Diverticular colovesical fistula: What should we really be doing?

BACKGROUND: Colovesical fistula secondary to diverticular disease is increasing in incidence. Presentation and severity may differ, but a common management strategy may be applied. The aim of this study is to evaluate the characteristics and perioperative management of patients with colovesical fistulae and determine optimal management. METHODS: From 2003 to 2012, all charts of surgical patients with diverticular colovesical fistulae at two different institutions were reviewed. Patient and presentation characteristics and perioperative management and outcomes were recorded. Patient groups with early and late catheter removal (< 8 and ≥ 8 days) were compared with significance level set at p < 0.05. RESULTS: Seventy-eight patient charts were reviewed. The mean duration of symptoms was 7.5 months. Laparoscopic assisted surgery was carried out in 35% of patients. Complex bladder repair was performed in 27%. Mean length of stay was 8 days. Mean urinary catheter duration was 13 days. Seventy percent of patients underwent postoperative cystogram, with 4% positive for extravasation. Patients with early catheter removal were significantly older, more likely to have received intraoperative methylene blue instillation, and less likely to have had a complex bladder repair (p < 0.05). Complication rate, length of stay, postoperative cystography, and stent use were similar for both catheter removal groups. CONCLUSIONS: Intraoperative methylene blue bladder instillation should be utilized to limit unnecessary bladder repairs. In the setting of negative methylene blue extravasation, surgeons may confidently remove urinary catheters in 7 days or less, in some cases as early as 48 h. In complex bladder repairs, cystogram is still an important adjunct, with those patients with negative studies benefiting from catheter removal at 7 days or less.

Treatment of fistula-in-ano using a porcine small intestinal submucosa anal fistula plug.

BACKGROUND: Porcine small intestinal submucosa (SIS) is a bioprosthetic collagen material used in the management of various surgical conditions, especially hernia repairs. We studied the effectiveness of porcine SIS Bioprosthetic plug (Surgisis AFP, Cook Biotech Inc., West Lafayette, IN, USA) in the treatment of fistula-in-ano. METHODS: A prospective multi-institutional study was conducted on 73 patients with anorectal fistulas of differing etiologies. All plugs were inserted in the operating room under anesthesia in patients with preoperative bowel preparation. Regular follow-up was scheduled at 2 weeks, 3, 6, and 12 months. The primary end point was complete closure of the fistula and cessation of drainage over the follow-up period. Seventy-eight AFPs were inserted in 73 patients (28 women and 45 men). Rectovaginal fistulas were excluded. Crohn's disease accounted for 11% (8/73) of the patients. Seventy-three percent of patients (n = 53) had primary fistulas whereas 27% (N = 20) had recurrent fistulas. RESULTS: The plug extrusion (fallout) rate was 9% (7/78). There was no difference in closure rates between primary and recurrent fistulas (primary = 20/53 = 38% and recurrent 8/20 = 40%). The overall patient success rate was 38% (28/73) and the plug success rate was 39.5% when plug fallouts were eliminated. The fistulas in four out of eight patients with Crohn's disease closed (50%). There were no intraoperative complications. There were four postoperative abscesses (4/73; 5%). CONCLUSIONS: Use of AFP for treatment of fistula-in-ano is safe and modestly effective in reasonable long-term (15 months) follow-up. This sphincter conserving procedure should be included in the armamentarium of surgeons in the management of transsphincteric or suprasphincteric fistulas.

Delayed transanal repair of persistent coloanal anastomotic leak in diverted patients after resection for rectal cancer.

