Palpable breast cancers are inherently different from nonpalpable breast cancers.

BACKGROUND: We examined the clinicopathologic profile of T1 cancers to determine whether palpable cancers are different from nonpalpable cancers. METHODS: A prospective database was reviewed. Palpable T1 cancers were compared with nonpalpable T1 cancers. Initial significance was determined by chi2 analysis. Factors found to be significant were then reanalyzed. controlling for tumor size by logistic or linear regression, as appropriate. RESULTS: Of 1263 T1 cancers treated between 1981 and 2000, 857 (68%) were palpable and 401 (32%) were nonpalpable. Palpability correlated with pathologic tumor size, mitotic grade, nuclear grade, high S-phase, lymphovascular invasion, nodal positivity, and lack of extensive intraductal component, multifocality, and multicentricity. There was no significant difference in estrogen receptor, progesterone receptor or Her-2/neu status, ploidy, or DNA index. Breast cancer-specific survival was worse for patients with palpable cancers. CONCLUSIONS: Palpable cancers are inherently different from nonpalpable cancers, with a less diffuse growth pattern, higher metastatic potential, higher proliferative activity, more nuclear abnormalities, and a worse prognosis.

Phase I and pharmacologic study of i.v. hydroxyurea infusion given with i.p. 5-fluoro-2'-deoxyuridine and leucovorin.

Preclinical data suggests that the action of fluoropyrimidines may be enhanced by the addition of hydroxyurea. We developed a phase I trial to determine the maximum tolerated dose and pharmacokinetics of i.v. hydroxyurea (HU) in combination with i.p. 5-fluoro-2'-deoxyuridine (FUdR) and leucovorin (LV). Eligible patients had metastatic carcinoma confined mostly to the peritoneal cavity, and adequate hepatic, renal and bone marrow function. Patients were treated with a fixed dose of FUdR (3 g) and LV (640 mg) administered on days 1--3. HU was administered as a 72-h infusion starting simultaneously with i.p. therapy on day 1. The following dose levels were studied: 2.0, 2.5, 3.0 and 3.6 g/m(2)/day. Pharmacokinetics were studied in blood and peritoneal fluid. Twenty-eight patients were accrued. Steady-state plasma and peritoneal fluid HU levels increased with increasing dose, and steady state was achieved within 12 h of continuous dosing. The steady-state HU plasma:peritoneal fluid concentration ratio ranged from 1.06 x 10(3) to 1.25 x 10(3) and the plasma HU clearance ranged from 4.63 to 5.81 l/h/m(2). Peritoneal fluid AUC = 137,639 +/- 43,914 microg/ml x min, t(1/2) = 100.9 +/- 56.4 min and Cl = 25.29 +/- 10.88 ml/min. Neutropenia represented the dose-limiting toxicity. We conclude that i.p. FUdR and LV in combination with i.v. HU is well tolerated. The addition of systemic HU increased the incidence of myelosuppression.

Non-inflatable sterile sheath for introduction of the flexible nasopharyngolaryngoscope.

Since the inception of the flexible nasopharyngolaryngoscope, sterility has been a primary concern. The increased incidence of hepatitis, tuberculosis, and acquired immunodeficiency syndrome has raised the fear of cross-contamination. Sterilization requires the use of ethylene oxide, which is economically disadvantageous, forcing most practitioners to disinfect rather than sterilize their nasopharyngolaryngoscopes. A presterilized, disposable sheath was designed in 1993. The system was cumbersome, because it required an air pump. Thus, it was not adopted by the majority of physicians. As a result, the manufacturer developed a new system, which I evaluated. It is cost-effective, smoother-surfaced, 70% thinner-walled, and much simpler to use. The disposable, single-use sheath is sterile, with no need for a pump or any additional device, and can be used anywhere at any time. I believe it will become the standard method for sterile introduction of the nasopharyngolaryngoscope.

Breast cancer after augmentation mammoplasty.

