Vitamin E and the Y4 agonist BA-129 decrease prostate cancer growth and production of vascular endothelial growth factor.

BACKGROUND: A biologically active form of vitamin E, alpha-tocopherol succinate (ATS), has been shown to induce apoptosis of hormone-refractory prostate cancer in vitro and inhibit cell growth in vivo. The gastrointestinal hormone peptide YY (PYY) has growth inhibitory activity against multiple cancer cell lines and is synergistic with ATS against breast and pancreatic cancer growth. BA-129, a specific Y4 receptor agonist, has growth inhibitory effects on pancreatic cancer in vitro. We investigated the effects of BA-129 and ATS on prostate cancer growth and evaluated their effects on vascular endothelial growth factor (VEGF) production. METHODS: A hormone-refractory human prostate cancer cell line, PC-3, was treated with ATS alone at 10 pg/ml, PYY or BA-129 alone at doses of 75 and 500 pmol/ml, or a combination of the two agents. Cell growth was measured by MTT assay and hemocytometry using trypan blue. Quantitative measurement of VEGF was performed by ELISA. Statistical analysis was achieved by ANOVA. RESULTS: ATS exhibited significant (P < 0.05) growth inhibitory effects in prostate cancer cells. PYY also inhibited growth (P < 0.05). ATS treatment reduced VEGF production (P < 0.05). PYY treatment increased VEGF. When ATS was given in combination with BA-129, VEGF production was further reduced (P < 0.05). CONCLUSIONS: Both PYY and ATS inhibit growth in hormone-refractory prostate cancer, with augmentation when used in combination. VEGF production is inhibited by vitamin E, but increased by PYY. ATS abolishes the augmented VEGF response to PYY. Our data suggest that PYY is involved in the regulation of VEGF production and prostate cancer growth.

Biomechanical analysis of the effect of varying suture pitch in tendon graft fixation.

The purpose of this study was to biomechanically assess the effect of varying suture pitch on the holding power of the Krackow suture technique for tendon graft fixation. Seven pairs of rabbit Achilles tendons were sutured with single No. 5 Ti-Cron suture using the Krackow technique. One tendon from each pair was sutured using a 0.5-cm suture pitch (half-pitch group) while the contralateral tendon from each pair was sutured with a 1.0-cm suture pitch (one-pitch group). The tendons were loaded to failure using a servohydraulic materials test system at a loading rate of 0.5 mm/sec. There were no statistically significant differences noted in suture slippage at failure (1.58 cm for half pitch versus 1.45 cm for one pitch) or maximal force to failure (158.5 N for half pitch versus 168.2 N one pitch) between the two treatment groups. However, the construct with the 1-cm suture pitch was significantly stiffer than the construct with the 0.5-cm suture pitch, with stiffness values of 106.2 N/cm and 91.4 N/cm, respectively. The most common mechanism of failure was slippage of the suture at the first suture throw and tearing of the first knot through the most distal portion of the tendon. Four constructs failed by suture rupture, two from each experimental group.

Alpha-tocopherol succinate inhibits growth of gastric cancer cells in vitro.

BACKGROUND: Vitamin E in the form of alpha-tocopherol succinate (ATS) has been shown to inhibit growth of several cancer cell lines in vitro, including pancreas, breast, and prostate. No data exist on the effect of ATS on gastric cancer cell viability. METHODS: A gastric cancer cell line in suspension form, KATO-III, was plated in 96-well plates at 30,000 cells per well with 100 microl RPMI media. The cells were allowed to incubate for 24 h and were then treated with ATS at doses of 25, 50, or 100 microg/ml. The ATS was dissolved in 1% EtOH solution and control cells received an identical solution of EtOH without ATS. Treated cells were incubated for 24, 48, or 72 h. At the completion of the treatment period, MTT assay was performed to determine cell viability. Statistical analysis was performed using Student's t test. RESULTS: All doses of ATS resulted in inhibition of growth of the KATO-III cells. Both 100 and 50 microg/cc doses inhibited growth at all time points (P<0.005), with 48- and 72-h treatments more effective than 24-h treatment. At 24 and 48 h, 100 microg/cc was more effective at inhibition of growth than 50 microg/ml (P<0.005), but by 72 h the effects of the doses were equivalent; 25 microg/ml inhibited cell growth only at 48 and 72 h. At all time points, 50 and 100 microg/ml doses were more effective at inhibiting cell growth than 25 microg/ml. Conclusions. ATS inhibits gastric carcinoma cell growth in vitro in a dose- and time-dependent fashion. In vivo studies are indicated to further evaluate the potential benefit of this antioxidant against gastric cancer.

