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Biomedical subjects

J Niederhuber

Publications and source records attributed to J Niederhuber.

14 recordsLinked to original sources
PubMed1996

NCCN Colorectal Cancer Practice Guidelines. The National Comprehensive Cancer Network.

In summary, the committee believes that a multidisciplinary approach is necessary for the management of the patient with colorectal cancer. The committee endorses the concept that treatment of patients on a clinical trial has priority over standard or accepted therapy. The recommended surgical procedure for managing resectable colon cancer is an en bloc resection; laparoscopic surgery should be done only in the context of a clinical trial. For patients with stage III disease, 5-FU-based adjuvant chemotherapy is recommended. A patient who has metastatic disease in the liver or lung should be considered for surgical resection if he or she is a candidate for surgery and if surgery can extend survival. The committee advocates a conservative post-treatment surveillance program for colon and rectal cancer patients. A determination of CEA should be done only if CEA was elevated at baseline and decreased following primary resection. Abdominal and pelvic CT scans should be utilized only when there are clinical indications of possible recurrence. Patients whose disease progresses during 5-FU-based therapy should be considered for treatment with irinotecan or encouraged to participate in a phase I or II clinical trial.

Colonic Neoplasms↗
PubMed1984

Constant intrarenal infusion of PGE1 into a canine renal transplant using a totally implantable pump.

A method was devised whereby PGE1 could be administered to a canine renal transplant recipient on a chronic basis. PGE1 was stored in the reservoir of an implantable pump and delivered continuously in high doses directly into the renal transplant artery. In the model studied a contralateral untreated transplant from the same donor served as a control. Sequential renal scans were used to study the effect of intraarterial PGE1 on the rejection process. Continuous delivery of PGE1 into the renal transplant artery did not prevent allograft failure under these conditions; blood flow diminished similarly in both PGE1-treated and untreated transplants. There were, however, striking differences in the histologic appearance of treated and untreated transplants. PGE1 perfusion resulted in the appearance of large numbers of polymorphonuclear leukocytes but few lymphocytes. In the untreated control allograft, however, the findings were typical of lymphocyte-mediated acute rejection. The distinctive differences noted histologically suggested that the local administration of PGE1 influenced the mechanism by which graft failure occurred. The ability to manipulate cell populations infiltrating an allograft represents a potentially important means for modifying the immune response.

Alprostadil↗
PubMed1983

Improved regional selectivity of hepatic arterial mitomycin by starch microspheres.

Biodegradable starch microspheres, 40 microns in diameter, were administered through hepatic arterial catheters in 16 subjects with primary and metastatic liver tumors. These microspheres temporarily obstruct blood flow at the precapillary arteriole (microcirculation) level. Our study was undertaken to determine whether such occlusion would enhance hepatic deposition of, and thereby decrease systemic exposure to, simultaneously administered hepatic arterial mitomycin C (mito). When mito (10 mg/m2 over 1 min) was given with 90 X 10(6) microspheres (10 subjects), there was a 17% to 70% reduction in systemic mito exposure. When mito (10 mg/m2 over 1 min) was given with 36 X 10(6) microspheres (six subjects), there was a 15% to 60% reduction in systemic exposure, which may correlate with dose-dependent shunting (8% to 29%) through the liver to the lung (and hence to the systemic circulation), attributed to the starch microspheres. No life-threatening myelosuppression was noted; hepatic toxicity consisted of transient pain and elevation of liver enzymes.

Adult↗
PubMed1982

Improved regional selectivity of hepatic arterial BCNU with degradable microspheres.

Starch microspheres 40 micrometers in diameter, which are rapidly degraded by serum amylase, have been administered through hepatic arterial catheters to five patients with primary and metastatic liver cancer to determine whether (1) arterial blood flow through the liver could be temporarily blocked, and (2) such occlusion at the level of the arteriolar capillary bed would enhance regional uptake and catabolism and decrease systemic exposure to simultaneously administered hepatic arterial bischlorethylnitrosourea (BCNU). It was possible with 10 ml of microspheres (9 X 10(6) microspheres/ml) injected into the hepatic artery to transiently (for 15-30 minutes) reduce hepatic flow by 80-100% in the five patients. When BCNU (50 mg/m2 in one minute) was given with microspheres there was a 30-90% reduction in systemic nitrosourea exposure and in peak levels. No myelosuppression was noted and hepatic toxicity consisted of acute pain due to BCNU and 1.5-2.0 fold transient enzyme elevations. One patient with cholangiocarcinoma showed a partial response lasting three months; three patients had stable disease and one patient with colon carcinoma had progressive disease. Thus, this pilot study suggests that concurrent intra-arterial microspheres and BCNU may have the potential to improve selective regional drug effect with marked diminution in systemic toxicity.

