Chan-Chao Changchien

High-dose-rate intracavitary brachytherapy (HDR-IC) in treatment of cervical carcinoma: 5-year results and implication of increased low-grade rectal complication on initiation of an HDR-IC fractionation scheme.

PURPOSE To report the treatment results and rectal/bladder complications of cervical carcinoma radically treated with high-dose-rate intracavitary brachytherapy (HDR-IC). The current policy of using three-fraction scheme was examined. METHODS AND MATERIALS Between November 1987 and August 1990, 173 patients with cervical carcinoma were treated with curative-intent radiation therapy. Whole pelvic irradiation was administered with 10-MV X ray. Dose to the central cervix was 40-44 Gy in 20-22 fractions, following by pelvic wall boost 6-14 Gy in three to seven fractions with central shielding. 60Co sources were used for HDR-IC, and 7.2 Gy was given to Point A for three applications, 1-2 weeks apart. Duration of follow-up was 5-7.8 years. RESULTS Twenty-eight patients (16%) developed central-regional recurrences. Overall 5-year actuarial pelvic control rate was 83%. By stage, 5-year actuarial pelvic control rates were 94%, 87%, and 72% for Stages IB + IIA, IIB + IIIA, and IIIB + IVA, respectively. Thirty-one patients (18%) developed distant metastasis. Overall 5-year actuarial survival rate was 58%. By stage, 5-year actuarial survival rates were 79%, 59%, and 41% for Stages IB + IIA, IIB + IIIA, and IIIB + IVA, respectively. Sixty-six (38%) and 19 patients (11%) developed rectal and bladder complications, respectively. For rectal complication, the overall actuarial rate was 38% at 5 years. By grade, 5-year actuarial rectal complication rates were 24%, 15%, 4%, and 3% for Grades 1-4, respectively. Overall prevalence of rectal complications was 37% and 14% at 2 and 5 years, respectively. Prevalence of low-grade rectal complication (Grades 1 and 2) was dominant at 2 years (30%), but declined to 8% at 5 years. Prevalence of high-grade, severe rectal complication (Grades 3 and 4) remained steady at 2 and 5 years (7% and 6%, respectively). Five-year actuarial bladder complication was 9%. Five-year prevalence of bladder complication was 2%. CONCLUSION Using a three-fraction scheme, survival rate appeared comparable with the existing results of the low-dose-rate technique. The incidence of rectal complication with this scheme remained relatively high. The increased part of rectal complication was predominantly low grade. This result suggested that therapeutic gain with this scheme may not be good enough to circumvent its biologic disadvantage. Numbers of fractions >3 must be considered in future trials.

Multiple uterine angioleiomyomas in a woman presenting with severe menorrhagia

BACKGROUND Angioleiomyoma is a rare benign neoplasm that originates from smooth muscle cells and contains thick-walled vessels. There were only five cases of uterine angioleiomyoma reported in the available English literatures. We present here the unique computed tomography finding in a patient with multiple uterine angioleiomyomas causing severe menorrhagia. CASE A 50-year-old, nulligravid woman consulted us with the complaint of menorrhagia for 3 years and progressively palpable lower abdominal mass for a half year. Laboratory findings were all within normal limits except lower hemoglobin concentration (6.2 g/dl). An abdomino-pelvic computed tomography (CT) showed that a huge 30-cm heterogeneously multilobulate mass with solid and laminated configuration, with cystic and multiseptal contents was found in left lower abdomen and pelvic cavity. At laparotomy, the area beneath the left broad ligament was filled with a well-encapsulated, elastic, ovoid, and lobulate mass that connected to the uterus and measured up to 20 cm in greatest diameter. The uterus was composed of a huge intramural tumor and measured 28 x 21 x 12 cm. The uterus and huge subserosal tumor were resected completely and a frozen section was obtained. The final histopathologic diagnosis was angioleiomyoma, a definitely benign soft tissue tumor. Eighteen months after surgery there was no recurrence. CONCLUSION Uterine angioleiomyoma should be considered when prominent tortuous vascular-like enhancing structures are noted on CT examination of a well-demarcated soft tissue mass arising from the uterus in pelvis. Either angiomyomectomy with tumor-free margins or hysterectomy proved to be an effective treatment in these cases, and resulted in a good recovery and a satisfactory outcome.

Leiomyosarcoma of the uterus: a clinicopathologic study of 21 cases.

