Anaplastic Kaposi Sarcoma of the Right Colon, in a Young Man With Acquired Immunodeficiency Syndrome: A Rare Variant in an Unreported Organ.

Kaposi sarcoma (KS) arises in the context of 4 epidemiologic-clinical settings: Classic, endemic, epidemic, and iatrogenic; the most serious types are endemic and epidemic, and visceral involvement occurs mostly in the latter. Several morphological variants of KS have been described, of which the anaplastic one is highly aggressive. We report the case of an anaplastic KS arising from the ascending colon in a 32-year-old human immunodeficiency virus (HIV)-positive male patient with a 6-year history of multiple mucocutaneous KS. Anaplastic KS is most frequent in endemic and classic settings; there are ten cases of anaplastic KS reported in HIV-positive male patients. There is now strong evidence that KS is a clonal neoplasm characterized by chromosomal instability at the molecular level. According to the morphological spectrum and contemporary hypotheses of oncogenesis, conventional KS should be considered an incipient endothelial neoplasia, multiple or single, and anaplastic KS, the fully developed stage of the malignant neoplasm.

Multivariate Prognostic Models for Patients with Stages I and Ii Colon Carcinoma: a Strobe-Compliant Retrospective Cohort Study.

Background: Colorectal cancer is the most frequent gastrointestinal malignancy worldwide. The value of adjuvant treatment is controversial in Stages I and II. Objective: The aim of this study was to construct post-operative prognostic models applicable to patients with stages I-II colon carcinoma (CC). Methods: This is a retrospective cohort study of patients with Stage I-II CC treated over a 25-year period. Exposure was defined as clinical, histopathological, and immunohistochemical factors (including CDX2 and MUC2 expression). Patients were randomly allocated to either a "modeling set" or a "validation set". Factors associated with recurrence, disease-free survival (DFS), and overall survival (OS) were defined in the "modeling set". Their performances were tested in the "validation set". Results: From a total of 556 recruited patients, 339 (61%) were allocated to the "modeling set" and 217 (39%) to the "validation set". Three models explaining recurrence, DFS, and OS were described. Tumor location in the left colon (Hazards ratio [HR] = 1.57; 95% Confidence interval [CI] 0.99-2.48), lymphocyte (HR = 0.46; 96% CI 0.27-0.88) and monocyte (HR = 0.99; 95% CI 0.99-1) counts, neutrophil/platelet ratio (HR = 1.3; 95% CI 0.74-2.3, and HR = 2.3; 95% CI 1.3-4.1; for second and third category, respectively), albumin/monocyte ratio (HR = 0.43; 95% CI 0.21-0.87), and microscopic residual disease after surgery (HR = 8.7; 95% CI 3.1-24) were independently associated with OS. T classification and expression of CDX2 and/or MUC2 were not independently associated with recurrence or prognosis. Conclusion: These models are simple and readily available, and distinguish the risk and prognosis in patients with CC stages I and II; these models require cheaper processes than the use of more sophisticated molecular biology techniques. They may guide either the need for adjuvant therapy versus post-operative surveillance only, as well as aid in the design of clinical trials.

Circulating miRNAs as Noninvasive Biomarkers for PDAC Diagnosis and Prognosis in Mexico.

Among malignant neoplasms, pancreatic ductal adenocarcinoma (PDAC) has one of the highest fatality rates due to its late detection. Therefore, it is essential to discover a noninvasive, early, specific, and sensitive diagnostic method. MicroRNAs (miRNAs) are attractive biomarkers because they are accessible, highly specific, and sensitive. It is crucial to find miRNAs that could be used as possible biomarkers because PDAC is the eighth most common cause of cancer death in Mexico. With the help of microRNA microarrays, differentially expressed miRNAs (DEmiRNAs) were found in PDAC tissues. The presence of these DEmiRNAs in the plasma of Mexican patients with PDAC was determined using RT-qPCR. Receiver operating characteristic curve analysis was performed to determine the diagnostic capacity of these DEmiRNAs. Gene Expression Omnibus datasets (GEO) were employed to verify our results. The Prisma V8 statistical analysis program was used. Four DEmiRNAs in plasma from PDAC patients and microarray tissues were found. Serum samples from patients with PDAC were used to validate their overexpression in GEO databases. We discovered a new panel of the two miRNAs miR-222-3p and miR-221-3p that could be used to diagnose PDAC, and when miR-221-3p and miR-222-3p were overexpressed, survival rates decreased. Therefore, miR-222-3p and miR-221-3p might be employed as noninvasive indicators for the diagnosis and survival of PDAC in Mexican patients.

