Incidence of Secondary Cancers After Neoadjuvant Therapy for Locally Advanced Rectal Cancer.

INTRODUCTION: Whether neoadjuvant chemoradiation for locally advanced rectal cancer (LARC) induces secondary cancers is controversial. This retrospective cohort study describes the incidence of secondary cancers in LARC patients. METHODS: We compared 364 LARC patients who received conventional (50.4 Gy) or short course neoadjuvant radiation (25 Gy x 5 fractions) followed by resection to 142 patients with surgically resected rectal cancer who did not receive radiation at a single institution from 2004 to 2018. Secondary cancer was defined as any nonmetastatic noncolorectal malignancy diagnosed via biopsy or definitive imaging criteria at least 6 mo after completion of neoadjuvant therapy or after resection in the comparison group. RESULTS: Among the neoadjuvant radiation group (364 patients, 40% female, age 61 ± 13 y), 32 patients developed 34 (9.3%) secondary cancers. Three cases involved a pelvic organ. Among the comparison group (142 patients, 39% female, age 64 ± 15 y), 15 patients (10.6%) developed a secondary cancer. Five cases involved pelvic organs. Secondary cancer incidence did not differ between groups. Latency period to secondary cancer diagnosis was 6.7 ± 4.3 y. Patients who received radiation underwent longer median follow-up (6.8 versus 4.5 y, P < 0.01) and were significantly less likely to develop a pelvic organ cancer (odds ratio 0.18; 95% confidence interval, 0.04-0.83; P = 0.02). No genetic mutations or cancer syndromes were identified among patients with secondary cancers. CONCLUSIONS: Neoadjuvant chemoradiation is not associated with increased secondary cancer risk in LARC patients and may have a local protective effect on pelvic organs, especially prostate. Ongoing follow-up is critical to continue risk assessment.

Fact or fiction? Does the position of the end-to-end (EEA) stapler spike matter for colorectal anastomoses using a double-stapled technique?

AIM: Surgeons often have strong opinions about how to perform colorectal anastomoses with little data to support variations in technique. The aim of this study was to determine if location of the end-to-end (EEA) stapler spike relative to the rectal transection line is associated with anastomotic integrity. METHOD: This study was a retrospective analysis of a quality collaborative database at a quaternary centre and regional hospitals. Patients with any left-sided colon resection with double-stapled anastomosis were included (December 2019 to August 2022). Our primary endpoint was a composite outcome including positive air insufflation test, incomplete anastomotic donut, or thin/eccentric donut. Our secondary endpoint was clinical leak. RESULTS: Overall, 633 patients were included and stratified by location of the stapler spike relative to the rectal transection line. Of note, 86 patients had an end-colon to anterior rectum ("reverse Baker") anastomosis with no crossing staple lines. The rates of the composite endpoint based on position of the stapler spike were 12.4% (anterior), 8.1% (through), 12.8% (posterior), 5.1% (corner), and 2.3% for the "reverse Baker" (p = 0.03). The overall rate of clinical leak was 3.8% and there were no differences between methods. In a multivariate analysis, the "reverse Baker" anastomosis was associated with decreased odds of poor anastomotic integrity when compared to anastomoses with crossing staple lines (OR 0.20, 95% CI: 0.05-0.87, p = 0.03). CONCLUSIONS: For anastomoses with crossing staple lines, the position of the stapler spike relative to the rectal staple line is not associated with differences in anastomotic integrity. In contrast, anastomoses with no crossing staple lines resulted in significantly lower rates of poor anastomotic integrity, but no difference in clinical leaks.

Development of a peripheral blood transcriptomic gene signature to predict bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common lung disease of extreme prematurity, yet mechanisms that associate with or identify neonates with increased susceptibility for BPD are largely unknown. Combining artificial intelligence with gene expression data is a novel approach that may assist in better understanding mechanisms underpinning chronic lung disease and in stratifying patients at greater risk for BPD. The objective of this study is to develop an early peripheral blood transcriptomic signature that can predict preterm neonates at risk for developing BPD. Secondary analysis of whole blood microarray data from 97 very low birth weight neonates on day of life 5 was performed. BPD was defined as positive pressure ventilation or oxygen requirement at 28 days of age. Participants were randomly assigned to a training (70%) and testing cohort (30%). Four gene-centric machine learning models were built, and their discriminatory abilities were compared with gestational age or birth weight. This study adheres to the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) statement. Neonates with BPD (n = 62 subjects) exhibited a lower median gestational age (26.0 wk vs. 30.0 wk, P < 0.01) and birth weight (800 g vs. 1,280 g, P < 0.01) compared with non-BPD neonates. From an initial pool (33,252 genes/patient), 4,523 genes exhibited a false discovery rate (FDR) <1%. The area under the receiver operating characteristic curve (AUC) for predicting BPD utilizing gestational age or birth weight was 87.8% and 87.2%, respectively. The machine learning models, using a combination of five genes, revealed AUCs ranging between 85.8% and 96.1%. Pathways integral to T cell development and differentiation were associated with BPD. A derived five-gene whole blood signature can accurately predict BPD in the first week of life.

