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Biomedical subjects

O F Bathe

Publications and source records attributed to O F Bathe.

At least 19 recordsLinked to original sources

Meta-analysis of pancreaticojejunostomy versus pancreaticogastrostomy reconstruction after pancreaticoduodenectomy.

BACKGROUND: Pancreaticoduodenectomy is the primary treatment for periampullary cancer. Associated morbidity is high and often related to pancreatic anastomotic failure. This paper compares rates of pancreatic fistula, morbidity and mortality after pancreaticoduodenectomy in patients having reconstruction by pancreaticogastrostomy with those in patients having reconstruction by pancreaticojejunostomy. METHODS: A meta-analysis was performed of all large cohort and randomized controlled trials carried out since 1990. RESULTS: Eleven articles were identified for inclusion: one prospective randomized trial, two non-randomized prospective trials and eight observational cohort studies. The meta-analysis revealed a higher rate of pancreatic fistula associated with pancreaticojejunostomy reconstruction (relative risk (RR) 2.62 (95 per cent confidence interval (c.i.) 1.91 to 3.60)). A higher overall morbidity rate was also demonstrated in this group (RR 1.43 (95 per cent c.i. 1.26 to 1.61)), as was a higher mortality rate (RR 2.51 (95 per cent c.i. 1.61 to 3.91)). CONCLUSION: Current literature suggests that the safer means of pancreatic reconstruction after pancreaticoduodenectomy is pancreaticogastrostomy, but much of the evidence comes from observational cohort study data.

Ampulla of Vater↗

IL-2 during in vitro priming promotes subsequent engraftment and successful adoptive tumor immunotherapy by persistent memory phenotypic CD8(+) T cells.

Adoptive T cell tumor immunotherapy potentially consists of two protective components by the transferred effector cells, the immediate immune response and the subsequent development of memory T cells. The extent by which adoptively transferred CD8(+) CTL are destined to become memory T cells is ambiguous as most studies focus on the acute effects on tumor shortly following adoptive transfer. In this study we show that a substantial fraction of the input CTL develop into memory cells that reject a s.c. tumor challenge. The use of exogenous IL-2 or a combination of IL-2 and IL-4, but not solely IL-4, during the ex vivo culture for the CTL inoculation was necessary for efficient development of CD8(+) memory T cells. Thus, an important component of adoptive immunotherapy using CTL is the production of CD8(+) Ag-specific memory cells which is primarily favored by IL-2 receptor signaling during ex vivo generation of the effector CTL.

Animals↗

Influence of Hispanic ethnicity on outcome after resection of carcinoma of the head of the pancreas.

BACKGROUND: Poor outcomes in Hispanic patients have been reported for tumors at a number of sites. The authors sought to determine whether a similar phenomenon occurs in Hispanics after the resection of solid epithelial tumors of the head of the pancreas. METHODS: Between 1983-1995, 273 patients with noncystic epithelial carcinoma of the head of the pancreas were evaluated. Resection was accomplished in 104 patients (38%); these patients were the focus of the current retrospective review. Of the patients who underwent resection, 26 (25%) were Hispanic and 78 (75%) were non-Hispanic. RESULTS: Although Hispanic patients tended to present at a significantly younger age and their serum bilirubin level was significantly higher, no other differences in clinical characteristics were observed. After resection, Hispanic patients had a median survival of only 11.4 months, whereas the non-Hispanic group had a median survival of 21.7 months (P = 0.009). Hispanic ethnicity, as well as age > 74 years and jaundice at the time of presentation also were found to be significant prognostic factors on multivariate analysis. Hispanic patients did not present with more advanced disease and no delays in assessment by a physician or in proceeding to surgery were observed. Furthermore, the rate of resection was the same in Hispanic patients and non-Hispanic patients. Long-term survival after palliative bypass was similarly worse in the Hispanic subgroup. CONCLUSIONS: Hispanic patients treated at the study center appeared to have a diminished survival after resection of a tumor of the head of the pancreas. No treatment-related factors were identified that could explain this discrepancy in outcome.

Aged↗

Diminished benefit from resection of cancer of the head of the pancreas in patients of advanced age.

