A REVIEW TO HONOR THE HISTORICAL CONTRIBUTIONS OF PAULINE GROSS, ALDRED WARTHIN, AND HENRY LYNCH IN THE DESCRIPTION AND RECOGNITION OF INHERITANCE IN COLORECTAL CANCER.

The present manuscript aimed to review the historical development and most important contributions regarding Lynch Syndrome since its first description, more than a century ago. In 1895, a reputed pathologist from Michigan University, Dr. Aldred Scott Warthin, got intrigued by the family history of a local seamstress called Pauline Gross. According to her prevision, she would present an early death due to cancer, which actually happened (from the uterus). Historically, her family was designated "Family G", comprising a group recognized as the longest and most detailed cancer genealogy that has ever been studied. Warthin concluded that its members had genetic susceptibility for cancer, and they are, nowadays, considered the first reported Lynch Syndrome family. At that time, however, the medical cancer community was far less receptive to the association between heredity and cancer, despite the description of other families with similar heredograms. Unfortunately, this historical fact remained somewhat dormant until another investigator inaugurated a new era in the understanding of family cancer clusters. After reports and studies from this family and many others, the condition initially called Cancer Family Syndrome was changed to the eponym Lynch Syndrome. This was a recognition of the extensive and dedicated work developed by Dr. Henry Lynch in describing various characteristics of the disease, and his efforts to establish the correct recommendations for its diagnosis and treatment. Although the future announces there is still far to go for a complete understanding of Lynch Syndrome, the remarkable contributions of Pauline's intuition, Warthin's perseverance, and Lynch's work consistency must never be forgotten by those who already have or will still benefit from this knowledge.

Content and tissue expression of Collagen I, Collagen IV, and Laminin in the Extracellular Matrix in Prostate Adenocarcinoma.

Prostate cancer is one of the most common neoplasm in the male population. It is not known why some tumors become more aggressive than others. Although most studies show changes in the expression of cell adhesion molecules and the extracellular matrix correlated with the Gleason score, no study has objectively measured the tissue content of these molecules. This study aims to measure the content and tissue expression of collagen type I and IV and laminin in the extracellular matrix of patients with prostate adenocarcinoma and correlate these findings with the Gleason score and clinical characteristics. Forty-one patients who underwent radical prostate surgery at the Urology Department of a reference Hospital in Brazil between January 2015 and December 2020 were studied. The tissue protein content was estimated under light microscopy at a final magnification of 200 × . The mean collagen I score in prostate adenocarcinoma tissue samples was 7.16 ± 1.03 pixels/field. The mean type IV collagen score was 3.44 ± 0.61 pixels/field. The mean laminin score was 5.19 ± 0.79 pixels/field. The total Gleason score was correlated with both collagen and laminin. All the correlations were negative, which shows that the higher the collagen/laminin expression was, the lower the total Gleason score (p-value < 0,05). According to the Pearson correlation analysis, age has no statistical relationship with collagen and laminin content. PSA, in turn, showed a correlation only with laminin, but r = -0.378 (p = 0.015). Among the associated diseases and lifestyle habits, there is only statistical significance in the comparison of alcoholism for collagen I. For collagen IV and laminin, no statistical significance was obtained with the clinical variables analyzed.

London Protocol under water-perfused HRM in a healthy population, towards novel 3D manometric parameters in an evaluation of anorectal functional disorders.

BACKGROUND/AIM: London Protocol (LP) and Classification allied to high-resolution manometry (HRM) technological evolution has updated and enhanced the diagnostic armamentarium in anorectal disorders. This study aims to evaluate LP reproducibility under water-perfused HRM, provide normal data and new parameters based on 3D and healthy comparison studies under perfusional HRM. METHODS: Fifty healthy (25 F) underwent water-perfused 36 channel HRM based on LP at resting, squeeze, cough, push, and rectal sensory. Additional 3D manometric parameters were: pressure-volume (PV) 104mmHg2.cm (resting, short and long squeeze, cough); highest and lowest pressure asymmetry (resting, short squeeze, and cough). Complementary parameters (CP) were: resting (mean pressure, functional anal canal length); short squeeze (mean and maximum absolute squeeze pressure), endurance (fatigue rate, fatigue rate index, capacity to sustain); cough (anorectal gradient pressure); push (rectum-anal gradient pressure, anal canal relaxation percent); recto-anal inhibitory reflex (anal canal relaxation percent). RESULTS: No difference to genders: resting (LP, CP, and 3D); short squeeze (highest pressure asymmetry); endurance (CP); cough (CP, highest and lowest pressure asymmetry); push (gradient pressure); rectal sensory. Higher pressure in men: short squeeze (maximum incremental, absolute, and mean pressure, PV, lowest pressure asymmetry); long squeeze (PV); cough (anal canal and rectum maximum pressure, anal canal PV); push (anal canal and rectum maximum pressure). Anal canal relaxation was higher in women (push). CONCLUSIONS: LP reproducibility is feasible under water-perfused HRM, and comparative studies could bring similarity to dataset expansion. Novel 3D parameters need further studies with healthy and larger data to be validated and for disease comparisons. KEY POINTS: • London Protocol and Classification allied with the technological evolution of HRM (software and probes) has refined the diagnostic armamentarium in anorectal disorders. • Novel 3D and deepening the analysis of manometric parameters before the London Classification as a contributory diagnostic tool. • Comparison of healthy volunteers according to the London Protocol under a perfusional high-resolution system could establish equivalence points.

