Comparison between tofacitinib and ustekinumab as a third-line therapy in refractory ulcerative colitis: A multicenter international study.

BACKGROUND: Ustekinumab and tofacitinib have recently been approved for the management of moderate to severe ulcerative colitis (UC). However, there is no evidence on how they should be positioned in the therapeutic algorithm. The aim of this study was to compare tofacitinib and ustekinumab as third-line therapies in UC patients in whom anti-TNF and vedolizumab had failed. METHODS: This was a multicenter retrospective observational study. The primary outcome was disease progression, defined as the need for steroids, therapy escalation, UC-related hospitalization and/or surgery. Secondary outcomes were clinical remission, normalization of C-reactive protein, endoscopic remission, treatment withdrawal, and adverse events. RESULTS: One-hundred seventeen UC patients were included in the study and followed for a median time of 11.6 months (q1-q3, 5.5-18.7). Overall, 65% of patients were treated with tofacitinib and 35% with ustekinumab. In the entire study cohort, 63 patients (54%) had disease progression during the follow-up period. Treatment with ustekinumab predicted increased risk of disease progression compared to treatment with tofacitinib in Cox regression analysis (HR: 1.93 [95% CI: 1.06-3.50] p = 0.030). Twenty-eight (68%) patients in the ustekinumab group and 35 (46%) in the tofacitinib group had disease progression over the follow-up period (log-rank test, p < 0.054). No significant differences were observed for the secondary outcomes. Six and 22 adverse events occurred in the ustekinumab and tofacitinib groups, respectively (15% vs. 31%, p = 0.11). CONCLUSIONS: Tofacitinib was more efficacious in reducing disease progression than ustekinumab in this cohort of refractory UC patients. However, prospective head-to-head clinical trials are needed as to confirm these data.

Quality of death in patients in advanced chronic liver disease and cancer patients managed by gastroenterologists in Portugal: are we doing it right?

INTRODUCTION: The incidence of chronic progressive diseases is rising and investment on quality of death and dying is of utmost importance to minimize physical and emotional suffering. There is still a gap in palliative care (PC) between patients with cancer and those with advanced chronic liver disease (ACLD). Our objectives were to characterize clinical attitudes and therapeutic interventions and to evaluate the differences in end-of-life care between inpatients with cancer and ACLD under gastroenterology care. METHODS: Retrospective cohort study, including patients with cancer or ACLD who died in a Gastroenterology department between 2012 and 2021. Demographic characteristics, clinical and endoscopic procedures and symptom control were compared between the groups. RESULTS: From 150 patients, 118 (78.7%) died with cancer and 32 (21.3%) died from ACLD without concomitant hepatocellular carcinoma. ACLD patients were more frequently male ( P  = 0.001) and younger ( P  = 0.001) than patients with cancer. Median time of hospitalization in the last month of life was 16 days for both groups. Discussion of prognosis with the patient was more frequent for cancer patients (35.6% versus 3.2%, P  < 0.001). Referral to PC occurred in 18.8% and 61% of the patients with ACLD and cancer respectively ( P  < 0.001). Endoscopic procedures were performed in half of the patients and were more likely to be unsuccessful in those with cancer. CONCLUSION: Clinical decisions were different between groups in terms of PC access and discussion of prognostic with the patient. It is urgent to define and implement metrics of quality of death and dying to prevent potentially inappropriate treatment.

Narrow Band Imaging versus White Light for the Detection of Sessile Serrated Colorectal Lesions: A Randomized Clinical Trial.

Background: Colorectal cancer (CRC) is a leading cause of cancer. The detection of pre-malignant lesions by colonoscopy is associated with reduced CRC incidence and mortality. Narrow band imaging has shown promising but conflicting results for the detection of serrated lesions. Methods: We performed a randomized clinical trial to compare the mean detection of serrated lesions and hyperplastic polyps ≥10 mm with NBI or high-definition white light (HD-WL) withdrawal. We also compared all sessile serrated lesions (SSLs), adenoma, and polyp prevalence and rates. Results: Overall, 782 patients were randomized (WL group 392 patients; NBI group 390 patients). The average number of serrated lesions and hyperplastic polyps ≥10 mm detected per colonoscopy (primary endpoint) was similar between the HD-WL and NBI group (0.118 vs. 0.156, p = 0.44). Likewise, the adenoma detection rate (55.2% vs. 53.2%, p = 0.58) and SSL detection rate (6.8% vs. 7.5%, p = 0.502) were not different between the two study groups. Withdrawal time was higher in the NBI group (10.88 vs. 9.47 min, p = 0.004), with a statistically nonsignificant higher total procedure time (20.97 vs. 19.30 min, p = 0.052). Conclusions: The routine utilization of narrow band imaging does not improve the detection of serrated class lesions or any pre-malignant lesion and increases the withdrawal time.

