The standard treatment of locally advanced rectal cancer is chemoradiation (CRT) followed by proctectomy and adjuvant chemotherapy. However, there is an emerging role for nonsurgical management after ...CRT or total neoadjuvant therapy (TNT) consisting of CRT and neoadjuvant chemotherapy. Endoscopic submucosal dissection (ESD) after CRT or TNT for rectal cancer, termed "salvage ESD," may be a viable nonsurgical option for carefully selected patients. We aimed to evaluate the feasibility and safety of salvage ESD.
A retrospective chart review of cases of salvage ESD for locally advanced rectal cancer and standard ESD for rectal tumors without prior CRT from July 2018 to August 2020 at our institution was performed. Clinical factors and imaging, procedural, and pathology results were collected and compared.
Twelve salvage ESD cases were compared with 27 standard ESD cases. Before CRT, 83.3% of lesions in the salvage ESD group were initially clinically staged as T3. The en-bloc resection rates were 92.7% and 91.7% (P = 1.00) and R0 resection rates 66.7% and 75.0% (P = .55) for the standard and salvage groups, respectively. In the salvage ESD group, no adverse events were observed, and 75.0% of the adenocarcinomas in the salvage ESD group had morphologically changed to hyperplasia or adenoma after CRT, with no identifiable lesions greater than T1 tumor depth.
Salvage ESD for locally advanced rectal cancer is technically feasible with low adverse event rates. There may be a diagnostic role in salvage ESD in assessing pathologic response to CRT and a possible therapeutic role in resection of residual lesions with the potential to avoid surgery.
Background
Extramural venous invasion (EMVI) on baseline MRI is associated with poor prognosis in patients with locally advanced rectal cancer. This study investigated the association of persistent ...EMVI after total neoadjuvant therapy (TNT) (chemoradiotherapy and systemic chemotherapy) with survival.
Methods
Baseline MRI, post-TNT MRI, and surgical pathology data from 175 patients with locally advanced rectal cancer who underwent TNT and total mesorectal excision between 2010 and 2017 were retrospectively analyzed for evidence of EMVI. Two radiologists assessed EMVI status with disagreement adjudicated by a third. Pathologic EMVI status was assessed per departmental standards. Cox regression models evaluated the associations between EMVI and disease-free and overall survival.
Results
EMVI regression on both post-TNT MRI and surgical pathology was associated with disease-free survival (hazard ratio, 0.17; 95% confidence interval (CI), 0.04–0.64) and overall survival (hazard ratio, 0.11; 95% CI, 0.02–0.68). In an exploratory analysis of 35 patients with EMVI on baseline MRI, only six had EMVI on pathology compared with 18 on post-TNT MRI; these findings were not associated (
p
= 0.2). Longer disease-free survival was seen with regression on both modalities compared with remaining positive. Regression on pathology alone, independent of MRI EMVI status, was associated with similar improvements in survival.
Conclusions
Baseline EMVI is associated with poor prognosis even after TNT. EMVI regression on surgical pathology is common even with persistent EMVI on post-TNT MRI. EMVI regression on surgical pathology is associated with improved DFS, while the utility of post-TNT MRI EMVI persistence for decision-making and prognosis remains unclear.
Pancreatic cancer is the fourth leading cause of cancer deaths and there currently is no reliable modality for the early detection of this disease. Here, we identify cancer-specific promoter DNA ...methylation of BNC1 and ADAMTS1 as a promising biomarker detection strategy meriting investigation in pancreatic cancer.
We used a genome-wide pharmacologic transcriptome approach to identify novel cancer-specific DNA methylation alterations in pancreatic cancer cell lines. Of eight promising genes, we focused our studies on BNC1 and ADAMTS1 for further downstream analysis, including methylation and expression. We used a nanoparticle-enabled methylation on beads (MOB) technology to detect early-stage pancreatic cancers by analyzing DNA methylation in patient serum.
