Money well spent: a comparison of hospital operating margin for laparoscopic and open colectomies.

BACKGROUND: Cost analysis after laparoscopic colectomy has been examined, although reports evaluating the effects of laparoscopy on hospital operating margin are lacking. We compared several cost/revenue measures, including hospital operating margin, between open and laparoscopic colectomies at an academic center. METHODS: Our cost-accounting database was queried for laparoscopic partial (LPC) and total colectomies (LTC), and open partial (OPC) and total colectomies (OTC) to analyze net revenue, total costs, and total hospital operating margin over a 4-year period. Laparoscopic and open colectomy cases were compared, with mean operating margin as the primary outcome. RESULTS: From July, 2002 through May, 2006, 842 patients were included for analysis with 138 undergoing laparoscopic colectomy. Net revenue was higher in the LTC group compared with open (US dollars 30,300 vs US dollars 26,800 [P = .02]), and lower in the LPC group (US dollars 15,300 vs US dollars 21,300 open [P < .0001]). Total costs were reduced in both the LPC and LTC groups compared with open [US dollars 11,700 vs US dollars 17,600 [P < .0001] and US dollars 18,000 vs US dollars 19,400 [P = .0019], respectively). LPC resulted in a similar HOM (US dollars 3,602) compared with OPC (US dollars 3,647; P = .35). LTC resulted in a higher HOM (US dollars 12,300) compared with OTC (US dollars 7,400; P = .02). CONCLUSIONS: LTC generates a significantly higher hospital operating margin than an OTC, although the margins are similar for LPC and OPC.

B7.1 expression eliminates tumor resistance to IL-12 gene therapy.

IL-12 gene therapy results in tumor regression in some, but not all, murine models. We hypothesized that expression of B7.1 on the tumor cell surface was necessary for IL-12-mediated tumor regression. In addition, we hypothesized that all cells must express B7.1 for this to be effective. To evaluate this hypothesis, tumor nodules were established in mice with either wild-type B16 melanoma or with B16 melanoma modified to express B7.1. IL-12 cDNA was transferred to the tumor by particle-mediated gene transfer. All tumors modified to express B7.1 regressed completely after IL-12 cDNA treatment. When the percent of B7.1-transfected B16 cells was decreased to 50%, no animals survived after treatment. Animals rendered tumor-free were then challenged with wild-type B16. Fifty percent of mice was protected from this tumor challenge. Expression of CD28 (the stimulatory B7.1 ligand) was significantly increased in both CD8(+) T cells and natural killer cell populations of mice rejecting tumor challenge compared to mice with tumor growth. These results suggest that the costimulatory molecule B7.1 is required for initial tumor sensitivity to IL-12 gene therapy and that protection from subsequent challenge with B7.1 (-) tumor is mediated by CD28(+) immune effector cells.

Cholecystitis caused by hemocholecyst from underlying malignancy.

Massive hemobilia is a well recognized clinical entity, particularly when it presents with jaundice, GI bleeding, and biliary pain. However, occult hemobilia is more difficult to diagnose and has seldom been reported because of its clinically silent nature. In fact, this is usually overlooked until complications arise. Hemocholecyst or clot within the gallbladder may rarely occur in this setting, leading to cystic duct obstruction and cholecystitis. Most previous reports describe cholecystitis resulting from hemocholecyst after iatrogenic trauma. We describe two cases in which hemocholecyst occurred from underlying malignancies, both resulting in cholecystitis (acute or chronic).

Mesh inguinodynia: a new clinical syndrome after inguinal herniorrhaphy?