AIM: Anastomotic leakage is a feared complication of colorectal surgery and can be devastating in low pelvic anastomosis. With the advent of nonoperative treatments for leakage, the question of management of persistent low colorectal and coloanal anastomosis arises. A review of patients who have undergone transanal repair of anastomotic leakage is presented. METHOD: A review of all anastomoses performed in the Division of Colorectal surgery at two institutions, from January 2000 to June 2008, was performed. Anastomotic leakage was defined as the finding at reoperation of a dehiscence, or radiographic findings of extravasation from the anastomosis, or the identification of intra-abdominal abscess formation at the site of the anastomosis, enterocutaneous fistula or rectovaginal fistula. Patients who underwent transanal repair of the leakage were identified. RESULTS: There were 663 low anterior resections performed during the study period. Of these, 36 experienced leakage of a low colorectal or coloanal anastomosis. Of these 36 patients, five underwent transanal repair of the anastomotic leak. All had had a low anterior resection for rectal cancer (coloanal=4; low colorectal anastomosis=1). Four had had prior chemoradiation and ileostomy defunctioning at the initial operation. The fifth had an ileostomy created to treat a leak. Six transanal repairs were performed, including endorectal advancement flap (n=3), dermal flap (n=1), direct suture repair (n=1) and debridement of an infected cavity (n=1). At the time of the present assessment, four patients had undergone reversal of ileostomy after radiographic evidence of complete healing and the fifth patient has a persistent leak. CONCLUSION: Transanal repair of a persistent low colorectal or coloanal anastomotic leakage is feasible in selected cases, even when chemoradiation has been performed.

Evolution of treatment of fistula in ano.

BACKGROUND: Fistula-in-ano is a common medical problem affecting thousands of patients annually. In the past, the options for treatment of fistula-in-ano were limited to fistulotomy and/or seton placement. Current treatment options also include muscle-sparing techniques such as a dermal island flap, endorectal advancement flap, fibrin sealent injection, anal fistula plug, and most recently ligation of the intersphincteric fistula tract (procedure). This study seeks to evaluate types and time trends for treatment of fistula-in-ano. METHODS: A retrospective review from 1975 to 2009 was performed. Data were collected and sorted into 5-year increments for type and time trends of treatment. Fistulotomy and partial fistulotomy were grouped as cutting procedures. Seton placement, fibrin sealant, dermal flap, endorectal flap, and fistula plug were grouped as noncutting procedures. Statistical analysis was performed for each time period to determine trends. RESULTS: With institutional review board approval, the records of 2,267 fistula operations available for analysis were included. Most of the patients were men (74 vs. 26%). Cutting procedures comprised 66.6% (n = 1510) of all procedures. Noncutting procedures were utilized in 33.4% (n = 757), including Seton placement alone 370 (16.3%), fibrin sealant 168 (7.4%), dermal or endorectal flap 147 (6.5%), and fistula plug 72 (3.2%). The distribution of operations grouped in 5-year intervals is as follows: 1975-1979, 78 cutting and one noncutting; 1980-1984, 170 cutting and 10 noncutting; 1985-1989, 54 cutting and five noncutting; 1990-1994, 37 cutting and six noncutting; 1995-1999, 367 cutting and 167 noncutting; 2000-2004, 514 cutting and 283 noncutting; 2005-2009, 290 cutting and 285 noncutting. The percentage of cutting and noncutting procedures significantly differed over time, with cutting procedures decreasing and noncutting procedures increasing proportionally (χ(2) linear-by-linear association, p < 0.05). CONCLUSIONS: Fistula-in-ano remains a common complex disease process. Its treatment has evolved to include a variety of noncutting techniques in addition to traditional fistulotomy. With the advent of more sphincter-sparing techniques, the number of patients undergoing fistulotomy should continue to decrease over time. Surgeons should become familiar with various surgical techniques so the treatment can be tailored to the patient.

Interventions for preventing neuropathy caused by cisplatin and related compounds.

