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Biomedical subjects

Oliver F Bathe

Publications and source records attributed to Oliver F Bathe.

9 recordsLinked to original sources

Complex hepatic surgery aided by a 1.5-tesla moveable magnetic resonance imaging system.

BACKGROUND: Resection represents the best treatment for potentially curable liver tumors; radiofrequency ablation (RFA) is an alternative. The curative potential of RFA may be hampered because the extent of burn is difficult to estimate by ultrasound. We postulated that intraoperative MRI (iMRI) would enable a more accurate assessment of ablation completeness. METHODS: We performed open hepatic surgery in an operating room equipped with a unique, retractable 1.5-T magnet. Patients were selected because it was anticipated that RFA (with or instead of resection) was likelihood and that iMRI might be helpful in making intraoperative decisions. After baseline MRI, lesions were further assessed by ultrasound at the time of open surgery. Lesions were resected and/or ablated, and further imaging confirmed the margins of the procedure. RESULTS: Nine patients underwent the procedure: 1 with metastatic carcinoid, 4 with hepatocellular carcinoma, and 4 with colorectal liver metastases. In 4 patients, iMRI had an effect on decision-making. In 5 individuals, there were nonlocal recurrences, and 1 patient who was never disease-free had a local recurrence. COMMENTS: Intraoperative MRI could potentially impact operative decision-making when ablating extensive disease. Its ability to prevent local recurrences must be determined. Moreover, the role of this technology in the overall treatment armamentarium must be defined.

Carcinoma↗

Vascular occlusion to decrease blood loss during hepatic resection.

BACKGROUND: Historically, the primary hazard with liver surgery has been intraoperative blood loss. This led to the refinement of inflow and outflow occlusive techniques. The utility of the different methods of inflow and outflow techniques for hepatic surgery were reviewed. METHODS: A search of the English literature (Medline, Embase, Cochrane library, Cochrane clinical trials registry, hand searches, and bibliographic reviews) using the terms "liver," "hepatic," "Pringle," "total vascular exclusion," "ischemia," "reperfusion," "inflow," and "outflow occlusion" was performed. RESULTS: A multitude of techniques to minimize blood loss during hepatic resection have been studied. The evidence suggests that inflow occlusion techniques are generally well tolerated. These should be used with caution in patients with cirrhosis, fibrosis, steatosis, cholestasis, and recent chemotherapy, and for prolonged time intervals. CONCLUSIONS: Harmful effects of intraoperative blood loss and transfusion occur during hepatic resection. Portal triad clamping (PTC) is associated with less blood loss compared with no clamping. In procedures with ischemic times <1 hour in length, PTC-C (continuous) is likely equal to PTC-I (intermittent). In patients with chronic liver disease or undergoing lengthy operations, PTC-I is likely superior to PTC-C. PTC is superior to total vascular exclusion except in patients with tumors that are large and deep seated, hypervascular, and/or abutting the hepatic veins or vena cava and in patients with increased right-sided heart pressures.

Blood Loss, Surgical↗

A unique dedifferentiated tumor of the retroperitoneum.

BACKGROUND: Dedifferentiated liposarcomas represent heterogeneous tumors with lipomatous and nonlipomatous elements starkly juxtaposed. It is thought that the high grade nonlipomatous elements of the tumor portend a worse prognosis. CASE PRESENTATION: A 19.8 kg heterogeneous retroperitoneal tumor was successfully and completely resected. Because of its extent, no additional treatment modalities were practicable. The tumor soon recurred. The recurrent tumor differed from the primary tumor in that it was more homogeneous, consisting mainly of nonlipogenic, calcific tissue. CONCLUSIONS: Dedifferentiated liposarcomas are known to have a very high recurrence rate. The biological behavior of dedifferentiated liposarcomas is likely dictated by the most aggressive element of these heterogeneous tumors.

Journal Article↗

Phase II study of neoadjuvant 5-FU + leucovorin + CPT-11 in patients with resectable liver metastases from colorectal adenocarcinoma.

