Prognostic factors and management of colorectal gastrointestinal stromal tumors

Introduction: The gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Even though it can be found in any location of the digestive tract, the colorectal GIST is rare. With this study, we aim to review the current knowledge regarding the prognosis and management of colorectal GIST. Methods: A literature search was conducted in PubMed, and 717 articles were collected. After analyzing these studies, 60 articles were selected to use in this review. Results: The mitotic index, as well as tumor size and location were identified as good discriminators of prognosis in various studies. Surgery remains the only curative therapy for potentially resectable tumors. However, even after surgical resection, some patients develop disease recurrence and metastasis, especially those with highrisk tumors. Therefore, surgical resection alone might be inadequate for the management of all colorectal GISTs. The discovery of GIST's molecular pathway led to a shift in its therapy, insofar as tyrosine kinase inhibitors became part of the treatment schemes for this tumor, revolutionizing the treatment's outcome and prognosis. Discussion/Conclusion: The controversy concerning colorectal GIST prognosis and treatment can be, in part, attributed to the limited number of studies in the literature. In this review, we gathered the most recent knowledge about the prognosis and management of GIST in this rare location and propose two algorithms for its approach. Lastly, we highlight the importance of an individualized approach in the setting of a multidisciplinary team. (AU)

Hope as a Lifeline: Imatinib Discontinuation in Patients With Oligometastatic Gastrointestinal Stromal Tumours.

BACKGROUND/AIM: This study explored how highly selected oligometastatic gastrointestinal stromal tumour (GIST) patients subjectively experienced the discontinuation of imatinib (IM) treatment. PATIENTS AND METHODS: Being an exploratory qualitative study, we applied a phenomenological and hermeneutical approach. We conducted in-depth semi-structured interviews with nine oligometastatic GIST patients who were in long-term clinical remission. The gathered data were interpreted using a thematic analysis. RESULTS: The analysis of the interview data revealed four main themes; getting one's life back, fear of recurrence, hope as a lifeline and the pros/cons of participating in this clinical trial. The participants disclosed that hope of being cancer free and without the side-effects of IM was essential for both participating in this study and enduring the uncertainty of drug discontinuation. CONCLUSION: Use of a qualitative approach in clinical trials can result in a better understanding of patients' perspectives and therefore lead to improved clinical practice.

Rare gastrointestinal metastases from primary lung cancer. Two case reports of patients managed with emergency surgery.

BACKGROUND: Lung cancer represents the second leading cause of death in US and the high mortality rate could be related to the diagnosis, usually, performed in an advanced metastatic stage. Gastrointestinal metastases from non-small cell lung cancer, are extremely rare and only few cases complicated by digestive haemorrhage and/or perforation have been reported in literature. MATERIAL AND METHODS: We report two cases of gastrointestinal metastases and their rare clinical onset with haemorrhage and perforation of the digestive tract. Both patients were admitted in an emergency setting. The first case was a 59-year-old man complained of abdominal pain and massive gastrointestinal haemorrhage. An upper gastrointestinal endoscopy revealed an ulcerated gastric mass and an emergency CT-scans showed a right lung mass with biopsy conclusive for a large cell lung cancer. The second case was a 62-year-old man with abdominal pain and shock due to gastrointestinal bleeding. He was submitted to an emergency CT-scan showing two lung nodules (1.0 and 3.5 cm of diameter) as well as widespread metastases, intraperitoneal free air and fluids. RESULTS: Both patients were surgical managed in emergency and pathology revealed the metastatic origin from an unknown large-cell lung cancer and a rare lung adenocarcinoma in the second one. CONCLUSIONS: Despite the rare clinical condition, in patients with a diagnosis of lung cancer managed in emergency for gastrointestinal complication, gastrointestinal metastases should be taken into account, and referred to the primary disease in order to tailor the best approach. KEY WORDS: Gastrointestinal metastases, Lung cancer, Tailored surgery.

Clinical characteristics and outcomes of primary versus secondary gastrointestinal mantle cell lymphoma.