BACKGROUND: Cisplatin and several related antineoplastic agents used to treat many types of solid tumors are neurotoxic, and most patients completing a full course of cisplatin chemotherapy develop a clinically detectable sensory neuropathy. Effective neuroprotective therapies have been sought. OBJECTIVES: To examine the efficacy of purported chemoprotective agents to prevent or limit the neurotoxicity of cisplatin and related agents among human patients. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Register (January 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1 2005), MEDLINE from (January 1966 to March 2005), EMBASE (from January 1980 to March 2005), LILACS (from January 1982 to March 2005), CINAHL (from January 1982 to March 2005) for randomized trials designed to evaluate neuroprotective agents used to prevent or limit neurotoxicity of cisplatin and related agents among human patients. SELECTION CRITERIA: Quasi-randomized or randomized controlled trials whose participants received cisplatin (or related compounds) chemotherapy with or without a potential neuroprotectant (amifostine, diethyldithiocarbamate, glutathione, Org 2766, or vitamin E) and were evaluated zero to six months after completing chemotherapy using quantitative sensory testing (primary) or other measures including nerve conduction studies or neurological impairment rating using validated scales (secondary). DATA COLLECTION AND ANALYSIS: We identified 16 randomized trials involving five possible chemoprotective agents. Each study was reviewed by two authors who extracted the data and reached consensus. The included trials involved five unrelated treatments and included many disparate measures of neuropathy, resulting in insufficient data for any one measure to combine the results in most instances. MAIN RESULTS: The one of five eligible amifostine trials (541 participants) using quantitative sensory testing demonstrated a favorable outcome in terms of amifostine neuroprotection, but the subclinical result was based on 14 participants receiving amifostine. Of the five eligible glutathione trials (327 participants), one used quantitative sensory testing but reported only qualitative analyses. Four eligible Org 2766 trials (311 participants) employed quantitative sensory testing reported disparate results; meta-analyses of three trials using comparable measures showed no significant vibration perception threshold neuroprotection. The remaining trial reported only descriptive analyses. The one eligible diethyldithiocarbamate trial (214 participants) and the one eligible vitamin E trial (27 participants) did not perform quantitative sensory testing. AUTHORS' CONCLUSIONS: At present, the data are insufficient to conclude if any of the purported neuroprotective agents (amifostine, diethyldithiocarbamate, glutathione, Org 2766, or Vitamin E) prevent or limit the neurotoxicity of platin drugs among human patients.

Phase I and pharmacologic study of paclitaxel and cisplatin with granulocyte colony-stimulating factor: neuromuscular toxicity is dose-limiting.

PURPOSE: To determine the maximum-tolerated doses (MTD), the principal toxicities, and the pharmacologic behavior of high doses of Taxol (paclitaxel; Bristol-Myers Squibb, New York, NY) combined with cisplatin and granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS: Untreated and minimally pretreated solid-tumor patients received 24-hour infusions of Taxol on day 1 followed by cisplatin on day 2 and G-CSF, 5 micrograms/kg/d subcutaneously (SC), beginning on day 3. Treatment was repeated every 3 weeks. Starting doses of Taxol and cisplatin were 135 and 75 mg/m2, respectively. RESULTS: The development of a severe peripheral neuropathy and/or severe myalgias precluded the chronic administration of Taxol and cisplatin with G-CSF at doses greater than 250 mg/m2 and 75 mg/m2, respectively. At this dose, the mean Taxol steady-state plasma concentration (Css) exceeds concentrations capable of inducing pertinent antimicrotubule effects in vitro. The severity of the neuropathy was related to the cumulative dose of Taxol, the magnitude of the dose administered during each treatment, and the presence of a pre-existing medical disorder associated with peripheral neuropathy. A proximal myopathy of modest severity also was documented. Although severe neutropenia occurred frequently, especially at the MTD, it was rarely associated with fever (8% of courses), and absolute neutrophil counts (ANCs) less than 500/microL never persisted for more than 5 days. Responses were noted in non-small-cell lung cancer (NSCLC) and head and neck, breast, and esophageal cancers. CONCLUSION: Taxol and cisplatin doses of 250 mg/m2 and 75 mg/m2, respectively, can be administered repetitively with G-CSF to untreated and minimally pretreated patients. However, these doses are not recommended for patients with pre-existing neuropathies until additional experience in high-risk patients is obtained. Although this Taxol dose is nearly 85% higher than the dose that can be combined with cisplatin in the absence of G-CSF, this high-dose regimen should not be used outside the investigational setting until a dose-response relationship has been demonstrated for Taxol in randomized clinical trials.

Neurotoxicity of Taxol.