Introdução: O cancro do cólon e reto é a neoplasia mais frequente considerando os dois géneros. . A deteção de lesões pré-malignas por colonoscopia está associada a uma redução da incidência e da mortalidade. Estudos sobre a utilização da luz de banda estreita (NBI) na deteção de lesões serreadas tiveram resultados promissores, mas heterogéneos. Métodos: Realizámos um ensaio clínico randomizado para comparar o número médio de lesões serreadas e lesões hiperplásicas ≥10 mm com NBI ou luz branca de alta-definição (HD-WL). Como resultados secundários comparámos a prevalência e as taxas de deteção de lesões serreadas sésseis, adenomas e todas as lesões. Resultados: Foram randomizados 782 doentes (392 no grupo HD-WL e 390 no grupo NBI). O número médio de lesões serreadas e hiperplásicas ≥10 mm não apresentou diferença estatisticamente significativa entre dois grupos (0.118 vs. 0.156, p = 0.44). A taxa de deteção de adenomas (55.2% vs. 53.2%, p = 0.58) e a taxa de deteção de lesões serreadas sésseis (6.8% vs. 7.5%, p = 0.502) também não foram diferentes. O tempo de retirada foi maior no grupo NBI (10.88 vs. 9.47 min, p = 0.004) e o tempo total de procedimento teve um ligeiro aumento não atingindo significância estatística (20.97 vs. 19.30 min, p = 0.052). Conclusão: A utilização da luz NBI por rotina não aumenta a deteção de lesões serreadas nem de qualquer lesão pré-maligna e aumenta o tempo de retirada na colonoscopia.

Jejunum cavernous haemangioma - A rare cause of gastrointestinal bleeding.

We report a case of a 69-year-old male patient with gastrointestinal bleeding manifesting with melaena. Upper and lower endoscopy were negative for the bleeding aetiology. On small bowel capsule endoscopy, several violaceous lesions in the proximal jejunum were identified. The patient was submitted to segmental intestinal resection being diagnosed with a cavernous jejunum haemangioma, a rare cause of acute intestinal bleeding.

Performance of Immunohistochemical and Molecular Methods in Detecting Microsatellite Instability in Gastric Cancer: A Multicenter Study.

INTRODUCTION: Microsatellite instability (MSI) is an important prognostic molecular biomarker for gastric cancer (GC). MSI status may be detected by immunohistochemistry (IHC) for mismatch repair (MMR) proteins and polymerase chain reaction (PCR). Idylla™ MSI assay has not been validated for GC but may prove to be a valid alternative. METHODS: In a series of 140 GC cases, MSI status was evaluated by IHC for MLH1, PMS2, MSH2, and MSH6; gold-standard pentaplex PCR panel (PPP) (BAT-25, BAT-26, NR-21, NR-24, and NR-27); and Idylla. Statistical analysis was performed using SPSS 27.0. RESULTS: PPP identified 102 microsatellite stable (MSS) cases and 38 MSI-high cases. Only 3 cases showed discordant results. Compared with PPP, the sensitivity was 100% for IHC and 94.7% for Idylla. Specificity was 99% for IHC and 100% for Idylla. MLH1 IHC alone showed sensitivity and specificity of 97.4% and 98.0%, respectively. IHC identified three indeterminate cases; all were MSS according to PPP and Idylla. CONCLUSION: IHC for MMR proteins represents an optimal screening tool for MSI status in GC. If resources are limited, isolated MLH1 evaluation may constitute a valuable option for preliminary screening. Idylla may help detect rare MSS cases with MMR-loss and define MSI status in indeterminate cases.

Role of Endoscopic Biopsies and Morphologic Features in Predicting Microsatellite Instability Status in Gastric Cancer: A Multicenter Comparative Study of Endoscopic Biopsies and Surgical Specimens.

