External beam radiotherapy ± chemotherapy in the treatment of anal canal cancer: a single-institute long-term experience on 100 patients.

One-hundred patients treated with curative radiotherapy (RT) ± chemotherapy (CT) for an anal canal carcinoma (T1-4N0-3M0) were retrospectively analyzed. Five- and 10-year local control (LC) rates were 73% and 67%, respectively. Acute and late G3-G4 toxicity rates were 32% and 12%, respectively. Two patients underwent a colostomy for a G4 anal toxicity. This study confirms the outcomes of RT ± CT in the treatment of anal canal cancer. Concomitant CT and LC statistically influenced Overall Survival and Colostomy-Free Survival. CT also statistically reduced the risk of nodal relapse. High rates of acute skin toxicity impose tailored volumes and techniques of irradiation.

Helical tomotherapy in the treatment of anal canal cancer: 3-year clinical experience

Objective: To report a single-center experience treating patients with squamous- cell carcinoma of the anal canal using helical Tomotherapy (HT) and concurrent chemotherapy (CT).Materials/Methods: From October 2007 to February 2011, 55 patients were treated with HT and concurrent CT (5-fluorouracil/capecitabin and mitomycin) for anal squamous-cell carcinoma. All patients underwent computed- tomography-based treatment planning, with pelvic and inguinal nodes receiving 36 Gy in 1.8 Gy/fraction. Following a planned 1-week break, primary tumor site and involved nodes were boosted to a total dose 59.4 Gy in 1.8 Gy/fraction. Dose-volume histograms of several organs at risk (OAR; bladder, small intestine, rectum, femoral heads, penile bulb, external genitalia) were assessed in terms of conformal avoidance. All toxicity was scored according to the CTCAE, v.3.0. HT plans and treatment were implemented using the Tomotherapy, Inc. software and hardware. For dosimetric comparisons, 3D RT and/or IMRT plans were also computed for some of the patients using the CMS planning system, for treatment with 6-18 MV photons and/or electrons with suitable energies from a Siemens Primus linear accelerator equipped with a multileaf collimator.Locoregional control and survival curves were compared with the log-rank test, and multivariate analysis by the Cox model.Results: With 360-degree-of-freedom beam projection, HT has an advantage over other RT techniques (3D or 5-field step-and-shot IMRT). There is significant improvement over 3D or 5-field IMRT plans in terms of dose conformity around the PTV, and dose gradients are steeper outside the target volume, resulting in reduced doses to OARs. Using HT, acute toxicity was acceptable, and seemed to be better than historical standards.Conclusions: Our results suggest that HT combined with concurrent CT for anal cancer is effective and tolerable. Compared to 3D RT or 5-field step-andshot IMRT, there is better conformity around the PTV, and better OAR sparing.

Could concomitant radio-chemotherapy improve the outcomes of early-stage node negative anal canal cancer patients? A retrospective analysis of 122 patients.

One hundred twenty-two early-stage anal canal cancer patients (median age: 69 years) were treated with curative radiotherapy with (70 patients) or without (52 patients) concomitant chemotherapy. Median follow-up was 65 months (range: 4-238). At multivariate analysis, concomitant chemotherapy significantly improved local control (p = .007). Local control significantly influenced all considered endpoints, except the metastases free survival. The global rates of G3-G4 acute and late toxicity were 13.1% and 8.2%, respectively, and they were not increased by concomitant chemotherapy. Finally, concomitant chemotherapy is efficacious and safe in the treatment of T1-2N0 anal canal cancer patients and should be prospectively studied.

Helical tomotherapy for the treatment of anal canal cancer: a dosimetric comparison with 3D conformal radiotherapy.

