Claudin 18.2 as a New Biomarker in Gastric Cancer-What Should We Know?

Gastric cancer (GC) remains a formidable global health challenge, ranking among the top-five causes of cancer-related deaths worldwide. The majority of patients face advanced stages at diagnosis, with a mere 6% five-year survival rate. First-line treatment for metastatic GC typically involves a fluoropyrimidine and platinum agent combination; yet, predictive molecular markers have proven elusive. This review navigates the evolving landscape of GC biomarkers, with a specific focus on Claudin 18.2 (CLDN18.2) as an emerging and promising target. Recent phase III trials have unveiled the efficacy of Zolbetuximab, a CLDN18.2-targeting antibody, in combination with oxaliplatin-based chemotherapy for CLDN18.2-positive metastatic GC. As this novel therapeutic avenue unfolds, understanding the nuanced decision making regarding the selection of anti-CLDN18.2 therapies over other targeted agents in metastatic GC becomes crucial. This manuscript reviews the evolving role of CLDN18.2 as a biomarker in GC and explores the current status of CLDN18.2-targeting agents in clinical development. The aim is to provide concise insights into the potential of CLDN18.2 as a therapeutic target and guide future clinical decisions in the management of metastatic GC.

Targeting KRAS in Pancreatic Ductal Adenocarcinoma: The Long Road to Cure.

Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of cancer-related mortality, and it is expected to play an even bigger part in cancer burden in the years to come. Despite concerted efforts from scientists and physicians, patients have experienced little improvement in survival over the past decades, possibly because of the non-specific nature of the tested treatment modalities. Recently, the discovery of potentially targetable molecular alterations has paved the way for the personalized treatment of PDAC. Indeed, the central piece in the molecular framework of PDAC is starting to be unveiled. KRAS mutations are seen in 90% of PDACs, and multiple studies have demonstrated their pivotal role in pancreatic carcinogenesis. Recent investigations have shed light on the differences in prognosis as well as therapeutic implications of the different KRAS mutations and disentangled the relationship between KRAS and effectors of downstream and parallel signaling pathways. Additionally, the recognition of other mechanisms involving KRAS-mediated pathogenesis, such as KRAS dosing and allelic imbalance, has contributed to broadening the current knowledge regarding this molecular alteration. Finally, KRAS G12C inhibitors have been recently tested in patients with pancreatic cancer with relative success, and inhibitors of KRAS harboring other mutations are under clinical development. These drugs currently represent a true hope for a meaningful leap forward in this dreadful disease.

Current clinical practice in the management of Brazilian patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC).

BACKGROUND AND OBJECTIVES: We aimed to describe the routine clinical practice of physicians involved in the treatment of patients with localized pancreatic ductal adenocarcinoma (PDAC) in Brazil. METHODS: Physicians were invited through email and text messages to participate in an electronic survey sponsored by the Brazilian Gastrointestinal Tumor Group (GTG) and the Brazilian Society of Surgical Oncology (SBCO). We evaluated the relationship between variable categories numerically with false discovery rate-adjusted Fisher's exact test p values and graphically with Multiple Correspondence Analysis. RESULTS: Overall, 255 physicians answered the survey. Most (52.5%) were medical oncologists, treated patients predominantly in the private setting (71.0%), and had access to multidisciplinary tumor boards (MTDTB; 76.1%). Medical oncologists were more likely to describe neoadjuvant therapy as beneficial in the resectable setting and surgeons in the borderline resectable setting. Most physicians would use information on risk factors for early recurrence, frailty, and type of surgery to decide treatment strategy. Doctors working predominantly in public institutions were less likely to have access to MTDTB and to consider FOLFIRINOX the most adequate regimen in the neoadjuvant setting. CONCLUSIONS: Considerable differences exist in the management of localized PDAC, some of them possibly explained by the medical specialty, but also by the funding source of health care.

PD-L1 testing in advanced gastric cancer-what physicians who treat this disease must know-a literature review.

