Management and staging of anal adenocarcinoma in the United States: a population-based analysis.

BACKGROUND: Anal adenocarcinoma is rare with no standardized treatment regimen or staging system. Therefore, different combinations of chemotherapy, radiation, and surgery are used in management. Within the staging system, tumor stage can be based on the depth of invasion, as for rectal adenocarcinoma, or size, as in anal squamous cell carcinoma. This study aimed to analyze patterns of care and clinically available staging systems for anal adenocarcinoma using a national database. METHODS: Adults diagnosed with anal adenocarcinoma were identified in the Surveillance, Epidemiology, and End Results database (2004-2019). In addition, 6 different treatment regimens were identified. Stages were categorized according to the American Joint Committee on Cancer classifications of rectal adenocarcinoma and anal squamous cell carcinoma. RESULTS: Of 1040 patients, 48% were female, the median age was 67 years, and 18% had distant metastases. Chemoradiotherapy + abdominoperineal resection was the most common treatment regimen (22%). Moreover, 5-year overall survival (OS) and disease-specific survival (DSS) were the highest for local excision only (67% and 85%) and the lowest in the alternative group (34% and 48%). After adjustment, the treatment groups that did not include surgery were associated with worse 5-year OS. In multivariable analysis, the T stage based on depth of invasion showed incrementally lower OS for T2 and T3 anal adenocarcinomas. CONCLUSION: Omission of surgical resection in combination with chemoradiotherapy was associated with worse OS and DSS, suggesting the relevance of surgery in anal adenocarcinoma management. Prognostically, rectal staging based on depth of invasion better discriminated between T stages, indicating that providers should consider using this system in practice.

A population-based analysis on the incidence of metachronous colon cancer after endoscopic resection of advanced adenomas with high-grade dysplasia: does location matter?

BACKGROUND: Advanced adenomas (AAs) with high-grade dysplasia (HGD) represent a risk factor for metachronous neoplasia, with guidelines recommending short-interval surveillance. Although the worse prognosis of proximal (vs distal) colon cancers (CCs) is established, there is paucity of evidence on the impact of laterality on the risk of subsequent neoplasia for these AAs. METHODS: Adults with HGD adenomas undergoing polypectomy were identified in the Surveillance, Epidemiology, and End Results database (2000-2019). Cumulative incidence of malignancy was estimated using the Kaplan-Meier method. Fine-Gray models assessed the effect of patient and disease characteristics on CC incidence. RESULTS: Of 3199 patients, 26% had proximal AAs. A total of 65 cases of metachronous adenocarcinoma were identified after polypectomy of 35 proximal and 30 distal adenomas with HGD. The 10-year cumulative incidence of CC was 2.3%; when stratified by location, it was 4.8% for proximal vs 1.4% for distal adenomas. Proximal location was significantly associated with increased incidence of metachronous cancer (adjusted hazard ratio, 3.32; 95% CI, 2.05-5.38). CONCLUSION: Proximal location of AAs with HGD was associated with >3-fold increased incidence of metachronous CC and shorter time to diagnosis. These data suggest laterality should be considered in the treatment and follow-up of these patients.

Contemporary management of rectal cancer.

The management of rectal cancer has undergone significant changes over the past 50 years, and this has been associated with major improvements in overall outcomes and quality of life. From standardization of total mesorectal excision to refinements in radiation delivery and shifting of chemoradiotherapy treatment to favor a neoadjuvant approach, as well as the development of targeted chemotherapeutics, these management strategies have continually aimed to achieve locoregional and systemic control while limiting adverse effects and enhance overall survival. This article highlights evolving aspects of rectal cancer therapy including improved staging modalities, total neoadjuvant therapy, the role of short-course and more selective radiotherapy strategies, as well as organ preservation. We also discuss the evolving role of minimally invasive surgery and comment on lateral pelvic lymph node dissection. Key message: Rectal cancer management is constantly evolving through refinements in radiation timing and delivery, modification of chemoradiotherapy treatment schedules, and increasing utilization of minimally invasive surgical techniques and organ preservation strategies. This manuscript aims to provide a synopsis of recent changes in the management of rectal cancer, highlighting contemporary modifications in neoadjuvant approaches and surgical management to enhance the knowledge of surgeons who care for this challenging population.