Primary gastrointestinal (GI) mantle cell lymphoma (MCL) is rare and the optimal management is unknown. We reviewed 800 newly diagnosed MCL cases and found 22 primary (2.8%) and 79 (9.9%) secondary GI MCL cases. Age, sex, and performance status were similar between primary and secondary cases. Secondary cases had more elevations in lactate dehydrogenase (28% vs 0%, P = 0.03) and a trend for a higher MCL international prognostic index (P = 0.07). Observation or local therapy was more common for primary GI MCL (29% vs 8%, P < 0.01), and autologous stem-cell transplant was more common for secondary GI MCL (35% vs 14%, P < 0.05). The median follow-up was 85 months. Primary and secondary GI MCL had similar 5-year progression-free survival (PFS) (30% vs 28%, P = 0.59) and overall survival (OS) (65% vs 66%, P = 0.83). The extent of GI involvement in primary GI MCL affected treatment selection but not outcome, with a 5-year PFS of 43% vs 14% vs 31% (P = 0.48) and OS of 57% vs 71% vs 69% (P = 0.54) in cases with single lesion vs multiple lesions in 1 organ vs multiple lesions in ≥2 organs. Less aggressive frontline treatment for primary GI MCL is reasonable. It is unknown whether more aggressive treatment can result in improved outcomes.

Gastrointestinal tract metastasis of lung cancer: The PD-L1 expression and correlated clinicopathological variables.

The gastrointestinal tract is a rare site for metastatic lung cancer. Programmed cell death-ligand 1 (PD-L1) expression in lung cancer is a biomarker for the response to anti-PD-1/PD-L1 therapy. We investigated clinicopathological features and PD-L1 expression in 25 gastrointestinal metastatic tumors from the lung and primary adenocarcinoma of the small bowel. The small bowel was the most common site (16/25; 64%) of gastrointestinal tract lung cancer metastasis. A total of 19 (76%) of the gastrointestinal metastasis showed PD-L1 expression in ≥5% of tumor cells, with 14 (56%) showing high expression levels (≥50%). In contrast, 21 (84%) expressed PD-L1 in ≥5% immune cells, including 4 (16%) showing a high expression levels (≥50%). The PD-L1 expression on tumor cells and immune cells in primary lung cancer and corresponding gastrointestinal metastasis was concordant in 13 (68%) and 11 (58%) of the 19 paired cases, respectively. Small-bowel metastasis of lung cancer was characterized by a higher incidence of perforation (31% vs. 0%), ulcerated mass (83% vs. 60%), and neoplastic PD-L1 expression (75% vs. 0%) compared to primary small-bowel adenocarcinoma. Gastrointestinal metastasis from lung cancer might be a potential target for immune checkpoint inhibitor therapy, given its high expression of PD-L1.

Resección laparoscópica de metástasis intestinales de melanoma maligno / Laparoscopic resection of malignant melanoma intestinal metastasis

Resumen Objetivos: El melanoma cutáneo presenta un alto potencial metastásico y constituye la fuente extraabdominal más frecuente de lesión del intestino delgado. El diagnóstico de metástasis gastrointestinales es a menudo una expresión de enfermedad avanzada, con una supervivencia media de entre 6 y 9 meses. Materiales y Método: Presentamos el caso de un paciente varón de 63 años diagnosticado de melanoma cutáneo que acudió a urgencias por dolor abdominal y estreñimiento. Se realizó una TC abdominal donde se informó de la existencia de 2 lesiones metastásicas a nivel de intestino delgado que condicionaban oclusión intestinal. Resultados: El paciente fue intervenido quirúrgicamente bajo abordaje laparoscópico con resección de los dos segmentos intestinales afectos y anastomosis intracorpórea. El informe histopatológico confirmó que se trataban de metástasis de melanoma. Discusión: La oclusión intestinal por metástasis de melanoma maligno es muy infrecuente. La cirugía es el tratamiento de elección en pacientes con metástasis intestinales de melanoma. El tratamiento quirúrgico puede mejorar el pronóstico y estaría indicado casos de metástasis únicas o pacientes sintomáticos con intención paliativa. El abordaje mínimamente invasivo ofrece resultados oncológicos similares a la laparotomía.

