Mucinous Degeneration on MRI After Neoadjuvant Therapy in Patients With Rectal Adenocarcinoma: Frequency and Association With Clinical Outcomes.

BACKGROUND. Patients with nonmucinous rectal adenocarcinoma may develop mucinous changes after neoadjuvant chemoradiotherapy, which are described as mucinous degeneration. The finding's significance in earlier studies has varied. OBJECTIVE. The purpose of this study was to assess the frequency of mucinous degeneration on MRI after neoadjuvant therapy for rectal adenocarcinoma and to compare outcomes among patients with nonmucinous tumor, mucinous tumor, and mucinous degeneration on MRI. METHODS. This retrospective study included 201 patients (83 women, 118 men; mean age, 61.8 ± 2.2 [SD] years) with rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy followed by total mesorectal excision from October 2011 to November 2015, underwent baseline and restaging rectal MRI examinations, and had at least 2 years of follow-up. Two radiologists independently evaluated MRI examinations for mucin content, which was defined as T2 hyperintensity in the tumor or tumor bed, and resolved differences by consensus. Patients were classified into three groups on the basis of mucin status: those with nonmucinous tumor (≤ 50% mucin content on baseline and restaging examinations), those with mucinous tumor (> 50% mucin content on baseline and restaging examinations), and those with mucinous degeneration (≤ 50% mucin content on baseline examination and > 50% content on restaging examination). The three groups were compared. RESULTS. Interreader agreement for mucin content, expressed as a kappa coefficient, was 0.893 on baseline MRI and 0.890 on restaging MRI. Of the 201 patients, 156 (77.6%) had nonmucinous tumor, 34 (16.9%) had mucinous tumor, and 11 (5.5%) had mucinous degeneration. Mucin status was not significantly associated with complete pathologic response (p = .41) or local or distant recurrence (both p > .05). The death rate during follow-up was not significantly different (p = .21) between patients with nonmucinous tumor (23.1%), those with mucinous tumor (29.4%), and those with mucinous degeneration (9.1%). In adjusted Cox regression analysis, with mucinous degeneration used as reference, the HR for the overall survival rate for the mucinous tumor group was 4.7 (95% CI, 0.6-38.3; p = .14), and that for the nonmucinous tumor group was 8.0 (95% CI, 0.9-59.9; p = .06). On histopathologic assessment, all 11 patients with mucinous degeneration showed acellular mucin, yet 10 of 11 patients showed viable tumor (i.e., in nonmucinous portions of the tumors). CONCLUSION. Mucinous degeneration on MRI is not significantly associated with pathologic complete response, recurrence, or survival. CLINICAL IMPACT. Mucinous degeneration on MRI is uncommon and should not be deemed an indicator of pathologic complete response.

Administration of an Anal Bulking Agent With Polyacrylate-Polyalcohol Copolymer Particles Versus Endoanal Electrical Stimulation With Biofeedback for the Management of Mild and Moderate Anal Incontinence: A Randomized Prospective Study.