Operative management of anastomotic leak after sigmoid colectomy for left-sided diverticular disease: Ileostomy creation may be as safe as colostomy creation.

AIM: The management of anastomotic leak after sigmoid colectomy for diverticular disease has not been well defined. Specifically, there is a lack of literature on optimal types of reoperations for leaks. The aim of this study was to describe and compare reoperative approaches and their postoperative outcomes. METHODS: We performed a retrospective cohort study using the NSQIP Colectomy Module (2012-2019) and single-institution chart review. Patients with diverticular disease who underwent elective sigmoid colectomy were included. Primary outcomes were anastomotic leak requiring reoperation and management of anastomotic leak. RESULTS: Of 37,471 patients who underwent sigmoid colectomy for diverticular disease, 1003 (2.7%) suffered an anastomotic leak, of whom 583 underwent reoperation. Of the 572 patients who were not initially diverted and underwent reoperation for leak, 302 (52.8%) were managed with stoma creation - 200 (35.0%) with colostomy and 102 (17.8%) with ileostomy. The remaining 47.2% underwent colectomy with reanastomosis, suturing of large bowel, and drainage. There were no differences in length of stay, readmission, or mortality between patients who underwent ileostomy or colostomy at reoperation (p > 0.05). Single-institution analysis demonstrated that 100% of patients with ileostomies underwent subsequent ileostomy closure, compared to 60% of patients with colostomies. CONCLUSIONS: In patients who suffer anastomotic leaks after sigmoid colectomy for diverticular disease and undergo reoperations, ileostomy at the time of reoperation appears to be safe, with comparable results to colostomy. Ileostomies were more frequently closed than colostomies. When faced with a colorectal anastomotic leak, ileostomy creation may be considered.

Fecal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) RNA Is Associated With Decreased Coronavirus Disease 2019 (COVID-19) Survival.

The clinical significance of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) RNA in stool remains uncertain. We found that extrapulmonary dissemination of infection to the gastrointestinal tract, assessed by the presence of SARS-CoV-2 RNA in stool, is associated with decreased coronavirus disease 2019 (COVID-19) survival. Measurement of SARS-CoV-2 RNA in stool may have utility for clinical risk assessment.

Large-scale provocation studies identify maladaptive responses to ubiquitous aeroallergens as a correlate of severe allergic rhinoconjunctivitis and asthma.

BACKGROUND: Allergic asthma (AA) and allergic rhinoconjunctivitis (ARC) are common comorbid environmentally triggered diseases. We hypothesized that severe AA/ARC reflects a maladaptive or unrestrained response to ubiquitous aeroallergens. METHODS: We performed provocation studies wherein six separate cohorts of persons (total n = 217) with ARC, with or without AA, were challenged once or more with fixed concentrations of seasonal or perennial aeroallergens in an aeroallergen challenge chamber (ACC). RESULTS: Aeroallergen challenges elicited fully or partially restrained vs. unrestrained evoked symptom responsiveness, corresponding to the resilient and adaptive vs. maladaptive AA/ARC phenotypes, respectively. The maladaptive phenotype was evoked more commonly during challenge with a non-endemic versus endemic seasonal aeroallergen. In an AA cohort, symptom responses evoked after house dust mite (HDM) challenges vs. recorded in the natural environment were more accurate and precise predictors of asthma severity and control, lung function (FEV1), and mechanistic correlates of maladaptation. Correlates included elevated levels of peripheral blood CD4+ and CD8+ T-cells, eosinophils, and T-cell activation, as well as gene expression proxies for ineffectual epithelial injury/repair responses. Evoked symptom severity after HDM challenge appeared to be more closely related to levels of CD4+ and CD8+ T-cells than eosinophils, neutrophils, or HDM-specific IgE. CONCLUSIONS: Provocation studies support the concept that resilience, adaptation, and maladaptation to environmental disease triggers calibrate AA/ARC severity. Despite the ubiquity of aeroallergens, in response to these disease triggers in controlled settings (ie, ACC), most atopic persons manifest the resilient or adaptive phenotype. Thus, ARC/AA disease progression may reflect the failure to preserve the resilient or adaptive phenotype. The triangulation of CD8+ T-cell activation, airway epithelial injury/repair processes and maladaptation in mediating AA disease severity needs more investigation.

Repetitive aeroallergen challenges elucidate maladaptive epithelial and inflammatory traits that underpin allergic airway diseases.

