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Biomedical subjects

D C Hohn

Publications and source records attributed to D C Hohn.

At least 19 recordsLinked to original sources
PubMed1991

Alternating hepatic intra-arterial floxuridine and fluorouracil: a less toxic regimen for treatment of liver metastases from colorectal cancer.

Hepatic intra-arterial (HIA) infusion of floxuridine (FUDR) via an implanted pump has shown promise in the treatment of colorectal cancer metastasized to the liver. However, the potential benefit of this therapy may be offset by the high incidence of treatment-limiting biliary toxicity. Although weekly HIA bolus of fluorouracil (5-FU) is effective against metastatic colorectal cancer to the liver with no biliary toxicity, it is limited by systemic side effects. In December 1986, we began a phase II trial of alternating HIA FUDR and 5-FU via the implanted pump in an attempt to extend the duration of treatment by obviating the limiting biliary (FUDR) and systemic (5-FU) drug toxic effects. Patients received continuous HIA FUDR at 0.1 mg/kg of body weight per day on days 1 through 8 followed by an HIA bolus of 5-FU at 15 mg/kg given via the pump sideport on days 15, 22, and 29, with the cycle repeated every 35 days. Sixty-eight patients were enrolled in this trial, and 64 were fully evaluable. Of the 64 patients, 30 (47%) previously had received chemotherapy. Major response (complete response plus partial response) was observed in 32 (50%) of 64 patients, and the median survival from pump implantation in all patients was 22.4 months. In contrast to the experience with the single-agent HIA FUDR regimen, no patient had treatment terminated because of drug toxicity. Alternating HIA FUDR and 5-FU has efficacy similar to that of HIA FUDR given alone, but when closely monitored and adjusted appropriately, is not associated with toxic effects requiring treatment termination.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Endoscopic laser recanalization is effective for prevention and treatment of obstruction in sigmoid and rectal cancer.

Patients with obstructing cancers are ineligible for preoperative chemotherapy and radiation unless they undergo surgical diversion. Endoscopic laser therapy (ELT) may provide an alternative to colostomy for these patients. We retrospectively reviewed all patients with distal sigmoid and rectal carcinomas who underwent ELT from January 1988 through April 1990. The majority of patients were referred for palliation of advanced disease. Thirty-seven patients underwent 123 ELT sessions (median, 2.5; range, one to 18). In 84% of patients, patency was maintained during a median follow-up of 31.5 weeks (range, one to 123). Morbidity and mortality were 2.5% (3/123) and 5% (1/37), respectively. Sixty-two percent had radiotherapy, chemotherapy, and/or surgery concurrent with ELT. Endoscopic laser therapy can safely and effectively reestablish and maintain luminal patency in patients with obstructing distal cancers. In addition, ELT can enable the administration of preoperative adjuvant radiotherapy and chemotherapy.

Adenocarcinoma↗
PubMed1990

Hepatic artery infusion pumps: cannulation techniques and other surgical considerations.

Long term hepatic artery chemotherapy for metastatic disease to the liver has been made practical by technologic advances in pumps and catheters. The surgical placement of these pumps and catheters can be associated with a significant morbidity unless careful attention is given to variations in hepatic arterial anatomy and to eliminating collateral arterial supply to the distal stomach and duodenum. Gastroduodenal devascularization should be performed in all patients and should be confirmed both with intra-operative fluorescein injection and postoperative scintigraphy scanning. Routine cholecystectomy avoids the complication of chemical cholecystitis. Exact placement of the catheter tip at the junction of the gastroduodenal artery and the hepatic artery with fixation of the catheter in this position by placement of bidirectional ligatures around the catheter bead will reduce the incidence of hepatic artery thrombosis and catheter migration. Intrahepatic arterial collateralization in most patients allows for ligation of variant lobar vessels with total liver perfusion through the remaining lobar arterial supply. This again can be confirmed intra-operatively with fluorescein injection and postoperatively with scintigraphy scanning. Strict attention to these technical details will allow continued use of this important therapeutic modality in the treatment of hepatic metastases and by minimizing surgical complications will encourage continued trials to improve the efficacy of long term hepatic arterial chemotherapy.