BACKGROUND: Chronic inguinodynia or neuralgia after conventional inguinal herniorrhaphy is rare, and diagnosing the exact cause is difficult. Treatment has ranged from local injection to remedial surgery with variable results. The increasing popularity of prosthetic mesh repairs (tension free, plug, or laparoscopic) has not eliminated these pain syndromes from occasionally occurring. Recommended management in these situations is extremely difficult. STUDY DESIGN: Since 1994, 117 inguinal reexplorations have been performed for inguinodynia and 20 of these patients had primary mesh herniorrhaphy. All 20 patients had mesh removal. Records were reviewed and patients contacted to evaluate outcomes. RESULTS: All 20 patients were evaluated (15 by telephone or direct contact, 5 by chart review). Three patients had their initial repair performed laparoscopically. Symptoms persisted for 12.2 +/- 1.7 months before remedial surgery. Four patients underwent inguinal reexploration and mesh removal; 16 had mesh removal plus ilioinguinal or iliohypogastric neurectomy. Good to excellent results were achieved in 12 out of 20 patients (60%). Average followup time was 15.9 +/- 3.1 months. Two of 3 patients who had laparoscopic herniorrhaphy had favorable outcomes (67%). Ten of the 16 patients who had mesh removal plus neurectomy reported good to excellent results (62%) compared with 2 of 4 reporting the same with mesh excision only (50%). Eleven patients had pain relief with preoperative nerve block. Of these, 9 had elective neurectomy resulting in good to excellent results in 5 (56%). CONCLUSIONS: Remedial inguinal exploration and mesh removal with or without neurectomy resulted in favorable outcomes in 60% of patients with mesh herniorrhaphy chronic inguinodynia (neuralgia). It appears that coincident neurectomy affords better results than mesh removal alone. Relief with nerve block did not predict favorable outcomes. Despite the popularity and favorable outcomes of prosthetic mesh repairs, persistent postoperative pain still occurs in a small cohort of patients. This may become more evident with the rising interest in laparoscopy. Correcting this problem once presented can be a formidable task. Remedial inguinal surgery with mesh removal and neurectomy will cure selected patients.

Antitumor mechanisms of attenuated Salmonella typhimurium containing the gene for human interleukin-2: a novel antitumor agent?

Currently, there is no long-term effective treatment for unresectable hepatic malignancies. Salmonella species are known to naturally track to the liver during active infection. To develop a biological vector for delivery of interleukin-2 (IL-2) to the liver for antitumor purposes, the thi 4550 attenuated strain of Salmonella typhimurium was used as a vector for IL-2. The gene for human IL-2 was cloned into plasmid pYA292 and inserted into the attenuated S typhimurium and renamed (thi 4550(pIL-2)]. MCA-38 murine adenocarcinoma cells were injected intrasplenically into C57BL/6 mice to produce hepatic metastases that were subsequently enumerated after 12 days. We previously have demonstrated that the thi 4550(pIL-2) produces biologically active IL-2 and that a single gavage feeding of 10(7) thi 4550(pIL-2) significantly reduced the number of hepatic metastases when compared with animals fed salmonella lacking the IL-2 gene or nontreated controls. The aims of the current studies were to determine which host effector cell populations were responsible for the antitumor effect seen with thi 4550(pIL-2) by depletion of natural killer (NK), cytotoxic T lymphocytes (CD8+), T helper (CD4+) cells, and Kupffer cells. Multiple experiments were conducted for each host effector cell population depleted. We found a consistent reduction in the mean number of hepatic metastases in animals fed thi 4550(pIL-2) (55.6 metastases; n = 54) when compared with controls (162.3 metastases; n = 53) (P < .0001). Depletion of NK cells and CD8+ T cells significantly inhibited the antitumor effect of thi 4550(pIL-2) (analysis of variance [ANOVA], P < .01). Elimination of CD4+ T cells and Kupffer cells had no significant impact on the antitumor effect of thi 4550(pIL-2) (ANOVA, P value was not significant). Salmonella IL-2 may represent a novel form of in vivo biotherapy for unresectable hepatic malignancies that employs the oral route of administration. Furthermore, both NK cells or CD8+ cells are required for the antitumor effect seen while CD4+ T cells and Kupffer cells do not appear to be as essential.

Patterns of hepatic and splenic colonization by an attenuated strain of Salmonella typhimurium containing the gene for human interleukin-2: a novel anti-tumor agent.

