Heung-Tat Ng

High cyclooxygenase-2 expression in cervical adenocarcinomas

OBJECTIVEnThe purpose of this study was to examine the relationships between cyclooxygenase-2 (COX-2) expression and prognostic factors in cervical carcinomas.nnnMETHODSnWe studied COX-2 expression in 53 women with cervical cancers, including 35 squamous cell carcinomas (SCCs), 1 adenosquamous cell carcinoma (ASCC), and 17 adenocarcinomas (ACs), using commercially available polyclonal antibodies on Formalin-fixed, paraffin-embedded tissues. Normal cervical tissues were obtained as from other patients with uterine myomas treated with a total hysterectomy (n = 16). The immunoreactivity was quantified using an immunohistochemical scoring system that approximates the use of an image analysis-based system.nnnRESULTSnTwenty-two cervical cancer tissues (41.5%), including 10 SCCs and 12 ACs, expressed COX-2 at a moderate to strong level, which significantly, differed from the negligible expression found in the control group of 16 normal cervical tissues (P = 0.001). Different cell types showed significantly different expression levels of COX-2 (SCC at 28.6% vs AC at 70.6%, P = 0.004). The presence of deep stromal invasion (n = 40) showed a significant inverse relationship to COX-2 expression (32.5% vs 69.2%, P = 0.02). The expression of COX-2 in well-differentiated carcinomas was significantly increased compared to that in moderately and poorly differentiated carcinomas (72.7% vs 33.3%, respectively, P = 0.018).nnnCONCLUSIONSnOverexpression of COX-2 was found in both SCC and AC, but SCCs showed infrequent and low expression. These findings suggest that increased COX-2 expression may play an important role in cervical adenocarcinomas.

Trisomy 12 in benign fibroma and granulosa cell tumor of the ovary

Chromosome studies were performed on two benign ovarian fibromas and one ovarian granulosa cell tumor. Trisomy 12 was found in all three cases, and additional abnormalities, monosomy 22 and the translocation t(3;9;21), were also observed in the granulosa cell tumor.

The outcome of the patients with recurrent cervical carcinoma in terms of lymph node metastasis and treatment

Of the 908 patients who underwent radical hysterectomy and pelvic lymphadenectomy for invasive cervical cancer from 1973 to 1983, 139 (or 15.30%) had recurrences. The recurrent rate in the 175 patients with positive pelvic lymph nodes was 32.6%, compared with a 11.2% in the 733 patients with negative nodes (P less than 0.001). This suggests that cervical cancer patients with negative nodes acquire better prognosis after surgical treatments. Not only is recurrence much less frequent in patients with negative nodes, but also the outcome of treatments is significantly in favor of such patients: (A) 51 recurrent patients refused further treatments owing to personal reasons. None survived over 3 years; (B) The survival rate is far higher for treated patients formerly with negative nodes. Sixty of the 82 patients achieved a 5-year survival of 17.74% compared with a 2-year survival of 21.64% only in 28 patients with positive nodes. This suggests that our treatments on patients with recurrent cervical cancer are more effective when the patients have previously had negative nodes, and that refusal of treatment results in quick death.

Is more radical more effective

Chen et al have published an interesting article entitled Is conization once following by simple hysterectomy sufficient for all clinical stage IA1 cervical squamous cell carcinoma? [1]. The authors found that only 4.2% of simple hysterectomies (SH; 2/48) needed postoperative adjuvant radiation [1]. Based on our understanding, only two patients had an upstaged pathological diagnosis (>T1a1 squamous cell carcinoma), and were given a so-called inadequate treatment, so they needed adjuvant therapy. By contrast, >95% of much more extensive surgeries (for example, modified radical hysterectomy) could be avoided for these patients, although the accurate percentage might be only 89.7%, since 68 patients had at least one risk factor in the cone specimens. We congratulate Chen et al for the success of their work. However, since this study challenged an old conceptdthe more radical, the more effectivedsome issues need to be discussed. First, how many patients or what percentage of patients who are given so-called inadequate treatment should we accept? It is not easy to respond to this question. For example, the cut-off value of the maternal serum Downs screening test is 1/270 [2,3], and laparoscopic cystectomy of ovarian mature teratoma is considered as a treatment of choice, based on the low incidence of malignant transformationdrepresenting <0.5% [4]. Now, in Chen et al’s report, it is 4.2%, which is nearly 5% by self-reporting, but 10.3% by accurate reporting if these 68 patients were all treated with SH. Is this acceptable? In addition, if the cases of reconization were added into the data pool for analysis, the percentage of upgraded cases might be as high as 23.8% (19/80). It is questionable whether physicians can accept the conclusion reached by the authors, that extra-fascial SH may be recommended for all clinical T1a1 cervical squamous cell carcinomas, regardless of the pathologic risk factors [1]. Second, the risk of lymph node metastases should be considered, since nearly 3% and 15% of the FIGO stage IA2 and IB cases showed metastases of the pelvic lymph nodes, suggesting that the authors failed to discuss an important issuedthe necessity of lymphadenectomy [5,6]. That is another limitation of this article, which focused only on types of hysterectomy in the management of microinvasive squamous cell carcinoma on cone specimens. Finally, the type of rescue therapy for inadequate surgery to deal with squamous cell carcinoma of the cervix could be

