Laparoscopic radical/total nephrectomy: a decade of progress.

The first laparoscopic radical/total nephrectomy for a renal tumor was performed in June 1990. Since that time, the procedure has evolved as numerous surgeons have contributed novel strategies and technical advances. The state of the art is reviewed, including transperitoneal laparoscopic and hand-assisted techniques, as well as the retroperitoneal approach. Operative and postoperative data are reviewed with the goal of determining four factors: the efficacy, efficiency, morbidity, and cost of the procedure. Within the limits of available follow-up for this novel procedure, it appears to be as effective as open surgery in rendering the patient tumor free. Although it clearly is a less painful and less disabling procedure than open surgery, our understanding of the efficiency of the laparoscopic procedure remains in flux. The operative times for laparoscopic radical/total nephrectomy are approaching those of traditional open radical nephrectomy, although intraoperative costs remain higher and thus must be balanced against decreased hospitalization and convalescence.

Laparoscopic cyst marsupialization in patients with autosomal dominant polycystic kidney disease.

PURPOSE: Autosomal dominant polycystic kidney disease is characterized by progressively enlarging renal cysts associated with hypertension, renal failure, pain, hematuria and infection. We explored the role of laparoscopic cyst marsupialization for managing cyst related problems. MATERIALS AND METHODS: In 4 male and 11 female adults with autosomal dominant polycystic kidney disease who had preserved renal function laparoscopic cyst marsupialization was done for pain unilaterally and bilaterally in 9 and 6, respectively. An average of 204 cysts per kidney (range 11 to 635) were decorticated or drained. RESULTS: Average operative time was 5.5 hours. Patients were discharged from the hospital after an average of 3.2 days. At a mean followup of 2.2 years (range 0.5 to 5) pain was decreased an average of 62% (range 30% to 90%) in 11 cases (73%). One patient had no improvement and 1 had subsequent worsening of pain postoperatively. Two patients with initial improvement had pain recurrence 4 and 36 months postoperatively, respectively. Hypertension resolved in 1 patient (7%), improved in 20% and did not change in 40%. In 33% of the cases hypertension worsened, requiring additional antihypertensive medication. Renal function remained stable in 13 patients (87%), improved in 1 (6.5%) and worsened in 1 (6.5%). Overall patients who underwent a bilateral procedure had better long-term pain relief and more improvement in hypertension. CONCLUSIONS: Laparoscopic cyst marsupialization may effectively decrease cyst associated pain. In some cases hypertension may be improved. Renal function remained stable in all except 1 patient. At a mean followup of 2.2 years the benefits of aggressive laparoscopic cyst decortication appear to be relatively long lasting when bilateral decortication is indicated. The benefits of unilateral cyst decortication are less predictable and of shorter duration.

Diagnosis and initial management of kidney stones.

The diagnosis and initial management of urolithiasis have undergone considerable evolution in recent years. The application of noncontrast helical computed tomography (CT) in patients with suspected renal colic is one major advance. The superior sensitivity and specificity of helical CT allow urolithiasis to be diagnosed or excluded definitively and expeditiously without the potential harmful effects of contrast media. Initial management is based on three key concepts: (1) the recognition of urgent and emergency requirements for urologic consultation, (2) the provision of effective pain control using a combination of narcotics and nonsteroidal anti-inflammatory drugs in appropriate patients and (3) an understanding of the impact of stone location and size on natural history and definitive urologic management. These concepts are discussed with reference to contemporary literature, with the goal of providing tools that family physicians can use in the emergency department or clinic.

Should laparoscopy be the standard approach used for radical nephrectomy?

Since its inception in June 1990, laparoscopic radical/total nephrectomy for renal tumor has been successfully applied worldwide to hundreds of patients. Recent 5-year follow-up data have shown this procedure to produce cancer control identical to that of open radical/total nephrectomy. Although in most centers the cost of the procedure remains higher than open surgery, the patient benefits of decreased pain, reduced hospitalization, less blood loss, and more rapid convalescence appear to be universal. At this time, we believe that laparoscopic radical/total nephrectomy for the treatment of renal tumors should become the new standard of care.