Evaluation of mismatch repair (MMR) protein and microsatellite instability (MSI) status plays a pivotal role in the management of gastric cancer (GC) patients. In this study, we aimed to evaluate the accuracy of gastric endoscopic biopsies (EBs) in predicting MMR/MSI status and to uncover histopathologic features associated with MSI. A multicentric series of 140 GCs was collected retrospectively, in which EB and matched surgical specimens (SSs) were available. Laurén and WHO classifications were applied and detailed morphologic characterization was performed. EB/SS were analyzed by immunohistochemistry (IHC) for MMR status and by multiplex polymerase chain reaction (mPCR) for MSI status. IHC allowed accurate evaluation of MMR status in EB (sensitivity: 97.3%; specificity: 98.0%) and high concordance rates between EB and SS (Cohen κ=94.5%). By contrast, mPCR (Idylla MSI Test) showed lower sensitivity in evaluating MSI status (91.3% vs. 97.3%), while maintaining maximal specificity (100.0%). These results suggest a role of IHC as a screening method for MMR status in EB and the use of mPCR as a confirmatory test. Although Laurén/WHO classifications were not able to discriminate GC cases with MSI, we identified specific histopathologic features that are significantly associated with MMR/MSI status in GC, despite the morphologic heterogeneity of GC cases harboring this molecular phenotype. In SS, these features included the presence of mucinous and/or solid components ( P =0.034 and <0.001) and the presence of neutrophil-rich stroma, distant from tumor ulceration/perforation ( P <0.001). In EB, both solid areas and extracellular mucin lakes were also discriminating features for the identification of MSI-high cases ( P =0.002 and 0.045).

Early intervention with biologic therapy in Crohn´s disease: how early is early?

BACKGROUND: Early biologic therapy within the first 18-24 months after diagnosis is associated with improved clinical outcomes in Crohn's disease [CD]. However, the definition of the best time to initiate biologic therapy remains unclear. We aimed to assess if there is an optimal timing for early biologic therapy initiation. METHODS: This was a multicentre retrospective cohort study including newly diagnosed CD patients who started anti-tumour necrosis factor [TNF] therapy within 24 months from diagnosis. The timing of initiation of biologic therapy was categorised as ≤6, 7-12, 13-18, and 19-24 months. The primary outcome was CD-related complications defined as a composite of progression of Montreal disease behaviour, CD-related hospitalisations, or CD-related intestinal surgeries. Secondary outcomes included clinical, laboratory, endoscopic, and transmural remission. RESULTS: We included 141 patients where 54%, 26%, 11%, and 9% started biologic therapy at ≤6, 7-12, 13-18, and 19-24 months after diagnosis, respectively. A total of 34 patients [24%] reached the primary outcome: 8% had progression of disease behaviour, 15% were hospitalised, and 9% required surgery. There was no difference in the time to a CD-related complication according to the time of initiation of biologic therapy within the first 24 months. Clinical, endoscopic, and transmural remission was achieved in 85%, 50%, and 29%, respectively, but no differences were found according to the time of initiation of biologic therapy. CONCLUSION: Starting anti-TNF therapy within the first 24 months after diagnosis was associated with a low rate of CD-related complications and high rates of clinical and endoscopic remission, although we found no differences with earlier initiation within this window of opportunity.

TIM-3 Is a Potential Immune Checkpoint Target in Cats with Mammary Carcinoma.

Recent findings in human breast cancer (HBC) indicate that T-cell immunoglobulin and mucin-domain-containing molecule-3 (TIM-3)-targeted therapies may effectively activate anticancer immune responses. Although feline mammary carcinoma (FMC) is a valuable cancer model, no studies on TIM-3 have been developed in this species. Thus, we evaluated the expression of TIM-3 by immunohistochemistry in total (t), stromal (s), and intra-tumoral (i) tumor-infiltrating lymphocytes (TILs) and in cancer cells, of 48 cats with mammary carcinoma. In parallel, serum TIM-3 levels were quantified using ELISA and the presence of somatic mutations in the TIM-3 gene was evaluated in 19 tumor samples. sTILs-TIM3+ were more frequent than iTILs-TIM-3+, with the TIM-3 ex-pression in sTILs and cancer cells being associated with more aggressive clinicopathological features. In contrast, the TIM-3 expression in iTILs and tTILs was associated with a more benign clinical course. Moreover, the serum TIM-3 levels were lower in animals with FMC when compared to healthy animals (p < 0.001). Only one somatic mutation was found in the TIM-3 gene, at intron 2, in one tumor sample. Altogether, our results suggest that the expression of TIM-3 among TILs subpopulations and cancer cells may influence the clinical outcome of cats with FMC, in line with the previous reports in HBC.

