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1.
Clin Colon Rectal Surg ; 37(3): 185-190, 2024 May.
Article in English | MEDLINE | ID: mdl-38606047

ABSTRACT

Desmoid disease, though technically a benign condition, is nevertheless a leading cause of morbidity and mortality in patients with familial adenomatous polyposis (FAP). Desmoid disease impacts approximately 30% of FAP patients, with several known risk factors. It runs the gamut in terms of severity-ranging from small, slow-growing asymptomatic lesions to large, focally destructive, life-threatening masses. Desmoids usually occur following surgery, and several patient risk factors have been established, including female sex, family history of desmoid disease, 3' APC mutation, and extraintestinal manifestations of FAP. Desmoid disease-directed therapy is individualized and impacted by desmoid stage, severity, postsurgical anatomy, and consequences of disease. Medical therapy consists of options in multiple classes of drugs: nonsteroidal anti-inflammatory drugs, hormonal therapy, tyrosine kinase inhibitors, and cytotoxic agents. Surgical excision is sometimes an option, but can be limited by common location of disease at the root of the small bowel mesentery. Palliative surgical treatments are often considered in management of desmoid disease. Intestinal transplantation for severe desmoid disease is an emerging and promising option, though long-term data on efficacy and survival is limited.

2.
Inflamm Bowel Dis ; 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38546722

ABSTRACT

BACKGROUND: Ileal pouch-anal anastomosis is a technically demanding procedure with many potential complications. Rediversion with an ileostomy is often the first step in pouch salvage; however, it may not be clear if an individual patient will undergo subsequent pouch salvage surgery. We aimed to describe the indications and short- and long-term outcomes of rediversion in our pouch registry. METHODS: We queried our institutional pouch registry for patients who underwent index 2- or 3-stage IPAA and subsequent rediversion at our institution between 1985 and 2022. Pouches constructed elsewhere, rediverted elsewhere, or those patients who underwent pouch salvage/excision without prior rediversion were excluded. Patients were selected for pouch salvage according to the surgeon's discretion. RESULTS: Overall, 177 patients (3.4% of 5207 index pouches) were rediverted. At index pouch, median patient age was 32 years and 50.8% were women. Diagnoses included ulcerative colitis (86.4%), indeterminate colitis (6.2%), familial adenomatous polyposis (4.0%), and others (3.4%). Median time from prior ileostomy closure to rediversion was 7.2 years. Indications for rediversion were inflammatory in 98 (55.4%) and noninflammatory in 79 (44.6%) patients. After rediversion, 52% underwent pouch salvage, 30% had no further surgery, and 18.1% underwent pouch excision. The 5-year pouch survival rates for inflammatory and noninflammatory indications were 71.5% and 94.5%, respectively (P = .02). CONCLUSION: Rediversion of ileoanal pouches is a safe initial strategy to manage failing pouches and is a useful first step in pouch salvage in many patients. Subsequent salvage surgery for noninflammatory indications had a significantly higher pouch salvage rate than those rediverted for inflammatory complications.


Rediversion with an ileostomy was a safe, useful first step in pouch salvage, and subsequent salvage surgery for noninflammatory indications had a significantly higher pouch salvage rate than those rediverted for inflammatory complications.

3.
ANZ J Surg ; 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38426390

ABSTRACT

We demonstrate the technical details of laparoscopic-assisted endoscopic 'clean sweep' for small bowel polyp clearance in Peutz Jeghers Syndrome. A 'clean sweep' reduces the risk for future recurrences but was previously performed with an open technique. A minimally invasive approach is safe, reduces bowel trauma and has good postoperative outcomes.

