Transcriptome and microbiome-immune changes across preinvasive and invasive anal cancer lesions.

Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy linked to high-risk Human papillomavirus (HPV) infection, which develops from precursor lesions like Low-Grade Squamous Intraepithelial Lesions (LGSIL) and High-Grade Squamous Intraepithelial Lesions (HGSIL). ASCC incidence varies across populations, posing increased risk for People Living with HIV (PLWH). Our investigation focused on transcriptomic and metatranscriptomic changes from Squamous Intraepithelial Lesions (SILs) to ASCC. Metatranscriptomic analysis highlighted specific bacterial species (e.g., Fusobacterium nucleatum, Bacteroides fragilis) more prevalent in ASCC than precancerous lesions. These species correlated with gene encoding enzymes (Acca, glyQ, eno, pgk, por) and oncoproteins (FadA, dnaK), presenting potential diagnostic or treatment markers. Unsupervised transcriptome analysis identified distinct sample clusters reflecting histological diagnosis, immune infiltrate, HIV/HPV status, and pathway activities, recapitulating anal cancer progression's natural history. Our study unveiled molecular mechanisms in anal cancer progression, aiding in stratifying HGSIL cases based on low- or high-risk progression to malignancy.

Prognostic Factors of Long-Term Outcomes after Primary Chemo-Radiotherapy in Non-Metastatic Anal Squamous Cell Carcinoma: An International Bicentric Cohort.

Anal squamous cell carcinoma (ASCC) is a rare malignancy with a rising incidence associated with human papillomavirus (HPV) infection. The locally advanced disease is associated with a 30% rate of treatment failure after standard chemoradiotherapy (CRT). We aimed to elucidate the prognostic factors for ASCC after curative CRT. A retrospective multicenter study of 176 consecutive patients with ASCC having completed CRT treated between 2010 and 2017 at two centers was performed. Complete response (CR), disease-free survival (DFS), and overall survival (OS) were analyzed by Kaplan-Meier estimates with log-rank tests. The hierarchical clustering on principal components (HCPC) method was employed in an unsupervised and multivariate approach. The CR rate was 70% and was predictive of DFS (p < 0.0001) and OS (p < 0.0001), where non-CR cases were associated with shorter DFS (HR = 16.5, 95% CI 8.19-33.21) and OS (HR = 8.42, 95% CI 3.77-18.81) in a univariate analysis. The median follow-up was 38 months, with a 3-year DFS of 71%. The prognostic factors for DFS were cT1-T2 (p = 0.0002), N0 (p = 0.035), HIV-positive (p = 0.047), HIV-HPV coinfection (p = 0.018), and well-differentiated tumors (p = 0.037). The three-year OS was 81.6%. Female sex (p = 0.05), cT1-T2 (p = 0.02) and well-differentiated tumors (p = 0.003) were associated with better OS. The unsupervised analysis demonstrated a clear segregation of patients in three clusters, identifying that poor prognosis clusters associated with shorter DFS (HR = 1.74 95% CI = 1.25-2.42, p = 0.0008) were enriched with the locally advanced disease, anal canal location, HIV-HPV coinfection, and non-CR. In conclusion, our results reinforce the prognostic value of T stage, N stage, sex, differentiation status, tumor location, and HIV-HPV coinfection in ASCC after CRT.

Laparoscopic Prophylactic Total Gastrectomy for Hereditary Diffuse Gastric Cancer in CDH1 Mutation Carriers.