BACKGROUND: Signifying the 2-compartments/1-disease paradigm, allergic rhinoconjunctivitis (ARC) and asthma (AA) are prevalent, comorbid conditions triggered by environmental factors (eg, house dust mites [HDMs]). However, despite the ubiquity of triggers, progression to severe ARC/AA is infrequent, suggesting either resilience or adaptation. OBJECTIVE: We sought to determine whether ARC/AA severity relates to maladaptive responses to disease triggers. METHODS: Adults with HDM-associated ARC were challenged repetitively with HDMs in an aeroallergen challenge chamber. Mechanistic traits associated with disease severity were identified. RESULTS: HDM challenges evoked maladaptive (persistently higher ARC symptoms), adaptive (progressive symptom reduction), and resilient (resistance to symptom induction) phenotypes. Symptom severity in the natural environment was an imprecise correlate of the phenotypes. Nasal airway traits, defined by low inflammation-effectual epithelial integrity, moderate inflammation-effectual epithelial integrity, and higher inflammation-ineffectual epithelial integrity, were hallmarks of the resilient, adaptive, and maladaptive evoked phenotypes, respectively. Highlighting a crosstalk mechanism, peripheral blood inflammatory tone calibrated these traits: ineffectual epithelial integrity associated with CD8+ T cells, whereas airway inflammation associated with both CD8+ T cells and eosinophils. Hallmark peripheral blood maladaptive traits were increased natural killer and CD8+ T cells, lower CD4+ mucosal-associated invariant T cells, and deficiencies along the TLR-IRF-IFN antiviral pathway. Maladaptive traits tracking HDM-associated ARC also contributed to AA risk and severity models. CONCLUSIONS: Repetitive challenges with HDMs revealed that maladaptation to disease triggers may underpin ARC/AA disease severity. A combinatorial therapeutic approach may involve reversal of loss-of-beneficial-function traits (ineffectual epithelial integrity, TLR-IRF-IFN deficiencies), mitigation of gain-of-adverse-function traits (inflammation), and blocking of a detrimental crosstalk between the peripheral blood and airway compartments.

Immunologic resilience and COVID-19 survival advantage.

BACKGROUND: The risk of severe coronavirus disease 2019 (COVID-19) varies significantly among persons of similar age and is higher in males. Age-independent, sex-biased differences in susceptibility to severe COVID-19 may be ascribable to deficits in a sexually dimorphic protective attribute that we termed immunologic resilience (IR). OBJECTIVE: We sought to examine whether deficits in IR that antedate or are induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection independently predict COVID-19 mortality. METHODS: IR levels were quantified with 2 novel metrics: immune health grades (IHG-I [best] to IHG-IV) to gauge CD8+ and CD4+ T-cell count equilibrium, and blood gene expression signatures. IR metrics were examined in a prospective COVID-19 cohort (n = 522); primary outcome was 30-day mortality. Associations of IR metrics with outcomes in non-COVID-19 cohorts (n = 13,461) provided the framework for linking pre-COVID-19 IR status to IR during COVID-19, as well as to COVID-19 outcomes. RESULTS: IHG-I, tracking high-grade equilibrium between CD8+ and CD4+ T-cell counts, was the most common grade (73%) among healthy adults, particularly in females. SARS-CoV-2 infection was associated with underrepresentation of IHG-I (21%) versus overrepresentation (77%) of IHG-II or IHG-IV, especially in males versus females (P < .01). Presentation with IHG-I was associated with 88% lower mortality, after controlling for age and sex; reduced risk of hospitalization and respiratory failure; lower plasma IL-6 levels; rapid clearance of nasopharyngeal SARS-CoV-2 burden; and gene expression signatures correlating with survival that signify immunocompetence and controlled inflammation. In non-COVID-19 cohorts, IR-preserving metrics were associated with resistance to progressive influenza or HIV infection, as well as lower 9-year mortality in the Framingham Heart Study, especially in females. CONCLUSIONS: Preservation of immunocompetence with controlled inflammation during antigenic challenges is a hallmark of IR and associates with longevity and AIDS resistance. Independent of age, a male-biased proclivity to degrade IR before and/or during SARS-CoV-2 infection predisposes to severe COVID-19.

Minimally Invasive and Robotic Surgery for Ulcerative Colitis.

Significant advancements have been made over the last 30 years in the use of minimally invasive techniques for curative and restorative operations in patients with ulcerative colitis (UC). Numerous studies have demonstrated the safety and feasibility of laparoscopic and robotic approaches to subtotal colectomy (including in the urgent setting), total proctocolectomy, completion proctectomy, and pelvic pouch creation. Data show equivalent or improved short-term postoperative outcomes with minimally invasive techniques compared to open surgery, and equivalent or improved long-term bowel function, sexual function, and fertility. Overall, while minimally invasive techniques are safe and feasible for properly selected UC patients, surgeons must remember to abide by the principles of high-quality proctectomy and pouch creation and convert to open if necessary.

Revision of Pancreatic Neck Margins Based on Intraoperative Frozen Section Analysis Is Associated With Improved Survival in Patients Undergoing Pancreatectomy for Ductal Adenocarcinoma.

