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Objective: Analyze our long-term experience with a less-popularized but stalwart approach, the stapled end-to-side ileocolic anastomosis., Background: The choice of technical approach to ileocolic anastomosis after ileocecal resection for Crohn's disease affects surgical outcomes and recurrence. Yet, despite heterogeneous data from different anastomotic configurations, there remains no clear guidance as to the optimal technique., Methods: In a retrospective cohort design, patients undergoing ileocolic anastomosis in the setting of Crohn's disease between 2016 and 2021 at two institutions were identified. Patient characteristics and surgical outcomes in terms of recurrence (surgical, clinical, and endoscopic) were studied., Results: In total, 211 patients were included. Before surgery, 80% were exposed to at least 1 cycle of systemic steroids and 71% had at least 1 biologic agent; 60% exhibited penetrating disease and 38% developed an intra-abdominal abscess. After surgery, one anastomosis leaked (0.5%). Over 2.4 years of follow-up (IQR = 1.3-3.9), surgical recurrence was 0.9%. Two-year overall recurrence-free and endoscopic recurrence-free survivals were 74% and 85% (95% CI = 68-81 and 80-91), respectively. The adjusted hazard ratio of endoscopic recurrence was 3.0 (95% CI = 1.4-6.2) for males and 5.2 (1.2-22) for patients who received systemic steroids before the surgery., Conclusion: The stapled end-to-side anastomosis is an efficient, reliable, and reproducible approach to maintain bowel continuity after ileocecal resection with durable outcomes. Our outcomes demonstrate low rates of disease recurrence and stand favorably in comparison to other more technically complex or protracted anastomotic approaches. This anastomosis is an ideal reconstructive approach after ileocecal resection for Crohn's disease., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The steep learning curve associated with learning laparoscopic techniques and limited training opportunities represents a challenge to general surgery resident training. The objective of this study was to use a live porcine model to improve surgical training in laparoscopic technique and management of bleeding. Nineteen general surgery residents (ranging from PGY 3 to 5) completed the porcine simulation and completed pre-lab and post-lab questionnaires. The institution's industry partner served as sponsors and educators on hemostatic agents and energy devices. Residents had a significant increase in confidence with laparoscopic techniques and the management of hemostasis ( P = .01 and P = .008, respectively). Residents agreed and then strongly agreed that a porcine model was suitable to simulate laparoscopic and hemostatic techniques, but there was no significant change between pre- and post-lab opinions. This study demonstrates that a porcine lab is an effective model for surgical resident education and increases resident confidence.

Restorative proctocolectomy with ileal pouch-anal anastomosis remains the gold standard treatment for patients with ulcerative colitis who desire restoration of intestinal continuity. Despite a significant cancer risk reduction after surgical removal of the colon and rectum, dysplasia and cancers of the ileal pouch or anal transition zone still occur and are a risk even if an anal canal mucosectomy is performed. Surgical care and maintenance after ileoanal anastomosis must include consideration of malignant potential along with other commonly monitored variables such as bowel function and quality of life. Cancers and dysplasia of the ileal pouch are rare but sometimes difficult-to-manage sequelae of pouch surgery., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