INFLUENCE OF NEOADJUVANT THERAPY ON THE RATIO OF LYMPH NODES.

BACKGROUND: To evaluate the relationship between the ratio of affected lymph nodes (LNR) and clinical and anatomopathological variables in patients with rectal adenocarcinoma submitted or not to neoadjuvant chemoradiotherapy. METHODS: The LNR was determined by dividing the number of compromised LNR by the total number of LNR dissected in the surgical specimen. Patients were divided into two groups: with QRT and without QRT. In each group, the relationship between LNR and the following variables was evaluated: degree of cell differentiation, depth of invasion in the rectal wall, angiolymphatic /perineural invasion, degree of tumor regression and occurrence of metastases. The LNR was evaluated in patients with more than 1, LNR (LNR >12) or less (LNR<12) in the surgical specimen with overall survival (OS) and disease-free survival (DFS). The results were expressed as the mean with the respective standard deviation. Qualitative variables were analyzed using Fisher's exact test, while quantitative variables were analyzed using the Kruskal -Wallis and Mann-Whitney tests. The significance level was 5%. RESULTS: We evaluated 282 patients with QRT and 114 without QRT, between 1995-2011. In the QRT Group, LNR showed a significant association with mucinous tumors (P=0.007) and degree of tumor regression (P=0.003). In both groups, LNR was associated with poorly differentiated tumors (P=0.001, P=0.02), presence of angiolymphatic invasion (P<0.0001 and P=0.01), perineural (P=0.0007, P=0.02), degree of rectal wall invasion (T3>T2; P<0.0001, P=0.02); Compromised LNR (P<0.0001, P<0.01), metastases (P<0.0001, P<0.01). In patients with QRT, LNR<12 was associated with DFS (5.889; 95%CI1.935-19.687; P=0.018) and LNR>12 with DFS and OS (17.984; 95%CI5.931-54.351; P<0.001 and 10.286; 95%CI 2.654-39.854; P=0.007, respectively). CONCLUSION: LNR was associated with histological aspects of poor prognosis, regardless of the use of QRT. In the occurrence of less than 12 evaluated LNR, the LNR was associated only with the DFS. BACKGROUND: • Assessment of the lymph nodes during pathological analysis of the surgical specimen is crucial to determine treatment and prognosis. BACKGROUND: • Neoadjuvance therapy reduces the number of lymph nodes, being lower than recommended, therefore the lymph node ratio can be an alternative analysis for a better prognosis.

IMPACT OF THE COVID-19 PANDEMIC ON THE EMERGENCY SURGICAL TREATMENT OF COLORECTAL CANCER.

BACKGROUND: Colorectal cancer (CRC) is the most common malignancy of the gastrointestinal tract and the third most common type of cancer worldwide. The COVID-19 pandemic, during the years 2020 and 2022, increased the difficulties in offering adequate early diagnosis and treatment to CRC patients worldwide. During this period, it was only possible to treat patients who evolved with complications, mainly intestinal obstruction and perforation. AIMS: To assess the impact of the COVID-19 pandemic on the treatment of patients with CRC. METHODS: A review of data from a total of 112 patients undergoing emergency surgical treatment due to complications of CRC was carried out. Of these, 78 patients underwent emergency surgery during the COVID-19 pandemic (2020/2021), and 34 were treated before the pandemic (2018/2019). Ethnic aspects, clinical symptoms, laboratory tests, histopathological variables, intra and postoperative complications, and 90-day postoperative follow-up were compared between the two groups. RESULTS: Between the years 2018 and 2019, 79.4% (27/34) of patients had intestinal obstruction, while 20.6% (7/34) had intestinal perforation. During the period of the COVID-19 pandemic (2020/2021), 1.3% (1/78) of patients underwent surgery due to gastrointestinal bleeding, 6.4% (5/78) due to intestinal perforation, and 92.3% (72/78) due to intestinal obstruction. No statistically significant differences were recorded between the two groups in ethnic aspects, laboratory tests, type of complications, number of lymph nodes resected, compromised lymph nodes, TNM staging, pre or intraoperative complications, length of stay, readmission, or mortality rate. When considering postoperative tumor staging, among patients operated on in 2018/2019, 44.1% were classified as stage III and 38.2% as stage IV, while during the pandemic period, 28.2% presented stage III and 51.3% stage IV, also without a statistically significant difference between the two periods. Patients operated on during the pandemic had higher rates of vascular, lymphatic and perineural invasion. CONCLUSIONS: The COVID-19 pandemic increased the rate of complications related to CRC when comparing patients treated before and during the pandemic. Furthermore, it had a negative impact on histopathological variables, causing worse oncological prognoses in patients undergoing emergency surgery.