Acta Obstet Gynecol Scand 2003; 82: 74–81.

The role of pretreatment squamous cell carcinoma antigen in predicting nodal metastasis in early stage cervical cancer

Purpose. To evaluate whether the presence of pelvic lymph node metastasis can be predicted by pretreatment squamous cell carcinoma antigen (SCC‐Ag) levels in early stage squamous cervical carcinoma.

The role of radical surgery followed by adjuvant therapy for high-risk early-stage cervical carcinoma patients with pelvic lymph node metastasis

OBJECTIVES To identify a subgroup of high-risk node-positive patients in early-stage cervical cancers and to determine the role of radical hysterectomy followed by adjuvant therapy to these patients. STUDY DESIGN We conducted a retrospective review of 482 surgically-treated patients of clinical stage Ib and IIa cervical carcinoma from July 1986 to December 1994 at Kaohsiung Chang Gung Memorial Hospital. Of these, 96 patients had pelvic lymph node metastases. Clinicopathological variables, including the level of pretreatment squamous cell carcinoma antigen (SCC-Ag), DNA flow cytometry analysis, and the use of different adjuvant therapies were studied. RESULTS Disease-free survival was significantly worse among patients with S-phase fraction greater than 20% and pretreatment SCC-Ag level above 5 ng/ml. Utilizing these significant variables, we identified two distinct risk groups. Those patients without any of the risk variables were categorized as the low-risk group. Those patients with either one or both risk variables were categorized as the high-risk group. Five-year disease-free survival rates were 74% in the low-risk group and 43% in the high-risk group, (P=0.034). Disease recurred in 30.2% of the low-risk patients and 45. 3% of the high-risk patients. No survival advantages were found by using different adjuvant therapies. CONCLUSIONS Radical hysterectomy should not be attempted if either the pretreatment SCC-Ag level is above 5 ng/ml or S-phase fraction of the tumor greater than 20% due to its limited value despite applying aggressive postoperative adjuvant therapy.

High immunohistochemical expression of TGF-β1 predicts a poor prognosis in cervical cancer patients who harbor enriched endoglin microvessel density.

Endoglin, a coreceptor for transforming growth factor &bgr;1 (TGF-&bgr;1) in vascular endothelial cells, is highly upregulated in tumor vessels and therefore is a specific biomarker for angiogenesis. Some studies have suggested that assessment of tumor angiogenesis may predict cancer response to chemotherapy and radiotherapy. In this study, we attempted to analyze the immunohistochemical expression of endoglin and TGF-&bgr;1 from 80 patients with different International Federation of Gynecology and Obstetrics (FIGO) stages of cervical cancer before they received concurrent chemoradiation and to investigate their prognostic significance. The median follow-up period was 86 months (range, 2–144 months). Endoglin staining was assessed by microvessel density (MVD), whereas TGF-&bgr;1 expression was semiquantified as negative, weakly, or strongly staining. A receiver operating characteristic curve was established for endoglin MVD in predicting survival; the optimal cutoff value was 11.125. With a Cox regression analysis, we found that an advanced FIGO stage (hazard ratio 4.66; 95% confidence interval 2.10–10.32, P<0.001) and endoglin MVD more than 11.125 (hazard ratio 12.21; 95% confidence interval 3.62–41.16, P=<0.001) were independent factors to predict survival. Interestingly, a strong TGF-&bgr;1 expression was significantly associated with poor survival only when the endoglin MVD value was higher than 10. Our study shows that evaluation of endoglin MVD by immunochemistry can be used as an independent prognostic marker for cervical cancer patients receiving concurrent chemoradiation. TGF-&bgr;1 also had an impact on survival only when endoglin MVD was enriched, suggesting its involvement in tumor progression in the later stage of angiogenesis.

Prenatal diagnosis of de novo interstitial deletion of proximal 4q by maternal serum screening for Down syndrome

Deletion of the proximal portion of chromosome 4q is apparently rare. To our knowledge, prenatal diagnosis of the interstitial deletion of 4q12–21.1 has never been reported. We present a prenatal case of 4q deletion in association with a positive Down syndrome screening test of an elevated maternal serum free beta human chorionic gonadotrophin (β‐hCG) level. The prenatal sonogram revealed intra‐uterine growth retardation (IUGR) and shortening of the femur. Facial dysmorphism included micrognathia, depressed nasal bridge and low‐set ears, these anomalies were evident at the postnatal examination. All of the anomalies were consistent with those described in proximal 4q deletion syndrome. Our case suggests that chromosome studies may be indicated for patients with high maternal serum free β‐hCG and IUGR in the early second trimester. Copyright

Synchronous presentation of uterine leiomyosarcoma and retroperitoneal liposarcoma: analysis by comparative genomic hybridization and review of the literature.

