Gastrointestinal Tract Malignancies Research Articles

Safety and effectiveness of sodium-glucose co-transporter 2 inhibitors in active cancer patients with heart failure: results of the observational TOSCA trial

Abstract Background Sodium-glucose co-transporter 2 inhibitors (SGLT2i) currently represent a pillar of heart failure (HF) treatment. However, cancer patients have not been included in landmark randomized controlled trials (RCTs), and data on safety and effectiveness in this population are lacking. Purpose Purpose of present study was to evaluate safety and effectiveness of SGLT2i in active cancer patients with HF. Methods TOSCA is a multi-centre observational trial including patients (≥ 18 years) with active cancer (diagnosis < 3 years) receiving SGLT2i for HF treatment. Patients were enrolled in two (prospective and retrospective) cohorts. The primary endpoint was safety (incidence of known and unexpected side effects). The secondary endpoint was effectiveness (ejection fraction (EF) increase, New York Heart Association (NYHA) class change, HF-related events). Exploratory endpoints included drug-drug interactions with anticancer and supportive care drugs, treatment of cancer therapy-related cardiac dysfunction (CTRCD), and changes in NT-proBNP. Results Eighty-three pts were enrolled (59 prospective - 24 retrospective). Median age was 71 (range 44-92) yrs, M/F 48/52%. The main cancer sites were breast, gastrointestinal tract, and hematological malignancies. Most cases (62%) received an active treatment (mainly chemotherapy) while on SGLT2i. Prevalent aetiology was drug-induced HF (37%) with reduced EF as the prevalent clinical presentation (39%). Prescribed agents were dapagliflozin in 60% and empagliflozin in 40% of cases on top of conventional guideline-directed medical therapy, with a median treatment duration of 3 (range 3-25) months. The incidence of urinary tract infection was 2.5%. No cases of genital infection, hypoglycemia, diabetic ketoacidosis, acute renal injury, thrombosis, and bone fractures were reported. Mean overall EF slightly increased (44.1% vs. 46.6%), and NYHA class improved (class improvement in 16%). Unplanned cardiology visits (1.2%), i.v. diuretics (1.2%), coronary angiography (5%), emergency access (2.5%), and new HF episodes (3.7%) rates were low. SGLT2i appeared effective in 31 cases of CTRCD. A relative reduction in mean NT-proBNP levels (2748 vs 1125pg/mL) was observed. No drug-drug interactions were reported. Conclusions SGLT2i appear to be safe and effective in active cancer patients with HF, with potential cardioprotective effect. No new safety warnings were recorded.

ERN GENTURIS guidelines on constitutional mismatch repair deficiency diagnosis, genetic counselling, surveillance, quality of life, and clinical management.

Constitutional mismatch repair deficiency (CMMRD), first described 25 years ago, confers an extremely high and lifelong cancer risk, including haematologic, brain, and gastrointestinal tract malignancies, and is associated with several non-neoplastic features. Our understanding of this condition has improved and novel assays to assist CMMRD diagnosis have been developed. Surveillance protocols need adjustment taking into account recent observational prospective studies assessing their effectiveness. Response to immune checkpoint inhibitors and the effectiveness and toxicity of other treatments have been described. An update and merging of the different guidelines on diagnosis and clinical management of CMMRD into one comprehensive guideline was needed. Seventy-two expert members of the European Reference Network GENTURIS and/or the European care for CMMRD consortium and one patient representative developed recommendations for CMMRD diagnosis, genetic counselling, surveillance, quality of life, and clinical management based on a systematic literature search and comprehensive literature review and a modified Delphi process. Recommendations for the diagnosis of CMMRD provide testing criteria, propose strategies for CMMRD testing, and define CMMRD diagnostic criteria. Recommendations for surveillance cover each CMMRD-associated tumour type and contain information on starting age, frequency, and surveillance modality. Recommendations for clinical management cover cancer treatment, management of benign tumours or non-neoplastic features, and chemoprevention. Recommendations also address genetic counselling and quality of life. Based on existing guidelines and currently available data, we present 82 recommendations to improve and standardise the care of CMMRD patients in Europe. These recommendations are not meant to be prescriptive and may be adjusted based on individual decisions.

