Prospective analysis of patient-reported outcomes and physician-reported outcomes with gynecologic cancer chemotherapy.

OBJECTIVE: Gynecologic cancer chemotherapy impacts the quality of life (QOL) of patients, with lasting adverse events that may require treatment adjustments or discontinuation. Consequently, real-time symptom monitoring before outpatient visits has resulted in improved QOL for patients and extended survival times. This study investigated whether there are differences between electronic patient-reported outcomes (e-PRO-CTCAE) and physician-assessed outcomes (NCI-CTCAE) evaluated in an outpatient setting in gynecologic cancer chemotherapy. METHODS: The study was conducted on 50 patients who received their first chemotherapy treatment at St. Marianna University Hospital Obstetrics and Gynecology from July 1, 2021 to December 31, 2022. PRO-CTCAE and NCI-CTCAE were evaluated at each instance of chemotherapy and 2 weeks after. The PRO-CTCAE was additionally collected weekly using e-PRO. RESULTS: The values for "Joint Pain," "Nausea," "Taste Disturbance," "Constipation," "Insomnia," "Fatigue," "Limb Edema," and "Concentration Impairment" were consistently higher in PRO-CTCAE than in NCI-CTCAE, indicating that physicians underestimated the severity of adverse events. In contrast, there was no significant difference in "Peripheral Neuropathy," demonstrating that physicians had a good understanding of this condition in patients. The weekly responses obtained from e-PRO revealed that symptom exacerbations peaked outside of clinic visits. CONCLUSIONS: This study demonstrated physicians tend to underestimate most adverse events. Moreover, the responses using e-PRO revealed peak symptom deterioration occurred outside of outpatient visits. This suggested that e-PRO and actions taken in response to them can improve patients' QOL.

Current state of fertility preservation for adolescent and young adult patients with gynecological cancer.

Although the incidence of the various gynecological cancers has been increasing in recent years, long-term survival is now possible for many patients thanks to advances in multimodality treatment. When treating gynecological cancer in adolescent and young adult (AYA) patients who desire future pregnancy, it is necessary to preserve the reproductive organs and their function to prevent loss of fertility. However, because treatment targets these organs, in the large majority of cases, patients must have these organs removed. In the subfield of oncofertility, treatment of the underlying disease takes priority, and the main principle is preventing delay in treatment. Close cooperation between obstetricians and gynecologists involved in reproductive medicine and oncologists involved in cancer treatment is necessary. In addition, it is important that clinicians work closely not only with other specialists but also with such medical professionals as nurses and counselors so that cancer patients of the AYA generation can be provided the support they need to fight their cancer with hope. Herein, we describe the current status of fertility-sparing therapy for AYA patients with gynecological cancer (cervical cancer, endometrial cancer, or ovarian cancer). In addition, we explain points to keep in mind during a patient's pregnancy after fertility preservation, the latest findings on assisted reproductive technology, and the challenges and prospects of fertility preservation therapy for patients with gynecologic cancer.

Primary malignant melanoma of uterine cervix treated with pembrolizumab as adjuvant immunotherapy.

This is the case report of primary malignant melanoma (MM) of uterine cervix treated by immune checkpoint inhibitor: the Pembrolizumab. Despite the merge of the novel drugs that has been strikingly improving prognosis of MM, we still struggle treatment of MM of uterine cervix that has aggressive characteristics with unknown etiology. We present our case to contribute its rarity of the disease case report, the primary MM of the uterine cervix that had poor response to pembrolizumab and had OS of 6 months. The treatment ineffectiveness is mainly considered for mucosal MM of low tumor mutation burden and its unusual type of pathology. Accumulation of retrospective studies exclusively on cervical melanoma needs to be proceeded to investigate on characteristics between poor and long survival to establish standardized treatment.

A simple technique of vaginal cuff closure to prevent tumor cell spillage in laparoscopic radical hysterectomy for uterine cervical cancer.