We identified two novel genes, BNC1 (92%) and ADAMTS1 (68%), that showed a high frequency of methylation in pancreatic cancers (n = 143), up to 100% in PanIN-3 and 97% in stage I invasive cancers. Using the nanoparticle-enabled MOB technology, these alterations could be detected in serum samples (n = 42) from patients with pancreatic cancer, with a sensitivity for BNC1 of 79% 95% confidence interval (CI), 66%-91% and for ADAMTS1 of 48% (95% CI, 33%-63%), whereas specificity was 89% for BNC1 (95% CI, 76%-100%) and 92% for ADAMTS1 (95% CI, 82%-100%). Overall sensitivity using both markers is 81% (95% CI, 69%-93%) and specificity is 85% (95% CI, 71%-99%).
Promoter DNA methylation of BNC1 and ADAMTS1 is a potential biomarker to detect early-stage pancreatic cancers. Assaying the promoter methylation status of these genes in circulating DNA from serum is a promising strategy for early detection of pancreatic cancer and has the potential to improve mortality from this disease.
Neoadjuvant chemotherapy and radiation followed by surgical resection of the rectum is a standard treatment for locally advanced rectal cancer. A subset of rectal cancer is caused by a deficiency in ...mismatch repair. Because mismatch repair-deficient colorectal cancer is responsive to programmed death 1 (PD-1) blockade in the context of metastatic disease, it was hypothesized that checkpoint blockade could be effective in patients with mismatch repair-deficient, locally advanced rectal cancer.
We initiated a prospective phase 2 study in which single-agent dostarlimab, an anti-PD-1 monoclonal antibody, was administered every 3 weeks for 6 months in patients with mismatch repair-deficient stage II or III rectal adenocarcinoma. This treatment was to be followed by standard chemoradiotherapy and surgery. Patients who had a clinical complete response after completion of dostarlimab therapy would proceed without chemoradiotherapy and surgery. The primary end points are sustained clinical complete response 12 months after completion of dostarlimab therapy or pathological complete response after completion of dostarlimab therapy with or without chemoradiotherapy and overall response to neoadjuvant dostarlimab therapy with or without chemoradiotherapy.
A total of 12 patients have completed treatment with dostarlimab and have undergone at least 6 months of follow-up. All 12 patients (100%; 95% confidence interval, 74 to 100) had a clinical complete response, with no evidence of tumor on magnetic resonance imaging,
F-fluorodeoxyglucose-positron-emission tomography, endoscopic evaluation, digital rectal examination, or biopsy. At the time of this report, no patients had received chemoradiotherapy or undergone surgery, and no cases of progression or recurrence had been reported during follow-up (range, 6 to 25 months). No adverse events of grade 3 or higher have been reported.
Mismatch repair-deficient, locally advanced rectal cancer was highly sensitive to single-agent PD-1 blockade. Longer follow-up is needed to assess the duration of response. (Funded by the Simon and Eve Colin Foundation and others; ClinicalTrials.gov number, NCT04165772.).
Despite improvements in surgical techniques, functional outcomes and quality of life after therapy for rectal cancer remain suboptimal. We sought to prospectively evaluate the effect of bowel, ...bladder, and sexual functional outcomes on health-related quality of life (QOL) in patients with restorative versus non-restorative resections after rectal cancer surgery. A cohort of 211 patients with clinical stage I-III rectal cancer who underwent open surgery between 2006 and 2009 at Memorial Sloan Kettering were included. Subjects were asked to complete surveys preoperatively and at 6, 12, and 24 months after surgery. Validated instruments were used to measure QOL, bowel, bladder, and sexual function. Univariable and multivariable regression analyses evaluated predictors of 24- month QOL. In addition, longitudinal trends over the study period were evaluated using repeated measures models. In total, 180 patients (85%) completed at least 1 survey, and response rates at each time point were high (>70%). QOL was most impaired at 6 and 12 months and returned to baseline levels at 24 months. Among patients who underwent sphincter-preserving surgery (SPS; n=153 85%), overall bowel function at 24 months was significantly impaired and never returned to baseline. There were no differences in QOL at 24 months between patients who underwent SPS and those who did not (p=.29). Bowel function was correlated with QOL at 24 months (Pearson correlation,.41; p<.001). QOL among patients who have undergone SPS for rectal cancer is good despite poor function. Patients with ostomies are able to adjust to the functional changes and, overall, have good global QOL. Patients with low anastomoses had lower global QOL at 24 months than patients with permanent stomas. Our findings can help patients set expectations about function and quality of life after surgery for rectal cancer with and without a permanent stoma.