BACKGROUND: There are few treatment options for mild-to-moderate anal incontinence with isolated internal anal sphincter defects or anal incontinence without muscle damage. Less-invasive techniques are generally favored. OBJECTIVE: To compare the results between the use of an anal bulking agent with polyacrylate-polyalcohol copolymer particles and endoanal electrical stimulation with biofeedback in patients with mild or moderate anal incontinence. DESIGN: This was a prospective parallel-group, single-institution, randomized clinical trial. SETTINGS: This study was conducted in an ambulatory setting at the Colorectal Physiology Service of the Hospital das Clinicas, Medical School, University of Sao Paulo. PATIENTS: This study included patients who had anal incontinence for >6 months with isolated internal anal sphincter muscle damage or absence of anatomical defects in the anorectal sphincter complex. INTERVENTIONS: Anal bulking agent and endoanal electrical stimulation with biofeedback. MAIN OUTCOME MEASURES: The primary outcome measure was the Cleveland Clinic Florida Fecal Incontinence Score, and the secondary outcome measures included quality of life, recommended procedures, and anorectal manometry. RESULTS: There were no significant between-group differences in mean age, sex, BMI, stool consistency, and Cleveland Clinic Florida Fecal Incontinence Score (p = 0.20) at baseline. After 12 months, the Cleveland Clinic Florida Fecal Incontinence Score was found to be significantly improved in patients treated with the bulking agent compared to those treated with electrical stimulation (mean, 6.2 vs 9.2; p = 0.002), though the anorectal manometry parameters did not change significantly. The mean anal Cleveland Clinic Florida Fecal Incontinence Score declined by 4.2 points in the bulking agent group compared to a decline of 0.8 in the electrical stimulation group (mean difference in decline: 3.4 points; 95% CI, 1.2-5.5). Quality-of life evaluation showed similar results between groups comparing baseline parameters with 12-month follow-up. LIMITATIONS: The short follow-up period of 1 year, atypical method of biofeedback, and unmatched baseline in some of the quality-of-life scales between the 2 groups limited this study. CONCLUSIONS: In patients with mild or moderate anal incontinence, the Cleveland Clinic Florida Fecal Incontinence Score significantly improved in the bulking agent with polyacrylate-polyalcohol copolymer group compared with the endoanal electrical stimulation with biofeedback group. See Video Abstract at http://links.lww.com/DCR/B938. ADMINISTRACIN DE UN GEL ANAL CON PARTCULAS DE COPOLMERO DE POLIACRILATOPOLIALCOHOL VERSUS ESTIMULACIN ELCTRICA ENDOANAL CON EJERCICIOS ANALES BIOFEEDBACK PARA EL MANEJO DE LA INCONTINENCIA ANAL LEVE Y MODERADA UN ESTUDI PROSPECTIVO ALEATORIZADO: ANTECEDENTES:Hasta la fecha, existen pocas opciones de tratamiento para la incontinencia anal de leve a moderada con defectos aislados del esfínter anal interno o la incontinencia anal sin daño muscular. Por lo general, se prefieren técnicas menos invasivas.OBJETIVO:El objetivo fue comparar los resultados entre el uso de un gel intra-anal con partículas de copolímero de poliacrilato-polialcohol y la estimulación eléctrica endoanal con ejercicios anales en pacientes con incontinencia anal leve o moderada.DISEÑO:Este fue un ensayo clínico aleatorio prospectivo de grupos paralelos, de una institución, realizado en cuatro etapas: base, procedimientos, postratamiento temprano y tardío.AJUSTE:Este estudio se realizó en el ambulatorio de Fisiología Colorrectal del Servicio de Coloproctología del Hospital das Clínicas, Facultad de Medicina, Universidad de São Paulo.PACIENTES:Paciente con incontinencia anal con más de 6 meses, con daño muscular aislado del esfínter anal interno o ausencia de defectos anatómicos en el esfínter anorrectal.INTERVENCIONES:Las intervenciones incluyeron la inyección del gel intra-anal y estimulación eléctrica endoanal con ejercicios anales.PRINCIPALES MEDIDAS DE RESULTADO:Indice de incontinencia fecal (Cleveland Clinic Florida), Indice de calidad de vida, los procedimientos recomendados y la manometría anorrectal.RESULTADOS:No hubo diferencias significativas entre los grupos en cuanto a la edad media, el sexo, el índice de masa corporal, la consistencia de las heces y la puntuación de incontinencia fecal (p = 0,20) al inicio del estudio. Después de 12 meses, la puntuación de incontinencia fecal mejoró significativamente en los pacientes tratados con el el gel intra-anal (media = 6,2) en comparación con los tratados con estimulación eléctrica (media = 9,2; p = 0,002), aunque los parámetros de manometría anorrectal no mejoraron significativamente. La puntuación anal media de incontinencia fecal disminuyó 4,2 puntos en el grupo del Gel intra-anal en comparación con 0,8 en el grupo de estimulación eléctrica (diferencia media en la disminución: 3,4 puntos; IC del 95%: 1,2 a 5,5). La evaluación de la calidad de vida mostró resultados similares entre los grupos que compararon los parámetros iniciales con un seguimiento de 12 meses.LIMITACIONES:Breve período de seguimiento de un año, métodos diferentes de ejercicios anales y línea de base sin igual en algunas de las escalas de calidad de vida entre los dos grupos.CONCLUSIONES:En pacientes con incontinencia anal leve y moderada, la puntuación de incontinencia fecal mejoró significativamente en el grupo de gel intra-anal con copolímero de poliacrilato-polialcohol en comparación con la estimulación eléctrica endoanal. Consulte Video Resumen en http://links.lww.com/DCR/B938. (Traducción- Dr Leonardo Alfonso Bustamante-Lopez).

