Complications following completion lymphadenectomy versus therapeutic lymphadenectomy for melanoma - A systematic review of the literature.

PURPOSE: Completion lymph node dissection (CLND) following a positive sentinel lymph node biopsy (SLNB) has been reported to be less morbid than lymphadenectomy for palpable disease (therapeutic lymph node dissection; TLND). The reporting of morbidity data can be heterogeneous, and hence no 'average' surgical complication rates of these procedures has been reported. This review aims to determine complications rates to inform patients undergoing surgery for metastatic melanoma. METHODS: A systematic review of English-language literature from 2000 to 2017, reporting morbidity information about CLND and TLND for melanoma, was performed. The methodological quality of the included studies was performed using the methodological index for non-randomised studies (MINORS) instrument and Detsky score. Pooled proportions of post-operative complications were constructed using a random effects statistical model. RESULTS: After application of inclusion and exclusion criteria, 18 articles progressed to the final analysis. In relation to TLND (1627 patients), the overall incidence of surgical complications was 39.3% (95% CI 32.6-46.2); including wound infection/breakdown 25.4% (95% CI: 20.9-30.3); lymphoedema 20.9% (95% CI: 13.8-29.1); and seroma 20.4% (95% CI: 15.9-25.2). For CLND (1929 patients), the overall incidence of surgical complications was 37.2% (95% CI 27.6-47.4); including wound infection/breakdown 21.6% (95% CI: 13.8-30.6); lymphoedema 18% (95% CI: 12.5-24.2); and seroma 17.9% (95% CI: 10.3-27). The complication rate was marginally lower for CLND but not to statistical significance. DISCUSSION: This study provides information about the incidence of complications after CLND and TLND. It can be used to counsel patients about the procedures and it sets a benchmark against which surgeons can audit their practice.

Complications of sentinel lymph node biopsy for melanoma - A systematic review of the literature.

PURPOSE: The complications reported after sentinel lymph node biopsy (SLNB) for melanoma is highly variable in the worldwide literature; the overall complication rate varies between 1.8% and 29.9%. With heterogeneous reporting of morbidity data, no 'average' complication rates of this procedure have been reported. This systematic review aims to determine the complications rates associated with SLNB. METHODS: A systematic review of English-language literature from 2000 to 2015, which reported morbidity information about SLNB for melanoma, was performed. The methodological quality of the included studies was performed using the methodological index for non-randomised studies (MINORS) instrument and Detsky score. Pooled proportions of specific post-operative complications were constructed using a random effects statistical model, and subgroups including lymph node basin and continent of origin of the study were compared. RESULTS: After application of inclusion and exclusion criteria, 21 articles progressed to the final analysis. 9047 patients were included. The overall complication rate was 11.3% (95% CI: 8.1-15.0). The incidence of infection was 2.9% (95% CI 1.5-4.6); seroma 5.1% (95% CI: 2.5-8.6); haematoma 0.5% (95% CI: 0.3-0.9) lymphoedema 1.3% (95% CI: 0.5-2.6) and nerve injury 0.3% (95% CI: 0.1-0.6). There was no statistically significant difference in morbidity between the sites of SLNB or between continents. DISCUSSION: This study provides information about the incidence of complications after SLNB. It can be used to counsel patients about the procedure and it sets a benchmark against which surgeons can audit their practice.

Holmium laser enucleation for prostate adenoma greater than 100 gm.: comparison to open prostatectomy.