Diet-induced shifts in the gut microbiota influence anastomotic healing in a murine model of colonic surgery.

Host diet and gut microbiota interact to contribute to perioperative complications, including anastomotic leak (AL). Using a murine surgical model of colonic anastomosis, we investigated how diet and fecal microbial transplantation (FMT) impacted the intestinal microbiota and if a predictive signature for AL could be determined. We hypothesized that a Western diet (WD) would impact gut microbial composition and that the resulting dysbiosis would correlate with increased rates of AL, while FMT from healthy, lean diet (LD) donors would reduce the risk of AL. Furthermore, we predicted that surgical outcomes would allow for the development of a microbial preclinical translational tool to identify AL. Here, we show that AL is associated with a dysbiotic microbial community characterized by increased levels of Bacteroides and Akkermansia. We identified several key taxa that were associated with leak formation, and developed an index based on the ratio of bacteria associated with the absence and presence of leak. We also highlight a modifiable connection between diet, microbiota, and anastomotic healing, potentially paving the way for perioperative modulation by microbiota-targeted therapeutics to reduce AL.

Endoscopic polypectomy for malignant polyps: Should tumor location (right versus left side) guide clinical decisions?

BACKGROUND: Current guidelines consider endoscopic resection appropriate treatment for malignant colon polyps with negative margins, low-grade histology, and no lymphovascular invasion. While increasing literature demonstrates a worse prognosis for advanced stage right- versus left-sided colon cancers after curative treatment, there is paucity of data regarding prognostic effect of location in patients undergoing endoscopic resection of T1 polyps. We hypothesized the more aggressive biologic behavior observed in advanced right-sided cancers would be similarly represented in malignant polyps, and this location would be associated with lower overall survival. METHODS: The National Cancer Database was queried for adults with T1NxMx tumors who underwent endoscopic polypectomy (2004-2017). Patients with positive margins or without follow-up information were excluded. RESULTS: A total of 2,337 patients met inclusion criteria; 22% had right-sided polyps. Endoscopically excised proximal tumors were more common in elderly, and those with public insurance and more comorbidities (all P < .01). Among patients with complete pathologic data, there were no statistical differences between right- and left-sided polyps with 1 cm median size, >92% without lymphovascular invasion, and 100% without tumor deposits. Univariate analysis showed 73% vs 86% 5-year overall survival for right versus left polyps (P < .01). After adjustment for available confounders, right-sided location remained significantly associated with worse overall survival (hazard ratio 1.49, 95% confidence interval 1.21-1.83). CONCLUSION: In this national cohort of patients with endoscopically excised malignant polyps, we identified right colon location as an independent prognostic factor associated with increased risk of mortality. Our data suggest polyp location should be taken into consideration when making clinical decisions regarding treatment and/or surveillance.

Colon and Rectal Cancer Management in Low-Resource Settings.

Colorectal cancer (CRC) incidence is rising in low- and middle-income countries, which also face disproportionate mortality from CRC, mainly due to diagnosis at late stages. Various challenges to CRC care exist at multiple societal levels in underserved populations. In this article, barriers to CRC care, strategies for screening, and treatment in resource-limited settings, and future directions are discussed within a global context.

A pilot study demonstrating the impact of surgical bowel preparation on intestinal microbiota composition following colon and rectal surgery.

