Prospective multicenter study of a synthetic bioabsorbable anal fistula plug to treat cryptoglandular transsphincteric anal fistulas.

BACKGROUND: Although interest in sphincter-sparing treatments for anal fistulas is increasing, few large prospective studies of these approaches have been conducted. OBJECTIVE: The study assessed outcomes after implantation of a synthetic bioabsorbable anal fistula plug. DESIGN: A prospective, multicenter investigation was performed. SETTING: The study was conducted at 11 colon and rectal centers. PATIENTS: Ninety-three patients (71 men; mean age, 47 years) with complex cryptoglandular transsphincteric anal fistulas were enrolled. Exclusion criteria included Crohn's disease, an active infection, a multitract fistula, and an immunocompromised status. INTERVENTION: Draining setons were used at the surgeon's discretion. Patients had follow-up evaluations at 1, 3, 6, and 12 months postoperatively. MAIN OUTCOME MEASURES: The primary end point was healing of the fistula, defined as drainage cessation plus closure of the external opening, at 6 and 12 months. Secondary end points were fecal continence, duration of drainage from the fistula, pain, and adverse events during follow-up. RESULTS: Thirteen patients were lost to follow-up and 21 were withdrawn, primarily to undergo an alternative treatment. The fistula healing rates at 6 and 12 months were 41% (95% CI, 30%-52%; total n = 74) and 49% (95% CI, 38%-61%; total n = 73). Half the patients in whom a previous treatment failed had healing. By 6 months, the mean Wexner score had improved significantly (p = 0.0003). By 12 months, 93% of patients had no or minimal pain. Adverse events included 11 infections/abscesses, 2 new fistulas, and 8 total and 5 partial plug extrusions. The fistula healed in 3 patients with a partial extrusion. LIMITATIONS: The study was nonrandomized and had relatively high rates of loss to follow-up. CONCLUSION: Implantation of a synthetic bioabsorbable fistula plug is a reasonably efficacious treatment for complex transsphincteric anal fistulas, especially given the simplicity and low morbidity of the procedure.

The effects of preoperative chemoradiotherapy on lymph node sampling in rectal cancer.

BACKGROUND: The current recommendation from the American Joint Committee on Cancer and the International Union Against Cancer is that 12 or more lymph nodes should be examined to appropriately stage rectal cancer. It is unclear if this metric is appropriate or achievable for patients who receive neoadjuvant therapy. OBJECTIVE: The purpose of this study was to review the effects of neoadjuvant chemoradiotherapy on the lymph node yield in patients with rectal cancer. DATA SOURCES: A comprehensive search was made of MEDLINE, PubMed, and Web of Science for articles published through December 2011. STUDY SELECTION: The descriptors rectal neoplasms, lymph nodes, lymph node yield, radiotherapy, and neoadjuvant therapy were used to identify articles that reported the lymph node yield with and without neoadjuvant chemoradiotherapy for rectal cancer. INTERVENTIONS: Patients received either chemoradiotherapy or no neoadjuvant treatment before undergoing total mesorectal excision for rectal cancer. MAIN OUTCOME MEASURES: The main outcome measures included the mean lymph node yield both with and without neoadjuvant treatment, the percentage of patients that received an adequate lymph node dissection, and the number of lymph nodes found to be positive for metastatic disease. RESULTS: A total of 7 studies were included in this review. They demonstrated a decrease in lymph node yield in patients who received neoadjuvant therapy, ranging from 7% to 53% based on the articles in this review. LIMITATIONS: A meta-analysis was not performed because of the limited complete data published on this subject. Consequently, there is heterogeneity in the studies that were selected for this review. CONCLUSIONS: Patients with rectal cancer who receive preoperative chemoradiotherapy should be anticipated to have a lower lymph node yield than patients who receive surgery alone. This calls into question if the current guideline of 12 lymph nodes is relevant, in particular, for those patients receiving neoadjuvant therapy.