PURPOSE: Options for treatment of large (greater than 100 gm.) prostatic adenomas have until now been limited to open surgery or transurethral resection by skilled resectionists. Considerable blood loss, morbidity, extended hospital stay and prolonged recovery occur with open surgery for large prostatic adenomas. Endoscopic surgery for benign prostatic hyperplasia has evolved during the last decade to offer the patient and surgeon significant advantages of transurethral removal of prostatic adenomas. Holmium laser enucleation of the prostate with transurethral tissue morcellation provides significant reductions in morbidity, bleeding and hospital stay for patients with large prostate adenomas. MATERIALS AND METHODS: A retrospective review of data on 10 cases of holmium laser enucleation and 10 open prostatectomies for greater than 100 gm. prostatic adenomas was performed from 1998 to 1999 at our institution. Patient demographics, indication for surgery, preoperative and postoperative American Urological Association (AUA) symptom scores, operating time, serum hemoglobin, resected prostatic weight, pathological diagnosis, length of stay and complications were compared. RESULTS: Patient age, indications for surgery (retention, failed medical therapy, high post-void residual, bladder calculi, bladder diverticula and azotemia) and preoperative AUA symptom scores were similar in both groups. Postoperative AUA symptom scores were significantly decreased (p <0.004) in both groups. Operating times were not significantly different. Serum sodium was unchanged by holmium laser enucleation (not significant), and postoperative hemoglobin was not significantly reduced in the holmium laser enucleation group but decreased significantly in the open prostatectomy group (mean decrease 2.9 +/- 0.7 gm., p = 0.0003). Resected weight was greater in the holmium laser enucleation group (151 versus 106 gm., p = 0.07). Length of stay was significantly shorter in the holmium laser enucleation group (2.1 versus 6.1 days, p <0.001). Complications in the holmium laser enucleation group included stress urinary incontinence in 4 cases, prostatic perforation in 1 and urinary retention in 1. No patient treated with holmium laser enucleation was discharged home with an indwelling catheter. Complications in the open prostatectomy group included bladder neck contractures in 2 cases, stress incontinence in 1 and urge incontinence in 1. All patients treated with open prostatectomy were discharged home with an indwelling catheter. CONCLUSIONS: Holmium laser enucleation is an effective, safe procedure for large prostatic adenomas with significantly lower morbidity, catheterization duration and length of stay. Performing holmium laser enucleation for large adenomas requires experience. Stress incontinence was seen frequently with laser but was short-term and self-limited. Holmium laser enucleation is a new procedure, and as experience and expertise increase, it may become an attractive alternative to open prostatectomy for patients with large prostate adenomas.

Fournier's gangrene in a modern surgical setting: improved survival with aggressive management.

OBJECTIVE: To examine the outcome of 23 consecutive patients with Fournier's gangrene. PATIENTS AND METHODS: Patients' charts were reviewed retrospectively from all those treated for Fournier's gangrene between July 1994 and July 1997 at the UCLA affiliated hospitals. RESULTS: Twenty-three patients were identified (mean age 51.7 years, range 13-71). The aetiologies included perirectal abscess (43%), urethral stricture (30%), scrotal abscess (21%) and unknown (4%). Predisposing factors included diabetes mellitus (43%), steroids or chemotherapy (21%), alcohol abuse (43%), malignancy (26%) and radiation therapy (9%). All 23 patients initially received wide debridement and placement of a percutaneous suprapubic tube. At the time of the first surgery, total scrotectomy was required in all, colostomy in 17% and penectomy in 4%. An additional 35% required eventual colostomy and an additional 9% required a penectomy. Patients underwent repeat debridement a mean of 2.5 times; the overall survival was 96%. CONCLUSION: Survival can be improved in patients with Fournier's gangrene by combining aggressive surgical and medical management. The keys to successful outcome included a high index of suspicion, prompt fluid resuscitation, rapid initiation of broad-spectrum antibiotics, a multidisciplinary approach, early surgical intervention with radical debridement, haemodynamic support in an intensive care setting, and frequent repeat operative debridement.

Effects of long-term oral administration of L-arginine on the rat erectile response.