OBJECTIVE: To test the hypothesis that complete, tumor-free resection at the pancreatic neck, achieved either en-bloc or non-en-bloc (ie, revision based on intraoperative frozen section [FS] analysis), is associated with improved survival as compared with incomplete resection (IR) in pancreatic ductal adenocarcinoma. SUMMARY BACKGROUND DATA: Given the likely systemic nature of pancreatic ductal adenocarcinoma, the oncologic benefit of achieving a histologically complete local resection, particularly through revision of a positive intraoperative FS at the pancreatic neck, remains controversial. METHODS: Clinicopathologic and treatment data were reviewed for 986 consecutive patients with ductal adenocarcinoma at the head, neck, or uncinate process of the pancreas who underwent open pancreatectomy as well as intraoperative FS analysis between 1998 and 2012 at Massachusetts General Hospital and between 1998 and 2013 at the University of Verona. Overall survival (OS) and perioperative morbidity and mortality were compared across 3 groups: complete resection achieved en-bloc (CR-EB), complete resection achieved non-en-bloc (CR-NEB), and IR. RESULTS: The CR-EB cohort comprised 749 (76%) patients, CR-NEB 159 patients (16%), and IR 78 patients (8%). Other than a higher incidence of vascular resection among CR-NEB and IR patients, no demographic, pathologic (eg, tumor grade, lymph node positivity, superior mesenteric artery involvement), or treatment factors (eg, neoadjuvant and adjuvant therapy use) differed between the groups. Median OS was significantly higher in patients with CR-EB (28 mo, P = 0.01) and CR-NEB resections (24 mo, P = 0.02) as compared with patients with IR resections (19 mo). After adjusting for clinicopathologic and treatment characteristics, CR-EB and CR-NEB margin status were found to be independent predictors of improved OS (relative to IR, CR-EB hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.49-0.86; CR-NEB HR 0.69, 95% CI 0.50-0.96). There were no intergroup differences in perioperative morbidity and mortality, including rates of pancreatic fistula. CONCLUSIONS: For patients with ductal adenocarcinoma at the head, neck, or uncinate process of the pancreas undergoing pancreatectomy, complete tumor extirpation via either en-bloc or non-en-bloc complete resection based on FS analysis is associated with improved OS, without an associated increased perioperative morbidity or mortality.

Early antimicrobial prophylaxis in autologous stem cell transplant recipients: Conventional versus an absolute neutrophil count-driven approach.

BACKGROUND: Autologous hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of developing life-threatening infections. There is discordance in published recommendations for timing of pre- and post-transplant antimicrobial prophylaxis in this patient population, and these recommendations are unsubstantiated by any published comparative analyses. METHODS: An observational, pre- and post-intervention study of consecutive autologous HSCT recipients was conducted over a 2-year period. In the pre-intervention cohort, antimicrobial prophylaxis was initiated on the day prior to transplant. In the post-intervention cohort, antimicrobials were initiated once absolute neutrophil count (ANC) reached ≤500 cells/mm3 . The primary outcome assessed was frequency of febrile occurrences. Secondary outcomes included total days of prophylaxis, positive blood cultures, all-cause mortality, Clostridioides difficile infection rates, and length of stay. RESULTS: A total of 208 patients were included in the final analysis, with 105 and 103 patients in the pre- and post-intervention cohorts, respectively. The majority of patients included were male. Lower rates of fever occurrences were observed in the post-intervention cohort (83% pre- vs. 69% post-intervention; p = 0.019). A significant reduction in the mean antibacterial days per patient was identified (9.7 vs. 4.6 days; p < 0.001). Other than lower rates of febrile neutropenia in the post-intervention cohort, no differences were identified in secondary outcomes. In multivariable analyses, ANC-driven prophylaxis was independently associated with decreased febrile events. CONCLUSIONS: Delaying prophylaxis until severe neutropenia was not associated with increased febrile events or other secondary clinical outcomes evaluated. This approach is associated with a significant reduction in antimicrobial exposure.

Recurrence of Clostridium Difficile and Cytomegalovirus Infections in Patients with Ulcerative Colitis Who Undergo Ileal Pouch-Anal Anastomosis.