The incidence of splenectomy is decreasing: lessons learned from trauma experience.

Over the past decade, splenic preservation has become a well-reported and accepted principle in trauma management. The reasons for splenic preservation may have influenced nontraumatic surgical management as well. To investigate the changing incidence and indications for splenectomy, we conducted a 10-year review of all splenectomies at our institution. During this time, between January 1, 1986, and December 31, 1995, 896 patients underwent splenectomy. Hospital charts and records were examined to determine the etiology and incidence of splenectomy. Indications were classified as: 1) trauma, i.e., performed for blunt or penetrating injury; 2) hematologic malignancy, i.e., therapy or staging of underlying leukemia, Hodgkin's lymphoma, or non-Hodgkin's lymphoma; 3) cytopenia, i.e., treatment of thrombocytopenia, anemia, or leukopenia; 4) iatrogenic, i.e., injury during another procedure; 5) incidental, i.e., required for adjacent organ resection; 6) portal hypertension, i.e., left-sided portal hypertension or during shunting procedure; 7) diagnostic, i.e., uncertainty excluding hematologic malignancy; or 8) other, i.e., miscellaneous indications. Trauma accounted for 41.5 per cent of all splenectomies during this time period, hematologic malignancy 15.4 per cent, cytopenia 15.6 per cent, incidental 12.3 per cent, iatrogenic 8.1 per cent, portal hypertension 2.3 per cent, diagnostic 2.0 per cent, and other 2.7 per cent. Comparing the first and second 5-year time periods, the following increases/decreases in average annual incidence were noted: splenectomy for all indications, -36.9 per cent; trauma, -32.9 per cent; hematologic malignancy, -51.4 per cent; cytopenia, 35.1 per cent; incidental, -35.9 per cent; iatrogenic, -30.2 per cent; diagnostic, +4.9 per cent, and other, -57 per cent. Traumatic injury to the spleen remains the most common indication for splenectomy, but the incidence has decreased dramatically over the past 10 years. Splenectomies for treatment of hematologic malignancies and cytopenia, as well as incidental and iatrogenic splenectomies, have also decreased significantly. Only the incidence of diagnostic splenectomy has remained stable. Although initiated within the field of trauma, the advantages of splenic preservation now appear to be well recognized beyond that field.

Transcatheter arterial chemoembolization as primary treatment for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) in Western populations has historically been associated with poor survival. METHODS: In this study, we conducted a 7-year retrospective analysis of patients with HCC undergoing transcatheter arterial chemoembolization (TACE) at our institution and examined demographics, outcomes, and complications. RESULTS: During the period of study, 39 patients (25 male [64%], mean age 58 [range 17 to 86]) underwent a total of 78 chemoembolization treatments. During the same time period, an additional 31 patients received supportive care only. The majority of patients had late stage disease (American Joint Committee on Cancer stage III, IVa, or IVb) with no statistical difference noted between the two groups (P = 0.2). However, patients receiving supportive care only had significantly worse hepatic dysfunction by Child's classification (P = 0.005). Twenty-nine patients (74%) had documented cirrhosis, with hepatitis C being the most common cause in 11 of 29 (38%). In patients undergoing TACE, overall actuarial survival was 35%, 20%, and 11% at 1, 2, and 3 years with a median survival of 9.2 months, significantly improved over the group receiving supportive care only (P < 0.0001). Median survival for the group receiving supportive care was less than 3 months. Neither age nor stage had a significant impact on survival. The most common complications of TACE included transient nausea, abdominal pain, vomiting, and fever. CONCLUSIONS: TACE is a safe and effective therapeutic option for selected patients with HCC not amenable to surgical intervention.