BACKGROUND: Following resection of liver metastases from colorectal cancer, 5-year survivals are reportedly 30 - 39%. It can be assumed that this clinical situation represents systemic disease. Therefore, it is postulated that systemic chemotherapy would improve outcomes, particularly in those whose disease is sensitive to the agents administered. One potential advantage of neoadjuvant chemotherapy is that it provides in vivo chemosensitivity data. Response to neoadjuvant chemotherapy could therefore guide adjuvant chemotherapy following resection of liver metastases from colorectal cancer. METHODS AND DESIGN: This is a prospective Phase II evaluation of outcomes in patients with potentially resectable liver metastases. Patients will receive neoadjuvant chemotherapy and will undergo resection. Postoperative chemotherapy will be directed by the degree of response to preoperative chemotherapy. All patients with Stage IV colorectal adenocarcinoma isolated to the liver that have disease that is amenable to complete ablation by resection, radiofrequency ablation, and/or cryoablation will be candidates for the trial. Patients will receive CPT-11 180 mg/m2 IV (over 90 minutes) on day 1 with 5-FU 400 mg/m2 bolus and 600 mg/m2 by 22 hour infusion and calcium folinate 200 mg/m2 on days 1 and 2, every 2 weeks. Altogether, six cycles of chemotherapy will be administered. Patients will then undergo resection and/or radiofrequency ablation. Patients who had stable disease or a clinical response with preoperative chemotherapy will receive an additional 12 cycles of CPT-11 180 mg/m2 IV (over 90 minutes) on day 1 with 5-FU 400 mg/m2 bolus and 600 mg/m2 by 22 hour infusion and calcium folinate 200 mg/m2 on days 1 and 2 (given every 2 weeks). Patients with resectable disease who had progressive disease during neoadjuvant chemotherapy will receive best supportive care or an alternative agent, at the discretion of the treating physician. Those patients who are not rendered free of disease following the neoadjuvant chemotherapy and surgery will receive best supportive care or an alternative agent, at the discretion of the treating physician. The primary endpoint of the study is disease-free survival. Secondary endpoints include overall survival, safety and feasibility, response to chemotherapy, and quality of life.

Adenocarcinoma↗

Initial antigen encounter programs CD8+ T cells competent to develop into memory cells that are activated in an antigen-free, IL-7- and IL-15-rich environment.

Although much is known concerning the immunobiology of CD8+ T memory cells, the initial events favoring the generation of CD8+ T memory cells remain poorly defined. Using a culture system that yields memory-like CD8+ T cells, we show that 1 day after Ag encounter, Ag-activated T cells developed into memory-like T cells, but this optimally occurred 3 days after Ag encounter. Key phenotypic, functional, and molecular properties that typify central memory T cells were expressed within 48 h when the activated CD8+ T cells were cultured with IL-7 or IL-15 in the absence of Ag or following transfer into normal mice. These data support a model whereby Ag activation of naive CD8+ T cells not only programs effector cell expansion and contraction but the potential to develop into a memory cell which ensues in an Ag-free environment containing IL-7 or IL-15.

Adoptive Transfer↗

Gastric decompression and enteral feeding through a double-lumen gastrojejunostomy tube improves outcomes after pancreaticoduodenectomy.

OBJECTIVE: The objective of this study was to assess the feasibility and safety of inserting a double-lumen gastrojejunostomy tube (GJT) after pancreaticoduodenectomy (PD) and to evaluate associated outcomes. BACKGROUND: Gastroparesis is a frequent postoperative event following PD. This often necessitates prolonged gastric decompression and nutritional support. A double-lumen GJT may be particularly useful in this situation: gastric decompression may be achieved through the gastric port without a nasogastric tube; enteral feeding may be administered through the jejunal port. METHODS: Thirty-six patients with periampullary tumors were randomized at the time of PD to insertion of GJT or to the routine care of the operating surgeon. Outcomes, including length of stay, complications, and costs, were followed prospectively. RESULTS: The 2 groups had similar characteristics. Prolonged gastroparesis occurred in 4 controls (25%) and in none of the patients who had a GJT (P = 0.03). Complication rates were similar in each group. Mean postoperative length of stay was significantly longer in controls compared with patients who had a GJT (15.8 +/- 7.8 days versus 11.5 +/- 2.9 days, respectively; P = 0.01). Hospital charges were 82,151 +/- 56,632 dollars in controls and 52,589 +/- 15,964 dollars in the GJT group (P = 0.036). CONCLUSIONS: In patients undergoing PD, insertion of a GJT is safe. Moreover, insertion of a GJT improves average length of stay. At the time of resection of periampullary tumors, GJT insertion should be considered, especially given this is a patient population in which weight loss and cachexia are frequent.