Groove Pancreatitis: Clinical Cases and Review of the Literature.

Introduction: Groove pancreatitis (GP) is a type of chronic segmental pancreatitis that affects the pancreatoduodenal groove area, and it is often misdiagnosed. Outflow obstruction of the minor papilla associated with alcohol consumption seems to be the main pathophysiological mechanism, and it affects mainly middle-aged males. Symptoms include nausea and postprandial vomiting from gastric outlet obstruction, weight loss, and abdominal pain. Despite modern advances, such as radiological and endoscopic methods, distinction between GP and pancreatic cancer remains a challenge, and histological examination is sometimes necessary. When a diagnosis can be obtained without a surgical specimen, management can be conservative in the absence of acute or chronic complications. Case Presentation: The authors present 2 clinical cases which portray the diagnostic workup and management decisions of this entity. Discussion/Conclusion: GP is a clinical entity, offering diagnostic and therapeutic challenges. Imaging exams are crucial in the diagnosis and follow-up, but surgery may be necessary in a significant number of cases due to the incapacity to rule out malignancy.

Introdução: A pancreatite da goteira (PG) constitui uma forma de pancreatite crónica segmentar, que afeta a área da goteira pancreatoduodenal, sendo frequentemente subdiagnosticada. O mecanismo fisiopatológico principal parece ser a obstrução ao fluxo da papila minor relacionada com o consumo de álcool. Esta patologia ocorre mais frequentemente em homens entre a 4a e 5a décadas de vida. A maioria dos doentes apresenta sintomas como náuseas e vómitos pós-prandiais, perda ponderal e dor abdominal. Apesar do desenvolvimento atual dos métodos radiológicos e endoscópicos, a distinção entre PG e neoplasia pancreática constitui um desafio diagnóstico e a avaliação histológica pode ser necessária. Se for possível obter o diagnóstico sem intervenção cirúrgica, o tratamento pode ser conservador na ausência de complicações agudas e crónicas. Apresentação do caso: Apresentamos 2 casos clínicos que demonstram a abordagem diagnóstica e a gestão de decisões terapêuticas nesta entidade. Discussão/Conclusão: A PG é uma entidade clínica que oferece com diagnóstico e terapêutica desafiantes. Apesar da importância crucial dos exames imagiológicos no diagnóstico e seguimento, a incapacidade de excluir um processo maligno torna necessária a intervenção cirúrgica numa parte significativa dos casos.

The Landscape of Tumor-Infiltrating Immune Cells in Feline Mammary Carcinoma: Pathological and Clinical Implications.

Feline mammary carcinoma (FMC) shares key molecular and clinicopathological features with human breast cancer. We have herein studied the inflammatory infiltrate of FMC in order to uncover potential therapeutic targets and prognostic markers. To this end, the expression of different markers (CD3, CD4, CD8, CD20, CD56, FoxP3, CD68 and CD163) was analyzed in total, stromal (s) and intratumoral (i) tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs), in 73 feline mammary carcinomas. The results revealed that higher percentages of sCD8+ TILs were associated with longer disease-free survival (p = 0.05) and overall survival (p = 0.021). Additionally, higher percentages of iCD4+ TILs correlated with positive lymph node status (p = 0.003), whereas CD163+ TAMs were associated with undifferentiated tumors (p = 0.013). In addition, sCD3+ (p = 0.033), sCD8+ (p = 0.044) and sCD68+ (p = 0.023) immune cells were enriched in triple negative normal-like carcinomas compared to other subtypes. Altogether, our results suggest that specific subsets of immune cells may play a major role in clinical outcome of cats with mammary carcinoma, resembling what has been reported in human breast cancer. These data further support the relevance of the feline model in breast cancer studies.

Aggressive Colorectal Cancer in an Inflammatory Bowel Disease Patient following Treatment with Vedolizumab: A Case Report.