Influência da terapia neoadjuvante na razão de linfonodos / Influence of neoadjuvant therapy on the ratio of lymph nodes

ABSTRACT Background: To evaluate the relationship between the ratio of affected lymph nodes (LNR) and clinical and anatomopathological variables in patients with rectal adenocarcinoma submitted or not to neoadjuvant chemoradiotherapy. Methods: The LNR was determined by dividing the number of compromised LNR by the total number of LNR dissected in the surgical specimen. Patients were divided into two groups: with QRT and without QRT. In each group, the relationship between LNR and the following variables was evaluated: degree of cell differentiation, depth of invasion in the rectal wall, angiolymphatic /perineural invasion, degree of tumor regression and occurrence of metastases. The LNR was evaluated in patients with more than 1, LNR (LNR >12) or less (LNR<12) in the surgical specimen with overall survival (OS) and disease-free survival (DFS). The results were expressed as the mean with the respective standard deviation. Qualitative variables were analyzed using Fisher's exact test, while quantitative variables were analyzed using the Kruskal -Wallis and Mann-Whitney tests. The significance level was 5%. Results: We evaluated 282 patients with QRT and 114 without QRT, between 1995-2011. In the QRT Group, LNR showed a significant association with mucinous tumors (P=0.007) and degree of tumor regression (P=0.003). In both groups, LNR was associated with poorly differentiated tumors (P=0.001, P=0.02), presence of angiolymphatic invasion (P<0.0001 and P=0.01), perineural (P=0.0007, P=0.02), degree of rectal wall invasion (T3>T2; P<0.0001, P=0.02); Compromised LNR (P<0.0001, P<0.01), metastases (P<0.0001, P<0.01). In patients with QRT, LNR<12 was associated with DFS (5.889; 95%CI1.935-19.687; P=0.018) and LNR>12 with DFS and OS (17.984; 95%CI5.931-54.351; P<0.001 and 10.286; 95%CI 2.654-39.854; P=0.007, respectively). Conclusion: LNR was associated with histological aspects of poor prognosis, regardless of the use of QRT. In the occurrence of less than 12 evaluated LNR, the LNR was associated only with the DFS.

RESUMO Contexto: Avaliar a relação entre a razão de linfonodos (RLA) acometidos e variáveis clínicas e anatomopatológicas em portadores de adenocarcinoma de reto submetidos ou não à quimiorradioterapia neoadjuvante. Métodos: A RLA foi determinada dividindo-se o número total de linfonodos (LFNs) dissecados no espécime cirúrgico pelo número de comprometidos. Os doentes foram divididos em dois grupos: com QRT e sem QRT. Em cada grupo foi avaliada a relação entre a RLA e as seguintes variáveis: grau de diferenciação celular, profundidade de invasão na parede retal, invasão angiolinfática/perineural, grau de regressão tumoral e ocorrência de metástases. Avaliou-se a RLA em pacientes com mais do que 12 LFNs (RLA>12) ou menos (RLA<12) na peça cirúrgica com a sobrevida global (SG) e sobrevida livre de doença (SLD). Os resultados foram expressos pela média com o respectivo desvio padrão. As variáveis qualitativas foram analisadas utilizando-se o teste exato de Fisher, enquanto as quantitativas pelos testes de Kruskal-Wallis e Mann-Whitney. O nível de significância foi de 5%. Resultados: Foram avaliados 282 pacientes com QRT e 114 sem QRT, entre 1995-2011. No Grupo QRT, RLA mostrou associação significativa com os tumores mucinosos (P=0,007) e grau de regressão tumoral (P=0,003). Nos dois grupos, a RLA associou-se com tumores pouco diferenciados (P=0,001 e P=0,02), presença de invasão angiolinfática (P<0,0001 e P=0,01), perineural (P=0,0007 e P=0,02), grau de invasão da parede retal (T3>T2; P<0,0001 e P=0,02); LFNs comprometidos (P<0,0001 e P<0,01), metástases (P<0,0001 e P<0,01). Nos pacientes com QRT, a RLA <12 associou-se com a SLD (5,889; IC95%1,935-19,687; P=0,018) e a RLA >12 com SLD e SG (17,984; IC95%5,931-54,351; P<0,001 e 10,286; IC95%2,654-39,854; P=0,007, respectivamente). Conclusão: A RLA associou-se a aspectos histológicos de mau prognóstico, independentemente do emprego de QRT. Na ocorrência de menos de 12 LFNs avaliados, a RLA associou-se apenas com a SLD.

Mucin levels in glands of the colonic mucosa of rats with diversion colitis subjected to enemas containing sucralfate and n-acetylcysteine alone or in combination.

