EP3 signaling is decoupled from the regulation of glucose-stimulated insulin secretion in ß-cells compensating for obesity and insulin resistance.

Of the ß-cell signaling pathways altered by obesity and insulin resistance, some are adaptive while others contribute to ß-cell failure. Two critical second messengers are Ca2+ and cAMP, which control the timing and amplitude of insulin secretion. Previous work has shown the importance of the cAMP-inhibitory Prostaglandin EP3 receptor (EP3) in mediating the ß-cell dysfunction of type 2 diabetes (T2D). Here, we used three groups of C57BL/6J mice as a model of the progression from metabolic health to T2D: wildtype, normoglycemic LeptinOb (NGOB), and hyperglycemic LeptinOb (HGOB). Robust increases in ß-cell cAMP and insulin secretion were observed in NGOB islets as compared to wildtype controls; an effect lost in HGOB islets, which exhibited reduced ß-cell cAMP and insulin secretion despite increased glucose-dependent Ca2+ influx. An EP3 antagonist had no effect on ß-cell cAMP or Ca2+ oscillations, demonstrating agonist-independent EP3 signaling. Finally, using sulprostone to hyperactivate EP3 signaling, we found EP3-dependent suppression of ß-cell cAMP and Ca2+ duty cycle effectively reduces insulin secretion in HGOB islets, while having no impact insulin secretion on NGOB islets, despite similar and robust effects on cAMP levels and Ca2+ duty cycle. Finally, increased cAMP levels in NGOB islets are consistent with increased recruitment of the small G protein, Rap1GAP, to the plasma membrane, sequestering the EP3 effector, Gɑz, from inhibition of adenylyl cyclase. Taken together, these results suggest that rewiring of EP3 receptor-dependent cAMP signaling contributes to the progressive changes in ß cell function observed in the LeptinOb model of diabetes.

Human Islet Expression Levels of Prostaglandin E2 Synthetic Enzymes, But Not Prostaglandin EP3 Receptor, Are Positively Correlated with Markers of ß-Cell Function and Mass in Nondiabetic Obesity.

Elevated islet production of prostaglandin E2 (PGE2), an arachidonic acid metabolite, and expression of prostaglandin E2 receptor subtype EP3 (EP3) are well-known contributors to the ß-cell dysfunction of type 2 diabetes (T2D). Yet, many of the same pathophysiological conditions exist in obesity, and little is known about how the PGE2 production and signaling pathway influences nondiabetic ß-cell function. In this work, plasma arachidonic acid and PGE2 metabolite levels were quantified in a cohort of nondiabetic and T2D human subjects to identify their relationship with glycemic control, obesity, and systemic inflammation. In order to link these findings to processes happening at the islet level, cadaveric human islets were subject to gene expression and functional assays. Interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) mRNA levels, but not those of EP3, positively correlated with donor body mass index (BMI). IL-6 expression also strongly correlated with the expression of COX-2 and other PGE2 synthetic pathway genes. Insulin secretion assays using an EP3-specific antagonist confirmed functionally relevant upregulation of PGE2 production. Yet, islets from obese donors were not dysfunctional, secreting just as much insulin in basal and stimulatory conditions as those from nonobese donors as a percent of content. Islet insulin content, on the other hand, was increased with both donor BMI and islet COX-2 expression, while EP3 expression was unaffected. We conclude that upregulated islet PGE2 production may be part of the ß-cell adaption response to obesity and insulin resistance that only becomes dysfunctional when both ligand and receptor are highly expressed in T2D.

Agonist-independent Gαz activity negatively regulates beta-cell compensation in a diet-induced obesity model of type 2 diabetes.