Introduction: The increased risk of bowel cancer in patients with inflammatory bowel disease can be related with the extent, duration and severity of inflammation or with the cancer immune surveillance interference of immunosuppressive drugs used in inflammatory bowel disease treatment. Therefore, the risk-benefit ratio associated with long-term therapeutic strategies should be based on the patient's age, sex, comorbidities and disease phenotype. Case Report: We present the case of a 76-year-old man with a history of melanoma stage Clark III and steroid-dependent left-sided colitis, refractory to mesalamine and thiopurines, with a diagnosis of a multifocal colorectal adenocarcinoma shortly after clinical and endoscopic remission 1 year after starting vedolizumab. Discussion: Vedolizumab is a gut-selective monoclonal anti-α4ß7-integrin antibody that inhibits lymphocyte migration into the gastrointestinal submucosa. Its effectiveness for induction and maintenance of remission and its favorable safety profile make it an alternative in patients with chronic refractory colitis and contraindications to anti-TNF-α. However, there is the hypothesis that, by reducing the migration of activated leukocytes to the gastrointestinal tract, it may also reduce immunosurveillance, increasing the colorectal malignancy risk in the long term. More studies are necessary to address this issue.

Introdução: O aumento do risco de neoplasias intestinais em doentes com doença inflamatória intestinal correlacionase com a extensão, duração e gravidade de inflamação assim como com o potencial efeito na vigilância imunitária associado aos fármacos imunossupressores utilizados no seu tratamento. Por isso, a avaliação do risco-benefício da utilização de estratégias terapêuticas a longo prazo deve basear-se no género, idade, comorbilidades e fenótipo da doença. Caso clínico: Os autores apresentam o caso de um homem de 76 anos com história pregressa de melanoma maligno estadio Clark III e colite ulcerosa esquerda cortico-dependente e refratária à terapêutica convencional, com o diagnóstico de um adenocarcinoma colo-rectal um ano após ter iniciado terapêutica com vedolizumab e ter atingido remissão clínica e endoscópica. Discussão: O vedolizumab é um anticorpo anti-integrina α4ß7 que inibe a migração dos linfócitos para a submucosa gastrointestinal. A sua eficácia na indução e manutenção da remissão e o seu perfil de segurança tornam-no uma boa alternativa em doentes com doença refratária e contraindicações para anti-TNF-α. Contudo, ao diminuir a migração dos leucócitos para o trato gastrointestinal, poderá reduzir a imunovigilância, aumentando o risco de neoplasia colo-rectal. No entanto, este é ainda um conceito teórico, sendo necessários mais estudos que o comprovem.

Secondary Sclerosing Cholangitis in a Critically Ill Patient with Severe SARS-CoV-2 Infection: A Possibly Emergent Entity during the Current Global Pandemic.

A 46-year-old woman without previous history of hepatobiliary disease was admitted to the intensive care unit due to SARS-CoV-2 infection. Admission blood tests revealed impending hyperinflammation in the context of systemic inflammatory response syndrome. She required 12 days of mechanical ventilation and vasopressor support. After admission, liver function tests became deranged in a cholestatic pattern and continued to worsen despite overall clinical improvement. Magnetic resonance cholangiopancreatography revealed liver abscesses, intrahepatic bile duct dilation with multiple strictures and some linear repletion defects at the bifurcation of the common hepatic duct. During endoscopic retrograde cholangiopancreatography, biliary casts were retrieved confirming the diagnosis of secondary sclerosing cholangitis in the critically ill patient triggered by a severe SARS-CoV-2 infection. Other causes of cholestasis and secondary sclerosing cholangitis were properly excluded. We present an illustrative case and discuss the current literature, focusing on SARS-CoV-2 infection contribution to the development of this potentially underdiagnosed and severe condition.

Uma mulher de 46 anos sem antecedentes de patologia hepatobiliar foi admitida na unidade de cuidados intensivos no contexto de infeção por SARS-CoV-2. Apresentava alterações analíticas interpretadas no contexto de síndrome de resposta inflamatória sistémica. Houve necessidade de suporte vasopressor e ventilação mecânica invasiva durante 12 dias. Após a admissão, verificou-se uma alteração das provas hepáticas com padrão colestático, com agravamento contínuo apesar da melhoria do quadro infecioso. A colangiografia por ressonância magnética revelou a presença de abcessos hepáticos, dilatação das vias biliares intrahepáticas com múltiplas estenoses e com alguns defeitos de repleção lineares na bifurcação do ducto hepático comum. Na colangiopancreatografia endoscópica retrógrada foram removidos cilindros bilares da via biliar, confirmando o diagnóstico de colangite esclerosante secundária associada aos cuidados intensivos, no contexto de uma infeção grave por SARS-CoV-2. Foram excluídas outras causas de colestase e colangite esclerosante secundária de forma exaustiva. Apresentamos um caso clínico ilustrativo com respetiva iconografia e revisão da literatura, com especial enfoque na contribuição da infeção por SARS-CoV-2 no desenvolvimento desta entidade clínica, potencialmente grave e subdiagnosticada.