4.
Dis Colon Rectum ; 67(3): 427-434, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38064246

ABSTRACT

BACKGROUND: Prophylactic surgery for familial adenomatous polyposis has evolved over several decades. Restorative proctocolectomy with IPAA provides an alternative to total abdominal colectomy with ileorectal anastomosis. We have previously shown that the rate of proctectomy and rectal cancer after total abdominal colectomy with ileorectal anastomosis in the "pre-pouch era" was 32% and 13%, respectively. OBJECTIVE: To determine the rate of proctectomy and rectal cancer among familial adenomatous polyposis patients and relative rectal sparing (fewer than 20 rectal polyps) selected for total abdominal colectomy with ileorectal anastomosis in the modern era. DESIGN: Retrospective cohort study. SETTING: Single tertiary care institution with a hereditary colorectal cancer registry. PATIENTS: Patients with familial adenomatous polyposis who underwent total abdominal colectomy with ileorectal anastomosis between 1993 and 2020. MAIN OUTCOME MEASURES: Incidence of proctectomy for any indication and rectal cancer. RESULTS: A total of 197 patients with a median age of 24 years (range, 10-67) were included. The median follow-up after total abdominal colectomy with ileorectal anastomosis was 13 years (interquartile range, 6-17). Sixteen patients (8%) underwent proctectomy. Indications included rectal cancer in 6 patients (3%; 2 stage I and 4 stage III), polyps with high-grade dysplasia in 4 (2%), progressive polyp burden in 3 (1.5%), defecatory dysfunction in 2 (1%), and anastomotic leak in 1 (0.5%). Among 30 patients (18%) with 20 or more rectal polyps at the time of total abdominal colectomy with ileorectal anastomosis, 8 patients (26%) underwent proctectomy and 3 patients developed rectal cancer (10%). Among 134 patients (82%) with fewer than 20 polyps, 8 patients (6%) underwent proctectomy and 3 patients developed rectal cancer (2%). Number of rectal polyps at the time of total abdominal colectomy with ileorectal anastomosis was associated with the likelihood of proctectomy (OR 1.1, p < 0.001) but not incident rectal cancer ( p = 0.3). LIMITATION: Retrospective data collection. CONCLUSIONS: Patients with familial adenomatous polyposis selected for total abdominal colectomy with ileorectal anastomosis by rectal polyp number have low rates of proctectomy and rectal cancer compared to historical controls. With appropriate selection criteria and surveillance, total abdominal colectomy with ileorectal anastomosis remains an important and safe treatment option for patients with familial adenomatous polyposis. See Video Abstract . RIESGO DE PROCTECTOMA DESPUS DE ANASTOMOSIS ILEORRECTAL EN POLIPOSIS ADENOMATOSA FAMILIAR EN LA ERA MODERNA: ANTECEDENTES:La cirugía profiláctica para la poliposis adenomatosa familiar (PAF) ha evolucionado durante varias décadas. La proctocolectomía restauradora con anastomosis anal con bolsa ileal (IPAA) proporciona una alternativa a la colectomía abdominal total con anastomosis ileorrectal (TAC/IRA). Anteriormente hemos demostrado que la tasa de proctectomía y cáncer de recto después de TAC/IRA en la era "pre-bolsa" era del 32% y el 13%, respectivamente.OBJETIVO:Determinar la tasa de proctectomía y cáncer de recto entre pacientes con PAF y pacientes con preservación rectal relativa (<20 pólipos rectales) seleccionados para TAC/IRA en la era moderna.DISEÑO:Estudio de cohorte retrospectivo.ÁMBITO:Institución única de atención terciaria con un registro de cáncer colorrectal hereditario.PACIENTES:Pacientes con PAF que se sometieron a TAC/IRA entre 1993 y 2020.MEDIDAS DE RESULTADO PRINCIPALES:Incidencia de proctectomía por cualquier indicación y cáncer de recto.RESULTADOS:Se incluyeron 197 pacientes con una mediana de edad de 24 años (rango 10-67). La mediana de seguimiento tras TAC/IRA fue de 13 años (RIC 6-17). 16 pacientes (8%) fueron sometidos a proctectomía. Las indicaciones incluyeron cáncer de recto en 6 (3%) (2 en estadio I y 4 en estadio III); pólipos con displasia de alto grado en 4 (2%); carga progresiva de pólipos en 3 (1,5%), disfunción defecatoria en 2 (1%); y fuga anastomótica en 1 (0,5%). Entre 30 pacientes (18%) con ≥20 pólipos rectales en el momento de TAC/IRA, 8 pacientes (26%) se sometieron a proctectomía y 3 pacientes desarrollaron cáncer de recto (10%). Entre 134 pacientes (82%) con <20 pólipos, 8 pacientes (6%) se sometieron a proctectomía y 3 pacientes desarrollaron cáncer de recto (2%). El número de pólipos rectales en el momento de TAC/IRA se asoció con la probabilidad de proctectomía (OR 1,1, p <0,001), pero no con la incidencia de cáncer de recto (p = 0,3).LIMITACIÓN:Recopilación de datos retrospectivos.CONCLUSIÓN:Los pacientes con PAF seleccionados para TAC/IRA por el número de pólipos rectales tienen tasas bajas de proctectomía y cáncer de recto en comparación con los controles históricos. Con criterios de selección y vigilancia adecuados, TAC/IRA sigue siendo una opción de tratamiento importante y segura para los pacientes con PAF. (Pre-proofed version ).