Laparoscopic nephroureterectomy. A new standard for the surgical management of upper tract transitional cell cancer.

Laparoscopic nephroureterectomy for upper tract TCC still remains somewhat controversial. Unlike laparoscopic radical nephrectomy, which has become widely accepted, LNU is still in its earliest stages. Although there are obvious benefits for the patient who has LNU--less pulmonary complications, less postoperative discomfort, a shorter hospital stay, a better cosmetic result, and a brief convalescence--there are significant concerns. The longer operative time creates a negative financial and professional inducement to learn this technique. Operative times need to fall into the 4-hour range or less to make the procedure cost-effective. Analysis of the efficacy of laparoscopic nephroureterectomy as a curative treatment modality is important. In the short-run, LNU seems to provide similar results to open nephroureterectomy for upper TCC. Although concerns over port site seeding, bladder recurrence, and intraperitoneal seeding have been voiced, these problems have not occurred. The higher incidence of local recurrence noted in the authors' series, however, is of concern and remains an unsettled issue. Despite these local recurrences, the overall cancer survival for a given grade and stage of upper tract TCC seem to be similar to survivals recorded after open nephroureterectomy. Still, the number of LNU cases remains small, and follow-up is brief. These patients need to be monitored closely, with follow-up CT scans over the next decade. The authors believe that there are still several significant hurdles standing in the path of LNU before it can become a widely accepted procedure. Issues of cost, training, and long-term efficacy must be answered definitively. To obtain these types of data, it will be necessary to create a multi-institutional, cooperative study to obtain sufficient numbers of patients with a more than 5-year follow-up on which to base future recommendations.

Evaluation of a chronic indwelling prototype mesh ureteral stent in a porcine model.

OBJECTIVES: Ureteral stents all share one general goal, drainage, and one major drawback, irritative symptoms in the kidney and bladder. In an effort to preserve drainage while minimizing irritation, a lightweight, self-expanding mesh stent was designed. Herein, we compare the in vivo tissue reaction and flow characteristics of the mesh stent to a standard 7F double-pigtail polyurethane stent. METHODS: Eight female Yucatan minipigs had bilateral stents placed: a mesh stent on one side and a standard 7F stent on the opposite side. Imaging and flow measurements were obtained in 4 pigs at 1 week and in another 4 pigs at 6 weeks. Following this procedure, the stents were removed, and the kidneys, ureters, and bladder were harvested en bloc for a blinded histopathologic analysis. RESULTS: The degree of stent-related tissue reactivity was low for both stents and appeared similar for the ureter and bladder. Overall, the mesh stent resulted in a decrease in inflammation along the urinary tract at 1 week, but this result was statistically insignificant (P = 0.55). Flow rate through the mesh stent tended to be greater than for the polyurethane stent both at 1 week and at 6 weeks. CONCLUSIONS: Overall, the mesh stent appeared to be well tolerated and provided for excellent flow.

Flow characteristics of 3 unique ureteral stents: investigation of a Poiseuille flow pattern.