Mental Health, Work Presenteeism, and Exercise in Inflammatory Bowel Disease.

BACKGROUND: Chronic diseases, such as IBD, can lead to anxiety and depression which can have a significant impact on productivity at work [presenteeism]. The aim of this study was to assess the prevalence of depression/anxiety, presenteeism and exercise levels among IBD patients. METHODS: This was a multicentre study whereby adult IBD patients, in clinical remission, were asked to answer a questionnaire anonymously. Hospital Anxiety and Depression Score [HADS], Stanford Presenteeism Scale [SPS-6] and Godin Exercise Score were also collected. RESULTS: A total of 585 patients were recruited. The majority had Crohn's disease [CD, 62.2%] and were male [53.0%], with a median age of 39 years [IQR 30-49]. A psychiatric diagnosis was present in 10.8% of patients prior to their IBD diagnosis. A further 14.2% of patients were psychiatrically diagnosed after IBD diagnosis, this being commoner in CD patients [41.6% of CD, p <0.01]. A raised HADS-Anxiety or a HADS-Depression score ≥8 was present in 46.1% of patients, with 27.4% having a score ≥11. Low presenteeism at work was present in 34.0%. Patients diagnosed with depression/anxiety had a more sedentary lifestyle [p <0.01], lower presenteeism at work [p <0.01] and a higher rate of unemployment [p <0.01]. CONCLUSIONS: A significant percentage of IBD patients in remission suffer from anxiety and/or depression. Risk factors for these are CD, female gender, use of biologic medications, long-standing and/or perianal disease. Depression/anxiety was associated with a sedentary lifestyle, lower presenteeism at work and unemployment. Validated screening tools and appropriate referrals to psychologists and/or psychiatrists should be employed within IBD clinics.

EBV and MSI Status in Gastric Cancer: Does It Matter?

We investigated the impactof microsatellite instability (MSI) and Epstein-Barr virus (EBV) status in gastric cancer (GC), regarding response to perioperative chemotherapy (POPChT), overall survival (OS), and progression-free survival (PFS). We included 137 cases of operated GC, 51 of which were submitted to POPChT. MSI status was determined by multiplex PCR and EBV status by EBV-encoded RNA in situ hybridization. Thirty-seven (27%) cases presented as MSI-high, and seven (5.1%) were EBV+. Concerning tumor regression after POPChT, no differences were observed between the molecular subtypes, but females were more likely to respond (p = 0.062). No significant differences were found in OS or PFS between different subtypes. In multivariate analysis, age (HR 1.02, IC 95% 1.002-1.056, p = 0.033) and positive lymph nodes (HR 1.82, IC 95% 1.034-3.211, p = 0.038) were the only prognostic factors for OS. However, females with MSI-high tumors treated with POPChT demonstrated a significantly increased OS compared to females with MSS tumors (p = 0.031). In conclusion, we found a high proportion of MSI-high cases. MSI and EBV status did not influence OS or PFS either in patients submitted to POPChT or surgery alone. However, superior survival of females with MSI-high tumors suggests that sex disparities and molecular classification may influence treatment options in GC.

