Banff 2022 Vascularized Composite Allotransplantation Meeting Report: Diagnostic criteria for vascular changes.

As more data become available, the Banff 2007 working classification of skin-containing vascularized composite allograft (VCA) pathology is expected to evolve and develop. This report represents the Banff VCA Working Group's consensus on the first revision of the 2007 scoring system. Prior to the 2022 Banff-CanXadian Society of Transplantation Joint Meeting, 83 clinicians and/or researchers were invited to a virtual meeting to discuss whether the 2007 Banff VCA system called for a revision. Unanimously, it was determined that the vascular changes were to be included in the first revision. Subsequently, 2 international online surveys, each followed by virtual discussions, were launched. The goals were (1) to identify which changes define severe rejection, (2) to grade their importance in the evaluation of severe rejection, and (3) to identify emerging criteria to diagnose rejection. A final hybrid (in-person and virtual) discussion at the Banff/Canadian Society of Transplantation Joint Meeting finalized the terminology, the definition, a scoring system, and a reporting system of the vascular changes. This proposal represents an international consensus on this topic and establishes the first revision of the Banff 2007 working classification of skin-containing vascularized composite allograft pathology.

Clinical, molecular, and histological characteristics of severely necrotic and fatal mpox in HIV-infected patients.

BACKGROUND: This case series of 5 patients with severely necrotic mpox highlights the predominantly necrotic nature of lesions seen in cases of severe mpox as shown by skin and lung biopsy, as well as the extensive dissemination of the infection, as shown by polymerase chain reaction (PCR) assessment in different body sites. CASE PRESENTATIONS: Patients were male, the median age was 37, all lived with HIV (2 previously undiagnosed), the median CD4+ cell count was 106 cells/mm3, and 2/5 were not receiving antiretroviral treatment. The most common complication was soft tissue infection. Skin and lung biopsies showed extensive areas of necrosis. Mpox PCR was positive in various sites, including skin, urine, serum, and cerebrospinal fluid. The initiation of antiretroviral treatment, worsened the disease, like that seen in immune reconstitution syndrome. Three patients died due to multiple organ failure, presumably associated with mpox since coinfections and opportunistic pathogens were ruled out. CONCLUSIONS: Severely necrotic manifestations of mpox in people living with advanced and untreated HIV are related to adverse outcomes.

Galectin-3 is overexpressed in advanced cirrhosis and predicts post-liver transplant infectious complications.

BACKGROUND & AIMS: Patients with advanced cirrhosis often have immune dysfunction and are more susceptible to infections. Galectin-3 is a ß-galactoside-binding lectin implicated in inflammation, immune regulation and liver fibrosis. We aim to investigate galectin-3 expression in advanced cirrhosis and its ability to predict post-transplant infectious complications. METHODS: We collected sera and liver samples from 129 cirrhotic patients at the time of liver transplantation and from an external cohort of 37 patients with alcoholic liver disease including alcoholic hepatitis (AH) at the time of diagnosis. Galectin-3 was assessed by ELISA, real-time PCR, immunohistochemistry and RNA-seq. Receiver operating characteristic curves and Cox proportional-hazards regression analysis were performed to assess the predictive power of galectin-3 for disease severity and post-transplant infections. RESULTS: Increased galectin-3 levels were found in advanced cirrhosis. Galectin-3 significantly correlated with disease severity parameters and inflammatory markers. Galectin-3 had significant discriminating power for compensated and advanced cirrhosis (AUC = 0.78/0.84, circulating/liver galectin-3; p < .01), and was even higher to discriminate severe AH (AUC = 0.95, p < .0001). Cox Proportional-hazard model showed that galectin-3, MELD-Na and the presence of SIRS predict the development of post-transplant infectious complications. Patients with circulating galectin-3 (>16.58 ng/ml) were at 2.19-fold 95% CI (1.12-4.29) increased risk, but when combined with MELD-Na > 20.0 and SIRS, the risk to develop post-transplant infectious complications, increased to 4.60, 95% CI (2.38-8.90). CONCLUSION: Galectin-3 is a novel biological marker of active inflammation and disease severity that could be clinically useful alone or in combination with other scores to discriminate advanced cirrhosis and predict post-transplant infectious complications.