Single-port laparoscopic right hemicolectomy: the first 100 resections.

BACKGROUND: Single-port laparoscopy remains a novel technique in the field of colorectal surgery. Several small series have examined its safety for colon resection. OBJECTIVE: Our aim was to analyze our entire experience and short-term outcomes with single-port laparoscopic right hemicolectomy since its introduction at our institution. We assert that this approach is feasible and safe for the wide array of patients and indications encountered by a colorectal surgeon. DESIGN: This is a retrospective analysis of prospectively gathered data for all patients who underwent single-port laparoscopic right hemicolectomy with the use of standard laparoscopic instrumentation, for malignant or benign disease, between July 2009 and November 2010 in a high-volume, academic, colorectal surgery practice. MAIN OUTCOME MEASURES: Demographic, clinical, operative, and pathologic factors were reviewed and analyzed. All conversions to conventional laparoscopic or open operations were considered in this analysis. RESULTS: One hundred patients underwent single-port laparoscopic right hemicolectomy during the study period. Mean age was 63 years, and 61% of the patients were men. Forty-three percent had undergone previous abdominal surgery, and the median body mass index was 26 (range, 18-46). Median ASA classification was 3 (range, 1-4). Five percent of the operations were performed urgently, and 56% were performed for carcinoma, of which half were T3 or T4 tumor stage. Median operative duration was 105 (range, 64-270) minutes. Mean and median blood loss was 106 and 50 mL. Two percent required conversion to multiport laparoscopy, and 4% converted to the open approach. Median postoperative stay was 4 (range, 2-48) days. Median lymph node number was 18 (range, 11-42). There was one mortality in this series. Morbidity, including wound infection, was 13%. CONCLUSIONS: This represents the largest experience with single-port laparoscopic right hemicolectomy to date. This technique was used with acceptable morbidity and mortality and without compromise of conventional oncologic parameters by colorectal surgeons experienced in minimally invasive technique. These findings support the use of a single-port approach for patients requiring right hemicolectomy.

Impact of a Personal Health Record Intervention Upon Surveillance Among Colorectal Cancer Survivors: Feasibility Study.

BACKGROUND: There are currently an estimated 1.5 million individuals living in the United States with colorectal cancer (CRC), and although the 5-year survival rate has increased, survivors are at risk for recurrence, particularly within the first 2-3 years after treatment. National guidelines recommend continued surveillance after resection to identify recurrence early on. Adherence among survivors ranges from 23% to 94%. Novel interventions are needed to increase CRC survivors' knowledge and confidence in managing their cancer and thus to increase adherence to follow-up surveillance. OBJECTIVE: The objective of this study is to develop and test the feasibility and efficacy of a stand-alone, web-based personal health record (PHR) to increase surveillance adherence among CRC survivors, with patient beliefs about surveillance as secondary outcomes. METHODS: A pre- and postintervention feasibility trial was conducted testing the efficacy of the colorectal cancer survivor (CRCS)-PHR, which had been previously developed using an iterative, user-centered design approach. RESULTS: The average age of the sample was 58 (SD 9.9) years, with 57% (16/28) male and the majority married (20/28, 71%) and employed full-time (15/28, 54%). We observed a significant increase in adherence to colonoscopy (before: 11/21, 52% vs after: 18/21, 86%; P=.005) and CEA (14/21, 67% vs 20/21, 95%; P=.01), as well as a slight increase in CT scans (14/21, 67% vs 18/21, 86%; P=.10). The only significant impact on secondary outcome (patient beliefs) was benefits of CEA test (P=.04), as most of the beliefs were high at baseline. CONCLUSIONS: This feasibility study lays the groundwork for continued development of the CRCS-PHR to increase CRC surveillance. Patient-centered technologies, such as the CRCS-PHR, represent an important potential approach to improving the receipt of guideline-concordant care and follow-up surveillance, and not just for CRC survivors. Researchers should continue to develop patient-centered health technologies with clinician implementation in mind to increase patient self-efficacy and surveillance adherence.