PURPOSE: To evaluate the tissue content of neutral and acidic mucins, sulfomucins and sialomucins in colonic glands devoid of intestinal transit after enemas containing sucralfate and n-acetylcysteine alone or in combination. METHODS: Sixty-four rats underwent intestinal transit bypass. A colonic segment was collected to compose the white group (without intervention). After derivation, the animals were divided into two groups according to whether enemas were performed daily for two or four weeks. Each group was subdivided into four subgroups according to the substance used: control group: saline 0.9%; sucralfate group (SCF): SCF 2 g/kg/day; n-acetylcysteine group (NAC): NAC 100 mg/kg/day; and SCF+NAC group: SCF 2 g/kg/day + NAC 100 mg/kg/day.Neutral and acidic mucins were stained by periodic acid-Schiff and alcian-blue techniques, respectively. The distinction between sulfomucins and sialomucin was made by the high alcian-blue iron diamine technique. The content of mucins in the colonic glands was measured by computerized morphometry. The inflammatory score was assessed using a validated scale. The results between the groups were compared by the Mann-Whitney's test, while the variation according to time by the Kruskal-Wallis' test (Dunn's post-test). A significance level of 5% was adopted. RESULTS: There was reduction in the inflammatory score regardless of the application of isolated or associated substances. Intervention with SCF+NAC increased the content of all mucin subtypes regardless of intervention time. CONCLUSIONS: The application of SCF+NAC reduced the inflammatory process of the colonic mucosa and increased the content of different types of mucins in the colonic glands of segments excluded from fecal transit.

Rectal Cancer Tissue Lipidome Differs According to Response to Neoadjuvant Therapy.

Rectal cancer (RC) is a gastrointestinal cancer with a poor prognosis. While some studies have shown metabolic reprogramming to be linked to RC development, it is difficult to define biomolecules, like lipids, that help to understand cancer progression and response to therapy. The present study investigated the relative lipid abundance in tumoral tissue associated with neoadjuvant therapy response using untargeted liquid chromatography-mass spectrometry lipidomics. Locally advanced rectal cancer (LARC) patients (n = 13), clinically staged as T3-4 were biopsied before neoadjuvant chemoradiotherapy (nCRT). Tissue samples collected before nCRT (staging) and afterwards (restaging) were analyzed to discover lipidomic differences in RC cancerous tissue from Responders (n = 7) and Non-responders (n = 6) to nCRT. The limma method was used to test differences between groups and to select relevant feature lipids from tissue samples. Simple glycosphingolipids and differences in some residues of glycerophospholipids were more abundant in the Non-responder group before and after nCRT. Oxidized glycerophospholipids were more abundant in samples of Non-responders, especially those collected after nCRT. This work identified potential lipids in tissue samples that take part in, or may explain, nCRT failure. These results could potentially provide a lipid-based explanation for nCRT response and also help in understanding the molecular basis of RC and nCRT effects on the tissue matrix.

Dipotassium Glycyrrhizininate Improves Skin Wound Healing by Modulating Inflammatory Process.

Wound healing is characterized by a systemic and complex process of cellular and molecular activities. Dipotassium Glycyrrhizinate (DPG), a side product derived from glycyrrhizic acid, has several biological effects, such as being antiallergic, antioxidant, antibacterial, antiviral, gastroprotective, antitumoral, and anti-inflammatory. This study aimed to evaluate the anti-inflammatory effect of topical DPG on the healing of cutaneous wounds by secondary intention in an in vivo experimental model. Twenty-four male Wistar rats were used in the experiment, and were randomly divided into six groups of four. Circular excisions were performed and topically treated for 14 days after wound induction. Macroscopic and histopathological analyses were performed. Gene expression was evaluated by real-time qPCR. Our results showed that treatment with DPG caused a decrease in the inflammatory exudate as well as an absence of active hyperemia. Increases in granulation tissue, tissue reepithelization, and total collagen were also observed. Furthermore, DPG treatment reduced the expression of pro-inflammatory cytokines (Tnf-α, Cox-2, Il-8, Irak-2, Nf-kB, and Il-1) while increasing the expression of Il-10, demonstrating anti-inflammatory effects across all three treatment periods. Based on our results, we conclude that DPG attenuates the inflammatory process by promoting skin wound healing through the modulation of distinct mechanisms and signaling pathways, including anti-inflammatory ones. This involves modulation of the expression of pro- and anti-inflammatory cytokine expression; promotion of new granulation tissue; angiogenesis; and tissue re-epithelialization, all of which contribute to tissue remodeling.

Intra-abdominal desmoid tumors in familial adenomatous polyposis: How much do clinical and surgical variables interfere with their development?

OBJECTIVE: Familial Adenomatous Polyposis is a complex hereditary disease that exposes the carrier to a great risk of Colorectal Cancer (CRC). After prophylactic surgery, intra-abdominal desmoid tumors are known to be one the most important cause of death. Therefore, recognition of increased-risk patients and modification of operative strategy may be crucial. AIM: The objective of this study was to estimate the desmoid tumor risk in relation to various surgical and clinical variables. METHODS: Patients who had undergone polyposis since 1958 were included in the study. After exclusion criteria were met, those who had developed desmoid tumors were selected to undergo further evaluation. RESULTS: The study revealed that the risk of developing desmoid tumors was associated with various factors such as sex ratio, colectomy, and reoperations. On the other hand, the type of surgery, family history, and surgical approach did not affect the risk of developing desmoid tumors. The data collected from 146 polyposis patients revealed that 16% had desmoid polyps. The sex ratio was 7:1, and the median age at colectomy was 28.6 years. Family history, multiple abdominal operations, and reoperations were some of the characteristics that were common in desmoid patients. CONCLUSION: Recognition of clinical (female sex) and surgical (timing of surgery and previous reoperations) data as unfavorable variables associated with greater risk may be useful during the decision-making process.