Carmustine↗
PubMed1982

Totally implanted system for intravenous chemotherapy in patients with cancer.

A totally implanted system for improved central venous access has been investigated in 20 patients with cancer (six with solid tumors, four with leukemia, and 10 with lymphomas) who were treated with aggressive chemotherapy regimens and who lacked peripheral venous sites. The system is implanted using local anesthesia and consists of a subcutaneous injection port connected to a Silastic catheter threaded through the subclavian vein into the superior vena cava. Injections and continuous infusions (for up to three weeks) of virtually all classes of antineoplastic agents, antibiotics, blood components, and intravenous solutions were administered through the system. The system was filled with heparinized saline and not otherwise flushed between uses. The system has remained functional for periods exceeding 450 days (mean 235 days). There was no significant local irritation and no system became infected. None of 18 large-bore catheters (0.63 mm lumen) became occluded (seven to 300 days), whereas five of six small-bore catheters (0.38 mm lumen) became occluded (90 to 420 days). Three of the occluded systems were replaced. Acceptance has been excellent, and patients have had no impediment to normal activities. This system appears to be an alternate means of safe and reliable central venous access with improved convenience and cosmetic acceptability.

Antineoplastic Agents↗
PubMed1969

Role of the kidney in staphylococcal enterotoxemia.

Highly purified staphylococcal enterotoxin B (SEB) is known to accumulate rapidly within the kidneys of experimental animals. The present study was performed to determine whether the predominant renal localization of SEB was of fundamental pathophysiologic importance in the development of lethal shock after the intravenous administration of this toxin to monkeys. Eight bilaterally nephrectomized Macaca mulatta given 10 mug of SEB per kg survived for an average time period less than half that of nephrectomized control animals (P < 0.001). Their survival time, however, was similar to that of control, sham-nephrectomized monkeys given an equal amount of SEB. Thus, no evidence was obtained to suggest that the kidney converted purified SEB to a more potent toxin. The glomerular filtration and proximal tubule cell accumulation of SEB possibly occurred as a nonspecific consequence of its molecular size, and such localization within the kidney might have served to reduce the quantity of SEB reaching some other site of toxic activity. Similar pathological and clinical findings were demonstrated in monkeys from both experimental and control groups; these could not be ascribed to SEB alone.

Animals↗
PubMedDate not supplied

Preoperative chemoradiation for marginally resectable adenocarcinoma of the pancreas.

Only 10% to 20% of patients with pancreatic cancer are considered candidates for curative resection at the time of diagnosis. We postulated that preoperative chemoradiation therapy might promote tumor regression, eradicate nodal metastases, and allow for definitive surgical resection in marginally resectable patients. The objective of this study was to evaluate the effect of a preoperative chemoradiation therapy regimen on tumor response, resectability, and local control among patients with marginally resectable adenocarcinoma of the pancreas and to report potential treatment-related toxicity. Patients with marginally resectable adenocarcinoma of the pancreas (defined as portal vein, superior mesenteric vein, or artery involvement) were eligible for this protocol. Patients received 50.4 to 56 Gy in 1.8 to 2.0 Gy/day fractions with concurrent protracted venous infusion of 5-fluorouracil (250 mg/m2/day). Reevaluation for surgical resection occurred 4 to 6 weeks after therapy. Fifteen patients (9 men and 6 women) completed preoperative chemoradiation without interruption. One patient required a reduction in the dosage of 5-fluorouracil because of stomatitis. Acute toxicity from chemoradiation consisted of grade 1 or 2 nausea, vomiting, diarrhea, stomatitis, palmar and plantar erythrodysesthesia, and hematologic suppression. CA 19-9 levels declined in all nine of the patients with elevated pretreatment levels. Nine of the 15 patients underwent a pancreaticoduodenectomy, and all had uninvolved surgical margins. Two of these patients had a complete pathologic response, and two had microscopic involvement of a single lymph node. With a median follow-up of 30 months, the median survival for resected patients was 30 months, whereas in the unresected group median survival was 8 months. Six of the nine patients who underwent resection remain alive and disease free with follow-up of 12, 30, 30, 34, 39, and 72 months, respectively. Preoperative chemoradiation therapy is well tolerated. It may downstage tumors, sterilize regional lymph nodes, and improve resectability in patients with marginally resectable pancreatic cancer. Greater patient accrual and longer follow-up are needed to more accurately assess its future role in therapy.