INTRODUCTION: The Laparoscopic Approach to Cervical Cancer (LACC) trial, a prospective randomized phase III clinical trial reported in 2018, unexpectedly showed inferior oncologic outcomes in laparoscopic radical hysterectomy (LRH) for cervical cancer compared with those in open surgery. It was proposed that the spillage of tumor cells into the peritoneal cavity might cause the inferiority of LRH. It has been suggested, based on retrospective studies, that transvaginal closure of the vaginal cuff before the colpotomy part of the surgery may prevent this. MATERIALS AND SURGICAL TECHNIQUE: Before starting colpotomy, we closed the vaginal cuff transvaginally. After the assessment of the cutline of the vagina, the vaginal mucosa is pulled at the eight sites using the sutures. The four pairs of sutures on the diagonal line are ligated. A purse string suture is additionally placed on the vaginal mucosa to close the vaginal cuff completely. After that, we start the intracorporeal colpotomy using a vaginal pipe. DISCUSSION: Our technique is simple and quick. The blood loss during the transvaginal procedures is minimal. The use of the vaginal pipe helps keep the vaginal cuff closed during the colpotomy. Our technique may be an alternative to the conventional approach closing the vaginal cuff.

Value of adjuvant chemotherapy and informed microscopic examination for occult gynecologic cancer detected upon risk-reducing salpingo-oophorectomy after chemotherapy for BRCA1/2-associated breast cancer: a case report.

BRCA1/2 mutation carriers are at high risk for type II ovarian, fallopian tube or peritoneal cancer. Although risk-reducing salpingo-oophorectomy plays an important role in the prevention of these BRCA1/2-associated gynecological cancers, occult ovarian, fallopian tube, or peritoneal cancer is discovered upon risk-reducing salpingo-oophorectomy in 1-4% of BRCA1/2 mutation carriers. Notably, around 30% of BRCA1/2 mutation carriers who undergo risk-reducing salpingo-oophorectomy have undergone adjuvant chemotherapy for breast cancer. We describe the discovery and treatment of occult cancer at the edge of the left fimbria in a BRCA1 mutation carrier who had, just a short time previously, undergone neoadjuvant paclitaxel plus carboplatin (TC) chemotherapy for triple-negative breast cancer. During subsequent risk-reducing salpingo-oophorectomy, a 5.5-mm nodule was observed at the edge of the left fimbria. Microscopic examination of the tumour tissue revealed high-grade serous carcinoma with degenerate tumour cells and fibrosis. Peritoneal fluid was negative for cancer cells. Two months later, hysterectomy, omentectomy and retroperitoneal lymphadenectomy were performed. The final diagnosis was stage FIGO IA fallopian tube cancer. Adjuvant chemotherapy (TC administered every 3 weeks) was applied, and there has been no evidence of recurrence for 5 years. In applying gynecologic surgery and adjuvant chemotherapy, we followed the general recommendation for stage IA fallopian tube cancer. There is no standard strategy for the treatment of occult fallopian tube cancer detected after chemotherapy for BRCA1-associated triple-negative breast cancer. According to our experience in this case, we believe the clinical value of staging laparotomy in cases of a small occult BRCA1/2-associated gynecological cancer should be further investigated.

Predictors for pathological parametrial invasion in clinical stage IIB cervical cancer.

OBJECTIVE: To examine predictors of pathological parametrial invasion in clinical stage IIB cervical cancer, and to examine prognostic factors in pathological stage IIB disease. METHODS: This study is an ancillary analysis of a nation-wide retrospective cohort examining 6,003 clinical stage IB-IIB cervical cancers. Women with clinical stage IIB disease who underwent primary radical hysterectomy with lymphadenectomy were examined (n = 714). Multivariate analysis was performed to identify independent clinico-pathological factors for pathological parametrial invasion and to identify independent prognostic factors in pathological stage IIB disease. RESULTS: Parametrial invasion was identified on the surgical specimen in 400 cases (56.0%, 95% confidence interval 52.4-59.7). On multivariate analysis, deep stromal invasion (DSI, adjusted-OR 3.922), multiple pelvic nodal metastases (adjusted-OR 3.266), lympho-vascular space invasion (adjusted-OR 2.333), and uterine corpus invasion (adjusted-OR 1.656) remained independent tumor factors for pathological parametrial invasion. In classification-tree models, tumors with DSI and multiple pelvic nodal metastases had the highest incidence of pathological parametrial invasion (75.0-87.7%); contrary, tumors without DSI had the lowest incidence (21.9%). Among patients with pathological stage IIB disease, the absolute difference in 5-year disease-free survival rates was 57.2%, ranging between 80.9% in those with squamous histology with none/single pelvic nodal metastasis and 23.7% in those with non-squamous histology with multiple pelvic nodal metastases. CONCLUSION: In clinical stage IIB cervical cancer, accuracy for pathological parametrial invasion is low-modest. With absence of DSI, only one in five clinical stage IIB diseases has pathological stage IIB disease. Survival of pathological stage IIB varies widely and is largely dependent on nodal factors.