Neurotoxicity, manifested primarily by a motor and sensory polyneuropathy, is the principal nonhematological side effect of Taxol. Available evidence suggests that Taxol produces a toxic effect involving either axons or ganglion cell bodies, or both, rather than a myelinopathy. As with other toxic polyneuropathies, patients with preexisting peripheral neuropathies, such as those caused by diabetes mellitus or ethanol, appear to be particularly predisposed to developing neurological toxicity. The incidence and severity of the neuropathic manifestations also appear to be related to the Taxol dose level, the cumulative dose of Taxol, and possibly to the use of Taxol in combination with cisplatin. Rarely, manifestations of autonomic and central nervous system dysfunction occur. Taxol also induces myalgias in the peri-treatment period, especially when used in high doses, and a myopathy has been noted in patients treated with high doses of Taxol administered alone and in combination with cisplatin. Although dose-response relationships for Taxol have not been clearly established, these neuromuscular effects are likely to become a significant clinical problem if higher doses of Taxol are used with hematopoietic colony-stimulating factors. The neuromuscular effects of Taxol, including symptoms, physical and electrophysiological manifestations, and predisposing factors, as well as agents that may be used for neuroprotection, are discussed in this report.

Metastatic and non-metastatic colorectal cancer (CRC) cells induce host metalloproteinase production in vivo.

Numerous studies have demonstrated the persistent localization of matrix metalloproteinase (MMP) expression to the interface between invading human colorectal cancer (CRC) cells and surrounding stroma supporting a role for MMPs in CRC invasion and metastasis. The present study sought to determine whether CRC cells of varying metastatic potential would have differential effects on host MMP release. Subcutaneous CRC tumors were generated in BALB/c nude mice using three CRC cell lines: SW480, SW620, and the highly metastatic SW620S5 clone. Representative samples from the subcutaneous CRC were then orthotopically implanted on the cecum of recipient nude mice. Subcutaneous and cecal tumors were analyzed for MMP expression via zymography, western blot, and RT-PCR. In vitro, none of the three cell lines expressed MMP-2 nor MMP-9. In contradistinction, the subcutaneous tumors expressed limited amounts of MMP-2 and MMP-9 while the cecal tumors expressed significant amounts of MMP-2 and MMP-9 as well as other smaller members of the MMP family. MMP-9 mRNA and protein was confirmed as host in origin by RT-PCR with mouse specific primers and a mouse MMP-9 molecular weight of 105 kDa as determined by zymography and western blot analysis. In situ hybridization also localized the mRNA for MMP-9 to the host stromal cells. In conclusion, CRC cells appear incapable of producing MMP-2 and MMP-9 in vitro but are capable of up-regulating host MMP production in vivo. Enhanced host MMP-9 production in metastatic CRC cell-derived subcutaneous and cecal tumors suggests that metastatic colon cells may acquire the expression of important MMP regulating factor(s) in vivo.

Thalidomide-induced neuropathy.

BACKGROUND: Thalidomide is effective for the treatment of some refractory dermatologic and oncologic diseases. Toxic neuropathy limits its use, as embryopathy can be avoided by contraceptive measures. OBJECTIVE: To describe the clinical, electrophysiologic, and pathologic features of thalidomide-induced peripheral neuropathy. METHODS: Clinical and electrophysiologic examinations were performed in seven patients with thalidomide-induced peripheral neuropathy. Thalidomide was used for graft-vs-host disease, pyoderma gangrenosum, and discoid lupus with dosages ranging from 100 to 1,200 mg/day for 5 to 16 months (cumulative dosages of 24 to 384 g). RESULTS: All seven patients had clinical and electrophysiologic evidence of a sensory more than motor, axonal, length-dependent polyneuropathy that presented as painful paresthesias or numbness. Sural nerve biopsies, done in three patients, showed evidence of Wallerian degeneration and loss of myelinated fibers. The symptoms, signs, and electrophysiologic data correlated with total cumulative dose of thalidomide. CONCLUSIONS: Thalidomide induces a dose-dependent sensorimotor length-dependent axonal neuropathy; it should be judiciously used with close neurologic monitoring.

Hospitalization in amyotrophic lateral sclerosis: causes, costs, and outcomes.