The inhibitory G protein alpha-subunit (Gαz) is an important modulator of beta-cell function. Full-body Gαz-null mice are protected from hyperglycemia and glucose intolerance after long-term high-fat diet (HFD) feeding. In this study, at a time point in the feeding regimen where WT mice are only mildly glucose intolerant, transcriptomics analyses reveal islets from HFD-fed Gαz KO mice have a dramatically altered gene expression pattern as compared with WT HFD-fed mice, with entire gene pathways not only being more strongly upregulated or downregulated versus control-diet fed groups but actually reversed in direction. Genes involved in the "pancreatic secretion" pathway are the most strongly differentially regulated: a finding that correlates with enhanced islet insulin secretion and decreased glucagon secretion at the study end. The protection of Gαz-null mice from HFD-induced diabetes is beta-cell autonomous, as beta cell-specific Gαz-null mice phenocopy the full-body KOs. The glucose-stimulated and incretin-potentiated insulin secretion response of islets from HFD-fed beta cell-specific Gαz-null mice is significantly improved as compared with islets from HFD-fed WT controls, which, along with no impact of Gαz loss or HFD feeding on beta-cell proliferation or surrogates of beta-cell mass, supports a secretion-specific mechanism. Gαz is coupled to the prostaglandin EP3 receptor in pancreatic beta cells. We confirm the EP3γ splice variant has both constitutive and agonist-sensitive activity to inhibit cAMP production and downstream beta-cell function, with both activities being dependent on the presence of beta-cell Gαz.

Angiogenesis and CD34 expression as a predictor of recurrence in oral squamous cell carcinoma.

PURPOSE: To assess immunohistologic features of angiogenesis of T1N0M0 oral squamous cell carcinoma (OSCC), and to identify predictors of regional recurrence. The identification of prognostic markers of early lymph node involvement in OSCC could allow for the use of more targeted biologic therapies for patients with early-stage tumors. PATIENTS AND METHODS: The study included patients treated for T1N0M0 OSCC at the Mayo Clinic from 1986 to 2001. All patients had initial surgical resection without neck dissection, and all had adequate follow-up with histologic specimens for review. Patients with lip, pharyngeal, or salivary gland tumors were excluded. Patient specimens were regraded and assessed for the histologic markers p53 and CD34 (penetrating and circumscribing patterns). The Kaplan-Meier method was used to estimate patient survival and survival free of regional recurrence. RESULTS: The study included 175 patients. The overall 5-year survival was 75%, and 5-year survival free of regional recurrence was 80.3%. Twenty-eight patients had regional recurrence. High-grade tumors (P = .03) and the penetrating pattern of CD34 (P = .02) were significantly associated with early regional metastasis from early-stage OSCC. The presence of p53 was not independently associated as a marker for regional metastasis. CONCLUSION: Early-stage T1 OSCC with high-grade lesions and a penetrating pattern of CD34 was associated with a statistically significant risk of cervical lymph node metastasis, compared with a circumscribing pattern of CD34.

Surgical treatment of early wound complications following primary total knee arthroplasty.

BACKGROUND: Wound-healing problems are a known complication after primary total knee arthroplasty. However, little is known about the clinical outcomes for patients who require surgical treatment of these early wound-healing problems. The purpose of the present study was to determine the incidence, risk factors, and long-term sequelae of early wound complications requiring surgical treatment. METHODS: The total joint registry at our institution was reviewed for the period from 1981 to 2004. All knees with early wound complications necessitating surgical treatment within thirty days after the index total knee arthroplasty were identified. The cumulative probabilities for the later development of deep infection and major subsequent surgery were determined. A case-control study in which these patients were matched with an equal number of controls was performed to attempt to identify risk factors for the development of early superficial wound complications requiring surgical intervention. RESULTS: From 1981 to 2004, 17,784 primary total knee arthroplasties were performed at our institution. Fifty-nine knees were identified as having early wound complications necessitating surgical treatment within thirty days after the index arthroplasty, for a rate of return to surgery of 0.33%. For knees with early surgical treatment of wound complications, the two-year cumulative probabilities of major subsequent surgery (component resection, muscle flap coverage, or amputation) and deep infection were 5.3% and 6.0%, respectively. In contrast, for knees without early surgical intervention for the treatment of wound complications, the two-year cumulative probabilities were 0.6% and 0.8%, respectively (p < 0.001 for both comparisons). A history of diabetes mellitus was identified as being significantly associated with the development of early wound complications requiring surgical intervention. CONCLUSIONS: Patients requiring early surgical treatment for wound-healing problems after primary total knee arthroplasty are at significantly increased risk for further complications, including deep infection and/or major subsequent surgery, specifically, resection arthroplasty, amputation, or muscle flap coverage. These results emphasize the importance of obtaining primary wound-healing after total knee arthroplasty.