Liposomal bupivacaine addition versus standard bupivacaine alone for colorectal surgery: a randomized controlled trial.

Aim: This study evaluated use of liposomal bupivacaine (LB) versus standard bupivacaine (SB) alone in quadratus lumborum (QL) blocks for laparoscopic colorectal surgery. Materials & methods: In this prospective, randomized controlled trial, patients received QL1 blocks with either LB (40 ml 0.125% SB plus 20 ml of LB) or SB (60 ml of 0.25% SB) with 30 ml per side. Opioid usage, pain scores, side effects and other medications were recorded. Results: For 78 patients (38 LB; 40 SB), all parameters were similar between groups, except that the LB group had a higher 48 h need for metoclopramide. Conclusion: LB provided no analgesic benefit over SB alone for QL blocks. Clinical Trials registration number: NCT03702621.

Lay abstract This study evaluated use of extended release bupivacaine (LB) versus standard bupivacaine (SB) alone in nerve blocks for laparoscopic colorectal surgery. Patients undergoing colorectal surgery received nerve blocks with either LB combined with SB, or SB alone. Opioid usage, pain scores, side effects and other medications were recorded. For 78 patients (38 LB + SB; 40 SB), all parameters were similar between groups, except that the LB group had a higher 48 h need for anti-nausea medication. LB provided no pain control benefit over SB alone for nerve blocks in colorectal surgery.

Functional imaging of the pelvic floor.

The clinical treatment of patients with anorectal and pelvic floor dysfunction is often difficult. Dynamic cystocolpoproctography (DCP) has evolved from a method of evaluating the anorectum for functional disorders to its current status as a functional method of evaluating the global pelvic floor for defecatory disorders and pelvic organ prolapse. It has both high observer accuracy and a high yield of positive diagnoses. Clinicians find it a useful diagnostic tool that can alter management decisions from surgical to medical and vice versa in many cases. Functional radiography provides the maximum stress to the pelvic floor, resulting in levator ani relaxation accompanied by rectal emptying-which is needed to diagnose defecatory disorders. It also provides organ-specific quantificative information about female pelvic organ prolapse-information that usually can only be inferred by means of physical examination. The application of functional radiography to the assessment of defecatory disorders and pelvic organ prolapse has highlighted the limitations of physical examination. It has become clear that pelvic floor disorders rarely occur in isolation and that global pelvic floor assessment is necessary. Despite the advances in other imaging methods, DCP has remained a practical, cost-effective procedure for the evaluation of anorectal and pelvic floor dysfunction. In this article, the authors describe the technique they use when performing DCP, define the radiographic criteria used for diagnosis, and discuss the limitations and clinical utility of DCP.

Single-port laparoscopic right hemicolectomy: a safe alternative to conventional laparoscopy.

PURPOSE: Single-port laparoscopic surgery has evolved from an effort to minimize tissue trauma, limit morbidity, and maximize cosmesis. Limited data exist comparing single-port with conventional laparoscopy for right colectomy. Our aim is to compare single-port with laparoscopic colectomy with regard to safety and feasibility. We assert that this approach can be adopted in a safe and efficacious manner while using standard laparoscopic instrumentation. METHODS: This is a retrospective analysis of prospectively gathered data regarding 16 single-port and 27 conventional laparoscopic right hemicolectomies performed by a single surgeon between January 2008 and February 2009. Demographics, operative outcomes, and morbidity were included and analyzed using either Student t test or Fisher exact probability test. RESULTS: Single-port and conventional laparoscopic groups were similar with regard to age, gender, body mass index, prior abdominal surgery, and co-morbidity. Seventy-five percent and 70% of the operations were performed for malignancy in the single-port and the conventional laparoscopy group, respectively (P = .69). Operative duration was 106 minutes in the single-port group vs 100 minutes in the conventional group (P = .64). Blood loss was 54 mL and 90 mL, respectively (P = .07). No conversions or additions of ports occurred. Hospital stay was 5.3 days in the single-port group vs 6 days in the conventional group (P = .53). Margins were negative in both groups. Mean lymph node number was 18 and 16 nodes (P = .92). There was one death in the conventional group (P = .44). Morbidity including wound infection was 18.8% and 14.9%, respectively (P = .73). CONCLUSIONS: These findings support single-port right colectomy as a safe and efficacious approach to right colon resections in patients eligible for laparoscopy with minimal additional equipment or learning curve for experienced laparoscopic colorectal surgeons. The single port was undertaken without an increase in morbidity or mortality. There was no increase in operative time with use of the single-port approach. Finally, adequate lymph node harvest and margin clearance was maintained.