BACKGROUND: It is thought that implants interfere with breast cancer diagnosis and that cancers in women who have had breast augmentation carry a worse prognosis. METHODS: A prospective breast cancer database was reviewed, comparing augmented and nonaugmented patients for details of histology, palpability, tumor size, nodal status, mammographic status, receptor status, nuclear grade, stage, and outcome. RESULTS: Ninety-nine cancers in augmented women and 2857 cancers in nonaugmented women were identified. Among these women, mammography was normal in 43% of those who had had augmentation and in 5% of those who had not. Augmented women were more likely to have palpable cancers (83% vs. 59%) and nodal involvement (48% vs. 36%), and less likely to have ductal carcinoma in situ (DCIS) (18% vs. 28%). When comparing only women younger than 50, the differences in invasiveness and nodal status lost significance. Cancers diagnosed in the 1990s were more likely to be nonpalpable and noninvasive than those diagnosed in the 1980s. This trend was more pronounced in the augmented population. CONCLUSIONS: Augmented patients were more likely to have palpable cancers, although the overall stage and outcome were similar to those of nonaugmented women. Although there have been significant improvements in our ability to diagnose early breast cancer over the past two decades, mammography continues to be suboptimal in augmented women.

Preoperative paclitaxel and radiotherapy for locally advanced breast cancer: surgical aspects.

INTRODUCTION: Approximately 15% of breast cancer patients present with large tumors that involve the skin, the chest wall, or the regional lymph nodes. Multimodality therapy is required, to provide the best chance for long-term survival. We have developed a regimen of paclitaxel, with concomitant radiation, as a primary therapy in patients with locally advanced breast cancer. METHODS: Eligible patients had locally advanced breast cancer (stage IIB or III). After obtaining informed consent, patients received paclitaxel (30 mg/m2 during 1 hour) twice per week for 8 weeks and radiotherapy to 45 Gy (25 fractions, at 180 cGy/fraction, to the breast and regional nodes). Patients then underwent modified radical mastectomy followed by postoperative polychemotherapy. RESULTS: Twenty-nine patients were enrolled. Of these, 28 were assessable for clinical response and toxicity, and 27 were assessable for pathological response. Objective clinical response was achieved in 89%. At the time of surgery, 33% had no or minimal microscopic residual disease. Chemoradiation-related acute toxicity was limited; however, surgical complications occurred in 41% of patients. CONCLUSIONS: Preoperative paclitaxel with radiotherapy is well tolerated and provides significant pathological response, in up to 33% of patients with locally advanced breast cancer, but with a significant postoperative morbidity rate.

ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy.

PURPOSE: We have previously shown that relative thymidylate synthase (TS) mRNA levels in primary gastric adenocarcinomas treated with fluorouracil (5-FU) and cisplatin are inversely associated with response and survival. This is a presumed function of TS as a target for 5-FU activity. We now test the hypotheses that the relative mRNA level of the excision repair cross-complementing (ERCC1) gene is inversely associated with response and survival as an independent function of cisplatin efficacy. PATIENTS AND METHODS: Patients had intact, untreated, primary gastric adenocarcinoma cancer and were evaluated for eligibility on a preoperative cisplatin infusion-5-FU protocol. cDNA, derived from primary gastric tumors before chemotherapy, was used to determine ERCC1 mRNA levels, expressed as the ratio of polymerase chain reaction (PCR) product of the ERCC1 gene and the beta-actin gene. RESULTS: The median ERCC1 mRNA level from 38 primary gastric cancers (33 assessable for response) was 5.8 x 10(-3) (range, 1.8 x 10(-3) to 19.5 x 10(-3)). Of 17 responding patients, 13 (76%) were less than or equal to 5.8 x 10(-3) and four were greater than 5.8 x 10(-3) (P = .003). The median survival for patients with ERCC1 mRNA levels less than or equal to 5.8 x 10(-3) has not been reached, whereas for those greater than 5.8 x 10(-3) it was 5.4 months (P = .034). The median TS mRNA level, 3.7 x 10(-3) (range, 0.9 to 18.9) also segregated responsive versus resistant tumors (P = .024). With both ERCC1 and TS mRNA levels below their medians, 11 of 13 patients (85%) responded; with both ERCC1 and TS mRNA levels above their medians, two of 10 patients (20%) responded (P = .003). CONCLUSION: Considered separately, either ERCC1 or TS mRNA levels in a primary gastric adenocarcinoma has a statistically significant relationship to response. ERCC1 mRNA levels have a statistically significant association with survival; in this cohort TS mRNA levels did not reach statistically significant association with survival as in our previous publication. Whether these molecular parameters are independent of each other as predictors of outcome remains to be determined.