PURPOSE: The pattern of flow in the stented ureter (intraluminal and/or extra luminal) has only been defined for the standard pigtail stent. No data are available on stent flow for any specialty stents. To our knowledge we present the first investigation characterizing the type of flow through a stent (Poiseuille versus nonPoiseuille flow). MATERIALS AND METHODS: Flow was measured in an unstented ureter, a standard 7Fr double pigtail stent and the 7/3Fr Tail stent, 7Fr Spirastent and 14/7Fr endopyelotomy stent using a previously developed stent flow model. In vitro pressure flow studies were also done in nonfenestrated 14/7Fr, Tail and standard 7Fr stents. These stents were infused at a constant flow rate of 2 to 10 ml. per minute with monitoring of the corresponding pressure gradients. Resistance to flow was determined for these stents using pressure flow plots and Poiseuille's law. RESULTS: In vivo the 7Fr pigtail, 14/7Fr endopyelotomy and 7/3Fr Tail stents had statistically similar flow rates. Flow through each of these stents exceeded the flow through an unstented ureter. The Spirastent had the least flow in all categories tested. There was no correlation of Poiseuille flow parameters measured in vitro for nonfenestrated stents with in vivo stent flow. CONCLUSIONS: In stented ureters fluid drains through and around the stent regardless of its design. The flow characteristics of these 3 specialty stents were not predictable according to lumen or stent size. In vitro Poiseuille's flow did not correlate with in vivo stent flow.

Laparoscopic versus open radical nephrectomy: a 9-year experience.

PURPOSE: The laparoscopic approach for renal cell carcinoma is slowly evolving. We report our experience with laparoscopic radical nephrectomy and compare it to a contemporary cohort of patients with renal cell carcinoma who underwent open radical nephrectomy. MATERIALS AND METHODS: From 1990 to 1999, 32 males and 28 females underwent 61 laparoscopic radical nephrectomies for suspicious renal cell carcinoma. Clinical data from a computerized database were reviewed and compared to a contemporary group of 33 patients who underwent open radical nephrectomy for renal cell carcinoma. RESULTS: Patients in the laparoscopic radical nephrectomy group had significantly reduced, estimated blood loss (172 versus 451 ml., p <0.001), hospital stay (3.4 versus 5.2 days, p <0.001), pain medication requirement (28.0 versus 78.3 mg., p <0.001) and quicker return to normal activity than patients in the open radical nephrectomy group (3.6 versus 8.1 weeks, p <0.001). The majority of laparoscopic specimens (65%) were morcellated. Operating time and cost were higher in the laparoscopic than the open nephrectomy group. Average followup was 25 months (range 3 to 73) for the laparoscopic and 27.5 months (range 7 to 90) for the open group. Renal cell carcinoma in 3 patients (8%) recurred in the laparoscopic group versus renal cell carcinoma in 3 (9%) in the open group. When stratified patients with tumors larger than 4 to 10 cm. experienced similar benefits and results as patients with tumors less than or equal to 4 cm. To date there have been no instances of trocar or intraperitoneal seeding in the laparoscopic radical nephrectomy group. CONCLUSIONS: Laparoscopic radical nephrectomy, although technically demanding, is a viable alternative for managing localized renal tumors up to 10 cm. It affords patients with renal tumors an improved postoperative course with less pain and a quicker recovery while providing similar efficacy at 2-year followup for patients with T1 and T2 tumors.

In vitro comparison of shock wave lithotripsy machines.