OBJECTIVE: As ALS progresses, extensive supportive care is required, including multidisciplinary outpatient care and hospitalization. The authors studied the causes, health care utilization, and outcomes for hospitalized patients with ALS. METHODS: With use of the 1996 Nationwide Inpatient Sample, an administrative database representing 20% of U.S. hospitals, 1,600 hospitalizations in patients with ALS were identified and compared with 5,364,728 non-ALS hospitalizations. RESULTS: The most common concurrent diagnoses in patients with ALS were dehydration and malnutrition (574 patients, 36%), pneumonia (507 patients, 32%), and respiratory failure (398 patients, 25%). Only 38% of patients with ALS were discharged to home without home health care compared with 73% of patients with non-ALS. Fifteen percent of patients with ALS died in the hospital compared with 3% of non-ALS patients. The average length of hospital stay and charges were greater for patients with ALS than for non-ALS patients (8.4 days and $19,810 for ALS patients and 5.4 days and $11,924 for non-ALS patients). Mortality was significantly associated with emergency room admission (versus nonemergency admission; OR = 1.60), increasing age (per year; OR = 1.03), respiratory failure (OR = 3.37), and pneumonia (OR = 2.02) (p < 0.01 for all comparisons). CONCLUSIONS: Patients with ALS have lengthy and costly hospital admissions, a high in-hospital mortality rate, and few routine discharges. Recognition of the issues that precipitate hospitalization may allow development of preventive strategies.

Mycophenolate mofetil: a safe and promising immunosuppressant in neuromuscular diseases.

The authors report the use mycophenolate mofetil (MM) in the treatment of neuromuscular diseases. Thirty-eight patients (32 with MG, three with inflammatory myopathy, and three with chronic acquired demyelinating neuropathy) were treated with MM for an average duration of 12 months. All patients tolerated MM without major side effects. Twenty-four patients improved either in their functional status or in their ability to reduce corticosteroid dose. Mean time to improvement was 5 months.

Relapse in Guillain-Barré syndrome after treatment with human immune globulin.

Seven adult patients received human immune globulin intravenously as initial therapy for Guillain-Barré syndrome. Although all patients initially stabilized or improved, five patients deteriorated 1 to 16 days after completion of treatment. In all five patients, clinical worsening included loss of at least one functional grade together with a decreased forced vital capacity. We subsequently treated each patient with a course of plasma exchange, which led to varying degrees of clinical improvement in four. In contrast to previously reported relapse rates for Guillain-Barré syndrome, our experience suggests that clinically significant relapses may occur in patients more often following human immune globulin therapy than after either plasma exchange or no therapy.

Total neuropathy score: validation and reliability study.

OBJECTIVE: To determine the validity and reliability of the total neuropathy score (TNS) in normal subjects and in subjects with diabetic polyneuropathy. BACKGROUND: Clinical research in peripheral neuropathy requires validated outcome measures. Multiple outcome measures have been used in clinical trials, including symptom measures, functional scales, quantitative clinical examinations, nerve conduction studies, computerized sensory examinations, and nerve biopsy. Each of these measures has its strengths and weaknesses. In two previous studies of toxic neuropathy from chemotherapeutic agents, the authors used the TNS as the outcome measure. The TNS combines information obtained from grading of symptoms, signs, nerve conduction studies, and quantitative sensory tests, and provides a single measure to quantify neuropathy. METHODS: The authors measured the inter- and intrarater reliability of the TNS and preformed a cross-sectional validation study of the TNS and its subscales with the Mayo Clinic measures of neuropathy, neuropathy symptom score (NSS), and the neurologic impairment score (NIS) in five healthy control subjects and 30 individuals with varying severities of diabetic polyneuropathy. RESULTS: Inter- and intrarater reliability of the TNS was excellent (0.966 and 0.986 respectively). The cross-sectional validation study showed excellent correlations among all measures of neuropathy. CONCLUSIONS: The total neuropathy score is a validated measure of peripheral nerve function and could be used as an end point for clinical trials of peripheral neuropathy.

Inter- and intraexaminer reliability of nerve conduction measurements in patients with diabetic neuropathy.