Capsaicin Decreases Kidney Iron Deposits and Increases Hepcidin Levels in Diabetic Rats with Iron Overload: A Preliminary Study.

Iron overload (IOL) increases the risk of diabetes mellitus (DM). Capsaicin (CAP), an agonist of transient receptor potential vanilloid-1 (TRPV1), reduces the effects of IOL. We evaluated the effects of chronic CAP administration on hepcidin expression, kidney iron deposits, and urinary biomarkers in a male Wistar rat model with IOL and DM (DM-IOL). IOL was induced with oral administration of iron for 12 weeks and DM was induced with streptozotocin. Four groups were studied: Healthy, DM, DM-IOL, and DM-IOL + CAP (1 mg·kg-1·day-1 for 12 weeks). Iron deposits were visualized with Perls tissue staining and a colorimetric assay. Serum hepcidin levels were measured with an enzyme-linked immunosorbent assay. Kidney biomarkers were assayed in 24 h urine samples. In the DM-IOL + CAP group, the total area of iron deposits and the total iron content in kidneys were smaller than those observed in both untreated DM groups. CAP administration significantly increased hepcidin levels in the DM-IOL group. Urinary levels of albumin, cystatin C, and beta-2-microglobulin were similar in all three experimental groups. In conclusion, we showed that in a DM-IOL animal model, CAP reduced renal iron deposits and increased the level of circulating hepcidin.

Sjögren Syndrome Induced by Immune Checkpoint Inhibitors in a Patient with Advanced Renal Cell Carcinoma.

This clinical quandary details a Mexican man, aged 77 years, who presented to the oncology clinic with a sternal mass. Based on the results, the patient fulfilled the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for Sjögren syndrome, thus the diagnosis triggered by immune checkpoint inhibitors was definitively established.

Coupe de Grace: Autopsy in COVID-19 Pandemic.

As the media informed the spread of a highly transmissible disease, our medical community faced the disappearance of a languishing ancient tool. Traditionally helping to explain unexplainable death, educate, audit, warn relatives, or contacts; autopsies vanished in a reassigned COVID-19 teaching hospital (Fig. 1).

Metabolic Syndrome Instead of Aflatoxin-Related TP53 R249S Mutation as a Hepatocellular Carcinoma Risk Factor.

BACKGROUND: Hepatocarcinogenesis has a variety of risk factors. In Mexico City, autopsies found 14% of hepatocellular carcinomas (HCCs) without cirrhosis. OBJECTIVE: The objective of the study was to explore if HCCs carry the TP53 R249S mutation that has linked them to aflatoxin exposure and describe the associated risk factors. METHODS: A retrospective review of consecutive cases of HCC was performed. Exposure to hepatotropic viruses, alcoholism, metabolic diseases, diabetes mellitus, and hypertension, as well as episodes of ascites, portal hypertension, and body mass index were retrieved. Slides were re-reviewed, macrodissected and DNA was extracted. TP53 exon 7 was amplified, purified, and used as a template for sequencing. RESULTS: In 14 years, 74 HCCs were identified in 1863 (4%) consecutive liver biopsies. No data were available in five excluded patients; the rest was submitted to exon 7 screening. Patients had a median age of 62 years, and 46 (67%) were male. Stage 4 fibrosis was observed in 46 patients (67%) and their associated risk factors were hepatitis C virus (39%, 18/46), alcoholism (20%, 9/46), hepatitis B virus (2%, 1/46), and 18 were cryptogenic. Fibrosis stage 3 or lower was observed in 23 (33%) patients without demonstrated liver disease; 8/23 had diabetes and 6/23, systemic hypertension. Steatohepatitic variants of HCC were observed in 4 and in 5, the remnant liver had steatohepatitis. A 238-bp fragment was obtained in each tumor without the expected TP53 R249S mutation. CONCLUSIONS: There was no evidence of aflatoxin exposure in HCCs, with and without the known "classical" risk factors. One-third of non-cirrhotic HCCs had steatohepatitis or conditions associated to metabolic syndrome.

Moderate and high intensity chronic exercise reduces plasma tumor necrosis factor alpha and increases the Langerhans islet area in healthy rats.