Animals↗
PubMed1990

Management of inguinal lymph node metastases from adenocarcinoma of the rectum.

Forty patients with inguinal lymph node metastases from rectal adenocarcinoma were reviewed. Patients were divided into three groups based on the extent of their disease: (1) patients with unresectable primary tumors; (2) patients with recurrent disease after abdominoperineal resection; and (3) patients with isolated inguinal lymph node metastases after abdominoperineal resection. Patients in Groups 1 and 2 underwent biopsy of their nodal metastases. Patients in Group 3 were treated by inguinal node dissection. Survival data were examined for each group, and four clinical and pathologic features were analyzed to determine their impact on prognosis: depth of invasion of the primary tumor (T1-2 vs. T3-4), number of positive lymph nodes in the rectal specimen (0-2 vs. greater than 2), extent of the inguinal lymph node metastases (unilateral vs. bilateral), and timing of the inguinal lymph node metastases (less than 1 vs. greater than 1 year after abdominoperineal resection). There were no five-year survivors in any group. Median survival was highest in those with isolated lymph node metastases, with 2 patients remaining free of disease, and was lowest in those with unresectable primary disease (7 months). Median survival was increased when inguinal LNM were unilateral (17 vs. 6 months; P less than 0.01) and when they occurred more than 1 year after abdominoperineal resection (21 vs. 7 months; P = 0.02). Stage of the primary lesion (depth of invasion and number of positive lymph nodes) did not affect survival. Of the 32 patients who underwent biopsy alone, only 1 developed a tumor-related groin complication. For patients with isolated inguinal lymph node metastases, inguinal node dissection is recommended for the purposes of local control and possible cure. For patients with extranodal disease, prophylactic excision of inguinal lymph node metastases is not warranted.

Adenocarcinoma↗
PubMed1990

Extracorporeal hemofiltration: a model for decreasing systemic drug exposure with intra-arterial chemotherapy.

Cisplatin (3 mg/kg) was infused through the hepatic artery in nine mongrel dogs. Four of these dogs underwent simultaneous extracorporeal hemofiltration (ECH) of the hepatic venous effluent using a high-flow, dual-lumen catheter placed in the vena cava at the level of the hepatic veins. Platinum levels were measured in the plasma, urine, and ultrafiltrate and in kidney and liver tissue. ECH significantly reduced systemic drug exposure as measured by the AUC for free and total platinum, by urinary excretion, and by 24-h kidney levels. Regional liver levels were minimally affected. Recovery of platinum in the ultrafiltrate was 40% +/- 14%. ECH resulted in efficient extraction of platinum and reduced systemic drug exposure with relative preservation of regional hepatic drug exposure.

Animals↗
PubMed1990

Chemoembolization for hepatocellular carcinoma.

Fifty-one patients with unresectable hepatocellular carcinoma (HCC) were treated with Gelfoam (absorbable gelatin sterile powder; The Upjohn Co, Kalamazoo, MI) chemoembolization. A mixture of Gelfoam powder, contrast media, and three drugs (doxorubicin, mitomycin, and cisplatin) was injected under fluoroscopic guidance via a percutaneous catheter into the hepatic artery until stagnation of blood flow was achieved. Of the 51 patients, 50 are assessable for response, and all are assessable for toxicity and complications. The median percent of liver replacement was 50% (range, 15% to 95%). By conventional response criteria, there were 12 partial responses (PRs) (24%), 13 minor responses (MRs) (26%), 12 stabilization of disease (SD) (24%), and 13 (26%) progressive disease (PD). Tumor liquefaction was noted on computed tomographic (CT) scan in 35 of 50 patients (70%). Of the 34 patients with elevated alpha-fetoprotein (AFP), 23 (68%) had a greater than 50% reduction following treatment. Responding patients were re-treated at the time of tumor progression if they still met the entry criteria. The median survival of assessable patients from the time of treatment was 207 days and from the diagnosis of the primary was 302 days. Fourteen patients remain alive at 3 months to 3 years following treatment. The vast majority of patients had transient pain, fever, nausea, and elevation in liver enzymes. Ascites developed in 14 patients. There were two treatment-related deaths: one from tumor hemorrhage and one from liver failure. Chemoembolization appears to have significant activity in patients with hepatocellular carcinoma and is relatively well tolerated.