Outcomes of Patients With Local Regrowth After Nonoperative Management of Rectal Cancer After Neoadjuvant Chemoradiotherapy.

BACKGROUND: Clinical complete responders after chemoradiation for rectal cancer are increasingly being managed by a watch-and-wait strategy. Nonetheless, a significant proportion will experience a local regrowth, and the long-term oncological outcomes of these patients is not totally known. OBJECTIVE: The purpose of this study was to analyze the outcomes of patients who submitted to a watch-and-wait strategy and developed a local regrowth, and to compare these results with sustained complete clinical responders. DESIGN: This was a retrospective study. SETTING: Single institution, tertiary cancer center involved in alternatives to organ preservation. PATIENTS: Patients with a biopsy-proven rectal adenocarcinoma (stage II/III or low lying cT2N0M0 at risk for an abdominoperineal resection) treated with chemoradiation who were found at restage to have a clinical complete response. INTERVENTIONS: Rectal cancer patients treated with chemoradiation who underwent a watch-and-wait strategy (without a full thickness local excision) and developed a local regrowth were compared to the remaining patients of the watch-and-wait strategy. MAIN OUTCOME MEASURES: Overall survival between groups, incidence of regrowth' and results of salvage surgery. RESULTS: There were 67 patients. Local regrowth occurred in 20 (29.9%) patients treated with a watch-and-wait strategy. Mean follow-up was 62.7 months. Regrowth occurred at mean 14.2 months after chemoradiation, half of them within the first 12 months. Patients presented with comparable initial staging, lateral pelvic lymph-node metastasis, and extramural venous invasion. The regrowth group had a statistically nonsignificant higher incidence of mesorectal fascia involvement (35.0% vs 13.3%, p = 0.089). All regrowths underwent salvage surgery, mostly (75%) a sphincter-sparing procedure. 5-year overall survival was 71.1% in patients with regrowth and 91.1% in patients with a sustained complete clinical response (p = 0.027). LIMITATIONS: This study was limited by its retrospective evaluation of patient selection for a watch-and-wait strategy and outcomes, as well as its small sample size. CONCLUSIONS: Local regrowth is a frequent event when following a watch-and-wait policy (29.9%); however, patients could undergo salvage surgical treatment with adequate pelvic control. In this series, overall survival showed a statistically significant difference from patients managed with a watch-and-wait strategy who experienced a local regrowth compared to those who did not. See Video Abstract at http://links.lww.com/DCR/B773.RESULTADOS DE LOS PACIENTES CON REBROTE LOCAL, DESPUÉS DEL MANEJO NO QUIRÚRGICO DEL CÁNCER DE RECTO, DESPUÉS DE LA QUIMIORRADIOTERAPIA NEOADYUVANTEANTECEDENTES:Los respondedores clínicos completos, después de la quimiorradiación para el cáncer de recto, se tratan cada vez más mediante una estrategia de observación y espera. No obstante, una proporción significativa experimentará un rebrote local y los resultados oncológicos a largo plazo de estos pacientes, no se conocen por completo.OBJETIVO:El propósito de este estudio, fue analizar los resultados de los pacientes sometidos a una estrategia de observación y espera, que desarrollaron un rebrote local, y comparar estos resultados con respondedores clínicos completos sostenidos.DISEÑO:Este fue un estudio retrospectivo.ENTORNO CLINICO.Institución única, centro oncológico terciario involucrado en alternativas a la preservación de órganos.PACIENTES:Pacientes con un adenocarcinoma de recto comprobado por biopsia (estadio II / III o posición baja cT2N0M0, en riesgo de resección abdominoperineal), tratados con quimiorradiación, y que durante un reestadiaje, presentaron una respuesta clínica completa.INTERVENCIONES:Los pacientes con cáncer de recto tratados con quimiorradiación, sometidos a una estrategia de observación y espera (sin una escisión local de espesor total) y que desarrollaron un rebrote local, se compararon con los pacientes restantes de la estrategia de observación y espera.PRINCIPALES MEDIDAS DE VALORACION:Supervivencia global entre los grupos, incidencia de rebrote y resultados de la cirugía de rescate.RESULTADOS:Fueron 67 pacientes. El rebrote local ocurrió en 20 (29,9%) pacientes tratados con una estrategia de observación y espera. El seguimiento medio fue de 62,7 meses. El rebrote se produjo a la media de 14,2 meses después de la quimiorradiación, la mitad de ellos dentro de los primeros 12 meses. Los pacientes se presentaron con una estadificación inicial comparable, metástasis en los ganglios linfáticos pélvicos laterales e invasión venosa extramural. El grupo de rebrote tuvo una mayor incidencia estadísticamente no significativa de afectación de la fascia mesorrectal (35,0 vs 13,3%, p = 0,089). Todos los rebrotes se sometieron a cirugía de rescate, en su mayoría (75%) con procedimiento de preservación del esfínter. La supervivencia global a 5 años fue del 71,1% en pacientes con rebrote y del 91,1% en pacientes con una respuesta clínica completa sostenida (p = 0,027).LIMITACIONES:Evaluación retrospectiva de la selección de pacientes para una estrategia y resultados de observar y esperar, tamaño de muestra pequeño.CONCLUSIONES:El rebrote local es un evento frecuente después de la política de observación y espera (29,9%), sin embargo los pacientes podrían someterse a un tratamiento quirúrgico de rescate con un adecuado control pélvico. En esta serie, la supervivencia global mostró una diferencia estadísticamente significativa de los pacientes manejados con una estrategia de observación y espera que experimentaron un rebrote local, en comparación con los que no lo hicieron. Consulte Video Resumen en http://links.lww.com/DCR/B773. (Traducción-Dr. Fidel Ruiz Healy).

