A perspective on physician-assisted dying.

This article discusses legalization of physician-assisted dying. Already much of the public is in favor of it, as are many physicians. Recent court decisions have so highlighted the diversity of thought on this issue that many people question whether there needs to be an absolute right or wrong. Patients who are dying slowly and painfully know that unnecessary suffering is being forced on them by conservative elements in our society. They feel that their desire for relief and for greater dignity and autonomy should receive more respect.

Optical breast lesion localization fiber: preclinical testing of a new device.

Preclinical testing was performed of an optical breast lesion localization fiber to guide surgical excision. The prototype device comprised dual 0.010- inch (0.254-mm)-diameter hooks attached to the tip of a 1,000-microns (0.03937-inch)-diameter optical fiber, which allowed retention in soft tissue after passage through a 17-gauge extra-thin-wall needle. The proximal end of the optical fiber was attached to a 15-mW, 635-nm diode laser, with a thumbscrew connector. The tip of the optical fiber was visible through several centimeters of breast tissue in two human mastectomy specimens, which facilitated determination of the location of the hooks. The optical localization fiber may allow lesions to be approached at surgery by many different paths. Clinical tests are indicated to further evaluate this device.

Conservative surgery and radiation in the treatment of synchronous ipsilateral breast cancers.

BACKGROUND: Conservative surgery (CS) and radiation therapy (RT) as an alternative to mastectomy is controversial in patients with two or more lesions in the same breast. The authors reviewed their experience with CS and RT in the management of patients with synchronous ipsilateral breast cancer (SIBC). METHODS: Of 1060 patients treated with CS and RT at the authors' facilities before December 1988, 13 (1.2%) presented with SIBC. All lesions were identified macroscopically and confirmed microscopically as carcinoma. After excision, patients were treated with radiation to the breast for a median tumor bed dose of 65 Gy, and regional lymphatics were treated as clinically indicated to a median dose of 48 Gy. These cases were retrospectively reviewed. RESULTS: As of February 1992, with a median follow-up of 71 months, the 5-year actuarial survival rate of the 13 patients was 81%. Three of the 13 (23%) had an ipsilateral breast recurrence, resulting in a 72-month actuarial breast recurrence rate of 25%, compared with a rate of 12% in our singular lesion population. Two of these patients remain alive, no evidence of disease at 135 and 93 months after diagnosis. The third patient had chest wall progression and died with metastatic disease at 64 months. Invasive lobular histology and three separate lesions were identified in two of the three patients with subsequent local recurrence. CONCLUSIONS: The local recurrence rate in conservatively treated patients with SIBC is greater than that seen in patients with single lesions, but because of the small sample size, significant conclusions are not possible. Although the data are limited on this subject, these results support consideration of CS and RT as an option in the management of selected patients who favor a breast conservation management approach.

The postoperative incidence of small bowel obstruction following standard, open appendectomy and cholecystectomy: a six-year retrospective cohort study at Yale-New Haven Hospital.

The incidence of postoperative small bowel obstruction (SBO) after standard, open appendectomy and cholecystectomy was calculated during a six-year period at a university medical center hospital, which is the larger of two local, community hospitals. A cohort of 567 patients who underwent either a standard, open appendectomy or cholecystectomy from 1 October 1985 through 30 September 1986 was assembled. Of these patients, 182 (32.1%) were readmitted to the hospital prior to 1 October 1991 and thereby received follow-up. The time-related incidence of readmission to the hospital with a specific diagnosis of SBO as estimated by the Kaplan-Meier method was tabulated. This analysis revealed the following incidence rates of postoperative SBO: 10.7% following appendectomy during 64 months of follow-up (n = 41) and 6.4% following cholecystectomy during 67 months (n = 141). The Kaplan-Meier product-limit incidence of postoperative SBO was significantly different for standard appendectomy versus standard cholecystectomy (Breslow-Cox P value < 0.0277). This implies that the anatomical position and/or the likelihood of perioperative infection associated with open, abdominal surgery plays a significant role in subsequent adhesion formation and development of SBO. These data may be compared to laparoscopic techniques in future studies.

Ten-year follow-up of breast carcinoma in situ in Connecticut.