The intestinal microbiota has been implicated in the pathogenesis of complications following colorectal surgery, yet perioperative changes in gut microbiome composition are poorly understood. The objective of this study was to characterize the perioperative gut microbiome in patients undergoing colonoscopy and colorectal surgery and determine factors influencing its composition. Using Illumina amplicon sequencing coupled with targeted metabolomics, we characterized the fecal microbiota in: (A) patients (n = 15) undergoing colonoscopy who received mechanical bowel preparation, and (B) patients (n = 15) undergoing colorectal surgery who received surgical bowel preparation, composed of mechanical bowel preparation with oral antibiotics, and perioperative intravenous antibiotics. Microbiome composition was characterized before and up to six months following each intervention. Colonoscopy patients had minor shifts in bacterial community composition that recovered to baseline at a mean of 3 (1-13) days. Surgery patients demonstrated substantial shifts in bacterial composition with greater abundances of Enterococcus, Lactobacillus, and Streptococcus. Compositional changes persisted in the early postoperative period with recovery to baseline beginning at a mean of 31 (16-43) days. Our results support surgical bowel preparation as a factor significantly influencing gut microbial composition following colorectal surgery, while mechanical bowel preparation has little impact.

Abdominal Surgical Procedures in Adult Patients With Cystic Fibrosis: What Are the Risks?

BACKGROUND: With advances in medical care, patients with cystic fibrosis are more commonly living into adulthood, yet there are limited data describing the need for GI surgery and its outcomes in adult cystic fibrosis patients. OBJECTIVE: We aim to use a national administrative database to evaluate trends in abdominal GI surgery and associated postoperative outcomes among adult cystic fibrosis patients. DESIGN: This was a national retrospective cohort study. SETTING: A national all-payor administrative database from 2000 to 2014 was used. PATIENTS: Patients included adults (age ≥18 years) with cystic fibrosis undergoing abdominal GI surgery. MAIN OUTCOME MEASURES: The primary outcome was trend over time in number of surgical admissions. Secondary outcomes included morbidity and mortality by procedure type. RESULTS: We identified 3075 admissions for abdominal surgery, of which 28% were elective. Major GI surgical procedures increased over the study period ( p < 0.01), whereas appendectomy and cholecystectomy did not demonstrate a clear trend ( p = 0.90). The most common procedure performed was cholecystectomy ( n = 1280; 42%). The most common major surgery was segmental colectomy ( n = 535; 18%). Obstruction was the most common surgical indication ( n = 780; 26%). For major surgery, in-hospital mortality was 6%, morbidity was 37%, and mean length of stay was 15.9 days (SE 1.2). LIMITATIONS: The study is limited by a lack of granular physiological and clinical data within the administrative data source. CONCLUSIONS: Major surgical admissions for adult patients with cystic fibrosis are increasing, with the majority being nonelective. Major surgery is associated with significant morbidity, mortality, and prolonged length of hospital stay. These findings may inform perioperative risk for adult patients with cystic fibrosis in need of GI surgery. See Video Abstract at http://links.lww.com/DCR/B850 . PROCEDIMIENTOS QUIRRGICOS ABDOMINALES EN PACIENTES ADULTOS CON FIBROSIS QUSTICA CULES SON LOS RIESGOS: ANTECEDENTES:Con los avances en la medicina, los pacientes con fibrosis quística viven más comúnmente hasta la edad adulta, pero hay datos escasos que describan la necesidad de cirugía gastrointestinal y sus resultados en pacientes adultos con fibrosis quística.OBJETIVO:Nuestro objetivo es utilizar una base de datos administrativa nacional para evaluar las tendencias en la cirugía gastrointestinal abdominal y los resultados posoperatorios asociados entre los pacientes adultos con fibrosis quística.DISEÑO:Estudio de cohorte retrospectivo nacional.AJUSTE:Base de datos administrativa nacional de todas las instituciones pagadoras desde 2000 a 2014.PACIENTES:Todos los pacientes adultos (edad> 18) con fibrosis quística sometidos a cirugía gastrointestinal abdominal.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la tendencia a lo largo del tiempo en el número de ingresos quirúrgicos. Los resultados secundarios incluyeron morbilidad y mortalidad por tipo de procedimiento.RESULTADOS:Identificamos 3.075 ingresos por cirugía abdominal de los cuales el 28% fueron electivos. Los procedimientos quirúrgicos gastrointestinales mayores aumentaron durante el período de estudio (p <0,01) mientras que la apendicectomía y la colecistectomía no demostraron una tendencia clara (p = 0,90). El procedimiento realizado con mayor frecuencia fue la colecistectomía (n = 1.280; 42%). La cirugía mayor más común fue la colectomía segmentaria (n = 535; 18%). La obstrucción fue la indicación quirúrgica más común (n = 780; 26%). Para la cirugía mayor, la mortalidad hospitalaria fue del 6%, la morbilidad del 37% y la estadía media de 15,9 días (EE 1,2).LIMITACIONES:El estudio está limitado por la falta de datos clínicos y fisiológicos granulares dentro de la fuente de datos administrativos.CONCLUSIONES:Los ingresos quirúrgicos mayores de pacientes adultos con fibrosis quística están aumentando y la mayoría no son electivos. La cirugía mayor se asocia con una morbilidad y mortalidad significativas y una estancia hospitalaria prolongada. Estos hallazgos pueden informar el riesgo perioperatorio para pacientes adultos con fibrosis quística que necesitan cirugía gastrointestinal. Consulte Video Resumen en http://links.lww.com/DCR/B850 . (Traducción-Dr. Felipe Bellolio ).