Subject(s)
Adenomatous Polyposis Coli , Proctectomy , Rectal Neoplasms , Humans , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Retrospective Studies , Anastomosis, Surgical , Rectal Neoplasms/surgery , Rectal Neoplasms/complications , Adenomatous Polyposis Coli/surgery , Adenomatous Polyposis Coli/complications
5.
Am J Surg ; 230: 16-20, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37914660

ABSTRACT

BACKGROUND: The mesentery has recently been implicated in the pathophysiology of Crohn's disease (CD), and several techniques have been developed to target the mesentery to reduce its influence on recurrence. We aimed to describe short-term safety and feasibility after these approaches. METHODS: This is a comparative, retrospective, single-center cohort study of consecutive CD patients undergoing primary or redo ileocolic resection from 2015 to 2022 with Kono-S anastomosis (KSA), extended mesenteric excision (EME) only, or both: mesenteric excision and exclusion (MEE). RESULTS: 186 patients underwent KSA (n â€‹= â€‹74), EME (n â€‹= â€‹66), or MEE (n â€‹= â€‹46). The groups had comparable baseline characteristics. The MEE group operative time was longer (median: 187 vs. KSA 170, EME 152 â€‹min, p â€‹< â€‹0.01). Postoperatively, the groups had similar lengths of stay (median 4 days), readmissions (9.1 â€‹%), major postoperative complications (6.5 â€‹%), and anastomotic leaks (1.1 â€‹%). CONCLUSION: Targeting the mesentery with novel surgical approaches for ileocolic Crohn's disease was safe and feasible for short-term follow-up.


Subject(s)
Crohn Disease , Humans , Crohn Disease/surgery , Colon/surgery , Cohort Studies , Retrospective Studies , Feasibility Studies , Ileum/surgery , Anastomosis, Surgical/methods , Postoperative Complications/epidemiology , Mesentery/surgery , Recurrence
6.
J Natl Compr Canc Netw ; 21(11): 1156-1163.e5, 2023 11.
Article in English | MEDLINE | ID: mdl-37935108

ABSTRACT

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) is rapidly increasing. Pathogenic germline variants (PGVs) are detected in 16% to 20% of patients who have EOCRC, highlighting a need for genetic counseling (GC) and multigene panel testing in these patients. We aimed to determine the rate of referral to GC and uptake and outcomes of germline testing in patients with EOCRC. METHODS: We conducted a retrospective cohort study of patients aged <50 years diagnosed with colorectal cancer (CRC) from 2010 to 2019 at Cleveland Clinic. Demographic data were extracted, including age, sex, self-reported race, and family history of CRC. The proportions of patients with GC referral and completion of GC and genetic testing were investigated, and genetic testing results were analyzed. Multivariable logistic regression analysis was conducted to identify factors independently associated with GC referral and uptake. RESULTS: A total of 791 patients with EOCRC (57% male and 43% female) were included; 62% were referred for GC, and of those who were referred, 79% completed a GC appointment and 77% underwent genetic testing. Of those who underwent testing, 21% had a PGV detected; 82% were in known CRC-associated genes, with those associated with Lynch syndrome and familial adenomatous polyposis the most common, and 11% were in other actionable genes. Referral to GC was positively associated with family history of CRC (odds ratio [OR], 2.11; 95% CI, 1.51-2.96) and more recent year of diagnosis (2010-2013 vs 2017-2019; OR, 5.36; 95% CI, 3.59-8.01) but negatively associated with older age at diagnosis (OR, 0.89; 95% CI, 0.86-0.92). CONCLUSIONS: Referral to GC for patients with EOCRC is increasing over time; however, even in recent years, almost 25% of patients were not referred for GC. We found that 1 in 5 patients with EOCRC carry actionable PGVs, highlighting the need for health systems to implement care pathways to optimize GC referral and testing in all patients with EOCRC.