Early return to surgery for evacuation of a postoperative hematoma after primary total knee arthroplasty.

BACKGROUND: Development of a postoperative hematoma is a reported complication after primary total knee arthroplasty. However, little is known about the clinical outcomes in patients who require surgical evacuation of an acute hematoma. The purpose of this study was to determine the incidence, risk factors, and long-term sequelae of postoperative hematomas requiring surgical evacuation. METHODS: From 1981 to 2004, 17,784 primary total knee arthroplasties were performed at our institution. Forty-two patients (forty-two knees) returned to the operating room within thirty days of the index arthroplasty for evacuation of a postoperative hematoma. A case-control study, with forty-two patients matched one-to-one with forty-two control subjects, was performed to attempt to identify risk factors for the development of postoperative hematoma requiring surgical evacuation. RESULTS: The rate of return to surgery within thirty days for evacuation of a postoperative hematoma was 0.24% (95% confidence interval, 0.17% to 0.32%). For patients undergoing postoperative hematoma evacuation, the two-year cumulative probabilities of undergoing subsequent major surgery (component resection, muscle flap coverage, or amputation) or having a deep infection develop were 12.3% (95% confidence interval, 1.6% to 22.4%) and 10.5% (95% confidence interval, 0.2% to 20.2%), respectively. In contrast, for knees without early hematoma evacuation, the two-year cumulative probabilities were 0.6% (95% confidence interval, 0.5% to 0.7%) and 0.8% (95% confidence interval, 0.6% to 0.9%), respectively (p < 0.001 for both outcomes). A history of a bleeding disorder was identified as having a significant association with the development of a hematoma requiring surgical evacuation (p = 0.046). CONCLUSIONS: Patients who return to the operating room within thirty days after the index total knee arthroplasty for evacuation of a postoperative hematoma are at significantly increased risk for the development of deep infection and/or undergoing subsequent major surgery. These results support all efforts to minimize the risk of postoperative hematoma formation.

Segmental vs. extended colectomy: measurable differences in morbidity, function, and quality of life.

PURPOSE: The colon coordinates fecal elimination while reabsorbing excess fluid. Extended colonic resection removes synchronous and prevents metachronous disease but may adversely alter bowel function and health-related quality of life to a greater degree than segmental resection. This study examined the short-term morbidity and long-term function and quality of life after colon resections of different extents. METHODS: Patients undergoing extended resections (n = 201, subtotal colectomy with ileosigmoid or total abdominal colectomy with ileorectal anastomosis) and segmental colonic resections (n = 321) during 1991 to 2003 were reviewed for perioperative outcomes and surveyed for bowel function and quality of life using an institutional questionnaire and a validated quality of life instrument (response rate: 70 percent). RESULTS: The most common indication for extended resections was multiple polyps, and for segmental resections, single malignancy. The complication-free rate was 75.4 percent after segmental resections, 42.8 percent after ileosigmoid anastomosis, and 60 percent after ileorectal anastomosis. Median daily stool frequency was two after segmental resections, four after ileosigmoid anastomosis, and five after ileorectal anastomosis, despite considerable dietary restrictions (55.6 percent) and medication use (19.6 percent daily) after ileorectal anastomosis. Significant proportions of patients felt restricted from preoperative social activity (31.5 percent), housework (20.4 percent), recreation (31.5 percent), and travel (42.6 percent) after ileorectal anastomosis. The overall quality of life after segmental resection, ileosigmoid anastomosis, and ileorectal anastomosis was 98.5, 94.9, and 91.2, respectively. CONCLUSIONS: Measurable compromises in long-term bowel function and quality of life were observed after extended vs. segmental resections. The relative differences in patient-related outcomes should be deliberated against the clinical benefits of extended resection for the individual patient.

Patient-reported activity level after total knee arthroplasty.

