The use of laparoscopic subtotal cholecystectomy for complicated cholelithiasis.

BACKGROUND: The risk of damage to the bile duct and structures in the hilum of the liver is significant when Calot's triangle cannot be safely dissected during laparoscopic cholecystectomy, and conversion to an open procedure often is performed. This is more common during emergency surgery, but may not render the procedure any easier. Traditionally, open subtotal cholecystectomy was performed, but with the advent of laparoscopic surgery, this has fallen from favor. The authors report their experience using laparoscopic subtotal cholecystectomy to avoid bile duct injury and conversion in difficult cases. METHODS: Laparoscopic subtotal cholecystectomy, performed when the cystic duct cannot be identified safely, consists of resecting the anterior wall of the gallbladder, removing all stones, and placing a large drain into Hartmann's pouch. The notes for all patients who underwent a laparoscopic subtotal cholecystectomy between 1 September 2001 and 31 December 2004 were retrospectively analyzed. RESULTS: Subtotal cholecystectomy was performed in 26 cases including 13 emergency and 13 elective procedures. The median age of the patients (15 women and 11 men) was 68 years (range, 36-86 years). The indications were severe fibrosis in 16 cases, inflammatory mass or empyema in 8 cases, and gangrenous gallbladder or perforation in 2 cases. The median postoperative inpatient stay was 5 days (range, 2-26 days). Five patients underwent postoperative endoscopic retrograde cholangiopancreatography: four for persistent biliary leak and one for a retained common bile duct stone. One patient required laparotomy for subphrenic abscess, and one patient (American Society of Anesthesiology [ASA] grade 4, presenting with biliary peritonitis) died 2 days postoperatively. One patient required a subsequent completion laparoscopic cholecystectomy for a retained gallstone. One patient had a chest infection, and two patients experienced port-site hernias. CONCLUSIONS: Laparoscopic subtotal cholecystectomy is a viable procedure during cholecystectomy in which Calot's triangle cannot be dissected. It averts the need for a laparotomy.

Tuberculosis and the art of macrophage manipulation.

Macrophages are first-line responders against microbes. The success of Mycobacterium tuberculosis (Mtb) rests upon its ability to convert these antimicrobial cells into a permissive cellular niche. This is a remarkable accomplishment, as the antimicrobial arsenal of macrophages is extensive. Normally bacteria are delivered to an acidic, degradative lysosome through one of several trafficking pathways, including LC3-associated phagocytosis (LAP) and autophagy. Once phagocytozed, the bacilli are subjected to reactive oxygen and nitrogen species, and they induce the expression of proinflammatory cytokines, which serve to augment host responses. However, Mtb hijacks these host defense mechanisms, manipulating host cellular trafficking, innate immune responses, and cell death pathways to its benefit. The complex series of measures and countermeasures between host and pathogen ultimately determines the outcome of infection. In this review, we focus on the diverse effectors that Mtb uses in its multipronged effort to subvert the innate immune responses of macrophages. We highlight recent advances in understanding the molecular interface of the Mtb-macrophage interaction.

A prospective randomized comparison of continuous infusion fluorouracil with a conventional bolus schedule in metastatic colorectal carcinoma: a Mid-Atlantic Oncology Program Study.

One hundred seventy-nine patients with advanced measurable colorectal cancer not previously treated with chemotherapy were entered into a prospective randomized clinical trial by the Mid-Atlantic Oncology Program (MAOP) to compare two schedules of delivery for single-agent fluorouracil (5-FU). The "standard" treatment was a schedule commonly employed in clinical practice, namely, a daily bolus dose administered intravenously (IV) for five consecutive days and repeated at 5-week intervals. The investigational treatment was a continuous infusion of 5-FU administered 24 hours a day for a protracted time (10 weeks or more). Both treatments were continued until the development of disease progression or unless interrupted for toxicity. Using stringent objective criteria requiring independent confirmation of x-ray or scan-documented response, the tumor response rate reached 7% (six of 87) for the bolus arm and 30% (26 of 87) for the infusion arms (P less than .001). Toxicity was substantially different for the two arms with major leukopenia observed only on the bolus arm, 22% developing grade 3 (severe) or grade 4 (life-threatening) leukopenia with four sepsis-related deaths. Hand-foot syndrome was observed only in the infusional arm, requiring treatment interruptions and dose reductions in 24% of patients, but with little impact on quality of life. In spite of the major difference in objective response rate, overall survival for the two groups was comparable. Administration of 5-FU as a continuous infusion for protracted periods clearly improves the therapeutic index for this agent in patients with advanced colon cancer with respect to response rate and reduced toxicity. This schedule appears workable in the community setting and yields response rates similar to those reported for 5-FU with high-dose leucovorin, but without the gastroin testinal toxicity profile of the latter combination.

Torsades de pointes associated with voriconazole use.

We describe 2 patients who developed prolonged QTc interval on electrocardiogram while being treated with voriconazole. The first patient had undergone induction chemotherapy for acute myelogenous leukemia, and her course had been complicated by invasive aspergillosis and an acute cardiomyopathy. She developed torsades de pointes 3 weeks after starting voriconazole therapy. She was re-challenged with voriconazole without recurrent QTc prolongation or cardiac dysfunction. The second patient had a significantly prolonged QTc interval while on voriconazole therapy. We recommend careful monitoring for QTc prolongation and arrhythmia in patients who are receiving voriconazole, particularly those who have significant electrolyte disturbances, are on concomitant QT prolonging medications, have heart failure such as from a dilated cardiomyopathy, or have recently received anthracycline-based chemotherapy. The potential for synergistic cardiotoxicity must be carefully considered.

Variation in the sequence and modification state of the human insulin gene flanking regions.

The nucleotide sequence of a highly repetitive sequence region upstream from the human insulin gene is reported. The length of this region varies between alleles in the population, and appears to be stably transmitted to the next generation in a Mendelian fashion. There is no significant correlation between the length of this sequence and two types of diabetes mellitus. We observe variation in the cleavability of a BglI recognition site downstream from the human insulin gene, which is probably due to variable nucleotide modification. This presumed modification state appears not to be inherited, and varies between tissues within an individual and between individuals for a given tissue. Both alleles in a given tissue DNA sample are modified to the same extent.

Regional distribution of cystic fibrosis-linked DNA haplotypes in Brazil: multicenter study.

The restriction fragment length polymorphism (RFLP) haplotypes of cystic fibrosis (CF) alleles vary between populations. To determine the distribution of two RFLPs (XV-2C and KM-19) that are tightly linked to the CF locus, we analyzed a white sample from five different states of Brazil. The haplotypes of 314 CF- and 237 non-CF-bearing chromosomes were uniformly distributed over the five states. The XV-2C allele and haplotype frequencies and the degree of linkage disequilibrium were determined. These were similar to values previously reported in southern European countries but different from results reported for northern and central Europe and North America. In contrast, although KM-19 allele frequencies differed between Brazilian states and European and North American countries, these frequencies were similar to values reported in black Americans. A significant proportion of Brazilian CF-bearing chromosomes had less common haplotypes, suggesting a heterogeneous distribution of CF gene mutations among Brazilians. Further studies are needed to identify the mutations affecting the Brazilian CF patients with various haplotypes.