Background: Patients with hereditary diffuse gastric cancer (HDGC) and germline mutations in the E-cadherin gene, CDH1, have a very high cumulative lifetime risk of developing diffuse gastric cancer. In these patients, it is formally recommended to perform a prophylactic total gastrectomy (PTG). Materials and Methods: We analyzed the course of patients with HDGC who have undergone PTG in our institution. Pedigree analysis, preoperative screening results, operative course, postoperative data, and complete stomach pathologic examination were performed in all patients. Results: Seven patients with confirmed CDH1 mutation underwent PTG, five were women, and average age was 27 years (range 17-42). Signet ring cell carcinoma was found in 1 patient in the preoperative surveillance endoscopic biopsies. Laparoscopic PTG was performed in all patients. There were two complications, an intestinal obstruction that required reintervention and an asymptomatic esophagojejunal anastomosis leak that resolved with conservative treatment. In all gastrectomy specimens, intramucosal signet ring cell carcinoma foci limited to the lamina propria were found (range 1-31), 83.5% were in the body-fundus region. The mean follow-up was 28.5 months (range 8-72). The mean weight loss was 9% (range 2-18). Postoperative symptoms associated with Dumping syndrome were the most frequent. All the patients reported of being very satisfied with the procedure and of having a better quality of life than expected before the procedure. Conclusion: Laparoscopic PTG is an excellent resource to prevent the development of advanced diffuse gastric cancer (DGC) in patients with HDGC with CDH1 mutation. The procedure was well tolerated with a high satisfaction rate and very good functional results. It should be considered in these patients due to the high risk of developing advanced DGC and the lack of effective and reliable surveillance studies.

Prognostic Impact of An Integrative Landscape of Clinical, Immune, and Molecular Features in Non-Metastatic Rectal Cancer.

Rectal Cancer (RC) is a complex disease that involves highly variable treatment responses. Currently, there is a lack of reliable markers beyond TNM to deliver a personalized treatment in a cancer setting where the goal is a curative treatment. Here, we performed an integrated characterization of the predictive and prognostic role of clinical features, mismatch-repair deficiency markers, HER2, CDX2, PD-L1 expression, and CD3-CD8+ tumor-infiltrating lymphocytes (TILs) coupled with targeted DNA sequencing of 76 non-metastatic RC patients assigned to total mesorectal excision upfront (TME; n = 15) or neoadjuvant chemo-radiotherapy treatment (nCRT; n = 61) followed by TME. Eighty-two percent of RC cases displayed mutations affecting cancer driver genes such as TP53, APC, KRAS, ATM, and PIK3CA. Good response to nCRT treatment was observed in approximately 40% of the RC cases, and poor pathological tumor regression was significantly associated with worse disease-free survival (DFS, HR = 3.45; 95%CI = 1.14-10.4; p = 0.028). High neutrophils-platelets score (NPS) (OR = 10.52; 95%CI=1.34-82.6; p = 0.025) and KRAS mutated cases (OR = 5.49; 95%CI = 1.06-28.4; p = 0.042) were identified as independent predictive factors of poor response to nCRT treatment in a multivariate analysis. Furthermore, a Cox proportional-hazard model showed that the KRAS mutational status was an independent prognostic factor associated with higher risk of local recurrence (HR = 9.68; 95%CI = 1.01-93.2; p <0.05) and shorter DFS (HR = 2.55; 95%CI = 1.05-6.21; p <0.05), while high CEA serum levels were associated with poor DFS (HR = 2.63; 95%CI = 1.01-6.85; p <0.05). Integrated clinical and molecular-based unsupervised analysis allowed us to identify two RC prognostic groups (cluster 1 and cluster 2) associated with disease-specific OS (HR = 20.64; 95%CI = 2.63-162.2; p <0.0001), metastasis-free survival (HR = 3.67; 95%CI = 1.22-11; p = 0.012), local recurrence-free survival (HR = 3.34; 95%CI = 0.96-11.6; p = 0.043) and worse DFS (HR = 2.68; 95%CI = 1.18-6.06; p = 0.012). The worst prognosis cluster 2 was enriched by stage III high-risk clinical tumors, poor responders to nCRT, with low TILs density and high frequency of KRAS and TP53 mutated cases compared with the best prognosis cluster 1 (p <0.05). Overall, this study provides a comprehensive and integrated characterization of non-metastatic RC cases as a new insight to deliver a personalized therapeutic approach.

