Lessons learned from more than 1,000 pancreas transplants at a single institution

OBJECTIVE: To determine outcome in diabetic pancreas transplant recipients according to risk factors and the surgical techniques and immunosuppressive protocols that evolved during a 33-year period at a single institution. SUMMARY BACKGROUND DATA: Insulin-dependent diabetes mellitus is associated with a high incidence of management problems and secondary complications. Clinical pancreas transplantation began at the University of Minnesota in 1966, initially with a high failure rate, but outcome improved in parallel with other organ transplants. The authors retrospectively analyzed the factors associated with the increased success rate of pancreas transplants. METHODS: From December 16, 1966, to March 31, 2000, the authors performed 1,194 pancreas transplants (111 from living donors; 191 retransplants): 498 simultaneous pancreas-kidney (SPK) and 1 simultaneous pancreas-liver transplant; 404 pancreas after kidney (PAK) transplants; and 291 pancreas transplants alone (PTA). The analyses were divided into five eras: era 0, 1966 to 1973 (n = 14), historical; era 1, 1978 to 1986 (n = 148), transition to cyclosporine for immunosuppression, multiple duct management techniques, and only solitary (PAK and PTA) transplants; era 2, 1986 to 1994 (n = 461), all categories (SPK, PAK, and PTA), predominantly bladder drainage for graft duct management, and primarily triple therapy (cyclosporine, azathioprine, and prednisone) for maintenance immunosuppression; era 3, 1994 to 1998 (n = 286), tacrolimus and mycophenolate mofetil used; and era 4, 1998 to 2000 (n = 275), use of daclizumab for induction immunosuppression, primarily enteric drainage for SPK transplants, pretransplant immunosuppression in candidates awaiting PTA. RESULTS: Patient and primary cadaver pancreas graft functional (insulin-independence) survival rates at 1 year by category and era were as follows: SPK, era 2 (n = 214) versus eras 3 and 4 combined (n = 212), 85% and 64% versus 92% and 79%, respectively; PAK, era 1 (n = 36) versus 2 (n = 61) versus 3 (n = 84) versus 4 (n = 92), 86% and 17%, 98% and 59%, 98% and 76%, and 98% and 81%, respectively; in PTA, era 1 (n = 36) versus 2 (n = 72) versus 3 (n = 30) versus 4 (n = 40), 77% and 31%, 99% and 50%, 90% and 67%, and 100% and 88%, respectively. In eras 3 and 4 combined for primary cadaver SPK transplants, pancreas graft survival rates were significantly higher with bladder drainage (n = 136) than enteric drainage (n = 70), 82% versus 74% at 1 year (P =.03). Increasing recipient age had an adverse effect on outcome only in SPK recipients. Vascular disease was common (in eras 3 and 4, 27% of SPK recipients had a pretransplant myocardial infarction and 40% had a coronary artery bypass); those with no vascular disease had significantly higher patient and graft survival rates in the SPK and PAK categories. Living donor segmental pancreas transplants were associated with higher technically successful graft survival rates in each era, predominately solitary (PAK and PTA) in eras 1 and 2 and SPK in eras 3 and 4. Diabetic secondary complications were ameliorated in some recipients, and quality of life studies showed significant gains after the transplant in all recipient categories. CONCLUSIONS: Patient and graft survival rates have significantly improved over time as surgical techniques and immunosuppressive protocols have evolved. Eventually, islet transplants will replace pancreas transplants for suitable candidates, but currently pancreas transplants can be applied and should be an option at all stages of diabetes. Early transplants are preferable for labile diabetes, but even patients with advanced complications can benefit.     