Biomarkers in Early Detection, Prognostication and Management of Gastrointestinal Tract Malignancies: A Review

Each year the risk of cancer cases is constantly on the rise. The reoccurrence of this dilemma is due to late diagnosis, and as a result the survival rate is low. This indicates the significance of creating more efficient instruments for timely detection of cancerous cells, assessment, as well as prognosis. Hence, the objective of this paper was to provide a critical review of biomarkers in early detection, prognostication and management of gastrointestinal tract malignancies by harvesting data from online sources and libraries. Data obtained reveals that gastrointestinal tracts (GI) malignancies, encompasses malignancies that may arise from the gastric, hepatic, colonic, esophagus, gallbladder, rectal and stomach tumors are a common kind of cancer and could affect 1.400,000 - 952,000,000 people worldwide. A potential method for improving the diagnosis as well as prognosis of GI malignancy is the use of biomarkers, which are quantifiable indicators of biological processes or state of the ailments. Significant development has been made recently in detecting and validating biomarkers for various clinical procedures. This review discuss the present situation of gastrointestinal cancer biomarker research, with an emphasis on moral issues and other clinical implications that may arise from the incorporation of biomarkers in clinical practices, and also the different category of biomarkers, including genetic, epigenetic, and protein-based markers, are examined, along with their contributions to future outcomes in the management of gastrointestinal malignancies.

Body mass index and risk of over 100 cancer forms and subtypes in 4.1 million individuals in Sweden: the Obesity and Disease Development Sweden (ODDS) pooled cohort study

Obesity, assessed by body mass index (BMI), is an established risk factor for 13 cancers. We aimed to identify further potential obesity-related cancers and to quantify their association with BMI relative to that of established obesity-related cancers. Using Cox regression models on 4,142,349 individuals in Sweden (mean age 27.1 years at weight measurement), we calculated hazard ratios (HRs) for the association between BMI and the risk of 122 cancers and cancer subtypes, grouped by topography and morphology. Cancers with a positive association (i.e., HR>1) at an α-level of 0.05 for obesity (BMI ≥30kg/m2) vs. normal weight (BMI 18.5-24.9kg/m2) or per 5kg/m2 higher BMI, for which obesity is not an established risk factor, were considered potentially obesity related. After 100.2 million person-years of follow-up, 332,501 incident cancer cases were recorded. We identified 15 cancers in men and 16 in women as potentially obesity related. These were cancers of the head and neck, gastrointestinal tract, malignant melanoma, genital organs, endocrine organs, connective tissue, and haematological malignancies. Among these, there was evidence of differential associations with BMI between subtypes of gastric cancer, small intestine cancer, cervical cancer, and lymphoid neoplasms (P values for heterogeneity in HRs <0.05). The HR (95% confidence interval) per 5kg/m2 higher BMI was 1.17 (1.15-1.20) in men and 1.13 (1.11-1.15) in women for potential obesity-related cancers (51,690 cases), and 1.24 (1.22-1.26) in men and 1.12 (1.11-1.13) in women for established obesity-related cancers (84,384 cases). This study suggests a large number of potential obesity-related cancers could be added to already established ones. Importantly, the magnitudes of the associations were largely comparable to those of the already established obesity-related cancers. We also provide evidence of specific cancer subtypes driving some associations with BMI. Studies accounting for cancer-specific confounders are needed to confirm these findings. Swedish Research Council, Swedish Cancer Society, Mrs. Berta Kamprad's Cancer Foundation, Crafoord Foundation, Cancer Research Foundation at the Department of Oncology, Malmö University Hospital, and China Scholarship Council.

Cerebrospinal fluid cytology: A theragnostic and prognostic tool- Experience from a tertiary cancer care centre in central India

: CSF examination is the gold standard for diagnosing leptomeningeal metastases. Malignant cells may access the subarachnoid space by hematogenous dissemination, spreading directly from parenchymal brain lesions, or spreading along the spinal cord or cranial nerves. Cytological detection of malignant cells in CSF is still a crucial decision point for systemic and intrathecal chemotherapy, and it has prognostic significance even with improvements in biochemical analysis and CNS imaging. Over the course of two years, a total of 397 patients—regardless of gender and age—were investigated. There were sixty-four cases with involvement of the central nervous system documented, comprising 42 hematologic malignancies and 22 solid tumors. Cell centrifugation (Cytospin) method were used to prepare smears and cell blocks where prepared, as feasible and indicated. : A cytological analysis of the cerebrospinal fluid showed that metastatic tumors were much more prevalent than primary central nervous system tumours. Lung tumors were the most frequent primary site in our analysis, with breast, gastrointestinal, and female genital tract malignancies following closely behind. CNS involvement has been reported in patients with Lymphoma (DLBCL) and Leukemia (most commonly ALL, but also AML and JMML) among hematological malignancies. Two cases of Retinoblastoma and one each of Medulloblastoma and an Atypical teratoid/rhabdoid tumor were observed in the pediatric age group.: Cerebrospinal fluid cytology is a simple and useful method, used as a primary diagnostic method in the evaluation of leptomeningeal metastases. This helps in the early detection of secondary CNS lesions and allows for timely intervention, prognosis, and prediction of overall survival.