The continent ileostomy (CI) was popularized by Nils Kock as a means to provide fecal continence to patients, most commonly in those with ulcerative colitis, after proctocolectomy. Although the ileal pouch-anal anastomosis (IPAA) now represents the most common method to restore continence after total proctocolectomy, CI remains a suitable option for highly selected patients who are not candidates for IPAA or have uncorrectable IPAA dysfunction but still desire fecal continence. The CI has exhibited a fascinating and marked evolution over the past several decades, from the advent of the nipple-valve to a distinct pouch design, giving the so-inclined and so-trained colorectal surgeon a technique that provides the unique patient with another option to restore continence. The CI continues to offer a means for appropriately selected patients to achieve the highest possible quality of life (QOL) and functional status after total proctocolectomy., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Surveillance pouchoscopy is recommended for patients with restorative proctocolectomy with ileal pouch-anal anastomosis in ulcerative colitis or familial adenomatous polyposis, with the surveillance interval depending on the risk of neoplasia. Neoplasia in patients with ileal pouches mainly have a glandular source and less often are of squamous cell origin. Various grades of neoplasia can occur in the prepouch ileum, pouch body, rectal cuff, anal transition zone, anus, or perianal skin. The main treatment modalities are endoscopic polypectomy, endoscopic ablation, endoscopic mucosal resection, endoscopic submucosal dissection, surgical local excision, surgical circumferential resection and re-anastomosis, and pouch excision. The choice of the treatment modality is determined by the grade, location, size, and features of neoplastic lesions, along with patients' risk of neoplasia and comorbidities, and local endoscopic and surgical expertise., Competing Interests: Declaration of interests CNB reports grants and personal fees from AbbVie, Janssen Canada, Pfizer, and Takeda Canada; and personal fees from Roche Canada, Bristol-Myers-Squibb Canada, Sandoz Canada, Mylan Pharmaceuticals, Takeda, and Medtronics Canada. DHB reports grants from Nextrast, Medtronic, and Takeda. WB reports consultant or speaker fees from Takeda, Braun, Johnson & Johnson, and Medtronic; and grants from VIFOR. RKC reports personal fees from AbbVie, Bristol Myers Squibb, Eli Lilly Janssen, Pfizer, Samsung Bioepis, and Takeda. SC reports personal fees from Pfizer and AbbVie. FAF reports personal fees from Arena, BMS, Braintree Labs, GI Reviewers, GSK, Innovation Pharmaceuticals, Iterative scopes, Janssen, Pfizer, and Sebela; and a data safety monitoring board role at Lilly and TheraVance. LAK reports personal fees from UpToDate and New Beta Innovation and grants from Varian Medical Systems. SE-H reports speaker fees from AbbVie, Bristol Myers Squibb, Janssen, Takeda, and Pfizer; and advisory board role at AbbVie, Prometheus, Bristol Myers, and UCB. SVK reports personal fees from Pfizer and grants from Gilead Sciences and TechLab. PGK reports personal fees from AbbVie, Janssen, Pfizer, Takeda, and Ferring; and grants from Pfizer and Takeda. GSK reports consulting fees from Janssen, Bristol Meyers Squibb, United Healthcare, Spherix Health, and TechLab; and an editor role at UpToDate. JTM reports personal fees from Intuitive Surgical. XL reports personal fees AbbVie, Arrowhead Pharmaceuticals, and PathAI. UN reports grants and personal fees from Takeda, Janssen, and AbbVie; and personal fees from Pfizer. DSP reports research grants from Atlantic, Finch, Janssen, Pfizer, Seres, Takeda, Vedanta, and Applied Molecular Transport; and consulting fees from Vedanta, Seres, and Otsuka. JP reports speaker fees from AbbVie. DKR reports consulting fees from Olympus, Boston Scientific, Arles Pharmaceutical, Braintree Laboratories, Lumendi, Norgine, Endokey, and GU supplies; and research support from Olympus and Braintree Laboratories. DTR reports personal fees from AbbVie, Altrubio, Allergan, Arena Pharmaceuticals, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corp–Syneos, Connect BioPharma, GalenPharma–Atlantica, Genentech–Roche, Gilead Sciences, InDex Pharmaceuticals, Ironwood Pharmaceuticals, Iterative Scopes, Janssen Pharmaceuticals, Lilly, Materia Prima, Pfizer, Prometheus Biosciences, Reistone, Takeda, and TechLab. AS reports consulting fees from Takeda, Ethicon, Pfizer, and Oasis. BS reports personal fees from AbbVie, Janssen, and Takeda. ES reports grants and personal fees from AbbVie, Janssen, Takeda; and grants from Astra-Zeneca, Pfizer, and Genentech; and personal fees from Seres Health, Protagonist Therapeutics, Celgene, Entera Health, Bristol Myers Squibb, and Evidera. RAS reports personal fees from Merck & Co. WJS reports personal fees from AbbVie, Takeda, UCB, Janssen, Gilead, Pfizer, and Tract. WJS reports grants, personal fees, and stock or stock options from Prometheus Biosciences; grants and personal fees from AbbVie, Abivax, Alimentiv, Arena Pharmaceuticals, Boehringer-Ingelheim, Celgene, Genentech (Roche), Gilead Sciences, Glaxo Smith Kline, Janssen, Lilly, Pfizer, Prometheus Biosciences, Seres Therapeutics, Shire, Surrozen, Takeda, and Theravance Biopharma; personal fees and stock or stock options from Beigene, Gossamer Bio, and Shoreline Bioscience; and personal fees from Allergan, Amgen, Applied Molecular Transport, Avexegen Therapeutics, Bausch Health (Salix), Beigene, Bellatrix Pharmaceuticals, Boston Pharmaceuticals, Bristol Myers Squibb, Celltrion, Cellularity, Conatus, Cosmo Pharmaceuticals, Escalier Biosciences, Ferring, Forbion, Equillium, Glanmark Pharmaceuticals, Immunic (Vital Therapies), Incyte, Index Pharmaceuticals, Intact Therapeutics, Kyowa Kirin Pharmaceutical Research, Kyverna Therapeutics, Landos Biopharma, Miraca Life Sciences, Nivalis Therapeutics, Novartis, Nutrition Science Partners, Oppilan Pharma, Progenity, Protagonist Therapeutics, Provention Bio, Reistone Biopharma, Ritter Pharmaceuticals, Shanghai Pharma Biotherapeutics, Sienna Biopharmaceuticals, Sigmoid Biotechnologies, Sterna Biologicals, Sublimity Therapeutics, and Thetis Pharmaceuticals. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Caring for a patient with a hostile abdomen is one of the most challenging clinical situations one can encounter. It requires specialized technical skill coupled with bold but thoughtful decision-making to achieve good outcomes. An approach to the patient with a complex, hostile abdomen must be individualized to account for the patient's personal details. However, implementing an experienced-based algorithm to help make the difficult decisions required in this setting can be helpful, as evidence-based studies are few. The purpose of this review is to provide a structured, evidence, and experienced-based approach to the challenges that the surgeon encounters when faced with a patient with a hostile abdomen, and to discuss perioperative and intraoperative surgical strategies that can lead to most successful outcomes., (Thieme. All rights reserved.)