Pretreatment colostomy in patients with anal squamous cell carcinoma: Risk factors for a permanent stoma.

BACKGROUND: The current standard of care for anal squamous cell carcinoma (SCC) is concurrent chemoradiation (CRT), which enables tumor eradication while preserving the anal sphincter. Patients with locally advanced tumors, however, may experience complications that preclude treatment before stoma creation. OBJECTIVE: To evaluate the reversal rate of pretreatment stomas and the risk factors associated with nonreversal. METHODS: This single-institution retrospective cohort study using a prospective database included patients diagnosed with anal SCC from January 2008 to December 2020 who required a stoma before curative CRT. RESULTS: In total, 651 patients were identified; 65 required a stoma before chemoradiation due to obstruction (43.1%), rectovaginal fistula (20%), and perianal sepsis (36.9%). The stoma was reversed in nine patients after a mean follow-up of 35.8 months. Risk factors associated with a permanent stoma were perianal sepsis (p = 0.010), interruptions during radiotherapy for more than 7 days (p = 0.010), male sex (p = 0.013), poor performance status (Eastern Cooperative Oncology Group [ECOG] ≥ 2) (p = 0.023), large tumors (p = 0.045), and cisplatin-based chemotherapy (p = 0.047). CONCLUSIONS: Pretreatment stomas are unlikely to be reversed, and risk factors for a permanent stoma are perianal sepsis, interruptions during radiotherapy for more than 7 days, male sex, poor performance status (ECOG ≥ 2), large tumors, and cisplatin-based chemotherapy.

Preoperative chemotherapy is a better strategy than upfront surgery in cT4 gastric cancer.