Laparoscopic colectomy: does the learning curve extend beyond colorectal surgery fellowship?

BACKGROUND AND OBJECTIVES: As minimally invasive colon and rectal resection has become increasingly prevalent over the past decade, the role that fellowship training plays has become an important question. This analysis examines the learning curve of one fellowship-trained colorectal surgeon in his first 100 cases. METHODS: This was a prospectively collected retrospective analysis of the first 100 laparoscopic colon and rectal resections performed between July 2007 and July 2008 by a colorectal (CRS) fellowship trained surgeon at a Veteran's Administration (VA) and county hospital. Included were all emergent and nonemergent laparoscopic cases. RESULTS: Mean age was 63(range, 36 to 91). The 100 resections included 42 right, 6 left, 32 sigmoid, 13 rectal, and 7 total abdominal colectomies. Indications were 55% cancer, 20% unresectable polyp, 18% diverticular, 4% inflammatory, and 3% other. Overall mortality was 3%. Overall morbidity including wound infection was 24%. Early and late groups were similar in age, ASA score, and indication. Conversion rate was 4%. No statistical difference was seen in mortality, morbidity, EBL, LOS, margin, lymph nodes, or conversions between the first and second 50 cases (P<0.05). Right and sigmoid colectomy operative time decreased by 40.0% and 19.6%, respectively. CONCLUSION: Prior investigators have demonstrated a significant learning curve for laparoscopic colorectal surgery. In the first 100 cases, there is no difference in mortality or morbidity between early and late cases. Alternatively, operative times decreased with experience. Laparoscopic training during CRS fellowship surpasses the learning curve in regard to safety and outcome, whereas operative efficiency improves over the first year of practice.

Evaluation of Circulating Tumor DNA for Methylated BCAT1 and IKZF1 to Detect Recurrence of Stage II/Stage III Colorectal Cancer (CRC).

BACKGROUND: Most recurrences of early-stage colorectal cancer detected with current surveillance measures are widespread and incurable. Circulating tumor DNA (ctDNA) may facilitate earlier diagnosis of recurrent colorectal cancer and improve cancer-related outcomes. METHODS: Plasma from patients undergoing standard surveillance after definitive treatment for stage II/III colorectal cancer was assayed with COLVERA and carcinoembryonic antigen (CEA) at a single time point. Results were correlated with radiographic imaging. Assay performance, including sensitivity and specificity for recurrence, were compared. Impact of potentially confounding variables was also explored. RESULTS: 322 patients were included in the final analysis, and 27 recurrences were documented over a median follow-up period of 15 months. Sensitivity for recurrence was 63% [confidence interval (CI), 42.4-80.6] and 48% (CI, 28.7-68.1) for COLVERA and CEA (≥5 ng/mL), respectively (P = 0.046), while specificity was 91.5% (CI, 87.7-94.4) and 96.3% (CI, 93.4-98.1), respectively (P = 0.016). Smoking and age were independent predictors of CEA but not COLVERA positivity. CONCLUSIONS: COLVERA was more sensitive but less specific than CEA in detecting recurrent colorectal cancer. Short median follow-up may have been responsible for apparent false positives in COLVERA. Studies with serial sampling and longer follow-up are needed to assess whether earlier detection of colorectal cancer recurrence translates into clinical benefit. IMPACT: This prospective study showed that COLVERA (a two-gene ctDNA assay) was more sensitive for detection of recurrence in a cohort of patients undergoing surveillance after definitive therapy for stages II and III colorectal cancer.