Objectives: Improved screening has decreased but not eliminated the need for emergent surgery for colon cancer (CC), many of which are performed by acute care surgery (ACS) surgeons. This retrospective review compares outcomes for CC resections on the ACS service to the surgical oncology and colorectal services (SO/CRS)., Methods: Retrospective review was performed for CC operations between 2014 and 2019. Data for margin status, cancer stage, number of lymph nodes dissected, time to medical oncology follow-up, and time to initiation of chemotherapy were collected. Patients with curative resection, who chose comfort care, presented on alternative services or with non-CC indications as well as those were lost to follow-up were excluded., Results: 36 ACS patients and 269 SO/CRS patients underwent CC resections. Most ACS patients presented emergently compared to the SO/CC group (83.3% vs 1%, P < .05) as well as with more advanced tumor stage. There were no statistically significant differences for presence of metastatic disease, number of lymph nodes obtained, or time to post-surgical care (in days) and chemotherapy initiation (in days). 3 (8%) EGS patients had positive margins compared to 6 (2%) CRS/SO patients due to the presence of perforated tumors in the ACS group ( p < .05). There were no statistically significant differences in 30- day or 1-year mortality despite the emergent presentation of the ACS patients., Discussion: These findings suggest that despite emergent presentation and advanced disease burden, ACS surgeons provide quality care to CC patients, both in the operating room and in coordination of care.

