologists score (ASA) III/IV (p=0.001), lower hemoglobin level (p<0.001), lower body mass index (p=0.001), higher neutrophil-lymphocyte ratio (p<0.001), D1 lymphadenectomy, advanced pT stage, pN+ and more advanced pTNM stage were related to low-PNI patient. Furthermore, 30-day (1.4 vs. 4.8%; p=0.036) and 90-day (3.3 vs. 10.5%; p=0.002) mortality rates were higher in low-PNI compared to high-PNI group. Disease-free and overall survival were worse in low-PNI patients compared to high-PNI (p<0.001 for both). ASA III/IV score, low-PNI, pT3/T4, and pN+ were independent risk factors for worse survival. CONCLUSIONS: Preoperative PNI can predict short- and long-term outcomes of patients with gastric cancer after curative gastrectomy. Low PNI is an independent factor related to worse disease-free and overall survival.

TUMOR MARKERS EXPRESSION LEVELS IN GASTRIC CANCER PATIENT'S PERIPHERAL BLOOD BY RT-PCR ASSESSMENT.

BACKGROUND: Hematological recurrence is the second most frequent cause of failure in the treatment of gastric cancer. The detection of circulating tumor markers in peripheral blood by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) method may be a useful tool to predict recurrence and determine the patient's prognosis. However, no consensus has been reached regarding the association between the tumor markers level in peripheral blood and its impact on patient survival. AIMS: To evaluate the expression of the circulating tumor markers CK20 and MUC1 in peripheral blood samples from patients with gastric cancer by qRT-PCR, and to verify the association of their expression levels with clinicopathological characteristics and survival. METHODS: A total of 31 patients with gastric adenocarcinoma were prospectively included in this study. CK20 and MUC1 expression levels were analyzed from peripheral blood by the qRT-PCR technique. RESULTS: There was no statistically significant (p>0.05) association between CK20 expression levels and clinical, pathological, and surgical features. Higher MUC1 expression levels were associated with female patients (p=0.01). There was a correlation between both gene levels (R=0.81, p<0.001), and CK20 level and tumor size (R=0.39, p=0.034). CONCLUSIONS: CK20 and MUC1 expression levels could be assessed by qRT-PCR from total peripheral blood samples of patients with gastric cancer. CK20 levels were correlated to MUC1 levels as well as to tumor size. There was no difference in disease-free survival and overall survival regarding both genetic markers expression in this series.

PALLIATIVE GASTRECTOMY VERSUS GASTRIC BYPASS FOR SYMPTOMATIC CLINICAL STAGE IV GASTRIC CANCER: A PROPENSITY SCORE MATCHING ANALYSIS.

BACKGROUND: Patients with clinical stage IV gastric cancer may require palliative procedures to manage complications such as obstruction. However, there is no consensus on whether performing palliative gastrectomy compared to gastric bypass brings benefits in terms of survival. AIMS: To compare the overall survival of patients with distal obstructive gastric cancer undergoing palliative surgical treatment, using propensity score matching analysis. METHODS: Patients who underwent palliative bypass surgery (gastrojejunostomy or partitioning) and resection between the years 2009 and 2023 were retrospectively selected. Initial and postoperative clinicopathological variables were collected. RESULTS: 150 patients were initially included. The derived group (n=91) presented more locally invasive disease (p<0.01), greater degree of obstruction (p<0.01), and worse clinical status (p<0.01), while the resected ones (n= 59) presented more distant metastasis (p<0.01). After matching, 35 patients remained in each group. There was no difference in the incidence of postoperative complications, but the derived group had higher 90-day mortality (p<0.01). Overall survival was 16.9 and 4.5 months for the resected and derived groups, respectively (p<0.01). After multivariate analysis, hypoalbuminemia (hazard ratio - HR=2.02, 95% confidence interval - 95%CI 1.17-3.48; p=0.01), absence of adjuvant chemotherapy (HR=5.97; 95%CI 3.03-11.7; p<0.01), and gastric bypass (HR=3,28; 95%CI 1.8-5.95; p<0.01) were associated with worse survival. CONCLUSIONS: Palliative gastrectomy was associated with greater survival and lower postoperative morbidity compared to gastric bypass. This may be due to better local control of the disease, with lower risks of complications and better effectiveness of chemotherapy.

PERIOPERATIVE CARE IN DIGESTIVE SURGERY: THE ERAS AND ACERTO PROTOCOLS - BRAZILIAN COLLEGE OF DIGESTIVE SURGERY POSITION PAPER.

BACKGROUND: The concept introduced by protocols of enhanced recovery after surgery modifies perioperative traditional care in digestive surgery. The integration of these modern recommendations components during the perioperative period is of great importance to ensure fewer postoperative complications, reduced length of hospital stay, and decreased surgical costs. AIMS: To emphasize the most important points of a multimodal perioperative care protocol. METHODS: Careful analysis of each recommendation of both ERAS and ACERTO protocols, justifying their inclusion in the multimodal care recommended for digestive surgery patients. RESULTS: Enhanced recovery programs (ERPs) such as ERAS and ACERTO protocols are a cornerstone in modern perioperative care. Nutritional therapy is fundamental in digestive surgery, and thus, both preoperative and postoperative nutrition care are key to ensuring fewer postoperative complications and reducing the length of hospital stay. The concept of prehabilitation is another key element in ERPs. The handling of crystalloid fluids in a perfect balance is vital. Fluid overload can delay the recovery of patients and increase postoperative complications. Abbreviation of preoperative fasting for two hours before anesthesia is now accepted by various guidelines of both surgical and anesthesiology societies. Combined with early postoperative refeeding, these prescriptions are not only safe but can also enhance the recovery of patients undergoing digestive procedures. CONCLUSIONS: This position paper from the Brazilian College of Digestive Surgery strongly emphasizes that the implementation of ERPs in digestive surgery represents a paradigm shift in perioperative care, transcending traditional practices and embracing an intelligent approach to patient well-being.

Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic.

Introduction: The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency. Methods: At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output. Results: Over the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020-2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19. Discussion: Research is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.