John Chumas

The management of pseudomyxoma peritonei

The management of nine patients with pseudomyxoma peritonei was reviewed. Aggressive surgical resection of tumor is the standard of treatment, with many patients requiring multiple laparotomies. Chemotherapy, including the use of cisplatin is not effective. Long‐term nutritional support provides a better quality of survival for select patients.

Uterine papillary serous carcinoma evolves via a p53-driven pathway

Uterine papillary serous carcinoma (UPSC) is a highly aggressive type of endometrial cancer that occurs in the absence of hyperestrogenism and endometrial hyperplasia. Biologically, UPSC belongs to a distinct group of aggressive neoplasms of the extended Müllerian epithelium that are characterized by hypoestrogenism, advanced disease at diagnosis, a serous papillary histotype, and a dismal prognosis. There is mounting evidence that loss of p53 function is critical for the molecular genetic cause of all tumors in this group. To further assess the role of p53 alterations in UPSC, we studied 40 patients using immunohistochemical expression analysis. Thirty-four tumors (85%) showed intense nuclear overexpression of p53, whereas six tumors (15%) were p53 negative. Thirteen p53-positive tumors had multiple samplings from distinct anatomic sites, and all showed complete concordance in p53 staining, suggesting that p53 alterations occur early in UPSC carcinogenesis. p53 positivity was associated with loss of hormone receptors. Thirty-nine cases were concomitantly analyzed for estrogen or progesterone receptor expression. Among those, 31 tumors were p53 positive but hormone receptor negative throughout, in contrast to only two tumors that were diffusely p53 positive and focally hormone receptor positive. Patients whose tumors overexpressed p53 had a statistically significant shorter survival than those whose tumors did not at 24 and 48 months (P = .03). This study represents one of the two largest analyses published to date that confirm the strong association between UPSC and p53 overexpression. Furthermore, we suggest that the concept of UPSC be broadened: UPSC is a p53-driven neoplasm that biologically is a kin to other serous papillary malignancies of the ovaries and peritoneum. This group of tumors bypasses the slow hormone-dependent pathway of tumorigenesis but instead undergoes early p53 alterations that lead to rapid tumor development.

Expression of connexin-43 in human myometrium and leiomyoma

OBJECTIVES The expression of connexin-43 was examined in human leiomyomas and in autologous myometrium. STUDY DESIGN Indirect immunofluorescence was used to detect connexin-43 gap junctions in myometrial and leiomyoma tissues and in primary cultures. Immunoblot and Northern analyses were used to examine the levels of connexin-43 protein and cx43 messenger ribonucleic acid in primary cultures. RESULTS Connexin-43 gap junctions were detected in leiomyoma tissue from nonpregnant premenopausal women but not in autologous myometrial tissue. Connexin-43 gap junctions form spontaneously in primary cultures of myometrium and leiomyoma in the presence of 17 beta-estradiol. Fluorescent dye injection confirmed that the gap junctions were coupled in the primary cells. Connexin-43 protein and messenger ribonucleic acid levels generally were higher in leiomyoma cells compared with those of autologous myometrial cells. Steady-state levels of cx43 messenger ribonucleic acid decreased with addition of medroxyprogesterone acetate to the cultures. CONCLUSIONS Differences in the levels of cx43 expression in leiomyoma and myometrial cells may reflect differences in responses to steroid hormones.

Loss of p53 function in uterine papillary serous carcinoma

In contrast to endometrioid carcinoma, uterine papillary serous carcinoma (UPSC) is an aggressive type of endometrial cancer. Loss of p53 function is critical for the molecular pathogenesis of UPSC. Both UPSC and its putative precursor, endometrial intraepithelial carcinoma (EIC), show abnormal p53 overexpression in most tumors. To further assess the nature of p53 alterations in UPSC, we systematically reevaluated a subset of our previous cohort of UPSC patients. In the current study, we correlate mutations of the p53 gene as detected by direct sequencing of exons 5 through 8 with p53 accumulation and expression of Waf-1 in 32 UPSC tumors. Waf-1 is a downstream effector of p53-mediated G1 arrest after DNA damage and, thus, an indicator of p53 functionality. Although 78% of tumors exhibited strong nuclear p53 immunoreactivity in 100% of tumor cells, we were able to detect p53 mutations in 53%. As expected, all p53 mutant tumors (17 cases) exhibited p53 overexpression. Seventy percent of those (12 tumors) showed concomitant lack of Waf-1 expression consistent with transcriptionally inactive p53, whereas the other five tumors showed Waf-1 staining in only a minor fraction of tumor cells consistent with p53-independent Waf-1 expression. In contrast, 47% (15 cases) of tumors failed to exhibit p53 mutations; interestingly, more than half of those (eight cases) showed strong nuclear p53 accumulation in all tumor cells but lacked concomitant Waf-1 expression. These findings are consistent with a mutation-dependent and -independent type of p53 inactivation in UPSC that are both associated with nuclear overexpression. Our findings suggest that the combined immunocytochemical analysis of p53 and Waf-1 is a valuable means of assessing the functional status of p53. In summary, p53 alterations are common in UPSC and probably responsible for its aggressive biological behavior.