We determined the inter- and intraexaminer reliability of nerve conduction measurements in six patients with diabetic peripheral neuropathy. Each patient was examined by six electromyographers on two separate occasions at least 1 week apart. We obtained attributes of nerve conduction at each examination and analyzed the data by analysis of variance. Intraexaminer reliability was high for 11 of 12 measurements, and interexaminer reliability was high for eight of twelve. Three of the four measurements that varied between examiners were either sensory or motor amplitudes, attributes frequently used to measure disease progression or to assess the result of therapeutic intervention. Our results suggest that longitudinal nerve conduction measurements used to assess worsening or improvement over time should optimally be performed by a single examiner to minimize the degree of variability associated with different examiners.

Clinical toxicities encountered with paclitaxel (Taxol).

Although paclitaxel (TAXOL) appears to be one of the most promising antineoplastic agents of the last decade, with demonstrated activity in advanced and refractory ovarian, breast, lung, and head and neck cancers, most clinical oncologists have had little experience with the agent. This is largely the result of the initially limited supply of paclitaxel and other obstacles encountered during early clinical development that restricted the drug's availability to a few investigational centers. Although a high incidence of major hypersensitivity reactions due to the Cremophor EL vehicle used in formulation disrupted and almost terminated the clinical development of paclitaxel, hypersensitivity reactions are no longer a serious problem consequent to the advent of effective premedication regimens and longer administration schemes. Instead, neutropenia is the principal toxicity of paclitaxel. At clinically relevant doses, absolute neutrophil count nadirs are severely depressed in most patients. The duration of severe neutropenia, however, is usually brief; treatment delays for unresolved hematologic toxicity are rare, and absolute neutrophil count nadirs are constant with repetitive dosing, suggesting that neutropenia is not cumulative. Asymptomatic sinus bradycardia has occurred in up to 29% of patients in phase II trials, and other cardiac disturbances, including atrioventricular conduction and bundle branch blocks, ventricular tachycardia, and possible ischemic manifestations, have been reported in approximately 3% of patients. Cardiac disturbances have primarily been noted in studies that used cardiac monitoring to more effectively detect and manage major hypersensitivity reactions. Although sinus bradycardia and conduction blocks appear to represent true toxicities, ventricular tachycardia and ischemic manifestations, which have largely been observed in patients with preexisting cardiac disease, may not be due to paclitaxel. In view of the lack of clinical significance of the cardiac effects and their infrequent occurrence, cardiac monitoring during paclitaxel is not recommended for patients without cardiac risk factors. However, until precise risk factors can be defined, patients with a significant antecedent cardiac history are generally not considered to be good candidates for paclitaxel therapy. Neurotoxicity, characterized principally by peripheral neurosensory manifestations, has generally been of mild to moderate severity, even in heavily pretreated patients at paclitaxel doses < or = 200 mg/m2. However, some patients have developed a severe sensory-motor polyneuropathy at higher doses of paclitaxel (given as a single agent or in combination with cisplatin). Patients with an antecedent peripheral neuropathy or coexisting medical illnesses associated with peripheral neuropathy (such as diabetes mellitus and substantial prior alcohol use) appear to be especially prone to developing peripheral neuropathy.(ABSTRACT TRUNCATED AT 400 WORDS)

Different patterns of glycolipid antibody reactivity: lower motor neuron syndromes vs. immunization.

High titers of serum antibodies against GM1 ganglioside occur frequently in patients with lower motor neuron (LMN) syndromes. We compared the specificities of the antiganglioside antibody reactivities in LMN patients with those arising after immunization of Lewis rats with several ganglioside containing preparations including purified GM1, human central nervous system (CNS) grey matter and white matter. Serums with high titers of anti-GM1 antibodies from patients with LMN syndrome usually showed limited cross-reactivity to other glycolipids but often bound to a Gal(beta 1-3)GalNAc-containing neoglycoprotein. In contrast, serums with anti-GM1 antibody arising after immunization showed broad cross-reactivity with other glycolipids but did not bind to the neoglycoprotein. We conclude that the serum patterns of antiganglioside antibody reactivity secondary to immunization with gangliosides and CNS components are different from the natural autoantibodies found in LMN patients. The antiganglioside antibodies seen in LMN patients are unlikely to be a result of autoreactivity to gangliosides after nervous tissue damage.

Anti-GM1 ganglioside antibodies with differing fine specificities in patients with multifocal motor neuropathy.