Analysis of long-term oncological results of clinical versus pathological responses after neoadjuvant treatment in locally advanced rectal cancer.

BACKGROUND: Nonoperative management after neoadjuvant treatment in low rectal cancer enables organ preservation and avoids surgical morbidity. Our aim is to compare oncological outcomes in patients with clinical complete response in watch and wait strategy with those who received neoadjuvant therapy followed by surgery with a pathological complete response. METHODS: Patients with non-metastatic rectal cancer after neoadjuvant treatment with clinical complete response in watch and wait approach (group 1, n = 26) and complete pathological responders (ypT0N0) after chemoradiotherapy and surgery (group 2, n = 22), between January 2011 and October 2018, were included retrospectively, and all of them evaluated and followed in a multidisciplinary team. A comparative analysis of local and distant recurrence rates and disease-free and overall survival between both groups was carried out. Statistical analysis was performed using log-rank test, Cox proportional hazards regression model, and Kaplan-Meier curves. RESULTS: No differences were found between patient's demographic characteristics in both groups. Group 1: distance from the anal verge mean 5 cm (r = 1-12), 10 (38%) stage III, and 7 (27%) circumferential resection margin involved. The median follow-up of 47 months (r = 6, a 108). Group 2: distance from the anal verge mean 7 cm (r = 2-12), 16 (72%) stage III, and 13 (59%) circumferential resection margin involved. The median follow-up 49.5 months (r = 3, a 112). Local recurrence: 2 patients in group 1 (8.3%) and 1 in group 2 (4.8%) (p = 0.6235). Distant recurrence: 1 patient in group 1 (3.8%) and 3 in group 2 (19.2%) (p = 0.2237). Disease-free survival: 87.9% in group 1, 80% in group 2 (p = 0.7546). Overall survival: 86% in group 1 and 85% in group 2 (p = 0.5367). CONCLUSION: Oncological results in operated patients with pathological complete response were similar to those in patients under a watch and wait strategy mediating a systematic and personalized evaluation. Surgery can safely be deferred in clinical complete responders.

Pre-Existing Tumoral B Cell Infiltration and Impaired Genome Maintenance Correlate with Response to Chemoradiotherapy in Locally Advanced Rectal Cancer.

Locally advanced rectal cancer (LARC) remains a medical challenge. Reliable biomarkers to predict which patients will significantly respond to neoadjuvant chemoradiotherapy (nCRT) have not been identified. We evaluated baseline genomic and transcriptomic features to detect differences that may help predict response to nCRT. Eligible LARC patients received nCRT (3D-LCRT 50.4 Gy plus capecitabine 825 mg/m2/bid), preceded by three cycles of CAPOX in high systemic-relapse risk tumors, and subsequent surgery. Frozen tumor biopsies at diagnosis were sequenced using a colorectal cancer panel. Transcriptomic data was used for pathway and cell deconvolution inferential algorithms, coupled with immunohistochemical validation. Clinical and molecular data were analyzed according to nCRT outcome. Pathways related to DNA repair and proliferation (p < 0.005), and co-occurrence of RAS and TP53 mutations (p = 0.001) were associated with poor response. Enrichment of expression signatures related to enhanced immune response, particularly B cells and interferon signaling (p < 0.005), was detected in good responders. Immunohistochemical analysis of CD20+ cells validated the association of good response with B cell infiltration (p = 0.047). Findings indicate that the presence of B cells is associated with successful tumor regression following nCRT in LARC. The prevalence of simultaneous RAS and TP53 mutations along with a proficient DNA repair system that may counteract chemoradio-induced DNA damage was associated with poor response.

Observational study of patients with gastroenteropancreatic and bronchial neuroendocrine tumors in Argentina: Results from the large database of a multidisciplinary group clinical multicenter study.