CD24+CD44+CD54+EpCAM+ gastric cancer stem cells predict tumor progression and metastasis: clinical and experimental evidence.

BACKGROUND: Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide. Specific and thorough identification of cancer cell subsets with higher tumorigenicity and chemoresistance, such as cancer stem cells (CSCs), could lead to the development of new and promising therapeutic targets. For better CSC identification, a complete or extended surface marker phenotype is needed to provide increased specificity for new cell targeting approaches. Our goal is to identify and characterize a putative extended phenotype for CSCs derived from patients with GC before treatment, as well as to evaluate its clinical value. In addition, we aim to ensure that cells with this phenotype have stemness and self-renewal capabilities. METHODS: This is a cohort study including 127 treatment-naïve patients with GC who attended the Instituto Nacional de Cancerología. Multiparametric flow cytometry analysis was performed to determine the extended phenotype of cells derived from gastric biopsies. The tumorigenic capability of cells identified in patients was assessed in a zebrafish model. RESULTS: CD24+CD44+CD54+EpCAM+ cells were present in all treatment-naïve patients included, with a median abundance of 1.16% (0.57-1.89%). The percentage of CD24+CD44+CD54+EpCAM+ cells was categorized as high or low using 1.19% as the cutoff for the CD24+CD44+CD54+EpCAM+ cell subset. Additionally, a higher TNM stage correlated with a higher percentage of CD24+CD44+CD54+EpCAM+ cells (Rho coefficient 0.369; p < 0.0001). We also demonstrated that a higher percentage of CD24+CD44+CD54+EpCAM+ cells was positively associated with metastasis. The metastatic potential of these cells was confirmed in a zebrafish model. Ultimately, under our conditions, we conclude that CD24+CD44+CD54+EpCAM+ cells are true gastric cancer stem cells (GCSCs). CONCLUSION: The CD24+CD44+CD54+EpCAM+ cells present in tissue samples from patients are true GCSCs. This extended phenotype results in better and more specific characterization of these highly tumorigenic cells. The relative quantification of CD24+CD44+CD54+EpCAM+ cells has potential clinical value, as these cells are associated with metastatic disease, making their presence an additional prognostic marker and possibly a target for the design of new antineoplastic treatments in the era of precision oncology. Overall, the extended CD24+CD44+CD54+EpCAM+ phenotype of GCSCs could support their isolation for the study of their stemness mechanisms, leading to the identification of better molecular targets for the development of both new therapeutic approaches such as oncoimmunotherapy and new diagnostic and clinical prognostic strategies for GC.

Somatic Mutational Landscape in Mexican Patients: CDH1 Mutations and chr20q13.33 Amplifications Are Associated with Diffuse-Type Gastric Adenocarcinoma.

The Hispanic population, compared with other ethnic groups, presents a more aggressive gastric cancer phenotype with higher frequency of diffuse-type gastric adenocarcinoma (GA); this could be related to the mutational landscape of GA in these patients. Using whole-exome sequencing, we sought to present the mutational landscape of GA from 50 Mexican patients who were treated at The Instituto Nacional de Cancerología from 2019 to 2020. We performed a comprehensive statistical analysis to explore the relationship of the genomic variants and clinical data such as tumor histology and presence of signet-ring cell, H. pylori, and EBV. We describe a potentially different mutational landscape between diffuse and intestinal GA in Mexican patients. Patients with intestinal-type GA tended to present a higher frequency of NOTCH1 mutations, copy number gains in cytobands 13.14, 10q23.33, and 12q25.1, and copy number losses in cytobands 7p12, 14q24.2, and 11q13.1; whereas patients with diffuse-type GA tended to present a high frequency of CDH1 mutations and CNV gains in cytobands 20q13.33 and 22q11.21. This is the first description of a mutational landscape of GA in Mexican patients to better understand tumorigenesis in Hispanic patients and lay the groundwork for discovering potential biomarkers and therapeutic targets.

