Is CT angiography sufficient for prediction of resectability of periampullary neoplasms?

The optimal preoperative evaluation of periampullary neoplasms remains controversial. The aim of this study was to analyze the accuracy of helical computed tomography (CT) and CT angiography with three-dimensional reconstruction in predicting resectability. Between March 1996 and May 1999, a total of 100 patients with periampullary neoplasms were prospectively staged by helical CT and CT angiography with three-dimensional reconstruction. Vascular involvement was graded from 0 to 4, with grade 0 representing no vascular involvement and grade 4 total encasement of either the superior mesenteric vein or artery. Patients with grade 4 lesions were considered unresectable. Sixty-eight patients underwent surgical exploration with intent to perform a pancreaticoduodenectomy. Forty-four lesions were grade 0, five were grade l, eight were grade 2, and 11 were grade 3. Resectability for grades 0 to 3 was 96%, 100%, 50%, and 9%, respectively, for an overall resectability rate of 76%. Resectability in patients with vascular encroachment (grade 2) is usually determined by the extent of local disease rather than the presence of extrapancreatic disease. Resection is rarely possible in patients with evidence of vascular encasement (grade 3). Additional imaging modalities such as diagnostic laparoscopy are superfluous in patients with no evidence of local vascular involvement on CT angiography (grades 0 and 1) because of the high resectability rate and infrequency of unsuspected distant metastatic deposits.

Utility of 18F-FDG positron emission tomography scanning on selection of patients for resection of hepatic colorectal metastases.

BACKGROUND: Hepatectomy represents a standard and potentially curative therapy for hepatic colorectal metastases. However, up to two thirds of patients explored for resection are found to have unsuspected disease, which precludes resection. METHODS: In order to determine if 18F-FDG positron emission tomography (PET) scanning may prevent unnecessary surgery, a group of 40 patients being considered for hepatic resection but at high risk for unresectable disease by clinical criteria were subjected to whole body 18F-FDG-PET scanning. Effect on clinical outcome was evaluated. In addition, PET findings in the 25 patients who underwent resection of hepatic metastases were directly compared with the resected specimen to determine the sensitivity of 18F-FDG PET scanning in the liver. RESULTS: Findings on 18F-FDG-PET scanning influenced the clinical management in 16 patients (40%) and directly altered management in 9 cases (23%). Six patients were spared laparotomy, and 3 others had PET-directed surgery that found extrahepatic tumor and spared the patient unwarranted liver resection. In 3 cases PET missed peritoneal metastases found on laparotomy. In these cases all missed tumors were less than 1 cm in size. Out of 52 resected hepatic lesions, 18F-FDG-PET detected 37. Within the liver, sensitivity of detection was also related to size. Only 25% of hepatic lesions smaller than 1 cm were detected by PET, while 85% of lesions larger than 1 cm were detected. CONCLUSIONS: FDG-PET is best for detecting extrahepatic disease. There are few false positives, and surgeons should carefully evaluate and biopsy extrahepatic positive sites. This test should be used for patients at high risk for extrahepatic disease and should be evaluated prospectively for all patients under consideration for liver resection.

Perspectives of anti-H. pylori vaccination.

Mucosal vaccination using different antigens in conjunction with adjuvants has been used for the prevention and even cure of Helicobacter infection in animal models. A phase I-II trial was recently performed on infected volunteers with urease and the heat labile enterotoxin from E. coli (LT). A significant decrease in bacterial density but no cure of infection was observed in some patients. The immune effectors which prevent or cure infection with Helicobacter are not well understood and will need to be more clearly defined in order to improve vaccination strategies. Future developments will likely include the following: generation of new mucosal adjuvants without gastrointestinal toxicity; combination of two or three different antigens in order to ensure broader efficacy; use of different routes of administration such as nasal or rectal; coadministration of anti-Helicobacter treatment and vaccine; development of alternate vaccine methods which do not require a mucosal adjuvant, i.e. antigen expression by live carriers or by DNA vaccination; combination of different vaccination methods, for instance DNA vaccination followed by a mucosal boost.

Resection of hilar cholangiocarcinoma--a European and United States experience.

