Benefit from upfront FOLFOXIRI and bevacizumab in BRAFV600E-mutated metastatic colorectal cancer patients: does primary tumour location matter?

BACKGROUND: Recent data suggest that BRAFV600E-mutated metastatic colorectal cancer (mCRC) patients with right-sided tumours and ECOG-PS = 0 may achieve benefit from the triplet regimen differently than those with left-sided tumours and ECOG-PS > 0. METHODS: The predictive impact of primary sidedness and ECOG-PS was evaluated in a large real-life dataset of 296 BRAFV600E-mutated mCRC patients treated with upfront triplet or doublet ± bevacizumab. Biological differences between right- and left-sided BRAFV600E-mutated CRCs were further investigated in an independent cohort of 1162 samples. RESULTS: A significant interaction effect between primary sidedness and treatment intensity was reported in terms of both PFS (p = 0.010) and OS (p = 0.003), with a beneficial effect of the triplet in the right-sided group and a possible detrimental effect in the left-sided. No interaction effect was observed between ECOG-PS and chemo-backbone. In the MSS/pMMR population, a consistent trend for a side-related subgroup effect was observed when FOLFOXIRI ± bevacizumab was compared to oxaliplatin-based doublets±bevacizumab (p = 0.097 and 0.16 for PFS and OS, respectively). Among MSS/pMMR tumours, the BM1 subtype was more prevalent in the right-sided group (p = 0.0019, q = 0.0139). No significant differences were observed according to sidedness in the MSI-H/dMMR population. CONCLUSIONS: Real-life data support the use of FOLFOXIRI ± bevacizumab only in BRAFV600E-mutated mCRC patients with right-sided tumours.

Racial differences in survival and response to therapy in patients with metastatic colorectal cancer: A secondary analysis of CALGB/SWOG 80405 (Alliance A151931).

BACKGROUND: The objective of this study was to evaluate the association between self-identified race and overall survival (OS), progression-free survival (PFS), and response to therapy among patients enrolled in the randomized Cancer and Leukemia Group B (CALGB)/SWOG 80405 trial. METHODS: Patients with advanced or metastatic colorectal cancer who were enrolled in the CALGB/SWOG 80405 trial were identified by race. On the basis of covariates (treatment arm, KRAS status, sex, age, and body mass index), each Black patient was exact matched with a White patient. The association between race and OS and PFS was examined using a marginal Cox proportional hazard model for matched pairs. The interaction between KRAS status and race was tested in the model. The association between race and response to therapy and adverse events were examined using a marginal logistic regression model. RESULTS: In total, 392 patients were matched and included in the final data set. No difference in OS (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.73-1.16), PFS (HR, 0.97; 95% CI, 0.78-1.20), or response to therapy (odds ratio [OR], 1.00; 95% CI, 0.65-1.52) was observed between Black and White patients. Patients with KRAS mutant status (HR, 1.31; 95% CI, 1.02-1.67), a performance statusscore of 1 (reference, a performance status of 0; HR, 1.49; 95% CI, 1.18-1.88), or ≥3 metastatic sites (reference, 1 metastatic site; HR, 1.67; 95% CI, 1.22-2.28) experienced worse OS. Black patients experienced lower rates and risk of grade ≥3 fatigue (6.6% vs 13.3%; OR, 0.46; 95% CI, 0.24-0.91) but were equally likely to be treated with a dose reduction (OR, 1.09; 95% CI, 0.72-1.65). CONCLUSIONS: No difference in OS, PFS, or response to therapy was observed between Black patients and White patients in an equal treatment setting of the CALGB/SWOG 80405 randomized controlled trial. LAY SUMMARY: Despite improvements in screening and treatment, studies have demonstrated worse outcomes in Black patients with colorectal cancer. The purpose of this study was to determine whether there was a difference in cancer-specific outcomes among Black and White patients receiving equivalent treatment on the CALGB/SWOG 80405 randomized clinical trial. In this study, there was no difference in overall survival, progression-free survival, or response to therapy between Black and White patients treated on a clinical trial. These findings suggest that access to care and differences in treatment may be responsible for racial disparities in colorectal cancer.