Background and Objective: Immune checkpoint inhibition has shed light on a new era in cancer therapy, and randomized clinical trials have demonstrated that a meaningful portion of the overall population of metastatic gastric cancer (GC) patients may derive clinical benefit from immunotherapy, which raises the relevance in identifying predictive biomarkers. Programmed cell death-ligand 1 (PD-L1) expression has demonstrated a significant association between level of expression and the magnitude of benefit derived from immune checkpoint inhibition in GC. Nevertheless, this biomarker shows several pitfalls that must be considered in the therapeutic decision to incorporate immune checkpoint inhibition as the standard of care of GC, such as spatial and temporal heterogeneity, interobserver variability, immunohistochemistry (IHC) assay, and influence by chemotherapy or radiation therapy. Methods: In the present comprehensive review, we revised the main studies regarding PD-L1 evaluation in GC. Key Content and Findings: Here we describe the molecular characteristics of the tumor microenvironment in GC, the obstacles in the interpretation of PD-L1 expression and present the data of the clinical trials that have evaluated the efficacy and safety of immune checkpoint inhibition and the association with the biomarker expression, both in first-line and later lines of therapy. Conclusions: From the emerging predictive biomarkers for immune checkpoint inhibition, PD-L1 has demonstrated a meaningful association between level of expression in tumor microenvironment and the magnitude of benefit derived from immune checkpoint inhibition in GC.

Unresectable metastatic colorectal cancer in fit patients - a practical algorithm of treatment sequencing from the Brazilian Group of Gastrointestinal Tumours (GTG).

Recent advances in biomarker-driven therapies have changed the landscape of unresectable metastatic colorectal cancer (mCRC) and brought not only access issues but also difficulties for the treating physician (especially generalist oncologists) in choosing the most suitable treatment for each individual patient. This manuscript proposes an algorithm developed by The Brazilian Group of Gastrointestinal Tumours with the aim of bringing easy-to-follow steps in the management of unresectable mCRC. The algorithm is based on evidence for fit patients to facilitate therapeutic decisions in the clinical practice and assumes that there are no access and resource limitations.

Current Molecular Profile of Gastrointestinal Stromal Tumors and Systemic Therapeutic Implications.

Gastrointestinal stromal tumors (GISTs) are malignant mesenchymal tumors arising from the intestinal pacemaker cells of Cajal. They compose a heterogenous group of tumors due to a variety of molecular alterations. The most common gain-of-function mutations in GISTs are either in the KIT (60-70%) or platelet-derived growth factor receptor alpha (PDGFRA) genes (10-15%), which are mutually exclusive. However, a smaller subset, lacking KIT and PDGFRA mutations, is considered wild-type GISTs and presents distinct molecular findings with the activation of different proliferative pathways, structural chromosomal and epigenetic changes, such as inactivation of the NF1 gene, mutations in the succinate dehydrogenase (SDH), BRAF, and RAS genes, and also NTRK fusions. Currently, a molecular evaluation of GISTs is imperative in many scenarios, aiding in treatment decisions from the (neo)adjuvant to the metastatic setting. Here, we review the most recent data on the molecular profile of GISTs and highlight therapeutic implications according to distinct GIST molecular subtypes.

Biomarkers in Anal Cancer: Current Status in Diagnosis, Disease Progression and Therapeutic Strategies.

Squamous cell carcinoma of the anal canal (SCCA) is a rare neoplasm, but with rising incidence rates in the past few decades; it is etiologically linked with the human papillomavirus (HPV) infection and is especially prevalent in immunocompromised patients, mainly those infected with HIV. Fluoropyrimidine-based chemoradiotherapy remains the cornerstone of the treatment of non-metastatic disease, but the locally advanced disease still presents high rates of disease recurrence and systemic therapy of SCCA is an unmet clinical need. Despite sharing common molecular aspects with other HPV-related malignancies, such as cervical and head and neck cancers, SCCA presents specific epigenomic, genomic, and transcriptomic abnormalities, which suggest that genome-guided personalized therapies should be specifically designed for this disease. Actionable mutations are rare in SCCA and immune checkpoint inhibition has not yet been proven useful in an unselected population of patients. Therefore, advances in systemic therapy of SCCA will only be possible with the identification of predictive biomarkers and the subsequent development of targeted therapies or immunotherapeutic approaches that consider the unique tumor microenvironment and the intra- and inter-tumoral heterogeneity. In the present review, we address the molecular characterization of SCCA and discuss potential diagnostic, predictive and prognostic biomarkers of this complex and challenging disease.