AIMS AND BACKGROUND: The standard treatment of anal canal cancer (ACC) is combined chemotherapy and radiation therapy (RT), which is complex because of the shape of the target volumes and the need to minimize the irradiation of normal pelvic structures. In this study we compared the dosimetric results of helical tomotherapy (HT) plans with traditional 3D conformal RT (3DRT) plans for the treatment of ACC. METHODS AND STUDY DESIGN: Twelve patients (median age 57 years, range 38-83; F/M 8/4) treated with HT and concurrent chemotherapy for locally advanced ACC were selected. All had histologically confirmed squamous-cell carcinoma. A clinical target volume including the tumor and pelvic and inguinal lymph nodes was treated with HT to a total dose of 36 Gy in 1.8-Gy daily fractions. Then a sequential boost of 23.4 Gy in 1.8-Gy daily fractions (total dose 59.4 Gy) was delivered to the tumor and involved nodes. For all 12 patients, 3DRT plans were generated for comparison. Treatment plans were evaluated by means of standard dose-volume histograms. Dose coverage of the planning target volumes (PTVs), homogeneity index (HI), and mean doses to organs at risk (OARs) were compared. RESULTS: The coverage of PTV was comparable between the two treatment plans. HI was better in the HT vs. 3DRT plans (1.25 and 3.57, respectively; p<0.0001). HT plans resulted in better sparing of OARs (p<0.0001). CONCLUSIONS: HT showed superior target dose conformality and significant sparing of pelvic structures compared with 3DRT. Further investigation should determine if these dosimetric improvements will improve clinical outcomes regarding locoregional control, survival, and treatment-related acute and late morbidity.

Role of brachytherapy in the treatment of cancers of the anal canal. Long-term follow-up and multivariate analysis of a large monocentric retrospective series.

BACKGROUND AND PURPOSE: There are few data on long-term clinical results and tolerance of brachytherapy in anal canal cancer. We present one of the largest retrospective analyses of anal canal cancers treated with external beam radiotherapy with/without (±) chemotherapy followed by a brachytherapy boost. MATERIALS AND METHODS: We performed a retrospective analysis of clinical results in terms of efficacy and toxicity. The impact of different clinical and therapeutic variables on these outcomes was studied. RESULTS: From May 1992 to December 2009, 209 patients received brachytherapy after external beam radiotherapy ± chemotherapy. Of these patients, 163 were stage II or stage IIIA (UICC 2002) and 58 were N1-3. According to age, ECOG performance status (PS), and comorbidities, patients received either radiotherapy alone (58/209) or radiochemotherapy (151/209). The median follow-up was 72.8 months. The 5- and 10-year local control rates were 78.6 and 73.9 %, respectively. Globally, severe acute and late G3-4 reactions (NCI-CTC scale v. 4.0) occurred in 11.2 and 6.3 % of patients, respectively. Univariate analysis showed the statistical impact of the pelvic treatment volume (p = 0.046) and of the total dose (p = 0.02) on the risk of severe acute and late toxicities, respectively. Only six patients required permanent colostomy because of severe late anorectal toxicities. CONCLUSION: After a long follow-up time, brachytherapy showed an acceptable toxicity profile and high local control rates in patients with anal canal cancer.

Risk factors and inflammatory markers in pouchitis

Individuals who do not respond to medical therapy for ulcerative colitis (UC) often undergo proctocolectomy followed by ileal-pouch anal anastomosis (IPAA) in hopes of resolving symptoms associated with UC. Inflammation of the ileal pouch, better known as pouchitis, is the most common complication of the IPAA procedure. The causes and development of pouchitis is not well understood. To better understand pathogenesis of pouchitis, pouch aspirates of patients having undergone IPAA were quantitatively analyzed for fecal IL-8, IL-17, and IL-23 levels. According to published literature IL-8 has been linked to pouchitis whereas IL-17 and IL-23 are associated with intestinal inflammation. The study had 80 participants, 33 patients diagnosed with Crohn's Disease (CD) of the pouch, 19 patients diagnosed with pouchitis, and 28 diagnosed with having normal pouches. Patient characteristics and histopathological findings for all patients were noted and statistically compared in addition to fecal cytokine levels. This study supported previous literature that IL-8 production was associated with pouch inflammation. However, IL-17 and IL-23 levels in both CD of the pouch and pouchitis were not significantly different to the levels noted in normal pouch.^

Endoluminal calprotectin measurement in assessment of pouchitis and a new index of disease activity: a pilot study

Pouchitis is the most common complication following proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis (UC). To provide a standardized definition of pouchitis clinical, endoscopic and histological markers were grouped and weighted in the pouch disease activity index (PDAI). However, the delay in the assessment of the final score due to the time requested for histological analysis remains the main obstacle to the index implementation in clinical practice so that the use of modified-PDAI (mPDAI) with exclusion of histologic subscore has been proposed. We tested the ability of calprotectin measurement in the pouch endoluminal content to mimic the histologic score as defined in the PDAI, the index that we adopted as gold standard for pouchitis diagnosis. Calprotectin was measured by ELISA in the pouch endoluminal content collected during endoscopy in 40 consecutive patients with J-pouch. In each patient PDAI and mPDAI were calculated and 15% of patients were erroneously classified by mPDAI. ROC analysis of calprotectin values vs. acute histological subscore ≥ 3 identified different calprotectin cut-off values with corresponding sensitivity and specificity allowing the definition and scoring of different range of calprotectin subscores. We incorporated the calprotectin score in the mPDAI obtaining a new score that shows the same specificity as PDAI for diagnosis of pouchitis and higher sensitivity when compared with mPDAI. The use of the proposed new score, once validated in a larger series of patients, might be useful in the early management of patients with symptoms of pouchitis.