Metastatic renal cell carcinoma to pancreas and gastrointestinal tract: a clinicopathological study of 3 cases and review of literature.

BACKGROUND: Renal Cell Carcinoma (RCC) metastasizes in approximately 20-30% cases. The most common sites for metastases are the lungs, bones, liver, and brain. Metastases of RCC in the gastrointestinal tract (GIT) are very rare. Metastatic RCC has a poor prognosis. We herein present a case series of three patients with metastatic disease in the colon, duodenum, and pancreas following complete resection of RCC. METHODS: Hematoxylin and Eosin and immunohistochemical slides of 3 cases of RCC metastatic to GIT were reviewed. These cases were diagnosed between 2002 and 2019 at French Medical Institute for Mothers and Children (FMIC), Kabul, Afghanistan, and Aga Khan University Hospital (AKUH), Karachi, Pakistan. We also present a detailed review of published literature. RESULTS: We reviewed cases of three patients, two females and one male, with a mean age of 57.3 years (range 40-67 years) who underwent nephrectomy for RCC. They developed metastases in the colon, pancreas, and duodenum, respectively 12-168 months (median time 156 months) following primary tumor resection. The patient with metastatic RCC in colon presented with abdominal pain and constipation. An ulcerated mass was found on colonoscopy 30 cm from the anal verge. Diagnosis of RCC with rhabdoid features was confirmed in both primary and metastatic tumors. The second patient developed a metastatic nodule in the head of pancreatic while the third patient developed metastatic nodules in the duodenum and pancreas which were detected by Computed Tomography (CT) scanning. Histopathological examination confirmed the presence of clear cell RCC in the metastatic nodules in both cases. CONCLUSION: Metastatic RCC should be considered in the differential diagnosis of mass in the gastrointestinal (including pancreaticobiliary) tract especially in presence of a past history of RCC. These patients should be screened thoroughly by physical examination and appropriate imaging studies.

Echinococcal hepatic lesion mimicking metastasis from colon cancer: two case reports.

BACKGROUND: Echinococcus is a worldwide zoonosis, primarily causing liver lesions. Accidentally detected, these lesions enter the differential diagnosis of a tumor, including metastasis. This situation is especially challenging in patients with colorectal cancer, as both diseases affect mainly the liver. CASE PRESENTATION: We report two patients with a newly diagnosed colorectal cancer. Pre- and intraoperatively radiological imaging revealed hepatic lesions which were resected on suspicion of colorectal cancer metastasis. Histology showed granulomatous lesions with characteristic parasitic membrane consistent with an echinococcal cyst. The diagnosis was confirmed by specific polymerase chain reaction. CONCLUSIONS: Focal hypoechoic liver lesion in patients with colorectal cancer should be primarily considered as a liver metastasis and resected whenever feasible. Other uncommon etiologies, including parasitic lesion as echinococcal cysts, should be taken in consideration, as this could lead to major changes of the management and prognosis of the affected patients.

Indocyanine Green Fluorescence Imaging-Guided Laparoscopic Surgery Could Achieve Radical D3 Dissection in Patients With Advanced Right-Sided Colon Cancer.