Mucin levels in glands of the colonic mucosa of rats with diversion colitis subjected to enemas containing sucralfate and n-acetylcysteine alone or in combination

ABSTRACT Purpose: To evaluate the tissue content of neutral and acidic mucins, sulfomucins and sialomucins in colonic glands devoid of intestinal transit after enemas containing sucralfate and n-acetylcysteine alone or in combination. Methods: Sixty-four rats underwent intestinal transit bypass. A colonic segment was collected to compose the white group (without intervention). After derivation, the animals were divided into two groups according to whether enemas were performed daily for two or four weeks. Each group was subdivided into four subgroups according to the substance used: control group: saline 0.9%; sucralfate group (SCF): SCF 2 g/kg/day; n-acetylcysteine group (NAC): NAC 100 mg/kg/day; and SCF+NAC group: SCF 2 g/kg/day + NAC 100 mg/kg/day.Neutral and acidic mucins were stained by periodic acid-Schiff and alcian-blue techniques, respectively. The distinction between sulfomucins and sialomucin was made by the high alcian-blue iron diamine technique. The content of mucins in the colonic glands was measured by computerized morphometry. The inflammatory score was assessed using a validated scale. The results between the groups were compared by the Mann-Whitney's test, while the variation according to time by the Kruskal-Wallis' test (Dunn's post-test). A significance level of 5% was adopted. Results: There was reduction in the inflammatory score regardless of the application of isolated or associated substances. Intervention with SCF+NAC increased the content of all mucin subtypes regardless of intervention time. Conclusions: The application of SCF+NAC reduced the inflammatory process of the colonic mucosa and increased the content of different types of mucins in the colonic glands of segments excluded from fecal transit.

Impact of the covid-19 pandemic on the emergency surgical treatment of colorectal cancer / Impacto da pandemia da covid-19 no tratamento cirúrgico emergencial do câncer colorretal

ABSTRACT BACKGROUND: Colorectal cancer (CRC) is the most common malignancy of the gastrointestinal tract and the third most common type of cancer worldwide. The COVID-19 pandemic, during the years 2020 and 2022, increased the difficulties in offering adequate early diagnosis and treatment to CRC patients worldwide. During this period, it was only possible to treat patients who evolved with complications, mainly intestinal obstruction and perforation. AIMS: To assess the impact of the COVID-19 pandemic on the treatment of patients with CRC. METHODS: A review of data from a total of 112 patients undergoing emergency surgical treatment due to complications of CRC was carried out. Of these, 78 patients underwent emergency surgery during the COVID-19 pandemic (2020/2021), and 34 were treated before the pandemic (2018/2019). Ethnic aspects, clinical symptoms, laboratory tests, histopathological variables, intra and postoperative complications, and 90-day postoperative follow-up were compared between the two groups. RESULTS: Between the years 2018 and 2019, 79.4% (27/34) of patients had intestinal obstruction, while 20.6% (7/34) had intestinal perforation. During the period of the COVID-19 pandemic (2020/2021), 1.3% (1/78) of patients underwent surgery due to gastrointestinal bleeding, 6.4% (5/78) due to intestinal perforation, and 92.3% (72/78) due to intestinal obstruction. No statistically significant differences were recorded between the two groups in ethnic aspects, laboratory tests, type of complications, number of lymph nodes resected, compromised lymph nodes, TNM staging, pre or intraoperative complications, length of stay, readmission, or mortality rate. When considering postoperative tumor staging, among patients operated on in 2018/2019, 44.1% were classified as stage III and 38.2% as stage IV, while during the pandemic period, 28.2% presented stage III and 51.3% stage IV, also without a statistically significant difference between the two periods. Patients operated on during the pandemic had higher rates of vascular, lymphatic and perineural invasion. CONCLUSIONS: The COVID-19 pandemic increased the rate of complications related to CRC when comparing patients treated before and during the pandemic. Furthermore, it had a negative impact on histopathological variables, causing worse oncological prognoses in patients undergoing emergency surgery.