Biologics in rectal cancer.

INTRODUCTION: Despite the use of multimodality therapy, locally advanced rectal cancer (LARC) still presents high rates of disease recurrence. Fluoropyrimidine-based chemotherapy concurrently with radiation therapy (RT) remains the cornerstone of neoadjuvant therapy of LARC, and novel therapies are urgently needed in order to improve the clinical outcomes. AREAS COVERED: We aim to summarize data from completed and ongoing clinical trials addressing the role of biological therapies, including monoclonal antibodies, immune checkpoint inhibitors (ICIs), antibody-drug conjugates, bispecific antibodies, and gene therapies in the systemic therapy of rectal cancer. EXPERT OPINION: Deeper understanding of the molecular biology of colorectal cancer (CRC) has allowed meaningful advances in the systemic therapy of metastatic disease in the past few years. The larger applicability of biological therapy in CRC, including genome-guided targeted therapy, antiangiogenics, and immunotherapy, gives us optimism for the personalized management of rectal cancer. Microsatellite instability (MSI) tumors have demonstrated high sensitivity to ICIs, and preliminary findings in the neoadjuvant setting of rectal cancer are promising. To date, antiangiogenic and anti-EGFR therapies in LARC have not demonstrated the same benefit seen in metastatic disease. The outstanding results accomplished by biomarker-guided therapy in metastatic CRC will guide future developments of biological therapy in LARC.

Clostridium difficile Infection Leading to Intestinal Pneumatosis in a Patient with a Recent Diagnosis of Pancreatic Cancer Local Recurrence: A Case Report and Literature Review.

Clostridium difficile infection (CDI) causing pneumatosis intestinalis (PI) is a rare event, described mostly in immunocompromised patients. We present the case of a 65-year-old female diagnosed with adenocarcinoma of the pancreas who underwent a duodenopancreatectomy with lymphadenectomy and adjuvant gemcitabine and capecitabine. Four months after the end of chemotherapy, she experienced abdominal pain and intermittent diarrhea which became aggravated within 6 months. CT scans revealed diffuse intestinal pneumatosis and recurrence of ductal adenocarcinoma. We hypothesize that local pancreatic cancer recurrence may lead to gastrointestinal dysmotility with consequent increased risk for CDI. The patient had almost complete resolution of PI during the CDI treatment, thus we believe that the CDI was directly responsible for PI in this case.

Brazilian Group of Gastrointestinal Tumours' consensus guidelines for the management of oesophageal cancer.

Oesophageal cancer is among the ten most common types of cancer worldwide. More than 80% of the cases and deaths related to the disease occur in developing countries. Local socio-economic, epidemiologic and healthcare particularities led us to create a Brazilian guideline for the management of oesophageal and oesophagogastric junction (OGJ) carcinomas. The Brazilian Group of Gastrointestinal Tumours invited 50 physicians with different backgrounds, including radiology, pathology, endoscopy, nuclear medicine, genetics, oncological surgery, radiotherapy and clinical oncology, to collaborate. This document was prepared based on an extensive review of topics related to heredity, diagnosis, staging, pathology, endoscopy, surgery, radiation, systemic therapy (including checkpoint inhibitors) and follow-up, which was followed by presentation, discussion and voting by the panel members. It provides updated evidence-based recommendations to guide clinical management of oesophageal and OGJ carcinomas in several scenarios and clinical settings.

Brazilian Group of Gastrointestinal Tumours' consensus guidelines for the management of gastric cancer.

Gastric cancer is among the ten most common types of cancer worldwide. Most cases and deaths related to the disease occur in developing countries. Local socio-economic, epidemiologic and healthcare particularities led us to create a Brazilian guideline for the management of gastric carcinomas. The Brazilian Group of Gastrointestinal Tumors (GTG) invited 50 physicians with different backgrounds, including radiology, pathology, endoscopy, nuclear medicine, genetics, oncological surgery, radiotherapy and clinical oncology, to collaborate. This document was prepared based on an extensive review of topics related to heredity, diagnosis, staging, pathology, endoscopy, surgery, radiation, systemic therapy and follow-up, which was followed by presentation, discussion, and voting by the panel members. It provides updated evidence-based recommendations to guide clinical management of gastric carcinomas in several scenarios and clinical settings.