The Clinical Features of Recurrent Endometrial Cancer in Japan: Chemotherapy Instead of Radiotherapy as Postoperative Adjuvant Treatment.

OBJECTIVE: Chemotherapy is a standard adjuvant treatment after primary surgery for endometrial cancer in Japan. We aimed to characterize the clinical features of recurrent endometrial cancer (REC) patients in Japan. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 112 REC patients who were primarily treated at 1 of 3 university hospitals in Japan from 2005 to 2012. We analyzed overall survival since the first recurrence (R-OS) in accordance with several factors. RESULTS: Median patient age was 64 years. The median follow-up period was 48 months. The distributions of cancer stage and histological subtype lacked distinctive features, and most patients had a high risk for recurrence at the time of the primary surgery. Although approximately 78% of patients received adjuvant chemotherapy, 85/112 patients (76%) experienced recurrence within 2 years after the initial treatment ended. For patients receiving adjuvant chemotherapy, regional lymph node (LN) and distant-site recurrence were more frequent (>40%) than vaginal or intra-abdominal recurrence. Median survival and 5-year R-OS were 27 months and 26.1%, respectively. The R-OS was significantly better for patients aged 65 years or older, those with negative peritoneal cytology at the time of primary surgery, those with recurrence within regional LN (eg, pelvic LN or para-aortic LN under the renal vein) and/or vagina, and those who underwent surgery and/or radiotherapy after recurrence. A multivariate analysis indicated that positive peritoneal cytology, a disease-free interval of less than 12 months, recurrent lesions in 2 or 3 areas, and treatment excluding surgery or radiotherapy were independent predictors of poor prognosis after recurrence. CONCLUSIONS: Adjuvant chemotherapy was insufficient to reduce the incidence of distant recurrence. The prognosis of patients recurred within regional LN and/or vagina was significantly better than that of patients with recurrence in other lesions because of treatment with surgery and/or radiotherapy. The disease-free interval was a significant prognostic factor for REC patients.

Glycan profiling using formalin-fixed, paraffin-embedded tissues: Hippeastrum hybrid lectin is a sensitive biomarker for squamous cell carcinoma of the uterine cervix.

AIM: Glycosylation of proteins is altered in cancer cells and distinctive glycan structures are associated with specific cancers, but little is known about the complete glycan profile of particular tumors. In this study, glycomic analysis of squamous cell carcinoma (SCC) of the uterine cervix was performed to search for useful markers. METHODS: A lectin microarray containing 45 lectins with different binding preferences that covered N- and O-linked glycans was coupled with evanescent field-activated fluorescent detection for glycomic analysis of SCC and normal squamous epithelium (NSE) of the cervix. Formalin-fixed, paraffin-embedded tissue specimens were obtained from 16 patients with uterine cervical cancer. Sections that included both tumor and non-tumor tissues were examined to detect alterations of glycans based on the lectin-binding pattern. RESULTS: Hippeastrum hybrid lectin was found to be a sensitive marker for distinguishing SCC of the cervix from NSE. It was the best lectin for discriminating SCC from other tissues according to receiver-operator curve analysis, as it showed a high sensitivity (81.8%), a high specificity (70.1%), and a large area under the curve (0.8182). Histochemistry confirmed specific cytoplasmic staining of SCC cells by Hippeastrum hybrid lectin, while there was little staining of cervical intraepithelial neoplasia and no staining of NSE. CONCLUSION: The present lectin microarray technique could be applied for tissue-based glycomic analysis of various tumors and for discovery of glycan-related biomarkers.

Combination of irinotecan (CPT-11) and nedaplatin (NDP) for recurrent patients with uterine cervical cancer.