BACKGROUND AND OBJECTIVES: The incidence of pancreatic cancer is increasing, and an increasing proportion of these patients is older than 65 years. The benefits of resection in the geriatric population, in whom major comorbidity is more likely, are poorly defined. The authors sought to determine the relative benefits of resection of cancer of the head of the pancreas in different age groups, with particular emphasis on the geriatric population. METHODS: Between 1983 and 1995, 273 patients presented to the University of Miami for evaluation of noncystic epithelial cancer of the head of the pancreas. Resection was performed in 104 patients, and these patients are the subject of this retrospective review. Mean length of follow-up for surviving patients was 37 +/- 24 months. Outcomes were compared in patients < 65 years old (group 1, n = 38), 65-74 years old (group 2, n = 47), and > 74 years old (group 3, n = 19). RESULTS: Total pancreatectomy was performed in 12 patients and pancreaticoduodenectomy was performed in 92 patients. The overall complication rate was similar in all groups, but major morbidity was highest in group 3 (P = 0.05). Median survival for patients in group 2 was 25.1 months. Survival was significantly shorter in patients from groups 1 and 3 (median survivals 12.4 months and 11.4 months, respectively; P = 0.02). Following control for Hispanic ethnicity, which was also a significant prognostic factor on univariate analysis, only the oldest age group had a significantly shorter survival than the other two groups. Age > 74 years and Hispanic ethnicity remained significant after multivariate analysis. CONCLUSIONS: Long-term survival after resection is truncated in older patients. This finding and the observation that the major complication rate is higher in the older subgroup emphasize the need to evaluate critically whether older patients should be submitted to radical resection.

Age Factors↗

Reversal of CD8+ T cell ignorance and induction of anti-tumor immunity by peptide-pulsed APC.

In the present report, we have studied the potential of naive and activated effector CD8(+) T cells to function as anti-tumor T cells to a solid tumor using OVA-specific T cells from TCR-transgenic OT-I mice. Adoptive transfer of naive OT-I T cells into tumor-bearing syngeneic mice did not inhibit tumor cell growth. The adoptively transferred OT-I T cells did not proliferate in lymphoid tissue of tumor-bearing mice and were not anergized by the tumor. In contrast, adoptive transfer of preactivated OT-I CTL inhibited tumor growth in a dose-dependent manner, indicating that E.G7 was susceptible to immune effector cells. Importantly, naive OT-I T cells proliferated and elicited an anti-tumor response if they were adoptively transferred into normal or CD4-deficient mice that were then vaccinated with GM-CSF-induced bone marrow-derived OVA-pulsed APC. Collectively, these data indicate that even though naive tumor-specific T cells are present at a relatively high fraction they remain ignorant of the tumor and demonstrate that a CD8-mediated anti-tumor response can be induced by Ag-pulsed APC without CD4 T cell help.

Animals↗

Radical resection of periampullary tumors in the elderly: evaluation of long-term results.

Increasingly, patients of advanced age are coming for evaluation of periampullary tumors. Although several studies have demonstrated the safety of resecting periampullary tumors in older patients, few long-term survival data have been reported. Between 1983 and 1992 various periampullary masses were resected in 70 patients over age 65 (range 65-87 years). Total pancreatectomy was performed in 11 patients, and 59 patients underwent pancreaticoduodenectomy. The mean duration of hospitalization was 17 +/- 15 days. Major complications occurred in 27 patients (39%), and operative mortality rate was 8.5%. Overall median survival was 24 months; and 5-year survival was 25%. Perioperative outcome was compared in patients aged 65 to 74 years and in patients > or =75 years old. The older age group required longer periods in the surgical intensive care unit postoperatively, but the long-term survival was similar in the two age groups. Radical resection with the intent to cure periampullary tumors is safe in selected patients of advanced age, and long-term survival is in the range of expected survival for younger patients with the same tumors.

Adenocarcinoma↗

Extent of resection in the management of duodenal adenocarcinoma.