We identified 1630 unrevised patients who underwent primary total knee arthroplasty (TKA) between 1995 and 2000. Patients were surveyed regarding clinical outcome and activity level, and were queried about actual participation in 40 different athletic activities. One thousand two hundred six patients (74%) responded at a mean of 5.7 years after arthroplasty. Average age at TKA was 67 years. Average University of California at Los Angeles (UCLA) activity level rating was 7.1. Satisfaction with activity level was 91%. Six hundred forty-three patients (53%) responded that their activities were limited by other joints. Patients older than 70 years at arthroplasty had lower UCLA ratings and Knee Society function scores (P < .0001) but higher self-assessment of activity vs peers (P = .001) than those younger than 70 years. Men had higher UCLA scores (P < .0001), Knee Society function scores (P < .0001), and higher self-assessment of activity level vs peers (P < .0001) than women. One hundred eighty-seven patients (16%) reported participating in heavy manual labor or sports deemed "not recommended" in a published Knee Society survey.

Patient reported activity after revision total knee arthroplasty.

A total of 335 patients underwent revision total knee arthroplasty (TKA) between 1995 and 2000 with a single implant design. These patients were surveyed regarding clinical outcome and activity level; 206 patients responded (62%). Average age at revision TKA was 69 years (range, 31-87 years). Average follow-up was 5.6 years (range, 3-9 years). Average University of California at Los Angeles activity level rating was 6.7 (range, 2-10). Satisfaction with activity level after TKA was 77%. Among the respondents, 126 (61%) indicated that their activities were limited by other joints. Patients younger than 70 years had higher University of California at Los Angeles activity level scores (P=.054) and Knee Society function scores (P < .001), but there was no difference in self-assessment of activity level vs peers (P = .81) compared to those older than 70 years. Patients most commonly reported participating in walking, stationary biking, swimming, and dancing. Twenty-three (12%) patients reported participating in heavy manual labor or sports deemed "not recommended" by Knee Society published guidelines.

Effect of infliximab on short-term complications in patients undergoing operation for chronic ulcerative colitis.

BACKGROUND: Total proctocolectomy and ileal pouch anal anastomosis (IPAA) is the preferred operation for patients with chronic ulcerative colitis (CUC) refractory to medical therapy. Infliximab (IFX), an antitumor necrosis factor-alpha antibody, has demonstrated efficacy in medical management of CUC. The aim of this study is to determine if IFX before IPAA impacts short-term outcomes. STUDY DESIGN: A prospective institutional database was retrospectively reviewed for short-term complications after IPAA for CUC. Postoperative outcomes were compared between patients who received pre-IPAA IFX and those who did not. RESULTS: Between 2002 and 2005, 47 patients received IFX before IPAA, and 254 patients received none. There were no gender (p = 0.16) or body mass index (p = 0.07) differences between groups. IFX patients were younger than non-IFX patients (mean age 28.1 to 39.3 years) (p < 0.001). In IFX patients, 70% were receiving preoperative IFX, azathioprine, and corticosteroids. Mortality was nil. Overall surgical morbidity was similar: 61.7% and 48.8%, IFX and non-IFX, respectively (p = 0.10). Anastomotic leaks (p = 0.02), pouch-specific (p = 0.01) and infectious (p < 0.01) complications were more common in IFX patients. Multivariable analysis revealed IFX as the only factor independently associated with infectious complications (odds ratio [OR] = 3.5; CI, 1.6-7.5). In a separate analysis, incorporating age, high-dose corticosteroids, azathioprine, and severity of colitis, IFX remained significantly associated with infectious complications (OR = 2.7; CI, 1.1-6.7). CONCLUSIONS: CUC patients treated with IFX before IPAA have substantially increased the odds of postoperative pouch-related and infectious complications. Additional prospective studies are required to determine if IFX alone or other factors contribute to the observed increases in infectious complications.

Pulmonary embolism: prognostic CT findings.