Neuroendocrine tumors (NET) include a spectrum of malignancies arising from neuroendocrine cells throughout the body. The objective of this clinical investigation of retrospectively and prospectively collected data was to describe the prevalence, demographic data, clinical symptoms and methods of diagnosis of NET and the treatment and long-term follow-up of patients with NET. Data were provided by the participating centers and assessed for consistency by internal reviewers. All the cases were centrally evaluated (when necessary) by the pathologists in our group. The tissue samples were reviewed by hematoxylin and eosin and immunohistochemical staining techniques to confirm the diagnosis of NET. In total, 532 cases were documented: 461 gastroenteropancreatic-NET (GEP-NET) and 71 bronchial NET (BNET). All the tumors were immunohistochemically defined according to the World Health Organization (WHO) and European Neuroendocrine Tumor Society criteria. The most common initial symptoms in GEP-NET were abdominal pain, diarrhea, bowel obstruction, flushing, gastrointestinal bleeding and weight loss. The most common tumor types were carcinoid (58.0%), non-functional pancreatic tumor (23.0%), metastatic NET of unknown primary (16.0%) and functional pancreatic tumor (3.0%). Of the BNET, 89.0% were typical and 11.0% atypical carcinoids. Of the patients with GEP-NET, 59.2% had distant metastasis at diagnosis. The locations of the primary tumors in GEP-NET were the small bowel (26.9%), pancreas (25.2%), colon-rectum (12.4%), appendix (7.6%), stomach (6.9%), esophagus (2.8%), duodenum (2.0%) and unknown primary (16.3%). The histological subtypes based on the WHO classification were well-differentiated NET (20.1%), well-differentiated neuroendocrine carcinomas (66.5%) and poorly differentiated neuroendocrine carcinomas (10.3%). Overall, 67.3% of the patients underwent surgery, 41.2% with curative intent and 26.1% for palliative purposes. The 5-year survival rates were 65.1% (95% confidence interval, 58.0-71.4%) in GEP-NET and 100.0% in typical carcinoid of the lung. This observational, non-interventional, longitudinal study aimed to accumulate relevant information regarding the epidemiology, clinical presentation and current practices in the treatment of NET patients in Argentina, providing insight into regional differences and patterns of care in this heterogeneous disease.

Diferencias clínicas y quirúrgicas entre pacientes con tuberculosis abdominal con y sin infección por el virus de inmunodeficiencia humana / Clinical and surgical differences in patients with abdominal tuberculosis infected and non infected by human immunodeficiency virus patient

La tuberculosis abdominal (TBa) ocurre en el 1 al 2,5 % del total de la tuberculosis diagnosticadas. Objetivos: Analizar las diferencias entre las características clínicas y quirúrgicas de la TBa en pacientes VIH positivos y VIH negativos. Materiales y métodos: Estudio descriptivo-analítico retrospectivo entre dos poblaciones asistidas entre los años 1989-2009 con diagnóstico de TBa. Once pacientes eran VIH positivos y 60 VIH negativos. Se analizaron variables clínicas, humorales, hallazgos quirúrgicos, procedimientos diagnósticos utilizados y los diferentes órganos abdominales afectados. En el análisis estadístico se utilizó la prueba del Chi cuadrado o el test de Fischer. También se calcularon el ODDS Ratio (OR) e intervalo de confianza al 95 %. Resultados: se diagosticaron 71 casos de TBa de los cuales 11 (15,5 %) fueron VIH positivos. de los 71 casos la edad media fue de 38 años, los síntomas más frecuentes observados fueron pérdida de peso 90,1 %, dolor abdominal 81,4 %, hipertermia 91,6 %, entre otros. el 8,5 % de los pacientes fallecieron. Al comparar ambas poblaciones, se observaron diferencias estadísticamente significativas en la población VIH positiva quienes fueron más jóvenes, más frecuentemente de género masculino, con menor tiempo de duración de los síntomas, presentando en menor frecuencia hipertermia y disminución de peso y más frecuentemente masa abdominal palpable y adenopatías en la cavidad abdominal. La mortalidad fue también mayor en este grupo. Conclusiones: La población presentó variables estadísticamente significativas para la edad, el género, tiempo de evolución de los síntomas, entre otras variaables que pueden ser de utilidad en su diagnóstico diferencial.