BACKGROUND: Patients with ulcerative colitis (UC) are at increased risk for infections such as Clostridium difficile and cytomegalovirus (CMV) colitis due to chronic immunosuppression. These patients often undergo multiple surgeries putting them at risk for recurrence of the infection. However, rates of recurrence in this setting and outcomes are not well understood. AIM: The aim of this study is to determine rates of recurrence of C difficile and CMV infection in patients undergoing multistage UC surgeries and effects of antibiotic prophylaxis on outcomes. METHODS: All patients with UC who underwent IPAA between 2001 and 2017 (at two tertiary referral centers were identified. History of C. difficile or CMV colitis prior to any surgery and recurrence after IPAA was noted RESULTS: A total of 633 patients with UC who underwent IPAA were identified, of whom 8.1% patients had C. difficile and 2.7% had CMV infections. 9.8% of C. difficile and 5.9% of CMV patients recurred after IPAA. Rates of abdominal sepsis (14.7% vs. 12.7%), 90-day mortality (0% vs. 0.4%), pouchitis (36.8% vs. 45.0%), or return to stoma (7.4% vs. 5.4%) were similar between patients who did or did not have infections. In patients with C. difficile infection prior to first surgery, none of the patients who received prophylaxis had recurrent infection. CONCLUSIONS: Rates of C. difficile and CMV infections remain high in patients undergoing surgery for UC, with substantial minority developing recurrent infection during subsequent surgical procedures. Antibiotic prophylaxis in patients with a history of C difficile may reduce the rate of recurrent infection.

Nanopore Sequencing of the Fungal Intergenic Spacer Sequence as a Potential Rapid Diagnostic Assay.

Fungal infections are being caused by a broadening spectrum of fungi, yet in many cases, identification to the species level is required for proper antifungal selection. We investigated the fungal intergenic spacer (IGS) sequence in combination with nanopore sequencing for fungal identification. We sequenced isolates from two Cryptococcus species complexes, C. gattii and C. neoformans, which are the main pathogenic members of this genus, using the Oxford Nanopore Technologies MinION device and Sanger sequencing. There is enough variation within the two complexes to argue for further resolution into separate species, which we wanted to see if nanopore sequencing could detect. Using the R9.4.1 flow cell, IGS sequence identities averaged 99.57% compared to Sanger sequences of the same region. When the newer R10.3 flow cell was used, accuracy increased to 99.83% identity compared to the same Sanger sequences. Nanopore sequencing errors were predominantly in regions of homopolymers, with G homopolymers displaying the largest number of errors and C homopolymers displaying the least. Phylogenetic analysis of the nanopore- and Sanger-derived sequences resulted in indistinguishable trees. Comparison of average percent identities between the C. gattii and C. neoformans species complexes resulted in only a 74 to 77% identity between the two complexes. Sequencing using the nanopore platform could be completed in less than an hour, and samples could be multiplexed in groups as large as 24 sequences in a single run. These results suggest that sequencing the IGS region using nanopore sequencing could be a potential new molecular diagnostic strategy.

Bowel Function After J-Pouch May Be More Complex Than Previously Appreciated: A Comprehensive Analysis to Highlight Existing Knowledge Gaps.