Total Neoadjuvant Therapy Versus Standard Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer: A Comparison of Short- and Long-term Oncologic Outcomes.

OBJECTIVE: To evaluate the impact of neoadjuvant multi-agent systemic chemotherapy and radiation (TNT) vs neoadjuvant single-agent chemoradiation (nCRT) and multi-agent adjuvant chemotherapy on overall survival (OS), tumor downstaging, and circumferential resection margin (CRM) status in patients with locally advanced rectal cancer. SUMMARY OF BACKGROUND DATA: Outside of clinical trials and small institutional reports, there is a paucity of data regarding the short and long-term oncologic impact of TNT as compared to nCRT. METHODS: Adult patients with stage II-III rectal adenocarcinoma were identified in the National Cancer Database [2006-2015]. RESULTS: Out of 8,548 patients, 36% received TNT and 64% nCRT. In the cohort, 13% had a pCR and 20% a neoadjuvant rectal (NAR) score <8. In multivariable analysis, as compared to nCRT, TNT demonstrated numerically higher pCR rates ( P = 0.05) but had similar incidence of positive CRM ( P = 0.11). Similar results were observed with NAR scores <8 as the primary endpoint. After adjusting for confounders, OS was comparable between the 2 groups. Additional factors independently associated with lower OS included male gender, uninsured status, low income status, high comorbidity score, poorly differentiated tumors, abdominoperineal resection, and positive surgical margins (all P <0.01). In separate models, both pCR and a NAR score <8 were associated with improved OS. CONCLUSION: In this national cohort, TNT was not associated with better survival and/or CRM negative status in comparison with nCRT, despite numerically higher downstaging rates. Further refinement of patient selection and treatment regimens are needed to establish effective neoadjuvant platforms to improve outcomes of patients with rectal cancer.

Intracorporeal and extracorporeal anastomosis for robotic-assisted and laparoscopic right colectomy: short-term outcomes of a multi-center prospective trial.

BACKGROUND: Studies to date show contrasting conclusions when comparing intracorporeal and extracorporeal anastomoses for minimally invasive right colectomy. Large multi-center prospective studies comparing perioperative outcomes between these two techniques are needed. The purpose of this study was to compare intracorporeal and extracorporeal anastomoses outcomes for robotic assisted and laparoscopic right colectomy. METHODS: Multi-center, prospective, observational study of patients with malignant or benign disease scheduled for laparoscopic or robotic-assisted right colectomy. Outcomes included conversion rate, gastrointestinal recovery, and complication rates. RESULTS: There were 280 patients: 156 in the robotic assisted and laparoscopic intracorporeal anastomosis (IA) group and 124 in the robotic assisted and laparoscopic extracorporeal anastomosis (EA) group. The EA group was older (mean age 67 vs. 65 years, p = 0.05) and had fewer white (81% vs. 90%, p = 0.05) and Hispanic (2% vs. 12%, p = 0.003) patients. The EA group had more patients with comorbidities (82% vs. 72%, p = 0.04) while there was no significant difference in individual comorbidities between groups. IA was associated with fewer conversions to open and hand-assisted laparoscopic approaches (p = 0.007), shorter extraction site incision length (4.9 vs. 6.2 cm; p ≤ 0.0001), and longer operative time (156.9 vs. 118.2 min). Postoperatively, patients with IA had shorter time to first flatus, (1.5 vs. 1.8 days; p ≤ 0.0001), time to first bowel movement (1.6 vs. 2.0 days; p = 0.0005), time to resume soft/regular diet (29.0 vs. 37.5 h; p = 0.0014), and shorter length of hospital stay (median, 3 vs. 4 days; p ≤ 0.0001). Postoperative complication rates were comparable between groups. CONCLUSION: In this prospective, multi-center study of minimally invasive right colectomy across 20 institutions, IA was associated with significant improvements in conversion rates, return of bowel function, and shorter hospital stay, as well as significantly longer operative times compared to EA. These data validate current efforts to increase training and adoption of the IA technique for minimally invasive right colectomy.