Aim: Cutaneous melanoma has a high metastatic potential, being the most frequent extra-abdominal source of small bowel metastasis. The diagnosis of gastrointestinal metastases is often an expression of advanced disease, with an average survival of 6-9 months. Materials and Method: We herein present the case of a 63-year-old male patient diagnosed with cutaneous melanoma who arrived to the emergency department complaining of abdominal pain and constipation. An abdominal CT scan was performed, it revealed two metastatic lesions in the small bowel which marked the mechanical obstruction. Results: Patient underwent a laparoscopy and both involved segments were removed. Pathology exam confirmed the diagnosis of melanoma metastases. Discussion: Surgery excision is the treatment of choice in patients with small bowel metastases from melanoma. Surgical management can improve the prognosis and it would be indicated in cases of single metastases or symptomatic patients with a palliative intention. Minimally invasive approach provides similar oncological results as conventional laparotomy. Small bowel obstruction due to metastases of malignant melanoma is extremely rare.

Neuroendocrine neoplasia of the gastrointestinal tract revisited: towards precision medicine.

Over the past 5 years, a number of notable research advances have been made in the field of neuroendocrine cancer, specifically with regard to neuroendocrine cancer of the gastrointestinal tract. The aim of this Review is to provide an update on current knowledge that has proven effective for the clinical management of patients with these tumours. For example, for the first time in the tubular gastrointestinal tract, well-differentiated high-grade (grade 3) tumours and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are defined in the WHO classification. This novel classification enables efficient identification of the most aggressive well-differentiated neuroendocrine tumours and helps in defining the degree of aggressiveness of MiNENs. The Review also discusses updates to epidemiology, cell biology (including vesicle-specific components) and the as-yet-unresolved complex genetic background that varies according to site and differentiation status. The Review summarizes novel diagnostic instruments, including molecules associated with the secretory machinery, novel radiological approaches (including pattern recognition techniques), novel PET tracers and liquid biopsy combined with DNA or RNA assays. Surgery remains the treatment mainstay; however, peptide receptor radionuclide therapy with novel radioligands and new emerging medical therapies (including vaccination and immunotherapy) are evolving and being tested in clinical trials, which are summarized and critically reviewed here.

Clinical and histological features of secondary carcinomas in gastrointestinal tract biopsies.

BACKGROUND: Secondary carcinoma involving the gastrointestinal (GI) tract is an uncommon finding in biopsy specimens. The diagnosis can be challenging for tumours mimicking a primary carcinoma and when the clinical context is unknown. METHODS AND RESULTS: A multicentre retrospective study was performed to evaluate the clinical and histological features of a series of secondary carcinoma in GI biopsies. A total of 197 cases from 190 patients (median age = 67 years; 57% females) were reviewed. In 16% of patients, the primary carcinoma was unknown. Most lesions presented endoscopically as mucosal or submucosal masses (58%). In 13%, the endoscopy was non-suspicious for malignancy. The most common tumours were carcinomas of the breast (38%), kidney (13%), lung (12%), prostate (8%) and ovary (7%). The sites of involvement were the stomach (34%), colon (27%), rectum (18%), duodenum (13%), oesophagus (5%), jejunum (3%) and anus (0.5%). Histological patterns of infiltration were mucosal (76%), submucosal (41%), lymphatic (14%), and epithelial colonisation (8%). Submucosal infiltration was found significantly more frequently in carcinomas of the prostate (67%) and lung (62%), compared with carcinomas of the ovary (27%) and breast (23%). Histological obstructive changes were observed in 36% of all cases, with the highest rate in prostate carcinoma (53%) and the lowest rate in kidney carcinoma (8%). CONCLUSION: Awareness of the main clinical and histological patterns of secondary carcinomas in GI tract biopsies may help pathologists to raise the possibility of this uncommon diagnosis and confirm it with the judicious use of immunohistochemistry.

Synchronous duodenum and descending colon metastasis from primary lung neuroendocrine small-cell carcinoma: A case report and review of the literature.