Original p53 status predicts for pathological response in locally advanced breast cancer patients treated preoperatively with continuous infusion 5-fluorouracil and radiation therapy.

PURPOSE/OBJECTIVE: 1) To test feasibility of preoperative continuous infusion (c.i.) 5-Fluorouracil (5-FU) and radiation (RT) in locally advanced breast cancer. 2) To study clinical and pathological response rates of 5-FU and radiation. 3) To attempt preliminary correlations between biological probes and pathological response. METHODS AND MATERIALS: Previously untreated, locally advanced breast cancer patients were eligible: only patients who presented with T3/T4 tumors that could not be resected with primary wound closure were eligible, while inflammatory breast cancer patients were excluded. The protocol consisted of preoperative c.i. infusion 5-FU, 200 mg/m2/day with radiotherapy, 50 Gy at 2 Gy fractions to the breast and regional nodes. At mastectomy, pathological findings were classified based on persistence of invasive cancer: pathological complete response (pCR) = no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of microscopic foci of invasive cells in either the breast or nodal specimens; no pathological response (pNR) = pathological persistence of tumor. For each patient pretreatment breast cancer biopsies were analyzed by immunohistochemistry for nuclear grade, ER/PR hormonal receptors, her2/neu and p53 overexpression. RESULTS: Thirty-five women have completed the protocol and are available for analysis. 5-FU was interrupted during radiation in 10 of 35 patients because of oral mucositis in 8 patients, cellulitis in 1, and patient choice in another. Objective clinical response rate before mastectomy was 71% (25 of 35 patients): 4 CR, 21 PR. However, in all 35 patients tumor response was sufficient to make them resectable with primary wound closure. Accordingly, all patients underwent modified radical mastectomy: primary wound closure was achieved in all patients. At mastectomy there were 7 pCR (20%), 5 pPR (14%) and the remaining 23 patients (66%) had pathological persistence of cancer (pNR). Variables analyzed as potential predictors for pathological response (pPR and pCR) were: initial TNM clinical stage, clinical response, nuclear grade, hormonal receptor status, p53 overexpression, and Her2/neu overexpression in the pretreatment tumor biopsy. Only initial p53 status (lack of overexpression at immunohistochemistry) significantly correlated with achievement of a pathological response to this regimen (p = 0.010). CONCLUSION: The combination of c.i. 5-FU and radiation was well tolerated and generated objective clinical responses in 71% of the patients. With the limitation of the small sample size, the complete pathological response achieved (20%) compares favorably with that reported in other series of neoadjuvant therapy for similar stage breast cancer. These preliminary data suggest that initial p53 status predicts for pathological response (pPR and pCR) to the combination of c.i. 5-FU and radiotherapy in locally advanced breast cancer.

Preoperative 5-fluorouracil and radiation therapy for locally advanced breast cancer.

BACKGROUND: Fifteen percent of breast cancer patients present with large tumors involving skin or chest wall. Often, surgery with primary wound closure is impossible. We used neoadjuvant chemoradiation in locally advanced breast cancer patients, in hopes of increasing resectability. METHODS: Eligible patients had locally advanced breast cancer deemed unresectable with primary wound closure. Patients received 8 weeks of infusional 5-fluorouracil (5-FU) 200 mg/m2 per day and radiation therapy to 50 Gy. Patients rendered resectable underwent modified radical mastectomy (MRM) followed up by chemotherapy. RESULTS: Of 30 evaluable patients, 73% had an objective clinical response. All were able to undergo MRM with primary wound closure; 63% had residual disease, 20% had minimal microscopic disease, and 17% had complete pathologic response. Treatment-related toxicity was minimal. Surgical morbidity was not increased. CONCLUSIONS: Infusional 5-FU with concomitant radiotherapy is well tolerated and effective at producing shrinkage in the majority of patients, converting inoperable breast cancer to easily resectable disease.

Systemic chemotherapy for gastric carcinoma followed by postoperative intraperitoneal therapy: a final report.