OBJECTIVE: This study aimed to examine the effects of moderate (MIT) and high-intensity training (HIT) chronic exercise on plasma tumor necrosis factor alpha (TNF-α) level and its impact on Langerhans islet morphology in healthy rats. METHODS: Two-month old normal male Wistar rats were divided into three groups: control (C, n=6), MIT (n=6), and HIT (n=4). The training protocol consisted in 24 sessions of running on a treadmill at 60-80% maximal oxygen consumption (VO2max) for MIT, and >80% VO2max for HIT. TNF-α and insulin were measured with ELISA tests. Duodenal pancreas was dissected to analyze the Langerhans islets by immunohistochemistry, a correlation analysis was performed with the nuclei/total islet area. Results: HIT and MIT rats showed lower TNF-α plasma levels than controls. Plasma insulin level decreased significantly in HIT compared with C and MIT. In addition, the islet area and nuclei density per islet were higher in the exercise groups compared with C. However, none of the groups showed PD1 immunoreactivity. CONCLUSIONS: Under healthy conditions, the chronic exercise reduced plasmatic TNF-α level, and in the same sense, increased the size of the Langerhans islets, depending to the exercise intensity.

Changing Trends in Gastric Polyps.

BACKGROUND: The prevalence of gastric polyps varies around the world reflecting regional associations. We describe demographic features of patients with gastric polyp diagnosis treated between 1980 and 2016 at a referral center in Mexico City and analyzed trends of polyp subtype. MATERIALS AND METHODS: We conducted a blind review of archival slides of gastric biopsies with polyp diagnosis from the years 1980, 1990, 2000, 2010, and 2016. Initial diagnosis; patient's gender, age and symptoms; and number and location of lesions were recorded. Blind slide review and trend analysis were performed. RESULTS: In 3887 gastric biopsies, 192 patients (4.93%) with epithelial polyps were identified. The median age of patients was 58 years; 73% were female. Polyps were single in 143/192 cases (74.4%), almost 67% in the oxyntic mucosa, and 85% were associated with dyspepsia. The prevalence was 0.5%, 1.6%, 1.9%, 4.6%, and 9.6% for the years 1980, 1990, 2000, 2010, and 2016, respectively, resulting in a rising trend in the prevalence of epithelial polyps of 380% in 46 years. Fundic gland polyps (FGPs) had a global frequency of 66.6% (128/192). They were identified for the first time in the third period of the study, with a frequency of 28.6% (6/21), 66.6% (35/53), and 78.3% (87/111) for the years 2000, 2010, and 2016, respectively. Contrary, hyperplastic polyps (HPs) decreased 20%. A relative prevalence of 3.29%, 0.97%, and 0.15% was observed for FGP, HP, and gastric adenoma, respectively. DISCUSSION: The 1400% change of FGP explains the increased prevalence of gastric polyps. Chronic treatment with proton pump inhibitors and Helicobacter pylori eradication are possible explanations.

Tumour budding in rectal cancer. A comprehensive review.

A unique and fundamental characteristic of malignant neoplastic cells is their ability to invade other tissues and metastasise. The first step in this process is the dissociation of some of these cells from the tumour invasion front, named tumour budding (TB). This phenomenon has become increasingly relevant in recent years due to its association with adverse clinicopathological characteristics and with the epithelial-mesenchymal transition. TB has been studied by mixing colon with rectal tumours, but it is clinically important to differentiate these types of tumours. A review in two databases without language restriction was performed from 1950 to 2017 about TB with an emphasis on rectal cancer. We present various aspects of TB, from its terminology and evaluation to its molecular aspects, through its clinical associations. TB is associated with adverse clinicopathological features, like lymphovascular invasion, lymph node metastasis, and decreased survival. More studies of the clinicopathological, molecular, and epidemiological characteristics of TB in rectal cancer are needed.