INTRODUCTION: Metastasis to the gastrointestinal tract from lung cancer is very uncommon and is often asymptomatic. Although small bowel metastasis may commonly occur, metastases to the stomach and colon are uncommon. CASE REPORT: In this paper, we present a previously healthy 57-year-old male patient, a 60-packet per year smoker, who was taken to the emergency room with complaints of increasing abdominal pain, rectal bleeding, weight loss, and dyspnea for the last three months. Endoscopic examination revealed polypoid lesions in the duodenum and the descending colon. We diagnosed neuroendocrine small-cell lung cancer based on histopathological and immunohistochemical staining.Management and outcome: A cisplatin (d1, 60 mg/m2/day)-etoposide (d1 to d3, 120 mg/m2/day) regimen was given every three weeks as palliative chemotherapy. After the three course of chemotherapy, the lung radiograph showed a decline in hilar expansion and there was no pleural effusion. Then, he died of acute respiratory failure two weeks after radiotherapy of brain. DISCUSSION: Gastrointestinal tract metastasis of lung cancer is recognized synchronously with or rarely before diagnosis. It is generally recognized after the diagnosis of lung cancer. These patients often have other concurrent body metastases. Prognosis is poor, and survival expectation is short. The most common metastases to the gastrointestinal tract are squamous and large cell lung cancer metastases. Our aim is to emphasize the importance of immunohistochemical examination for masses in the gastrointestinal tract and to present this rare case of synchronous duodenal and colonic metastases of small-cell lung cancer.

Reporte de caso: metástasis gástrica de carcinoma endometrial, una localización inusual / Case report: gastric metastasis of endometrial carcinoma, an unusual localization

INTRODUCCIÓN: el carcinoma endometrial es la sexta entidad maligna más común a nivel mundial. En la mayoría de casos se diagnóstica de forma temprana. Recurre principalmente a cúpula vaginal y a nivel linfático, sin embargo, se han descrito metástasis a vagina, peritoneo y pulmones, entre otros. PRESENTACIÓN DEL CASO: paciente femenina adulta mayor con antecedente de carcinoma endometrial hace 7 años, tratado quirúrgicamente con estudio histopatológico que evidenciaba un miometrio infiltrado en un 95% sin invasión a otros órganos y linfadenectomía libre de lesión (estadio FIGO IB), quien consulta por dolor abdominal localizado en mesogastrio y deposiciones melénicas, evidenciándose una lesión gástrica, con resultado de biopsia que reporta carcinoma pobremente diferenciado con positividad focal para vimentina compatible con metástasis gástrica secundaria a carcinoma endometrial. Se indica manejo sistémico con quimioterapia, se documenta respuesta total de la lesión. DISCUSIÓN: las lesiones tumorales a nivel de estómago son primarios en su gran mayoría, una metástasis a este nivel es inusual. En el momento del diagnóstico de una metástasis gástrica, la mitad de las pacientes presentan concomitante compromiso de otros órganos. El carcinoma endometrial no está descrito dentro de los primarios que generan este compromiso. CONCLUSIÓN: el caso expuesto es un reto clínico, que representa un vacío en la evidencia actual; se comparte la experiencia de un manejo exitoso. Son necesarios más estudios para evaluar el pronóstico, opciones de tratamiento y definir la pertinencia de métodos de tamización para la detección temprana de estos casos.

INTRODUCTION: the endometrial carcinoma is the sixth cancer worldwide. Usually it is diagnosed in early stages. The sites of recurrence includes vaginal cuff and lymph nodes, however some metastasis have been described to vagina, peritoneum and lungs, among others. CASE REPORT: Elder female with history of an endometrial carcinoma 7 years ago, surgically treated. With histopathology that reported myometrial infiltration in a 95% without invasion to other organs and lymphadenectomy free of neoplasm (FIGO IB), who consult at the emergency room due to abdominal pain and black stool, with further studies that make evident a gastric lesion with biopsy reported as a poorly differentiated carcinoma, vimentin positive, compatible with gastric metastasis secondary to an endometrial carcinoma. Chemoterapy was indicated, documenting total posterior response of the lesion. DISCUSSION: Secondary lessions in stomach are rare. If they are present at the moment of diagnosis half of the patients concomitantly have metastasis in other organs. The endometrial carcinoma hasn't been described as a common localization that result in this compromise. CONCLUSION: the case exposed is a clinical challenge, a therapeutic success is shared. Limited evidence is available. Further studies are necessary to evaluate the prognosis, therapeutic options and to define the relevance of screening tests for early detection.

Breast Cancer Metastasis Masquerading as Primary Colon and Gastric Cancer: A Case Report.