Adolescent↗
PubMed1989

A randomized trial of continuous intravenous versus hepatic intraarterial floxuridine in patients with colorectal cancer metastatic to the liver: the Northern California Oncology Group trial.

In 1983, the Northern California Oncology Group (NCOG) instituted a randomized trial of intravenous (IV) versus intraarterial (IA) floxuridine (FUDR) administered via an implantable pump for patients with colorectal cancer metastatic to the liver. The study objectives were to compare the hepatic response rate, time to hepatic progression, and toxicity for the two treatment arms. The study design, which allowed patients failing IV FUDR to crossover to the IA arm, prevents a meaningful comparative analysis of survival. Patients with liver-only metastases (N = 143) were randomized, 76 to the IV arm and 67 to the IA arm, and 115 patients (65 IV, 50 IA) were fully evaluable. Of the 65 patients in the IV arm, 28 crossed over to IA treatment after failing IV FUDR. The dose-limiting toxicity of IV FUDR was diarrhea, whereas biliary toxicity limited both the dose and duration of IA FUDR therapy. Of the first 25 patients treated with IA FUDR at a dose of .3 mg/kg/day, 10 developed radiographically evident biliary strictures, and three developed permanent jaundice. With reduction of the initial IA FUDR dose to .2 mg/kg/day, and adoption of a policy of early dosage reduction, treatment interruption, or termination of therapy for persistent elevations in alkaline phosphatase, only two further cases of serious biliary toxicity occurred. However, 26 of the 50 IA FUDR patients ultimately had therapy terminated because of drug toxicity rather than disease progression. When compared with systemic infusion, infusion into the hepatic artery greatly enhanced the antitumor activity of FUDR against colorectal liver metastases. Although biliary toxicity is the most serious limitation of this form of therapy, biliary stricture and jaundice usually can be averted through careful monitoring of liver enzymes and early dosage reduction.

Adult↗
PubMed1988

Extravasation. A serious complication of the split-sheath introducer technique for venous access.

The use of split-sheath introducers to place venous access catheters results in the potential for subcutaneous extravasation and tissue injury or necrosis. We present six cases that demonstrate this complication and illustrate the probable mechanism. The safe use of these catheters requires verification that blood can be aspirated from the catheter and a high index of suspicion for extravasation when symptoms develop.

Adult↗
PubMed1987

Immunodeficiency-associated thrombocytopenic purpura (IDTP). Response to splenectomy.

Immunodeficiency-associated thrombocytopenic purpura (IDTP) is a feature of the acquired immunodeficiency syndrome--related complex. Current therapeutic modalities for IDTP include splenectomy and the administration of corticosteroids or other agents. Empiric treatment of IDTP has been analogous to that for immunologic thrombocytopenic purpura (ITP). The present report reviews 15 patients who underwent splenectomy for IDTP, demonstrates the successful use of surgical therapy, and defines our indications for splenectomy in the treatment of this disorder. Thirteen of 15 patients had initially failed to respond to steroid therapy. Fourteen patients (93%) initially responded to splenectomy, with platelet counts increasing to 150 X 10(9)/L (150,000/mm3) or greater. A continuing complete response was achieved in nine patients (60%) following splenectomy. After postsurgical adjunctive therapy, durable remission was achieved in 73% (11/15) of the patients. Complications occurred in three patients, and there were no deaths. The mean follow-up was 12.4 months. Splenectomy may be performed in the treatment of IDTP with acceptable morbidity and likelihood of response.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Toxicities and complications of implanted pump hepatic arterial and intravenous floxuridine infusion.