BACKGROUND: The optimal lymph node dissection with central vascular ligation is an important part for oncological outcomes after laparoscopic right-sided colon cancer surgery. Few studies have examined the clinical value of indocyanine green fluorescence imaging-guided D3 dissection for right-sided colon cancer. OBJECTIVES: We assessed the clinical value of indocyanine green fluorescence imaging-guided laparoscopic surgery in improving the radicality of lymph node dissection for right-sided colon cancer by comparing the outcomes of conventional laparoscopic surgery. DESIGN: The data were retrospectively reviewed and analyzed. SETTING: This study was conducted at a single university hospital. PATIENTS: A 1:2 matched case-control study included 25 patients undergoing fluorescence imaging-guided laparoscopic surgery and 50 patients undergoing conventional laparoscopic surgery for clinical T3 or T4 right-sided colon cancer between June 2016 and December 2017. MAIN OUTCOME MEASURES: The extent of D3 dissection and pathological results (tumor stage, lymph node yield, and number of metastatic lymph nodes) were analyzed. RESULTS: The 2 groups were similar in baseline characteristics. The numbers of harvested pericolic and intermediate lymph nodes were not different between the 2 groups. The numbers of central lymph nodes (14 vs 7, p < 0.001) and total harvested lymph nodes (39 vs 30, p = 0.003) were significantly higher in the fluorescence group than in the conventional group. In the multivariate analysis, the use of indocyanine green fluorescence imaging was an independently related factor for the retrieval of higher numbers of overall and central lymph nodes. The number of metastatic lymph nodes was not significantly different between the 2 groups. LIMITATIONS: The results of this study were limited by its small patient numbers and retrospective nature. CONCLUSIONS: Real-time indocyanine green fluorescence imaging of lymph nodes may improve the performance of more radical D3 lymph node dissection during laparoscopic right hemicolectomy for advanced right-sided colon cancer. See Video Abstract at http://links.lww.com/DCR/B150. LA CIRUGÍA LAPAROSCÓPICA GUIADA POR IMÁGENES DE FLUORESCENCIA VERDE INDOCIANINA PODRÍA LOGRAR UNA DISECCIÓN RADICAL D3 EN PACIENTES CON CÁNCER DE COLON AVANZADO DEL LADO DERECHO: La disección óptima de los ganglios linfáticos con ligadura vascular central es una parte importante para los resultados oncológicos después de la cirugía laparoscópica de cáncer de colon del lado derecho. Pocos estudios han examinado el valor clínico de la disección D3 guiada por imágenes de fluorescencia verde indocianina para el cáncer de colon del lado derecho.Evaluamos el valor clínico de la cirugía laparoscópica guiada por imagen de fluorescencia verde indocianina para mejorar la radicalidad de la disección de ganglios linfáticos para el cáncer de colon del lado derecho mediante la comparación de los resultados de la cirugía laparoscópica convencional.Los datos se revisaron y analizaron retrospectivamente.Este estudio se realizó en un solo hospital universitario.Un estudio de casos y controles emparejado 1:2 incluyó a 25 pacientes sometidos a cirugía laparoscópica guiada por imágenes de fluorescencia y 50 pacientes sometidos a cirugía laparoscópica convencional para cáncer de colon derecho clínico T3 o T4 entre Junio de 2016 y Diciembre de 2017.Se analizó el alcance de la disección D3 y los resultados patológicos (estadio tumoral, rendimiento de los ganglios linfáticos y número de ganglios linfáticos metastásicos).Los dos grupos fueron similares en las características basicas. El número de ganglios linfáticos pericólicos e intermedios recolectados no fue diferente entre los dos grupos. El número de ganglios linfáticos centrales (14 vs 7, p < 0.001) y el total de ganglios linfáticos recolectados (39 vs 30, p = 0.003) fueron significativamente mayores en el grupo de fluorescencia que en el grupo convencional. En el análisis multivariante, el uso de imágenes de fluorescencia verde indocianina fue un factor independiente relacionado para la recuperación de un mayor número de ganglios linfáticos centrales y globales. El número de ganglios linfáticos metastásicos no fue significativamente diferente entre los dos grupos.Los resultados de este estudio fueron limitados por su pequeño número de pacientes y su naturaleza retrospectiva.Las imágenes de fluorescencia verde indocianina en tiempo real de los ganglios linfáticos pueden mejorar el rendimiento de la disección más radical de los ganglios linfáticos D3 durante la hemicolectomía derecha laparoscópica para el cáncer de colon avanzado del lado derecho. Consulte Video Resumen en http://links.lww.com/DCR/B150.