Usefulness and Usability of a Personal Health Record and Survivorship Care Plan for Colorectal Cancer Survivors: Survey Study.

BACKGROUND: As a result of improvements in cancer screening, treatment, and supportive care, nearly two-thirds of individuals diagnosed with colorectal cancer (CRC) live for 5 years after diagnosis. An ever-increasing population of CRC survivors creates a need for effective survivorship care to help manage and mitigate the impact of CRC and its treatment. Personal health records (PHRs) and survivorship care plans provide a means of supporting the long-term care of cancer survivors. OBJECTIVE: The purpose of this study is to characterize the usefulness of a CRC PHR and survivorship care plan and to describe the usability of these technologies in a population of CRC survivors. To our knowledge, this is the first study to assess a PHR and survivorship care plan specifically targeting CRC survivors. METHODS: Twenty-two patients with CRC were recruited from surgery clinics of an academic medical center and Veterans Affairs hospital in Indianapolis and provided access to an online Colorectal Cancer Survivor's Personal Health Record (CRCS-PHR). Survey data were collected to characterize the usefulness of the CRCS-PHR and describe its usability in a population of CRC survivors. CRC survivors were surveyed 6 months after being provided online access. Means and proportions were used to describe the usefulness and ease of using the CRC website. Open-ended questions were qualitatively coded using the constant comparative method. RESULTS: CRC survivors perceived features related to their health care (ie, summary of cancer treatment history, follow-up care schedule, description of side effects, and list of community resources) to be more useful than communication features (ie, creating online relationships with family members or caregivers, communicating with doctor, and secure messages). CRC survivors typically described utilizing traditional channels (eg, via telephone or in person) to communicate with their health care provider. Participants had overall positive perceptions with respect to ease of use and overall satisfaction. Major challenges experienced by participants included barriers to system log-in, lack of computer literacy or experience, and difficulty entering their patient information. CONCLUSIONS: For CRC, survivors may find the greater value in a PHR's medical content than the communication functions, which they have available elsewhere. These findings regarding the usefulness and usability of a PHR for the management of CRC survivorship provide valuable insights into how best to tailor these technologies to patients' needs. These findings can inform future design and development of PHRs for purposes of both cancer and chronic disease management.

Perioperative Management of Patients with Colovesical Fistula.

BACKGROUND: Colovesical fistula (CVF) is an uncommon complication of diverticulitis. Substantial heterogeneity exists in the perioperative management of this condition. We seek to evaluate the role of bladder leak testing, closed suction drainage, prolonged bladder catheter usage, and routine postoperative cystogram in the management of CVF. STUDY DESIGN: This is a retrospective study from a single academic health center investigation patients undergoing operation for diverticular CVF from 2005 to 2015 (n = 89). RESULTS: Patients undergoing operative repair for diverticular CVF resection had a mortality of 4% and overall morbidity of 46%. Intraoperative bladder leak test was performed in 36 patients (40%) and demonstrated a leak in 4 patients (11%). No patients with a negative intraoperative bladder leak test developed a urinary leak. Overall, five (6%) patients developed postoperative bladder leak. Three were identified by elevated drain creatinine and two by cystogram. The diagnostic yield of routine cystogram was 3%. All bladder leaks were diagnosed between postoperative day 3 and 7. Of patients with a postoperative bladder leak, none required reoperation and all resolved within 2 months. CONCLUSIONS: There is significant variability in the management of patients undergoing operation for CVF. Routine intraoperative bladder leak test should be performed. Cystogram may add cost and is low yield for routine evaluation for bladder leak after operation for CVF. Urinary catheter removal before postoperative day 7 should be considered.