Subject(s)
Colorectal Neoplasms , Genetic Counseling , Humans , Male , Female , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/genetics , Retrospective Studies , Genetic Testing/methods , Referral and Consultation
8.
Ann Surg Open ; 3(3): e177, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36199484

ABSTRACT

Management of patients with rectal cancer can be complex, requiring significant care coordination and decisions that balance functional and oncologic outcomes. Objective: To characterize care coordination occurring during surgical consultation for rectal cancer and consequences of using face-to-face time in clinic for care coordination. Methods: Secondary analysis was performed on audio recordings of clinic visits with colorectal surgeons to discuss surgery for rectal cancer at 5 academic medical centers. Analysis included the content of communication related to types of care coordination, specific details and conditions under which care coordination was conducted, and consequences. Results: The cohort included 18 patients seen by 8 surgeons. Care coordination consumed much of the conversation; on average 23.7% (SD 14.6) of content. Communication about care coordination included gathering information from work-up already performed, logistics for completing further work-up, gathering multidisciplinary opinions, and logistics for treatment planning. Obtaining imaging results was particularly challenging and surgeons went to great lengths to gather this information. To mitigate information gaps, surgeons asked patients about critical clinical details. Patients expressed remorse when they could not provide needed information, relay technical details, or had missing reports. Surgeons voiced frustration at the system related to the need to gather information from multiple sources and coordinate logistics. Surgeons worked to inform patients about their disease and discuss important lifestyle and cancer-related tradeoffs. However, the ability to solicit patient input and engage in shared decision making was often limited by incomplete data or conditioned on approval by a multidisciplinary tumor board. Conclusion: Much of the conversation between surgeons and patients with rectal cancer is consumed by care coordination. Organizing care coordination outside of the clinic visit would likely improve the experience for both patients and surgeons, addressing both clinician burnout and variation in management and outcomes.