BACKGROUND: It has been postulated that segmental duodenal resection (SR) is not an adequate operation for patients with adenocarcinoma of the duodenum and that pancreaticoduodenectomy (PD) is the procedure of choice, regardless of the tumor site. However, data from previous studies do not clearly support this position. METHODS: We reviewed the records of 63 patients treated for duodenal adenocarcinoma from 1979 through 1998. Perioperative outcome, patient survival, and extent of lymphadenectomy were compared in patients who underwent PD and SR. RESULTS: The overall morbidity for PD and SR was 27% and 18%, respectively (not significant [NS]). Patients who underwent SR had a 5-year survival of 60% versus 30% for patients who underwent PD (NS). Lymph node status was a prognostic factor for survival (P = 0.014). The mean number of lymph nodes in the specimens was 9.9 +/- 2.1 for PD and 8.3 +/- 4.4 for SR (NS). CONCLUSIONS: Segmental duodenal resection for patients with duodenal adenocarcinoma is associated with acceptable postoperative morbidity and long-term survival. The procedure is especially well suited for distal duodenal tumors. Clearance of lymph nodes and outcome are comparable to PD.

Actuarial Analysis↗

A subcutaneous or subfascial jejunostomy is beneficial in the surgical management of extrahepatic bile duct cancers.

BACKGROUND: Extrahepatic bile duct cancers are rare tumors with a dismal prognosis. Even after a resection, obstructive cholestasis and other biliary complications are the rule. To facilitate retrograde access to the biliary tree for treatment of such biliary complications, a modified Roux-en-Y hepaticojejunostomy is constructed such that the afferent limb is brought up as a subcutaneous or subfascial jejunostomy (SJ). The safety and utility of construction of an SJ was evaluated in patients with extrahepatic cholangiocarcinoma. METHODS: From 1985 to 1997, 24 patients with extrahepatic bile duct cancers received an SJ as part of their management. Demographic data, operative data, tumor characteristics, and postoperative courses were retrospectively reviewed. All but 3 patients were followed to the time of death. RESULTS: The average age of the patients was 62 +/- 9 years. The tumor was resected in 17 patients. Major complications occurred in 5 patients (21%). There was 1 operative death (4%). None of the complications could be attributed to construction of the SJ, although 1 patient had a soft tissue infection at the site of the percutaneous access of the SJ. Frequent dilatations of biliary strictures were required in 5 patients, and 1 patient eventually required insertion of an internal biliary stent. These procedures could all be accomplished through the SJ. CONCLUSIONS: The SJ is a technically simple and safe addition to the management of resectable and unresectable extrahepatic bile duct cancers, particularly proximal lesions. The procedure facilitates brachytherapy if indicated, and it allows convenient management of postoperative biliary complications, including recurrent strictures.

Aged↗

Expression of receptors for estrogen and progesterone in malignant colonic mucosa as a prognostic factor for patient survival.

BACKGROUND AND OBJECTIVES: Estrogen receptors (ER) and progesterone receptors (PR) have been detected in both normal and malignant colonic mucosa, but the prognostic value of this observation is unknown. We aimed to define the prognostic significance of the presence of ER and PR in malignant cells from colorectal adenocarcinoma specimens. METHODS: An immunohistochemical assay for ER and PR was performed on paraffinized sections from 65 colorectal adenocarcinoma specimens. Survival curves were analyzed to define the prognostic implications of ER and PR. RESULTS: Twenty nine (45%) tumors tested receptor positive (32% for ER and 23% for PR). Tumors of advanced stage were more likely to express receptors than early stage tumors (56% vs. 32%; P = 0.01). Median survival of patients with neoplasms expressing PR was 30 months. For patients whose tumors did not express any receptors, median survival had not been reached at the time of follow-up (P = 0.04). Similarly, patients with tumors expressing both receptors had significantly reduced survival (median survival = 20 months; P = 0.003). CONCLUSIONS: Expression of receptors for sex steroids correlates with advanced stage disease. Expression of PR by the tumor cells is associated with a shorter patient survival. The results suggest that sex steroids may play a role in carcinogenesis and tumor progression.

Adenocarcinoma↗

Metastasectomy as a cytoreductive strategy for treatment of isolated pulmonary and hepatic metastases from breast cancer.