Ideal culture time for improvement in sperm motility from testicular sperm aspirates of men with azoospermia

PURPOSE: The motility of testicular derived spermatozoa reflects viability and predicts success during intracytoplasmic sperm injection. Although improvements in sperm motility are seen after incubation for extended periods, no guidelines suggest duration or media use for optimal improvement in motility. MATERIALS AND METHODS: Between July 1999 and February 2005 testicular aspirations were performed on 95 men with azoospermia, including 51 with obstructive azoospermia and 44 with nonobstructive azoospermia. Sperm motility was determined at initial collection and following incubation for 24 or 48 hours in processing media or Ham's F10 + protein. A mixed regression model controlling for testis side, media and baseline motility was created to analyze the change in motility between 24 and 48 hours. RESULTS: Mean motility improved from 3% to 20% at 24 hours and 25% at 48 hours for OA cases and from 0% to 5% at 24 hours and 11% at 48 hours for nonobstructive azoospermia cases. The improvement in motility from 24 to 48 hours was significant for obstructive azoospermia cases (p = 0.001). While media was a nonsignificant factor in regression models, when patients were grouped into categories of motility change there was a significantly better response to F10 compared to processing media (p = 0.03). CONCLUSIONS: Incubation in processing media or Ham's F10 + albumin media improves sperm motility with significant improvement noted between 24 and 48 hours for obstructive azoospermia cases. Ham's F10 + albumin media may provide extra benefit for cases of nonobstructive azoospermia or nerve injury. These results suggest the ideal timing of oocyte retrieval for intracytoplasmic sperm injection correlates with 48-hour sperm incubation for obstructive azoospermia cases, and 24 hours for nonobstructive azoospermia and nerve injury cases.     

Differential adoption of laparoscopy by treatment indication

PURPOSE: The diffusion of laparoscopic renal surgery has been gradual. While surgery for benign and malignant kidney disease is usually within the urological domain, donor nephrectomy is multidisciplinary. Therefore, we compared the use of laparoscopy by procedure indication (kidney donor, and benign and malignant kidney disease) to examine potential specialty specific associations with the slow uptake of this technology. MATERIALS AND METHODS: Data on 53,461 patients undergoing nephrectomy for all indications between 1998 and 2003 were abstracted from the Nationwide Inpatient Sample using International Classification of Diseases, 9th Revision, Clinical Modification procedure and diagnostic codes. Generalized estimating equations were fitted to measure the association between laparoscopy use and the procedure indication (kidney donor, benign kidney disease and kidney cancer). RESULTS: The use of laparoscopy varied by treatment indication. In 2003, 33% of kidney donors underwent a laparoscopic approach compared to 22% and 16% of patients with benign and malignant kidney disease, respectively (p <0.0001). After adjusting for patient and hospital differences patients with benign (adjusted OR 0.71, 95% CI 0.58-0.94) and malignant (adjusted OR 0.51, 95% CI 0.35-0.74) kidney disease were significantly less likely to undergo laparoscopic nephrectomy than kidney donors. CONCLUSIONS: These data highlight that the use of laparoscopic renal surgery varies by procedure indication with slower adoption of laparoscopy for malignant or benign indications than for donor nephrectomy. This variation was not readily explained by differences in measurable patient and hospital factors. Further characterization of provider and nonclinical characteristics may provide additional insight into differences in the adoption of this technology, which appears to be a specialty specific phenomenon.     

Comparative analysis of urinary incontinence severity after autologous fascia pubovaginal sling, pubovaginal sling and tension-free vaginal tape