RESUMO RACIONAL: O câncer colorretal (CCR) é a doença maligna mais comum do trato gastrointestinal sendo o terceiro tipo de câncer mais comum em todo o mundo. A pandemia de COVID-19 durante os anos de 2020 e 2022 aumentou as dificuldades em se oferecer diagnóstico e tratamento precoce adequado aos pacientes com CCR em todo o mundo. Nesse período, só foi possível tratar os pacientes que evoluíram com complicações representadas, principalmente, pela obstrução e perfuração intestinal. OBJETIVOS: Avaliar o impacto da pandemia de COVID-19 no tratamento de pacientes com CCR. MÉTODOS: Foi realizada uma revisão dos dados de um total de 112 pacientes submetidos ao tratamento cirúrgico de urgência devido complicações do CCR. Destes, 78 pacientes foram submetidos a cirurgia de emergência durante o período da pandemia de COVID-19 (2020/2021), e 34 pacientes foram operados no período anterior à pandemia (2018/2019). Aspectos étnicos, sintomas clínicos, exames laboratoriais, variáveis histopatológicas, complicações intra e pós-operatórias e acompanhamento pós-operatório de 90 dias foram analisados comparando os dois grupos. RESULTADOS: Entre os anos 2018 e 2019, 79,4% (27/34) dos pacientes apresentaram obstrução intestinal enquanto 20,6% (7/34) perfuração intestinal. Durante o período da pandemia de COVID-19 (2020/2021) 1,3% (1/78) dos pacientes foram operados por hemorragia digestiva baixa, 6,4% (5/78) por perfuração intestinal e 92,3% (72/78) por obstrução intestinal. Não foram registradas diferenças estatisticamente significativas entre os dois grupos nos aspectos étnicos, exames laboratoriais, tipo de complicações, número de linfonodos ressecados, linfonodos comprometidos, estadiamento TNM, complicações pré ou intraoperatórias, tempo de internação, readmissão e taxa de mortalidade. Ao considerar o estadiamento tumoral pós-operatório, entre os pacientes operados em 2018/19, 44,1% foram classificados como estágio III e 38,2% como estágio IV, enquanto no período pandêmico, 28,2% apresentaram estágio III e 51,3% estágio IV, também sem diferença estatisticamente significativa entre os dois períodos. Doentes operados durante a pandemia apresentaram maiores índices de invasão vascular, linfática e perineural. CONCLUSÕES: A pandemia de COVID-19 aumentou as taxas de complicações relacionadas ao CCR, comparando pacientes tratados antes e durante a pandemia. Além disso, teve impacto negativo nas variáveis histopatológicas, causando piores prognósticos oncológicos em pacientes submetidos a cirurgias de emergência.

Intra-abdominal desmoid tumors in familial adenomatous polyposis: How much do clinical and surgical variables interfere with their development?

Abstract Objective: Familial Adenomatous Polyposis is a complex hereditary disease that exposes the carrier to a great risk of Colorectal Cancer (CRC). After prophylactic surgery, intra-abdominal desmoid tumors are known to be one the most important cause of death. Therefore, recognition of increased-risk patients and modification of operative strategy may be crucial. Aim: The objective of this study was to estimate the desmoid tumor risk in relation to various surgical and clinical variables. Methods: Patients who had undergone polyposis since 1958 were included in the study. After exclusion criteria were met, those who had developed desmoid tumors were selected to undergo further evaluation. Results: The study revealed that the risk of developing desmoid tumors was associated with various factors such as sex ratio, colectomy, and reoperations. On the other hand, the type of surgery, family history, and surgical approach did not affect the risk of developing desmoid tumors. The data collected from 146 polyposis patients revealed that 16% had desmoid polyps. The sex ratio was 7:1, and the median age at colectomy was 28.6 years. Family history, multiple abdominal operations, and reoperations were some of the characteristics that were common in desmoid patients. Conclusion: Recognition of clinical (female sex) and surgical (timing of surgery and previous reoperations) data as unfavorable variables associated with greater risk may be useful during the decision-making process.

A fusion protein comprising pneumococcal surface protein A and a pneumolysin derivate confers protection in a murine model of pneumococcal pneumonia.

PspA and pneumolysin are two important vaccine candidates, able to elicit protection in different models of pneumococcal infection. The high immunogenic potential of PspA, combined with a possible adjuvant effect of pneumolysin derivatives (due to their ability to interact with TLR-4) could greatly improve the immunogenicity and coverage of a protein-based pneumococcal vaccine. A chimeric protein including the N-terminal region of PspA in fusion with the pneumolysin derivative, PlD1, has been shown to induce high antibody levels against each protein, and protect mice against invasive challenge. The aim of the present study was to investigate the cellular response induced by such vaccine, and to evaluate protection in a murine model of lobar pneumococcal pneumonia. Pneumococcal pneumonia was induced in BALB/c mice by nasal instillation of a high dose of a serotype 14 strain with low virulence. Airway inflammation was confirmed by total and differential cell counts in BAL and by histological analysis of the lungs, and bacterial loads were measured 7 days after challenge. Cytokine levels were determined in the bronchoalveolar fluid (BALF) of mice immunized with rPspA-PlD1 fusion after challenge, by flow cytometry and ELISA. After challenge, the mice developed lung inflammation with no invasion of other sites, as demonstrated by histological analysis. We detected significant production of TNF-α and IL-6 in the BALF, which correlated with protection against pneumonia in the group immunized with rPspA-PlD1. In conclusion, we found that the rPspA-PlD1fusion is protective against pneumococcal pneumonia in mice, and protection is correlated with an early and controlled local inflammatory response. These results are in agreement with previous data demonstrating the efficacy of the fusion protein against pneumococcal sepsis and reinforce the potential of the rPspA-PlD1 protein chimera as a promising vaccine strategy to prevent pneumococcal disease.

