Biomedical subjects
Publications and source records attributed to S C Rubin.
Chromosome analysis of a well-differentiated adenocarcinoma of the endometrium revealed an abnormal karyotype 48,XX,+i(1q)+10 in all metaphases examined. Abnormalities of chromosomes #1 and #10 may be important in endometrial carcinoma and should be carefully evaluated in cases with more complex karyotypes.
Postmenopausal bleeding can be an alarming symptom for both the patient and the physician because, although in a majority of these cases no pathology is present, the risk of malignancy must be considered. It is important for the physician to fully understand the pathophysiology, differential diagnosis, and the methods of evaluating and treating this disorder in order to ensure the health and comfort of the patient.
Since there is no reliable noninvasive way of establishing status of disease in ovarian cancer patients, second-look laparotomy has become an accepted part of the management of these patients. In women with no clinical evidence of disease who undergo laparotomy, more than half are found to have cancer. The operation is used following a planned program of chemotherapy when the physician is faced with a dilemma: Stop chemo and run the risk of recurrence or continue and increase the risk of toxicity? Second-look laparotomy helps resolve this problem by determining the true status of the disease.
The nomenclature of the lymph node groups draining the pelvic organs has been poorly standardized. This has impaired understanding of the natural history of gynecologic malignancies and led to difficulties in communication among specialists treating those diseases. In order to assess the extent of this problem, members of the Society of Gynecologic Oncologists and other physicians treating pelvic malignancy were asked to label a diagram of the pelvic lymph nodes. The lack of uniformity in the answers confirms the need for a simple, clinically relevant system of nomenclature. Such a system is proposed.
Endometrial curettage often is done as a routine procedure at the time of cervical conization, although the indications for this are unclear. Of 207 consecutive cone biopsies done recently at the Medical College of Pennsylvania, 199 (96%) included endometrial curettage. Two patients exhibited mild endometrial hyperplasia; the rest had no significant abnormality. Three uterine perforations (1.5%) occurred. Routine endometrial curettage is not necessary at the time of conization, and should be limited to patients with specific indications for sampling the endometrium, based on history, physical examination, and the finding of abnormal glandular cells on cytology. It is estimated that the elimination of routine curettage would result in a savings of over $100 per patient.
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The first known case of malignant change occurring in leiomyomatosis peritonealis disseminata is reported. Six months after leiomyomatosis peritonealis disseminata was found at cesarean section, the patient experienced rapid growth of the pelvic tumor and diffuse bony metastases. The most cellular areas of the pelvic lesions and the bony metastases were very similar histologically. No other primary site was identified. Despite combination chemotherapy and hormonal manipulations, the patient experienced a rapidly declining course and died within two years.
Seventy-five cases of primary squamous cell carcinoma of the vagina treated at the University of Pennsylvania are reviewed with long-term follow-up presented. These comprised 2.5% of all female genital malignancies treated during 1958 to 1980 inclusive. Patients treated during that time with non-squamous cell cancers have been excluded. Patients are analyzed with regard to stage, therapy, complications, and survival. Sixty-five percent of patients were stage I or II. Five-year survival for the entire group was 45%. Patients treated with radical surgery other than exenteration did well, with 7 of 8 surviving 5 years. Serious treatment complications were mostly related to radiation therapy and primarily involved the bowel and bladder. Three patients died of complications. Recurrence carried a grave prognosis as 30 of 33 patients with recurrence died of disease. Most recurrences were diagnosed within the first year following treatment. Patients with advanced disease were more likely to have distant recurrences. Although radiation therapy is generally the treatment of choice, radical surgery can yield excellent results when used in carefully selected patients. With meticulous attention to radiation dosage and technique it is hoped that treatment morbidity can be reduced. Optimal treatment of advanced disease may require some form of adjuvant systemic therapy.
From 1960 to 1979 there were a total of 14 patients followed at the University of Pennsylvania with early cervical carcinoma who had histologically documented metastases to the para-aortic nodes and who were treated with extended-field radiotherapy. Thirteen of these patients were stage IB and one was stage IIA. All patients underwent exploratory laparotomy and lymph node dissection, followed by extended-field radiotherapy. Six patients are alive with NED for greater than 5 years; one patient is alive with NED at 3 years. An additional patient is now alive and well almost 3 years from a biopsy documented recurrence treated with chemotherapy, and 6 years from initial diagnosis. Thus 8 of 14 patients have enjoyed a long-term survival. Five patients experienced severe treatment-related morbidity. Two had long-term survival, two died of disease, and one died of radiation complications with NED on autopsy. Each of the six patients that died of disease had recurrences at distant sites. One also had a pelvic recurrence. These patients appear to have a prognosis quite different from that of patients with locally advanced cervical cancer metastatic to the para-aortic nodes and deserve aggressive treatment. The need for adjuvant systemic therapy is stressed.
Using antisera to human beta2-microglobulin and an immunofluorescent technique, beta2-microglobulin was found to be localized along tubular and glomerular basement membranes of renal bipsies studied. Since beta2-microglobulin is a subunit of HLA preparations, it may also serve as an indirect marker for the presence of HLA antigens in these structures.
Ovarian cancer affects over 25,000 women each year in the United States. The performance of appropriate surgery for ovarian cancer is critical in directing further therapies and improving survival. Systematic surgical staging must be performed in patients who appear to have early stage ovarian cancer because a significant proportion of these women have occult metastases. A marked improvement in survival has been demonstrated in patients with bulky disease if all masses larger than 2 cm can be surgically removed. Despite the dramatic effect of surgery on the subsequent course of the disease, recent studies show that only a minority of women with ovarian cancer receive appropriate initial surgery. We review the evidence and rationale for systematic surgical treatment of ovarian cancer.
BACKGROUND: Photodynamic therapy (PDT) combines photosensitizer drug, oxygen, and laser light to kill tumor cells on surfaces. This is the initial report of our phase II trial, designed to evaluate the effectiveness of surgical debulking and PDT in carcinomatosis and sarcomatosis. METHODS: Fifty-six patients were enrolled between April 1997 and January 2000. Patients were given Photofrin (2.5 mg/kg) intravenously 2 days before tumor-debulking surgery. Laser light was delivered to all peritoneal surfaces. Patients were followed with CT scans and laparoscopy to evaluate responses to treatment. RESULTS: Forty-two patients were adequately debulked at surgery; these comprise the treatment group. There were 14 GI malignancies, 12 ovarian cancers and 15 sarcomas. Actuarial median survival was 21 months. Median time to recurrence was 3 months (range, 1-21 months). The most common serious toxicities were anemia (38%), liver function test (LFT) abnormalities (26%), and gastrointestinal toxicities (19%), and one patient died. CONCLUSIONS: Photofrin PDT for carcinomatosis has been successfully administered to 42 patients, with acceptable toxicity. The median survival of 21 months exceeds our expectations; however, the relative contribution of surgical resection versus PDT is unknown. Deficiencies in photosensitizer delivery, tissue oxygenation, or laser light distribution leading to recurrences may be addressed through the future use of new photosensitizers.
The decline in deaths from cervical cancer in the US, as well as the improved survival of women with advanced disease have resulted, according to Dr. Rubin, from widespread application of routine screening with the Pap test, the emergence of gynecologic oncology as a distinct medical subspecialty, and the completion of important clinical trials.