Immunofluorescence in Robotic Colon and Rectal Surgery.

The indocyanine green fluorescence imaging system is a surgical tool with increasing applications in colon and rectal surgery that has received growing acceptance in various surgical disciplines as a potentially valid method to enhance surgical field visualization, improve lymph node retrieval, and decrease anastomotic leak. Small noncomparative prospective trials have shown that intraoperative fluorescence imaging is a safe and feasible method to assess anastomotic perfusion and that its use may impact anastomotic leak rates. However, larger prospective and randomized studies are required to validate its role and impact in colorectal surgery. The purpose of this article is to review the current status of the use of immunofluorescence in colon and rectal surgery, as well as new applications in robotic colon and rectal resections.

A Cost-Effectiveness Evaluation of Surgical Approaches to Proctectomy.

BACKGROUND: Robotic surgery is increasingly used for proctectomy, but the cost-effectiveness of this approach is uncertain. Robotic surgery is considered more expensive than open or laparoscopic approaches, but in certain situations has been demonstrated to be cost-effective. We examined the cost-effectiveness of open, laparoscopic, and robotic approaches to proctectomy from societal and healthcare system perspectives. METHODS: We developed a decision-analytic model to evaluate one-year costs and outcomes of robotic, laparoscopic, and open proctectomy based on data from the available literature. The robustness of our results was tested with one-way and multi-way sensitivity analyses. RESULTS: Open proctectomy had increased cost and lower quality of life (QOL) compared with laparoscopy and robotic approaches. In the societal perspective, robotic proctectomy costs $497/case more than laparoscopy, with minimal QOL improvements, resulting in an incremental cost-effectiveness ratio (ICER) of $751,056 per quality-adjusted life year (QALY). In the healthcare sector perspective, robotic proctectomy resulted in $983/case more and an ICER of $1,485,139/QALY. One-way sensitivity analyses demonstrated factors influencing cost-effectiveness primarily pertained to the operative cost and the postoperative length of stay (LOS). In a probabilistic sensitivity analysis, the cost-effective approach to proctectomy was laparoscopic in 42% of cases, robotic in 39%, and open in 19% at a willingness-to-pay (WTP) of $100,000/QALY. CONCLUSIONS: Laparoscopic and robotic proctectomy cost less and have higher QALY than the open approach. Based on current data, laparoscopy is the most cost-effective approach. Robotic proctectomy can be cost-effective if modest differences in costs or postoperative LOS can be achieved.

Cost-effectiveness Evaluation of Laparoscopic Versus Robotic Minimally Invasive Colectomy.