9.
Dis Colon Rectum ; 65(11): 1351-1361, 2022 11 01.
Article in English | MEDLINE | ID: mdl-34840307

ABSTRACT

BACKGROUND: Desmoid disease is a leading cause of morbidity and mortality in patients with familial adenomatous polyposis. Abdominal desmoid disease usually follows total proctocolectomy with IPAA or total abdominal colectomy with ileorectal anastomosis. Sex, extraintestinal manifestations, and a 3'-mutation location have been identified as risk factors, but surgical risk factors are poorly understood. We hypothesized that pouch construction creates a higher risk of desmoid formation due to the increased stretch of the small-bowel mesentery. OBJECTIVE: This study aimed to investigate the surgical risk factors for desmoid formation. DESIGN: This was a retrospective, single-center, registry-based cohort study. SETTINGS: This study was conducted at a single academic institution with a prospectively maintained hereditary colorectal cancer database between 1995 and 2015. PATIENTS: All patients with familial polyposis (total 345) who underwent either proctocolectomy with a pouch or colectomy with an ileorectal anastomosis during the study period and met inclusion criteria were selected. MAIN OUTCOME MEASURES: The development of symptomatic abdominal desmoid disease was the primary end point. Associations between desmoid formation and resection type, surgical approach, and other patient factors were analyzed. RESULTS: A total of 172 (49%) patients underwent proctocolectomy/ileoanal pouch, whereas 173 (51%) underwent total colectomy/ileorectal anastomosis. Overall, 100 (28.9%) developed symptomatic desmoids after surgery. On univariable analysis, open surgery and pouch surgery were associated with desmoid development, along with extracolonic manifestations, family history of desmoids, mutation location, and a high desmoid risk score. On multivarible analysis, proctocolectomy with pouch was most strongly associated with desmoid disease ( p < 0.01). LIMITATIONS: This study was limited by its retrospective nature, the lack of uniform desmoid screening, and the variable duration of follow-up. Unanalyzed confounding factors include polyposis severity and number of surgeries. CONCLUSIONS: Patients with polyposis who underwent total proctocolectomy with pouch by any approach had significantly greater risk of developing desmoid disease than total colectomy with ileorectal anastomosis, even when accounting for other risk factors. See Video Abstract at http://links.lww.com/DCR/B822 .RESULTADOS DE LOS PACIENTES SOMETIDOS A RESECCIÓN INTESTINAL ELECTIVA ANTES Y DESPUÉS DE LA IMPLEMENTACIÓN DE UN PROGRAMA DE DETECCIÓN Y TRATAMIENTO DE ANEMIA. ANTECEDENTES: Se sabe que los pacientes anémicos que se someten a una cirugía electiva de cáncer colorrectal tienen tasas significativamente más altas de complicaciones posoperatorias y peores resultados. OBJETIVO: Mejorar las tasas de detección y tratamiento de la anemia en pacientes sometidos a resecciones electivas de colon y recto a través de una iniciativa de mejora de calidad. DISEO: Comparamos una cohorte histórica de pacientes antes de la implementación de nuestro programa de detección de anemia y mejora de la calidad del tratamiento con una cohorte prospectiva después de la implementación. ENTORNO CLINICO: Hospital de atención terciaria. PACIENTES: Todos los pacientes adultos con un nuevo diagnóstico de cáncer de colon o recto sin evidencia de enfermedad metastásica entre 2017 y 2019. INTERVENCIONES: Detección de anemia y programa de mejora de la calidad del tratamiento. PRINCIPALES MEDIDAS DE RESULTADO: El resultado primario fue el costo hospitalario por ingreso. RESULTADOS: Un total de 84 pacientes se sometieron a resección electiva de colon o recto antes de la implementación de nuestro proyecto de mejora de calidad de la anemia y 88 pacientes se sometieron a cirugía después. En la cohorte previa a la implementación, 44/84 (55,9 %) presentaban anemia en comparación con 47/99 (54,7 %) en la cohorte posterior a la implementación. Las tasas de detección (25 % a 86,4 %) y tratamiento (27,8 % a 63,8 %) aumentaron significativamente en la cohorte posterior a la implementación. El costo total medio por admisión se redujo significativamente en la cohorte posterior a la implementación (costo medio $16 827 vs. $25 796, p = 0,004); esta reducción significativa se observó incluso después de ajustar los factores de confusión relevantes (proporción de medias: 0,74, IC del 95 %: 0,65 a 0,85). El vínculo mecánico entre el tratamiento de la anemia y la reducción de costos sigue siendo desconocido. No hubo diferencias significativas en las tasas de transfusión de sangre, complicaciones o mortalidad entre los grupos. LIMITACIONES: El diseño de antes y después está sujeto a sesgos temporales y de selección. CONCLUSIONES: Demostramos la implementación exitosa de un programa de detección y tratamiento de anemia. Este programa se asoció con un costo por admisión significativamente reducido. Este trabajo demuestra el valor y los beneficios posibles de la implementación de un programa de detección y tratamiento de la anemia. Consulte Video Resumen en http://links.lww.com/DCR/C15 . (Traducción- Dr. Francisco M. Abarca-Rendon ).