BACKGROUND: Chemotherapy (CMT) followed by surgery is recommended by Western countries for advanced gastric cancer (GC). However, cT4 GC usually undergoes upfront surgery, due to symptoms. This study aimed to evaluate if preoperative CMT is a better strategy than upfront surgery in cT4 GC. METHODS: All cT4 GCs who underwent curative gastrectomy were included. Patients were divided according to their initial treatment: upfront surgery (SURG) or CMT + SURG. RESULTS: Among the 226 GC initially staged as cT4, 150 underwent SURG and 76 CMT + SURG. Groups were similar concerning age, comorbidities, American Society of Anesthesiologists, gastrectomy performed, and postoperative complications. The CMT + SURG group had less advanced pTNM. Median overall survival (OS) was 32 and 58.5 months for SURG and CMT + SURG, respectively (p = 0.04). Patients who received perioperative or adjuvant CMT had better OS compared to surgery alone (49.4 vs. 15.9 months, p < 0.001). OS was similar for those receiving preoperative and adjuvant CMT. Non-CMT, pN+, and R1 resection were independent risk factors for worse OS. CONCLUSION: Multimodal treatment associating CMT with surgery, regardless of whether the approach is pre- or postoperative, is essential to improve the survival of cT4 GC. As tolerance to adjuvant treatment is reduced, preoperative CMT is a better strategy than upfront surgery in these patients.

Gastrectomy for elderly gastric cancer patients: A propensity score-matching analysis.

BACKGROUND: Although D2-gastrectomy is the most effective treatment for resectable gastric cancer (GC), it is unclear whether elderly patients have increased risk of morbidity and worse survival. This study aimed to compare the short- and long-term outcomes of older age (OA) patients with those of less advanced age (LAA). METHODS: GC patients undergoing curative gastrectomy were retrospectively analyzed and divided into two groups: OA (>75 years) and LAA (<75 years). Propensity score-matching (PSM) analysis using seven variables was conducted to reduce selection bias. RESULTS: Among 586 patients, 494 (84.3%) were classified as LAA and 92 (15.7%) as OA. OA patients had worse clinical status, higher rates of D1-lymphadenectomy, subtotal gastrectomy, and Lauren type; higher mortality and worse survival. No difference in pathological tumor-node-metastasis (pTNM) stage was observed between groups. Preoperative chemotherapy was performed more frequently in the LAA group. After PSM (92 OA: 92 LAA), all variables included in PSM were matched, and mortality rates and survival became similar between groups. In multivariate analysis, American Society of Anaesthesiologists score III/IV was an independent factor associated with a 90-day mortality after PSM. CONCLUSION: Gastrectomy in elderly GC patients has similar outcomes compared with younger ones. Clinical status and disease stage are more important than the patient's age.

Gastric cancer with microsatellite instability displays increased thymidylate synthase expression.

BACKGROUND: Gastric cancer (GC) with microsatellite instability (MSI) is a less aggressive disease and associated with resistance to 5-fluorouracil (5-FU)-based chemotherapy (CMT). Thymidylate synthase (TS) is inhibited by 5-FU, and another potential mediator of therapeutic resistance to 5-FU. Therefore, we aimed to analyze the association between MSI and TS expression in GC, and its impact on disease outcomes. METHODS: We retrospectively evaluated GC who underwent D2-gastrectomy. MSI and TS were analyzed by immunohistochemistry. We also investigated p53 expression, PD-L1 status, and tumor-infiltrating lymphocytes (CD4 and CD8). RESULTS: Out of 284 GC, 60 (21.1%) were MSI. Median TS-score for all cases was 16.5. TS expression was significantly higher in MSI compared to microsatellite-stable (MSS; p < 0.001). Considering both status, GC were classified in four groups: 167 (58.8%) MSS + TS-low; 57 (20.1%) MSS + TS-High; 24 (8.5%) MSI + TS-low; and 36 (12.7%) MSI + TS-high. MSI + TS-high group had less advanced pTNM stage, higher CD8+T cells levels (p < 0.001) and PD-L1 positivity (p < 0.001). Normal p53 expression was related to MSI GC (p < 0.001). Improved survival was observed in MSI + TS-high, but no survival benefit was seen with CMT. CONCLUSION: MSI GC was associated with high TS levels, which may explain therapeutic resistance to 5-FU. Additionally, MSI + TS-high showed better survival, but without improvement with CMT.