LKB-1 Expression and High-Risk Histopathology are Independent Prognostic Factors for Patients with Oral Cavity Carcinoma.

BACKGROUND: The expression of liver kinase B1 (LKB-1) has been associated with prognosis in squamous cell carcinoma of the oral cavity (SCCOC). This study aimed to define the prognostic role of LKB-1 expression for patients with SCCOC and the suitability of its integration into a multivariate prognostic model. METHODS: A retrospective cohort study of patients with SCCOC was conducted in a cancer center. Expression of LKB-1 was evaluated by immunohistochemistry, and multivariate analysis defined prognostic factors associated with recurrence, recurrence-free survival (RFS), and overall survival (OS). The logistic regression model was used to construct a predictive computer software program. RESULTS: Of the 201 patients in this study, 104 (51.7%) experienced recurrence of their disease. Lower expression of LKB-1, high-risk histopathology, and advanced tumor-node-metastasis (TNM) stages were independent factors via multivariate analysis associated with the increased recurrence risk, poor RFS, and poor OS. If lack of LKB-1 expression is considered the reference category, the factors independently associated with recurrence were low (odds ratio [OR], 0.157; 95% confidence interval [CI], 0.044-0.557), intermediate (OR, 0.073; 95% CI, 0.017-0.319), and intense (OR, 0.047; 95% CI, 0.007-0.304) expression of LKB-1. This model permitted construction of a computer software program capable of prediction with receiver operating characteristic analysis (area under the curve, 0.925) and led to the definition of five prognostic groups with a biologic gradient. CONCLUSION: These results suggest that LKB-1 expression in patients with SCCOC is of robust prognostic value and complements the TNM staging system. The proposed model requires external validation in prospective observational studies.

Portal Dissemination of Fusarium graminearum in a Patient with Acute Lymphoblastic Leukemia and Febrile Neutropenia.

We present the case of a man with acute lymphoblastic leukemia and prolonged profound neutropenia, who developed an invasive infection by Fusarium graminearum, acquired via non-cutaneous entry, with gastrointestinal symptoms, sigmoid perforation and liver abscesses due to portal dissemination. The etiologic agent was identified using the 18S-ITS1-5.8S-ITS2-28S rRNA sequence gene, from a liver biopsy. The infection was resolved with surgical drainage and antifungal treatment based on voriconazole. As far as we know, there are no previous reports in the literature of cases of human infection due to Fusarium graminearum.

Nutritional Indexes as Predictors of Survival and Their Genomic Implications in Gastric Cancer Patients.

Gastric cancer is an aggressive malignancy with poor prognosis. Although obesity is a risk factor, an association between overweight and better survival has been reported. We explored the genomic implications of such association. Data from 940 patients were analyzed using Cox regression models and ROC curves to assess body mass index (BMI) and prognostic nutritional index (PNI) as predictors of survival. The exome sequencing of a random subset was analyzed to determine copy number variation (CNV) and single nucleotide variation (SNV), using Kruskal-Wallis and chi-square tests to evaluate their clinical implications. Overall survival was lower in patients with BMI ≤ 24.9 and PNI ≤ 29 (p < 0.001). BMI and survival were directly correlated (HR: 0.972, 95% CI: 0.953, 0.992; p-value < 0.007). A higher PNI correlated with improved survival (HR: 0.586, 95% CI: 0.429, 0.801; p-value <0.001). We found a PNI cutoff point of 41.00 for overall survival. Genomic analysis showed an association between lower BMI, less CNV events (p-value = 0.040) and loss of tumor suppressor genes (p-value = 0.021). BMI and PNI are independent factors for overall survival in gastric cancer, probably linked to variations in genomic intratumoral alterations.

Prognostic Factors and Differences in Survival of Right and Left Colon Carcinoma: A STROBE Compliant Retrospective Cohort Study.