Subject(s)
Adenomatous Polyposis Coli , Fibromatosis, Aggressive , Adenomatous Polyposis Coli/surgery , Anastomosis, Surgical , Cohort Studies , Humans , Postoperative Complications , Retrospective Studies
10.
Dis Colon Rectum ; 64(7): e391-e394, 2021 07 01.
Article in English | MEDLINE | ID: mdl-33872285

ABSTRACT

INTRODUCTION: When patients with familial adenomatous polyposis have a severely affected rectum, it is usually assumed that endoscopic control is impossible or unwise. The standard approach is proctectomy with either an end ileostomy or an IPAA. Here we show that application of aggressive, multistage snare polypectomy to this situation can be effective and allow the patient to avoid surgery, at least in the short term. TECHNIQUE: Standard polypectomy using snare excision with coagulation is used, taking 2 or 3 sessions, and beginning with the largest polyps. The procedures are performed with the patient under general anesthesia. Endoscopic mucosal resection technique with fluid injection to lift polyps is not necessary. RESULTS: Complete control of the rectal polyps, sustained for at least 2 years, is possible without functional sequelas. CONCLUSIONS: Patients with familial adenomatous polyposis with severe rectal polyposis can be offered multistage rectal polypectomy and safely avoid proctectomy.


Subject(s)
Adenomatous Polyposis Coli/surgery , Polyps/surgery , Proctectomy/instrumentation , Proctocolectomy, Restorative/adverse effects , Rectum/surgery , Adenomatous Polyposis Coli/diagnosis , Adenomatous Polyposis Coli/pathology , Adult , Anastomosis, Surgical/methods , Colorectal Neoplasms/prevention & control , Humans , Male , Polyps/diagnosis , Proctectomy/classification , Proctectomy/methods , Proctocolectomy, Restorative/methods , Rectal Neoplasms/pathology , Rectum/pathology , Safety , Treatment Outcome , Young Adult
11.
Surg Clin North Am ; 99(5): 849-858, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31446913

ABSTRACT

When making high-stakes decisions with their patients, surgeons may have only one opportunity to get a life-changing conversation right. These loaded conversations cover immense ground. Bad news, emotion, prognosis, treatment choices, and patient goals all play a part in coming up with the right plan for each individual patient. Surgeons and patients may overlook important factors when the language and process of informed consent is substituted for decision-making. "Best Case/Worst Case" is a communication tool based in scenario planning that promotes shared decision-making in high-stakes surgical conversations and is discussed at length in this review.


Subject(s)
Decision Making , Physician-Patient Relations , Prognosis , Truth Disclosure , Humans , Informed Consent , Patient Participation , Surgeons
12.
J Pediatr Surg ; 52(6): 1026-1030, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28343662

ABSTRACT

PURPOSE: Previously, we demonstrated enhanced adaptation after small bowel resection (SBR) in intestinal-specific retinoblastoma (Rb)-deficient mice along with elevated levels of insulin-like growth factor 2 (IGF2) expression within the villi. The purpose of this study was to verify that the insulin-like growth factor 1 receptor (IGF1R) plays a role in this phenomenon. METHODS: Inducible and intestinal specific Rb and IGF1R double knockout mice (iRb/IGF1R-IKO) (n=4) and Rb single knockout mice (iRb-IKO) (n=5) underwent 50% mid SBR. On post-operative day 28, mice were harvested, and structural adaptation was measured as changes in crypt depth and villus height. Rates of enterocyte proliferation were recorded. IGF2 expression within the remnant villi was measured via RT-PCR. RESULTS: Both iRb-IKO and iRb/IGF1R-IKO mice demonstrated enhanced adaptation with at least a 45% increase in both crypt depth and villus height in the proximal and distal remnant bowel. Both groups showed elevation of IGF2 expression in the remnant villi, but there were no differences between the two groups. CONCLUSION: Epithelial IGF1R is dispensable for IGF2-mediated enhanced intestinal adaptation in retinoblastoma-deficient mice. Our findings suggest that IGF2 signals for enhanced adaptation in cells outside of the epithelium. Further investigation is needed to study the IGF2/IGF1R signaling interaction within the mesenchyme. LEVEL OF EVIDENCE: Animal study - not clinical.