Liver transplantation center in México with low-volume and excellent results / Centro de trasplante hepático en México con bajo volumen y excelentes resultados

Background: Orthotopic liver transplantation (OLT) is the treatment of choice for end stage liver disease. Many studies show an inverse relationship between the number of procedures and operative mortality. Objective: The objective of the study is to show the results of our center and determine if it can have comparable results to high volumen centers. Method: This is a retrospective study which analyzed the information of patients with OLT at our institution from 1985 to December 31, 2012. Depending on date of transplantation, the study was divided into three stages. Stage 1: from 1985 to 1999. Stage 2: from 2000 to 2007. Stage 3: from 2008 to 2012. In the 1, 2 and 3 stage 22, 37 and 56 OLT were performed respectively. Results: Perioperative mortality was significantly lower between Stage 3 vs. Stage 1 and 2 (3.5% vs. 50% and 21.7%, p = 0.001). Patient survival was also better at 1 and 5 years at Stage 3 (94.4%, 87.8%) vs. era 2 (77.6%, 66.17%) and Stage 1 (47% and 29%) (p = 0.001). Conclusion: In conclusion, the present results of OLT at our program are excellent despite being a low-volume center.

Antecedentes: El trasplante hepático ortotópico (THO) es el tratamiento de elección para la insuficiencia hepática terminal. Numerosos estudios muestran una relación inversa entre el número de procedimientos y la mortalidad operatoria. Objetivo: El objetivo de este estudio es mostrar los resultados de nuestro centro y determinar si puede tener resultados equiparables a los obtenidos en centros de alto volumen. Método: Es un estudio retrospectivo en el que se analizó la información de pacientes con THO en nuestra institución, de 1985 al 31 de diciembre de 2012. Dependiendo de la fecha del THO, el estudio se dividió en tres etapas: etapa 1, de 1985 a 1999; etapa 2, de 2000 a 2007; y etapa 3, de 2008 a 2012. En las etapas 1, 2 y 3 se realizaron 22, 37 y 56 THO, respectivamente. Resultados: La mortalidad perioperatoria fue menor de manera significativa en la etapa 3 en comparación con las etapas 1 y 2 (3.5 vs. 50 y 21.7%; p = 0.001). La supervivencia de los pacientes a 1 y 5 años fue mejor en la etapa 3 (94.4 y 87.8%) que en la etapa 2 (77.6 y 66.17%) y en la etapa 1 (47 y 29%) (p = 0.001). Conclusión: En conclusión, los resultados actuales en THO en nuestro programa son excelentes, a pesar de ser un centro de bajo volumen.

Association between AT1 and AT2 angiotensin II receptor expression with cell proliferation and angiogenesis in operable breast cancer.

Angiotensin II (ANGII) has been associated with vascular proliferation in tumor and non-tumor models through its receptors AT1 and AT2. Our objective was to determine AT1 and AT2 receptor expression in operable breast cancer and its association with tumor grade, vascular density, and cellular proliferation. Seventy-seven surgically malignant breast tumors with no distant metastasis were included, and 7 benign lesions were used as controls. AT1 and AT2 receptor expression was determined by RT-PCR and immunohistochemistry (IHC) in 68 out of the 77 malignant lesions and in the 7 benign lesions. AT1 and AT2 receptor expression was detected in 35.3 and 25 % of cases, in both RT-PCR and IHC. Tumors that express AT1 showed an increase in T3 stage (92.3 vs. 7.7 % p < 0.001), mitotic index (4 ± 1 vs 2 ± 1, p = 0.05), vascular density (15 ± 3 vs 8 ± 5, p = 0.05), and cellular proliferation (85 ± 18 vs 55 ± 10, p = 0.01) versus AT1-negative lesions. Non-differences between clinical-pathologic variables and AT2 expression were found. AT1 receptor expression was associated to enhance angiogenesis and cellular proliferation rate, but no relationship with AT2 was found. ANGII and its peptides might play a role in the development and pathophysiology of breast cancer, and this could be valuable in the in the development of targeted therapies.

Changes in receptivity epithelial cell markers of endometrium after ovarian stimulation treatments: its role during implantation window.