Currently, there is no effective treatment for unresectable hepatic malignancies. Salmonella sp. are known to naturally track to the liver during active infection. A live biological vector was developed for delivery of Interleukin-2 (IL-2) to the liver for anti-tumor purposes. The avirulent and highly immunogenic c4550 strain of Salmonella typhimurium was used to express the IL-2 protein [renamed c4550(pIL-2)]. We have previously demonstrated that the c4550(pIL-2) produces biologically active IL-2 (up to 46.2 IU/ml) and that a single gavage feeding of 10(7) colony forming units (cfu) of c4550(pIL-2) significantly reduced the number of hepatic metastases when compared to animals fed salmonella lacking the IL-2 gene or non-treated controls. The goal of the current studies was to determine the pattern of splenic and hepatic colonization of Salmonella-IL2. Hepatic and splenic colonization was determined following administration of 10(7) cfu of c4550(pIL-2) and c4550(pYA292) via a single gavage feeding to C57BL/6 mice. Five experiments of antibiotic regimen administration were conducted where splenic and hepatic homogenates were cultured after 14 days of parenteral and/or oral antibiotics. The natural history of hepatic and splenic colonization was also determined for animals without antibiotic treatment. Despite administration of various antibiotic regimens using different routes, eradication of salmonella with and without IL-2 was not achieved. Salmonella, however, was not cultured from hepatic and splenic tissue at 4 months after a single gavage feeding of salmonella with no specific treatment. In conclusion, oral administration of c4550(pIL-2) may represent a novel form of in vivo biotherapy for unresectable hepatic malignancies. Antibiotics do not accelerate eradication of this bacteria and it appears that c4550(pIL-2) follows the natural pathophysiological of salmonella infection in which eradication from the splenic and hepatic tissue occurs over a period of 2-4 months.

Attenuated Salmonella typhimurium containing interleukin-2 decreases MC-38 hepatic metastases: a novel anti-tumor agent.

Currently, there is no long-term effective treatment for unresectable hepatic malignancies. Salmonella sp. are known to naturally track to the liver during active infection. To develop a biological vector for delivery of Interleukin-2 (IL-2) to the liver for anti-tumor purposes, the avirulent and highly immunogenic chi 4550 strain of Salmonella typhimurium was used as a vector for IL-2. The gene for human IL-2 was cloned into plasmid pYA292 (renamed pIL-2) and inserted into the attenuated Salmonella typhimurium and renamed [chi 4550 (pIL-2)]. This transformant was found to produced biologically active IL-2 demonstrated by NK cell activation in a 4 hour chromium release cytotoxicity assay. To determine anti-tumor potential, MCA-38 murine adenocarcinoma cells were injected intrasplenically into C57BL/6 mice to produce hepatic metastases and metastases were subsequently enumerated after 12 days. Statistical significance was determined by ANOVA with Fisher's test for significance. Hepatic metastases enumerated by blinded observers revealed that the mean number of metastases was 106.4 in control mice, 103.7 in mice gavage fed attenuated salmonella without IL-2 [chi 4550(pYA292)], and 44.3 in mice fed the chi 4550(pIL2); (ANOVA: p < 0.01). Culture of livers and spleens in mice administered a single gavage dose of salmonella demonstrated persistent colonization for up to 4 weeks. No observable toxicity was seen to either IL-2 or salmonella. These studies demonstrate that the chi 4550(pIL2) is a novel form of in vivo biotherapy which produces biologically active IL-2 and employs the oral route of administration to stimulate an immune response against malignancy in the liver.

Genomic structure of NKG5, a human NK and T cell-specific activation gene.

We reported previously the isolation of a cDNA clone, designated NKG5, encoding a secreted protein that is expressed only in natural killer and T cells and is strongly upregulated upon cell activation. In this report we have isolated the NKG5 gene from a human placental genomic library and sequenced the gene and two kilobases of 5'-flanking DNA. Comparison with the cDNA sequence reveals that the NKG5 gene consists of five exons and four introns. Intron 1 contains a DNA segment that was reported to occur as an exon in 519, a closely related cDNA clone that was isolated from a T-cell library. This result indicates that NKG5 and 519 are alternative splicing products of a single gene. The 5'-flanking region of the NKG5 gene was analyzed for homology with the promoter regions of cytokines and other activation-induced genes showing lymphocyte-specific expression. Several segments displaying sequence similarity were identified. We also identified numerous sequence elements that have strong similarity to known binding sites for transcriptional regulatory proteins including T cell-specific and activation-specific regulatory factors. These findings are consistent with the cell-specific expression and the tight regulatory control that is observed for the NKG5 gene.