BACKGROUND: Because only approximately 50% of gastric carcinomas are resectable for cure, the authors hypothesized that effective systemic preoperative (neoadjuvant) chemotherapy, aimed at decreasing the size and extent of the primary tumor and eradicating distant microscopic disease, may increase the rate of resectability and have a greater impact on survival than postoperative (adjuvant) treatment alone. In addition, because the peritoneal cavity is the most common site of first recurrence after successful gastric cancer resection, intraperitoneal (IP) chemotherapy seemed a logical choice for postoperative (adjuvant) treatment. METHODS: Fifty-nine patients with invasive primary gastric adenocarcinoma who were deemed resectable for cure entered a clinical trial that called for 2 cycles of protracted infusion 5-fluorouracil with weekly leucovorin and cisplatin chemotherapy followed by surgery. Approximately 3-4 weeks after potentially curative surgery, patients were scheduled to receive two cycles of IP 5-fluoro-2'deoxyuridine and cisplatin. RESULTS: Of the 59 patients studied, 58 (98%) received both cycles of systemic chemotherapy. Fifty-six patients (95%) underwent surgery: 40 patients (71%) had resections intended to cure for Stage 0-IIIB disease, 15 patients (27%) had palliative surgery for Stage IV gastric carcinoma, and one patient died intraoperatively without being staged. Two patients refused surgery, and the remaining patient died of progressive disease prior to surgery. Thirty-one of the 40 patients who underwent curative surgery completed both cycles of postoperative IP therapy; 4 patients received only 1 cycle. Three patients (5%) died secondary to treatment complications. There were two operative deaths, and one patient died of peritonitis associated with Grade 4 granulocytopenia. Nine of the 40 patients (23%) whose carcinomas were resected for cure had recurrent carcinoma. With a median follow-up period now exceeding 45 months, the calculated median survival for the 59 patients entered into the trial is >4 years. CONCLUSIONS: This program of preoperative systemic and postoperative IP chemotherapy has been found to be safe and appears to decrease gastric carcinoma recurrence rates and increase survival compared with historic controls.

Thymidylate synthase mRNA level in adenocarcinoma of the stomach: a predictor for primary tumor response and overall survival.

PURPOSE: We tested the hypothesis that polymerase chain reaction (PCR) quantitation of the enzyme thymidylate synthase (TS) within a primary adenocarcinoma of the stomach, has an inverse relationship to response and survival for patients who receive fluorouracil (5FU)-based chemotherapy. PATIENTS AND METHODS: Before systemic chemotherapy, the genetic expression of TS (TSmRNA level) was determined using a PCR method. Gene expression was calculated by determining the ratio between the amount of radiolabeled PCR product with the linear amplification range of the TS gene and the beta-actin gene. Chemotherapy consisted of two cycles of protracted infusion (PI) 5FU 200 mg/m2/d administered for 3 weeks with leucovorin 20 mg/m2/w. Cisplatin 100 mg/m2 was administered on day 1. RESULTS: Sixty-five patients with primary gastric cancer had a median TS mRNA level of 4.6 x 10(-3) (range, 0.9 to 20.1 x 10(-3)). Thirty-five percent of patients had measurable responses in their primary tumors. The mean gastric cancer TSmRNA level in responding and resistant patients is statistically significant (P < .001). The median survival time was 43+ months for treated patients with TSmRNA levels less than the median and 6 months for those with TS m-RNA levels greater than the median (P = .003). CONCLUSION: The genetic expression of TS (TSmRNA level) influences response to 5FU-based chemotherapy and survival for a cohort of patients with primary gastric cancer. Confirmation of these data could lead to therapeutic decisions based on specific molecular properties within a tumor.

Bowel obstruction in cancer patients.

OBJECTIVE: To examine the efficacy of various interventions on bowel obstruction occurring in patients with a history of cancer. DESIGN: Retrospective case series. SETTING: A university comprehensive cancer center. PATIENTS: Sixty-one patients presenting with 81 episodes of intestinal obstruction. RESULTS: Sixty-nine episodes of obstruction affected the small bowel, including 24 complete obstructions. There were 12 episodes of large-bowel obstruction, eight of which were complete. Five patients (8.2%) had concurrent small- and large-bowel obstruction. In 59 cases, the cause was established: 36 (61%) were due to metastatic tumor and 23 (39%) were due to benign conditions. Of the 49 episodes of partial bowel obstruction, 42 (86%) initially were treated medically. Nineteen (45%) of these 42 cases of obstruction resolved after 8.7 +/- 11.1 days (mean +/- SD) of conservative management. Twenty-two patients with partial obstruction were treated surgically, with relief of obstruction in 15 cases (68%). Of the 32 episodes of complete obstruction, 26 (81%) were initially managed conservatively; in only one case (3.8%) did obstruction resolve. Surgery successfully relieved the obstruction in 16 (76%) of 21 patients. Twenty-six patients received parenteral nutrition at home as the major treatment for obstruction; 22 (85%) experienced relief of nausea and vomiting. Patients with malignant obstructions survived 0 to 24 months (median, 4.7 months); the median survival for those treated surgically was 5.0 months. CONCLUSIONS: In patients with a history of cancer, partial obstruction (but not complete obstruction) frequently resolves with medical management. Surgical intervention relieves most cases of partial or complete obstruction regardless of benign or malignant cause, but survival often is limited in the latter group. The entire intestinal tract should be evaluated in all patients, since 8.2% of patients in this series had concurrent small- and large-bowel obstructions. Home parenteral nutrition often provides symptomatic palliation in patients not amenable to surgical relief.