Excellent Response to Olaparib in a Patient with Metastatic Pancreatic Adenocarcinoma with Germline BRCA1 Mutation after Progression on FOLFIRINOX: Case Report and Literature Review.

Metastatic pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. Until recently, cytotoxic chemotherapy was the only treatment option. Currently, there are subgroups of patients with PDAC either with somatic or germline mutations who are candidates for targeted agents. Germline mutations in the BRCA1 and BRCA2 genes promote the incapacity of tumor cells to recover from DNA-accumulated damage caused by cytotoxic drugs, like platinum agents, and, most recently, through a diverse process by poly(adenosine diphosphate-ribose) polymerase inhibitor (PARPi). A 59-year-old female who was treated for a triple negative breast cancer 8 years ago with surgery, adjuvant chemotherapy and radiotherapy, presented with increasing back pain. Investigation revealed multiple liver nodules and a large mass in the head of the pancreas. Biopsy confirmed PDAC. She received 13 cycles of FOLFIRINOX, achieving partial response both in the liver and pancreatic lesion, with resolution of symptoms. Due to increasing neuropathy, chemotherapy was stopped, and the patient was followed. Sixteen months later, her CA19-9 levels increased. Given limiting neuropathy, the patient was restarted on FOLFIRI only. After 8 cycles, there was disease progression plus uncontrolled back pain. A mutational test was requested and confirmed a BRCA1 germline mutation. The patient was started on olaparib. After 3 cycles, images showed a significant response and after 6 cycles, it remained stable, with persistent fall in CA19-9 levels. She is currently on treatment, with ongoing response. In conclusion, patients with metastatic PDAC and BRCA mutation may benefit from PARPi even after progression on chemotherapy. We hypothesize that olaparib works even in the setting of disease progression and not solely as a maintenance therapy following platinum-based therapy. Randomized trials are needed investigating the role of olaparib following disease progression in PDAC.

Gastric neuroendocrine tumor: A practical literature review.

Gastric neuroendocrine tumors are gastric neoplasms originating from enterochromaffin type cells and are inserted in a larger group, named gastroenteropancreatic neuroendocrine tumors. They are considered rare and variable in terms of their clinical, morphological and functional characteristics and may be indolent or aggressive. They are classified into types I, II and III, according to their pathophysiology, behavior and treatment. Their diagnosis occurs, in most cases, incidentally during upper digestive endoscopies, presenting as simple gastric polyps. Most cases (type I and type II) are related to hypergastrinemia, can be multiple and are treated by endoscopic resection, whenever possible. The use of somatostatin analogs for tumor control may be one of the options for therapy, in addition to total or subtotal gastrectomy for selected cases. Adjuvant chemotherapy is only reserved for poorly differentiated neuroendocrine carcinomas. Although rare, gastric neuroendocrine tumors have an increasing incidence over the years, therefore deserving more comprehensive studies on its adequate treatment. The present study reviews and updates management recommendations for gastric neuroendocrine tumors.

BRAZILIAN CONSENSUS ON INCIDENTAL GALLBLADDER CARCINOMA.

BACKGROUND: Incidental gallbladder cancer is defined as a cancer discovered by histological examination after cholecystectomy. It is a potentially curable disease. However, some questions related to their management remain controversial and a defined strategy is associated with better prognosis. AIM: To develop the first evidence-based consensus for management of patients with incidental gallbladder cancer in Brazil. METHODS: Sixteen questions were selected, and 36 Brazilian and International members were included to the answer them. The statements were based on current evident literature. The final report was sent to the members of the panel for agreement assessment. RESULTS: Intraoperative evaluation of the specimen, use of retrieval bags and routine histopathology is recommended. Complete preoperative evaluation is necessary and the reoperation should be performed once final staging is available. Evaluation of the cystic duct margin and routine 16b1 lymph node biopsy is recommended. Chemotherapy should be considered and chemoradiation therapy if microscopically positive surgical margins. Port site should be resected exceptionally. Staging laparoscopy before reoperation is recommended, but minimally invasive radical approach only in specialized minimally invasive hepatopancreatobiliary centers. The extent of liver resection is acceptable if R0 resection is achieved. Standard lymph node dissection is required for T2 tumors and above, but common bile duct resection is not recommended routinely. CONCLUSIONS: It was possible to prepare safe recommendations as guidance for incidental gallbladder carcinoma, addressing the most frequent topics of everyday work of digestive and general surgeons.