Nuove strategie endoscopiche e mininvasive nel trattamento delle fistole anastomotiche pouch-anali e colorettali : endoluminal vacuum-assisted therapy (Endosponge®) first stage vs second stage treatment

La fistola anastomotica è una delle complicanze più temute nella chirurgia colo-rettale. Le anastomosi colo-rettali basse , le colo-anali e le pouch anali hanno un rischio più elevato di sviluppare una fistola anastomotica . La terapia endoluminale a pressione negativa (Endosponge®) è stata proposta come strategia di trattamento, tuttavia, la tempistica migliore in cui attuare la procedura rimane ancora poco definita. Lo scopo dello studio è confrontare i risultati ottenuti con l'Endosponge® come trattamento di prima linea rispetto a quelli in cui è stato applicato a seguito del fallimento di ulteriori trattamenti. Lo studio retrospettivo monocentrico ha incluso pazienti con fistola anastomotica trattati con Endosponge® in un periodo di tempo compreso tra novembre 2019 e novembre 2022. L'Endosponge® è stato applicato come prima linea o come salvataggio. Il dispositivo è stato applicato nella sede della deiscenza e periodicamente sostituito fino alla guarigione. La risoluzione del leak anastomotico è stata confermata con esame endoscopico. Dei 25 pazienti inclusi, 9 sono stati sottoposti a Endosponge® come trattamento di prima linea, mentre 16 sono stati sottoposti a Endosponge® di salvataggio. La deiscenza anastomotica è stata diagnosticata dopo un intervallo di tempo mediano di 14 giorni (range 10-413) nel primo gruppo e di 38 giorni (range 11-362) nel secondo (p=0,82). L'Endosponge® è stato applicato dopo 7 giorni (range 1-60) dalla diagnosi di fistola anastomotica nel primo gruppo e dopo 76 giorni (range 6-780) nel secondo gruppo (p=0,058). La risoluzione della fistola anastomotica è stata ottenuta in una percentuale di casi maggiore nel primo gruppo rispetto al secondo 88,9% vs 37,6% (p =0,033). Lo studio conferma l'efficacia dell'Endosponge® nel trattamento delle fistole anastomotiche colorettali basse quando utilizzato precocemente e come trattamento di prima linea.

Histopathological evaluation and risk factors related to the development of pouchitis in patients with ileal pouches for ulcerative colitis

OBJECTIVE: Many changes in mucosal morphology are observed following ileal pouch construction, including colonic metaplasia and dysplasia. Additionally, one rare but potential complication is the development of adenocarcinoma of the reservoir. The aim of this study was to evaluate the most frequently observed histopathological changes in ileal pouches and to correlate these changes with potential risk factors for complications. METHODS: A total of 41 patients were enrolled in the study and divided into the following three groups: a non-pouchitis group (group 1) (n = 20; 8 males; mean age: 47.5 years) demonstrating optimal outcome; a pouchitis without antibiotics group (group 2) (n = 14; 4 males; mean age: 47 years), containing individuals with pouchitis who did not receive treatment with antibiotics; and a pouchitis plus antibiotics group (group 3) (n = 7; 3 males; mean age: 41 years), containing those patients with pouchitis who were administered antibiotics. Ileal pouch endoscopy was performed, and tissue biopsy samples were collected for histopathological analysis. RESULTS: Colonic metaplasia was found in 15 (36.6%) of the 41 patients evaluated; of these, five (25%) were from group 1, eight (57.1%) were from group 2, and two (28.6%) were from group 3. However, no correlation was established between the presence of metaplasia and pouchitis (p = 0.17). and no differences in mucosal atrophy or the degree of chronic or acute inflammation were observed between groups 1, 2, and 3 (p > 0.45). Moreover, no dysplasia or neoplastic changes were detected. However, the degree of mucosal atrophy correlated well with the time of postoperative follow-up (p = 0.05). CONCLUSIONS: The degree of mucosal atrophy, the presence of colonic metaplasia, and the degree of acute or chronic inflammation do not appear to constitute risk factors for the development of pouchitis. Moreover, we observed that longer postoperative follow-up times were associated with greater degrees of mucosal atrophy.