Hepatocellular carcinoma outcomes based on indicated treatment strategy.

Hepatocellular carcinoma (HCC) in Western populations historically has been associated with poor survival. In this study, we conducted a 7-year retrospective analysis of patients evaluated at our institution with HCC to determine the effects of newer treatment strategies on outcome. During the period of study, 117 patients [86 (74%) male; mean age, 59 years (range, 16-85)] were evaluated with treatment as follows: surgical resection in 22 (19%), chemoembolization with or without systemic chemotherapy in 40 (35%), systemic treatment alone in 16 (13%), orthotopic liver transplantation in 8 (7%), and supportive care only in 31 (26%). Sixty-nine patients (59%) had documented cirrhosis, with hepatitis C being the most common cause in 27 of 69 (39%). In patients receiving no treatment, median survival was just under 3 months, with only two 1-year survivors. Patients with orthotopic liver transplantation had 1-, 2-, and 3-year survival rates of 87, 87, and 58 per cent compared with 69, 52, and 43 per cent in surgically resected patients. Survival after chemoembolization was 35, 20, and 11 per cent at 1, 2, and 3 years, whereas survival after systemic chemotherapy was 30 and 15 per cent at 1 and 2 years, respectively. One-year survival was improved in noncirrhotic patients compared with cirrhotics (47% vs 29%; P < 0.05) but was no different in patients younger than 55 years compared with older patients (38% vs 38%). When possible, surgical treatment strategies offer superior survival.

Management of bronchobiliary fistula as a late complication of hepatic resection.

Bronchobiliary fistula is an uncommon but remarkable complication after hepatic resection. The case reported illustrates the clinical presentation and preferred initial management of these fistulae. A 61-year-old white male underwent two wedge resections for colorectal metastases to the liver with removal of a portion of the right diaphragm. Four years later, he developed obstructive jaundice secondary to tumor recurrence in the porta hepatis, which required endoscopic stent placement, radiation, and chemotherapy. Almost 2 years later, he developed frank biliptysis. Percutaneous transhepatic cholangiography (PTC) revealed occlusion of the common hepatic duct stent and a bronchobiliary fistula. With adequate reestablishment of common duct drainage, the patient rapidly improved and was discharged free of symptoms. Bronchobiliary fistulae are rare complications of hepatic resection that can present from days to years after operation. Endoscopic retrograde cholangiopancreatography and PTC are the diagnostic studies of choice and offer the possibility of therapeutic intervention. Although large series in the literature emphasize the surgical management of bronchobiliary fistulae, the reoperative procedures tend to be complicated, with a significant morbidity and mortality. Nonsurgical interventions via endoscopic retrograde cholangiopancreatography or PTC are more recently notably successful when resolution of a distal biliary obstruction is accomplished. Only after aggressive attempts at nonoperative, interventional techniques have failed should operative approaches be entertained.

Chronic illness in a general practice.

A study of chronic problems among 11416 patients in a metropolitan group practice in Australia is reported. The study was designed to ascertain the significance of chronic problems in the community by determining prevalence rates for the practice population. The data were obtained from the practice records. Chronic problems had been defined and recorded by the practice doctors for a period of five years. There were 296 separate problems which were divided into organic, psychosocial, or undifferentiated types. Half of the patients had chronic problems. The incidence of chronic problems increased with age but was highest in the 20-30 years and 50-60 years age groups. There was an average of 2.32 problems per patient. Females had problems more often than males and also a greater number of problems, particularly of a psychosocial nature (1.9:1). Prevalence rates for the 50 most common problems are listed. It was concluded that chronic health problems are significant in all age groups and that general practice has a most important role in the provision of continuing care for these patients.