Statistics from the Connecticut Tumor Registry from 1979 to 1988 were examined, and individual medical records from 1979 to 1983 were also reviewed. Three hundred nineteen medical records were available for review, documenting 220 cases of ductal carcinoma in situ and 102 cases of lobular carcinoma in situ. In 1979, there were 33 new cases of ductal carcinoma in situ reported to the Connecticut Tumor Registry, representing 1.8% of all breast cancers. There has been a yearly increase in ductal carcinoma in situ, with 200 new cases, or 7.4% of all breast cancers, reported in 1988. Forty-eight (22%) of 217 patients with ductal carcinoma in situ had bilateral breast involvement with ductal carcinoma in situ or an invasive breast cancer. Ten (83%) of 12 mastectomy specimens from patients with ductal carcinoma in situ who presented with nipple discharge demonstrated residual tumor, suggesting a more diffuse involvement. Two of the three reported recurrences involved nipple discharge. Thirty-seven (16.8%) of the 220 patients with ductal carcinoma in situ and six (5.9%) of the 102 patients with lobular carcinoma in situ were diagnosed as having another unrelated cancer. Ongoing clinical trials will direct optimum therapy for patients increasingly diagnosed as having ductal carcinoma in situ.

Reversible changes in tumor growth and metastatic behavior induced by immune pressure.

Prolonged exposure to host immunity was studied for its effect on several characteristics of a cloned 3-methylcholanthrene-induced fibrosarcoma. One million cells of a clone 10-O were injected subcutaneously into normal C3H/HeJ mice (clone 10-N) or tumor-immune mice (clone 10-I). After 10 passages in immune mice, 1 X 10(6) cells from 10-I tumor were transferred back into normal mice (clone 10-R). After 5 to 10 additional in vivo passages, clone 10-O, 10-N, 10-I, and 10-R tumors were transplanted into normal mice and observed for tumor growth rate, tumorigenicity, antigen specificity, metastatic potential, and plating efficiency. Clone 10-I after 10 passages in immunized mice grew significantly more slowly than did 10-O or 10-N clones, required more tumor cells to cause 50% tumor incidence in normal mice (tumorigenicity), and completely lost its capacity to metastasize spontaneously or experimentally. The plating efficiency in vitro of 10-I was also less than that of 10-O or 10-N. All these changes reversed after 5 to 10 passages of 10-I clone back into normal mice (10-R). Although immune pressure induced qualitative antigenic changes, as demonstrated by a tumor-rejection assay, and resulted in no cross-reactivity with control tumor clones (antigen specificity), the degree of immune response to its autologous clone in immune mice (immunogenicity) remained constant. These results suggest that several unrelated characteristics of this clone 10 can be phenotypically changed during the same period by immune pressure.

Liver cell adenoma: diagnosis and treatment of a rare hepatic neoplastic process.

Liver adenomatosis is a rare entity in which multiple liver cell adenomas (more than 10) occur in patients with no prior history of steroid use or glycogen storage disease. This report describes a case of liver adenomatosis, distinguishes liver adenomatosis from other benign liver lesions, and discusses the diagnosis and treatment of this disorder.

The effect of immunity on pulmonary metastasis of a methylcholanthrene-induced fibrosarcoma and three of its clones.

A 3-Methylcholanthrene (MC)-induced fibrosarcoma and three of its clones were investigated for their metastatic potential in normal and tumor immune mice. The growth rates of the four tumors in vivo were similar. However, the mean survival times of the tumor-bearing mice were markedly different. Clone 10, the most immunogenic, showed very high metastatic potential and short survival, while clone 27, the least immunogenic, produced few metastases, resulting in much longer survival. Moderate numbers of metastases were produced by highly immunogenic 3-AM (parental tumor), and poorly immunogenic clone 34. Spleen cells from mice bearing highly immunogenic tumors lost their ability to neutralize tumors by day 28 after tumor inoculation, while those from mice bearing poorly immunogenic tumors remained cytotoxic, indicating that highly immunogenic tumors also induced immune suppression in the hosts. Immunization with specific tumors decreased the number of pulmonary metastases by 3 to 35-fold. Immunization with tumors that shared antigens provided protection against metastatic tumors as well as the local tumors. In contrast, immunization with antigenically different tumors gave no protection.

