Surgical outcomes after breast cancer surgery: measuring acute lymphedema.

BACKGROUND: Studies of lymphedema have used inconsistent measures and criteria. The purpose of this pilot study was to measure the onset and incidence of acute lymphedema in breast cancer survivors using strict criteria for limb evaluation. MATERIALS AND METHODS: Eligible women were those undergoing breast cancer surgery that included axillary staging and/or radiation therapy of the breast. Arm volume, strength, and flexibility were measured preoperatively and quarterly. Lymphedema was defined as a greater than 10% increase in limb volume. Additional strength and flexibility assessments were done at these times. RESULTS: In 30 evaluable patients, half underwent modified radical mastectomy and half lumpectomy, with half of the lumpectomy patients undergoing axillary node staging. Of the 30 patients 27% were Stage 0; the rest were Stage I (27%), IIA (13%), IIB (23%), and IIIA (7%). One subject was IIIB postoperatively. There were 2 women with a 10% or greater change in limb volume; the change was detected in one woman at 3 months (5% incidence) and in the second woman at 6 months (11% incidence). Both had undergone mastectomy and axillary dissection and one of these two women had symptoms of tingling and numbness in the affected arm that began at 3 months. Overall, 35% of the sample experienced symptoms by 3 months, which included numbness, aching, and tingling of the entire upper extremity, but without volume changes. The relationship between undergoing modified radical mastectomy and experiencing symptoms in the affected limb at 3 months was significant (P = 0.05). CONCLUSIONS: In this interim report strict methods of measurement and limb volume comparisons detected acute lymphedema at 3 months in 5% of the sample, and at 6 months in 11% of the sample. Furthermore, symptoms were detected in 35% without volume changes at 3 months postoperatively, which may warn of lymphedema occurrence within the next 3 months. This may assist clinical evaluation of symptoms in the postoperative period and support early referral to lymphedema experts.

HER-2/neu expression in pancreatic adenocarcinoma: relation to tumor differentiation and survival.

HER-2/neu expression in pancreatic adenocarcinoma has been inconsistently reported and has not been fully evaluated with respect to histologic grade and tumor grade heterogeneity. We studied HER-2/neu expression in a series of 79 primary pancreatic carcinomas using immunohistochemical methods, with expression scored for each histologic grade represented in each tumor. We found significantly lower expression of HER-2/neu in poorly differentiated (PD) portions of tumors-those areas lacking glandular differentiation-compared to well-differentiated (WD) and moderately differentiated (MD) portions of tumors. Forty-two of 68 (62%) invasive tumors with WD or MD glands showed moderate or strong expression of HER-2/neu in WD/MD areas; only 6 of 32 (19%) invasive tumors with PD areas showed similar expression in PD. In mutually exclusive patient sets, we also found a statistically different prevalence of HER-2/neu expression in patients with PD (6/32 cases; 19%) and without PD (29/47 cases; 62%) tumors (p < 0.001). Twenty-three cases had directly comparable areas of PD versus MD or WD. In 19 of 23 cases HER-2/neu expression was graded comparatively lower (or negative) in areas of PD than in MD or WD. Overall 46 of 79 cases (58%) showed moderate to strong HER-2/neu expression inclusive of all histologic grades, and 63 of 79 (80%) cases were HER-2/neu positive, if including weak or focal staining. There was no significant difference in the survival of patients with HER-2/neu-positive versus-negative tumors or in patients with versus without PD tumors. We have confirmed that although HER-2/neu gene expression is common to many pancreatic carcinomas, it is not common to tumors lacking glandular differentiation. HER-2/neu gene expression could not be related to survival differences--perhaps due to overall poor survival within adenocarcinomas of the pancreas--but the pattern of HER-2/neu expression suggests a relationship to glandular differentiation and early oncogenesis.

Antitumor efficacy of interleukin-2 alone and in combination with adriamycin and dacarbazine in murine solid tumor systems.

Recombinant interleukin-2 (IL-2)/chemotherapy combinations have recently entered clinical trial. The rationale for sequencing has primarily been empiric or based on in vitro data. To establish in vivo models for chemoimmunotherapy trials, we investigated IL-2 alone and in combination with dacarbazine (DTIC) and adriamycin. IL-2 (as a single agent given i.v. at 1-3 x 10(5) Cetus units once daily for 5 days, repeated 7-10 days later), was highly active against an immunogenic line of colon adenocarcinoma no. 11/A [tumor growth inhibition (T/C) = 0% with cures]. It was modestly active against colon adenocarcinoma no. 38 (T/C = 39%), mammary adenocarcinoma no. 16/C (T/C = 18%), and B16 melanoma (T/C = 21%). IL-2 was inactive against colon adenocarcinoma no. 7/A (T/C = 83%). Combination trials were done using DTIC and IL-2 against colon no. 7/A and upstaged colon no. 11/A. The combination of adriamycin and IL-2 was tested against mammary adenocarcinoma no. 16/C. In the DTIC/IL-2 combination trials, the combination was superior over either agent used alone. In the IL-2/adriamycin trials, the combination was no better than adriamycin alone at optimum dosages.

Activity of datelliptium acetate (NSC 311152; SR 95156A) against solid tumors of mice.

Datelliptium acetate (NSC 311152) is a water soluble analogue of ellipticine. It is a solid tumor selective compound. In vitro, in a disk diffusion, soft agar colony formation assay (25 micrograms/disk), the compound demonstrated solid tumor selectivity (compared to leukemia L1210) against colon adenocarcinoma 38 and pancreas ductal carcinoma 03. Upon intravenous administration, NSC 311152 was effective in vivo against a variety of murine solid tumors. Responses at maximum tolerated doses were: colon #07/A (T/C = 33%); 0.60 log cell kill), #38 [T/C = 0%; 4.2 log cell kill), colon #51/A (T/C = 2%; 1.2 log cell kill), undifferentiated colon #26/A (T/C = 38%; 0.4 log kill), mammary #16/C (T/C = 10%; 1.7 log cell kill), and pancreatic ductal carcinoma #03 (T/C = 0%; 80% cures through day 38). It was ineffective against pancreas #02 (T/C = 45%), mammary 17/A (T/C = 53%), and 17/A/ADR (T/C = 52%). At efficacious doses acute neurotoxicity (i.e. stupor and lethargy) and weight loss were noted (with rapid recovery from both toxicities). There were no delayed toxicities. The agent was slightly necrotizing and produced pain on SC injections. In lieu of its preclinical efficacy and toxicity profiles, we recommend further clinical investigation of this agent.

Antitumor efficacy of PD115934 (NSC 366140) against solid tumors of mice.

PD115934 (NSC 366140) is a soluble pyrazoloacridine derivative presently undergoing preclinical toxicology evaluation with the anticipation of Phase I human investigation. The agent displayed both human and murine solid tumor selectivity in vitro in a soft agar disk diffusion assay, relative to its activity against murine L1210 leukemia. In vivo it was highly active against solid tumors colon adenocarcinoma 38 and pancreas ductal carcinoma 03, which was consistent with the cellular cytotoxicity seen in the disk diffusion assay. A log cell kill of greater than 4.0 was demonstrated in vivo against both models. PD115934 was administered by both bolus and infusional therapy. After completion of these trials, it was determined that this compound was a schedule category III agent, i.e., a schedule-independent agent with peak plasma level toxicity. The main toxicity encountered with infusional therapy was myelosuppression. With bolus therapy, central nervous system toxicities were dose limiting. On the basis of our preclinical infusion studies, we recommend a 2-h infusion twice weekly in humans in order to obtain a total dose of 360 mg/m2 over 8 weeks.