Inflammatory Bowel Disease Patients' Perspectives during COVID-19 Pandemic: Results from a Portuguese Survey.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) do not seem to be at increased risk of infection by SARS-CoV-2, but there is a concern whether immunosuppressive therapy may be associated with more severe disease. Several clinical practice recommendations have been published to help guide IBD care during the COVID-19 pandemic. Nonetheless, few studies have addressed patients' perspectives and fears. We aimed to evaluate Portuguese IBD patients' perspectives on the clinical management of their disease during the SARS-CoV-2 pandemic as well as the impact on their professional life. METHODS: An anonymous electronic survey was created using REDCap and was distributed by the Portuguese Association of Inflammatory Bowel Disease (APDI) between May and August 2020. Patients' perspectives on immunosuppressive therapy, disease management, interaction with gastroenterology departments, and the impact of the pandemic in their professional life were assessed. Patients' proposals to improve medical care were also evaluated. Descriptive analysis and logistic regression were performed. RESULTS: A total of 137 participants answered the survey (79.6% females, mean age 41.7 ± 12.1 years). Although having IBD and receiving treatment with immunosuppressors (thiopurines, steroids, or biologics) were considered promotors of anxiety, most patients (85.4%) agreed that disease remission was a priority and only a minority of patients interrupted their treatment during the pandemic. In multivariate analysis, active disease, biologic treatment, and use of corticosteroids in the last 3 months were perceived by the patients as high-risk features for increased risk of SARS-Cov-2 infection and more severe disease. Fifty-nine patients (44%) believed that their follow-up was influenced by the pandemic and only 58.8% felt that they had the opportunity to discuss their therapeutic options with their doctor. Sixty-three patients (46.0%) were working from home during the pandemic, although this decision was related to IBD and immunosuppressive therapy in only 36.5 and 39.7% of the cases, respectively. Areas where care could have been improved during the pandemic were identified by patients, namely enhancement of the communication with IBD professionals, conciliation of telemedicine with face-to-face appointments, and facilitation of the interaction between patients and employers. CONCLUSION: Most patients agreed that maintaining IBD remission is crucial, and only a minority of the patients stopped their treatment as per their own initiative. IBD status only had a small influence on patients' professional activity during the COVID-19 outbreak, with most changes being related to the pandemic itself.

Prevalence of Barrett's esophagus in a Southern European country: a multicenter study.

BACKGROUND: Identification of Barrett's esophagus (BE) with the treatment of dysplasia is essential to prevent esophageal adenocarcinoma (EAC). Moreover, determination of BE prevalence is important to define subsequent management strategies. However, precise estimates on BE prevalence from several European countries are lacking. We aimed to determine BE prevalence in a Southern European country. METHODS: A cross-sectional, multicenter study from November 2019 to February 2020 was performed defining BE as a columnar extent in the distal esophagus greater than or equal to 1 cm with intestinal metaplasia. RESULTS: A total of 1550 individuals, 51% male with a mean age of 62 (SD = 15) years undergoing upper endoscopy were included. The overall BE prevalence was 1.29% (95% confidence interval: 0.73-1.85); significantly higher in men [2.05% (1.06-3.04)] vs. women [0.53% (0.01-1.04)]. Of the 20 BE patients, eight were newly diagnosed and 12 were under surveillance. The median extent was C3 (min 0; max 16) M4.5 (min 2; max 16). One patient each had EAC (0.06%) and high-grade dysplasia (0.06%) at the time of endoscopy. There was no difference in prevalence between geographical regions, centers, use of sedation or experience of endoscopists. Considering all reports, 93% used standardized terminology, 23% accurate photodocumentation and 69% photodocumented the esophagogastric junction (EGJ). Furthermore, 80% used Prague classification, 55% Seattle protocol, 60% distance to the squamocolumnar junction, 75% to the EGJ and 40% to the hiatal pinch. When considering only reports with EGJ photodocumentation or Prague classification, the prevalence was 1.78% (0.91-2.64) or 1.03% (0.53-1.53). CONCLUSION: We report for the first time BE prevalence in Southern Europe and report a low overall prevalence in an unselected population. Future studies need to determine progression rates and how to improve quality metrics.

VISTA Is a Diagnostic Biomarker and Immunotherapy Target of Aggressive Feline Mammary Carcinoma Subtypes.

Feline mammary carcinoma (FMC) is a common neoplasia, showing aggressive clinicopathological features, without viable therapeutic options. The study of tumor microenvironment has gained importance, due to the ability to control tumor progression by regulating the immune response. Considering the lack of knowledge, feline serum VISTA levels from cats with mammary carcinoma were compared with healthy controls, and with serum levels of PD-1/PD-L1, CTLA-4, LAG-3, IL-6, and TNF-α. In parallel, VISTA tumor expression was evaluated in FMC samples. The obtained data revealed that serum VISTA levels were significantly higher in cats presenting HER2-positive (p = 0.0025) or triple-negative subtypes (p = 0.0019), with higher serum levels in luminal A (p = 0.0025) correlated to the presence of metastasis (p = 0.0471). Furthermore, in HER2-positive or triple-negative tumors, correlations were obtained between serum VISTA levels and the serum levels of the above-mentioned molecules. In tumors, VISTA expression revealed a stronger intensity in cancer cells, when compared to TILs (p < 0.0001). Stratifying the samples by subtypes, a higher number of VISTA-positive TILs was observed in the HER2-positive subtype, compared with triple-negative tumors (p = 0.0138). In conclusion, results support the development of therapeutic strategies for HER2-positive and triple-negative FMC subtypes, reinforcing the use of cats as a human oncology model.