A Proposal for Novel Standards of Histopathology Reporting for D3 Lymphadenectomy in Right Colon Cancer: The Mesocolic Sail and Superior Right Colic Vein Landmarks.

BACKGROUND: Strong agreement exists concerning the standards of pathologic reporting for total mesorectal excision and complete mesocolic excision. It represents a quality standard that correlates with survival. However, no agreed standards of reporting are available to define D3 lymphadenectomy for right colectomy. OBJECTIVE: The purpose of this study was to define anatomopathological standards of specimen quality obtained from the surgical specimen when an oncologic right hemicolectomy with D3 lymphadenectomy has been correctly performed. DESIGN: This study was conducted in 2 different phases. The first part consisted of a cadaver-based study of right colon anatomy, and the second part consisted of a prospective assessment of a series of surgical specimens obtained after right hemicolectomy for cancer. SETTINGS: The anatomic phase of the study was performed in collaboration with the University of Valencia Department of Anatomy and Embryology. The second part was performed at a colorectal unit of a tertiary hospital. PATIENTS: Seventeen cadavers were used for the first phase, and 65 surgical specimens were examined for the second part of the study. MAIN OUTCOME MEASURES: In each specimen, the pathologists looked for anatomic structures defined as markers of quality standards of the D3 lymphadenectomy during the first phase. Specimens were classified as complete, partial, and incomplete D3 lymphadenectomy. RESULTS: Twenty percent of specimens were classified as incomplete D3 lymphadenectomy, 31% as partial, and 49% as complete. A median number of 14 (6-64), 22 (11-47), and 29 (14-55) lymph nodes were isolated (p = 0.01). Similarly, the median numbers of lymph nodes isolated in the area of D3 lymphadenectomy were 0 in incomplete, 1 (0-5) in Partial, and 3 (0-8) in Complete D3 lymphadenectomy specimens (p = 0.0001). LIMITATIONS: A large multicenter study with adequate power is needed. CONCLUSIONS: We propose the right mesocolic sail and trunk of superior right colic vein as new and reproducible anatomopathologic standards of D3 lymphadenectomy in oncologic right hemicolectomy. See Video Abstract at http://links.lww.com/DCR/B149. PROPUESTA PARA NUEVOS ESTÁNDARES HISTOPATOLÓGICOS EN LA LINFADENECTOMÍA D3 EN EL CÁNCER DE COLON DERECHO: LA VELA MESOCÓLICA Y LA VENA CÓLICA DERECHA SUPERIOR: Existe un claro acuerdo sobre los estándares de calidad patológicos para la escisión total del mesorrecto y la escisión completa del mesocolon. Son considerados "estándar de calidad" que se correlaciona con la supervivencia. Sin embargo, no se dispone de estándares de calidad para definir la linfadenectomía D3, en la colectomía derecha.Definir los estándares anatomopatológicos de calidad obtenidos de una muestra quirúrgica, cuando se ha realizado correctamente una hemicolectomía derecha oncológica, con linfadenectomía D3.Dos fases diferentes. La primera parte consistió en un estudio basado en la anatomía del colon derecho, realizado en cadáveres, y la segunda parte consistió en una evaluación prospectiva de una serie de muestras quirúrgicas obtenidas después de la hemicolectomía derecha para cáncer.La fase anatómica del estudio se realizó en colaboración con el Departamento de Anatomía y Embriología de la Universidad de Valencia. La segunda parte se realizó en la Unidad Colorrectal de un hospital terciario.Se utilizaron diecisiete cadáveres para la primera fase y se examinaron 65 muestras quirúrgicas para la segunda parte del estudio.En cada muestra, los patólogos buscaron estructuras anatómicas definidas, como marcadores de los estándares de calidad de la linfadenectomía D3, durante la primera fase. Las muestras se clasificaron como linfadenectomía D3 completa, parcial e incompleta.El veinte por ciento de las muestras se clasificaron como "Linfadenectomía D3 Incompleta", el 31% como "Parcial" y el 49% como "Completa." Se aisló una media de 14 (6-64), 22 (11-47) y 29 (14-55) ganglios linfáticos respectivamente (p = 0,01). Del mismo modo, el número medio de ganglios linfáticos aislados en el área de la linfadenectomía D3 fue 0 en "Incompleta", 1 (0-5) en "Parcial" y 3 (0-8) en muestras de "Linfadenectomía D3 Completa" (p = 0,0001).Se necesita un estudio multicéntrico con potencia adecuada.Proponemos la vela mesocólica derecha y el tronco de la vena cólica derecha superior, como estándares anatomopatológicos nuevos y reproducibles de linfadenectomía D3, en hemicolectomía derecha oncológica. Consulte Video Resumen en http://links.lww.com/DCR/B149.