Ideal strategy for nonvariceal upper gastrointestinal bleeding.

Over 300 000 hospital admissions in the United States each year are due to patients with upper gastrointestinal (GI) bleeding (UGIB). Common etiologies of nonvariceal UGIB include peptic ulcers, mucosal erosions of the esophagus, stomach or duodenum, Mallory-Weiss tears, Dieulafoy lesions, upper GI tract malignancy, or other etiology. Peptic ulcers classified as Forrest Ia, Ib, or IIa require endoscopic hemostasis, while IIb ulcers may be considered for endoscopic clot removal with endoscopic treatment of any underlying major stigmata. Endoscopic hemostasis for ulcers classified as Forrest IIc or III is not advised due to the low risk of recurrent bleeding. Endoscopic hemostasis in ulcer bleeding can be achieved using injection, thermal, and/or mechanical modalities. This review focuses on the currently recommended endoscopic therapies of patients presenting with acute nonvariceal upper gastrointestinal hemorrhage.

Impact of Neoadjuvant Treatment on Body Composition in Patients with Locally Advanced Gastric Cancer.

Neoadjuvant chemotherapy (NT) followed by radical surgery is the standard treatment for locally advanced gastric cancer (GC). The incidence of sarcopenia in upper gastrointestinal tract malignancies is very high, and it may be increased after NT. This study aimed to evaluate the impact of NT on body composition. A retrospective study of patients with locally advanced GC undergoing gastrectomy who had received NT in a tertiary hospital between 2012 and 2019 was conducted. CT measured the skeletal muscle index, total psoas area, and visceral and subcutaneous adipose tissue before and after NT. Of the 180 gastrectomies for GC, 61 patients received NT. During NT, changes in body composition were observed with a decrease in the skeletal muscle mass index (SMMI -2.5%; p < 0.001), and these changes were significantly greater in men (SMMI -10.55%). Before surgery, patients who received NT presented 15% more sarcopenia than those without NT (p = 0.048). In conclusion, patients with locally advanced gastric cancer who receive NT have significant changes in body composition during chemotherapy. These changes, which are at the expense of a loss of muscle mass, lead to an increased incidence of pre-surgical sarcopenia.

Role of Positron Emission Tomography/Computed Tomography (PET/CT) in Assessment and Follow-up of Gastrointestinal Tract Malignancies

Positron Emission Tomography/Computed Tomography (PET/CT) is a highly advanced imaging method that has several uses in oncology, such as determining the stage of cancer, evaluating the effectiveness of treatment, reevaluating the stage of cancer, and monitoring for the return of cancer over time. PET advancement has brought out a new capacity in medical diagnosis: being able to non-invasively examine the physiological condition of interior tissues. The integration of PET with simultaneous CT combines two procedures that enable the diagnosis of metabolic or receptor-specific abnormalities together with precise anatomical localization. In comparison to PET alone, the PET/CT combination is more effective in accurately identifying the location of abnormalities and distinguishing between normal and abnormal uptake of FDG along with additional tracers. PET/CT has become an essential component of management guidelines in many diseases such as lung, breast, and lymphoproliferative malignancies. The ability to image metabolic processes like glucose metabolism adds to the information provided by structural imaging, especially in the context of treatment monitoring, where metabolic changes can often precede structural changes.