The authors sought to examine the utility of resection in conjunction with adjuvant chemotherapy for treatment of metastases from breast cancer isolated to the liver or lungs. Limitations of regional therapy were examined and potential agents for systemic therapy were reviewed. As resection of metastases is a controversial therapeutic approach, no clinical trials are available for review. Rather, evidence for a potential role for surgery rests on retrospective studies of small series of patients. Technical advances have rendered resection of liver and lung metastases safe. Long-term results as reported by other investigators support the role of metastasectomy in selected patients. The site of failure following ablation of liver metastases is usually in the liver. Following resection of lung metastases, nonpulmonary and disseminated recurrences are most common. Adjuvant therapy with docetaxel or any other agent or combination with significant activity against visceral metastases might potentiate long-term results.

Breast Neoplasms↗

Day-care laparoscopic appendectomies.

OBJECTIVE: To demonstrate the safety of laparoscopic appendectomy in a day-care setting and to compare patients selected for laparoscopic versus open appendectomy. DESIGN: A retrospective, nonrandomized study. SETTING: A community hospital in a small town in British Columbia. PATIENTS: Ninety-four consecutive patients with a clinical diagnosis of acute appendicitis. INTERVENTIONS: Each patient underwent laparoscopic or open appendectomy as selected by the operating surgeon. OUTCOME MEASURES: Duration of operation and of hospital stay, morbidity and mortality. RESULTS: The average operating time was 32 minutes for open appendectomy and 36 minutes for laparoscopic appendectomy. Two (4%) of the 52 patients who had a laparoscopic appendectomy had significant complications; 1 of them required reoperation for intra-abdominal abscess. Thirty-nine (75%) of the laparoscopic appendectomies were done as day-care procedures. The average length of stay for the remaining patients was 2.1 days. The overall complication rate for patients who underwent open appendectomy was 20%. The average length of stay for these patients was 3.2 days; no patient was discharged within 24 hours. CONCLUSIONS: Laparoscopic appendectomy can be safely performed as a day-care procedure, even for selected patients with gangrenous or perforated appendices. Patients typically selected for open appendectomy include children and those with more advanced infection.

Adolescent↗

Liver as a focus of impaired oxygenation and cytokine production in a porcine model of endotoxicosis.

OBJECTIVES: To determine whether the liver is a focus of insufficient oxygenation and whether liver is a source of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in a porcine model of endotoxicosis. DESIGN: In vivo, prospective, controlled, repeated-measures, experimental study. SETTING: Experimental physiology laboratory in a university. SUBJECTS: Juvenile pigs, weighing 22 to 35 kg. INTERVENTIONS: Catheters for blood sampling were inserted into the carotid artery, portal vein, hepatic vein, and pulmonary artery of anesthetized animals. Ultrasonic flow probes were placed on the portal vein and the hepatic artery. During surgery, normal saline was infused intravenously at 25 mL/kg/hr. Following stabilization, animals were allocated randomly to one of two groups. The endotoxemic group (n = 6) received 50 mg/kg of purified Escherichia coli lipopolysaccharide infused into the external jugular vein over 1 hr. The control group (n = 6) received a sham saline infusion infused over 1 hr. Once the endotoxin or sham infusion was initiated, the rate of the intravenous saline infusion was increased to 48 mL/kg/hr for the remainder of the experiment. Measurements were obtained before the endotoxin or sham infusion, immediately after the infusion, and every 30 mins thereafter for 4 hrs. MEASUREMENTS AND MAIN RESULTS: Blood gases, lactate, and bioactive TNF and IL-6 concentrations were measured from the carotid artery, portal vein, hepatic vein, and pulmonary artery. The porcine model is characterized by systemic hypotension, pulmonary hypertension, and maintenance of cardiac output. Despite decreased hepatic oxygen delivery in endotoxemic animals (p < .02), there was no change in hepatic oxygen consumption compared with controls. Throughout the experiment, there was net hepatic consumption of lactate in both groups. There was no significant hepatic production (or consumption) of TNF or IL-6 in either group. CONCLUSIONS: In this porcine model of endotoxicosis, there is a reduction of hepatic oxygen delivery but dysoxia is not present. The liver is not a source of TNF or IL-6 in this model of endotoxicosis.