PURPOSE: Nitric oxide (NO), the neurotransmitter responsible for mediating penile erection in the rat, is synthesized from L arginine by nitric oxide synthase (NOS) in a reaction blocked by L-NAME (N-omega-nitro-L-arginine methyl ester). To determine whether dietary supplementation of L-arginine can stimulate penile erection and whether ancillary pathways for penile erection may exist, a series of experiments were conducted in the Fischer 344 rat. MATERIALS AND METHODS: Adult male (5 month old) and aged (20 month old) rats were fed L-arginine (2.25%) and L-NAME (0.7%) dissolved in tap water for 8 weeks. Animals (n = 6) underwent electrical field stimulation (EFS) of the cavernosal nerve to induce erection and both maximal intracavernosal pressure (MIP) and mean arterial pressure (MAP, mm. Hg +/- SEM) were measured. Tissue and serum levels of L-arginine were measured by an automated amino acid analyzer. Penile eNOS (endothelial) and nNOS (neuronal) content were measured by western blot densitometry. Total penile NOS enzyme activity was measured by the L-arginine to L-citrulline conversion assay. RESULTS: The L-arginine fed animals demonstrated a significant increase in EFS-induced MIP when compared to the controls in both the adult (104 +/- 4 vs. 86 +/- 6, p = 0.04) and aged (87 +/- 5 vs. 66 +/- 4, p = 0.02) animals, without changes in MAP. L-NAME virtually abolished the MIP in adult rats (8 +/- 3, p < 0.0001), while increasing the MAP (186 +/- 8, p < 0.0001). Serum and penile tissue levels of L-arginine were increased by 64-148% in all groups compared to control animals. Penile eNOS and nNOS content remained unchanged in control and treated animals. Penile NOS activity was increased nearly 100% in the L-arginine treated groups vs. controls. CONCLUSIONS: Long-term oral administration of supra-physiologic doses of L-arginine improves the erectile response in the aging rat. We postulate that L-arginine in the penis may be a substrate-limiting factor for NOS activity and that L-arginine may up-regulate penile NOS activity but not its expression. The blockade of penile erection by EFS with L NAME suggests that if ancillary corporeal vasodilator mechanisms develop, a basal level of NO synthesis is still required for activation and relaxation of the corporeal smooth muscle. These data support the possible use of dietary supplements for treatment of erectile dysfunction.

Effect of aerobic and anaerobic environments on antistaphylococcal activities of five fluoroquinolones.

A previously established in vitro pharmacodynamic system was used to evaluate the antistaphylococcal activities of five fluoroquinolones under both aerobic and anaerobic conditions. Staphylococcus aureus ATCC 29213 was exposed to a 5-micrograms/ml concentration of each of the following fluoroquinolones: ciprofloxacin, ofloxacin, temafloxacin, sparfloxacin, and clinafloxacin. Terminal elimination half-lives of 4, 6, 8, 8, and 13 h were simulated for the respective drugs. Each fluoroquinolone was bactericidal under both aerobic and anaerobic conditions. However, the bactericidal activity of each fluoroquinolone was delayed by anaerobiosis. This difference in fluoroquinolone activity under aerobic and anaerobic conditions could not be attributed to any particular parameter or physiochemical property but was most likely caused by a combination of factors (e.g., variations in hydrophobicity, intracellular pH, antibiotic concentration, and structure-activity relationships). Fluoroquinolone uptake studies were also performed to investigate the possibility of active, energy-dependent transport mechanisms in S. aureus ATCC 29213. Uptake studies indicated that active efflux does occur in S. aureus ATCC 29213.

Bactericidal action of gentamicin against enterococci that are sensitive, or exhibit low- or high-level resistance to gentamicin.

Treatment of serious enterococcal infection involves the use of penicillin-aminoglycoside combination therapy if the aminoglycoside minimum inhibitory concentration (MIC) is < or = 2000 micrograms/ml, and the organism is susceptible to penicillin or ampicillin. We evaluated killing of 15 enterococci that differ in their susceptibility to gentamicin using time-kill studies at different gentamicin concentrations. Sensitive strains had a uniform population killed by gentamicin concentrations equal to or above the MIC. Low-level resistant strains (MIC > or = 8 but < or = 2000 micrograms/ml of gentamicin) had a diverse population with large numbers of cells killed at one-half the MIC, while the highly resistant strains (MIC > 2000 micrograms/ml) showed no killing by any concentration of gentamicin.

Evaluation of activity of temafloxacin against Bacteroides fragilis by an in vitro pharmacodynamic system.