Level of interleukin 17 in inflammatory bowel disease and its relation with disease activity

BackgroundInflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the gastrointestinal tract (GIT).It results in progressive intestinal epithelium structural and functional damage that necessitates lifetime medication.Thereis imbalance in the production of T helper 1 (Th1), Th2 and Th17 cytokines. This plays a crucial role in the chronic inflammatory process and the defective immune response to pathogenic agents; thus promoting the recurrence of the disease.Our aim of this study was to detect serum IL-17 levels in IBD patients and its relation with disease activity.MethodsThis was a single center case control study, conducted at hepatology and gastroenterology unit, Mansoura specialized Medical Hospital, Egypt.Patients who were included were aged 18–65 years, diagnosed either Ulcerative Colitis (UC)or Crohn’s Disease (CD) based on previous colonoscopy.IBD activity was measured for UC using the MAYO score and CD using the CD activity index (CDAI). Fifty five patients were UC, 24 patients were CD, 21 patients were control.Patients who were excluded were under 15 years old, with history of GIT malignancy, or any serious comorbidities. Study protocol was approved by Institution Research Board (IRB) of Mansoura Medical College.All patients were subjected to full history taking, routine physical examination, colonoscopy and laboratory investigations including serum IL-17 levels by ELISA besides CBC, CRP, ESR and fecal calprotectin.ResultsSerum IL-17 level was increased significantly among UC; median (min-max) = 72(21–502)pg/ml, in CD 54.5(25–260) versus control 19 (14–35), P < 0.001.However, it was not correlated to the disease activity either Mayo score of UC or CDAI of CD.There was significant correlation to the extent of inflammation in UC affecting the colon (either proctosigmoiditis, left sided colitis or pan colitis), also to the type of CD (either inflammatory, stricturing or fistulizing) by P < 0.05.It was not correlated significantly with any of the IBD activity markers (CRP, ESR, or fecal calprotectin).Yet there was negative significant correlation with Hb level (r =-0.28, p = 0.005).There was not significant association between median serum level of IL-17 & duration of disease (P = 0.6).However, median IL-17 was higher among hospitalized cases than non-hospitalized (73 & 55, pg/ml respectively; p < 0.002). AUC was significantly differentiating between IBD and control group = 0.993 with the best-detected cut off point from curve 32 pg/ml yielding sensitivity of 97.5% and specificity of 95.2%.ConclusionSerum IL-17 increases in colonic inflammation significantly more than in control group, however its increase is not correlated to IBD activity.

An Uncommon Tumor in Stomach in A Young Girl

Introduction: Gastrointestinal stromal tumours (GIST) are rare tumours of the Gastrointestinal tract. They are the most common mesenchymal tumour of the gastrointestinal tract. All GISTs are malignant.Among all Gastrointestinal tract malignancies GIST Comprises 0.1- 3%. The most common location is stomach. They are usually found in elderly and they are not common in pediatric age group. Case Report: A girl aged 16 years presented with the history of melena, hematemesis with dyspepsia. Physical examination revealed mild tenderness over right hypochondrium. On examination, multiple hypopigmented patches noted over both upper limbs. CECT abdomen showed a well-defined heterogeneously enhancing predominantly exophytic necrotic soft tissue SOL over the greater curvature of the proximal body of the stomach with intraluminal extension. Her complete blood count and routine biochemical tests were within normal limits. Endoscopic biopsy from the polyploid lesion along the greater curvature show fragmented bits of gastric mucosa involved by a tumour composed of sheets and fascicles of round to oval cells having eosinophilic to vacuolated cytoplasm and a few spindle cells. Histopathological examination revealed a mesenchymal neoplasm favouring GIST.. Then wide local excision of the stomach was done and sent for histopathological examination. The stomach mass was diagnosed as Epithelioid GIST which was confirmed by immunohistochemistry. Conclusion: GISTs are most common mesenchymal tumours of GI tract. They are malignant in nature. The primary treatment of choice is surgery followed by chemotherapy.

Analysing Immunohistochemical Co-expression of CDH17, CK7 and CK20 in Lower Gastrointestinal Tumours: A Cross-sectional Study