OBJECTIVE: Evaluate the cost-effectiveness of open, laparoscopic, and robotic colectomy. BACKGROUND: The use of robotic-assisted colon surgery is increasing. Robotic technology is more expensive and whether a robotically assisted approach is cost-effective remains to be determined. METHODS: A decision-analytic model was constructed to evaluate the 1-year costs and quality-adjusted time between robotic, laparoscopic, and open colectomy. Model inputs were derived from available literature for costs, quality of life (QOL), and outcomes. Results are presented as incremental cost-effectiveness ratios (ICERs), defined as incremental costs per quality-adjusted life year (QALY) gained. One-way and probabilistic sensitivity analyses were performed to test the effect of clinically reasonable variations in the inputs on our results. RESULTS: Open colectomy cost more and achieved lower QOL than robotic and laparoscopic approaches. From the societal perspective, robotic colectomy costs $745 more per case than laparoscopy, resulting in an ICER of $2,322,715/QALY because of minimal differences in QOL. From the healthcare sector perspective, robotics cost $1339 more per case with an ICER of $4,174,849/QALY. In both models, laparoscopic colectomy was more frequently cost-effective across a wide range of willingness-to-pay thresholds. Sensitivity analyses suggest robotic colectomy becomes cost-effective at $100,000/QALY if robotic disposable instrument costs decrease below $1341 per case, robotic operating room time falls below 172 minutes, or robotic hernia rate is less than 5%. CONCLUSIONS: Laparoscopic and robotic colectomy are more cost-effective than open resection. Robotics can surpass laparoscopy in cost-effectiveness by achieving certain thresholds in QOL, instrument costs, and postoperative outcomes. With increased use of robotic technology in colorectal surgery, there is a burden to demonstrate these benefits.

Impact of adjuvant chemotherapy on outcomes in appendiceal cancer.

BACKGROUND: The impact of using adjuvant chemotherapy following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with appendiceal adenocarcinoma is not known. The aim of this study was to assess the impact of adjuvant chemotherapy following complete cytoreduction in patients with appendiceal adenocarcinoma. METHODS: Retrospective medical record review of all patients with appendiceal adenocarcinoma treated at our institution between 2006 and 2015. Kaplan-Meier plots were used to summarize overall survival (OS) and relapse-free survival over time, and log-rank tests and Cox proportional hazards models were used to test for differences in survival between groups. RESULTS: A total of 103 patients with appendiceal adenocarcinoma received care at our institution during the study period. Complete cytoreduction (cytoreductive score 0-1) was achieved in 68 patients (66%). Of these 68 patients, 26 received adjuvant chemotherapy. The most common regimens were capecitabine (n = 11), capecitabine plus oxaliplatin (n = 7), and 5-FU plus oxaliplatin (n = 6). Tumor histopathology and grade, and the ability to achieve complete cytoreduction were significant predictors of overall survival. The median OS for non-low-grade and well-differentiated tumor patients who received adjuvant chemotherapy following complete cytoreduction was 9.03 years, compared to 2.88 years for patients who did not receive adjuvant chemotherapy (P = .02). Among low-grade and well-differentiated tumor patients who underwent complete cytoreduction, there was no statistically significant difference in OS between those who received adjuvant chemotherapy and those who did not. CONCLUSION: Adjuvant chemotherapy seems to have benefit in appendiceal cancer patients with non-low-grade or well-differentiated tumor type but not in low-grade or well-differentiated tumors.

Spectrum of Early Postoperative Multidetector Computed Tomography Findings Following Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy.

OBJECTIVE: To review and describe imaging findings on multidetector computed tomography in the early postoperative period after cytoreductive surgery with concomitant hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). METHODS: This was a retrospective review of consecutive patients undergoing early (≤60 days) postoperative abdominopelvic multidetector computed tomography scans after CRS + HIPEC from 2014 to 2018 at a single institution. Two radiologists separately assessed bowel wall thickening, bowel wall enhancement, bowel dilation, ascites, and pleural effusion(s) and identified any other significant finding(s). RESULTS: Thirty-two patients met the inclusion criteria. The majority of patients demonstrated bowel wall thickening (53%; n = 17) and ascites (72%; n = 23), whereas postoperative ileus (35%; n = 10), pleural effusion(s) (24%; n = 7), and bowel wall hyperenhancement (6%; n = 1) were less common. Significant findings included anastomotic leak/perforation (13%; n = 4), fistula (13%; n = 4), abscess (13%; n = 4), and bladder leak (6%; n = 2). CONCLUSIONS: Multidetector computed tomography is an excellent imaging modality to identify common postoperative findings as well as complications following CRS + HIPEC.