Improvements in preoperative imaging, patient selection, and refined operative techniques have allowed a more radical surgical approach to hilar cholangiocarcinoma. A total of 269 patients with histologically proven cholangiocarcinoma were treated during a 20-year period under the direction of one surgeon (LHB) over three separate time periods in different institutions: 131 patients at the Hepatobiliary Unit of Hammersmith Hospital, London, England, from January 1977 to September 1985; 48 patients at Inselspital, University of Bern, Switzerland, between October 1986 and October 1990; and 90 patients at Memorial Sloan-Kettering Cancer Center, New York, between March 1991 and April 1997. An increase in the use of concomitant hepatectomy was noted over these time periods, paralleled by an increase in achieving negative margins and in survival. Hilar cholangiocarcinoma should not be considered an incurable disease, but patients should be aggressively evaluated for possible curative resection before any intervention is performed. Good long-term results can be achieved and cure is possible provided a complete tumor resection with negative margins is obtained.

Radiologic features of complications arising from dropped gallstones in laparoscopic cholecystectomy patients.

OBJECTIVE: Because laparoscopic cholecystectomy has become the accepted treatment for symptomatic cholelithiasis, radiologists frequently encounter patients who have had this surgery. Although the radiologic features of postoperative bile duct injury are well documented, the imaging features of less well-known complications remain poorly described. One such unusual complication is abscess formation caused by dropped gallstones. CONCLUSION: Although the incidence of dropped gallstones is an uncommon complication of laparoscopic cholecystectomy, it should be recognized as a potential source of both intraabdominal and intrathoracic abscess formation in any patient presenting months to years after undergoing laparoscopic cholecystectomy. These abscesses are not necessarily confined to the right upper quadrant.

Immunization of BALB/c mice with Helicobacter urease B induces a T helper 2 response absent in Helicobacter infection.

BACKGROUND & AIMS: Infection with Helicobacter induces a T helper type 1 response in mice and humans. Mice can be cured or protected from infection with Helicobacter by mucosal immunization with recombinant H. pylori urease B subunit (rUreB). This study characterizes the immune response of infected mice immunized with rUreB. METHODS: BALB/c mice were infected with H. felis. Two weeks later, they were orally immunized four times with rUreB and cholera toxin (CT) at weekly intervals. Controls were only infected or sham-immunized with CT. Animals were killed at various times after immunization. Splenic CD4(+) cells were obtained and cultured in vitro with rUreB to evaluate antigen-specific proliferation and induction of interferon gamma and interleukin 4 secretion. RESULTS: All rUreB-immunized mice (n = 8) were cured from infection 3 weeks after the fourth immunization. Immunization induced a proliferative response of splenic CD4(+) cells, a progressive decrease in interferon gamma secretion, and a concomitant increase in interleukin 4 secretion after each immunization. A simultaneous increase in rUreB specific serum immunoglobulin G1 levels was observed in infected/immunized mice. CONCLUSIONS: In BALB/c mice, therapeutic mucosal immunization with rUreB induces progressively a Th2 CD4(+) T cell response resulting in the elimination of the pathogen.

Percutaneous tumor ablation: increased necrosis with combined radio-frequency ablation and intratumoral doxorubicin injection in a rat breast tumor model.

PURPOSE: To determine whether a combination of intratumoral doxorubicin injection and radio-frequency (RF) ablation increases tumor destruction compared with RF ablation alone in an animal tumor model. MATERIALS AND METHODS: R3230 mammary adenocarcinoma 1.2-1.5-cm- diameter nodules (n = 110) were implanted subcutaneously in 84 female Fischer rats. For initial experiments (n = 46), tumors were treated with (a) conventional, monopolar RF (250 mA +/- 25 [SD] at 70 degrees C +/- 1 for 5 minutes) ablation alone; (b) direct intratumoral doxorubicin injection (volume, 250 microL; total dose, 0.5 mg) alone; (c) combined therapy (doxorubicin injection immediately followed by RF ablation); (d) RF ablation and injection of 250 microL of distilled water; or (e) no treatment. In subsequent experiments, amount of doxorubicin (0.02-2.50 mg; n = 40 additional tumors) and timing of doxorubicin administration (2 days before to 2 days after RF ablation; n = 24 more tumors) were varied. Pathologic examination, including staining for mitochondrial enzyme activity and perfusion, was performed, and the resultant tumor destruction from each treatment was evaluated. RESULTS: Coagulation diameter was 6.7 mm +/- 0.6 for tumors treated with RF ablation alone and 6.9 mm +/- 0.7 for those treated with RF ablation and water (P =.52), while intratumoral doxorubicin injection alone produced only 2.0-3.0 mm of coagulation (P <.001). Increased coagulation was observed only with combined doxorubicin injection and RF therapy (P <.001). Coagulation was dependent on concentration and timing of doxorubicin administration, with greatest coagulation (11.5 mm +/- 1.1) observed for doxorubicin administered within 30 minutes of RF ablation. CONCLUSION: Adjuvant intratumoral doxorubicin injection increases coagulation in solid tumors compared with RF ablation alone. Increased tumor destruction is also seen when doxorubicin is administered after RF ablation, which suggests that RF ablation may sensitize tumors to chemotherapy. Such combination therapies may, therefore, offer improved methods for ablating solid tumors.