PURPOSE: Autologous fascia, Pelvicol implant and polypropylene are common materials used in suburethral anti-incontinence procedures. We explored the relative effectiveness of the autologous fascia pubovaginal sling, Pelvicol pubovaginal sling and Gynecare TVT on self-reported postoperative urinary incontinence. MATERIALS AND METHODS: The study was a mailed cross-sectional survey of health related quality of life 1 to 3 years after suburethral anti-incontinence surgery performed at our institution. The Incontinence Symptom Index was used to assess the presence and severity of urinary incontinence symptoms and the Incontinence Impact Questionnaire-7 was used to assess impairment. Regression models were developed to identify factors with an independent effect on the presence, severity and impairment of urinary incontinence symptoms. RESULTS: The questionnaire was returned by 69% of eligible respondents (173 of 250). Those with previous incontinence surgery (OR 11.0, 95% CI 2.3-51.4) and medical comorbidities (OR 1.6, 95% CI 1.1-2.2) were more likely to report urinary incontinence symptoms, ie incontinence symptom index greater than 0. Symptom severity, which was analyzed only in respondents with urinary incontinence symptoms, was greater in the Pelvicol than in the autologous fascia pubovaginal sling and TVT groups (each p <0.01). No significant difference was observed between the TVT and autologous fascia pubovaginal sling groups (p = 0.15). Also associated with higher urinary incontinence symptom severity scores were body mass index (p = 0.03), a history of incontinence surgery (p = 0.01) and lower education (p <0.01). Impairment from urinary incontinence, as assessed by the Incontinence Impact Questionnaire-7, was associated with body mass index, severe depression and current smoking (each p = 0.01) but not with surgical treatment group. CONCLUSIONS: Women who received an autologous fascia pubovaginal sling or TVT reported lower symptom severity scores than those who had a Pelvicol pubovaginal sling. Impairment was not associated with procedure type. These findings suggest better outcomes with autologous fascia pubovaginal sling and TVT. Randomized, controlled trials are needed to confirm these findings.     

The role of laparoscopy in penetrating abdominal trauma.

BACKGROUND: Minimally invasive surgery has become increasingly utilized in the trauma setting. When properly applied, it offers several advantages, including reduced morbidity, lower rates of negative laparotomy, and shortened length of hospital stay. The purpose of this study was to evaluate the role of laparoscopy in the management of trauma patients with penetrating abdominal injuries. METHODS: We conducted a 3-year retrospective chart review of 4541 trauma patients admitted to our urban Level II trauma center. Penetrating abdominal injuries accounted for 209 of these admissions. Patients were divided into 3 treatment groups based on the characteristics of their abdominal injuries. Management was either observation, immediate laparotomy, or screening laparoscopy. RESULTS: Thirty-three patients were observed in the Emergency Department based on their initial physical examination and radiologic studies. After Emergency Department evaluation, 154 patients underwent immediate laparotomy. In this group, 119 therapeutic laparotomies, 11 nontherapeutic laparotomies, and 24 negative laparotomies were performed. A review of the negative laparotomies revealed that possibly 8 of 10 gun shot wounds and all 14 stab wounds could have been done laparoscopically. Twenty-two patients underwent laparoscopic evaluation, 9 of which were converted to open procedures. CONCLUSION: Minimally invasive surgical techniques are particularly helpful as a screening tool for anterior abdominal wall wounds and lower chest injuries to rule out peritoneal penetration. Increased use of laparoscopy in select patients with penetrating abdominal trauma will decrease the rate of negative and nontherapeutic laparotomies, thus lowering morbidity and decreasing length of hospitalization. As technology and expertise among surgeons continues to improve, more therapeutic intervention may be done laparoscopically in the future.     

Serum antielastase and neutrophil elastase levels in PiM phenotype cigarette smokers with airflow obstruction

In order to assess blood factors which might explain why some cigarette smokers develop airflow obstruction while others do not, we compared two groups of PiM phenotype volunteers matched for age, sex and total pack-years of cigarette smoking; one group had airflow obstruction and the other did not. Functional levels of alpha-2-macroglobulin (alpha-2-M) and alpha-1-protease inhibitor (alpha-1-PI) were separately assessed by a protease binding procedure. Neutrophils were isolated from blood by counterflow centrifugation, and their elastase content was assayed with 3H-elastin-SDS (sodium dodecyl sulfate). The obstructed and nonobstructed groups were not different with respect to functional or immunoreactive levels of alpha-1-PI and alpha-2-M or elastase levels in their neutrophils. We do not find imbalances of circulating elastase or antielastase levels in PiM phenotype smokers with airflow obstruction.     