BACKGROUND: To compare the expression of receptivity markers in epithelial and stromal cells in the endometrium of ovulatory women and infertile with hypothalamic pituitary dysfunction (HPD), untreated or treated with clomiphene citrate (CC), or with recombinant follicle stimulating hormone (rFSH). METHODS: Twelve control ovulatory and 32 anovulatory women, 22 of whom received ovulation induction with CC (n = 12) or rFSH (n = 10). Endometrial biopsies were obtained during the mid-secretory phase. Hormonal secretion was measured by chemiluminescence immunoassay, endometrial dating and cellular expression and distribution of receptivity proteins were evaluated by quantitative immunohistochemistry. RESULTS: CC or rFSH treatments, modified the expression of epithelial receptivity markers, such as Glycodelin A, beta-catenin, CD166/ALCAM and IGF-1R, but not in stromal markers. Also, a change in their cell distribution was observed. CONCLUSIONS: Treatment of infertile women with HPD modified the expression and distribution of receptivity markers in the mid-secretory phase of the endometrium in epithelial but not stromal cells, which can help to explain changes in the receptivity of the endometrium during treatments and suggest an important role of these cells in the receptivity window.

In vivo dual targeting of the oncogenic Ether-à-go-go-1 potassium channel by calcitriol and astemizole results in enhanced antineoplastic effects in breast tumors.

BACKGROUND: The oncogenic ether-à-go-go-1 potassium channel (EAG1) activity and expression are necessary for cell cycle progression and tumorigenesis. The active vitamin D metabolite, calcitriol, and astemizole, a promising antineoplastic drug, target EAG1 by inhibiting its expression and blocking ion currents, respectively. We have previously shown a synergistic antiproliferative effect of calcitriol and astemizole in breast cancer cells in vitro, but the effect of this dual therapy in vivo has not been studied. METHODS: In the present study, we explored the combined antineoplastic effect of both drugs in vivo using mice xenografted with the human breast cancer cell line T-47D and a primary breast cancer-derived cell culture (MBCDF). Tumor-bearing athymic female mice were treated with oral astemizole (50 mg/kg/day) and/or intraperitoneal injections of calcitriol (0.03 µg/g body weight twice a week) during 3 weeks. Tumor sizes were measured thrice weekly. For mechanistic insights, we studied EAG1 expression by qPCR and Western blot. The expression of Ki-67 and the relative tumor volume were used as indicators of therapeutic efficacy. RESULTS: Compared to untreated controls, astemizole and calcitriol significantly reduced, while the coadministration of both drugs further suppressed, tumor growth (P < 0.05). In addition, the combined therapy significantly downregulated tumoral EAG1 and Ki-67 expression. CONCLUSIONS: The concomitant administration of calcitriol and astemizole inhibited tumor growth more efficiently than each drug alone, which may be explained by the blocking of EAG1. These results provide the bases for further studies aimed at testing EAG1-dual targeting in breast cancer tumors expressing both EAG1 and the vitamin D receptor.

Hepatocellular carcinoma arising in a telangiectatic hepatocellular adenoma.

Telangiectatic hepatocellular adenoma is a rare, recently recognized subtype of benign liver tumor that may very rarely undergo transformation into hepatocellular carcinoma. We report an unusual case of a 75-year-old woman with no history of oral contraceptive use that underwent malignant transformation of a telangiectactic hepatocellular adenoma. No risk factors for adenoma development were identified in this otherwise healthy woman. Radiological characteristics, gross features and histopathology are herein described. In conclusion, telangiectatic hepatocellular adenoma can undergo malignant transformation. Further studies are needed to better clarify the factors associated with malignant progression.

[Phyllodes tumor of the breast: clinicopathologic analysis of 22 cases]. / Tumor filodes de la mama. Anláisis clínico e histopatológico de 22 casos.

INTRODUCTION: Phyllodes tumors of the breast are uncommon fibroepithelial neoplasms that have potential for recurrence. They are classified as benign, borderline, and malignant, based on a constellation of histologic characteristics that includes the degree of stromal hypercellularity, cytologic atypia and mitotic activity. OBJECTIVE: To analyze the clinical and pathological features of 22 women treated at a referral center in Mexico City. MATERIAL AND METHODS: We performed a retrospective analysis of women with phyllodes tumors of the breast treated at our institution between 1998 and 2011. Age, tumor size, surgical method, stromal cellular atypia, mitotic activity, stromal overgrowth, histological classification and surgical margin status were analyzed to determine their possible association with tumor recurrence. RESULTS: Mean patient age at presentation was 42 years. Ten of them (43.5%) had late menarche. Six patients (27.27%) used hormones. Twenty patients (91%) had tumor detected by self-examination. Mean size of the lesion was 7.4 cm. Most lesions were located in the upper outer quadrant (77.3%) and in the left breast (59.1%). Fourteen patients (63.6%) were treated with conservative surgery. Three patients (13.6%) presented local recurrence, two as benign tumors and one patient with two recurrences, first as benign tumor thereafter as malignant phyllodes tumor at 72 and 108 months respectively. CONCLUSIONS: . In our study, surgical positive margin status is the main prognostic factor for recurrence.