Aged↗

Therapeutic limitations in tumor-specific CD8+ memory T cell engraftment.

BACKGROUND: Adoptive immunotherapy with cytotoxic T lymphocytes (CTL) represents an alternative approach to treating solid tumors. Ideally, this would confer long-term protection against tumor. We previously demonstrated that in vitro-generated tumor-specific CTL from the ovalbumin (OVA)-specific OT-I T cell receptor transgenic mouse persisted long after adoptive transfer as memory T cells. When recipient mice were challenged with the OVA-expressing E.G7 thymoma, tumor growth was delayed and sometimes prevented. The reasons for therapeutic failures were not clear. METHODS: OT-I CTL were adoptively transferred to C57BL/6 mice 21-28 days prior to tumor challenge. At this time, the donor cells had the phenotypical and functional characteristics of memory CD8+ T cells. Recipients which developed tumor despite adoptive immunotherapy were analyzed to evaluate the reason(s) for therapeutic failure. RESULTS: Dose-response studies demonstrated that the degree of tumor protection was directly proportional to the number of OT-I CTL adoptively transferred. At a low dose of OT-I CTL, therapeutic failure was attributed to insufficient numbers of OT-I T cells that persisted in vivo, rather than mechanisms that actively suppressed or anergized the OT-I T cells. In recipients of high numbers of OT-I CTL, the E.G7 tumor that developed was shown to be resistant to fresh OT-I CTL when examined ex vivo. Furthermore, these same tumor cells no longer secreted a detectable level of OVA. In this case, resistance to immunotherapy was secondary to selection of clones of E.G7 that expressed a lower level of tumor antigen. CONCLUSIONS: Memory engraftment with tumor-specific CTL provides long-term protection against tumor. However, there are several limitations to this immunotherapeutic strategy, especially when targeting a single antigen. This study illustrates the importance of administering large numbers of effectors to engraft sufficiently efficacious immunologic memory. It also demonstrates the importance of targeting several antigens when developing vaccine strategies for cancer.

Animals↗

Hepatic vein injury during laparoscopic cholecystectomy: the unappreciated proximity of the middle hepatic vein to the gallbladder bed.

Uncontrollable hemorrhage during laparoscopic cholecystectomy occurs in 0.1% to 1.9% of all cases, with 88% originating from the gallbladder bed. The anatomical proximity between major branches of the middle hepatic vein and the gallbladder bed, and hence the risk of intraoperative bleeding, is unclear. CT scans of 20 random patients were retrospectively reviewed to identify the closest distance between branches of the middle hepatic vein and the gallbladder bed. The vein diameter was also recorded. Risk factors for intraoperative bleeding during laparoscopic cholecystectomy were also retrospectively reviewed. Large branches (mean diameter = 2.1 mm) of the middle hepatic vein are directly adjacent to the gallbladder bed in 10% of patients. An additional 10% of cases also possess branches within 1 mm of the gallbladder bed. Chronically scarred and contracted gallbladder disease may increase the risk of significant bleeding, requiring conversion. Twenty percent of all cases will display a large branch of the middle hepatic vein adherent or immediately adjacent to the gallbladder fossa. These patients are at increased risk for intraoperative bleeding. Furthermore, contracted gallbladders with evidence of chronic disease may be at increased risk for significant hemorrhage.

Aged↗