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.

Dual Checkpoint Inhibition with Ipilimumab plus Nivolumab After Progression on Sequential PD-1/PDL-1 Inhibitors Pembrolizumab and Atezolizumab in a Patient with Lynch Syndrome, Metastatic Colon, and Localized Urothelial Cancer.

Immune checkpoint blockade (ICB) is an approved therapy for advanced metastatic mismatch repair (MMR)-deficient cancer regardless of tissue of origin. Although therapy is effective initially, recurrence rates are significant, and long-term outcomes remain poor for most patients. It is not currently recommended to give sequential ICB for advanced MMR-deficient colorectal cancer (CRC) or for patients with metastatic cancer from Lynch syndrome. The need for subsequent therapy options in advanced MMR-deficient cancer beyond the first ICB regimen arises in clinical practice, and there are often no effective standard chemotherapies or other targeted therapies. We report the case of a Lynch syndrome patient with metastatic CRC and urothelial cancer who was treated sequentially with pembrolizumab (targeting PD1), atezolizumab (targeting PD-L1), brief rechallenge with pembrolizumab, and finally the combination of ipilimumab (targeting CTLA-4) and nivolumab (targeting PD1). Over a 28-month period the patient experienced prolonged disease control with each different regimen the first time it was given, including metabolic response by positron emission tomography and computed tomography scanning and tumor marker reductions. The case suggests that some patients with advanced MMR-deficient CRC may experience meaningful clinical benefit from multiple sequential ICB regimens, a strategy that can be further tested in clinical trials. KEY POINTS: The case exemplifies clinical benefit from sequential immune checkpoint blockade in a patient with Lynch syndrome with advanced metastatic colorectal cancer and urothelial cancer.Metabolic response, with decreased fluorodeoxyglucose avidity on positron emission tomography and computed tomography, and reductions in tumor markers, such as carcinoembryonic antigen, were helpful in this case to monitor disease status over a 28-month period of therapy.The concept of sequential immune checkpoint blockade in patients with advanced mismatch repair-deficient cancer merits further study to determine which patients are most likely to benefit.

Diagnostic flow-chart to identify bowel involvement in patients with stage IIIC-IV ovarian cancer: Can laparoscopy improve the accuracy of CT scan?

OBJECTIVE: This study investigates the diagnostic power of CT scan combined with exploratory laparoscopy (EXL) at identifying large bowel involvement in patients with stage IIIC-IV primary Epithelial Ovarian Cancer (EOC) by comparing with the macroscopic surgical findings at laparotomy. METHODS: All patients with FIGO Stage IIIC-IV EOC who had Visceral Peritoneal Debulking (VPD) were included in the study. Results of CT scan, EXL and laparotomy (LPT) with regards to the bowel involvement were prospectively recorded in an ad hoc study form. Setting LPT findings as the gold standard, positive and negative predictive value (PPV/NPV), sensitivity, specificity and accuracy of CT and EXL were calculated. In addition, the diagnostic power of the combination CT scan + EXL was investigated. RESULTS: Ninety-four out of 177 patients (53.2%) had a bowel resection during VPD. CT-scan alone had sensitivity, specificity, PPV, NPV and accuracy of 56.7%, 72.4%, 70.8%, 58.5% and 63.8% respectively. EXL alone 84.4%, 93.8%, 93.8%, 84.3%, 88.8%. CT combined with EXL detected bowel involvement with a sensitivity, specificity, PPV, NPV and accuracy of 87.5%, 70.4%, 77.8%, 82.6% and 79.6% and respectively. The combined tests showed a statistically significant improvement vs. CT scan alone (p < 0001) in sensitivity, NPV and accuracy, with non-significant difference in specificity and PPV. CONCLUSIONS: CT-scan alone shows a limited diagnostic power at detecting large bowel involvement in patients with stage IIIC-IV EOC. The combination of CT scan with EXL increases the diagnostic power and enables to appropriately plan the bowel resection and consent the patients.