Quantificação da função esfincteriana pela medida da capacidade de sustentação da pressão de contração voluntária do canal anal

RACIONAL: Tem sido demonstrado que a pressão máxima de contração voluntária e a pressão média de repouso não refletem a real situação clínica do paciente portador de incontinência fecal, não traduzem a realidade funcional do canal anal, além de poder estar comprometendo a conduta a ser tomada devido ao não-encaminhamento à terapêutica específica. OBJETIVO: Com a hipótese de que contrair e manter a contração é mais importante que simplesmente contrair, mesmo com pico momentaneamente elevado de pressão, analisou-se a capacidade de sustentação da pressão de contração voluntária do canal anal com o intuito de quantificar a função esfincteriana relativa à continência fecal. MATERIAL E MÉTODOS: Submeteram-se a exame manométrico anorretal 72 pacientes (56 mulheres) portadores de incontinência fecal de vários graus e 15 (9 mulheres) indivíduos continentes (normais), avaliando-se a pressão média de repouso, a pressão máxima de contração voluntária e a capacidade de sustentação da pressão de contração voluntária. RESULTADOS: Os indivíduos continentes apresentaram valores normais de pressão média de repouso e de pressão máxima de contração voluntária, além de adequada capacidade de sustentação da pressão de contração voluntária. Os pacientes incontinentes apresentaram pressão média de repouso e pressão máxima de contração voluntária com valores pressóricos normais ou abaixo do normal e perfil semelhante de capacidade de sustentação da pressão de contração voluntária, ou seja, moderada na fase inicial e ruim nas fases intermediária e final, com queda da mesma superior a 35% em 78% dos pacientes. A pressão máxima de contração voluntária apresenta excelente especificidade (100%) porém, sensibilidade baixa (46%) para incontinência fecal. Comparativamente, a capacidade de sustentação da pressão de contração voluntária apresenta elevadas especificidade (93%) e sensibilidade (78%) para incontinência fecal. Embora a pressão máxima de contração voluntária não indique falso-positivos, apresenta 72% de falso-negativos. A probabilidade deste fato acontecer com a medida de capacidade de sustentação da pressão de contração voluntária é, praticamente, 20% menor, valor estatisticamente significativo. CONCLUSÃO: O indicativo de função esfincteriana é melhor analisado pela capacidade de sustentação. A capacidade de sustentação traduz com mais exatidão, a capacidade funcional do canal anal em relação à continência voluntária, sendo isoladamente, melhor que a pressão máxima de contração voluntária.

Prevenção e diagnóstico de lesões HPV induzidas e carcinoma anal em mulheres atendidas na rede básica de saúde da cidade de Botucatu pelo método escovado do canal anal

Pós-graduação em Bases Gerais da Cirurgia - FMB

Evolução dos doentes com citologia oncótica alterada e colposcopia anal normal

A citologia anal vem sendo usada para rastreamento do carcinoma anal e suas lesões precursoras nas populações de risco. Quando o raspado do canal anal mostra alterações citológicas está indicada o exame com colposcópio e ácido acético para identificar e realizar biópsia para confirmar o achado. Poucos estudos mostram o seguimento dos doentes tratados de condilomas acuminados perianais. Temos usado os métodos em associação e encontrado lesões subclínicas em metade dos doentes, cujo exame proctológico não revelava doença HPV induzida. Essas lesões são tratadas com tópicos. Entretanto, algumas citologias estavam alteradas e a colposcopia anal não revelou doença HPV induzida. O objetivo deste estudo foi observar o comportamento dessas lesões no seguimento semestral, durante 12 meses, e avaliar se a periodicidade da reavaliação foi suficiente para evitar o aparecimento das lesões de alto grau ou superior. Encontramos 58 (21%) entre 273 doentes nessas condições. As reavaliações de 22 deles após um ano mostraram que as colposcopias permaneceram normais em 17 (74%), sendo que em cinco (22%) a citologia voltou aos padrões normais e 12 (52%) persistiram com alterações. Os outros seis (26%) desenvolveram lesões clínicas ou subclínicas provocadas pelo HPV. As contagens de linfócitos T CD4 dos doentes HIV-positivos foram inferiores nos doentes cujas lesões progrediram. Os resultados permitiram concluir que as alterações podem progredir ou regredir neste grupo distinto de doentes, sendo relacionada à imunidade, e que o intervalo de seis meses é suficiente para cada reavaliação.