IS IT POSSIBLE TO OPTIMIZE STAPLED HEMORRHOIDOPEXY OUTCOMES BY ENLARGING OPERATIVE CRITERIA INDICATIONS? RESULTS OF A TAILORED PROCEDURE WITH ASSOCIATED RESECTION IN A COMPARATIVE PERSONAL SERIES.

BACKGROUND: Since its introduction, stapled hemorrhoidopexy has been increasingly indicated in the management of hemorrhoidal disease. AIM: Our primary end point was to evaluate the incidence of recurrent disease requiring another surgical intervention. On a secondary analysis, we also compared pain, complications, and patient's satisfaction after a tailored surgery. METHODS: We retrospectively reviewed 196 patients (103 males and 93 females) with a median age of 47.9 years (range, 17-78) who were undergoing stapled hemorrhoidopexy alone (STG; n=65) or combined surgery (CSG; n=131, stapled hemorrhoidopexy associated with resection). RESULTS: Complications were detected in 11 (5.6%) patients (4.6% for STG vs. 6.1% for CSG; p=0.95). At the same time, symptoms recurrence (13.8% vs. 8.4%; p=034), reoperation rate for complications (3.1% vs. 3.0%; p=1.0), and reoperation rate for recurrence (6.1% vs. 4.6%; p=1.0) were not different among groups. Grade IV patients were more commonly managed with simultaneous stapling and resection (63% vs. 49.5%), but none of them presented symptoms recurrence nor need reoperation due to recurrence. Median pain score during the first week was higher in CSG patients (0.8 vs. 1.7). After a follow-up of 24.9 months, satisfaction scores were similar (8.6; p=0.8). CONCLUSION: Recurrent symptoms were observed in 10% of patients, requiring surgery in approximately half of them. Even though the association of techniques may raise pain scores, a tailored approach based on amplified indication criteria and combined techniques seems to be an effective and safe alternative, with decreased relapse rates in patients suffering from more advanced hemorrhoidal disease. Satisfaction scores after hemorrhoidopexy are high.

STUDY OF ANORECTAL PHYSIOLOGY PRE AND POS NEOADJUVANT THERAPY FOR RECTAL CANCER BY ANORECTAL MANOMETRY AND JORGE-WEXNER SCORE.

BACKGROUND: The treatment of distal rectal cancer may be accompanied by evacuation disorders of multifactorial etiology. Neoadjuvant chemoradiotherapy (NCRT) is part of the standard treatment for patients with locally advanced extraperitoneal rectal cancer. The assessment of anorectal function after long-term NCRT in patients with cancer of the extraperitoneal rectum has been poorly evaluated. OBJECTIVE: The aim of the present study was to evaluate the effects of NCRT on anorectal function and continence in patients with extraperitoneal rectal cancer. METHODS: Rectal adenocarcinoma patients undergoing neoadjuvant therapy were submitted to functional evaluation by anorectal manometry and the degree of fecal incontinence using the Jorge-Wexner score, before and eight weeks after NCRT. The manometric parameters evaluated were mean resting anal pressure (ARp), maximum voluntary contraction anal pressure (MaxSp) and average voluntary contraction anal pressure (ASp). All patients underwent the same NCRT protocol based on the application of fluoropyrimidine (5-FU) at a dosage of 350 mg/m2 associated with folic acid at a dosage of 20 mg/m2, intravenously, in the first and last week of treatment, concomitantly with conformational radiotherapy with a total dose of 50.4Gy, divided into 28 daily fractions of 1.8Gy. For statistical analysis of the quantitative variables with normal distribution, the mean, standard deviation, median and interquartile range were calculated. For comparison of two related samples (before and eight weeks after NCRT), Wilcoxon's non-parametric test was used. RESULTS: Forty-eight patients with rectal cancer were included in the study, with a mean age of 62.8 (39-81) years, 36 (75%) of whom were male. The use of NCRT was associated with a decrease in the values of ARp (55.0 mmHg vs 39.1 mmHg, P<0.05) and ASp (161.9 mmHg vs 141.9 mmHg, P<0.05) without changing MaxSp values (185,5 mmHg vs 173 mmHg, P=0.05). There was no worsening of the incontinence score eight weeks after the use of NCRT (3.0 vs 3.3; P>0.05). CONCLUSION: NCRT was associated with a reduction in the values of ARp and the ASp. There was no change in MaxSp, as well as in the degree of fecal continence by the Jorge-Wexner score.

