Michael P. Hopkins

Ginseng face cream and unexplained vaginal bleeding

A case of postmenopausal bleeding attributed to the use of topical ginseng is reported. Ginseng appears to have an estrogen-like effect on genital tissues.

Radical hysterectomy versus radiation therapy for stage IB squamous cell cancer of the cervix

Three hundred forty‐five patients with Stage IB squamous cell carcinoma of the cervix were treated at the University of Michigan Medical Center from 1970 to 1985. The overall cumulative 5‐year survival rate was 89% and the mean age was 44.6 years. In 213 patients undergoing radical hysterectomy the cumulative 5‐year survival rate was 92%; 14 patients were explored for radical hysterectomy that was not performed due to high risk features and their survival rate was 50%. Ninetyseven patients underwent radiation therapy as initial treatment and had a 5‐year survival rate of 86%. There was no significant difference when radiation therapy was compared with radical hysterectomy (P = 0.098). The survival rates for lesions 3 cm or smaller were 94% for radical hysterectomy and 88% for radiation therapy. When the lesion was larger than 3 cm, the survival rates were 82% with radical surgery and 73% with radiation therapy. Metastatic disease to lymph nodes was present in 26 of the 213 patients undergoing radical hysterectomy. When 1 to 3 nodes were involved 16 of 19 patients survived and when 4 to 10 nodes were involved 3 of 7 patients survived. The addition of radiation therapy did not influence survival. Complications were similar in both treatment groups. Fistulas occurred in 4 of 213 patients undergoing radical hysterectomy and 1 of 111 undergoing radiation. Second surgery for a complication was required in 6 of 213 patients undergoing radical hysterectomy and 7 of 111 undergoing radiation. Survival and complication rates in early stage squamous cell carcinoma of the cervix are equal with either radical surgery or radiation therapy.

Rapid growth of leiomyoma in patient receiving tamoxifen

A 49-year-old patient with breast cancer had a leiomyoma that rapidly enlarged shortly after she started therapy with tamoxifen. Exploratory laparotomy was necessary to confirm the diagnosis. The rapid growth may have resulted from the estrogen agonist properties of tamoxifen or alternatively by ovarian stimulation resulting in endogenous estrogen production.

Stage IB squamous cell cancer of the cervix: Clinicopathologic features related to survival

Three hundred forty-five patients with stage IB squamous cell carcinoma of the cervix were treated at the University of Michigan Medical Center from 1970 through 1985. The overall cumulative 5-year survival was 89%. The clinical characteristics included mean age 44.6 years, nulliparity 10%, married 93%, obese 38%, hypertension 32%, diabetes mellitus 5%, smoking 54%, symptoms of bleeding 68%, positive cytologic smear 83%. Lymph nodes were diseased in 45 of 261 (17%) with 26 unilateral (10%) and 19 bilateral (7%). Tumor differentiation showed: grade 1, 112 (33%); grade 2, 144 (42%); grade 3, 86 (25%). Factors that did not influence survival included age, presence or absence of positive cervical cytologic smear, the interval from previous papanicolaou smear, hypertension, smoking history, patients blood type, and transfusion at radical hysterectomy. In all patients survival was significantly influenced by the following features: tumor classified as well differentiated (95%) or poorly differentiated (82%); tumor size less than 3 cm (91%) or greater than 3 cm (76%); negative lymph nodes (93%) or positive lymph nodes (61%). When three or fewer lymph nodes were involved, the survival was 79% compared with 33% when four or more lymph nodes were involved. In 213 patients undergoing radical hysterectomy the cumulative 5-year survival was significantly influenced by the amount of residual cervical disease: no residual disease, 100%; less than 50% penetration, 96%; greater than 50% penetration, 83%. Involvement of the lower uterine segment reduced survival to 73% compared with 95% when the lower segment was uninvolved. One hundred seventeen patients without angiolymphatic invasion had a 97% cumulative 5-year survival whereas 70 patients without disease in the lymph nodes but with angiolymphatic invasion had an 88% cumulative 5-year survival rate. A Cox model, multiple proportional hazard analysis was performed for all patients, and the factors that influenced survival included tumor grade, tumor size, presence of metastatic disease in the lymph nodes, and diabetes mellitus. In patients undergoing radiation therapy, the tumor grade and size were significant factors in survival. In patients undergoing radical hysterectomy, survival was influenced by the depth of cervical penetration and lower uterine segment involvement whereas the tumor grade, tumor size, patients age, and removal of ovaries were not significant.

Radical vulvectomy. The decision for the incision

Background. An analysis of survival and complications related to the type of radical vulvectomy operation performed is reported.