Introduction: Lower gastrointestinal tract malignancies, especially colorectal malignancy constitute one of the most common malignancies worldwide and most common cause of cancer-related deaths in developed countries. It accounts for third most common malignancy in men and the second most common in women worldwide. In this context, CDH17 and CK20 are emerging markers for diagnosis, prognosis, and for targeted therapy in the future. Aim: To assess the expression of immunohistochemical markers like CDH17, CK7 and CK20 in lower gastrointestinal tumours. Materials and Methods: This cross-sectional study was conducted in the Department of Pathology, Chengalpattu Medical College, Chengalpattu, Tamil Nadu, India, for the duration one year six months, April 2020-October 2021. All cases of lower gastrointestinal tract malignancies obtained as small biopsies or resected specimens of about 40 cases were included in this study. For all cases, four sections were taken: one for Haematoxylin and Eosin (H&amp;E) stain and the other three for immunohistochemical stains for CDH17, CK7, and CK20, respectively. The sections were stained using a standard protocol. Histopathological categorisation, pathological staging, and grading of lower gastrointestinal carcinomas were conducted in conjunction with the immunohistochemical markers CDH17, CK7, and CK20. Descriptive statistics, including frequency and percentages, were calculated. The association between categorical variables was analysed by Kruskal-Wallis test. Results: Among the 40 cases, the expression of the CDH17, CK20, and CK7 markers showed 95.00% positivity (38 cases) for CDH17 and 92.50% positivity (37 cases) for CK20, whereas CK7 was found to be negative in 95.00% (38 cases) of the cases. Conclusion: The expression of CDH17 and CK20 in lower gastrointestinal malignancies, especially in the colorectum, was strong and diffuse. In contrast, the CK7 marker was not expressed in lower gastrointestinal malignancies. Thus, the IHC markers CDH17 and CK20 can be routinely employed as cocktail markers in lower gastrointestinal malignancies, especially in colorectal carcinoma of unknown primary origin.

Exosomal-miR-522-3p derived from cancer-associated fibroblasts accelerates tumor metastasis and angiogenesis via repression bone morphogenetic protein 5 in colorectal cancer.

Colorectal cancer (CRC) is a gastrointestinal tract malignancy. Exosomes secreted by cancer-associated fibroblasts (CAFs) are reported to participate in tumor progression by delivering noncoding RNA or small proteins. However, the function of exosomal miR-522-3p in CRC remains unclear. CAFs were derived from tumor tissues, and exosomes were identified by western blot or TEM/NTA and originated from CAFs/NFs. The viability, invasion, and migration of HUVECs and CRC cells was examined using MTT, Transwell, and wound healing assays, respectively. The molecular interactions were validated using dual luciferase reporter assay and RIP. Xenograft and lung metastasis mouse models were generated to assess tumor growth and metastasis. Exosomes extracted from CAFs/NFs showed high expression of CD63, CD81, and TSG101. CAF-derived exosomes significantly increased the viability, angiogenesis, invasion, and migration of HUVECs and CRC cells, thereby aggravating tumor growth, invasion, and angiogenesis in vivo. miR-522-3p was upregulated in CAF-derived exosomes and CRC tissues. Depletion of miR-522-3p reversed the effect of exosomes derived from CAFs in migration, angiogenesis, and invasion of HUVECs and CRC cells. Furthermore, bone morphogenetic protein 5 (BMP5) was identified as a target gene of miR-522-3p, and upregulation of BMP5 reversed the promoting effect of miR-522-3p mimics or CAF-derived exosomes on cell invasion, migration, and angiogenesis of HUVECs and CRC cells. Exosomal miR-522-3p from CAFs promoted the growth and metastasis of CRC through downregulating BMP5, which might provide new strategies for the treatment of CRC.

Minimally invasive treatment of multiple primary tumors of the gastrointestinal tract. Clinical observation

For now days we don’t have any guidelines for the treatment of synchronous and metachronous tumors of the upper and lower gastrointestinal tract. In this case report, we are talking about optimal treatment strategy in a patient with early gastric cancer, a neuroendocrine tumor of the sigmoid colon, and a locally advanced rectal cancer. The patient underwent laparoscopic gastrectomy and endoscopic excision of the early neuroendocrine tumor of the sigmoid colon. View of the local advanced rectal cancer patient underwent combined preoperative “sandwich” treatment with 2 courses of chemotherapy before a long course of chemoradiotherapy and 2 courses of chemotherapy after. The treatment was well tolerated. Ten weeks later, the patient gets surgical procedure: laparoscopic low anterior resection with loop colostomy followed by adjuvant chemotherapy. At the end of chemotherapy colostomy closure was done. The minimally invasive surgical treatment is safe and feasible in patients with synchronous malignancies of upper and lower gastrointestinal tract. Fast track rehabilitation and minimal surgical trauma ensure timely delivery of chemotherapy.

Clinical characteristics and prognostic outcomes for adenocarcinoma of esophagogastric junction in early-onset patients: a population-based appraisal.