PURPOSE: We tested the hypothesis that shock wave lithotripsy machines vary in the ability to fragment stones to small size. MATERIALS AND METHODS: Calcium oxalate monohydrate, calcium hydrogen phosphate dihydrate, cystine and magnesium ammonium phosphate hexahydrate calculi were fragmented in vitro with the 22 kV. Dornier HM3, section sign 20 kV. Storz Modulith SLX, parallel, 15.6 kV. Siemens Lithostar C, paragraph sign 24 kV. Medstone STS-T,** 26 kV. HealthTronics LithoTron 160,daggerdagger 20 kV. Dornier Doli section sign and 22.5 kV. Medispec Econolithdouble daggerdouble dagger lithotriptors. Stones were given 500 or 2,000 shocks, or the Food and Drug Administration limit. Post-lithotripsy fragment size was characterized using sequential sieves and compared. RESULTS: Stone mass was statistically similar in the cohorts (p >0.94). Fragment size decreased as the number of shocks increased when the machine and stone composition were constant. Magnesium ammonium phosphate hexahydrate calculi were completely fragmented by all devices. At Food and Drug Administration treatment limits the mean incidence per device of calcium hydrogen phosphate dihydrate, calcium oxalate monohydrate, cystine and magnesium ammonium phosphate hexahydrate stones rendered into fragments greater than 2 mm. was 0% for the HM3, Modulith SLX and Lithostar C, 10% for the STS-T, 3% for the LithoTron 160, 29% for the Doli and 18% for the Econolith (p = 0. 04); 0% for the HM3, Modulith SLX, Lithostar C, STS-T and LithoTron 160, 4% for the Doli and 9% for the Econolith (p = 0.15); 1% for the HM3, 0% for the Modulith SLX, 1% for the Lithostar C, 10% for the STS-T, 14% for the LithoTron 160, 3% for the Doli and 9% for the Econolith (p = 0.44); and 1% for the HM3, 0% for the Modulith SLX, 1% for the Lithostar C, 10% for the STS-T, 14% for the LithoTron 160, 3% for the Doli and 9% for the Econolith (p = 0.44), respectively. CONCLUSIONS: Shock wave lithotriptors vary in fragmentation ability. The HM3, Modulith SLX and Lithostar C machines yield smaller fragments than other machines.

Laparoscopic augmentation cystoplasty with different biodegradable grafts in an animal model.

PURPOSE: Recently a variety of biodegradable organic materials have been used for bladder wall replacement. We sought to study the effectiveness of 4 different types of biodegradable materials for bladder augmentation using laparoscopic techniques. MATERIALS AND METHODS: Thirty one minipigs underwent successful transperitoneal laparoscopic partial cystectomy and subsequent closure (6 control) or patch augmentation (25): porcine bowel acellular tissue matrix (ATM) (6), bovine pericardium (BPC) (6), human placental membranes (HPM) (6) or porcine small intestinal submucosa (SIS) (7). An intracorporeal suturing technique with the EndoStitch device (U.S. Surgical, Norwalk, CT) and Lapra-Ty clips (Ethicon, Enodsurgery Inc. Cincinnati, OH) was used to anastomose the graft to the bladder wall. Postoperatively, a urethral catheter was left for one week. Bladders were evaluated by cystoscopy at 6 and 12 weeks and harvested at 12 weeks. RESULTS: Grafts remained in place in all groups except for the BPC group, where all grafts failed to incorporate. For the ATM and SIS groups, at 6 weeks, there was mucosal coverage of the grafts without evidence of encrustation. In the control group, at 12 weeks, the bladder capacity was 23% less than preoperatively. In the ATM, HPM and SIS groups, at 12 weeks, the bladder capacities were larger than preoperatively by 16%, 51% and 43% respectively; also the grafts had contracted to 70%, 65%, and 60% of their original sizes, respectively. Histologically, there was patchy epithelialization of ATM and SIS grafts with a mixture of squamoid and transitional cell epithelia. The graft persisted as a well-vascularized fibrous band in HPM, ATM, and SIS without evidence of significant inflammatory response. CONCLUSION: A laparoscopic technique for partial bladder wall replacement using a free graft is feasible. The biodegradable grafts of ATM, HPM and SIS are tolerated by host bladder and are associated with predominantly only mucosal regeneration at 12 weeks post-operatively.

Clinical effectiveness of new stent design: randomized single-blind comparison of tail and double-pigtail stents.