Characterization of high- and low-metastatic clones derived from a methylcholanthrene-induced murine fibrosarcoma.

A methylcholanthrene-induced fibrosarcoma (3AM) and several of its clones were evaluated for pulmonary metastasis, growth rate, and chromosome composition. Heterogeneity was observed in the three parameters, and no correlation was found between growth rate and metastatic potential. Furthermore, three clones (10, 34, and 27) were identified with distinctive, high or low, metastatic potential and marker chromosomes. The marker chromosomes characteristic for each clone were identified in the early passages of the parental 3AM line, indicating the preexistence of the different cell types in the original neoplasm. The three clones were then characterized as to tendency to adhere to vascular endothelium, immunogenicity, and antigenic specificity. Clone 10, with two large metacentric markers (T2, 4 and T10, 15) and the highest metastatic potential (221 foci/lung), expressed the highest endothelial attachment and immunogenicity. Clone 27 was characterized with an extremely low rate of metastasis (nine foci/lung) and a T2, 7 large acrocentric marker, while clone 34 was characterized with a moderate rate of metastasis (107.5 foci/lung) and a T4, 16 acrocentric marker. Antigenically, clone 10 cross-reacted with clones 34 and 27 and 3AM, while clones 27 and 34 cross-reacted with clone 10 and 3AM but not with each other, suggesting that, within the original tumor, there were common tumor antigens shared by some cells but no universal antigen shared by all cells.

Effect of cyclophosphamide on mice bearing methylcholanthrene-induced fibrosarcomas.

Mice bearing large methylcholanthrene-induced fibrosarcomas lost the ability to respond in vitro to mitogen stimulation and to specifically neutralize autologous tumor cells in vivo. This depressed immune capability was due to active suppression, since spleen cells from advanced tumor-bearing mice could suppress the mitogen response of normal spleen cells and could inhibit tumor rejection when adoptively transferred to mice previously immunized against the tumor. Treatment with cyclophosphamide (CY) was found to affect the immune capability of the host, in addition to have a direct effect on the tumor. The number of cells in the lymph nodes and spleen, as well as their response to concanavalin A and lipopolysaccharide (but not phytohemagglutinin), decreased initially but returned to normal by Day 14. Most importantly, when CY was administered one day after tumor inoculation, the treated animals developed the ability to neutralize tumor at the same time as untreated controls but retained this capability as the tumors became advanced. Treatment with a single dose of CY as late as 11 or 20 days after tumor inoculation maintained or restored the tumor-neutralizing capacity of spleen cells. CY appears to alter the antitumor response of the host by inhibiting both cytotoxic and suppressor cells, but the cytotoxic cells recover rapidly, whereas the suppressor cells do not.

Circulating immune complexes in colon cancer patient sera.

Sera from 29 colon cancer patients and 16 elderly normal controls were compared using the Raji radioimmunoassay and the Clq binding assay. By the Raji assay 11 of 29 cancer patients had evidence of circulating complexes, while by the Clq assay only 4 of the 29 patients had complexes. There was no significant difference between the levels of circulating complexes in the patient or control groups. With respect to individual patients the results obtained by the Raji assay did not correlate with those obtained by the Clq binding assay.

Adjuvant immunotherapy of malignant melanoma.

A vaccine made of irradiated Vibrio cholerae neuroaminidase (VCN) treated autochthonous tumor cells plus BCG was utilized in combination with surgery or with chemotherapy for Stage II and Stage III malignant melanoma, respectively. A few patients with Stage I melanoma were treated with surgery and BCG. Most of the studies were carried out on a prospective, randomized protocol. When the results with conventional therapy were compared with the results of conventional therapy plus immunotherapy, no beneficial effects of the immunotherapy were seen. Stratification insured comparability in both immunotherapy and nonimmunotherapy groups. We conclude that VCN treated tumor cells plus BCG, when administered according to the protocol utilized here, offer patients with malignant melanoma no substantial benefit when compared with conventional therapy.