PURPOSE: To retrospectively determine whether three computed tomographic (CT) findings-ventricular septal bowing (VSB), ratio between the diameters of right ventricle (RV) and left ventricle (LV), and embolic burden-are associated with short-term death, defined as in-hospital death or death within 30 days of CT, whichever was longer, due to acute pulmonary embolism (PE). MATERIALS AND METHODS: Institutional Review Board approval was obtained, and patient information was reviewed in compliance with HIPAA regulations. A total of 1193 patients with CT scans positive for PE from January 1, 1997, to December 31, 2002, who had given authorization for retrospective research were included. Scans were independently reviewed by two observers. CT findings were compared with risk of death by using univariate analysis (chi(2) statistic) and multivariate logistic regression. Interobserver variability (kappa statistic or intraclass correlation coefficient), sensitivity, and specificity of CT findings for predicting death were calculated. A third observer reviewed discrepant cases post hoc. RESULTS: Fifty-four percent of patients were women and 46% were men (mean age, 63 years +/- 16). For observer 1, VSB was associated with death in univariate (odds ratio [OR], 1.98; P = .04) and multivariate modeling (OR, 1.97; P = .05). Interobserver variability was only fair (kappa = 0.54) for VSB, and observer 2 found no association with death (OR, 1.52; P = .22). For both observers, VSB had low sensitivity (21% and 18%) and high specificity (88% and 87%) for predicting death. Neither RV/LV diameter ratio nor embolic burden was associated with increased risk of death. For observer 3, VSB was associated with death in univariate (OR, 2.10; P = .05) and multivariate analyses (OR, 2.18; P = .05). CONCLUSION: CT-depicted VSB is predictive of death due to PE, but with low sensitivity and high interobserver variability. RV/LV diameter ratio and embolic burden are not associated with short-term death due to PE.

Surgery versus conservative therapy in carpal tunnel syndrome in people aged 70 years and older.

BACKGROUND: Carpal tunnel syndrome is common in the general population, with a prevalence that increases with age. Although good satisfaction has been described after carpal tunnel release, little is known about the long-term outcome of treatment in elderly individuals with carpal tunnel syndrome. METHODS: The authors reviewed data from a population-based sample of 102 patients aged 70 years and older with carpal tunnel syndrome. They used valid and sensitive mailed follow-up outcome [Boston Carpal Tunnel, satisfaction (American Academy of Orthopaedic Surgeons), and health status (Short Form-36) questionnaires to assess symptoms, functional status, expectations of treatment, and satisfaction with the results at a minimum of 2 years after initial diagnosis. RESULTS: Seventy patients with a mean age of 77.0 years (range, 70.2 to 88.5 years) responded to the survey, with a mean follow-up of 4.8 years. Patients who had surgery were more likely to have had more severe disease than those treated nonoperatively (Mantel-Haentzel test, p < 0.001). Satisfaction was 93 percent after surgical treatment and 54 percent after nonsurgical treatment. Patients who had surgery had significantly better relief of symptoms (t test, p < 0.01), functional status (t test, p < 0.05), satisfaction (t test, p < 0.001), and expectations with treatment (t test, p < 0.05) scores as compared with those who had nonsurgical treatment. CONCLUSIONS: In patients over the age of 70, surgery appears to be associated with better symptom relief, functional status, satisfaction, and expectations with treatment than nonoperative therapy does. Age should not be considered a contraindication for carpal tunnel surgery, nor should nonoperative therapy be favored in this age group.

Factors affecting outcomes of open surgical repair of pararenal aortic aneurysms: a 10-year experience.

PURPOSE: Few large series document surgical outcomes for patients with pararenal abdominal aortic aneurysms (PAAAs), defined as aneurysms including the juxtarenal aorta or renal artery origins that require suprarenal aortic clamping. No standard endovascular alternatives presently exist; however, future endovascular branch graft repairs ultimately must be compared with the gold standard of open repair. To this end, we present a 10-year experience. METHODS: Between 1993 and 2003, 3058 AAAs were repaired. Perioperative variables, morbidity, and mortality were retrospectively assessed. Renal insufficiency was defined as a rise in the concentration of serum creatinine by > or = 0.5 mg/dL. Factors predicting complications were identified by multivariate analyses. Morbidity and 30-day mortality were evaluated with multiple logistic regression analysis. RESULTS: Of a total of 3058 AAA repairs performed, 247 were PAAAs (8%). Mean renal ischemia time was 23 minutes (range, 5 to 60 minutes). Cardiac complications occurred in 32 patients (13%), pulmonary complications in 38 (16%), and renal insufficiency in 54 (22%). Multivariate analysis associated myocardial infarction with advanced age (P = .01) and abnormal preoperative serum creatinine (>1.5 mg/dL) (P = .08). Pulmonary complications were associated with advanced age (P = .03), renal artery bypass (P = .02), increased mesenteric ischemic time (P = .01), suprarenal aneurysm repair (P < .0008), and left renal vein division (P = .01). Renal insufficiency was associated with increased mesenteric ischemic time (P = .001), supravisceral clamping (P = .04), left renal vein division (P = .04), and renal artery bypass (P = .0002), but not renal artery reimplantation or endarterectomy. New dialysis was required in 3.7% (9/242). Abnormal preoperative serum creatinine (>1.5 mg/dL) was predictive of the need for postoperative dialysis (10% vs 2%; P = .04). Patients with normal preoperative renal function had improved recovery (93% vs 36%; P = .0002). The 30-day surgical mortality was 2.5% (6/247) but was not predicted by any factors, and in-hospital mortality was 2.8% (7/247). Median intensive care and hospital stays were 3 and 9 days, respectively, and longer stays were associated with age at surgery (P = .007 and P = .0002, respectively) and any postoperative complication. CONCLUSIONS: PAAA repair can be performed with low mortality. Renal insufficiency is the most frequent complication, but avoiding renal artery bypass, prolonged mesenteric ischemia time, or left renal vein transection may improve results.