Abdominal tuberculosis (TBA) occurs in 1 to 2,5 % of total tuberculosis diagnosed. Objective: To analyze the differences between clinical and surgical characteristics of the TBA in HIV patients and HIV non-reactive reagents. Materials and Methods: A retrospective descriptive-analyticstudy of two groups assisted in the years 1989-2009 with a diagnosis of TBA. Eleven patients were HIV positive and 60 HIV-negative. We analyzed the clinical, laboratory findings and surgical findings, the diagnostic procedures used and the abdominal organs affected. Statistical analysis used Chi square test or Fischer test. Also calculated the Odds Ratio (OR) and confidence interval 95 %. Results: We diagnosed 71 cases of TBA of which 11 (15,5%) were HIV positive. Of the 71 cases the average age was 38 years, the most common symptoms observed were weight loss (90,1 %), abdominal pain (81,4 %), hyperthermia (91,6 %). 8,5 % of the patients died. HIV positive and negative were compared finding statistically significant differences in the HIV who were younger, more often male, with shorter duration of symptoms. In this population weight reduction and hyperthermia was less frequently in contrast with frequently palpable abdominal mass and lymphadenopathy in the abdominal cavity. Mortality was higher in among HIV positive patients. Conclusions: the present population statistically significnt variables for age, gender and time in the presence of sympotoms, among other variable that may be useful in the differential diagnosis.

Diferencias clínicas y quirúrgicas entre pacientes con tuberculosis abdominal con y sin infección por el virus de inmunodeficiencia humana / Clinical and surgical differences in patients with abdominal tuberculosis infected and non infected by human immunodeficiency virus patient

La tuberculosis abdominal (TBa) ocurre en el 1 al 2,5 % del total de la tuberculosis diagnosticadas. Objetivos: Analizar las diferencias entre las características clínicas y quirúrgicas de la TBa en pacientes VIH positivos y VIH negativos. Materiales y métodos: Estudio descriptivo-analítico retrospectivo entre dos poblaciones asistidas entre los años 1989-2009 con diagnóstico de TBa. Once pacientes eran VIH positivos y 60 VIH negativos. Se analizaron variables clínicas, humorales, hallazgos quirúrgicos, procedimientos diagnósticos utilizados y los diferentes órganos abdominales afectados. En el análisis estadístico se utilizó la prueba del Chi cuadrado o el test de Fischer. También se calcularon el ODDS Ratio (OR) e intervalo de confianza al 95 %. Resultados: se diagosticaron 71 casos de TBa de los cuales 11 (15,5 %) fueron VIH positivos. de los 71 casos la edad media fue de 38 años, los síntomas más frecuentes observados fueron pérdida de peso 90,1 %, dolor abdominal 81,4 %, hipertermia 91,6 %, entre otros. el 8,5 % de los pacientes fallecieron. Al comparar ambas poblaciones, se observaron diferencias estadísticamente significativas en la población VIH positiva quienes fueron más jóvenes, más frecuentemente de género masculino, con menor tiempo de duración de los síntomas, presentando en menor frecuencia hipertermia y disminución de peso y más frecuentemente masa abdominal palpable y adenopatías en la cavidad abdominal. La mortalidad fue también mayor en este grupo. Conclusiones: La población presentó variables estadísticamente significativas para la edad, el género, tiempo de evolución de los síntomas, entre otras variaables que pueden ser de utilidad en su diagnóstico diferencial.(AU)