Bowel obstruction caused by colonic metastasis of lung adenocarcinoma: a case report and literature review.

INTRODUCTION: Lung cancer is the most common cause of cancer-related deaths globally. Metastatic disease is often found at the time of initial diagnosis in the majority of lung cancer patients. However, colonic metastases are rare. This report describes an uncommon case of colonic metastasis from lung adenocarcinoma. CASE PRESENTATION: A 64-year-old female presented to her gastroenterologist for progressively worsening abdominal pain and constipation. Exploratory colonoscopy revealed a large rectosigmoid mass resulting in near total rectal occlusion. Her specialist recommended she immediately go to her regional hospital for further workup. On admission, she complained of continued abdominal pain and constipation. Notably, she had a past medical history of non-small cell lung cancer (T1bN3M0 stage IIIB), diagnosed 1 year prior. She was thought to be in remission following radiation and immunotherapy with pembrolizumab. Upon hospital admission, she underwent an urgent colostomy, ileocecectomy and anastomosis, and rectosigmoid mass resection with tissue sampling. Pathology confirmed the diagnosis of colonic metastasis from primary lung adenocarcinoma. Treatment was with systemic chemotherapy followed by localized radiation to the pelvic region was started. She did not respond well to these therapies. Subsequent imaging showed refractory tumor growth in the pelvic region. Treatment could not be completed due to the patient experiencing a debilitating stroke, and she was transitioned to hospice care. CONCLUSIONS: Clinicians should have a low threshold for intestinal investigation and considerations for colonic metastasis when patients with a history of primary lung cancer have abdominal symptoms.

A Granulation Polyp in the Colon Masquerading as Metastatic Cancer.

A 60-year-old Caucasian male was diagnosed with lung adenocarcinoma and multiple metastases to the bone, spleen, and brain. He underwent radiotherapy for the brain and lumbar spine metastases, plus chemotherapy (cisplatin and pemetrexed). The chemotherapy was discontinued due to vomiting and hyponatremia, and nivolumab was then administered. Eight months later, 18F-fluorodeoxyglucose positron emission tomography showed tracer uptake in the colon. Colonoscopy revealed a reddish multinodular polyp in the sigmoid colon. The polyp showed irregular microvessels. No colonic mucosal surface structures were observed. Colonic metastasis of the lung carcinoma was highly suspected; the polyp was therefore surgically removed. The histological analysis revealed granulation tissue and suppurative inflammation without neoplastic changes. We diagnosed the lesion as a granulation polyp. Despite the difficulty in diagnosing these lesions due to their rarity and similarity to metastatic colon tumors, we suggest that recognizing the endoscopic features of the polyp surface may allow a preoperative diagnosis.

Linitis plastica of the colon due to metastases of invasive lobular breast carcinoma.

Colon metastases from breast carcinoma are relatively rare and the invasive lobular subtype tends to metastasize more frequently due to its peritoneal dissemination. A 67-year-old female with a lobular subtype breast neoplasm was treated via a surgical resection ten years previously, with subsequent radiotherapy and adjuvant chemotherapy. She is currently in clinical remission. A colonoscopy was performed due to a recent onset cachexia syndrome, which identified diffuse linitis plastica of the colon. Biopsies confirmed that it was secondary to infiltration by cancer cells of invasive lobular breast carcinoma (ILBC). In conclusion, linitis plastica of the colon may be a new presentation of colon metastases from ILBC.