Multiple primary malignant neoplasms are not uncommon, whereas 2 different types of primary sarcomas simultaneously presenting in 1 individual is quite unusual. We encountered a patient presenting with a uterine sarcoma and another retroperitoneal mass at the same time. These 2 tumors showed distinct pathologic and immunohistochemical features. The diagnosis of a synchronous presentation of a uterine leiomyosarcoma and a retroperitoneal sclerosing well-differentiated liposarcoma was rendered. Further study by comparative genomic hybridization showed unrelated genomic alterations of these 2 tumors. Nevertheless, other common genetic alterations such as balanced translocations, point mutations, or epigenetic modifications could still exist because of the limitation of findings by comparative genomic hybridization. In conclusion, both metastasis and multiple primary tumors should always be taken into consideration in differential diagnosis while encountering synchronous sarcomas.

Evaluation of Pegylated Liposomal Doxorubicin in the Treatment Of Both Platinum- and Paclitaxel-Refractory Epithelial Ovarian Cancer

Summary Objective Pegylated liposomal doxorubicin (PLD) is a stealth liposomal form of doxorubicin that has been approved for the treatment of patients with relapsed ovarian cancer. Previous studies have shown a response rate of about 25% in patients who had treatment failure with prior platinum- and/or paclitaxel-based regimens. Our purpose was to determine the anti-tumor activity of PLD in Asian patients with both platinum- and paclitaxel- refractory epithelial ovarian cancer, and to evaluate the toxicity of this drug in these heavily pretreated patients. Materials and Methods Between January 2000 and December 2003, 18 patients with documented relapsed disease, who had had prior treatment with both platinum- and paclitaxel-based regimens within 6 months, were enrolled. They were treated with PLD 40 mg/m 2 intravenous infusion every 4 weeks. Anti-tumor responses and adverse effects were evaluated based on WHO criteria and Common Toxicity Criteria, respectively. Results All 18 patients were assessable for response and toxicity. Five patients (27.8%) experienced a response (3 complete responses, 2 partial responses), four patients (22.2%) had stable disease, while nine patients (50.0%) had progressive disease. The median progression-free survival was 14 weeks. Median overall survival was 48 weeks. There was no grade 3 or 4 leukopenia or thrombocytopenia. Non-hematologic toxicities included grade 2 hand-foot syndrome in one patient and grade 1 stomatitis in three patients. Two patients experienced severe skin pigmentation. There was no treatment delay due to toxicity. Conclusion PLD at a dose of 40 mg/m 2 every 4 weeks was generally well tolerated and effective, even for a heavily pretreated Asian population. These results may provide some information for further clinical trials integrating PLD with front-line therapy.

Pelvic Castleman's disease presenting as an adnexal tumor

Castleman’s disease, first described in 1954 (1), is a rare benign disorder of unknown etiology characterized by a proliferation of lymphoid tissues. It is also known as angiofollicular lymph node hyperplasia, angiomatous lymphoid hamartoma, lymphoid hamartoma, and giant lymph node hyperplasia. Flendrig et al. (2) distinguished two basic histopathologic types and one mixed variant, which Keller et al. (3) designated the hyaline-vascular, plasma-cell, and hyaline-vascular plasma-cell types. Two clinical entities also have been described: a unicentric presentation with disease confined to a single anatomic lymph node-bearing region and a multicentric presentation characterized by generalized lymphadenopathy, systemic symptoms, hepatosplenomegaly, and a more aggressive clinical course with the potential for malignant transformation (4–6). In 70% of cases, this tumor occurs in the mediastinum (3), and the neck (7), pancreas (8), pelvis (9–13), and axillary and inguinal lymph nodes (14) are uncommon sites of involvement. In gynecologic practice, the condition appears to be extremely rare. We report a patient with unicentric Castleman’s disease of the hyaline-vascular type in the pelvic retroperitoneum, which initially presented as an adnexal tumor.