Evidence-based recommendations for gastrointestinal cancers during the COVID-19 pandemic by the Brazilian Gastrointestinal Tumours Group.

PURPOSE: As of 2020, the world is facing the great challenge of the COVID-19 (Coronavirus disease 2019) pandemic, caused by the SARS-CoV-2 virus. While the overall mortality is low, the virus is highly virulent and may infect millions of people worldwide. This will consequently burden health systems, particularly by those individuals considered to be at high risk of severe complications from COVID-19. Such risk factors include advanced age, cardiovascular and pulmonary diseases, diabetes and cancer. However, few data on the outcomes of cancer patients infected by SARS CoV-2 exist. Therefore, there is a lack of guidance on how to manage cancer patients during the pandemic. We sought to propose specific recommendations about the management of patients with gastrointestinal malignancies. METHODS: The Brazilian Gastrointestinal Tumours Group board of directors and members sought up-to-date scientific literature on each tumour type and discussed all recommendations by virtual meetings to provide evidence-based-and sometimes, expert opinion-recommendation statements. Our objectives were to recommend evidence-based approaches to both treat and minimise the risk of COVID-19 for cancer patients, and simultaneously propose how to decrease the use of hospital resources at a time these resources need to be available to treat COVID-19 patients. RESULTS: Overall and tumour-specific recommendations were made by stage (including surgical, locoregional, radiotherapy, systemic treatments and follow-up strategies) for the most common gastrointestinal malignancies: esophagus, gastric, pancreas, bile duct, hepatocellular, colorectal, anal cancer and neuroendocrine tumours. CONCLUSIONS: Our recommendations emphasise the importance of treating cancer patients, using the best evidence available, while simultaneously taking into consideration the world-wide health resource hyperutilisation to treat non-cancer COVID-19 patients.

Brazilian consensus on incidental gallbladder carcinoma / Consenso brasileiro de carcinoma incidental de vesícula biliar

ABSTRACT Background: Incidental gallbladder cancer is defined as a cancer discovered by histological examination after cholecystectomy. It is a potentially curable disease. However, some questions related to their management remain controversial and a defined strategy is associated with better prognosis. Aim: To develop the first evidence-based consensus for management of patients with incidental gallbladder cancer in Brazil. Methods: Sixteen questions were selected, and 36 Brazilian and International members were included to the answer them. The statements were based on current evident literature. The final report was sent to the members of the panel for agreement assessment. Results: Intraoperative evaluation of the specimen, use of retrieval bags and routine histopathology is recommended. Complete preoperative evaluation is necessary and the reoperation should be performed once final staging is available. Evaluation of the cystic duct margin and routine 16b1 lymph node biopsy is recommended. Chemotherapy should be considered and chemoradiation therapy if microscopically positive surgical margins. Port site should be resected exceptionally. Staging laparoscopy before reoperation is recommended, but minimally invasive radical approach only in specialized minimally invasive hepatopancreatobiliary centers. The extent of liver resection is acceptable if R0 resection is achieved. Standard lymph node dissection is required for T2 tumors and above, but common bile duct resection is not recommended routinely. Conclusions: It was possible to prepare safe recommendations as guidance for incidental gallbladder carcinoma, addressing the most frequent topics of everyday work of digestive and general surgeons.