[National consensus of diagnosis and treatment of non-small cell lung cancer]. / Consenso nacional de diagnóstico y tratamiento del cáncer de pulmón de células no pequeñas.

Mexican specialists in oncology, oncologic surgery, thoracic surgery, pneumology, pathology, molecular biology, anesthesiology, algology, psychology, nutrition, and rehabilitation (all of them experts in lung cancer treatment) in order to develop the National Consensus on Lung Cancer. The consensus has been developed as an answer to the need of updated Mexican guidelines for the optimal treatment of the disease, as well as to the requirements that such guidelines be established by multidisciplinary panel, depicting the current attention given to cancer lung cases in Mexico. Thus, this paper analyses the epidemiological review, screening, diagnosis, staging, pathology, translational medicine, and the suitable therapies for early, locally advanced, and metastatic disease in the first, second, and third lines of management, as well as rehabilitation and palliative measures.

Agreement between incisional and excisional biopsies for hormone receptors and her2 in breast cancer.

INTRODUCTION: Breast cancer is the leading cause of cancer mortality in Mexican women. OBJECTIVE: The objective of the study was to identify concordances among core needle biopsy (CNB) and excisional biopsies (EB) regarding diagnosis, hormonal receptors (HR), and human epidermal growth factor receptor 2 (Her2). MATERIALS AND METHODS: Core number, demographic data, histological type, and treatment were documented for each sample. Reported HR and Her2 score from both samples were compiled. RESULTS: 70 women with both CNB/EB were included. Median age was 58 (36-87) years; initial diagnosis in CNB were invasive ductal 56 (80%), lobular 10 (14%), and mixed 4 (6%) carcinomas. Diagnostic agreement among CNB and EB was of 97%, k = 0.65. A concordance of 92% (k = 0.75), 75% (k = 0.26), and 67% (k = 0.46) was observed for estrogen receptors, progesterone receptors, and Her2 determinations, and positive predictive values in CNB were 0.96, 0.89, and 0.44, respectively. CONCLUSION: HR and Her2 concordances using manual-immunohistochemistry (IHC) were found within the range of values obtained using automatized-IHC. When compared to tumor heterogeneity, technical/reading errors contribute more to discordances.

INTRODUCTION: El cáncer de mama es la principal causa de mortalidad por cáncer en mujeres mexicanas. OBJETIVO: Identificar la concordancia entre la biopsia con aguja de corte (BAC) y la biopsia escisional (BE) con respecto al diagnóstico, receptores hormonales (RH) y Her2. MATERIAL Y MÉTODOS: Se registró el número de fragmentos cilíndricos, datos demográficos, tipo histológico y tratamiento. Se recopilaron resultados de RH y Her2. RESULTADOS: Se incluyeron 70 mujeres con mediana de edad de 58 años. El diagnóstico inicial en BAC fue carcinoma ductal invasivo 56 (80%), lobular 10 (14%) y mixtos 4 (6%). El acuerdo de diagnóstico entre BAC y BE fue del 97%, k = 0.65. Se observó una concordancia de 92% (k = 0.75), 75% (k = 0.26) y 67% (k = 0.46) para las determinaciones de receptor de estrógenos (RE), receptor de progesterona (RP) y Her2, y los valores predictivos positivos en BAC fueron 0.96, 0.89 y 0.44, respectivamente. CONCLUSIÓN: Los RH y la concordancia de Her2 mediante inmunohistoquímica (IHC) manual se encuentran dentro del rango de valores obtenidos mediante el uso de IHC automatizada. Los errores técnicos/de lectura contribuyeron más a discordancia que la heterogeneidad tumoral.