Toxicities and complications were prospectively analyzed in patients with liver metastases receiving hepatic intra-arterial (IA) and systemic intravenous (IV) floxuridine (FUDR) with the Infusaid (Intermedics-Infusaid Corp., Norwood, MA) implantable pump. Among 55 patients treated with IA FUDR (0.3-0.1 mg/kg/day X 14, every 28 days), elevations in liver enzyme values, not attributable to disease progression, developed in 96% of patients. Serious biliary toxicity occurred in 31 patients (56%). In 16, biliary sclerosis was documented radiographically and was diagnosed clinically in 15 additional patients. Ten patients were hospitalized for biliary toxicity, including five who required cholecystectomy for acalculous cholecystitis. Because of the high reported incidence of serious gastroduodenal toxicity after IA FUDR infusion, our procedure for hepatic arterial cannulation was designed to eliminate misperfusion of the stomach and duodenum with drug; none of our patients experienced FUDR-associated gastroduodenal ulceration or bleeding. Cyclic IV FUDR (0.05-0.15 mg/kg/day X 14, every 28 days) was administered to 31 participants of the Northern California Oncology Group trial (3L-82-1) of IV versus IA FUDR. Dose-limiting toxicity was diarrhea. Serious toxicities were: protracted diarrhea (three), dermatitis (two), tear duct stenosis (two), and stomatitis (two). Three patients were hospitalized for toxicity. No hematologic or biliary toxicity occurred. The optimal route for treatment of hepatic metastases with continuous FUDR infusion has not yet been established. Systemic IV infusion has low morbidity, but preliminary response data need to be substantiated in controlled clinical trials before there can be widespread clinical application. High response rates for IA infusion have been previously documented. Morbidity due to acalculous cholecystitis and gastroduodenal ulceration can now be avoided. Despite significant progress in characterization of hepatobiliary toxicity, it remains dose-limiting. Continuous IA FUDR infusion should remain under the aegis of dedicated treatment centers until standardized protocols with diminished toxicity are established.

Alkaline Phosphatase↗
PubMed1986

Home support of patients with end-stage malignant bowel obstruction using hydration and venting gastrostomy.

Palliative terminal care of patients with malignant bowel obstruction is a major clinical and ethical challenge. These patients are often mentally alert and ambulatory, but are kept in the hospital for hydration, nasogastric suction, and pain control. Parenteral nutrition requires frequent metabolic monitoring, is expensive, and is ethically questionable. We have used an alternative method of home management for 27 patients who met the following criteria: inoperable bowel obstruction due to untreatable cancer, an estimated life expectancy of between 2 weeks and 3 months, and understanding of the goals and limits of therapy. Hydration was provided by 10 percent dextrose and electrolyte solutions administered as overnight infusions through long-term central venous catheters. Thirteen patients with complete bowel obstruction required a venting gastrostomy which, when connected to passive drainage, relieved nausea and vomiting. The mean duration of survival was 64 days (range 9 to 223 days). Acceptance by patients and families was excellent, although most acknowledged increased costs due to limited insurance coverage for outpatient care. Seven patients returned to the hospital for terminal care (average stay 3.2 days), and 20 chose to die at home. The mean daily expense for fluids and supplies was +73.50, with an overall cost decrease of $900,000 compared with inpatient care. Home support with fluids and gastric venting is a humane, cost-effective alternative to in-hospital care for selected patients.

Abdominal Neoplasms↗
PubMed1986

Sclerosing cholangitis associated with hepatic arterial FUDR chemotherapy: radiographic-histologic correlation.

During a 2-year period, cholangiography was performed on 17 patients with clinical evidence of cholestasis who were receiving hepatic intraarterial floxuridine (IA-FUDR) infusions for treatment of metastatic colorectal adenocarcinoma. The development of cholestasis was associated with persistently elevated alkaline phosphatase, but serial CT examinations of the liver showed no progression of the tumor. All patients had cholangiographic abnormalities (by endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography, or operative cholangiography) of the biliary ductal system similar to those in idiopathic sclerosing cholangitis. Certain features, however, appear specific to IA-FUDR-induced cholestasis. All patients studied had segmental involvement at the common hepatic duct bifurcation. The cystic duct and gallbladder were often involved, but the distal common bile duct was spared. Histologic features of periportal and periductal fibrosis were present in specimens obtained from percutaneous liver biopsy in three patients, cholecystectomy in four patients, and autopsy in two patients. When clinical signs of hepatic dysfunction occur in the absence of tumor progression, biliary sclerosis must be suspected.