BACKGROUND: Functional outcomes following J-pouch for ulcerative colitis have been studied, but lack standardization in which symptoms are reported. Furthermore, the selection of symptoms studied has not been patient centered. OBJECTIVE: This study aimed to utilize a validated bowel function survey to determine which symptoms are present after J-pouch creation, and whether patients display a functional profile similar to low anterior resection syndrome. DESIGN: This study is a retrospective analysis of a prospectively maintained single-center database. SETTINGS: This study was conducted at the colorectal surgery center of a tertiary care academic hospital PATIENTS:: Included were 159 patients with J-pouch, ≥6 months after ileostomy reversal. MAIN OUTCOME MEASURES: The primary outcomes were individual answers to the Memorial Sloan Kettering Cancer Center Bowel Function Instrument. The original Bowel Function Instrument validation cohort was used as an historical comparison (n = 127). RESULTS: The mean total Bowel Function Instrument score for the J-pouch cohort was 59.9 ± 9.7 compared with a reported average score of 63.7 ± 11.6 for patients with low anterior resection in the validation cohort (p < 0.001), indicating worse bowel function in patients with J-pouch. When evaluating the Bowel Function Instrument subscales, patients with J-pouch reported frequency subscale scores of 18.2 ± 3.8, diet scores of 12.2 ± 3.8, and urgency scores of 15.9 ± 3.7, compared with 21.7 ± 4.5 (p < 0.001), 14.1 ± 3.7 (p < 0.001), and 15.0 ± 3.9 (p = 0.04) for patients undergoing rectal resection. Furthermore, 90.4% of patients with J-pouch state that they are sometimes, rarely, or never able to wait 15 minutes to get to the toilet. In addition, 56.4% of patients report having another bowel movement within 15 minutes of the last bowel movement, sometimes, always, or most of the time, and 50.6% of patients say that they sometimes, rarely, or never feel like their bowels have been totally emptied after a bowel movement. LIMITATIONS: This study is limited because it took place at a single center and the Bowel Function Instrument was only validated for patients undergoing rectal resection. CONCLUSIONS: Patients that undergo J-pouch surgery exhibit a constellation of bowel function symptoms that is more complex than fecal incontinence and frequency alone, despite the focus on these functional outcomes in the literature. See Video Abstract at http://links.lww.com/DCR/B73. LA FUNCIÓN INTESTINAL DESPUÉS DE LA BOLSA EN J PUEDE SER MÁS COMPLEJA DE LO QUE SE APRECIABA ANTERIORMENTE: UN ANÁLISIS EXHAUSTIVO PARA RESALTAR LAS BRECHAS DE CONOCIMIENTO EXISTENTES: Se han estudiado los resultados funcionales después de la bolsa en J para la colitis ulcerosa, pero carecen de estandarización en la que se informen los síntomas. Además, la selección de los síntomas estudiados no se ha centrado en el paciente.Utilizar una encuesta validada de la función intestinal para determinar qué síntomas están presentes después de la bolsa en J y si los pacientes muestran un perfil funcional similar al síndrome de resección anterior baja.Análisis retrospectivo de una base de datos de un solo centro mantenida prospectivamente.Centro de cirugía colorrectal de un hospital académico de atención terciaria.159 pacientes con bolsa en J, ≥6 meses después de la reversión de ileostomía.Instrumento para la función intestinal del "Memorial Sloan Kettering Cancer Center"; cohorte de validación original de instrumentos de función intestinal utilizada como comparación histórica (n = 127).La puntuación media total del instrumento de función intestinal para la cohorte de bolsa J fue 59.9 ± 9.7 en comparación con un puntaje promedio reportado de 63.7 ± 11.6 para pacientes con resección anterior baja en la cohorte de validación (p < 0.001), lo que indica peor función intestinal en pacientes con bolsa en J. Al evaluar las subescalas del instrumento de función intestinal, los pacientes con bolsa en J informaron puntuaciones de subescala de frecuencia de 18.2 ± 3.8, puntuaciones de dieta de 12.2 ± 3.8 y puntuaciones de urgencia de 15.9 ± 3.7, en comparación con 21.7 ± 4.5 (p < 0.001), 14.1 ± 3.7 (p < 0.001) y 15.0 ± 3.9 (p = 0.04) respectivamente para pacientes con resección rectal. Además, el 90.4% de los pacientes con bolsa en J afirman que a veces, rara vez o nunca pueden esperar 15 minutos para llegar al baño. Además, el 56.4% de los pacientes reportan haber tenido otra evacuación intestinal dentro de los 15 minutos posteriores a la última evacuación intestinal, a veces, siempre o la mayor parte del tiempo, y el 50.6% de los pacientes dicen que a veces, rara vez o nunca sienten que sus intestinos han sido vaciados totalmente después de una evacuación intestinal.Estudio en un solo centro, instrumento de función intestinal validado solo para pacientes con resección rectalLos pacientes que se someten a una bolsa en J exhiben una constelación de síntomas de la función intestinal que es más compleja que la incontinencia fecal y la frecuencia sola, a pesar del enfoque en estos resultados funcionales en la literatura.Consulte Video Resumen en http://links.lww.com/DCR/B73. (Traducción-Dr. Gonzalo Federico Hagerman).

Superior pathologic and clinical outcomes after minimally invasive rectal cancer resection, compared to open resection.

BACKGROUND: While the ACOSOG and ALaCaRT trials found that laparoscopic resections for rectal cancer failed to demonstrate non-inferiority of pathologic outcomes when compared with open resections, the COLOR II and COREAN studies demonstrated non-inferiority of clinical outcomes, leading to uncertainty regarding the value of minimally invasive (MIS) techniques in rectal cancer surgery. We analyzed differences in pathologic and clinical outcomes between open versus MIS resections for rectal cancer. METHODS: We identified patients who underwent resection for stage II or III rectal adenocarcinoma from the National Cancer Database (2010-2015). Surgical approach was categorized as open or MIS (laparoscopic or robotic). Logistic regression and Cox proportional hazard analysis were used to assess differences in outcomes and survival. Analysis was performed in an intention-to-treat fashion. RESULTS: A total of 31,190 patients who underwent rectal adenocarcinoma resection were identified, of whom 52.8% underwent open resection and 47.2% underwent MIS resection (31.0% laparoscopic, 16.2% robotic). After adjustment for patient, tumor, and institutional characteristics, MIS approaches were associated with significantly decreased risk of positive circumferential resection margins (OR 0.82, 95% CI 0.72-0.94), increased likelihood of harvesting ≥ 12 lymph nodes (OR 1.12, 95% CI 1.04-1.21), shorter length of stay (OR 0.57, 95% CI 0.53-0.62), and improved overall survival (HR 0.90, 95% CI 0.83-0.98). CONCLUSIONS: MIS approaches to rectal cancer resection were associated with improved pathologic and clinical outcomes when compared to the open approach. In this nationwide, facility-based sample of cancer cases in the United States, our data suggest superiority of MIS techniques for rectal cancer treatment.

Facility Type is Associated with Margin Status and Overall Survival of Patients with Resected Intrahepatic Cholangiocarcinoma.