BACKGROUND Breast cancer is the most common malignancy in women worldwide. Despite treatment, recurrence and metastasis are common. Lobular breast cancer most commonly metastasizes to the lungs, liver, lymph nodes, and sites in the brain. Metastasis to the gastrointestinal tract is rare, with few cases reported to date. CASE REPORT This report describes a patient with late colon and gastric metastases from lobular breast cancer mimicking primary colon and gastric cancers. CONCLUSIONS Immunohistochemical methods can help differentiate metastatic breast disease to the gastrointestinal tract from primary gastrointestinal malignancy.

Renal Pelvis Urothelial Carcinoma With Bowel Metastases.

Urothelial carcinoma is the fourth most common genitourinary tumor with the majority of the tumor involving the urinary bladder. Only 5% involves the renal pelvis and ureter. Metastatic urothelial carcinoma of the renal pelvis frequently involves the lymph nodes, lung, liver, bone, and peritoneum. We share rare interesting F-FDG PET/CT images of a 60-year-old man with metastatic urothelial carcinoma of the renal pelvis to the bowel.

Prognostic impact of tumour burden in stage IV neuroendocrine neoplasia: A comparison between pancreatic and gastrointestinal localizations.

BACKGROUND: Although prognosis of NENs is affected by several features including tumour burden, the specific role of this factor in pancreatic NENs (PanNENs) and gastrointestinal NENs (GI NENs) is not well established. AIM: To compare the prognostic role of tumour burden in PanNENs and GI NENs. PATIENTS AND METHODS: This study was a retrospective analysis of stage IV PanNENs and GI NENs. Tumours were classified based on liver tumour volume (<25% or >25%). Overall survival as assessed by Kaplan-Meier curves, and Cox proportional hazards method was used to perform risk factor analysis. RESULTS: The analysis included 300 patients, including 166 panNENs (55.3%) and 134 GI NENs (44.7%). A total of 158 patients (52.7%) had G2 tumours, 107 had G1 tumours (35.7%), and 35 had G3 tumours (11.6%). Tumour liver involvement >25% was observed in 187 patients (62.3%): 106 PanNENs (56.7%), and 81 GI NENs (43.3%) (p = 0.551). Bone metastases were present in 45 patients (15%): 22 PanNENs (13.2%) and 23 GI NENs (17.1%) (p = 0.416). Characteristics of the PanNENs, including: grading (G2 vs G1, HR = 3.7; G3 vs G1, HR = 16.40), liver involvement > 25% (HR = 3.09), and bone metastases (HR = 2.27) were independent predictors for poor survival, whereas the only significant risk factor in GI NENs was grading (G2 vs G1, HR = 4.36; G3 vs G1, HR = 8.60). CONCLUSIONS: PanNENs and GI NENs have different risk profiles. Liver tumour volume and the presence of bone metastases significantly affect survival in patients with PanNENs but has no impact on the clinical outcomes of GI NENs.

Metastatic breast cancers have reduced immune cell recruitment but harbor increased macrophages relative to their matched primary tumors.

The interplay between the immune system and tumor progression is well recognized. However, current human breast cancer immunophenotyping studies are mostly focused on primary tumors with metastatic breast cancer lesions remaining largely understudied. To address this gap, we examined exome-capture RNA sequencing data from 50 primary breast tumors (PBTs) and their patient-matched metastatic tumors (METs) in brain, ovary, bone and gastrointestinal tract. We used gene expression signatures as surrogates for tumor infiltrating lymphocytes (TILs) and compared TIL patterns in PBTs and METs. Enrichment analysis and deconvolution methods both revealed that METs had a significantly lower abundance of total immune cells, including CD8+ T cells, regulatory T cells and dendritic cells. An exception was M2-like macrophages, which were significantly higher in METs across the organ sites examined. Multiplex immunohistochemistry results were consistent with data from the in-silico analysis and showed increased macrophages in METs. We confirmed the finding of a significant reduction in immune cells in brain METs (BRMs) by pathologic assessment of TILs in a set of 49 patient-matched pairs of PBT/BRMs. These findings indicate that METs have an overall lower infiltration of immune cells relative to their matched PBTs, possibly due to immune escape. RNAseq analysis suggests that the relative levels of M2-like macrophages are increased in METs, and their potential role in promoting breast cancer metastasis warrants further study.

Surgery for gastrointestinal metastases of malignant melanoma - a retrospective exploratory study.