Subject(s)
Adaptation, Physiological , Insulin-Like Growth Factor II/metabolism , Intestinal Mucosa/metabolism , Intestine, Small/surgery , Receptor, IGF Type 1/metabolism , Retinoblastoma Protein/deficiency , Short Bowel Syndrome/metabolism , Animals , Biomarkers/metabolism , Intestinal Mucosa/physiology , Intestine, Small/metabolism , Intestine, Small/physiology , Mice , Mice, Knockout , Postoperative Period , Real-Time Polymerase Chain Reaction , Short Bowel Syndrome/physiopathology
13.
J Pediatr Surg ; 50(6): 943-7, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25818318

ABSTRACT

PURPOSE: Intestinal adaptation structurally represents increases in crypt depth and villus height in response to small bowel resection (SBR). Previously, we found that neither epidermal growth factor receptor (EGFR) nor insulin-like growth factor 1 receptor (IGF1R) function was individually required for normal adaptation. In this study, we sought to determine the effect of disrupting both EGFR and IGF1R expression on resection-induced adaptation. METHODS: Intestinal-specific EGFR and IGF1R double knockout mice (EGFR/IGF1R-IKO) (n=6) and wild-type (WT) control mice (n=7) underwent 50% proximal SBR. On postoperative day (POD) 7, structural adaptation was scored by measuring crypt depth and villus height. Rates of crypt cell proliferation, apoptosis, and submucosal capillary density were also compared. RESULTS: After 50% SBR, normal adaptation occurred in both WT and EGFR/IGF1R-IKO. Rates of proliferation and apoptosis were no different between the two groups. The angiogenic response was less in the EGFR/IGF1R-IKO compared to WT mice. CONCLUSION: Disrupted expression of EGFR and IGF1R in the intestinal epithelial cells does not affect resection-induced structural adaptation but attenuates angiogenesis after SBR. These findings suggest that villus growth is driven by receptors and pathways that occur outside the epithelial cell component, while angiogenic responses may be influenced by epithelial-endothelial crosstalk.


Subject(s)
Adaptation, Physiological , ErbB Receptors/metabolism , Intestine, Small/physiology , Intestine, Small/surgery , Receptor, IGF Type 1/metabolism , Animals , Apoptosis , Cell Proliferation , Epithelial Cells/physiology , Intestinal Mucosa/metabolism , Intestine, Small/blood supply , Mice, Knockout , Neovascularization, Physiologic
14.
J Pediatr Surg ; 50(6): 948-53, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25818317

ABSTRACT

PURPOSE: Intestinal adaptation involves villus lengthening, crypt deepening, and increased capillary density following small bowel resection (SBR). Mice lacking the proangiogenic chemokine CXCL5 have normal structural adaptation but impaired angiogenesis. This work evaluates the impact of incomplete adaptive angiogenesis on the functional capacity of the intestine after SBR. METHODS: CXCL5 knockout (KO) and C57BL/6 wild-type (WT) mice underwent 50% SBR. Magnetic resonance imaging measured weekly body composition. Intestinal absorptive capacity was evaluated through fecal fat analysis. Gene expression profiles for select macronutrient transporters were measured via RT-PCR. Postoperative crypt and villus measurements were assessed for structural adaptation. Submucosal capillary density was measured through CD31 immunohistochemistry. RESULTS: Comparable postoperative weight gain occurred initially. Diminished weight gain, impaired fat absorption, and elevated steatorrhea occurred in KO mice after instituting high-fat diet. Greater postoperative upregulation of ABCA1 fat transporter occurred in WT mice, while PEPT1 protein transporter was significantly downregulated in KO mice. KO mice had impaired angiogenesis but intact structural adaptation. CONCLUSION: After SBR, KO mice display an inefficient intestinal absorption profile with perturbed macronutrient transporter expression, impaired fat absorption, and slower postoperative weight gain. In addition to longer villi and deeper crypts, an intact angiogenic response may be required to achieve functional adaptation to SBR.