RESUMO Racional: Carcinoma incidental da vesícula biliar é definido como uma neoplasia descoberta por exame histológico após colecistectomia videolaparoscópica. É potencialmente uma doença curável. Entretanto algumas questões relacionadas ao seu manuseio permanecem controversas e uma estratégia definida está associada com melhor prognóstico. Objetivo: Desenvolver o primeiro consenso baseado em evidências para o manuseio de pacientes com carcinoma incidental da vesícula biliar no Brasil. Métodos: Dezesseis questões foram selecionadas e para responder as questões e 36 membros das sociedades brasileiras e internacionais foram incluídos. As recomendações foram baseadas em evidências da literatura atual. Um relatório final foi enviado para os membros do painel para avaliação de concordância. Resultados: Avaliação intraoperatória da peça cirúrgica, uso de bolsas para retirar a peça cirúrgica e exame histopatológico de rotina, foram recomendados. Avaliação pré-operatória completa é necessária e deve ser realizada assim que o estadiamento final esteja disponível. Avaliação da margem do ducto cístico e biópsia de rotina do linfonodo 16b1 são recomendadas. Quimioterapia deve ser considerada e quimioradioterapia indicada se a margem cirúrgica microscópica seja positiva. Os portais devem ser ressecados excepcionalmente. O estadiamento laparoscópico antes da operação é recomendado, mas o tratamento radical por abordagem minimamente invasiva deve ser realizado apenas em centros especializados em cirurgia hepatopancreatobiliar minimamente invasiva. A extensão da ressecção hepática é aceitável até que seja alcançada a ressecção R0. A linfadenectomia padrão é indicada para tumores iguais ou superiores a T2, mas a ressecção da via biliar não é recomendada de rotina. Conclusões: Recomendações seguras foram preparadas para carcinoma incidental da vesícula biliar, destacando os mais frequentes tópicos do trabalho diário do cirurgião do aparelho digestivo e hepatopancreatobiliar.

PANCREATIC NEUROENDOCRINE TUMORS: SURGICAL RESECTION.

INTRODUCTION: Pancreatic neuroendocrine tumors (pNET) correspond to about 3% of all tumors in pancreas and could be presented as a difficult diagnosis and management. OBJECTIVE: To review the diagnosis and treatment of the pNET available in scientific literature. METHOD: A bibliographic survey was performed by means of an online survey of MeSH terms in the Pubmed database. A total of 104 articles were published in the last 15 years, of which 23 were selected as the basis for the writing of this article. RESULTS: pNET is an infrequent neoplasia and their incidence, in USA, is about 1:100.000 inhabitants/year. Thereabout 30% of them produce hormones presenting as a symptomatic disease and others 70% of the cases could be silent disease. Magnetic Resonance Imaging (MRI) and/or Computed Tomography (CT) have similar sensitivy to detect pNET. They are very important when associated to nuclear medicine mainly Positron Emission Tomography (PET-CT) Gallium-68 to find primary tumor and its staging. The appropriate treatment should be chosen based on characteristics of the tumor, its staging and associated comorbidities. CONCLUSION: The surgical resection is still the best treatment for patients with ressectable pancreatic NETs. However, the size, grade, tumor functionality, stage and association with multiple endocrine neoplasia type 1 (MEN-1) are important to define who will be eligible for surgical treatment. In general, tumors bigger than 2 cm are eligible for surgical treatment, except insulinomas whose surgical resection is recommended no matter the size.

Pancreatic neuroendocrine tumors: surgical resection / Tumores neuroendócrinos ressecáveis do pâncreas: abordagem cirúrgica

ABSTRACT Introduction: Pancreatic neuroendocrine tumors (pNET) correspond to about 3% of all tumors in pancreas and could be presented as a difficult diagnosis and management. Objective: To review the diagnosis and treatment of the pNET available in scientific literature. Method: A bibliographic survey was performed by means of an online survey of MeSH terms in the Pubmed database. A total of 104 articles were published in the last 15 years, of which 23 were selected as the basis for the writing of this article. Results: pNET is an infrequent neoplasia and their incidence, in USA, is about 1:100.000 inhabitants/year. Thereabout 30% of them produce hormones presenting as a symptomatic disease and others 70% of the cases could be silent disease. Magnetic Resonance Imaging (MRI) and/or Computed Tomography (CT) have similar sensitivy to detect pNET. They are very important when associated to nuclear medicine mainly Positron Emission Tomography (PET-CT) Gallium-68 to find primary tumor and its staging. The appropriate treatment should be chosen based on characteristics of the tumor, its staging and associated comorbidities. Conclusion: The surgical resection is still the best treatment for patients with ressectable pancreatic NETs. However, the size, grade, tumor functionality, stage and association with multiple endocrine neoplasia type 1 (MEN-1) are important to define who will be eligible for surgical treatment. In general, tumors bigger than 2 cm are eligible for surgical treatment, except insulinomas whose surgical resection is recommended no matter the size.