BACKGROUND: Right-colon cancer (RCC) presents differences with Left-colon cancer (LCC) in terms of Overall survival (OS), but certain reports provide conflicting findings. Our objective is to define differences regarding prognostic factors in RCC and LCC by multivariate analysis. METHODS: Retrospective cohort including patients treated from 1992-2016. The Kaplan-Meier and Cox models were used to define prognostic factors. RESULTS: 871 patients had RCC and 748 LCC; mean age was 58.1. Location was associated with socioeconomic status, body mass, blood hemoglobin, serum albumin, lymphocyte count and Prognostic nutritional index (PNI). Distribution of TNM stages was similar between groups, as well as gender, age, surgical morbidity/mortality; 72.3% of RCC and 83.2% of LCC were well/moderately differentiated (p <0.0001). Mean surgical lymph-node retrieval was 19.3 (SD14.6) for RCC and 15.7 (SD13.1) for LCC (p <0.0001). Median OS was 5.2 (95% CI 3.9-6.5) for RCC, and 3.2 years (95% CI 2.1-4.4) for LCC (p = 0.426). OS was different between RCC and LCC by stratified analyses within PNI, TNM, differentiation and R classification. RCC presents different OS in stages IIIC, and IVB than LCC. CONCLUSION: Differences between RCC and LCC were mainly by immunonutritional variables. Differences in OS were found after stratified analysis of PNI, TNM stages, differentiation degree, and R classification. Location of the neoplasm in the colon should be considered in the design of clinical trials in patients with colon cancer.

Association of the prognostic nutritional index and overall survival in patients with colorectal cancer: A STROBE compliant retrospective cohort study.

BACKGROUND: The TNM classification does not completely reflect the prognosis of patients with colorectal cancer (CRC). Several clinical factors have been used to increase its prognostic value, but factors pertaining to the patient's immunonutritional status have not usually been addressed. The aim of this study is to evaluate the role of Prognostic nutritional index (PNI) and other well-known prognostic factors by multivariate analysis in a cohort of patients with CRC. METHODS: This is a retrospective cohort study of consecutive patients with CRC managed in a cancer center between January 1992 and December 2016. Cox's model was used to define the association of the PNI and other factors with Overall survival (OS). RESULTS: A total of 3301 patients were included: 47.7% were female and 52.3% were male, with a mean age of 58.7 years. By bivariate analysis, PNI was strongly associated with OS (Risk ratio [RR] 0.968, 95% Confidence interval [CI] 0.962-0.974; P < 0.001). On multivariate analysis, PNI was an independent explanatory variable (as continuous variable and as categorized variable; RR 0.732, 95% CI 0.611-0.878; RR 0.656, 95% CI 0.529-0.813 and RR 0.646, 95% CI 0.521-0.802, for quintiles 2, 3, and 4-5, respectively); a biological gradient effect was demonstrated. The final prognostic model included PNI, location of the neoplasia in the colorectum, basal hemoglobin, lymphocyte count, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, TNM stage, differentiation degree, R classification, and postoperative complications. CONCLUSIONS: PNI is a significant and independent prognostic factor in patients with CRC. Its prognostic value adds precision to the TNM staging system including specific subgroups of patients with CRC; it should be evaluated in prospective clinical studies.

Clinicopathological features related to survival in adenocarcinoma of the Vaterian system in a Mexican population.

Adenocarcinomas of the ampulla of Vater account for 0.5% of malignant neoplasms of the gastrointestinal tract and 6% to 20% of malignant periampullary neoplasms, with most patients being candidates for elective surgery. Our objective was to evaluate the clinicopathological prognostic factors of ampullary adenocarcinomas after surgical resection in a Mexican population. From the records of the Department of Pathology at the Instituto Nacional de Cancerología, México, cases diagnosed as adenocarcinomas of the ampulla of Vater were selected over a period of 11 years, from January 2005 to September 2015. Cases with a pancreaticoduodenectomy report were included, and from each case, demographic and pathological data of the surgical specimen were obtained. Univariate and multivariate statistical analyses were performed using the log-rank test and Cox regression. Of 157 cases diagnosed as ampullary adenocarcinomas, 104 patients were excluded as not eligible for surgical treatment at the time of diagnosis. In the remaining 53 patients, a pancreaticoduodenectomy was performed. The mean age of the entire group was 55.4 years, and most were men. Intestinal-type adenocarcinomas were more frequent (77.4%) than pancreatobiliary-type (15.1%), with most being without perineural invasion, well to moderately differentiated, and less than 3 cm in size. Lymph node metastasis and age greater than 65 years had a negative impact on overall survival of the patients. The most convenient classification of malignant epithelial tumors of the Vaterian system is according to the histopathologic phenotype grouped into intestinal-, pancreatobiliary-, and mixed-type adenocarcinomas, as well as uncommon variants.