Mice are protected from Helicobacter pylori infection by nasal immunization with attenuated Salmonella typhimurium phoPc expressing urease A and B subunits.

Live Salmonella typhimurium phoPc bacteria were tested as mucosal vaccine vectors to deliver Helicobacter pylori antigens. The genes encoding the A and B subunits of H. pylori urease were introduced into S. typhimurium phoPc and expressed under the control of a constitutive tac promoter (tac-ureAB) or a two-phase T7 expression system (cT7-ureAB). Both recombinant Salmonella strains expressed the two urease subunits in vitro and were used to nasally immunize BALB/c mice. The plasmid carrying cT7-ureAB was stably inherited by bacteria growing or persisting in the spleen, lungs, mesenteric or cervical lymph nodes, and Peyer's patches of immunized mice, while the plasmid carrying tac-ureAB was rapidly lost. Spleen and Peyer's patch CD4+ lymphocytes from mice immunized with S. typhimurium phopc cT7-ureAB proliferated in vitro in response to urease, whereas cells from mice given S. typhimurium phoPc alone did not. Splenic CD4+ cells from mice immunized with phoPc cT7-ureAB secreted gamma interferon and interleukin 10, while Peyer's patch CD4+ cells did not secrete either cytokine. Specific H. pylori anti-urease immunoglobulin G1 (IgG1) and IgG2A antibodies were detected following immunization, confirming that both Th1- and Th2-type immune responses were generated by the live vaccine. Sixty percent of the mice (9 of 15) immunized with S. typhimurium phoPc cT7-ureAB were found to be resistant to infection by H. pylori, while all mice immunized with phoPc tac-ureAB (15 of 15) or phoPc (15 of 15) were infected. Our data demonstrate that H. pylori urease delivered nasally by using a vaccine strain of S. typhimurium can trigger Th1- and Th2-type responses and induce protective immunity against Helicobacter infection.

Oral immunization with urease and Escherichia coli heat-labile enterotoxin is safe and immunogenic in Helicobacter pylori-infected adults.

BACKGROUND & AIMS: Oral immunization with Helicobacter pylori urease can cure Helicobacter infection in animals. As a step toward therapeutic immunization in humans, the safety and immunogenicity of oral immunization with recombinant H. pylori urease were tested in H. pylori-infected adults. METHODS: Twenty-six H. pylori-infected volunteers were randomized in a double-blind study to four weekly oral doses of 180, 60, or 20 mg of urease with 5 microg heat-labile enterotoxin of Escherichia coli (LT), LT alone, or placebo. Side effects and immune responses were evaluated weekly after immunization, and gastric biopsy specimens were obtained after 1 month and 6 months for histology and quantitative cultures. RESULTS: Diarrhea was noted in 16 of 24 (66%) of the volunteers who completed the study. Antiurease serum immunoglobulin A titers increased 1. 58-fold +/- 0.37-fold and 3.66-fold +/- 1.5-fold (mean +/- SEM) after immunization with 60 and 180 mg urease, respectively, whereas no change occurred in the placebo +/- LT groups (P = 0.005). Circulating antiurease immunoglobulin A-producing cells increased in volunteers exposed to urease compared with placebo (38.9 +/- 13. 6/10(6) vs. 5.4 +/- 3.1; P = 0.018). Eradication of H. pylori infection was not observed, but urease immunization induced a significant decrease in gastric H. pylori density. CONCLUSIONS: H. pylori urease with LT is well tolerated and immunogenic in H. pylori-infected individuals. An improved vaccine formulation may induce curative immunity.