Estudo da fisiologia anorretal pré e pós terapia neoadjuvante para câncer de reto por manometria anorretal e escore de Jorge-Wexner / Study of anorectal physiology pre and pos neoadjuvant therapy for rectal cancer by anorectal manometry and jorge-wexner score

ABSTRACT Background: The treatment of distal rectal cancer may be accompanied by evacuation disorders of multifactorial etiology. Neoadjuvant chemoradiotherapy (NCRT) is part of the standard treatment for patients with locally advanced extraperitoneal rectal cancer. The assessment of anorectal function after long-term NCRT in patients with cancer of the extraperitoneal rectum has been poorly evaluated. Objective: The aim of the present study was to evaluate the effects of NCRT on anorectal function and continence in patients with extraperitoneal rectal cancer. Methods: Rectal adenocarcinoma patients undergoing neoadjuvant therapy were submitted to functional evaluation by anorectal manometry and the degree of fecal incontinence using the Jorge-Wexner score, before and eight weeks after NCRT. The manometric parameters evaluated were mean resting anal pressure (ARp), maximum voluntary contraction anal pressure (MaxSp) and average voluntary contraction anal pressure (ASp). All patients underwent the same NCRT protocol based on the application of fluoropyrimidine (5-FU) at a dosage of 350 mg/m2 associated with folic acid at a dosage of 20 mg/m2, intravenously, in the first and last week of treatment, concomitantly with conformational radiotherapy with a total dose of 50.4Gy, divided into 28 daily fractions of 1.8Gy. For statistical analysis of the quantitative variables with normal distribution, the mean, standard deviation, median and interquartile range were calculated. For comparison of two related samples (before and eight weeks after NCRT), Wilcoxon's non-parametric test was used. Results: Forty-eight patients with rectal cancer were included in the study, with a mean age of 62.8 (39-81) years, 36 (75%) of whom were male. The use of NCRT was associated with a decrease in the values of ARp (55.0 mmHg vs 39.1 mmHg, P<0.05) and ASp (161.9 mmHg vs 141.9 mmHg, P<0.05) without changing MaxSp values (185,5 mmHg vs 173 mmHg, P=0.05). There was no worsening of the incontinence score eight weeks after the use of NCRT (3.0 vs 3.3; P>0.05). Conclusion: NCRT was associated with a reduction in the values of ARp and the ASp. There was no change in MaxSp, as well as in the degree of fecal continence by the Jorge-Wexner score.

RESUMO Contexto: O tratamento do câncer retal distal pode ser acompanhado por distúrbios evacuatórios de etiologia multifatorial. A quimiorradioterapia neoadjuvante faz parte do tratamento padrão para pacientes com câncer retal extraperitoneal localmente avançado. A avaliação da função anorretal após neoadjuvância de longa duração em pacientes com câncer de reto extraperitoneal tem sido pouco estudada. Objetivo: O objetivo do presente estudo foi avaliar os efeitos da neoadjuvância na função anorretal e na incontinência em pacientes com câncer retal extraperitoneal. Métodos: Pacientes com adenocarcinoma de reto candidatos à terapia neoadjuvante foram submetidos a avaliação funcional por manometria anorretal e avaliação do grau de incontinência fecal pelo escore de Jorge-Wexner, pré e oito semanas após a neoadjuvância. Os parâmetros manométricos avaliados foram pressão anal média de repouso, pressão anal de contração voluntária máxima e pressão anal média de contração voluntária. Todos os pacientes foram submetidos ao mesmo protocolo de neoadjuvância baseado na aplicação de fluoropirimidina (5-FU) na dosagem de 350 mg/m2 associada ao ácido fólico na dosagem de 20 mg/m2, por via intravenosa, na primeira e última semana de tratamento, concomitantemente à radioterapia conformacional com dose total de 50,4Gy, dividida em 28 frações diárias de 1,8Gy. Para análise estatística das variáveis quantitativas com distribuição normal, foram calculados a média, desvio padrão, mediana e intervalo interquartil. Para comparação de duas amostras relacionadas (antes e oito semanas após a neoadjuvância, foi utilizado o teste não paramétrico de Wilcoxon. Resultados: Quarenta e oito pacientes com câncer retal foram incluídos no estudo, com média de idade de 62,8 (39-81) anos, sendo 36 (75%) do sexo masculino. O uso de neoadjuvância foi associado à diminuição dos valores de média de pressão de repouso (55,0 mmHg vs 39,1 mmHg, P<0,05) e média de pressão de contração voluntária (161,9 mmHg vs 141,9 mmHg, P<0,05) sem alterar os valores de pressão de contração voluntária máxima ((185,5 mmHg vs 173 mmHg, P=0.05)). Não houve piora do escore de incontinência oito semanas após o uso da quimiorradioterapia neoadjuvante (3,0 vs 3,3; P>0,05). Conclusão: A neoadjuvância associou-se à redução dos valores de média de pressão de repouso e média dos valores contração voluntária. Não houve alteração nos valores de contração voluntária máxima, bem como no grau de continência fecal pelo escore de Jorge-Wexner.

Pouchitis: insight into the pathogenesis and clinical aspects.

Ulcerative colitis (UC) is a chronic intestinal inflammatory disease and familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease. Both diseases, despite being different, may require the same surgical procedure: proctocolectomy with ileal pouch-anal anastomosis (IPAA). The main complication after this procedure is pouch inflammation (pouchitis). This inflammatory complication can affect up to 60 percent of patients who receive IPAA for UC, and a very small percentage of the FAP patients. The purpose of this review was to determine the current molecular mechanisms in its pathogenesis and detail the risk factors involved in pouchitis, its diagnosis, and treatment.