Objective: We hypothesized that postoperative oral steroid taper after ileal pouch-anal anastomosis for inflammatory bowel disease would not be associated with pelvic septic complications., Background: Recent data has emphasized the possible association between biologic medication use and pelvic sepsis following ileal pouch-anal anastomosis. Limited contemporary data exist examining the effects of steroid use on these complications., Methods: Consecutive patients undergoing ileal pouch-anal anastomosis for inflammatory bowel disease at a single institution from January 2009 to December 2013 were included. Factors associated with anastomotic leak and pelvic sepsis were assessed using univariate and multivariate analysis., Results: A total of 686 patients were included (mean age 39.5 years, 59% males). Postoperative oral steroid taper was associated with both anastomotic leak and pelvic sepsis on univariate analysis. Stress dose intravenous steroid use was not associated with complications. Multivariate analysis indicated total proctocolectomy (odds ratio [OR] 2.2; confidence interval [CI] 1.01-4.7, P = 0.047), and postoperative oral steroid taper (OR 2.3; CI 1.06-5.1; P = 0.035) as independent factors significantly associated with pelvic sepsis., Conclusions: Prolonged postoperative oral steroid taper after ileal pouch-anal anastomosis should be avoided. If preoperative steroid weaning is not possible before a planned total proctocolectomy and ileal pouch-anal anastomosis, patients should undergo an initial total abdominal colectomy., (© 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Laparoscopic ileal pouch-anal anastomosis (IPAA) is associated with recovery benefits when compared with open IPAA. There is limited data on long-term quality of life and functional outcomes, which this study aimed to assess., Methods: An IRB-approved, prospectively maintained database was queried to identify patients undergoing laparoscopic IPAA (L), case-matched with open IPAA (O) based on age ± 5 years, gender, body mass index (BMI) ± 5 kg/m 2 , diagnosis, date of surgery ± 3 years, stapled/handsewn anastomosis, omission of diverting loop ileostomy and length of follow-up ± 3 years. We assessed functional results, dietary, social, work, sexual restrictions and the Cleveland Clinic global quality of life score (CGQoL) at 1, 2, 3, 4, 5 and 10 years postoperatively. Functional outcomes were assessed based on number of stools (day/night) and seepage protection use (day/night). Variables were evaluated with Kaplan-Meier survival curves, uni- and multivariable analyses., Results: Out of 4595 IPAAs, 529 patients underwent L, of whom 404 patients were well matched 1:1 to an equivalent number of O based on all criteria. Median follow-ups were 2 (0.5-17.8) versus 2.4 (0.5-22.2) years in L versus O, respectively (p = 0.18). L was associated with significantly decreased number of stools at night and less frequent pad usage at 1 year, both during the day and at night. Functional outcomes became similar during further follow-up. L was also associated with improved overall CGQoL, and energy scores at 1 year postoperatively, and decreased social restrictions for 1-2 years. There were no significant differences in quality of health, dietary, work or sexual restrictions. Laparoscopy was not associated with increased risk of pouch failure (p = 0.07) or significantly different causes of pouch failure when compared to O., Conclusions: Laparoscopic and open IPAA are associated with equivalent long-term functional outcomes, quality of life and pouch survival rates. Laparoscopic technique is associated with temporary benefits lasting 1 or 2 years.