Cholangiography↗
PubMed1986

Total hepatic arterial perfusion after occlusion of variant lobar vessels: implications for hepatic arterial chemotherapy.

The surgical placement of hepatic arterial cannulas, followed by intra-arterial chemotherapy, is a promising technique for the treatment of unresectable hepatic malignancies. Complete perfusion of the liver with drugs is essential, but may be difficult to achieve in some patients with variant arterial anatomy. In 79 patients, we encountered 15 with variant anatomy that precluded standard single or dual cannulation techniques. In 12 patients variant lobar arteries were ligated at surgery. Postoperative transarterial coil occlusion was used in three patients. In each case, the remaining hepatic lobar artery was perfused with a single catheter. Complete bilobar hepatic perfusion was documented by a technetium 99m macroaggregated albumin scan in 13 of 15 (87%) patients. Of patients scanned more than 5 days after occlusion, six of six (100%) had full perfusion of the region supplied by the variant lobar vessels. Postocclusion hepatic arteriography demonstrated translobar collateral vessels that provided perfusion of the region of the occluded variant artery. There was no added morbidity from lobar arterial occlusion and no disparity in tumor response between perfusion by direct cannulation and perfusion by collateral flow. Occlusion of variant hepatic lobar arteries in conjunction with single catheter cannulation to infuse the remaining lobar vessels is a useful technique to provide total hepatic arterial perfusion in patients with variant hepatic arterial anatomy.

Adult↗
PubMed1985

The role of splenectomy in multimodality treatment of thrombotic thrombocytopenic purpura.

Current treatment modalities for thrombotic thrombocytopenic purpura (TTP) include plasmapheresis (PP), splenectomy, steroids, dextran, other antiplatelet agents, and vinca alkaloids. Prior to the development of PP and use of multimodality treatment for TTP, mortality rates exceeded 50%. This report reviews 11 patients treated for TTP, demonstrates the successful use of splenectomy as salvage therapy, and defines our indications for splenectomy in the treatment of this disorder. Ten of 11 patients were initially treated with PP; three responded completely and one died of fulminant disease. Six patients had a transient partial response to plasmapheresis and were subsequently treated with splenectomy, steroids, and dextran-70. Initial plasmapheresis resulted in improvement in laboratory values and clinical status in those patients requiring splenectomy. Durable remission (6-48 months) was achieved in 91% of patients with minimal morbidity.

Adult↗
PubMed1985

Avoidance of gastroduodenal toxicity in patients receiving hepatic arterial 5-fluoro-2'-deoxyuridine.

Gastroduodenal inflammation and ulceration have been frequently observed in patients receiving continuous hepatic arterial infusions of 5-fluoro-2'-deoxyuridine (FUDR) for liver malignancy. Thirty-five patients with metastatic colon cancer received hepatic arterial FUDR administered with implanted infusion pumps. At surgery, particular care was taken to identify and divide those vessels arising from the hepatic arteries distal to the point of cannulation that supplied the superior border of the distal stomach and proximal duodenum. None of the patients developed signs or symptoms of gastritis or ulcer attributable to chemotherapy. We contend that gastritis and ulcer in patients receiving hepatic arterial FUDR are due to misperfusion of drug into the upper gastrointestinal tract and that these complications can be largely avoided by use of appropriate surgical techniques.

Colonic Neoplasms↗
PubMed1977

Antimicrobial systems of the surgical wound. I. A comparison of oxidative metabolism and microbicidal capacity of phagocytes from wounds and from peripheral blood.

Oxygen consumption glucose oxidation via the hexose monophosphate shunt, and superoxide production by resting and stimulated leukocytes derived from rabbit blood and from experimental rabbit wounds five to seventeen days old were measured and compared. In vitro killing of staphylococci by blood and wound leukocytes was also measured. In all of these studies there were no significant functional differences between blood and wound cells. The data presented suggest that under the same in vitro conditions, blood and wound leukocytes are functionally equivalent, that tissue mobilization does not cause alteration of wound leukocytes, and that aging of the wound does not impair the microbicidal capacity of wound leukocytes.

Animals↗