Circulating inflammation-related markers and advanced gastric premalignant lesions.

BACKGROUND AND AIM: Chronic Helicobacter pylori infection causes gastric mucosal inflammation as an important antecedent of gastric cancer. We aimed to evaluate associations of blood markers of inflammation with gastric intestinal metaplasia and dysplasia in H. pylori-infected individuals. METHODS: We compared pre-treatment serum levels of immune-related and inflammation-related markers between 99 individuals with intestinal metaplasia or dysplasia and 75 control individuals with non-atrophic gastritis within an H. pylori eradication trial in Mexico. Serum levels of 28 markers measured with Luminex bead-based assays were categorized in tertiles as low (T1), middle (T2), and high (T3). Logistic regression models were used to calculate age-adjusted and sex-adjusted odds ratios and 95% confidence intervals. All statistical tests were two-sided, and significance values were adjusted for multiple comparisons using false discovery rate methods. RESULTS: Five markers were nominally associated (Ptrend  < 0.05) with the presence of advanced premalignant gastric lesions. Adjusted odds ratios (95% confidence interval) of T2 and T3 versus T1 were 4.09 (1.65-10.17) and 3.08 (1.23-7.68) for CCL3/MIP1A, 3.21 (1.33-7.75) and 2.69 (1.10-6.57) for CCL20/MIP3A levels, 1.79 (0.77-4.18) and 2.39 (1.02-5.60) for IL-1ß, 1.34 (0.56-3.19) and 3.02 (1.29-7.12) for IL-4, and 1.07 (0.44-2.59) and 3.07 (1.32-7.14) for IL-5, respectively. Two (IL-4 and IL-5) of the five markers had false discovery rate adjusted Ptrend  < 0.2. CONCLUSIONS: Our results suggest that certain Th2 and other cytokines may have a role in promoting carcinogenesis in the setting of H. pylori infection. Additional research is needed to replicate these findings, extend to pre-diagnostic samples, and elucidate the underlying mechanisms.

Carcinoma epidermoide puro-combinado de vesícula biliar / Gallbladder epidermoid carcinoma

Background: Gallbladder epidermoid carcinoma is rare and more common in women over 55 years of age. Aim: To report the features of 15 patients with gallbladder epidermoid carcinoma. Material and Methods: Review of medical records of patients with gallbladder cancer in an oncology service. Results: Of 207 patients with gallbladder cancer, 15patients aged 53-72years, 93% women had an epidermoid component in their cancer. Forty percent were diabetic and 33% had cholelithiasis. All had locoregional extension of the tumor. A cholecystectomy was done in nine patients (using open surgery in six). In six patients, only a biopsy was done. Median survival was 4.2 months. Conclusions: Gallbladder epidermoid carcinoma is uncommon and has a bad prognosis.

Carcinoma epidermoide primario del estómago: reporte de tres casos / Primary squamous cell carcinoma of the stomach: report of three cases

Gastric squamous cell carcinoma (SCC) is a rare type of cancer. We report three patients with the tumor. A 65 years old male presenting with weight los and heartburn. An upper gastrointestinal endoscopy revealed an ulcerated tumor whose biopsy disclosed a gastric epidermoid carcinoma. The patient was operated and chemotherapy was attempted, but he died five months later. A 39 years old male with an antral tumor corresponding to an epidermoid carcinoma. He was operated and received chemotherapy and radiotherapy and died one year later. A 79 years old female with a distal antral tumor corresponding to a undifferentiated epidermoid carcinoma. She received palliative therapy and died two months later.