Randomized prospective study of totally extraperitoneal inguinal hernia repair: fixation versus no fixation of mesh.

BACKGROUND: Fixation of the mesh during laparoscopic totally extraperitoneal (TEP) inguinal hernia repair is thought to be necessary to prevent recurrence. However, mesh fixation may increase postoperative pain and lead to an increased risk of complications. We questioned whether elimination of fixation of the mesh during TEP inguinal hernia repair leads to decreased postoperative pain or complications, or both, without an increased rate of recurrence. METHODS: A randomized prospective single-blinded study was carried out in 40 patients who underwent laparoscopic TEP inguinal hernia repair with (Group A=20) or without (Group B=20) fixation of the mesh. RESULTS: Patients in whom the mesh was not fixed had shorter hospital length of stay (8.3 vs 16.0 hours, P=0.01), were less likely to be admitted to the hospital (P=0.001), used less postoperative narcotic analgesia in the PACU (P=0.01), and were less likely to develop urinary retention (P=0.04). No significant differences occurred in the level of pain, time to return to normal activity, or the difficulty of the operation between the 2 groups. No hernia recurrences were observed in either group (follow-up range, 6 to 30 months, median=19). CONCLUSIONS: Elimination of tack fixation of mesh during laparoscopic TEP inguinal hernia repair significantly reduces the use of postoperative narcotic analgesia, hospital length of stay, and the development of postoperative urinary retention but does not lead to a significant reduction in postoperative pain. Eliminating tacks does not lead to an increased rate of recurrence.

Quality-of-life after total pancreatectomy: is it really that bad on long-term follow-up?

While selected pancreatic diseases may be best treated by total pancreatectomy (TP), the anticipated sequelae of pancreatic insufficiency make TP an undesirable alternative. Our aim was to determine if patients undergoing TP have a worse quality of life (QoL) than age- and gender-matched controls and poor long-term glycemic control. Ninety-nine patients undergoing TP from 1985 through 2002 were identified. The 34 survivors with no recurrent malignancy were surveyed with the Short Form-36 (SF-36), the Audit of Diabetes Dependent QoL (ADD QoL), the European Organization for Research and Treatment in Cancer Pancreas 26 (EORTC PAN 26), and our institutional questionnaire. Operative morbidity and mortality were 32% and 5%, respectively. Three late postoperative deaths (3%) were attributed to hypoglycemia. Of the 34 surviving patients, 27 (79%) agreed to participate at a mean of 7.5 years postoperatively. Seven patients had required 12 hospitalizations for poor glycemic control. Per the SF-36, two domains (role physical and general health) were decreased compared with an age- and gender-matched national population (P < .05). The ADD QoL demonstrated an overall decrease in QoL related specifically to the diabetes mellitus (P < .01), but comparison with insulin-dependent diabetics from other causes showed no significant difference in QoL. The EORTC PAN 26 instrument also showed measurable effects on QoL. Total pancreatectomy can be performed safely. QoL after TP is decreased compared with age- and gender-matched controls but not with diabetes from other causes; however, the changes are not overwhelming. TP should remain a viable option but in selected patients.

