Arthur W. Boddie

Resectable gastric carcinoma. An evaluation of preoperative and postoperative chemotherapy

Patients with locoregional gastric carcinoma often die because of the low rates of curative resection and frequent appearance of distant metastases (mainly peritoneal and hepatic). To evaluate the feasibility of preoperative and postoperative chemotherapy, 25 consecutive previously untreated patients with potentially resectable locoregional gastric carcinoma received two preoperative and three postoperative courses of etoposide, 5‐fluorouracil, and cisplatin (EFP). Ninety‐eight courses (median, five courses; range, two to five courses) were administered. Six patients had major responses to EFP. Eighteen patients (72%) had curative resections, and three specimens (12%) contained only microscopic carcinoma. At a median follow‐up of 25 months, the median survival of 25 patients was 15 months (range, 4 to 32+ months). Peritoneal carcinomatosis was the most common indication of failure. One patient died of postoperative complications, but there were no deaths due to chemotherapy. EFP‐induced toxic reactions were moderate. Preoperative and postoperative chemotherapy for locoregional gastric carcinoma is feasible, and additional studies to develop regimens that could result in 5% to 10% complete pathologic responses may be warranted.

Multivariate analysis of prognostic factors in regional cutaneous metastases of extremity melanoma

In 135 patients with regional cutaneous recurrence of extremity melanoma, the prognostic significance of 12 clinical and pathologic variables was analyzed in four alternative Cox stepwise regression models and by single variable analysis. A highly significant fit of the regression (P < 0.01) identified four factors that particularly influenced survival: the presence of intradermal or mixed (as opposed to purely subcutaneous) metastases (P < 0.001), sex (P = 0.032), excision of regional cutaneous metastases with or without perfusion (P = 0.033), and the presence of subcutaneous metastases (P = 0.201). Not predictive of survival were age at diagnosis; site of primary; anatomic location, number, size, or distance from the primary of the regional cutaneous metastases; time since primary treatment; number of positive regional lymph nodes; and single‐ or triple‐drug perfusion.

Hepatic arterial infusion with floxuridine and cisplatin: Overriding importance of antitumor effect versus degree of tumor burden as determinants of survival among patients with colorectal cancer

Cisplatin (CDDP) was combined with floxuridine (FUDR) and delivered into the hepatic arteries of 29 patients as induction therapy for colorectal cancer metastatic to the liver. Mitomycin C and FUDR combination was substituted after progression or when response had peaked. Chemotherapy was delivered with an Infusaid pump (Infusaid Corp; Norwood, Mass; 14 patients), Medtronic programmable drug administration device (Medtronic, Inc, Minneapolis; two patients), or percutaneously placed catheters (13 patients). Complete disappearance of liver metastases was observed in four patients and 11 additional patients had a partial remission as determined by computed tomography (CT) scan and substantiated at times by angiography, for a total response rate of 52%. Response as determined by imaging techniques coincided with a concurrent decrease in carcinoembryonic antigen (CEA) and improvement in performance status. The severity of tumor burden was correlated with the response to therapy and survival. Among those patients who responded to arterial chemotherapy, differences in disease severity did not significantly influence survival. Median survival among responders with greater than 25% liver replacement by tumor was 14 months (P = .28), compared with 28 months for those patients with less than 25% liver replacement. In contrast, differences in tumor burden significantly affected survival among patients who failed to respond to chemotherapy; median survival among nonresponding patients with greater than 25% liver replacement was 4 months, compared with 8 months for those who had less than 25% liver replacement (P = .01). The presence of minimal extrahepatic disease at the time of initiation of intraarterial treatment did not seem to have a significant detrimental effect on survival. The study suggests that hepatic tumor response to arterial administration of CDDP and FUDR and mitomycin C and FUDR is clinically significant because it overrides the effect of tumor burden on survival among patients who have colorectal cancer with liver metastases and may offer effective palliation.

Hepatic hyperthermia by total isolation and regional perfusion in vivo

Abstract A pump-oxygenator and isolation-perfusion circuit were used to selectively elevate hepatic temperature in 33 dogs to either 37, 41, or 43°C. Temperatures were maintained for 10–30 min. Survival was 75% in 8 dogs after 37°C × 30 min, 40% in 10 dogs after 41°C × 30 min (not significant), 40% in 5 dogs after 43°C × 10 min (not significant), and 0% in 10 dogs after 43°C × 30 min ( P ⩽ 0.01). Animals subjected to 43°C × 30 min hepatic perfusion exhibited an increase in fatal intraoperative arrhythmias despite maintenance of relatively normal blood pressure, systemic temperature, blood gases, and electrolytes. Six animals (2 after 43°C × 10-min perfusion, 4 after 43°C × 30-min perfusion) developed a postoperative symptom complex of progressive obtundation, fever, oliguria, hypotension, and death. Blood cultures were negative. Laboratory values in some animals suggested hepatic necrosis and early hepatic and renal failure but did not completely explain the clinical picture observed. The most striking finding in hyperthermically perfused animals was a diffuse hepatocyte vacuolopathy which on serial liver biopsies in surviving animals progressed to ballooning degeneration then complete resolution. This study demonstrates that temperatures suitable for thermotherapy of hepatic malignancies have hepatotoxic effects which are both temperature and time dependent. Present studies attempt to modulate the toxicity of hepatic hyperthermia by use of perfusate additives.

Proton NMR examination of tumor cells of high or low metastatic potential.

Three rat 13762NF mammary adenocarcinoma clones and cell lines of different metastatic potentials (MTLn3, MTC, and MTPa) were studied for their proton nuclear magnetic resonance spectral characteristics as intact cells in vitro and after chloroform/methanol, neuraminidase, or ethanol treatments. The intact-cell spectral characteristics of the highly metastatic tumor cell clone MTLn3 were clearly distinguished from the less metastatic clone MTC or the parental MTPa cell line on the basis of spectral peaks in the range of 0·9 to 1·45 p.p.m. broad peaks near 2·0 p.p.m., and peaks in the range of 2·75 to 3·2 p.p.m. Glycoproteins are among the molecules known to have resonances in these upfield spectral regions, and these tumor cell subpopulations have previously been shown to possess characteristic quantitative differences in cell surface, metastasis-associated glycoproteins. Treatment of the cells with neuraminidase or ethanol, or extraction with chloroform/methanol increased spectral detail and also revealed characteristic differences in spectral peaks between the tumor cell subpopulations. The identity of the cellular components responsible for these spectral characteristics are unknown, but some clearly arise from differences in the extractable lipids present in the tumor cell subpopulations. Further study will be required to determine if the spectral differences described in this preliminary report are directly related to the known biochemical characteristics of the highly metastatic clone, and if the observations have general relevance to metastatic potential or are a singular feature of these cells. However, these initial results suggest that manipulation of factors which allow unmasking of spectral detail combined with the use of prescribed tumor cell subpopulations may aid in using proton NMR to identify and define biochemical or structural differences related to the metastatic potential of tumor cells.