The Prognosis and Treatment of Stage I Adenocarcinoma of the Cervix

&NA; A review of 125 patients with stage I adenocarcinoma of the cervix is reported. The subtypes included endocervical (60), adenosquamous (38), papillary (15), clear cell (nine), and mucoid (three). The cumulative 5‐year survival was 60%, and was significantly related to the following: tumor differentiation—well‐differentiated 80%, moderately differentiated 69%, poorly differentiated 41%; lymph node status—nodes positive 28%, nodes negative 82%; the amount of residual disease present in the cervix after radical hysterectomy; and the interval from the previous pelvic examination. Survival was not significantly influenced by histologic subtype, patient age, number of positive lymph nodes, or tumor size beyond 3 cm. Treatment included radical hysterectomy with or without bilateral salpingo‐oophorectomy, radiation therapy, radiation therapy with hysterectomy, and hysterectomy followed by radiation therapy. The best cumulative 5‐year survival (93%) was found in patients treated by radical hysterectomy without bilateral salpingo‐oophorectomy, whereas the poorest survival (18%) was in those treated by standard hysterectomy followed by radiation therapy. Ovarian conservation seems to be an acceptable alternative to bilateral salpingo‐oophorectomy in the young patient undergoing radical hysterectomy.

Clinicopathologic features of ovarian mixed mesodermal tumors and carcinosarcomas

Over a 27-year period there were 15 patients treated at the University of Michigan Medical center for carcinosarcomas or mixed mesodermal tumors of the ovary. Overall median survival was 11 months. Median survival was 4 months in patients with carcinosarcomas and 13 months in patients with mixed mesodermal tumors (P = 0.066). Patients with a chondrosarcomatous element had a significantly longer median survival than patients with mixed mesodermal tumors lacking cartilaginous differentiation (P = 0.031). The presence of a rhabdomyosarcomatous element did not affect survival. The size of the primary tumor, presence of ascites, FIGO stage, and degree of initial resection (optimal versus suboptimal) did not affect survival. There was no difference in survival between patients receiving postoperative chemotherapy and patients undergoing postoperative irradiation.

Squamous cell carcinoma of the vulva: Prognostic factors influencing survival

One hundred seventy-two cases of patients with squamous cell cancer of the vulva treated at the University of Michigan Medical Center from 1975 to 1988 are reported. The mean age was 66 years with a range of 21 to 101 years. The distribution by stage included Stage I, 65; Stage II, 44; Stage III, 50; and Stage IV, 13 patients. Groin node dissections performed on 145 patients showed negative nodes, 58%; unilateral positive nodes, 28%; and bilateral positive nodes, 14%. The distribution of patients with positive nodes was influenced by stage: Stage I, 14%; Stage II, 23%; Stage III, 72%; Stage IV, 92%. The overall cumulative 5-year survival was 71% and this was significantly influenced by stage of disease: Stage I, 94%; Stage II, 91%; Stage III, 36%; Stage IV, 26%. Stages I/II and III/IV were combined for analysis. In Stages I/II, survival was significantly influenced by tumor grade while size, patient age, and lymph node status did not influence survival. In Stage III/IV, survival was significantly influenced by tumor size, node status, and number of positive nodes while grade, patient age, and tumor location did not influence survival. Squamous cell cancer of the vulva is effectively treated with radical surgery but advanced-stage disease with regional metastases significantly alters survival.

Regulation of epidermal growth factor and insulin-like growth factor I receptors by estradiol and progesterone in normal and neoplastic endometrial cell cultures

Growth factors are polypeptides which regulate cell proliferation through binding to specific receptor proteins. Normal and neoplastic human endometrium have been shown to express epidermal growth factor (EGF) and insulin-like growth factor I (IGF-1) receptors. Endometrial cell cultures were used to test modulation of EGF and IGF-1 receptors in response to steroid hormones. Endometrial gland and stroma cells were separated by enzymatic dispersion and were incubated in medium containing estradiol (10, 100, or 1000 pg/ml) or progesterone (1, 10, or 100 ng/ml) followed by radioligand assays. Normal endometrial cultures (n = 6) treated with estradiol demonstrated 40% less EGF binding than control cultures (P less than 0.05), while IGF-1 binding was unaffected. Stromal cells treated identically decreased in only one treatment group. Progesterone treatment stimulated a significant increase in EGF and IGF-1 receptors in gland cultures. Cultures derived from adenocarcinoma (n = 2) demonstrated decreased EGF binding compared with normal endometrium (P less than 0.05). Carcinoma cells treated with progesterone resulted in a dose-dependent increase in EGF binding over control (P less than 0.05). These data illustrate effects of steroid hormones upon growth factor receptors in human endometrium, and suggest involvement of growth factors in the regulation of normal and neoplastic endometrial growth.

Characterization of epidermal growth factor receptor in normal and neoplastic human endometrium

Growth factors, including epidermal growth factor (EGF), have been implicated in the growth of several types of cancer. This study compares EGF receptors in normal and neoplastic endometrium. Membrane fractions were isolated from surgical specimens. Radioreceptor assays demonstrated the presence of receptors with a dissociation constant of 0.64 nmol/1 in normal endometrium. Affinity crosslinking revealed receptor molecular weight of 150 to 170 kiloDaltons (KD). A survey of samples (n = 37) revealed progressive decrease of EGF receptors in cancers of increasing grade: Grade 1–2 adenocarcinoma decreased 34% from control (n = 6, P < 0.01), whereas Grade 3 adenocarcinoma decreased 90% (n = 7, P <0.01) and sarcoma decreased by 72% (n = 3, P < 0.01). The dissociation constant and molecular weight of the receptor in neoplastic endometrium did not differ significantly from normal. The inverse relationship with grade suggests receptor alteration or down regulation by hormones and/or growth factors.