Quantitation of intratumoral thymidylate synthase expression predicts for resistance to protracted infusion of 5-fluorouracil and weekly leucovorin in disseminated colorectal cancers: preliminary report from an ongoing trial.

A clinical trial for patients with measurable, disseminated colorectal cancer is being conducted to determine: (1) if intratumoral expression of thymidylate synthase (TS) affects response to protracted-infusion 5-fluorouracil (5FU); and (2) whether intratumoral expression of TS increases when clinical resistance is found after response to 5-FU. Polymerase chain reaction technology is employed to determine TS expression. Using beta-actin as an internal standard, TS expressions for 26 patients range from 0.5 x 10(-3) to 22.6 x 10(-3). Currently, 22 patients are evaluable for response and TS quantitation of their measurable tumour. 8 patients (36%) have had partial responses; 3 responding patients had been previously treated with 5-FU. A strong statistical association between TS expression and resistance to therapy has been found (P = 0.004). No patient with TS expression of 4.0 x 10(-3) or greater has responded. On average, patients previously treated with 5-FU have slightly higher levels of TS expression in their measurable tumours (P = 0.4). Whether responding patients will develop increased expressions of TS upon clinical progression of their cancer remains to be determined. Confirmation of these results in a larger cohort could lead to a scientific rationale for deciding upon specific therapy for patients with disseminated colorectal cancers.

Left atrial metastasis from hepatocellular carcinoma: a case report.

This is the second reported case of a patient with hepatocellular carcinoma in whom the presence of a solitary, left atrial metastatic tumor was confirmed with the aid of transesophageal echocardiography. The tumor was discovered during computed tomography scanning at a follow-up examination after a 3-month regimen of chemotherapy. The patient had exhibited no signs of cardiac involvement, which may have been the result of the relatively small size of the tumor. Surgical excision of the tumor was successfully undertaken, and the patient's postoperative course was uneventful. In this case, transesophageal echocardiography was valuable in providing information regarding the exact location of the tumor and its relation to surrounding anatomical structures.

Comparative study of infectious complications of different types of chronic central venous access devices.

BACKGROUND: Various devices for central venous access are widely used in patients with cancer. The authors studied the incidence of infectious complications affecting these different devices. METHODS: A retrospective study of 111 central venous access devices (VAD) placed in 1992 was conducted. RESULTS: Subcutaneous ports were placed in 42 patients, single lumen Groshong catheters in 45, single lumen Hickman catheters in 15, double lumen Hickman catheters in 5, and double lumen Groshong catheters in 4. Prognostic factors analysis was performed with the log rank test and Cox's multivariate analysis. Different VAD types were compared with the likelihood ratio test. There was no significant difference in the risk of VAD-related infection between Hickman and Groshong catheters. Double lumen catheters were slightly more likely to cause infectious complications than single lumen catheters, although the difference was not statistically significant (P = 0.072 and 0.083 for bacteremia and site infection, respectively). No significant difference was observed in the risk of infection between subcutaneous ports and external catheters. Multivariate analysis using Cox's proportional hazards model demonstrated age younger than 50 years as the only significant risk factor, thus younger patients should be monitored more closely. CONCLUSIONS: No significant difference was observed in the risk of infection between subcutaneous ports and external catheters. There was a slightly higher risk of infection in double lumen catheters than single lumen catheters, although the difference did not reach statistical significance. Considering the small sample size, the results should be confirmed in larger prospective studies.