Malignancies of the upper gastrointestinal tract are rare in early-onset patients outside the hereditary genetic disorders. There are few reports describing adenocarcinoma of the esophagogastric junction (AEG) in extremely early-onset patients aged under 50years old. The aim of this study was to describe the clinicopathological features and prognosis of adenocarcinoma of esophagogastric junction (AEG) in early-onset patients among three successive periods: 1975-1989 (period 1), 1990-2004 (period 2), and 2005-2017 (period 3). Between 1975 and 2017, data were extracted from the Surveillance, Epidemiology, and End Results database, and 18,278 patients with AEG were enrolled. Three age groups of patients were identified: < 50, 50-69, and ≥ 70years of age. Clinicopathological characteristics and prognostic outcomes were reviewed and compared among three groups over three periods (1975-89, 1990-04, and 2005-2017). Multivariate Cox regression analysis was performed to adjust for covariate effects related to both overall survival (OS) and cancer-specific survival (CSS). Among three age groups, early-onset patients were more likely to present with higher tumor grade, advanced nodal, and distant metastatic disease at diagnosis than other groups (p < 0.01 for both). In comparison to the older group, a higher proportion of patients in the early-onset group received chemotherapy and radiation treatment. After adjusting for covariates, early-onset patients had a better CSS and OS than elderly patients. Early-onset AEG patients were more likely than other age groups to present with advanced disease upon diagnosis. However, the prognosis of early-onset patients was better than their older counterparts after adjustment for covariates. The dissimilarities in tolerance to treatment among early-onset, middle-aged, and elderly patients could be the reason for this difference.

APC-Related Phenotypes and Intellectual Disability in 5q Interstitial Deletions: A New Case and Review of the Literature

The 5q deletion syndrome is a relatively rare condition caused by the monoallelic interstitial deletion of the long arm of chromosome 5. Patients described in literature usually present variable dysmorphic features, behavioral disturbance, and intellectual disability (ID); moreover, the involvement of the APC gene (5q22.2) in the deletion predisposes them to tumoral syndromes (Familial Adenomatous Polyposis and Gardner syndrome). Although the development of gastrointestinal tract malignancies has been extensively described, the genetic causes underlying neurologic manifestations have never been investigated. In this study, we described a new patient with a 19.85 Mb interstitial deletion identified by array-CGH and compared the deletions and the phenotypes reported in other patients already described in the literature and the Decipher database. Overlapping deletions allowed us to highlight a common region in 5q22.1q23.1, identifying KCNN2 (5q22.3) as the most likely candidate gene contributing to the neurologic phenotype.

Metastasis to Ascending Colon from Squamous Cell Carcinoma Cervix: Unusual Presentation

Ascending colon is an unusual site of metastasis from primary carcinoma cervix. Unusual sites of metastasis from squamous cell carcinoma (SCC) cervix include bones, stomach, duodenum, colon, skin. Squamous cell carcinoma is a rare malignancy of gastrointestinal tract (GI). Metastasis of SCC of cervix to GI tract is uncommon and has been reported only in a handful of cases. It may present with intestinal obstruction requiring debulking surgery. Management is palliative and role of chemotherapy or radiation is unclear. In this report we discuss a 47 year old female with history of squamous cell carcinoma of cervix treated in 2014. She developed local recurrence in 2019 and received pelvic re radiation. She presented with intestinal obstruction and on evaluation diagnosed to have metastatic squamous cell carcinoma of ascending colon.

Bacteria in cancer initiation, promotion and progression.

Cancer cells originate from a series of acquired genetic mutations that can drive their uncontrolled cell proliferation and immune evasion. Environmental factors, including the microorganisms that colonize the human body, can shift the metabolism, growth pattern and function of neoplastic cells andshapethe tumour microenvironment. Dysbiosis of the gut microbiome is now recognized as a hallmark of cancer by the scientific community. However, only a few microorganisms have been identified that directly initiate tumorigenesis or skew the immune system to generate a tumour-permissive milieu. Over the past two decades, research on the human microbiome and its functionalities within and across individuals has revealed microbiota-focused strategies for health and disease. Here, we review the evolving understanding of the mechanisms by which the microbiota acts in cancer initiation, promotion and progression. We explore the roles of bacteria in gastrointestinal tract malignancies and cancers of the lung, breast and prostate. Finally, we discuss the promises and limitations of targeting or harnessing bacteria in personalized cancer prevention, diagnostics and treatment.