Abdominal tuberculosis (TBA) occurs in 1 to 2,5 % of total tuberculosis diagnosed. Objective: To analyze the differences between clinical and surgical characteristics of the TBA in HIV patients and HIV non-reactive reagents. Materials and Methods: A retrospective descriptive-analyticstudy of two groups assisted in the years 1989-2009 with a diagnosis of TBA. Eleven patients were HIV positive and 60 HIV-negative. We analyzed the clinical, laboratory findings and surgical findings, the diagnostic procedures used and the abdominal organs affected. Statistical analysis used Chi square test or Fischer test. Also calculated the Odds Ratio (OR) and confidence interval 95 %. Results: We diagnosed 71 cases of TBA of which 11 (15,5%) were HIV positive. Of the 71 cases the average age was 38 years, the most common symptoms observed were weight loss (90,1 %), abdominal pain (81,4 %), hyperthermia (91,6 %). 8,5 % of the patients died. HIV positive and negative were compared finding statistically significant differences in the HIV who were younger, more often male, with shorter duration of symptoms. In this population weight reduction and hyperthermia was less frequently in contrast with frequently palpable abdominal mass and lymphadenopathy in the abdominal cavity. Mortality was higher in among HIV positive patients. Conclusions: the present population statistically significnt variables for age, gender and time in the presence of sympotoms, among other variable that may be useful in the differential diagnosis.(AU)

Vasoespasmo por cocaína y ergotamina en un paciente HIV positivo / Cocaine and Ergotamine Vasospasm in an HIV Patient

La cocaína es un alcaloide muy difundido para el consumo como estimulante. Tiene una potente acción vasoconstrictora y anestésica, la cual sumada al efecto de otras drogas como la ergotamina, puede producir vasoespasmo generalmente de miembros inferiores, así como la aparición de otras afecciones cutáneas que frecuentemente se observan en los pacientes adictos a drogas. Presentamos un caso grave de intoxicación con cocaína y ergotamina seguido de necrosis de los miembros inferiores y de un miembro superior, que debieron ser amputados

Cocaine is a widespread alkaloid, that consumers usually prefer as a stimulant Vasomotor and anesthetic effects, are strong. When other vasoconstrictor drugs, such as ergotamine, simultaneously added, extreme vasospasm, mostly of limbs, and cutaneous injuries, can develop. We communicate a serious case of cocaine and ergotamine intoxication, followed by necrosis of both legs and one arm. Therefore, the three extremities must have been to be amputated

Mesotelioma maligno del pericardio / Malignant mesothelioma of the pericardium

El mesotelioma maligno es un tumor que se presenta en relación 1: 4000 pacientes autopsiados por neoplasias malignas. La localización pericárdica es la menos frecuente, constituyendo menos del 2 por ciento del total de tumores cardíacos. Se presenta un caso en el que el tumor produjo un síndrome de taponamiento cardíaco, sin ser diagnosticado en vida a pesar de efectuarse una biopsia pericárdica subxifoidea. El paciente murió bruscamente, halládose en la autopsia dicho tumor infiltrando la aurícula derecha y haciendo protusión en la cavidad, englobando la arteria coronaria derecha. Esto último podría ser responsable de la muerte. Se comparan los hallazgos clínicos y patológicos con 30 casos extraídos de la literatura reciente

Mesotelioma maligno del pericardio / Malignant mesothelioma of the pericardium

El mesotelioma maligno es un tumor que se presenta en relación 1: 4000 pacientes autopsiados por neoplasias malignas. La localización pericárdica es la menos frecuente, constituyendo menos del 2 por ciento del total de tumores cardíacos. Se presenta un caso en el que el tumor produjo un síndrome de taponamiento cardíaco, sin ser diagnosticado en vida a pesar de efectuarse una biopsia pericárdica subxifoidea. El paciente murió bruscamente, halládose en la autopsia dicho tumor infiltrando la aurícula derecha y haciendo protusión en la cavidad, englobando la arteria coronaria derecha. Esto último podría ser responsable de la muerte. Se comparan los hallazgos clínicos y patológicos con 30 casos extraídos de la literatura reciente (AU)