An in vitro pharmacodynamic system has been successfully adapted to simulate in vivo antimicrobial pharmacokinetics under anaerobic conditions. This system was used to perform time-kill kinetic studies which were designed to compare the activity of temafloxacin to ciprofloxacin and cefotetan against two strains of Bacteroides fragilis (ATCC 25285 and ATCC 23745). All experiments were performed as single-dose, 24-h, duplicate runs. Starting bacterial inocula of 10(7) CFU/ml were exposed to starting antimicrobial concentrations of 5 micrograms of temafloxacin per ml, 5 micrograms of ciprofloxacin per ml, and 100 micrograms of cefotetan per ml. Terminal half-lives of 8, 4, and 4 h were simulated for each antimicrobial agent. Temafloxacin was rapidly bactericidal against B. fragilis. Ciprofloxacin was not bactericidal (< 3 log10 unit decline in bacterial numbers) to either strain of B. fragilis. Cefotetan was bactericidal (> or = 3 log10 unit decline in bacterial numbers) to each strain but killed at a slower rate than temafloxacin. Times to 3 log10 unit declines of strain ATCC 25285 were 2, 4, and > 24 h, whereas those of strain ATCC 23745 were 4, 4, and > 24 h for temafloxacin, cefotetan, and ciprofloxacin, respectively. Total logarithmic declines of strain ATCC 25285 were > 4.5, > 4.5, and 2.9 log10 CFU/ml, whereas those of strain ATCC 23745 were 4.1, > 4.5, and 1.2 log10 CFU/ml for each drug, respectively. These and other studies demonstrated that temafloxacin showed potential as an agent that could have been further developed for use in the treatment of anaerobic infections. However, the drug was removed from the market by its manufacturer because of toxicity issues. Although the release of newer fluoroquinolones that possess significant activity against anaerobic bacteria does not appear imminent, the time-kill studies performed in this study demonstrate that further research is warranted in the development of fluoroquinolones which possess significant antianaerobic activity.

Clostridium difficile colonization in residents of long-term care facilities: prevalence and risk factors.

OBJECTIVE: To determine the period prevalence of Clostridium difficile disease and asymptomatic carriage in the residents of long-term care facilities (LTCF) and to characterize the risk factors for colonization or associated disease. DESIGN: Period prevalence survey. SETTING: Two long-term care facilities in St. Paul, MN. PARTICIPANTS: Specimens were collected from 225 LTCF residents. MEASUREMENTS: The dependent variable was the culture result for C. difficile, which was isolated and identified using selective culture media and a commercial anaerobe identification kit. Tissue culture assay was used to detect the ability of each C. difficile isolate to produce toxin. Independent variables (including gender, age, race, current medical diagnoses, severity of underlying disease, case mix, current clinical symptoms, current medications, antibiotic use within 4 weeks prior to specimen procurement, and other pertinent history) were obtained from the current medical record of each participant. RESULTS: Of 225 stool cultures that were obtained, 16 (7.1%) were positive for C. difficile. None of the residents with a positive culture was symptomatic. History of nosocomial infection and the use of antibiotics in general, cephalosporins, trimethoprim/sulfamethoxazole (TMP/SMX), and histamine-2 blockers were significantly associated with positive C. difficile culture (P < or = 0.05) by univariate analyses. Trends towards significance (0.05 < 0.10) were noted for narcotic use, previous hospitalization, LTCF, and non-insulin-dependent diabetes mellitus. Logistic regression analysis revealed significant, independent predictors of positive culture: antibiotic use in general (P = 0.028; relative risk = 3.31), histamine-2 antagonist use (P = 0.038; relative risk = 3.27), cephalosporin use (P = 0.038; relative risk = 4.66), and TMP/SMX use (P = 0.007; relative risk = 8.45). CONCLUSIONS: The use of antibiotics, particularly cephalosporins and TMP/SMX, is a significant risk factor for asymptomatic carriage of C. difficile in long-term care facilities. The use of H-2 blockers was also a significant risk factor for carriage; however, this finding has not been reported previously and should be confirmed by independent studies. These medications should be used judiciously in the LTCF population. When diarrheal diseases are encountered in LTCF residents, a high index of suspicion for C. difficile infection should be maintained and the appropriate diagnostic and therapeutic measures taken.

Effect of yogurt on clindamycin-induced Clostridium difficile colitis in hamsters.