Colorectal cancer (CRC) cells show some alterations in lipid metabolism, including an increased fatty acid elongation. This study was focused on investigating the effect of a small interfering RNA ...(siRNA)-mediated decrease in fatty acid elongation on CRC cells' survival and migration. In our study, the elongase 4 (
) and elongase 6 (
) genes were observed to be highly overexpressed in both the CRC tissue obtained from patients and the CRC cells cultured in vitro (HT-29 and WiDr cell lines). The use of the siRNAs for
and
reduced cancer cell proliferation and migration rates. These findings indicate that the altered elongation process decreased the survival of CRC cells, and in the future, fatty acid elongases can be potentially good targets in novel CRC therapy.
A watch-and-wait strategy is a nonoperative alternative to sphincter-preserving surgery for patients with locally advanced rectal cancer who achieve a clinical complete response after neoadjuvant ...therapy. There are limited data about bowel function for patients undergoing this organ-preservation approach.
The purpose of this study was to compare bowel function in patients with rectal cancer managed with a watch-and-wait approach with bowel function in patients who underwent sphincter-preserving surgery (total mesorectal excision).
This was a retrospective case-control study using patient-reported outcomes.
The study was conducted at a comprehensive cancer center.
Twenty-one patients underwent a watch-and-wait approach and were matched 1:1 with 21 patients from a pool of 190 patients who underwent sphincter-preserving surgery, based on age, sex, and tumor distance from the anal verge.
Bowel function was measured using the Memorial Sloan Kettering Cancer Center Bowel Function Instrument.
Patients in the watch-and-wait arm had better bowel function on the overall scale (median total score, 76 vs 55; p < 0.001) and on all of the subscales, with the greatest difference on the urgency/soilage subscale (median score, 20 vs 12; p < 0.001).
The study was limited by its retrospective design, small sample size, and temporal variability between surgery and time of questionnaire completion.
A watch-and-wait strategy correlated with overall better bowel function when compared with sphincter-preserving surgery using a comprehensive validated bowel dysfunction tool. See Video Abstract at http://links.lww.com/DCR/B218. FUNCIÓN EVACUATORIA INFORMADA POR PACIENTES EN CÁNCER RECTAL MANEJADO CON UNA ESTRATEGIA DE OBSERVAR Y ESPERAR DESPUÉS DE LA TERAPIA NEOADYUVANTE: UN ESTUDIO DE CASOS Y CONTROLES: Observar y esperar es una alternativa no operativa a la cirugía de preservación del esfínter para pacientes con cáncer rectal localmente avanzado que logran una respuesta clínica completa después de la terapia neoadyuvante. Hay datos limitados sobre la función evacuatoria en pacientes sometidos a este abordaje para preservación de órganos.Evaluar la función evacuatoria en pacientes con cáncer rectal manejados con observar y esperar comparado a pacientes sometidos a cirugía de preservación de esfínteres (escisión mesorrectal total).Estudio retrospectivo de casos y controles utilizando resultados reportados por pacientes.Centro especializado oncológico.21 pacientes se sometieron a observar y esperar y se compararon con 21 pacientes de un grupo de 190 pacientes que se sometieron a cirugía de preservación de esfínteres controlando por edad, sexo y la distancia del tumor al borde anal.Función evacuatoria utilizando un instrumento de valoración del Centro de Cáncer Memorial Sloan Kettering.Los pacientes de observar y esperar demostraron mejor función evacuatoria en la escala general (puntuación total media, 76 versus 55; p <0,001) y en todas las subescalas, con la mayor diferencia en la subescala de urgencia / ensuciamiento fecal (puntuación media, 20 versus 12; p <0,001).Diseño retrospectivo, numero de muestra pequeño y variabilidad temporal entre la cirugía y el tiempo de finalización del cuestionario.Observar y esperar se correlacionó con mejor función evacuatoria en general en comparación con la cirugía de preservación del esfínter utilizando una herramienta integral validada para la disfunción evacuatoria. Consulte Video Resumen en http://links.lww.com/DCR/B218. (Traducción-Dr. Adrián Ortega).