Background & Aims: Few studies have compared endoscopic balloon dilation (EBD) with ileocolic resection (ICR) in the treatment of primary ileocolic strictures in patients with Crohn's disease (CD)., Methods: We performed a retrospective study to compare postprocedure morbidity and surgery-free survival among 258 patients with primary stricturing ileo(colic) CD (B2, L1, or L3) initially treated with primary EBD (n = 117) or ICR (n = 258) from 2000 through 2016. Patients with penetrating disease were excluded from the study. We performed multivariate analyses to evaluate factors associated with surgery-free survival., Results: Postprocedural complications occurred in 4.7% of patients treated with EBD and salvage surgery was required in 44.4% of patients. Factors associated with reduced surgery-free survival among patients who underwent EBD included increased stricture length (hazard ratio, 2.0; 95% CI, 1.3-3.3), ileocolonic vs ileal disease (hazard ratio, 10.9; 95% CI, 2.6-45.4), and decreased interval between EBD procedures (hazard ratio, 1.2; 95% CI, 1.1-1.4). There were no significant differences in sex, age, race, or CD duration between EBD and ICR groups. Patients treated with ICR were associated with more common postoperative adverse events (32.2%; P < .0001), but a reduced need for secondary surgery (21.7%; P < .0001) and significantly longer surgery-free survival (11.1 ± 0.6 vs 5.4 ± 0.6 y; P < .001)., Conclusions: In this retrospective study, we found that although EBD is initially successful with minimal adverse events, there is a high frequency of salvage surgery. Initial ICR is associated with a higher morbidity but a longer surgery-free interval. The risks and benefits should be balanced in selecting treatments for individual patients., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The aim of the present study was to assess the short-term and long-term consequences of diverting loop ileostomy (DLI) omission in ileal pouch-anal anastomosis (IPAA) surgery complicated by postoperative pelvic sepsis., Methods: This was a retrospective review of a prospectively maintained database. Of 4031 patients who underwent IPAA in 1983-2014, 357 developed IPAA-related pelvic sepsis with or without anastomotic dehiscence. Patients with Crohn's disease or cancer were excluded. The patient cohort was divided into two groups, depending on the presence or absence of DLI. Patient characteristics, short-term and long-term outcomes were compared. Long-term pouch survival was estimated with the Kaplan-Meier method. Quality of life (QOL) in the groups was compared at the latest follow-up., Results: Three hundred and twenty-six patients developing pelvic sepsis had diversion at the time of IPAA (D group) and in 31 who developed pelvic sepsis DLI had been omitted (O group). The length of hospital stay was significantly longer in the O group 11.5 (3-33) days versus 8 (2-59) days in the D group (p = 0.006). Forty-eight percent of patients from the O group with anastomotic leak underwent reoperation and had a DLI formed at this second procedure versus 12% in the D group requiring reoperation (p < 0.0001). In long-term follow-up, there was no difference in pouch survival between the groups: 99 versus 97% after 5 years and 88 versus 87% after 10 years, in the O group and D group, respectively (p = 0.40). There was no difference in QOL observed between the groups., Conclusions: Omission of DLI in selected patients who had IPAA surgery did not increase pouch failure or adversely affect QOL in the long term, if pelvic sepsis occurred.

Aim: Surgical technique constantly evolves in response to the pressure of progress. Ileal pouch anal anastomosis (IPAA) is a good example. We analysed the effect of changes in practice on the technique of IPAA and its outcomes., Method: Patients undergoing primary IPAA at this institution were divided into three groups by date of the IPAA: those operated from 1983 to 1993, from 1994 to 2004 and from 2005 to 2015. Demographics, patient comorbidity, surgical techniques, postoperative outcomes, pouch function and quality of life were analysed., Results: In all, 4525 patients had a primary IPAA. With each decade, increasing numbers of surgeons were involved (decade I, 8; II, 16; III, 31), patients tended to be sicker (higher American Society of Anesthesiologists score) and three-staged pouches became more common. After an initial popularity of the S pouch, J pouches became dominant and a mucosectomy rate of 12% was standard. The laparoscopic technique blossomed in the last decade. 90-day postoperative morbidity by decade was 38.3% vs 50% vs 48% (P < 0.0001), but late morbidity decreased from 74.2% through 67.1% to 30% (P < 0.0001). Functional results improved, but quality of life scores did not. Pouch survival rate at 10 years was maintained (94% vs 95.2% vs 95.2%; P = 0.06)., Conclusion: IPAA is still evolving. Despite new generations of surgeons, a more accurate diagnosis, appropriate staging and the laparoscopic technique have made IPAA a safer, more effective and enduring operation., (Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.)

Colorectal serrated polyps are intermediate lesions in the serrated neoplastic pathway, which account for up to 30% of colorectal cancers. This pathway is biologically distinct from the adenoma-to-carcinoma sequence, with associated cancers exhibiting mutations in the BRAF oncogene, DNA promoter hypermethylation, and microsatellite instability. An evolving understanding of these unique lesions has led to the development of a more accurate classification, improved endoscopic identification, and tailored clinical management guidelines. This article reviews serrated polyps and serrated polyposis syndrome., (© Thieme Medical Publishers.)