RESUMO Introdução: Os tumores neuroendócrinos pancreáticos (TNE-P) correspondem a cerca de 3% de todas as neoplasias no pâncreas e são de diagnóstico e manejo difíceis. Objetivo: Revisar o diagnóstico e tratamento desses tumores disponíveis na literatura científica atual. Método: Foi realizado levantamento bibliográfico por meio de pesquisa online de MeSH terms na base de dados do Pubmed. Ao todo foram analisados 104 artigos publicados nos últimos 15 anos, dos quais 23 foram selecionados como base para a redação deste artigo. Resultados: TNE-P é neoplasia pouco frequente com incidência estimada em 1: 100.000 habitantes/ano. Cerca de 30% produzem hormônios, ditos funcionantes, que se apresentam como doença sintomática e outros 70% podem se apresentar como doença silenciosa. Como recurso diagnóstico o uso de tomografia computadorizada ou ressonância nuclear magnética apresentam níveis de sensibilidade parecidas. Sua associação à recursos da medicina nuclear são de grande valia para localização de tumores primários e estadiamento, destacando-se o uso da tomografia por emissão de pósitrons (PET-CT) com Gálio-68. A decisão terapêutica deve ser baseada nas características tumorais, estadiamento e comorbidades associadas. Conclusão: A abordagem cirúrgica permanece como a terapia de escolha para pacientes com TNE-P ressecáveis. No entanto, a seleção de pacientes para tratamento cirúrgico deve seguir critérios baseados em funcionalidade do tumor, grau, estágio e associação com neoplasia múltipla tipo 1. De forma geral, tumores maiores de 2 cm têm indicação cirúrgica, excetuando-se os insulinomas, cuja proposta cirúrgica independe de seu tamanho.

Complete Response for More than 4 Years following Neoadjuvant FOLFOX and Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for a Patient with Advanced Gastric Cancer with Extensive Peritoneal Carcinomatosis.

BACKGROUND: Peritoneal carcinomatosis is usually a terminal disease with short median survival in patients with gastric cancer. Systemic FOLFOX is one of the most used regimens in the first-line treatment of metastatic gastric cancer. However, there is scarce evidence that cytoreductive surgery (CRS) and intraperitoneal heated chemotherapy (HIPEC) improves oncological outcomes of patients with advanced gastric cancer. METHODS: Herein we present a case of a young woman with advanced gastric cancer with omental and peritoneal metastases who achieved an excellent response after 6 months of FOLFOX followed by CRS and HIPEC. RESULTS: A 53-year-old woman was diagnosed with advanced gastric carcinoma, with extensive omental caking and several peritoneal implants measuring 2 cm at the largest diameter. The patient received mFOLFOX6 for 6 months with excellent clinical and radiographic response. She was then submitted to a D2 total gastrectomy followed by CRS and HIPEC with mitomycin. The final pathology report showed a focal adenocarcinoma in the stomach measuring 0.4 mm with no residual tumor in the peritoneum (ypT1ypN0). The patient has been well and disease free for more than 4 years. CONCLUSION: While still controversial, CRS followed by HIPEC may be a curative therapeutic option for highly selected patients.

TWELVE YEARS OF EXPERIENCE USING CHOLECYSTOJEJUNAL BY-PASS FOR PALLIATIVE TREATMENT OF ADVANCED PANCREATIC CANCER.

BACKGROUND: The cholecistojejunal bypass is an important resource to treat obstructive jaundice due to advanced pancreatic cancer. AIM: To assess the early morbidity and mortality of patients with pancreatic cancer who underwent cholecystojejunal derivation, and to assess the success of this procedure in relieving jaundice. METHOD: This retrospective study examined the medical records of patients who underwent surgery. They were categorized into early death and non-early death groups according to case outcome. RESULTS: 51.8% of the patients were male and 48.2% were female. The mean age was 62.3 years. Early mortality was 14.5%, and 10.9% of them experienced surgical complications. The cholecystojejunostomy procedure was effective in 97% of cases. There was a tendency of increased survival in women and patients with preoperative serum total bilirubin levels below 15 mg/dl. CONCLUSION: Cholecystojejunal derivation is a good therapeutic option for relieving jaundice in patients with advanced pancreatic cancer, with acceptable rates of morbidity and mortality.