Outcomes for patients with Lynch Syndrome in Manitoba.

e22548 Background: Lynch Syndrome (LS) is the leading cause of hereditary colorectal cancer (CRC) and is also associated with an increased risk of extracolonic cancers including endometrial, ovarian, upper gastrointestinal tract and genitourinary malignancies. Since 2013 in Manitoba, Canada, all CRC surgical specimens in patients ≤70 undergo reflex screening for the mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, PMS2) via immunohistochemistry. Since 2016, all endometrial cancers (EC) in patients ≤60 undergo similar reflex screening. The aim of this study was to examine the demographics, treatments and outcomes of patients with LS in Manitoba who have had a cancer diagnosis. Methods: Patients with pathogenic/likely pathogenic (P/LP) LS gene variants in Manitoba from 1999 were identified using records from the Program of Genetics and Metabolism. Those with a cancer diagnosis were identified using the Manitoba Cancer Registry (MCR). Non-melanomatous skin cancers and in-situ cancers were excluded. Descriptive statistics were used to report patient characteristics, LS gene variants, cancer diagnoses, treatments and outcomes. A survival analysis was undertaken using a matched cohort of patients with a diagnosis of CRC from 2004 to 2021 to compare overall survival (OS) between those with and without LS gene variants. A landmark survival analysis was performed to compare OS between those who had CRC before or after LS diagnosis. Results: 311 individuals with P/LP LS gene variants (96% pathogenic) and a record in the MCR were identified. The most common gene was MLH1 (33%), followed by MSH2 (29%), MSH6 (20%), PMS2 (16%) and EPCAM (2%). Most (72%) LS diagnoses occurred after 2014. There were 310 cancer diagnoses. The most common cancers amongst patients with LS were CRC (56%), EC (21%), urinary tract (5%), and ovarian (4%). Most cancer diagnoses (56%) occurred between 40-59 years old; 52% had stage I-II disease; 89% underwent surgery, 17% radiation &amp; 40% received systemic therapy. Of 12 patients diagnosed with cancer at &lt; 30 years old, 7 (58%) carried an MLH1 variant and 5 (42%) an MSH2 variant. 75 patients had ≥2 cancer diagnoses, 27 with an MLH1 variant (range 2-4); 30 MSH2 (2-5), 7 MSH6 (2-3), 9 PMS2 (2-3), 2 EPCAM (2-3). Using a matched CRC cohort to compare OS between those with and without LS, controlling for age, stage, sex, year of diagnosis, income quintile and treatment received, LS diagnosis was associated with a trend towards lower risk of death (HR 0.456, 95% CI 0.205-1.012, p = 0.053). There was no difference in OS according to whether a CRC diagnosis occurred pre- or post- LS diagnosis (p = 0.120). Conclusions: In this population-based study, the most common cancer diagnoses in patients with LS were CRC and EC. Many patients were diagnosed at a young age &amp; experienced multiple cancer diagnoses. More LS diagnoses occurred after 2014, supporting the role of reflex tumor testing. Amongst those diagnosed with CRC, LS is associated with a trend towards improved OS.

Cutaneous Metastase of Rectal Neuroendocrine Carcinoma Revealed on 18F-FDG PET/CT.

Rectal neuroendocrine carcinomas constitute <1% of all neuroendocrine carcinomas and <1% of all gastrointestinal tract malignancies. Cutaneous metastases of rectal neuroendocrine carcinoma are rarer than visceral metastases. We represent a 71-year-old man who was diagnosed with neuroendocrine tumor grade 3 originating from the rectum 1 year ago. He was referred for 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography for restaging after 6 cycles of chemotherapy and radiotherapy. Intensely increased 18F-FDG uptake in the right cutaneous inguinal region was consistent with neuroendocrine carcinoma metastasis with biopsy from the same region.

A Systematic Approach to Patients with Elevated Levels of Serum Amylase or Lipase

Serum amylase and lipase tests are routinely performed in patients presenting with abdominal pain or even during regular health screening. Elevated serum levels of these two enzymes are often encountered in clinical practice. The differential diagnosis is broad and includes acute pancreatitis, chronic pancreatitis, gastrointestinal tract obstruction, malignancies, and other disease conditions. In this article, we review the pathophysiology of elevated amylase and lipase, possible conditions that cause the increase, and diagnostic strategies for such patients. We conclude that a systematic approach to patients with elevated amylase and/or lipase is critical to making an accurate diagnosis and initiating appropriate treatment.