MiR-195 suppresses colon cancer proliferation and metastasis by targeting WNT3A.

MicroRNAs (miRNAs) are a novel class of diagnostic and therapeutic target in cancer. Here, we aimed to explore the effects and mechanism of miR-195 regulation in colon cancer. The expressions of several putative miRNAs in colon tumors, compared to those in normal tissues, were investigated by bioinformatical analysis of a Gene Expression Omnibus database. Quantitative real-time PCR analysis (qRT-PCR) was used to validate the identified changes in normal tissues, primary tumors, and metastatic tumors. MTT, soft agar colony formation, and transwell assays were used to evaluate the effects of miR-195 overexpression or inhibition on cell viability, proliferation, migration, and invasion. Targets of miR-195 were identified by TargetScan, and subsequently verified by qRT-PCR and Western blot. The role of miR-195 in the ß-catenin pathway was also studied using RT-PCR and Western blot. MiR-195 expression was downregulated in colon carcinoma tissues and negatively correlated with the metastatic potential. While transfecting miR-195 mimics decreased the proliferation, migration, and invasion of colon cancer cells, miR-195 inhibition exerted opposing effects. WNT3A was identified as a direct target of miR-195. ß-catenin was also downregulated by miR-195 in colon cancers. MiR-195 downregulation is associated with the enhanced proliferation, migration, and invasion of colon cancer. MiR-195 directly downregulates WNT3A. Our results indicate that miR-195 is a potential diagnostic marker and therapeutic target for improving the clinical management of colon cancer.

Sepsis increases perioperative metastases in a murine model.

BACKGROUND: Cancer surgery can promote tumour metastases and worsen prognosis, however, the effect of perioperative complications on metastatic disease remains unclear. In this study we sought to evaluate the effect of common perioperative complications including perioperative blood loss, hypothermia, and sepsis on tumour metastases in a murine model. METHODS: Prior to surgery, pulmonary metastases were established by intravenous challenge of CT26LacZ colon cancer cells in BALB/c mice. Surgical stress was generated through partial hepatectomy (PH) or left nephrectomy (LN). Sepsis was induced by puncturing the cecum to express stool into the abdomen. Hemorrhagic shock was induced by removal of 30% of total blood volume (i.e. stage 3 hemorrhage) via the saphenous vein. Hypothermia was induced by removing the heating apparatus during surgery and lowering core body temperatures to 30 °C. Lung tumour burden was quantified 3 days following surgery. RESULTS: Surgically stressed mice subjected to stage 3 hemorrhage or hypothermia did not show an additional increase in lung tumour burden. In contrast, surgically stressed mice subjected to intraoperative sepsis demonstrated an additional 2-fold increase in the number of tumour metastases. Furthermore, natural killer (NK) cell function, as assessed by YAC-1 tumour cell lysis, was significantly attenuated in surgically stressed mice subjected to intraoperative sepsis. Both NK cell-mediated cytotoxic function and lung tumour burden were improved with perioperative administration of polyI:C, which is a toll-like receptor (TLR)-3 ligand. CONCLUSIONS: Perioperative sepsis alone, but not hemorrhage or hypothermia, enhances the prometastatic effect of surgery in murine models of cancer. Understanding the cellular mechanisms underlying perioperative immune suppression will facilitate the development of immunomodulation strategies that can attenuate metastatic disease.

Metastatic Malignancy to the Colon and Rectum: A Report of 14 Cases from One Single Institute.