Diagnostic accuracy of FDG-PET/MRI versus pelvic MRI and thoracic and abdominal CT for detecting synchronous distant metastases in rectal cancer patients.

PURPOSE: We compared the diagnostic accuracy of detecting distant metastases for baseline rectal cancer staging between PET/MRI and conventional staging (CS). MATERIALS AND METHODS: This prospective study from November 2016 to April 2018 included 101 rectal adenocarcinoma patients for primary staging. These patients underwent whole-body PET/MRI in addition to CS (pelvic MRI and thoracic and abdominal contrast-enhanced CT). Different readers analyzed CS and PET/MRI findings for primary tumor, nodal, and metastatic staging. The presence, number, and location of metastases were recorded according to the organ involved (non-regional lymph nodes (LNs), liver, lungs, or others). Lesions were defined as positive, negative, or indeterminate. The number of lesions per organ was limited to 10. The McNemar test was used to compare the accuracies. RESULTS: PET/MRI exhibited a higher accuracy in detecting metastatic disease than CS in all patients (88.4% vs. 82.6%, p = 0.003) and in patients with extramural vascular invasion (EMVI) (88.9% vs. 85.5%, p = 0.013). The detection rate of PET/MRI was superior to that of CS for all lesions [84.1% vs. 68.9%, p = 0.001], as well as those in the liver (89.2% vs. 84.2%), non-regional LNs (90.0% vs. 36.7%), and lungs (76.4% vs. 66.9%). PET/MRI correctly classified 19/33 (57.5%) patients with indeterminate lesions on CS. CONCLUSION: PET/MRI yields higher accuracy than CS for detecting distant synchronous metastases in the baseline staging of patients with rectal cancer and EMVI. PET/MRI exhibited a higher detection rate than CS for identifying non-regional LNs, hepatic lesions, and pulmonary lesions as well as correctly classifying patients with indeterminate lesions. TRIAL REGISTRATION: NCT02537340.

Role of Magnification Chromoendoscopy in the Management of Colorectal Neoplastic Lesions Suspicious for Submucosal Invasion.

BACKGROUND: Correctly predicting the depth of tumor invasion in the colorectal wall is crucial for successful endoscopic resection of superficial colorectal neoplasms. OBJECTIVE: The aim of this study was to assess the accuracy of magnifying chromoendoscopy in a Western medical center to predict the depth of invasion by the pit pattern classification in patients with colorectal neoplasms with a high risk of submucosal invasion. DESIGN: This single-center retrospective study, from a prospectively collected database, was conducted between April 2009 and June 2015. SETTINGS: The study was conducted at a single academic center. PATIENTS: Consecutive patients with colorectal neoplasms with high risk of submucosal invasion were included. These tumors were defined by large (≥20 mm) sessile polyps (nonpedunculated), laterally spreading tumors, or depressed lesions of any size. INTERVENTIONS: Patients underwent magnifying chromoendoscopy and were classified according to the Kudo pit pattern. The therapeutic decision, endoscopic or surgery, was defined by the magnification assessment. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values of magnifying chromoendoscopy for assessment of these lesions were determined. RESULTS: A total of 123 lesions were included, with a mean size of 54.0 ± 37.1 mm. Preoperative magnifying chromoendoscopy with pit pattern classification had 73.3% sensitivity, 100% specificity, 100% positive predictive value, 96.4% negative predictive value, and 96.7% accuracy to predict depth of invasion and consequently to guide the appropriate treatment. Thirty-three rectal lesions were also examined by MRI, and 31 were diagnosed as T2 lesions. Twenty two (70.1%) of these lesions were diagnosed as noninvasive by magnifying colonoscopy, were treated by endoscopic resection, and met the curative criteria. LIMITATIONS: This was a single-center retrospective study with a single expert endoscopist experience. CONCLUSIONS: Magnifying chromoendoscopy is highly accurate for assessing colorectal neoplasms suspicious for submucosal invasion and can help to select the most appropriate treatment. See Video Abstract at http://links.lww.com/DCR/A920.