Subject(s)
Adaptation, Physiological , Intestine, Small/blood supply , Intestine, Small/surgery , Neovascularization, Physiologic , Animals , Chemokine CXCL5 , Intestinal Absorption , Intestinal Mucosa/pathology , Intestine, Small/physiology , Mice, Inbred C57BL , Mice, Knockout
15.
J Gastrointest Surg ; 19(3): 451-7, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25519080

ABSTRACT

INTRODUCTION: Short bowel syndrome (SBS) is a morbid clinical condition that results from massive small-bowel resection (SBR). After SBR, there is a dramatic weight loss in the acute postoperative period. Our aim was to determine the impact of a high-protein diet (HPD) on weight gain and body composition in mice after SBR. METHODS: C57BL/6 mice underwent 50 % proximal SBR. Postoperatively, mice were randomly selected to receive standard rodent liquid diet (LD) (n = 6) or an isocaloric HPD (n = 9) for 28 days. Mice weights were recorded daily. Body composition analyses were obtained weekly. Student's t test was used for statistical comparisons with p < 0.05 considered significant. RESULTS: Mice that were fed HPD after SBR returned to baseline weight on average at postoperative day (POD) 8 versus mice that were fed LD that returned to baseline weight on average at POD 22. Total fat mass and lean mass were significantly greater by POD 14 within the HPD group. Both groups of mice demonstrated normal structural adaptation. CONCLUSION: HPD results in greater weight gain and improved body composition in mice after SBR. This finding may be clinically important for patients with SBS since improved weight gain may reduce the time needed for parenteral nutrition.


Subject(s)
Dietary Proteins/administration & dosage , Digestive System Surgical Procedures/adverse effects , Intestine, Small/surgery , Short Bowel Syndrome/diet therapy , Weight Gain , Adaptation, Physiological , Animals , Body Composition , Mice , Mice, Inbred C57BL , Postoperative Period , Random Allocation , Short Bowel Syndrome/etiology
16.
Surgery ; 156(2): 412-8, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24713095

ABSTRACT

BACKGROUND: After massive small bowel resection (SBR), a postoperative diet high in fat is associated with enhanced villus growth. The purpose of this study was to further elucidate the quantity and composition of enteral fat in structural and metabolic changes after SBR. METHODS: C57/Bl6 mice underwent a 50% proximal SBR. Mice were then randomized to receive a low-fat diet (12% kcal fat), medium-fat diet (44% kcal fat), or high-fat diet (HFD; 71% kcal fat) ad libitum. In a separate experiment, mice underwent 50% proximal SBR and then were randomized to liquid diets of 42% kcal of fat in which the fat was composed of menhaden oil, milk fat, or olive oil. After 2 weeks, mice underwent body composition analysis and the small intestine was harvested. RESULTS: Mice that ingested the greatest amount of enteral fat (HFD) had the greatest percent lean mass. When the effects of the different kinds of enteral fat were analyzed, mice that consumed menhaden oil had the greatest percent lean mass with the greatest overall retention of preoperative weight. CONCLUSION: These findings suggest that enteral fat enriched in omega-3 fatty acids may offer clinically relevant metabolic advantages for patients with short gut syndrome.


Subject(s)
Body Composition , Diet, High-Fat , Intestine, Small/surgery , Animals , Disease Models, Animal , Energy Intake , Enteral Nutrition , Fatty Acids, Omega-3/administration & dosage , Fish Oils/administration & dosage , Glucose Transporter Type 2/genetics , Humans , Male , Mice , Mice, Inbred C57BL , Postoperative Complications/diet therapy , RNA, Messenger/genetics , RNA, Messenger/metabolism , Short Bowel Syndrome/diet therapy , Short Bowel Syndrome/genetics , Short Bowel Syndrome/pathology , Sodium-Glucose Transporter 1/genetics , Up-Regulation , Weight Loss
17.
Reproduction ; 130(5): 599-601, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16264090

ABSTRACT

The oldest assisted reproductive technologies (ART)-conceived child is only 27 years old. Thus, the effects of ART on longevity are unknown, and it will be many years before this can be assessed in humans. We recently reported that culturing preimplantation mouse embryos under suboptimal conditions results in differences in how the offspring perform in behavioral assays that reflect anxiety (elevated zero maze) and spatial memory (Morris hidden water maze; Ecker et al. 2004). Here we monitored the mice generated in our previous study and found no difference in their longevity.


Subject(s)
Blastocyst/physiology , Embryo Culture Techniques , Longevity , Reproductive Techniques, Assisted , Aging , Animals , Female , Genotype , Male , Mice , Mice, Inbred Strains , Models, Animal , Regression Analysis , Sex Factors
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