The effects of systemic immunization of pulmonary clearance of Pseudomonas aeruginosa

Systemic immunization with gram-negative organisms enhances the subsequent pulmonary clearance of these organisms. We studied the early time course of this phenomenon and related it to the time of appearance of polymorphonuclear leukocytes (PMN) and anti-Pseudomonas antibody in bronchoalveolar lavage (BAL). Mice were immunized intraperitoneally twice, separated by 1 wk, with 10(8) formalin-treated Pseudomonas aeruginosa. Two weeks later, they received an intrabronchial inoculum of 2.9 X 10(6) or 4.6 X 10(7) Pseudomonas organisms. Two, 4, and 6 h later, clearance and total PMN and anti-Pseudomonas antibody in the BAL were assessed. Clearance was enhanced in immunized mice at the lower inoculum. At the higher inoculum, bacteria were growing in lungs of both groups, although they were inhibited in immunized mice. Total PMN in the BAL increased progressively in both groups of mice, but net recruitment was diminished with the high inoculum. There were significant differences in the PMN in the BAL between control and immunized mice with high inoculum. Anti-Pseudomonas IgG first appeared in the BAL at 2 h, anti-Pseudomonas IgM at 6 h. These data suggest that anti-Pseudomonas IgG is an effective early pulmonary opsonin. Further, with high inoculums, immunization may aid pulmonary defenses by diminishing the magnitude of the decrement of PMN in the lung.     

Influence of coronary collateral blood flow on the development of exertional ischemia and Q wave infarction in patients with severe single-vessel disease

The functional significance of coronary collateral flow from a nonobstructed supply artery was studied in 121 patients with severe (greater than or equal to 80%) single-vessel disease, 64 with and 57 without Q wave infarction. All patients underwent exercise thallium imaging and coronary angiography. On angiography, collateral flow was present in 85% of 74 occluded arteries compared with only 17% of 47 arteries with subtotal obstruction (p less than .001). Collateral flow was not seen in arteries with lesions of less than 90% obstruction. Collateral flow was present in 100% of 29 occluded arteries in patients without Q wave infarction compared with only 76% of 45 occluded arteries with Q wave infarction (p less than .005). Clinical variables did not correlate with collateral flow. Collateral flow did not prevent ischemia on exercise thallium imaging in patients without Q wave infarction: 30 of 33 (91%) with collateral flow had reversible thallium defects compared with 24 of 24 (100%) without collateral flow (p = NS). In patients with Q wave infarction, partially reversible exercise thallium defects (peri-infarctional ischemia) were more common with flow to the area from either subtotal obstruction (73%) or collateral flow (45%) than with no flow from total occlusion (27%; p = .05). In patients with severe single-vessel disease the presence of collateral flow is principally determined by coronary occlusion. Collateral flow may protect from Q wave infarction but does not prevent exercise ischemia on thallium imaging.     

To thin or not to thin: the use of the anterolateral thigh flap in the reconstruction of intraoral defects.

The anterolateral thigh (ALT) flap has achieved popularity recently for free-flap reconstruction of intraoral defects following excision of squamous cell carcinoma. We have assessed the feasibility of the ALT flap as a free flap for oral lining and the potential use of the thinned ALT flap in a one-stage reconstruction. We used the ALT flap to reconstruct the oral cavity in 18 consecutive patients between December 2000 and December 2001 following intraoral resection of squamous cell carcinoma. Twelve patients underwent reconstruction using a standard ALT flap, four patients received a thinned ALT flap in a one-stage procedure, one patient received a standard ALT flap in combination with a fibula flap and one patient received a combination of a standard ALT flap and vascularised iliac bone. There were no complications in any of the 14 cases in which a standard ALT flap was used. Two of these flaps were thinned subsequently as secondary procedures. Of the four thinned ALT flaps, one flap failed completely and two flaps experienced partial necrosis. In all but one case the donor site was closed directly with minimal donor-site morbidity. The ALT flap is a versatile flap that can be used in combination with other flaps for more complex defects with minimal donor-site morbidity and is a useful alternative in the armamentarium of the head and neck surgeon. Thinning of the flap is best performed as a secondary procedure, should it be required.