BACKGROUND AND PURPOSE: Stent morbidity appears to be secondary to lower urinary tract irritation. In an effort to decrease stent morbidity, a "one size fits all" Tail stent (Microvasive [Boston Scientific] Natick, MA) was developed with a 7F proximal pigtail and 7F shaft which tapers to a lumenless straight 3F tail. PATIENTS AND METHODS: We randomized 60 patients in a single-blind fashion to a 7F tail stent or 7F double-pigtail Percuflex stent. Patients were evaluated at the time of stent removal and 2 weeks later with a standardized questionnaire assessing: irritative lower tract symptoms individually and on a total scale of 0 (no symptoms) to 30 (worst symptoms), obstructive lower tract symptoms (on a total scale of 0-20), and upper tract irritative symptoms (on a total scale of 0-10). RESULTS: Patient age, weight, and height were similar in the two groups. Complications, including fever, urinary tract infections, emergency room visits, and the need for antispasmodics and pain medication, also demonstrated no significant difference. At the time of stent removal, patients who received a tail stent had significantly less urinary frequency and a statistically significant (21%) decrease in overall irritative voiding symptoms (12.2 v 15.4; p = 0.048). Two weeks after stent removal, the total irritative voiding symptoms was markedly decreased in both groups (7.1 in the Tail v 5.3 in the double-pigtail group; p = 0.15). Obstructive bladder and flank symptoms were not significantly different in the two stent groups, either at the time of stent removal or at 2 weeks after removal. CONCLUSION: In this randomized, single-blind study, the 7F Tail stent produced significantly less irritative symptoms than did the standard 7F double-pigtail stent. Obstructive symptoms tended to be less with the new stent, while flank symptoms were similar.

Laparoscopic midsagittal hemicystectomy and replacement of bladder wall with small intestinal submucosa and reimplantation of ureter into graft.

BACKGROUND AND PURPOSE: A variety of biodegradable organic materials have been used for bladder wall replacement. In some instances, partial replacement has been done using laparoscopic reconstructive techniques. However, to date, this activity has been limited to small patches. Herein, we present the initial experience with laparoscopic sagittal hemicystectomy and the use of laparoscopic reconstructive techniques to replace half of the bladder with small-intestinal submucosa (SIS) and to reimplant the ureter into SIS. MATERIALS AND METHODS: Six female minipigs (20-25 kg) underwent transperitoneal laparoscopic sagittal hemicystectomy; the excised bladder wall was replaced with a 5 x 15-cm patch of SIS (Cook Biotechnology, Spencer, IN). The ipsilateral ureter was reimplanted through a small incision in the graft and secured with two sutures. Cystoscopy and cystometrograms were performed under general anesthesia preoperatively and at 6 and 12 weeks postoperatively. Tissues were harvested at 12 weeks. RESULTS: The procedure was successful in six animals (left three, right three). During cystoscopy at 12 weeks, the area of the graft was not distinguishable from normal mucosa. Cystometrograms revealed maintenance of volume and compliance, with volumes of 338, 343, and 369 mL and intravesical leak-point pressures of 37, 59, and 39 cm H2O at 0, 6, and 12 weeks, respectively. Antegrade ureterograms demonstrated extrinsic obstruction, minimal (two), moderate (three), or complete (one), at the ureterovesical junction. The kidney associated with the completely obstructed ureter was grossly hydronephrotic at sacrifice. Histologically, patchy epithelialization of the graft with a mixture of squamoid and mature transitional-cell epithelium was found. CONCLUSIONS: Laparoscopic hemicystectomy with replacement of the bladder wall and implantation of the ureter into the SIS graft is a feasible procedure. Clinical application awaits improvements in the method of ureteral reimplantation and longer follow-up to assess for ingrowth of muscle and nerve fibers.