Antibodies to gangliosides were detected in sera from three of 19 patients with chronic inflammatory polyneuropathy (CIP) by a thin-layer chromatogram overlay technique. All three of the patients fell into a clinical subset of the group that had multifocal motor neuropathy, and in all three patients the antibodies reacted with GM1 ganglioside. However, the fine specificities of the antibodies differed as demonstrated by cross-reactivity with different gangliosides in each of the three patients. The antibodies in patient 1 reacted with GM1, GD1b, and asialo-GM1 suggesting that the terminal Gal(beta 1-3)GalNAc moiety that is common to these three glycolipids is an important part of the epitope(s). This was confirmed by showing reactivity of the antibodies with Gal(beta 1-3)GalNAc conjugated to bovine serum albumin. Patient 2 had antibodies that did not react with GD1b, but cross-reacted with GM2 ganglioside suggesting that the epitope(s) involved the inner portion of the oligosaccharide moiety that is shared between GM1 and GM2. Patient 3 had antibodies that reacted with GM1 and asialo-GM1, but they did not cross-react with either GD1b or GM2. These results provide further evidence for a relationship between motor nerve syndromes and anti-GM1 antibodies and also suggest that GM1 could be a principal target antigen since other reactive gangliosides differed among the patients. However, the possible pathogenic effects of anti-GM1 antibodies on motor nerves remain to be established.

Wallerian degeneration in peripheral nerve disease.

This article first reviews the different classes of nerve injury. The temporal evolution of electrophysiologic changes occurring during Wallerian degeneration in humans is then described, followed by a description of sequential structural changes and cellular responses that occur after nerve transection. The final section focuses on the basis for resurgent research interest in Wallerian degeneration and the different research approaches being taken to answer basic science and clinical questions.

Laparoscopic transcystic management of choledocholithiasis.

Our objective was to review our community hospital experience with laparoscopic management of choledocholithiasis from 1991 to 1997. We performed a retrospective review of all case records of patients with choledocholithiasis managed surgically at St. Francis Hospital during the study period. Data regarding the history, presentation, investigations, operative details, and follow-up were recorded. Procedures were performed by multiple attending surgeons supervising surgical residents. All common bile duct explorations (CBDEs) were performed by a transcystic approach and followed routine cholangiography. In most cases, cystic duct dilatation over a guide wire was followed by transcystic CBDE with choledochoscopy. Stone extraction was accomplished through a combination of flushing, basket manipulation, fragmentation, retrieval, or advancement of stones through the ampulla. Data were analyzed using SPSS computer software, and P < 0.05 was considered statistically significant. During the period of study there were 1053 laparoscopic cholecystectomies with and without cholangiography and 100 total CBDE performed. Of these, 54/100 had an attempt at laparoscopic CBDE. There were 39 females and 15 males, with a median age of 52 years (range 14-88). Presentation included acute cholecystitis or biliary colic (63%), gallstone pancreatitis (20%), and jaundice or cholangitis (17%). Successful laparoscopic stone removal was achieved in 36 of 54 (67%) cases. Eighteen of the remainder (33%) were converted to an open procedure. Size, number, position of stones, technical difficulties in accessing the common bile duct, and patient factors contributed to open conversion. The rate of successful laparoscopic CBDE improved for each individual surgeon from an average of 22 per cent in the first half of the study period (1991-1994) to 87 per cent in the second half (1995-1997). There was no operative mortality. Significant morbidity in the laparoscopic group included one retained stone and two cases of postoperative pancreatitis. There were three false negative preoperative endoscopic retrograde cholangiopancreatography examinations. Multivariate analysis showed that experience of the individual surgeon was the only significant factor predicting successful laparoscopic CBDE. Low initial success rate in the early phase of the study period improved dramatically to reach an overall success rate of 87 per cent in the second half. Laparoscopic management of common bile duct stones is possible in a community setting with a high success rate and minimal morbidity. It precludes excessive use of endoscopic retrograde cholangiopancreatography with its own set of complications but is associated with a significant learning curve. It is currently our preferred therapeutic approach for choledocholithiasis discovered pre- or intraoperatively.