Yogurt exhibits in vitro bactericidal activity against a variety of pathogenic microorganisms, including Clostridium difficile. In the present studies, we tested whether yogurt ingestion could prevent or ameliorate antibiotic associated colitis in the clindamycin-treated hamster model. Male golden Syrian hamsters were given 5 mg/kg clindamycin subcutaneously 24 hr before and 6 hr following inoculation with 0.5 ml of less than 10, 10(3), 10(5), or 10(6) CFU/ml of C. difficile. Hamsters in the control group ingested chow and water ad libitum, whereas the experimental group ingested chow and a 1:1 (v/v) mixture of yogurt and water ad libitum, beginning 24 hr before the first injection of clindamycin and continuing throughout the course of the study. Animals were monitored for colonization with C. difficile, pathological evidence of colitis, and death. Mortality was 100% in yogurt-treated animals, and all animals showed histological changes of severe colitis. Fecal and intestinal segment cultures were positive for C. difficile in all animals. Thus, in the hamster model, we found no evidence to support the possible efficacy of yogurt in the prevention of C. difficile colitis.

Human infections associated with Bordetella bronchiseptica.

This study examines the potential of Bordetella bronchiseptica to act as a human pathogen. After encountering two patients from whom B. bronchiseptica was isolated, we searched the literature and found 23 reports in which a human infection was reported in association with B. bronchiseptica. As a basis for evaluating these cases, we summarize the literature about the current microbiological status of B. bronchiseptica, the pathology and pathogenic mechanisms associated with the microorganism, and the likelihood of it acting as a commensal or colonizer. From this review we conclude that B. bronchiseptica has been rarely isolated from humans despite their considerable exposure to animal sources. Evidence suggests that B. bronchiseptica may be rarely encountered as a commensal or colonizer of the respiratory tract of humans and rarely in association with infection. When found as a probable pathogen, most infections have been respiratory tract in origin and have occurred in severely compromised hosts.

A general ampC active site oligonucleotide probe for gram-negative rods.

We have developed a 33 mer probe that hybridizes to the serine active site of the chromosomal ampC beta-lactamase gene of Pseudomonas aeruginosa and the Enterobacteriaceae. We tested this probe against a variety of Enterobacteriaceae, and a series of 23 P. aeruginosa by dot-blots and selected Southern blots. This probe is an alternative or supplement to enzyme studies for characterizing the class of a Gram-negative rod's beta-lactamase and is a useful tool for studies of Pseudomonas beta-lactamase regulation.

Antibacterial activity of cefoperazone and cefoperazone plus sulbactam in a neutropenic site model.

Efficacy of cefoperazone versus cefoperazone plus sulbactam was studied in a rabbit neutropenic site infection model against a broad range of clinical isolates including six isolates each of staphylococci, enterococci, pneumococci, Enterobacteriaceae, and Pseudomonas aeruginosa. Therapy of cefoperazone plus sulbactam demonstrated enhanced efficacy against the staphylococci, pseudomonads, and Enterobacteriaceae. The activity of cefoperazone against enterococci and pneumococci was not enhanced or inhibited by the addition of sulbactam. Increased concentrations of cefoperazone found at the infection sites when sulbactam was added to the therapeutic regimen indicates that sulbactam provided a protection to cefoperazone from beta-lactamases produced by staphylococci and Enterobacteriaceae. The combination improved the efficacy of cefoperazone in this animal model.

Treatment evaluation of experimental staphylococcal infections: comparison of beta-lactam, lipopeptide, and glycopeptide antimicrobial therapy.

LY 146032, teicoplanin, vancomycin, oxacillin, cephalothin, cefamandole, ampicillin plus sulbactam, and cefoperazone plus sulbactam were studied against six isolates of staphylococci (including both Staphylococcus aureus and coagulase negative staphylococci) using in vivo and in vitro methods. In vitro susceptibility measurements demonstrated that all six isolates were sensitive to LY 146032 and vancomycin and that five of six isolates were sensitive to tiecoplanin, cefamandole, ampicillin plus sulbactam, and cefoperazone plus sulbactam. Comparison of antimicrobial therapy in an in vivo rabbit model demonstrated that cefoperazone plus sulbactam was active against the greatest number of isolates (five of six) based on a reduction of greater than or equal to 5.0 log10 colony forming units per milliliter (CFU/ml) from growth control at the end of the animal treatment study. Vancomycin and oxacillin were equal in achieving reductions of greater than or equal to 5.0 log10 CFU/ml in four of the six isolates. Comparing each isolate's in vivo outcome to in vitro data shows that in vitro susceptibility tests overpredict the sensitivity of these six isolates to LY 146032 and vancomycin, are variable for teicoplanin, cefamandole, ampicillin plus sulbactam, and cefoperazone plus sulbactam, and underpredict for oxacillin.