Cellular transformation induces phenotypically diverse populations of tumour-infiltrating T cells
, and immune checkpoint blockade therapies preferentially target T cells that recognize cancer cell ...neoantigens
. Yet, how other classes of tumour-infiltrating T cells contribute to cancer immunosurveillance remains elusive. Here, in a survey of T cells in mouse and human malignancies, we identified a population of αβ T cell receptor (TCR)-positive FCER1G-expressing innate-like T cells with high cytotoxic potential
(ILTCKs). These cells were broadly reactive to unmutated self-antigens, arose from distinct thymic progenitors following early encounter with cognate antigens, and were continuously replenished by thymic progenitors during tumour progression. Notably, expansion and effector differentiation of intratumoural ILTCKs depended on interleukin-15 (IL-15) expression in cancer cells, and inducible activation of IL-15 signalling in adoptively transferred ILTCK progenitors suppressed tumour growth. Thus, the antigen receptor self-reactivity, unique ontogeny, and distinct cancer cell-sensing mechanism distinguish ILTCKs from conventional cytotoxic T cells, and define a new class of tumour-elicited immune response.
To assess long-term outcomes with robotic versus laparoscopic/thoracoscopic and open surgery for colorectal, urologic, endometrial, cervical, and thoracic cancers.
Minimally invasive surgery provides ...perioperative benefits and similar oncological outcomes compared with open surgery. Recent robotic surgery data have questioned long-term benefits.
A systematic review and meta-analysis of cancer outcomes based on surgical approach was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines using Pubmed, Scopus, and Embase. Hazard ratios for recurrence, disease-free survival (DFS), and overall survival (OS) were extracted/estimated using a hierarchical decision tree and pooled in RevMan 5.4 using inverse-variance fixed-effect (heterogeneity nonsignificant) or random effect models.
Of 31,204 references, 199 were included (7 randomized, 23 database, 15 prospective, 154 retrospective studies)-157,876 robotic, 68,007 laparoscopic/thoracoscopic, and 234,649 open cases. Cervical cancer: OS and DFS were similar between robotic and laparoscopic 1.01 (0.56, 1.80), P =0.98 or open 1.18 (0.99, 1.41), P =0.06 surgery; 2 papers reported less recurrence with open surgery 2.30 (1.32, 4.01), P =0.003. Endometrial cancer: the only significant result favored robotic over open surgery OS; 0.77 (0.71, 0.83), P <0.001. Lobectomy: DFS favored robotic over thoracoscopic surgery 0.74 (0.59, 0.93), P =0.009; OS favored robotic over open surgery 0.93 (0.87, 1.00), P =0.04. Prostatectomy: recurrence was less with robotic versus laparoscopic surgery 0.77 (0.68, 0.87), P <0.0001; OS favored robotic over open surgery 0.78 (0.72, 0.85), P <0.0001. Low-anterior resection: OS significantly favored robotic over laparoscopic 0.76 (0.63, 0.91), P =0.004 and open surgery 0.83 (0.74, 0.93), P =0.001.
Long-term outcomes were similar for robotic versus laparoscopic/thoracoscopic and open surgery, with no safety signal or indication requiring further research (PROSPERO Reg#CRD42021240519).
The advent of immune checkpoint inhibition therapy has dramatically improved survival in patients with skin melanoma. Survival outcomes after resection of anorectal melanoma treated with immune ...checkpoint inhibition have not been reported.