Complicated diverticulitis: is it time to rethink the rules?

INTRODUCTION: Much of our knowledge and treatment of complicated diverticulitis (CD) are based on outdated literature reporting mortality rates of 10%. Practice parameters recommend elective resection after 2 episodes of diverticulitis to reduce morbidity and mortality. The aim of this study is to update our understanding of the morbidity, mortality, characteristics, and outcomes of CD. METHODS: Three hundred thirty-seven patients hospitalized for CD were retrospectively analyzed. Characteristics and outcomes were determined using chi-squared and Fisher exact tests. RESULTS: Mean age of patients was 65 years. Seventy percent had one or more comorbidities. A total of 46.6% had a history of at least one prior diverticulitis episode, whereas 53.4% presented with CD as their first episode. Overall mortality rate was 6.5% (86.4% associated with perforation, 9.5% anastomotic leak, 4.5% patient managed nonoperatively). A total of 89.5% of the perforation patients who died had no history of diverticulitis. Steroid use was significantly associated with perforation rates as well as mortality (P< 0.001 and P = 0.002). Comorbidities such as diabetes, collagen-vascular disease, and immune system compromise were also highly associated with death (P = 0.006, P = 0.009, and P = 0.003, respectively). Overall morbidity was 41.4%. Older age, gender, steroids, comorbidities, and perforation were significantly associated with morbidity. CONCLUSION: Today, mortality from CD excluding perforation is reduced compared with past data. This, coupled with the fact that the majority of these patients presented with CD as their first episode, calls into question the current practice of elective resection as a stratagem for reducing mortality. Immunocompromised patients may benefit from early resection. New prospective data is needed to redefine target groups for prophylactic resection.

Impact of primary resection on the outcome of patients with perforated diverticulitis.

BACKGROUND: Primary resection has replaced the conventional drainage procedure in the management of patients with generalized peritonitis complicating diverticular disease of the colon. This study investigates the impact of primary resection on operative mortality, identifies predictors of mortality, and compares the results with those of our earlier experience. HYPOTHESIS: Primary resection of the perforated diseased segment of the colon is associated with lower mortality rates than the drainage procedure in patients with Hinchey stages 3 and 4 diverticulitis. DESIGN: Retrospective analysis. SETTING: Tertiary care referral center. PATIENTS: We included 138 consecutive patients who underwent emergent operation for generalized peritonitis complicating diverticular disease of the colon (Hinchey stages 3 and 4) during a period of 16 years (January 1983 to May 1999). MAIN OUTCOME MEASURES: The 30-day mortality rate was analyzed and predictors of mortality identified. RESULTS: Patients were classified as having spreading purulent peritonitis (n = 44, 31.9%), diffuse peritonitis (n = 64, 46.4%), or fecal peritonitis (n = 30, 21.7%). One hundred thirty-one patients (94.9%) underwent primary resection, 6 patients (4.3%) underwent resection and primary anastomosis, and 1 patient required total colectomy and end ileostomy. Thirteen of the 138 patients in the present group died (1983-1998), representing a perioperative mortality rate of 9%. There was no significant difference in mortality when compared with our earlier study (1972-1982), which had a mortality rate of 12%, considering that more than 25% of the patients in that group were managed by colostomy and drainage alone. Factors identified univariately as predictors of mortality were age of more than 70 years (P = .047), 2 or more comorbid conditions (P<.01), obstipation at initial examination (P = .02), use of steroids (P = .01), and perioperative sepsis (P<.001). CONCLUSIONS: Primary resection has become the standard practice for patients with generalized peritonitis complicating diverticulitis. Mortality rates have not significantly declined despite more aggressive surgical management of the septic source. Because advanced age, comorbid conditions, and perioperative sepsis predict mortality, it is suggested that further reduction in mortality will require improvement in medical management of perioperative sepsis and comorbid conditions.

Double-blind, prospective, randomized study of warmed, humidified carbon dioxide insufflation vs standard carbon dioxide for patients undergoing laparoscopic cholecystectomy.