BACKGROUND: Many studies have demonstrated associations between surgical resections at academic centers and improved outcomes, particularly for complex operations. However, few studies have examined this relationship in intrahepatic cholangiocarcinoma (ICC). The hypothesis of this study was that facility type is associated with improved postoperative outcomes and survival for patients with ICC who undergo resection. METHODS: Patients with stages 1 to 3 ICC who underwent hepatectomy were identified using the National Cancer Database (NCDB) (2004-2014). Facilities were categorized as academic or community centers per Commission on Cancer designations. High-volume hospitals were those that performed 11 or more hepatectomies per year. Multilevel logistic mixed-effects models to identify predictors of outcomes and parametric survival-time models were used to determine overall survival (OS). RESULTS: The study identified 2256 patients. Of these patients, 423 (18.8%) were treated at community centers, and 1833 (81.3%) were treated at academic centers. Nearly all high-volume centers were academic facilities (98.5% academic vs. 1.5% community centers), whereas low-volume centers were mixed (65.5% academic vs. 34.5% community centers) (p < 0.001). Surgery performed at an academic center was an independent predictor of decreased positive margins (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.51-0.98; p = 0.04), a lower 90-day mortality rate (OR, 0.62; 95% CI, 0.39-0.97; p = 0.03), and improved OS (hazard ratio [HR], 0.78; 95% CI, 0.63-0.96; p = 0.02). Facility hepatectomy volume was not independently associated with any short- or long-term outcomes. CONCLUSIONS: Treatment at an academic center is associated with fewer positive resection margins, a decreased 90-day mortality rate, and improved OS for patients who undergo ICC resection. Facility surgical volume was not shown to be significantly associated with any postoperative outcomes after adjustment for patient and disease characteristics.

High Risk of Proximal and Local Neoplasms in 2206 Patients With Anogenital Extramammary Paget's Disease.

BACKGROUND: Extramammary Paget's disease is an uncommon intraepidermal adenocarcinoma with poorly defined clinical implications. OBJECTIVE: The purpose of this research was to estimate the risk of second primary neoplasms in patients with extramammary Paget's disease. DESIGN: This was a retrospective analysis of the Surveillance, Epidemiology, and End Results Registry (1973-2014). SETTINGS: The study included population-based cancer registries from the United States. PATIENTS: Patients who were diagnosed with anogenital Paget's disease were included. MAIN OUTCOME MEASURES: Risk of second primary development was measured. RESULTS: We identified 108 patients with anal Paget's disease, 421 patients with male genital (scrotum or penis) Paget's, and 1677 patients with female genital (vagina or vulva) Paget's. Median follow-up time was 5.9 years. The risk of developing colorectal adenocarcinoma was 18.5% for patients with anal Paget's disease. Eighty percent of colorectal adenocarcinoma diagnoses were synchronous (within 2 mo) to anal Paget's diagnoses, whereas metachronous tumors occurred at a median time of 2.4 years. Of patients with anal Paget's disease, 8.3% developed an anal adenocarcinoma or nonsmall cell cancer. In male patients with genital Paget's, the risk of proximal genitourinary malignancy was 9.7%, scrotal or testicular adenocarcinoma was 0.4%, and penile or scrotal squamous carcinoma was 1.7%. In female patients with genital Paget's, the risk of proximal genitourinary malignancy was 3.0%, vaginal or vulvar adenocarcinoma was 1.4%, and vaginal or vulvar squamous neoplasm was 1.0%. Five-year overall survival was 59.7%, 73.5%, and 80.7% in patients with anal, male genital, and female genital Paget's (p < 0.001). LIMITATIONS: The registry did not record surveillance schedule, provider specialty, or nonprocedural therapies for extramammary Paget's disease. CONCLUSIONS: In the largest published cohort of patients with extramammary Paget's disease, patients with anal Paget's had a much higher risk of both proximal and local neoplasms as compared with patients with genital Paget's. Patients with anal Paget's also experienced worse survival as compared with those with purely genital Paget's. See Video Abstract at http://links.lww.com/DCR/B20. ALTO RIESGO DE NEOPLASIAS PROXIMALES Y LOCALES EN 2206 PACIENTES CON ENFERMEDAD DE PAGET EXTRAMAMARIA ANOGENITAL:: La enfermedad de Paget extramamaria es un adenocarcinoma intraepidérmico poco frecuente con implicaciones clínicas poco definidas.Estimar el riesgo de segundas neoplasias primarias en pacientes con enfermedad de Paget extramamaria.Análisis retrospectivo del Registro de Vigilancia, Epidemiología y Resultados Finales (1973-2014).Registros de base poblacional en cáncer de los Estados Unidos.Pacientes que fueron diagnosticados con enfermedad de Paget anogenital.Riesgo de desarrollo un cáncer primario adicional.Se identificaron 108 pacientes con Paget anal, 421 pacientes con Paget genital masculino (escroto o pene) y 1677 pacientes con Paget genital femenino (vagina o vulva). Tiempo mediano de seguimiento fue de 5,9 años. El riesgo de desarrollar adenocarcinoma colorrectal fue del 18,5% para los pacientes con Paget anal. El ochenta por ciento de los diagnósticos de adenocarcinoma colorrectal fueron sincrónicos (dentro de los 2 meses) a los diagnósticos de Paget anal, mientras que los tumores metacrónicos ocurrieron en un tiempo promedio de 2,4 años. De los pacientes con Paget anal, el 8.3% desarrolló un adenocarcinoma anal o cáncer de células no pequeñas. En los pacientes masculinos con Paget genital, el riesgo de malignidad genitourinaria proximal fue del 9,7%, el adenocarcinoma escrotal o testicular fue del 0,4% y el carcinoma escamoso del pene o escroto fue del 1,7%. En pacientes femeninas con Paget genital, el riesgo de malignidad genitourinaria proximal fue de 3.0%, el adenocarcinoma vaginal o vulvar fue de 1.4% y la neoplasia escamosa vaginal o vulvar fue de 1.0%. La supervivencia general a cinco años fue del 59.7%, 73.5% y 80.7% en pacientes con anal, genital masculino y genital femenino, respectivamente (p <0.001).El registro no señalo el cronograma de vigilancia, la especialidad del proveedor o las terapias sin procedimiento para la enfermedad de Paget extramamaria.En la cohorte más grande publicada de pacientes con enfermedad de Paget extramamaria, los pacientes con Paget anal demostraron un riesgo mucho mayor de neoplasias proximales y locales en comparación con los pacientes con Paget genital. Los pacientes con Paget anal además demostraron una peor supervivencia en comparación con aquellos con Paget aislada genital. Vea el Resumen del Video en http://links.lww.com/DCR/B20.