Contemporary Management of Sigmoid Volvulus.

BACKGROUND: Sigmoid volvulus is an uncommon cause of bowel obstruction that is historically associated with high morbidity and mortality. The objective of this study was to evaluate contemporary management of sigmoid volvulus and the safety of primary anastomosis in patients with sigmoid volvulus. METHODS: The National Surgical Quality Improvement Project from 2012 to 2015 was queried for patients with colonic volvulus who underwent left-sided colonic resection. A propensity score-matched analysis was performed to compare patients with sigmoid volvulus undergoing colectomy with primary anastomosis without proximal diversion to colectomy with end colostomy. RESULTS: Two thousand five hundred thirty-eight patients with sigmoid volvulus were included for analysis. Patients had a median age of 68 years (interquartile range, 55-80) and 79% were fully independent preoperatively. Fifty-one percent of operations were performed emergently. One thousand eight hundred thirteen (71%) patients underwent colectomy with anastomosis, 240 (10%) colectomy with anastomosis and proximal diversion, and 485 (19%) colectomy with end colostomy. Overall, 30-day mortality and morbidity were 5 and 40%, respectively. After propensity score matching, mortality, overall morbidity, and serious morbidity were similar between groups. CONCLUSIONS: Sigmoid volvulus occurs in elderly and debilitated patients with significant morbidity, mortality, and lifestyle implications. In selected patients, anastomosis without proximal diversion in patients with sigmoid volvulus results in similar outcomes to colectomy with end colostomy.

Bowel Preparation Is Associated with Reduced Morbidity in Elderly Patients Undergoing Elective Colectomy.

BACKGROUND: Bowel preparation in elderly patients is associated with physiologic derangements that may result in postoperative complications. The aim of this study is to determine the impact of bowel preparation on postoperative outcomes in elderly patients. METHODS: Patients age 75 years and older who underwent elective colectomy were identified from the 2012-2014 American College of National Surgical Quality Improvement Program (ACS-NSQIP database). Patients were grouped into no bowel preparation, mechanical bowel preparation (MBP), oral antibiotic preparation (OABP), or combined MBP + OABP. Logistic regression modeling was conducted to calculate risk-adjusted 30-day outcomes. RESULTS: There were 4829 patients included in the analysis. Morbidity was 34.3% in no bowel prep, 32.4% in MBP, 24.8% in OABP, and 24.6% in MBP + OABP groups (p < 0.001). The MBP + OABP group compared with no bowel prep was associated with reduced rates of anastomotic leak, ileus, superficial surgical site infection (SSI), organ space SSI, respiratory compromise, and reduced length of stay. There was no difference in the rate of acute kidney injury between the groups. CONCLUSION: MBP + OABP was associated with reduced morbidity compared with no bowel preparation in elderly patients undergoing elective colorectal resection. MBP alone was not associated with differences in outcomes compared with no bowel preparation. The use of MBP + OABP is safe and effective in elderly patients undergoing elective colectomy.

IL-1beta activates C/EBP-beta and delta in human enterocytes through a mitogen-activated protein kinase signaling pathway.

The enterocyte is an active participant in the inflammatory and metabolic response to sepsis, endotoxemia and other critical illnesses and is the site for cytokine and acute phase protein production in these conditions. The role of the CCAAT/enhancer binding protein (C/EBP) family of transcription factors in the response to inflammatory stimuli in the enterocyte is not well understood. In the present study, we treated Caco-2 cells with IL-1beta and determined C/EBP DNA binding activity by electrophoretic mobility shift assay. The involvement of the alpha, beta, and delta isoforms was determined by supershift analysis and Western blot analysis of proteins from the nuclear fraction. The role of the mitogen-activated protein kinase (MAPK) signaling pathway was assessed by treating cells with the MAPK inhibitor PD-98059. Treatment of the Caco-2 cells with IL-1beta resulted in increased CCAAT/enhancer binding protein DNA binding activity. Supershift analysis and Western blotting indicated that this response to IL-1beta mainly reflected the delta isoform, and to a lesser degree the beta isoform. Treatment of the cells with PD-98059 inhibited the IL-1beta-induced increase in beta and delta activity. The results suggest that members of the CCAAT/enhancer binding protein family of transcription factors are activated in enterocytes during inflammatory conditions characterized by high levels of IL-1beta.