Radiotherapy not only plays a pivotal role in the cancer care pathways of many patients with pelvic malignancies, but can also lead to significant injury of normal tissue in the radiation field (pelvic radiation disease) that is sometimes as challenging to treat as the neoplasms themselves. Acute symptoms are usually self-limited and respond to medical therapy. Chronic symptoms often require operative intervention that is made hazardous by hostile surgical planes and unforgiving tissues. Management of these challenging patients is best guided by the utmost caution and humility.

Background: Clostridium difficile infection (CDI) is increasingly recognized in patients with ulcerative colitis with ileal pouch-anal anastomosis (IPAA). The aim of this study was to identify clinical risk factors for treatment-refractory or recurrent CDI in patients with IPAA., Methods: We identified patients with IPAA for underlying ulcerative colitis and a positive polymerase chain reaction stool test for C. difficile at the Center for Ileal Pouch Disorders during the period from October 2010 to November 2013. Demographic clinical variables were compared between the refractory or recurrent CDI and nonrecurrent CDI groups., Results: Patients with IPAA with refractory or recurrent symptoms (refractory/recurrent CDI, the study group, N = 19) were compared with patients with a single antibiotic-responsive episode of ileal pouch CDI (nonrecurrent CDI, the control group, N = 21). The frequency of pouchitis before the index CDI was similar in the study and control groups (63.2% versus 66.7%, P = 0.82). Postoperative mechanical abnormalities occurred in 16 patients (84.2%) in the study group versus 7 patients (33.3%) in the control group (P = 0.0008). There were no differences between the two groups regarding hospitalization, non-C. difficile antibiotic use, the use of gastric acid-reducing therapy, or immunosuppressives before or after the index CDI. Six of 15 patients (40.0%) in the study group versus 1 of 15 patients (7.1%) in the control group had a low serum level of IgG1 (P = 0.031)., Conclusions: Refractory or recurrent disease is common in patients with ileal pouch with CDI. The presence of postsurgery mechanical intestinal complications or low serum immunoglobulin level may be risk factors for refractory or recurrent CDI in this patient population.

Background: Long-term consequences of anastomotic leak after restorative proctectomy for rectal cancer, in terms of bowel function and quality of life, have been poorly delineated., Objective: The purpose of this study is to evaluate the impact of anastomotic leak, when intestinal continuity can still be maintained, on bowel function and quality of life in patients undergoing rectal cancer resection with low colorectal or coloanal anastomoses., Design: From 1980 to 2010, 864 patients undergoing restorative resection for rectal cancers were identified from a prospective cancer database. Anastomotic leak detected by a combination of clinical, radiographic, and operative means was diagnosed in 52 (6%) patients., Main Outcome Measures: Patients with anastomotic leak were compared with those without anastomotic leak for functional outcomes and quality of life at 1 year and most recent follow-up (mean 3.2 years) by using Short-Form 36 questionnaires (physical and mental component scales) and the Fecal Incontinence Severity Index., Results: American Society of Anesthesiologists' class (p = 0.48), cancer stage (p = 0.39), and the use of neoadjuvant therapy (p = 0.4) were similar in the 2 groups. Patients with anastomotic leak were younger (56 years vs 61 years; p = 0.007), more likely to be male (82% vs 64%; p = 0.008), and more likely to have undergone proximal diversion at proctectomy (51.9% vs 26.6%; p = 0.001). One year after proctectomy, patients with anastomotic leak had worse physical and mental component scores (p = 0.01), more frequent daytime (p = 0.001) and nighttime bowel movements (p = 0.03), and worse control of solid stool (p = 0.01) in comparison with those without an anastomotic leak. At most recent follow-up (leak, 3.3 years vs no leak, 2.4 years), patients with an anastomotic leak reported worse mental component scores and increased use of perineal pads., Conclusion: Anastomotic leak after restorative resection for rectal cancer leads to early adverse consequences on bowel function and quality of life even when anastomotic continuity can be maintained. These findings may help counsel patients and clinicians regarding anticipated outcomes over the long term.