Role of p53 alteration in primary peritoneal carcinoma

SummaryAlthough the clinicopathologic features of primary peritoneal carcinoma (PPC) in women are relatively well defined, the molecular pathogenesis of the disease has not been examined. The object of this study was to assess the biological significance of p53 alterations in PPC. Twenty-nine PPCs studied for p53 protein accumulation with monoclonal antibody DO-7 consisted of 26 serous carcinomas, one clear cell carcinoma, one tumor with endometrioid features, and one malignant mixed müllerian tumor. P53 was overexpressed in 83% of all PPCs and in 81% of the serous PPCs. Among eight immunopositive tumors with at least two distinct anatomic sites sampled, six tumors showed concordance, whereas two tumors showed discordance for p53 immunopositivity. The latter two tumors support the concept of a multifocal origin of PPC. This is the first report to suggest that loss of p53 function plays an important role in the development of PPC and might contribute to the poor prognosis of this disease. Parallels to serous papillary carcinomas of the uterus and ovary are discussed.

Ovarian metastases from stage IB adenocarcinoma of the cervix

At the time carcinoma of the cervix is treated by radical surgery, it is believed that ovarian preservation is possible, and will prevent surgical menopause, with its risks of osteoporosis, vaginal dryness, and “hot flashes.” However, the data originally used to justify ovarian preservation was based on clinical experience with squamous cell carcinoma of the cervix. Little if any data exist to justify this treatment rationale in patients with adenocarcinoma of the cervix. Two patients who presented with clinical Stage IB adenocarcinoma of the cervix, subsequently underwent radical surgical treatment. Pathologic review of the operative specimens revealed microscopic metastasis to the ovaries in both patients. It is suggested that ovarian preservation at the time of radical surgical treatment for adenocarcinoma of the cervix has not had its safety established, and that sacrificing the ovaries and providing hormonal replacement postoperatively may be a safer course.

Herpetiform cutaneous metastases following negative second look laparotomy for ovarian adenocarcinoma

SummaryCutaneous metastases from gynecologic malignancy are rarely reported, and when present are invariably accompanied by intraperitoneal disease. In the present case extensive metastases to the skin of the abdomen, groin, thigh and perineum appeared six weeks following extensive “second look” laparotomy which revealed no evidence of intraperitoneal or retroperitoneal disease. The appearance of cutaneous metastases was preceded by only a one month history of leg swelling, erythema, and a markedly elevated serum CA-125. Problems in the differential diagnosis and management of this clinical situation are discussed.

The clinical significance of thrombocytosis in women presenting with a pelvic mass

Objectives : We attempted to determine the clinical usefulness of a preoperative platelet count for predicting malignancy in patients presenting with a pelvic mass. Additionally, in patients in whom a preoperative serum CA 125 level was also determined, the clinical usefulness was compared. Study design : A retrospective review of charts of 241 patients presenting with a pelvic mass was carried out. The patients were then divided by pathologic diagnosis into group 1, benign disease ( n = 102), and group 2, invasive ( n = 121) or borderline ( n = 78) malignancies. Thrombocytosis (platelet count >400,000/(µl) was present in 16% ( n = 16) of patients in group 1 and in 56% ( n = 78) of patients in group 2 ( p 35 U/ml) occurred in 14% ( n = 8) of group 1 and in 81% ( n = 60) of group 2 ( p 2 test was used to analyze results of data. Results : Statistically significant differences in preoperative platelet count and serum CA 125 values were found between group 1 and group 2 patients. The specificity and positive predictive value for thrombocytosis (84% and 83%) compared well with those for serum CA 125 (86% and 88%). The combined use of the tests resulted in specificity of 96% and positive predictive value of 95%. Conclusions : Preoperative platelet count is a test that is rapidly available and easily obtained. The test results may be of value in planning the original management of women presenting with a pelvic mass.

Laparoscopic gonadectomy for gonadal dysgenesis

Females with a 46,XY karyotype have approximately a 25% chance of developing a malignancy in the dysgenetic gonad. For this reason, it has been recommended that all patients with Y-chromosomal material and dysgenetic gonads undergo exploratory laparotomy and gonadectomy. This report describes laparoscopic adnexectomy in a patient with gonadal dysgenesis

Duodenal trichobezoar caused by compression of the superior mesenteric artery

Trichobezoars can occur in young women who have a history of trichotillomania, trichophagia, gastric dysmotility, and psychiatric dysfunction. A 6-year-old anorexic girl presented with a fixed right-upper-quadrant abdominal mass. Exploratory celiotomy for a duodenal trichobezoar led to removal of the large foreign body, via a duodenotomy, and prompted a Ladd procedure, in which the duodenum was moved from beneath the compressing superior mesenteric artery to relieve underlying duodenal narrowing.