Quantitative proteomics reveals proteins involved in the progression from non-cancerous lesions to gastric cancer.

Gastric cancer is one of the most aggressive malignancies affecting humankind. With almost a million cases globally, it sits in fifth position in terms of incidence, and third in terms of mortality. The progression of this disease is slow, with prolonged and sequential precancerous stages including chronic gastritis, intestinal metaplasia, dysplasia, and finally gastric cancer. Here we used the iTRAQ approach combined with high-resolution mass spectrometry analysis to describe the spectrum of the gastric cancer cascade. Biopsies from three stages: chronic gastritis, intestinal metaplasia, and gastric adenocarcinoma, were selected for analysis by quantitative proteomics. We identified and reported quantitative data for 3914 different proteins quantified with high confidence, uncovering pathways and processes dysregulated between the different stages. Intestinal metaplasia is characterized by the down-regulation of ribosomal proteins, with overexpression of cell survival proteins such as GSTP1 and EPCAM. The transformation to gastric cancer involves overexpression of the DNA replication and the spliceosome pathways. The impairment of mitochondrial pathways was correlated with down-regulation of SIRT3 and SIRT5, and overexpression of enzymes supporting the glycolytic phenotype, such as HK3 and PCK2. Several proteins found dysregulated during the progression of gastric cancer have potential to be used as specific biomarkers and/or therapeutic targets.

Postradiation Synovial Sarcoma of the Common Bile Duct: A Previously Unreported Anatomic Site.

Synovial sarcoma is a ubiquitous neoplasm predominantly affecting soft tissues of young adults of any gender; few cases have been described in the digestive system, mostly in the stomach. The (X;18)(p11.2; q11.2) translocation yields unique SS18-SSX fusion genes. Synovial sarcoma has been related to radiotherapy, but no synovial sarcoma has been associated with the digestive system. This article describes the case of a synovial sarcoma arising along the extrahepatic biliary tree, 10 years after the application of an abdominal radiotherapy schedule due to a retroperitoneal metastatic seminoma in a male who developed progressive obstructive jaundice. Ninety percent of the analyzed cells carried the SS18 gene with separation of sequences, thus denoting a translocation. There are only 8 post-radiotherapy synovial sarcomas that have been reported previously, and this is the first report of a radiotherapy-related synovial sarcoma arising from the extrahepatic biliary tree, and the second case described in this anatomic region.

[Primary squamous cell carcinoma of the stomach. Report of three cases]. / Carcinoma epidermoide primario del estómago. Reporte de tres casos.

Gastric squamous cell carcinoma (SCC) is a rare type of cancer. We report three patients with the tumor. A 65 years old male presenting with weight los and heartburn. An upper gastrointestinal endoscopy revealed an ulcerated tumor whose biopsy disclosed a gastric epidermoid carcinoma. The patient was operated and chemotherapy was attempted, but he died five months later. A 39 years old male with an antral tumor corresponding to an epidermoid carcinoma. He was operated and received chemotherapy and radiotherapy and died one year later. A 79 years old female with a distal antral tumor corresponding to a undifferentiated epidermoid carcinoma. She received palliative therapy and died two months later.

[Gallbladder epidermoid carcinoma]. / Carcinoma epidermoide puro-combinado de vesícula biliar.

BACKGROUND: Gallbladder epidermoid carcinoma is rare and more common in women over 55 years of age. AIM: To report the features of 15 patients with gallbladder epidermoid carcinoma. MATERIAL AND METHODS: Review of medical records of patients with gallbladder cancer in an oncology service. RESULTS: Of 207 patients with gallbladder cancer, 15patients aged 53-72years, 93% women had an epidermoid component in their cancer. Forty percent were diabetic and 33% had cholelithiasis. All had locoregional extension of the tumor. A cholecystectomy was done in nine patients (using open surgery in six). In six patients, only a biopsy was done. Median survival was 4.2 months. CONCLUSIONS: Gallbladder epidermoid carcinoma is uncommon and has a bad prognosis.