HYPOTHESIS: Patients undergoing warmed, humidified carbon dioxide (CO2) insufflation for laparoscopic cholecystectomy will (1) maintain a warmer intraoperative core temperature, (2) have their surgeon experience less fogging of the camera lens, and (3) have less postoperative pain than patients undergoing laparoscopic cholecystectomy with standard CO2 insufflation. DESIGN: A double-blind, prospective, randomized study comparing patients undergoing laparoscopic cholecystectomy with standard CO2 insufflation vs those receiving warmed, humidified CO2 (Insuflow Filter Heater Hydrator; Lexion Medical, St Paul, Minn) was performed. Main variables included patient core temperature, postoperative pain, analgesic requirements, and camera lens fogging. RESULTS: One hundred one blinded patients (69 women, 32 men) undergoing laparoscopic cholecystectomy were randomized into 2 groups-52 receiving standard CO2 insufflation (group A) and 49 receiving warmed, humidified CO2 (group B). Mean patient intraoperative core temperature change (group A decreased by 0.03 degrees C, group B increased by 0.29 degrees C, P =.01) and mean abdominal pain (Likert scale, 0-10) at 14 days postoperatively (group A, 1.0; group B, 0.3; P =.02) were different. Other variables (camera lens fogging, early postoperative pain, narcotic requirements, recovery room stay, and return to normal activities) between groups were similar. CONCLUSION: While patients undergoing laparoscopic cholecystectomy with warmed, humidified CO2 had several advantages that were statistically significant, no major clinically relevant differences between groups A and B were evident.

Quality-of-life assessment of surgical reconstruction after laparoscopic cholecystectomy-induced bile duct injuries: what happens at 5 years and beyond?

HYPOTHESIS: Quality of life of patients after biliary reconstruction for laparoscopic injuries is comparable to that of patients after laparoscopic cholecystectomy. DESIGN: Outcomes study. SETTING: Tertiary referral center. PATIENTS: Records of 59 consecutive patients undergoing surgical reconstruction of the biliary tract after injury induced by laparoscopic cholecystectomy between 1990 and 1997 were reviewed. Hepp-Couinaud technique or Roux-en-Y hepaticojejunostomy was used in 53 patients; other procedures included cholangiojejunostomy, choledochorrhaphy, and hepaticoduodenostomy. INTERVENTIONS: Quality-of-life questionnaires (36-Item Short-Form Health Survey [SF-36]) were mailed to each patient in the group and to patients who underwent uneventful laparoscopic cholecystectomy, matched individually by year, sex, and age group. Values from the general population matched by age and sex were gathered (national norms). Minimum time of follow-up was 5 years. RESULTS: Eighty-nine (81%) of 110 potential respondents to the survey completed the SF-36 questionnaires. All 8 values evaluated in the SF-36 questionnaire (physical functioning, role-physical, bodily pain, general health perceptions, vitality, social functioning, role-emotional, and mental health index) for patients undergoing biliary reconstruction were similar to those of both their matched controls (all P >.10) and national norms (all P >.05). The standardized physical component scale was also similar between the 2 groups (cases vs controls, 51 vs 48; P =.47), as was the standardized mental component scale (cases vs controls, 55 vs 55; P =.60). CONCLUSIONS: With a minimum of 5 years of follow-up, the quality of life after surgical biliary reconstruction compares favorably with that of both patients undergoing uneventful laparoscopic cholecystectomy and national norms.

Comparison of wear and osteolysis in hip replacement using two different coatings of the femoral stem.

We compared the clinical and radiographic results of two matched series of total hip arthroplasties, one with hydroxyapatite-coated femoral stems, the other with a similar but porous-coated femoral stem. The prevalence of radiographic osteolysis was 16% in hips with hydroxyapatite-coated stems and 43% in hips with porous-coated femoral stems. In hips with hydroxyapatite-coated stems, osteolysis was always limited to Gruen zones 1 and 7. In contrast, distal osteolysis was present around 26% of the porous-coated stems. At 7 years, the survival-free rate of distal osteolysis was 100% in hips with hydroxyapatite-coated stems but 90% in hips with porous-coated stems (p=0.04). Circumferential hydroxyapatite coating of the femoral component reduced the occurrence of osteolysis and eliminated distal osteolysis at 5-10 years of follow-up. In addition, hydroxyapatite coating did not alter the wear rate.