Common presence of Helicobacter DNA in the gallbladder of patients with gallstone diseases and controls.

BACKGROUND: Several species of Helicobacter colonise the biliary tract of animals and cause hepatobiliary diseases. Helicobacter species have also been identified in the gallbladder of a high proportion of Chilean patients with gallbladder cancer. AIM: To determine the presence of Helicobacter species, particularly Helicobacter pylori and Helicobacter bilis, in the gallbladder of patients with non-malignant gallbladder diseases and control patients. PATIENTS AND METHODS: DNA was extracted from gallbladder samples from 122 consecutive patients undergoing cholecystectomy. The presence of Helicobacter genus-specific or Helicobacter pylori and Helicobacter bilis species-specific DNA was determined by polymerase chain reaction and sequence analysis. The presence of Helicobacter pylori-specific immunoglobulin G in the serum (n=84) and bile (n=104) samples was determined by enzyme linked immunosorbent assay. RESULTS: Helicobacter DNA was detected in 61 (50.0%) gallbladder samples: 29 of 60 (48.3%) patients with symptomatic gallstone, six of 10 (60.0%) patients with asymptomatic gallstones, 11 of 15 (73.3%) patients with other biliary diseases, and 15 of 37 (40.5%) control patients, respectively. Among them, 39 samples were positive for Helicobacter pylori but none were positive for Helicobacter bilis. Sequence analysis of Helicobacter genus-positive samples showed that 56 samples were Helicobacter pylori and five were Helicobacter species 'Liver 3' strain. Overall, there was no significant difference in the detection rate of Helicobacter DNA or the levels of serum and bile Helicobacter pylori-specific immunoglobulin G in the various biliary disease groups compared with control patients. Neither was there any significant difference in the blood biochemistry and liver function tests between patients with positive and negative Helicobacter DNA detection. CONCLUSION: Helicobacter species' DNA are commonly present in the gallbladder of patients with gallstone diseases and in controls, implying that Helicobacter infection alone may not play a significant role in the formation of gallstones. However, our results do not exclude the possibility of Helicobacter infection as a cofactor in the development of gallstones.

Selective internal radiation therapy (SIRT) with 90Yttrium microspheres for extensive colorectal liver metastases.

BACKGROUND/AIMS: SIRT (selective internal radiation therapy) is a new modality for the treatment of nonresectable liver tumors which has been reported to achieve high response rates. We report our initial experience in patients with extensive colorectal liver metastases. METHODOLOGY: Thirty-eight (38) patients were treated with SIRT between February 1997 and November 1998. Liver involvement was < 25% in 19 patients, 25-50% in 9 and > 50% in 10. Patients received 90Yttrium microspheres into the hepatic artery via an arterial port and subsequent 4-weekly cycles of hepatic artery chemotherapy with 5-fluorouracil. RESULTS: SIRT was well tolerated and no treatment-related mortality was observed. Responses to SIRT as indicated by falling tumor markers and serial 3-monthly computed tomography scans were seen in over 90% of patients. Estimated survival at 6, 12 and 18 months was 70%, 46% and 46%, respectively, and was principally determined by the development of extrahepatic metastases. CONCLUSIONS: SIRT is well tolerated in patients with extensive colorectal liver metastases and achieves encouraging liver tumor responses, which are well maintained by hepatic artery chemotherapy. The modality warrants wider use and investigation.

Development of a dendritic cell (DC)-based vaccine for patients with advanced colorectal cancer.

BACKGROUND/AIMS: An ability to induce a specific immune response to cancer would provide an important new dimension in its management. We report our initial work investigating the safety and efficacy of a dendritic cell vaccine in patients with colorectal cancer. METHODOLOGY: Fifteen (15) patients with advanced colorectal cancer had vaccines prepared from autologous dendritic cells pulsed with tumor RNA and keyhole limpet hemocyanin. Vaccines were administered intravenously and patients were observed in hospital for 2 days. Thereafter, consultations were at monthly intervals at which time booster doses were given to a total of 4. Patients were monitored with weekly blood tests, including carcinoembryonic antigen, and 3-monthly computed tomography scans. RESULTS: Flow cytometry confirmed dendritic cell phenotype and in vitro function was confirmed by mixed lymphocyte reaction. No major adverse effects were observed. Eleven of 13 patients tested developed a positive keyhole limpet hemocyanin skin test and in 7 the carcinoembryonic antigen fell suggesting some in vivo anticancer effect. To date no dramatic clinical responses have been observed but follow-up is very short. CONCLUSIONS: The therapy was well tolerated. Dendritic cells were verified by phenotype and in vitro function. The positive keyhole limpet hemocyanin skin test confirms in vivo function by effective vaccination to keyhole limpet hemocyanin. Demonstration of any anticancer efficacy will require further follow-up.