BACKGROUND: Cutaneous melanoma has a rapidly increasing incidence in Sweden, and it has more than doubled in the last two decades. In recent years, new systemic treatments for patients with metastatic disease have increased overall survival. The role of surgery in the metastatic setting has been unclear, and no randomized data exist. Many surgeons still perform metastasectomies; however, the exact role probably has to be redefined. The aim of this single-institution study was to retrospectively examine the safety and efficacy of surgery in abdominal melanoma metastases and to identify prognostic and predictive factors. METHODS: Retrospective analysis of a consecutive series of all patients with stage IV melanoma with gastrointestinal metastases that underwent abdominal surgery at a single center between January 2010 and December 2018. Fifteen patients who underwent in total 18 abdominal procedures, both acute and elective, were identified and included in the study. RESULTS: Out of 18 laparotomies, six (33%) were emergency procedures due to ileus (n = 4), small bowel perforation (n = 1), and abdominal abscess (n = 1). Twelve procedures (66%) were elective with the most common indication being persistent anemia (58%, n = 7), abdominal pain and anemia (33%, n = 4), and abdominal pain (8%, n = 1). All procedures were performed by laparotomy. There were 19 small bowel resections, 3 partial colon resections, and 2 omental resections. Radical resection was possible in 56% (n = 10) of cases and 67% (n = 8) when only considering elective procedures. In 17 of 18 procedures (94%), there were mild or no surgical complications (Clavien-Dindo grades 0-I). The median overall survival was 14 months with a 5-year survival of 23%. CONCLUSIONS: Patients with abdominal melanoma metastases can safely undergo resection with a high grade of radical procedures when performed in the elective setting. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03879395 . Registered 15 March 2019.

Clinical and endoscopic findings of patients with cutaneous Kaposi sarcomaand gastrointestinal involvement. Experience in a single center of Lima-Peruin the last 3 years.

INTRODUCTION: Kaposi sarcoma is a low-grade angioproliferative neoplasm strongly associated with infection by herpes virus type 8 (HHV-8). Gastrointestinal (GI) involvement is an infrequent finding, whose clinical and endoscopic characteristics are poorly defined in the literature. OBJECTIVE: The aim of our study was to describe the clinical and endoscopic findings of patients with gastrointestinal Kaposi Sarcoma. MATERIALS AND METHODS: We reviewed all clinical histories, endoscopic and anatomopathologic reports of all patients with cutaneous Kaposi sarcoma (CKS) who came to Cayetano Heredia Gastroenterology Service during the period between August 2015 to October 2018. We included all patients with CKS that had gastrointestinal involvement confirmed with biopsy. RESULTS: We found 50 patients with cutaneous Kaposi sarcoma. Thirteen patients had gastrointestinal Kaposi sarcoma (26%). 53.8% (7/13 cases) were asymptomatic. 92.3% (12/13 cases) had HIV infection. Nine of the twelve HIV+ patients had CD4 count below 200 cells/µl. When Kaposi affects GI tract, the mayority have multiple GI organs affected. Stomach and colon are the most common sites affected. CONCLUSION: Gastrointestinal involvement was presented in 26% of our patients with cutaneos Kaposi sarcoma, a half of them had no GI symptoms. The majority of cases were young male and had HIV in AIDS stage. The mortality in our series was 15.3% at 6 months of follow-up.

Current Challenges in Diagnosis and Assessment of the Response of Locally Advanced and Metastatic Renal Cell Carcinoma.

Locally advanced and metastatic renal cell carcinoma (RCC) present a specific set of challenges to the radiologist. The detection of metastatic disease is confounded by the ability of RCC to metastasize to virtually any part of the human body long after surgical resection of the primary tumor. This includes sites not commonly included in routine surveillance, which come to light after the patient becomes symptomatic. In the assessment of treatment response, the phenomenon of tumor heterogeneity, where clone selection through systemic therapy drives the growth of potentially more aggressive phenotypes, can result in oligoprogression despite overall disease control. Finally, advances in therapy have resulted in the development of immuno-oncologic agents that may result in changes that are not adequately evaluated with conventional size-based response criteria and may even be misinterpreted as progression. This article reviews the common challenges a radiologist may encounter in the evaluation of patients with locally advanced and metastatic RCC. ©RSNA, 2019.