Interleukin-10 activates the transcription factor C/EBP and the interleukin-6 gene promoter in human intestinal epithelial cells.

BACKGROUND: Interleukin (IL)-6 is produced by enterocytes in response to sepsis and after treatment with IL-1beta. The IL-6 promoter contains binding sites for multiple transcription factors, including nuclear factor-kappaB and C/EBP. The anti-inflammatory cytokine IL-10 downregulates nuclear factor-kappaB activity, but its effects on C/EBP activation and IL-6 production in the enterocyte are not known. METHODS: Caco-2 cells were treated with IL-1beta, IL-10, or a combination of the cytokines. C/EBP DNA binding activity was determined by electrophoretic mobility shift assay and IL-6 levels by enzyme-linked immunosorbent assay. IL-6 promoter activation was assessed by luciferase assay. RESULTS: IL-10 treatment of cultured Caco-2 cells resulted in increased C/EBP DNA binding activity. Supershift analysis revealed upregulated DNA binding activity of C/EBP-beta but not C/EBP-delta. To examine if the increased DNA binding reflected gene activation, cells were transfected with a wild-type IL-6 promoter luciferase construct or with a mutated C/EBP binding site. IL-10 potentiated IL-1 beta-induced IL-6 promoter activity. Replacing the wild-type promoter with the promoter containing a mutated C/EBP DNA binding sequence blocked the effect of IL-10. When cells were treated with 0.5 ng/mL of IL-1 beta for 24 hours, IL-6 production increased, and this response to IL-1 beta was potentiated several-fold by IL-10. CONCLUSIONS: IL-10 may activate the IL-6 gene in stimulated enterocytes by upregulating the expression and activity of C/EBP.

Early debridement for necrotizing pancreatitis: is it worthwhile?

BACKGROUND: The timing for debridement of necrotizing pancreatitis is controversial. We reviewed our experience with early and delayed surgical debridement in patients with necrotizing pancreatitis. STUDY DESIGN: The records of patients diagnosed with acute necrotizing pancreatitis from January 1993 through June 2000 were reviewed retrospectively. Data were analyzed with respect to Ranson's, APACHE II, and multiple organ failure scores, etiology, presence of infection, overall and ICU length of stay, time to first debridement, number of debridements, fluid requirements, days to enteral feeding, transfusion requirements, complications, and mortality. RESULTS: Twenty-six patients (18 males, 8 females, mean age 51 years) were diagnosed with acute necrotizing pancreatitis. The admission Ranson's score was 4.8, the APACHE II score was 11.7, and multiple organ failure score was 4.2. All but one patient underwent pancreatic debridement (4.3 debridements per patient). Eighteen patients (69%) had infected pancreatic necrosis. The timing of debridement was based on patients' condition and surgeon's preference. The presentation and demographics of patients who underwent early (<2 weeks) or late (>2 weeks) debridement did not differ significantly. Patients debrided early had a trend toward higher mortality (29% versus 18%) and experienced a higher number of major complications (p < 0.05). The six patients (23%) who died were older, had multiple organ failure scores, and more often had Candida in the infected necrosis (p < .05). CONCLUSIONS: Early debridement for acute necrotizing pancreatitis might not improve survival and might even be associated with increased number of complications. Most patients diagnosed with necrotizing pancreatitis eventually need debridement, but it might be beneficial to delay debridement if the patient's condition allows for it.

Hyperthermia-induced heat shock activates the transcription factor c/EBP-beta and augments IL-6 production in human intestinal epithelial cells.