Teamwork is needed for better care

In a recent issue of the Taiwanese Journal of Obstetrics and Gynecology, an interesting article by Hsu et al entitled A surgeon’s help with the management of bowel problems related to gynecology is truly neededdcomparison of two periods of 24 years, concluded that gynecological problems frequently involve the colon or rectum, and that cervical cancer-related problems are still the most common type requiring a colorectal surgeon [1]. There is no doubt that with advanced techniques, anesthesia, antibiotics, and medical care, especially postoperative care, many extensive and radical surgeries can be completed in the treatment of many kinds of surgical illnesses, especially for cancer patients [2,3]. For example, in the management of epithelial ovarian cancer, muchmore extensive andactive surgerymight be a crucial step for partial improvement of survival in epithelial ovarian cancer patients, since optimal debulking surgery, including diaphragmatic surgery, and possible bowel resection and systematic lymphadenectomy, might improve overall survival in advancedstage patients [4,5]. However, it is unclear whether there are any differences in progression-free survival, quality of life, and morbidity between the standard surgery and ultra-radical/extensive surgery in the management of advanced-stage epithelial ovarian cancer; and, importantly, the cost-effectiveness has not been investigated [6]. In addition, surgery for bowel obstruction in relapse epithelial ovarian cancer is associatedwith highmorbidity andmortality rates, especially in emergency cases, comparedwith other gynecological oncological procedures and, most crucially, optimal debulking did not predict survival or successful palliation from surgery for bowel obstruction [7]. In addition, patients with epithelial ovarian cancer who received aggressive care did not have improvement in survival, because short disease remissions and increasing hospitalizations with significant clinical events were found in thesepatients [8]. Theseconflicteddata question the old concept of some surgeons that much more radical surgery, especially through traditional exploratory laparotomy, is the cornerstone of successful treatment [9]. Based on the above, we completely agree with Dr Hsu’s comment that “a surgeon’s help with the management of bowel problems related to gynecology is truly needed.” However, we should emphasize that the patients will obtain the best benefits and best-quality patient care from a well-trained and cooperative team of specialists, including medical care, anesthesia, rehabilitation, and nutritional and psychological support. As

Uterine sarcoma part III—Targeted therapy: The Taiwan Association of Gynecology (TAG) systematic review

Uterine sarcoma is a very aggressive and highly lethal disease. Even after a comprehensive staging surgery or en block cytoreduction surgery followed by multimodality therapy (often chemotherapy and/or radiation therapy), many patients relapse or present with distant metastases, and finally die of diseases. The worst outcome of uterine sarcomas is partly because of their rarity, unknown etiology, and highly divergent genetic aberration. Uterine sarcomas are often classified into four distinct subtypes, including uterine leiomyosarcoma, low-grade uterine endometrial stromal sarcoma, high-grade uterine endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Currently, evidence from tumor biology found that these tumors showed alternation and/or mutation of genomes and the intracellular signal pathway. In addition, some preclinical studies showed promising results for targeting receptor tyrosine kinase signaling, phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway, various kinds of growth factor pathways, Wnt/beta-catenin signaling pathway, transforming growth factor β/bone morphogenetic protein signal pathway, aurora kinase A, MDM2 proto-oncogene, histone deacetylases, sex hormone receptors, certain types of oncoproteins, and/or loss of tumor suppressor genes. The current review is attempted to summarize the recurrent advance of targeted therapy for uterine sarcomas.

A Clinical Trial of 3 Doses of Transdermal 17β-estradiol for Preventing Postmenopausal Bone Loss: A Preliminary Study

Background: It is well documented that a daily oral dose of 0.625 mg of conjugated equine estrogen or 1‐2 mg of 17β‐estradiol is needed to prevent postmenopausal bone loss. Recent studies have indicated that a lower dose of estrogen may be as effective in maintaining bone mass. The purpose of this study was to evaluate the effects of 3 dosages of transder‐mally administered 17β‐estradiol gel in postmenopausal women stratified by oophorectomy and natural menopause. Methods: One hundred and twenty postmenopausal women were randomly selected to form 4 groups. Three groups of women were treated with a transdermal administration of estradiol gel at a daily dosage of 1.25, 2.5 and 5.0 g (containing 0.75, 1.5, and 3 mg of 17β‐estradiol/day), respectively. The 4th group of women, receiving estriol 2 mg/day p.o., was studied concurrently as a control. Bone mineral density was measured by quantitative computed tomography of the vertebrae from T12 to L3 at baseline, then at 6‐month intervals for 1 year. Results: Women in all groups receiving 17β‐estradiol gel obtained a significant increase in bone mass, with the exception of the 1.25 g/day group, which showed a minimal increment at the 6‐month period, compared with the control group. Comparisons of the increments in bone mass after estrogen therapy for both natural and surgical menopausal subjects found that there was a more prominent response in surgical menopausal women receiving a dosage of 2.5 g/day. Conclusion: Estradiol gel at the dosage of 1.25 g/day, equivalent to 17β‐estradiol 0.75 mg/day, effectively prevented bone loss in postmenopausal women after a 12‐month treatment period. The therapeutic effect of estrodiol gel on bone mass was more prominent in the surgical menopausal groups at the dosage of 2.5 g/day. The atrophic ovaries may therefore play a crucial role in the subsequent decades of postmenopausal women.