Selective internal radiation therapy with 90yttrium microspheres for extensive colorectal liver metastases.

Increasing attention has been given to treatments for colorectal liver metastases ever since hepatic resection was established as being worthwhile. Given the high proportion of patients who die of colorectal cancer with liver-only disease, it seems appropriate to be developing and investigating methods of local liver tumor ablation. Selective internal radiation therapy (SIRT) is a relatively new, not widely used, modality suitable for use even in patients with extensive liver involvement. Fifty patients with advanced, nonresectable, colorectal liver metastases were treated with SIRT between February 1997 and June 1999. Estimated liver involvement was less than 25% in 30 patients, 25% to 50% in 13, and greater than 50% in seven. A single dose of between 2.0 and 3.0 GBq of 90yttrium microspheres was injected into the hepatic artery via a subcutaneous port and followed at 4-week intervals by regional chemotherapy with 5-fluorouracil. SIRT was well tolerated with no treatment-related mortality, although some treatment-related morbidity did occur including a 12% incidence of duodenal ulceration. Responses to SIRT were assessed by serial carcinoembryonic antigen (CEA) measurements and CT scans. Median CEA values 1 and 2 months after SIRT (expressed as percentage of initial CEA) were 19 and 13, respectively. Patients were assigned to one of two groups based on whether or not extrahepatic disease (EHD) developed within 6 months of SIRT. Median survival from SIRT for group 1 (EHD) (n = 26) was 6.9 months (range 1.3 to 18.8 months) and estimated survival +/- standard error at 6, 12, and 18 months was 57.7 +/- 3.8%, 23.1 +/- 4.8%, and 0%, respectively. For group 2 (no EHD) (n = 24), median survival was 17.5 months (range 1.0 to 30.3 months) with estimated survival at 6, 12, 18, 24, and 30 months of 79.2 +/- 2.9%, 66.7 +/- 3.6%, 55.9 +/- 3.3%, 25.2 +/- 4.4%, and 16.8 +/- 5.0%, respectively. This difference is statistically significant by log-rank test (P < 0.010). SIRT is a highly effective and well-tolerated regional treatment for extensive colorectal liver metastases. Tumor marker data suggest that substantial destruction of liver tumors can be achieved in more than 90% of patients by a single treatment. Survival times, particularly for those who do not develop extrahepatic metastases for some time, appear to be extended. SIRT warrants further use and investigation in patients with advanced colorectal liver metastases.

Serum proinflammatory cytokine response in patients with advanced liver tumors following selective internal radiation therapy (SIRT) with (90)Yttrium microspheres.

PURPOSE: To determine the changes in serum levels of proinflammatory cytokines within 48 h after selective internal radiation treatment (SIRT) in patients with advanced liver cancers. METHODS AND MATERIALS: Twenty-eight patients with advanced liver cancers who underwent SIRT were recruited into the study. Serum levels of interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha, and interferon-gamma were determined prior to and 3, 6, 12, 24, and 48 h after SIRT. Their changes were correlated to adverse reactions following treatment as assessed by constitutional symptom scores, and routine blood and liver function tests at 24 and 48 h post-SIRT and falls in serum carcinoembryonic antigen (CEA) level 1 month post-SIRT. RESULTS: Serum IL-6 levels were significantly increased at 24 (p < or = 0.05) and 48 h (p < or = 0.01) post-SIRT. In contrast, there was no significant change in the serum levels of other cytokines studied. The increase in serum IL-6 at 24 h post-SIRT was significantly correlated with the changes in serum alanine transferase (p < or = 0.05) and C-reactive protein (p < or = 0.001) levels and total leukocyte counts (p < or = 0.001) at both 24 and 48 h post-SIRT. Changes in serum IL-6 level were also significantly correlated to the rise of serum aspartate transaminase levels at 48 h post-SIRT (p < or = 0.001), but not with the scores of constitutional symptoms or the changes of serum CEA at 1 month post-SIRT. CONCLUSION: Absence of significant changes in most of proinflammatory cytokines studied confirmed that SIRT is a reasonably safe and well-tolerated treatment with minimal side-effect from the point of view of cytokine-related inflammation. The correlation of serum IL-6 changes with several liver enzymes and C-reactive protein but not with clinical symptom scores or serum CEA levels suggests that the rise in IL-6 levels in the first 48 h following SIRT most likely reflect normal liver cell damage rather than tumor cell damage.