In vitro activity of LY 264826 compared with that of vancomycin against 100 clinical isolates each of methicillin-resistant Staphylococcus aureus and Clostridium difficile.

The in vitro activity of LY 264826, a new glycopeptide antibiotic, was compared with that of vancomycin against 100 strains each of methicillin-resistant Staphylococcus aureus and Clostridium difficile. LY 264826 was more active, by weight, than vancomycin against the isolates tested. The human serum protein binding of LY 264826 was 15.3% (range, 9.8 to 21.8%).

In vitro antibacterial effect of yogurt on Escherichia coli.

We investigated the bactericidal and bacteriostatic effects of yogurt on three strains of Escherichia coli: human toxigenic (078:H11), rabbit pathogenic (RDEC-1) and rabbit nonpathogenic [015:K14(L):H4]. Approximately 10(6) organisms were incubated in yogurt, milk, broth, and modifications of these materials. Aliquots were removed at various intervals and plated on MacConkey's agar for enumeration of E. coli. Yogurt was bactericidal (at least 5 log10 reduction in bacterial counts) to all three strains of E. coli with less than 10 CFU/ml remaining by 9 hr. In contrast, all three strains replicated rapidly in milk and broth, reaching maximum concentrations by 9 hr. The E. coli strains survived and multiplied in milk acidified to the same pH as the yogurt. Yogurt (native pH 4.1-4.4) in which the pH was brought up to and maintained at pH 5.5 or pH 7 for 8 hr was not bactericidal to E. coli. Heat-treated yogurt and the filtered supernatant of centrifuged yogurt (both containing no yogurt bacteria) were only bacteriostatic. We conclude that both live yogurt bacteria and a pH near 4.5 are necessary for the bactericidal activity of yogurt. The possibility that yogurt ingestion could protect against infection via other foods contaminated with pathogenic E. coli merits further in vivo investigation.

Comparative efficacy of cefoperazone, cefoperazone plus sulbactam, ciprofloxacin, clindamycin, metronidazole, and penicillin G against anaerobic bacteria in an animal model.

Treatment efficacy of various antimicrobial regimens against anaerobes was studied in semipermeable chambers simulating a closed-space, locally neutropenic infection site in rabbits. Bacteroides fragilis, Bacteroides melaninogenicus, Clostridium perfringens, and Peptostreptococcus anaerobius were inoculated (at a mean of 5.3 log10 CFU/ml in prereduced pooled rabbit serum) into the chambers (one isolate per chamber) in triplicate. Antimicrobial therapy consisted of cefoperazone, cefoperazone plus sulbactam, ciprofloxacin, clindamycin, metronidazole (against the gram-negative anaerobes), or penicillin G (against the gram-positive anaerobes), beginning 4 hours after organism inoculation and continuing every 6 hours for 16 doses. With the use of anaerobic techniques for specimen acquisition, transport, and culture, quantitative bacterial findings were measured at the start of therapy and at various time points thereafter. Antibiotic concentrations were measured in blood and chamber fluid by liquid chromatography or bioassay methods. At the end of the study in vivo organisms were reduced by at least 3 log10 CFU/ml from drug-free growth control chambers by all the antimicrobial regimens tested except for cefoperazone against B. fragilis and ciprofloxacin against the three isolates tested. The addition of sulbactam to cefoperazone inhibited B. fragilis beta-lactamase activity and eradicated B. fragilis in vivo. In vivo results with this model confirmed in vitro susceptibilities of all tested antimicrobials except ciprofloxacin and should provide useful indications of the potential clinical efficacy of other new agents against anaerobes.