Background: In 1968, Burrington first described use of the reverse gastric tube esophagoplasty for esophageal replacement in children with esophageal atresia or acquired stenosis. There are few documented cases of long-term follow-up of these patients., Case Report: We describe a 41-year-old female who presented with progressive dysphagia 40 years after reverse gastric tube for a congenital esophageal stenosis as an infant. Repeated endoscopic dilations were unsuccessful in relieving her symptoms, and she subsequently underwent a modified Ivor-Lewis esophagogastrectomy with resection of the reverse gastric tube and reconstruction using her remaining gastric remnant., Conclusions: This report describes what we believe to be the longest recorded follow-up after reverse gastric tube esophagoplasty and highlights the potential for long-term complications after surgery for congenital anomalies., (Copyright © 2011. Published by Elsevier Inc.)

Background: How to best risk-stratify patients with metastatic melanoma in the sentinel node (SN) is controversial. Not all node-positive disease is equivalent in terms of disease-free or overall survival, and some have suggested that submicrometastatic disease, characterized by <0.1 mm tumor burden, can represent a distinct classification not associated with a chance for recurrence or death. We hypothesize that all patients with metastatic melanoma cells in the sentinel node have potentially life-threatening disease., Study Design: This is a retrospective review of an IRB-approved, prospectively maintained melanoma database of >1,100 patients. All invasive melanoma patients who had an SN biopsy and at least 1 year of followup were included. Patients with metastatic melanoma in the SN were divided into groups according to diameter of SN tumor burden: node-negative, <0.1 mm (submicrometastatic), 0.1 to 1.0 mm, and >1.0 mm. Statistical methods included the Jonckheere-Terpstra method, Fisher's exact tests, and Kaplan-Meier method., Results: From July 1, 1998 to July 1, 2007, 578 patients with invasive melanoma underwent SN procedure. Median followup was 2.2 years. There was a statistically significant difference in the proportion of patients who experienced a recurrence between the node-negative group (11%) and the <0.1 mm group (24%) (p = 0.049). Patients in the submicrometastatic group have a statistically significant (p = 0.048) earlier recurrence than those in the node-negative group., Conclusions: These results suggest that patients with submicrometastatic SN disease should not be treated as node-negative, as it appears to represent a more biologically aggressive melanoma, associated with a substantially faster time to recurrence. We cannot agree with recent proposals that patients with very small tumor burden in the SN can be treated as node-negative and be spared completion node dissection.

Background: Macrophages undergo maladaptive alterations after trauma. In this study, we assessed the role of Kupffer cells in hepatic microcirculatory response to endothelin-1 (ET-1) after femur fracture (FFx) and cecal ligation and puncture (CLP)., Methods: Sprague-Dawley rats (200-300 g) underwent sham, FFx, CLP, or FFx + CLP. To ablate Kupffer cells, group 1 animals were treated with gadolinium chloride, and group 2 animals received saline. Hepatic microcirculation was assessed by intravital microscopy. Liver mitochondrial redox state and tissue oxygen (tPo2) were determined by NADH and ruthenium fluorescence, respectively. Liver damage was estimated by alanine aminotransferase levels. Differences were assessed using analysis of variance followed by Student-Newman-Keuls post hoc test., Results: After 10 minutes of ET-1, CLP and FFx + CLP caused significant reduction in hepatic perfusion index (2.5-fold and 5-fold vs. sham, p < 0.05, respectively), redox state (36% and 45% vs. sham, p < 0.01, respectively), tPo2 (10% and 12% vs. sham, p < 0.05, respectively), and more liver damage compared with sham and FFx-treated animals. Kupffer cell depletion restored microcirculation, redox state, and tPo2 and abrogated hepatocellular damage., Conclusion: Kupffer cells contribute directly to hepatic microcirculatory dysfunction and liver injury after inflammatory stress. Furthermore, Kupffer cell depletion ameliorates the microcirculatory perturbations of trauma and sepsis. Thus, modulation of Kupffer cell response may prove beneficial.