Avaliação manométrica anal de crianças com encoprese

INTRODUÇÃO: A constipação crônica é doença comum na infância, ocorrendo em 5 a 10% dos pacientes pediátricos, considerada a segunda maior causa de procura nos consultórios de pediatria, sendo a encoprese decorrente de constipação grave associada à impactação fecal no reto. Dentre os exames diagnósticos, a manometria anal é utilizada para a avaliação de pacientes com distúrbios funcionais, como a constipação intestinal e a incontinência fecal, em alguns serviços para a avaliação de pacientes com encoprese, pois pode trazer informações sobre o mecanismo evacuatório e possíveis lesões esfincterianas anais. OBJETIVO: Verificar alterações manométricas em pacientes com encoprese. MÉTODOS: Foi realizado estudo de 40 manometrias anais de crianças constipadas com encoprese (G1) e 12 crianças constipados sem encoprese (G2). Foram obtidos os seguintes dados: pressões de repouso, contração e evacuação do canal anal e ampola retal, ponto de maior pressão, reflexo inibitório anal e sensibilidade retal. As manometrias foram realizadas com o aparelho Alacer de perfusão com 8 canais. RESULTADOS: Não foram encontradas diferenças nas pressões de repouso, contração e evacuação do canal anal entre os grupos. Chamou-nos a atenção a ausência de necessidade de maior volume retal para desencadear o reflexo inibitório anal. Não houve diferença da incidência de anismus entre os dois grupos, demonstrando que não se trata de fator importante na manutenção da encoprese, mas sim da constipação. CONCLUSÃO: Não houve necessidade de maior volume para desencadear o reflexo inibitório anal. O anismus não foi diferente entre os dois grupos, não sendo importante na manutenção da encoprese.

A NOTES Modification of the Transanal Pull-Through

Transanal endorectal pull-through (TAEPT) surgery is primarily performed for rectosigmoid aganglionosis, generally with excellent results. There is evidence that overstretching the anus and tension traction in the sigmoid during the procedure could impair the final continence of the patient. Many researchers suggest the use of small umbilical or laparoscopic access to aid in colon mobilization, thus preventing excessive handling within the anal canal. We assumed that transabdominal mobilization of the sigmoid could be prevented by utilizing the NOTES (natural orifices transluminal endoscopic surgery) technique. We performed a TAEPT with NOTES access of the sigmoid vascular pedicle, keeping the surgery exclusively transanal, which prevented scars in the abdomen and minimized the stretching of perineal structures.

Colorectal cancer in familial adenomatous polyposis: Are there clinical predictive factors?

Background: Familial Adenomatous Polyposis (FAP) is a hereditary disorder with multiple colorectal polyps that exhibit an almost inevitable risk of colorectal cancer (CRC) in untreated patients. Goals: To evaluate clinical features related to CRC risk at diagnosis. Material and methods: Charts from 88 patients were reviewed to collect information regarding age, family history, symptoms, polyposis severity and association with CRC. Results: 41 men (46.6%) and 47 women (53.4%) were assisted. CRC was detected in 53 patients (60.2%), with a frequency of 9.1% under 20 years, 58% between 21-40 and 85% over 41 years of age. Average age of patients without CRC was lower at treatment (29.5 vs. 40.0 years; p=0.001). Family history was reported by 58 patients (65.9%), whose average age did not differ from those who didn`t report it (33.4 vs. 34.4; p=0.17). Asymptomatic patients comprised 10.2% of the total; in this group, CRC incidence was much lower when compared to those presenting symptoms (1.1% vs. 65.8%; p=0.001). Patients without CRC presented a shorter length of symptoms (15.2 vs. 26.4 months; p=0.03) and less frequent weight loss (11.4% vs. 33.9%; p=0.01). At colonoscopy, polyposis was classified as attenuated in 12 patients (14.3%), who presented greater average age (48.2 vs. 33.3 years; p=0.02) and equal CRC incidence (58.3% vs. 58.3%; p=0.6) when compared to those with classic polyposis. Conclusions: The risk of CRC in FAP patients 1) increases significantly after the second decade; 2) is associated with higher age, weight loss, presence and duration of simptomatology; 3) is similar in patients with attenuated or classic phenotype. (C) 2010 AEC. Published by Elsevier Espana, S.L. All rights reserved.