This study aimed to compare survival outcomes following surgical resection of anorectal melanoma between patients who received immune checkpoint inhibition and patients who did not.
This study is a retrospective analysis of data from a prospectively maintained database.
This study was conducted at a comprehensive cancer center.
Patients who underwent surgery for anorectal melanoma between 2006 and 2017 were included. They were stratified according to the use of immune checkpoint inhibition.
The primary outcomes measured were overall and disease-specific survival.
Of the 47 patients included in the analysis, 29 (62%) received immune checkpoint inhibition therapy. Twenty-two (76%) of the 29 patients received immune checkpoint inhibition after detection of metastasis or disease progression rather than in the neoadjuvant or adjuvant setting. Overall survival did not differ significantly between patients who received immune checkpoint inhibition therapy and patients who did not (median, 52 and 20 months; 5-year rate, 41% vs 35%; p = 0.25). Disease-specific survival also did not differ significantly. Our analysis did not identify any clinical or pathological features associated with response to immune checkpoint inhibition therapy or with survival.
This study was limited by its relatively small sample and retrospective design and by the heterogeneous treatment regimen in the immune checkpoint inhibition group.
Immune checkpoint inhibition therapy by itself does not appear to improve survival in patients who undergo resection or excision of anorectal melanoma. Combinations of immune checkpoint inhibition with other therapeutic modalities warrant further investigation. See Video Abstract at http://links.lww.com/DCR/B499. MELANOMA DE LA MUCOSA ANORRECTAL EN LA ERA DE LOS INHIBIDORES DEL PUNTO DE CONTROL INMUNOLÓGICO: ¿DEBEMOS DE CAMBIAR NUESTRO PARADIGMA DEL MANEJO QUIRÚRGICO: El advenimiento de la terapia de los inhibidores del punto de control inmunológico, han mejorado dramáticamente la supervivencia en pacientes con melanoma de piel. No se han informado los resultados de supervivencia después de la resección del melanoma anorrectal, tratado con inhibidores del punto de control inmunológico.Comparar los resultados de supervivencia después de la resección quirúrgica de melanoma anorrectal entre pacientes que recibieron y no recibieron inhibidores del punto de control inmunológico.Análisis retrospectivo de una base de datos mantenida prospectivamente.Centro oncológico integral.Pacientes que se sometieron a cirugía por melanoma anorrectal entre 2006 y 2017. Los pacientes fueron estratificados según el uso de inhibidores del punto de control inmunológico.Supervivencia global y específica de la enfermedad.De los 47 pacientes incluidos en el análisis, 29 (62%) recibieron terapia de inhibidores del punto de control inmunológico. Veintidós (76%) de los 29 pacientes recibieron inhibidores del punto de control inmunológico después de la detección de metástasis o progresión de la enfermedad, en vez de administración adyuvante o neoadyuvante. La supervivencia global no varió significativamente entre los pacientes que recibieron o no recibieron terapia de inhibidores del punto de control inmunológico (mediana, 52 y 20 meses, respectivamente; tasa a 5 años, 41% frente a 35%, respectivamente; p = 0,25). La supervivencia específica de la enfermedad tampoco varió significativamente. Nuestro análisis no identificó ninguna característica clínica o patológica, asociada con la respuesta a la terapia de inhibidores del punto de control inmunológico o con la supervivencia.Muestra relativamente pequeña y diseño retrospectivo. Régimen de tratamiento heterogéneo en el grupo de inhibidores del punto de control inmunológico.La terapia por sí sola, de inhibidores del punto de control inmunológico, no parece mejorar la supervivencia en pacientes que se someten a resección o escisión de melanoma anorrectal. Las combinaciones de inhibidores del punto de control inmunológico con otras modalidades terapéuticas, merecen una mayor investigación. Consulte Video Resumen en http://links.lww.com/DCR/B499. (Traducción-Dr. Fidel Ruiz Healy).
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