Laparoscopic nephrectomy in patients with end-stage renal disease and autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is often characterized by end-stage renal disease (ESRD) and problems including pain, hematuria, and infection. Open nephrectomy is curative; however, the morbidity of the procedure is considerable. Between 1995 and 1998, 11 laparoscopic nephrectomies were performed on nine symptomatic patients (five men and four women) with ESRD and ADPKD. Two patients underwent a staged bilateral laparoscopic nephrectomy. All patients presented with abdominal or flank pain and an abdominal mass. Other clinical problems included hypertension in eight patients, urinary tract infections in two patients, and gross hematuria in one patient. Seven patients were receiving long-term dialysis treatment, and two patients had undergone prior renal transplantation. Patients were evaluated for preoperative and postoperative pain, analgesic use, hospital course, and convalescence. The overall average operative time was 6.3 hours, with an average estimated blood loss of 153 mL. Eight nephrectomy specimens were removed by morcellation, and three specimens were removed intact through a 7- to 12-cm incision. The average hospital stay was 3 days, and the average time to normal activity was 5 weeks. With a mean follow-up of 31 months, all nine patients reported elimination of their preoperative pain based on a pain analogue score. Six major and two minor complications occurred, including blood transfusion, a vena cavotomy, splenic cyanosis, pulmonary embolism, clotted arteriovenous fistula, and brachial plexus injury. Incisional hernias occurred in two of the three patients who underwent open removal. One patient noted improvement, and two patients noted resolution of their hypertension postoperatively. Laparoscopic nephrectomy in patients with ADPKD and ESRD offers an effective alternative to open nephrectomy to manage renal-related pain. This procedure provides the benefits of minimal intraoperative blood loss, minimal postoperative pain, brief hospital stay, and rapid convalescence.

Laparoscopic nephroureterectomy for upper tract transitional cell cancer: the Washington University experience.

PURPOSE: Laparoscopic nephroureterectomy has only recently been done to treat patients with upper tract transitional cell carcinoma. We retrospectively evaluated our experience with and long-term followup of laparoscopic nephroureterectomy, compared our results to those of contemporary series of open nephroureterectomy and reviewed the literature. MATERIALS AND METHODS: We reviewed the charts of and followed up by telephone 25 patients who underwent laparoscopic nephroureterectomy between May 1991 and June 1998, and 17 who underwent open nephroureterectomy between March 1990 and January 1997. Demographic, perioperative and followup data were compared. We performed a MEDLINE search and reviewed the literature on laparoscopic nephroureterectomy for upper tract transitional cell carcinoma. RESULTS: Laparoscopic nephroureterectomy required twice the operating time of open nephroureterectomy (7.7 versus 3.9 hours). However, patients who underwent the laparoscopic procedure had a 74% decrease in analgesia requirements (37 versus 144 mg. morphine sulfate equivalent), a 63% shorter hospital stay (3.6 versus 9.6 days) and a 72% more rapid convalescence (2.8 versus 10 weeks). Subsequent bladder transitional cell carcinoma and overall cancer specific survival were similar at a mean followup of 2 years. There was no sign of trocar site or peritoneal seeding after laparoscopic nephroureterectomy. CONCLUSIONS: Although laparoscopic nephroureterectomy is a longer operation, it has the same efficacy and is better tolerated by patients than open nephroureterectomy for upper tract transitional cell carcinoma. As operating time decreases due to surgeon experience and the recent development of hand assisted laparoscopy, laparoscopic nephroureterectomy may soon become the procedure of choice for the ablative management of upper tract transitional cell carcinoma.

Laparoscopic bladder neck suspension fails the test of time.

PURPOSE: Initial reports on laparoscopic bladder neck suspension have suggested success rates similar to those of traditional bladder neck suspension. We compare long-term success rates of laparoscopic and transvaginal Raz bladder neck suspension. MATERIALS AND METHODS: A total of 100 patients with anatomical stress urinary incontinence underwent extraperitoneal laparoscopic bladder neck suspension with securing of the endopelvic fascia to Cooper's ligament (58, laparoscopy group) or transvaginal Raz bladder neck suspension (42, transvaginal group). Patients were evaluated by chart review and telephone questionnaire to determine whether they had urinary incontinence. RESULTS: The 2 groups were similar in terms of age, mean body mass index, preoperative bladder capacity and post-void residual. Mean followup was 45 months (range 14 to 71) in 50 laparoscopy group (86%) and 59 months (range 35 to 72) in 29 transvaginal group (70%) patients. Only 15 of 50 laparoscopy group (30%) and 10 of 29 transvaginal group (35%) patients were completely continent at followup. There was no statistically significant difference in the success rates for the 2 groups. Mean time to failure for both groups was 18 to 24 months. CONCLUSIONS: With long-term followup laparoscopic bladder neck suspension demonstrated poor success rates similar to other minimally invasive surgical therapies for stress urinary incontinence. Any new surgical technique for treatment of stress urinary incontinence should have a mean followup of more than 2 years to determine true clinical efficacy.