BACKGROUND: Metastatic malignancy occurs rarely in the colon or rectum. We presented 14 patients with colorectal metastasis (CRM). METHODS: A retrospective review was conducted on a computerized colorectal tumor database at the Taipei Veterans General Hospital from January 2000 to June 2013. RESULTS: The incidence of CRM was 0.19% (14 in 7,524 patients). There were 6 males and 8 females with a mean age of 66.9 ± 13.6 years. Origins of the CRM included lung cancers (n = 3), prostate cancers (n = 2), and others (n = 1, respectively). Clinical presentations were not specific and colonoscopic pictures were indistinguishable from primary colorectal cancers; 5 of the 9 biopsies identified metastasis. Eight patients had extracolonic metastasis and 6 patients had CRM only. Significantly better survival was observed in the CRM-only group (p = 0.037). The mean interval from the treatment of primary tumor to the diagnosis of CRM was 30.2 ± 49.0 months. The mean survival time after CRM was 24.9 ± 30.8 months. CONCLUSION: Clinical features and colonoscopic findings of CRM were indistinguishable from primary colorectal cancer. Histopathological review of the biopsy could be helpful in identifying the primary lesion. Surgical resection with curative intent provided longer survival in CRM-only patients.

A case of aseptic meningitis in a cetuximab-experienced patient with metastatic colon cancer.

Cetuximab is a monoclonal antibody against epidermal growth factor receptor and is used in the treatment of head and neck cancer, non-small cell lung cancer, and colorectal cancer. This case report describes a rare (<1% incidence) side effect of cetuximab administration: aseptic meningitis. We report a case which is, to our knowledge, the only case at the time of submission of this manuscript of aseptic meningitis in a patient being treated for metastatic colon cancer who was not cetuximab-naïve. This case report may help inform clinicians about the identification and outcome of this adverse event.

Two rare cases of synchronous and metachronous colonic metastases in patients with advanced gastric cancer.

BACKGROUND: Patients with advanced gastric cancer (GC) may ultimately die because GC mostly leads to synchronous or metachronous metastasis. However, colonic metastasis of GC is extremely rare. According to a PubMed search of papers published from May 1968 to March 2017, only 21 patients with GC (10 patients from 10 case reports and 11 patients from a retrospective study) have been found to have colonic metastasis. In this report, we present two cases of synchronous and metachronous colonic metastases of advanced GC. CASE PRESENTATION: Two patients with advanced GC received a diagnosis of colonic metastasis based on colonoscopic findings and computed tomography images, and the diagnosis was confirmed through pathological immunohistochemical analysis. Herein, we describe the management and outcomes of these metastases. CONCLUSIONS: Submucosal swelling and segmental bowel wall thickening observed through colonoscopy in patients with advanced GC might indicate colonic metastasis.

Multidisciplinary Diagnostic and Surgical Management of Adenocarcinoma Gingival Metastases.

Colon cancer is the third leading cause of cancer-related mortality worldwide and colon cancer metastases in rare sites, such as the oral cavity, lead to a worse prognosis. Oral metastasis is a rare clinical condition and it represents only the 1% among all oral cavity neoplasms. A multidisciplinary approach is recommended to carry out a correct diagnostic procedure that allows distinguishing between metastatic and primitive lesions of the oral cavity. Quick diagnosis and management are fundamental to take an appropriate action as early as possible, as usually the prognosis in patients with oral metastases of colon carcinoma is poor. Aim of this brief clinical report is to underline how the quick diagnosis and management of gingival lesions can be crucial for the correct management of those uncommon oral diseases and for having a better prognosis of the primary cancer.

[Colonic metastases from carcinoma of the lung, an unusual presentation. Case report and literature review]. / Metástasis a colon de un carcinoma de pulmón, una presentación inusual. Reporte de un caso y revisión de la literatura.

The symptomatic metastasis of the colon from a pulmonary cancer is rare; however, the global incidence of pulmonary cancer is 12.9%. It is an infrequent site of metastasis, with a prevalence of less than 0.5% in patients with pulmonary cancer. One of the most common manifestation is intestinal obstruction. We present a case report of a patient with an acute lower intestinal bleeding from multiple metastasis lesion of the colon as the initial manifestation of a non-small cell lung carcinoma.