Improvement in co-morbidities following weight loss from gastric bypass surgery.

BACKGROUND: Clinical observation reveals a close association between morbid obesity and a variety of serious medical conditions. This report describes the changes observed in some of these co-morbid conditions, following weight loss achieved by silastic ring gastric bypass (SRGBP). METHODS: Between 1990 and 1998, 157 severely obese patients aged 15-62 years underwent SRGBP. Initial and follow-up data was recorded prospectively on a computerized database, with minor subsequent additions being achieved by phone call or questionnaire. Particular attention was given to associated co-morbidities and improvement in these that occurred during follow-up. Median pre-operative BMI was 45 (33-97). Patients were followed for a median 2.5 years. At 2 years post-SRGBP, median BMI was 28 (20-52). Weight loss was statistically significant (p<0.0001). RESULTS: Before surgery 42 patients were being treated for hypertension and 34 for asthma. Withdrawal of all medication for these conditions was achieved sometime after surgery in 18 and 17 patients respectively. NIDDM was present in 19 patients before surgery and subsequently resolved completely in 18. Eleven of the 12 patients with recognized obstructive sleep apnea before surgery had resolution of this after surgery. Dyslipidemia was present in the majority of patients before surgery and resolved or improved following surgery in almost all instances. CONCLUSIONS: The findings indicate that reliable and substantial weight loss can be accomplished by gastric bypass surgery with accompanying major reductions in associated co-morbidities. Such benefits suggest that greater attention should be given to this form of treatment for those with severe obesity.

Hepatic artery access ports: recognizing and avoiding the problems.

BACKGROUND: Regional approaches to the management of hepatic tumours are appropriate in some clinical situations and include hepatic arterial chemotherapy (HAC) and selective internal radiation therapy (SIRT). Both require access to the hepatic artery, which is conveniently achieved with a subcutaneously placed port. Placement and use of these ports may be associated with a variety of technical problems which can impact adversely on the outcome of the treatment. The present paper outlines the problems related to port usage for regional hepatic therapies, with emphasis on the technical aspects of insertion and interpretation and management of subsequent problems. METHODS: Hepatic artery port placement was attempted in 129 patients for use with either SIRT and/or HAC. Ports were used or flushed at monthly intervals. RESULTS: Successful port insertion was achieved in 127 patients, of whom 87 received HAC alone, seven received SIRT alone, 28 patients received both and in five patients the port was never used. Methylene blue injection was used to identify anomalous arterial anatomy, which was found in 26 of 95 patients (27%), and significant extrahepatic 'access', which was seen in 25 patients (26%) after initial placement. Forty-six instances of technical problems preventing continued use of the port occurred in 43 patients after a median of 4 (0-36) cycles of chemotherapy, including hepatic artery thrombosis (n = 26), catheter blockage (n = 4), duodenal fistula (n = 3), gastrointestinal (GI) bleeding (n = 3), side-effects (n = 3), access problems (n = 3), extravasation (n = 3) and infection (n = 1). CONCLUSION: Methods used to identify, manage and in some instances prevent the occurrence of these problems are discussed.

Hepatic resection for metastases in colorectal carcinoma.

AIMS: To outline the role of liver resection in the treatment of colorectal liver metastases, with particular reference to hospital morbidity, mortality and subsequent survival. METHODS: Seventy major liver resections were performed in Wellington by the senior author (RSS) between 1987 and 1997 for colorectal metastases. Fifty-three entailed resection alone with intent to cure, nine were associated with additional cryotherapy and in eight hepatic arterial chemotherapy was subsequently given. Resection was the initial form of liver treatment in all 70 patients. Patients were aged between 29 and 76 years with a median of 60.0 years. All patients were judged pre-operatively to have tumour confined to a resectable portion of the liver. Data were collected prospectively and held in a computerised database. Follow-up was available on all patients. RESULTS: Median operating theatre time was five hours and median blood loss was 1500 mL (60 mL-25 L). Eighty percent of resections entailed four or more liver segments. Postoperative morbidity occurred in 26 (37.1%) and 30-day mortality was 5.7%. Median hospital stay was 11 days (2-67). In the 53 patients who underwent resection alone, the three and five-year actuarial survival rates, including the 30-day mortality, were 62.0% and 27.2%, respectively. Dukes stage of the primary was the only significant prognostic factor found in this subgroup of patients (p<0.05). CONCLUSIONS: Resection of colorectal liver metastases can achieve extension of life and long-term survival in selected patients. However, it remains a major undertaking and is probably best performed in units with appropriate expertise and experience.