Animals↗

Splanchnic origin of cytokines in a porcine model of mesenteric ischemia-reperfusion.

BACKGROUND: The purpose of this study was to determine whether the gut or the liver was the source of tumor necrosis factor (TNF), interleukin-6 (IL-6), and endogenous endotoxin in a porcine model of mesenteric ischemia-reperfusion. METHODS: Endotoxin, TNF, and IL-6 levels were measured from the carotid artery (CA), portal vein (PV), and hepatic vein (HV) every 30 minutes for 330 minutes in anesthetized pigs after occlusion of the superior mesenteric artery (SMA; n = 7) and after sham operation (n = 7). In animals subjected to mesenteric ischemia, the SMA clamp was released twice: once at 240 minutes (for 40 seconds) and once at 300 minutes (for the remainder of the experiment). RESULTS: In control animals, TNF and IL-6 levels remained at baseline at all vascular sites for the duration of the experiment. In the SMA ligation group, TNF levels peaked before release of the SMA clamp. Compared with TNF levels in the CA (27 +/- 3.7 pU/ml, unchanged from baseline), TNF levels were higher in the PV and in the HV (47 +/- 1.7 and 44 +/- 4.0 pU/ml, respectively; p < 0.05). In contrast, IL-6 appeared in the circulation immediately after first release of the SMA clamp. At this instant, compared with levels in the CA (1381 +/- 305 pU/ml), IL-6 levels in the PV and HV were higher (1884 +/- 276 and 1795 +/- 213 pU/ml, respectively; p < 0.05). Endotoxin remained at baseline levels (1.0 +/- 0.3 endotoxin unit/ml) throughout the experiment in both groups of animals, and gut efflux of endotoxin never exceeded gut influx. CONCLUSIONS: TNF is produced in a partially perfused splanchnic bed during SMA clamping (e.g., pancreas, duodenum, liver, left colon). IL-6 is produced in gut during SMA clamping and is released when the SMA is unclamped. There is no apparent splanchnic release of endotoxin during or after SMA clamping in this model.

Animals↗

Gut is not a source of cytokines in a porcine model of endotoxicosis.

BACKGROUND: We sought to determine whether ischemic gut is a source of endotoxin, tumor necrosis factor (TNF), and interleukin-6 (IL-6) in a porcine model of endotoxicosis. METHODS: Under general anesthesia pigs underwent neck dissection and laparotomy for placement of catheters in the carotid artery and portal vein and application of an ultrasonic flow probe around the portal vein. Endotoxin, TNF, and IL-6 levels were measured from the carotid artery and the portal vein during a 4 hour period in animals given endotoxin (50 mg/kg; n = 6) and in animals in the control group (n = 6). Gut fluxes of the substances of interest were calculated as the product of concentration and portal venous flow. A tonometer placed in the terminal ileum was used to monitor mucosal pH. RESULTS: Small bowel mucosal pH was significantly depressed in endotoxemic animals (6.8 +/- 0.1) when compared with baseline (7.1 +/- 0.1; p < 0.05) and control levels. In the control group portal venous levels of endotoxin, TNF, and IL-6 did not change significantly from baseline levels (1.5 +/- 0.4 endotoxin units (EU)/ml, 24 +/- 3 pU/ml, and 1.3 +/- 0.4 nU/ml, respectively). In the endotoxemic animals portal venous endotoxin and TNF levels peaked immediately after the endotoxin infusion (2186 +/- 437 EU/ml, and 293 +/- 125 pU/ml, respectively), and portal venous IL-6 levels peaked at 180 minutes (168 +/- 21 nU/ml). At no time did endotoxin, TNF, or IL-6 levels differ between arterial and portal venous blood, and at no time did efflux from the gut significantly exceed gut influx in either the control or endotoxemic animals. CONCLUSIONS: Ischemic gut as indicated by decreased mucosal pH is not associated with gut release of endotoxin, IL-6, or TNF in this porcine model of endotoxicosis.

Animals↗