BACKGROUND: Interleukin (IL)-6 production is increased in gut mucosa during sepsis and endotoxemia. The heat shock response augments IL-6 production under these conditions, but the mechanism is not known. We hypothesized that heat shock stimulates IL-6 production in enterocytes by increasing expression and activity of the transcription factor C/EBB. STUDY DESIGN: Cultured Caco-2 cells, a human intestinal epithelial cell line, underwent induction of the heat shock response by hyperthermia (43 degrees C for 1 hour). Other cells were kept at 37 degrees C. Cells were then treated with 0.5 ng/mL human recombinant IL-1beta for 4 hours. C/EBP-beta and delta DNA binding activity was determined by electrophoretic mobility shift assay and supershift analysis. In additional experiments, Caco-2 cells were transfected with expression plasmids for C/EBP-beta and delta, after which cells were subjected to hyperthermia and treatment with IL-1beta. RESULTS: C/EBP-beta, but not delta, protein levels and DNA binding activity were increased in Caco-2 cells expressing the heat shock response. Induction of the heat shock response augmented IL-6 production in IL-1beta-treated cells overexpressing C/EBP-beta, but not delta. CONCLUSIONS: Increased IL-6 production in IL-1beta-treated enterocytes expressing the heat shock response might be caused by upregulated expression and activity of CIEBP-beta. Because recent studies suggest that IL-6 might be an antiinflammatory cytokine and might exert protective effects in gut mucosa and enterocytes, understanding mechanisms by which the heat shock response augments IL-6 production might have important clinical implications.

Mucosal and enterocyte IL-6 production during sepsis and endotoxemia--role of transcription factors and regulation by the stress response.

BACKGROUND: Sepsis and endotoxemia are associated with increased production of interleukin-6 (IL-6) in gut mucosa. Mucosal IL-6 may regulate enterocyte acute phase protein synthesis and intestinal IgA production. In addition, increased IL-6 has been proposed to be a mechanism of loss of mucosal integrity in critical illness. The purpose of this review is to describe current knowledge of the regulation of IL-6 production in the enterocyte/mucosa during inflammation caused by sepsis and endotoxemia. DATA SOURCES: Recent publications describing the influence of sepsis, endotoxemia, and proinflammatory cytokines on mucosal/enterocyte IL-6 production. CONCLUSIONS: IL-6 production is increased in gut mucosa during sepsis and endotoxemia and in cultured enterocytes after treatment with endotoxin or proinflammatory cytokines. The IL-6 gene is regulated by multiple transcription factors, including NF-kappaB, AP-1, and C/EBP. Because of the multiple important biological roles of IL-6, understanding the cellular and molecular mechanisms of mucosal/enterocyte IL-6 production as well as methods to modulate IL-6 production is of clinical importance in the setting of sepsis and other critical illness.

Quality of life in patients undergoing ileal pouch-anal anastomosis at the University of Cincinnati.

BACKGROUND: In 1978, Drs. Fischer and Martin were among the first to preserve anorectal continence and create a pelvic reservoir in adult patients, in what has become the ileal pouch-anal anastomosis (IPAA). METHODS: Here we review our institutions' experience with 379 of these procedures from 1978 to present. To assess the specific health concerns of patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP) and determine the effects of IPAA on health-related quality of life, we evaluated patients with the SF-36, the Rating Form of Inflammatory Bowel Disease Patient Concerns (RFIPC), time trade-off questions, and a gamble question. RESULTS: IPAA patients did not differ from the general population in seven of eight general health categories assessed by the SF-36. When compared with the UC population as a whole using the RFIPC they had reduced concerns in almost all areas. In addition, time trade-off and gamble questions indicated that these patients, as a group, are willing to accept a significant risk of dying in order to achieve their results of the IPAA. CONCLUSIONS: This high level of satisfaction has led to the referral of patients who would not have otherwise considered a procedure requiring permanent ileostomy.