Treatment options for benign prostatic hyperplasia.

OBJECTIVE: To examine current treatment options for benign prostatic hyperplasia with emphasis on randomized, clinical trials and our current management approach. QUALITY OF EVIDENCE: Benign prostatic hyperplasia remains difficult to define clinically or measure objectively. As a result, research has been fairly weak. With newer treatments, however, more definitive studies have been reported. MAIN FINDINGS: Transurethral resection of the prostate remains the criterion standard for severe disease. Watchful waiting, medical management, or early surgical intervention are all valid options for moderate disease and should be tailored to the characteristics and desires of individual patients. Recent minimally invasive surgical techniques, such as microwave and laser surgery, have not yet achieved the quality of evidence to be generally recommended. CONCLUSIONS: Management of benign prostatic hyperplasia should be individualized to patients' circumstances and personal choices.

Reinnervation of isolated islets of Langerhans transplanted beneath the kidney capsule in the rat.

Neural regulation of islets of Langerhans mediates responses to stress and food ingestion. Transplantation of isolated islets offers hope to patients with insulin dependent diabetes mellitus but denervation of isolated islets may affect the capacity for appropriate metabolic control. Previous examination of the endocrine response to stress in islet autografted dogs revealed differences consistent with loss of neural regulation. Therefore, in the present study, islets grafted in rats were examined for extent and nature of reinnervation. Islets isolated from syngeneic donors were grafted under the kidney capsule of Wistar-Furth rats (n = 7) after 3 wk of streptozotocin induced diabetes. After 4 mo, graft-bearing kidneys were recovered and processed for double immunofluorescence. Antibodies were directed against (a) neuron associated proteins: synapsin (SYN) and L1; (b) neurotransmitters; tyrosine hydroxylase (TH), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and calcitonin gene-related peptide (CGRP); and (c) islet hormones: insulin and somatostatin. SYN and L1 immunoreactivities in nerve fibres suggested reinnervation of the grafted islets although fibres were not associated with structures within the transplanted islets as in intact islets. CGRP immunoreactivity was observed in fibres and in a subpopulation of cells within intact islets but only in cells of the grafted islets. VIP, TH, and NPY immunoreactivities were found in nerve fibres of intact islets but only VIP was observed in fibres of grafted islets suggesting an absence of sympathetic reinnervation. In conclusion, transplanted islets of Langerhans become reinnervated but with a distribution and complement of neurotransmitters distinct from intact islets.

Glucoregulatory response to moderate exercise in long-term islet cell autografted dogs.

The glucoregulatory response to moderate treadmill exercise (approximately 60% maximum heart rate; 60 min at 100 m/min, 12% grade) was examined in six controls and six pancreatectomized dogs that had been normoglycemic and insulin independent for more than 1 year since autograft of isolated islets of Langerhans (Tx). There were no significant intergroup differences in plasma glucose levels during exercise, but return to baseline after exercise was delayed in Tx (p less than 0.05). In Tx, the initially suppressed insulin levels rose above baseline from 30 to 60 min. Within Tx, exercise-induced levels of plasma glucagon and epinephrine were more variable than control and strongly correlated (r = 0.81, p less than 0.001), perhaps indicating that the A cells within the grafted islets were regulated by circulating beta-adrenergic agonists. We conclude that the isolated islets were removed from direct central control. In Tx dogs, the variable counterregulatory responses and the diminished recovery of plasma glucose after exercise indicate reliance on alternative glucoregulatory mechanisms.