Tumor microenvironment of human breast cancer, and feline mammary carcinoma as a potential study model.

In recent years, the tumor microenvironment (TME) has been a research hotspot, as it is composed of distinct cellular and non-cellular elements that may influence the diagnosis, prognosis, and treatment of breast cancer patients. Cancer cells are able to escape immune control through an immunoediting process which depends on complex communication networks between immune and cancer cells. Thus, a better understanding of the immune cell infiltrate in the breast cancer microenvironment is crucial for the development of more effective therapeutic approaches. In this review article, we overview the different actors that orchestrate the complexity of the TME, including tumor infiltrating lymphocytes (TILs), natural killer cells, tumor infiltrating dendritic cells (TIDCs), tumor associated macrophages (TAMs), tumor associated neutrophils (TANs), cancer associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs), distinct pro-angiogenic factors and immune checkpoint biomarkers. Additionally, we summarize the recent advances in the TME of feline mammary carcinoma (FMC). FMC has been proposed as a reliable cancer model for the study of human breast cancer, as they share clinicopathological, histopathological and epidemiological features, as well as the pathways involved in cancer initiation and progression.

Anaplastic Mammary Carcinoma in Cat.

Clinical, pathological, and immunohistochemical findings related to a feline mammary tumor with similar features to canine anaplastic mammary carcinoma are herein described for the first time. A female cat was presented for clinical evaluation with gastrointestinal signs, oedema, erythema, and painful lesion in the right inguinal region. Three weeks later, the mass had doubled in size and radiographic revaluation of the thoracic cavity revealed a metastatic pattern. Due to the poor prognosis and decline of the clinical status the owners decided for euthanasia. Post-mortem examination exposed a mammary tumoral mass with subcutaneous oedema, an enlargement of the right inguinal lymph node, and nodules in several organs. Histological analysis confirmed the presence of large pleomorphic epithelial cells, often grouped in small clusters with bizarre nuclei. Immunohistochemical study of the different lesions was performed and both primary tumor and regional metastasis showed tumor cells to be negative estrogen receptor alpha, positive progesterone receptor, positive HER-2, and positive pan-cytokeratin. Given that the clinical history was compatible with an inflammatory mammary carcinoma, the cyclooxygenase-2 expression levels were evaluated and presented a weak immunoreactivity. Regarding the distant metastatic lesions, tumor cells were negative for ER-α and PR and, positive both for HER-2 and pan-cytokeratin.

Tyrosine Kinase Inhibitors Are Promising Therapeutic Tools for Cats with HER2-Positive Mammary Carcinoma.

Feline mammary carcinoma (FMC) is a common neoplasia in cat, being HER2-positive the most prevalent subtype. In woman's breast cancer, tyrosine kinase inhibitors (TKi) are used as a therapeutic option, by blocking the phosphorylation of the HER2 tyrosine kinase domain. Moreover, clinical trials demonstrated that TKi produce synergistic antiproliferative effects in combination with mTOR inhibitors, overcoming resistance to therapy. Thus, to uncover new chemotherapeutic strategies for cats, the antiproliferative effects of two TKi (lapatinib and neratinib), and their combination with a mTOR inhibitor (rapamycin), were evaluated in FMC cell lines (CAT-M, FMCp and FMCm) and compared with a human breast cancer cell line (SkBR-3). Results revealed that both TKi induced antiproliferative effects in all feline cell lines, by blocking the phosphorylation of EGFR members and its downstream effectors. Furthermore, combined treatments with rapamycin presented synergetic antiproliferative effects. Additionally, the DNA sequence of the her2 TK domain (exons 18 to 20) was determined in 40 FMC tissue samples, and despite several mutations were found none of them were described as inducing resistance to therapy. Altogether, our results demonstrated that TKi and combined protocols may be useful in the treatment of cats with mammary carcinomas, and that TKi-resistant FMC are rare.