Adenocarcinoma↗
PubMedDate not supplied

Totally implanted drug delivery system for hepatic arterial chemotherapy.

A totally implanted drug delivery system for hepatic arterial chemotherapy was evaluated in 13 patients with metastatic (11 colon and one carcinoid) or primary (one hepatoma) cancer of the liver. During laparotomy, a Silastic catheter was positioned in the hepatic artery for infusion to the entire liver arterial vasculature as ascertained by low-flow radionuclide angiography with 99Tc-macroaggregated albumin. The catheter was connected to a subcutaneously implanted model 400 Infusaid pump (Metal Bellows Corp, Sharon, MA). Each pump had a 50-ml volume and a set rate (3--6 ml/day) and required refill every 8--16 days. A side port bypassed the pumping mechanism and allowed direct catheter injection for nuclide angiography, for bolus drug administration, or for clearing of a blocked catheter. Pump refills and side port injections were performed by percutaneous injection. The 13 patients in this ongoing study received a median of 6 months (range, 4.5--17) of continuous hepatic arterial infusion. The pump performed reliably with stable (+/- 10%) flow rates and only one malfunction in 2800 cumulative days of use. Flow distribution determined by low-flow radionuclide angiography did not change in 12 patients. Patient acceptance was excellent, with the ability to participate fully in normal daily activities. Eleven patients showed partial hepatic tumor regressions documented by physical examination and nuclide liver scans. All patients were treated with 5-fluorodeoxyuridine. Two patients failed 5-fluorodeoxyuridine therapy and subsequently responded briefly to dichloromethotrexate. This implanted system should facilitate future investigation of regional chemotherapy using these and other agents.

Adult↗
PubMedDate not supplied

Implanted system for intraventricular drug infusion in central nervous system tumors.

We have developed a totally implanted drug delivery system capable of maintaining constant cerebrospinal fluid (CSF) drug levels through continuous intraventricular infusion in outpatients. This system was used to infuse methotrexate (MTX) intraventricularly in seven patients with incurable CNS malignancies. One patient with meningeal diffuse histiocytic lymphoma, five patients with grade III--IV astrocytomas, and one patient with melanoma metastatic to the brain were treated with this system for 4--40+ weeks. The system consists of an Infusaid pump (Metal Bellows Corp, Sharon, MA), implanted subcutaneously in the infraclavicular fossa, which delivers a drug-containing solution at a set rate (3--5 mg/day) through a subcutaneous silastic catheter to a Rickham ventriculostomy reservoir and into a lateral ventricle. System placement and maintenance were readily tolerated. Constant MTX infusion at rates of 0.5--10 mg/day generated corresponding constant CSF drug levels in the range of 2--30 microM. Simultaneous serum MTX levels were undetectable (less than 0.01 microM), indicative of a 200- to 3000-fold selective regional concentration advantage for this approach. CNS toxic effects included transient meningism and fever (four patients), transverse myelitis (one), and the development of a diffuse hypodensity of the white matter on computerized tomographic scan which was not associated with any neurologic deficit (two). The usual systemic toxic effects (myelosuppression and mucositis) of MTX were not seen. The patient with meningeal lymphoma has had a complete remission of meningeal disease continuing past 10 months. Computerized tomography showed that three of the five high-grade astrocytomas had 25% size reductions in tumors lasting 2--6 months. This system may provide a means for improved treatment of meningeal tumor although its role in the treatment of intraparenchymal brain tumors is less clear. Of greater consequence, however, is the demonstrated ability of this system to maintain a controlled CSF drug level which should prove useful in many areas of therapeutic research.

Adult↗