Comparable perioperative outcomes, long-term outcomes, and quality of life in a retrospective analysis of ulcerative colitis patients following 2-stage versus 3-stage proctocolectomy with ileal pouch-anal anastomosis.

PURPOSE: Many surgeons assume 3-stage ileal pouch-anal anastomosis (IPAA) is safer than 2-stage IPAA in patients with active ulcerative colitis (UC), although recent data suggest outcomes are comparable. This study aimed to compare perioperative complications, late complications, and functional outcomes after 2- versus 3-stage IPAA in patients with active UC. METHODS: A retrospective review was conducted of patients who underwent 2- or 3-stage IPAA for active UC from 2000 to 2015 in a high-volume institution. Patients completed quality-of-life surveys 6 months following ileostomy reversal. Perioperative and late complications were recorded. Outcomes were compared with the Fisher exact test, and multivariable logistic regression was used to adjust for potential confounders. RESULTS: We identified 212 patients who underwent 2- or 3-stage IPAA for active UC, of whom 157 patients (74.1%) underwent 2-stage procedures and 55 (25.9%) underwent 3-stage procedures. More patients undergoing 2-stage procedures were taking immunomodulators preoperatively (46.3% vs. 23.1%, p = 0.01), but there was no difference in use of steroids (p = 0.09) or biologic agents (p = 0.85). Three-stage procedures were more likely to be urgent (78.6% vs. 30.2%, p < 0.001). There were no differences in perioperative complications (p = 0.50), anastomotic leak (p = 0.94), pouchitis (p = 0.45), pouch failure (p = 0.46), perceived quality of life (p = 0.68), number of bowel movements per day (p = 0.27), or sexual satisfaction (p = 0.21) between the 2- and 3-stage groups. CONCLUSIONS: Patients undergoing 2-stage compared to 3-stage IPAA for active ulcerative colitis have comparable outcomes and quality of life following ileostomy reversal. Two-stage IPAA appears to be safe and appropriate, even in high-risk patients.

Applying Enhanced Recovery Pathways to Unique Patient Populations.

Enhanced Recovery after Surgery (ERAS) pathways have become popular in colorectal surgery due to their associated decrease in length of stay (LOS), complications, and readmission rate. However, it is unclear if these pathways are safe, feasible, or effective in unique patient populations such as elderly patients, urgent/emergent surgeries, patients with specific comorbidities, inflammatory bowel disease, or pediatric patients. Enhanced recovery pathways appear safe in elderly patients, associated with decreased complications, though with slightly lower rates of adherence and increased LOS and readmission rates. Modified ERAS pathways have been applied to urgent and emergent surgeries, resulting in decreased morbidity and LOS. There have been no studies that performed subgroup analyses of ERAS pathways in patients with specific comorbidities. Studies investigating patients with inflammatory bowel disease on enhanced recovery pathways are extremely limited, but suggest that they are safe and feasible. Data on ERAS pathways in pediatric patients are still emerging. Therefore, though data are sparse, enhanced recovery pathways appear to be safe in unique patient populations, with similar efficacy in decreasing LOS and complications. There is an urgent need for more studies investigating these specific patient groups to aid perioperative decision making by colorectal surgeons.