This study addresses the microvascular mechanisms by which a remote, mild stress such as blunt trauma sensitizes the liver to injury. Rats received closed femur fracture (FFx), and 24 h later livers were isolated and perfused at a similar starting flow rate for assessment of vascular response to endothelin-1 (ET-1). Sinusoidal volumetric flow (QS), red blood cell velocity (VRBC), and sinusoidal diameter (Ds) were determined by intravital microscopy. Baseline portal resistance in livers from FFx rats was not changed. The FFx group showed a lower baseline VRBC (322.9 +/- 26.4 and 207.3 +/- 17.2 microm/s in sham and FFx,) and QS (28.4 +/- 4.2 and 17.6 +/- 2.1 pL/s in sham and FFx, P < 0.05). ET-1 caused a decrease in the VRBC in sham but no change after FFx. In contrast, Ds was unchanged by ET-1 in sham but decreased in FFx (10.3 +/- 0.4 to 10.7 +/- 0.5 vs. 10.6 +/- 0.4 to 9.0 +/- 0.4 microm at 10 min in sham and FFx groups, P < 0.05). The overall result of these changes was a greater decrease in sinusoidal flow in FFx compared with sham. There was no significant change in mRNA for ET-1, endothelin A (ETA) receptor, or iNOS (inducible nitric oxide synthase) in FFx compared with sham. However, endothelin B (ETB) receptor mRNA and eNOS (endothelial nitric oxide synthase) mRNA were increased in the FFx group (ETB, 54.81 +/- 8.08 in sham vs. 83.28 +/- 8.19 in FFx; eNOS, 56.11 +/- 2.53 in sham vs. 83.31 +/- 5.51 in FFx; P < 0.05) while the levels of these proteins remained unchanged. Caveolin-1 (cav-1) protein levels were elevated in FFx, and coimmunoprecipitation with both ETB and eNOS showed increased associations with these proteins, suggesting a possible inactivation of eNOS. The eNOS activity was also blunted in FFx animals in the presence of increased cav-1 expression. Taken together, these results demonstrate that remote trauma sensitizes the liver to the sinusoidal constrictor effect of ET-1. We propose that this hyperresponsiveness occurs as a result of uncoupling of the ETB receptor from eNOS activity mediated by interaction of eNOS and possibly the ETB receptor with increased caveolin-1. This vascular sensitization that occurs after FFx may contribute to the exacerbation of injury during subsequent stresses.

We conducted this study to elucidate the role of endothelins (ET-1) in mediating the hepatic microcirculatory dysfunction observed in response to sepsis. Following 24 h of cecal ligation and puncture (CLP), we performed intravital microscopy both in vivo and on isolated perfused livers. Portal resistance increased in response to ET-1 in both sham and septic rats, with no significant difference between the two in either in vivo or in isolated livers. Sinusoidal volumetric flow (Qs) was evaluated using red blood cell velocity (V(RBC)) and sinusoidal diameter (Ds) to determine microvascular hemodynamic integrity. Qs decreased in response to ET-1 in livers from CLP rats compared with sham (P < 0.05, CLP vs. sham) in both in vivo and isolated livers. In vivo infusion of ET-1 resulted in greater constriction of sinusoids in the CLP group compared with sham (P < 0.05), resulting in higher sinusoidal resistance. Microvascular hyper-responsiveness was accompanied by hepatocellular injury in CLP rats, but not in sham rats. RT-PCR was performed to measure mRNA levels of ET-1, its receptors ET(A) and ET(B), inducible and constitutive nitric oxide (NO) synthase (iNOS and eNOS, respectively), and heme oxygenase 1 (HO-1). After CLP, both ET-1 and ET(B) mRNA increased, whereas ET(A) mRNA tended to decrease, although the change was not statistically significant. Livers from CLP rats showed no significant change in levels of eNOS mRNA, but showed a significant increase in iNOS expression (13.5-fold over sham). There was no change in the level of HO-1 mRNA between sham and CLP groups. Taken together, these results suggest that sepsis sensitizes the hepatic microcirculation to ET-1. More importantly, an impaired microcirculatory flow due to ET-1 in sepsis contributes to hepatic injury. Further, localized imbalances between endothelins and NO may mediate the altered microvascular response during sepsis.