BACKGROUND: The clinical activity of combination of irinotecan (CPT-11) and nedaplatin (NDP) for recurrent patients with uterine cervical cancer was evaluated retrospectively. METHODS: Intravenous CPT-11 was given at 60 mg/m(2) (days 1, 8, 15), followed by NDP 80 mg/m(2) (day 1), every 4 weeks. RESULTS: According to the medical records, 29 cases have received this regimen since 2000. Median age was 57 years (range, 29-80), and performance status (PS) of the patients was 18 cases with PS 0, 10 cases with PS 1, and 1 case with PS 2, respectively. Clinical stage was as follows: 3 cases of stage Ib1, 2 cases of Ib2, 2 cases of IIa, 10 cases of IIb, 8 cases of IIIb, and 4 cases of IVb. There were 27 cases of squamous cell carcinoma and 2 cases of adenocarcinoma. Concerning hematological toxicity of grade 3 or more, neutropenia, leukopenia, and febrile neutropenia were observed in 79.3 %, 96.6 %, and 13.8 % of cases, respectively. For nonhematological toxicity, nausea, anorexia, joint pain, and confusion were observed in only 1 case, respectively, and as a result, in 7 cases chemotherapy was not completed. Among 26 cases with clinically evaluable lesions, there were 7 complete responses, 3 partial responses, 7 stable disease, and 9 progressive disease; the clinical response rate was 38.5 %. Median progression-free survival was 7 months (range, 0-38 months). CONCLUSION: The combination of CPT-11 and NDP seems to be active for patients with recurrent uterine cervical cancer.

Clinical study on the efficacy of fluvoxamine for psychological distress in gynecologic cancer patients.

BACKGROUND: Diagnosis of cancer causes psychological distress. The present study investigated the safety and efficacy of fluvoxamine therapy in gynecologic cancer patients with either adjustment disorder or major depression after cancer was diagnosed. METHODS: Screening with the Hospital Anxiety and Depression Scale (HADS) was conducted at least 2 weeks after notification of the diagnosis of cancer in 214 gynecologic cancer patients hospitalized between January 2007 and December 2008. The HADS cutoff score was set at 11 points or greater. Informed consent to the study was obtained from 10 patients, and fluvoxamine was administered for 8 weeks. As primary end points, the safety and efficacy of fluvoxamine were evaluated using the HADS and the SF-36. As a secondary end point, the Clinical Global Impression was determined. RESULTS: The total HADS score, the anxiety score, and the depression score were significantly reduced after 6, 4, and 6 weeks of treatment, respectively. The SF-36 revealed significant improvement in vitality, mental health, and role (emotional) after 8 weeks of treatment. In the 5 patients with adjustment disorder, only the HADS anxiety score was significantly reduced after 4 weeks. In the 5 patients with major depression, the total HADS score, the anxiety score, and the depression score were significantly reduced after 6, 8, and 6 weeks, respectively. According to the SF-36, the adjustment-disorder groups showed significant improvement in mental health after 8 weeks of treatment, whereas the major-depression group showed significant improvement in vitality and role (emotional) after 8 weeks. No adverse events occurred in any subject. Assessment of the Clinical Global Impression suggested that fluvoxamine improved psychological distress in all 10 subjects. CONCLUSIONS: The present findings suggest that fluvoxamine is useful for alleviating psychological distress, including adjustment disorder and major depression, in gynecologic cancer patients. Management of psychological distress after diagnosis of cancer is important.

[A case of serous surface papillary carcinoma of the peritoneum metastatic to the brain].

A case of brain metastasis from peritoneal serous surface papillary carcinoma (SSPC) was reported. This 68-year-old woman was admitted to our department because of decreased consciousness level for the last few days. Her medical past history revealed breast cancer and SSPC of the peritoneum at the age of 64. On admission she was comatose and irritable. Serum and urine examination revealed the syndrome of inappropriate secretion of antidiuretic hormone that was treated with strict restriction of water intake. MRI of the brain demonstrated a nonspecific mass in the subcortical area of the right superior parietal lobule. The mass was successfully removed in en bloc fashion. Pathological diagnosis was SSPC that was compatible with the previous diagnosis obtained from the peritoneum four years previously. Although the patient received whole brain radiation therapy postoperatively, her condition deteriorated rapidly. She died four months after brain surgery. SSPC of the peritoneum is a rare malignant tumor that is defined as a primary tumor histologically indistinguishable from serous carcinoma of the ovary, diffusely involving the peritoneal surface but sparing or only superficially invading the ovaries. Because of the prolongation of survival resulting from advanced chemotherapy for SSPC of the peritoneum, more patients live long enough to develop brain metastasis. Therefore, SSPC of the peritoneum should be kept in mind in the differential diagnosis of a primary site for brain metastasis.

Side population is increased in paclitaxel-resistant ovarian cancer cell lines regardless of resistance to cisplatin.

OBJECTIVES: In recent years, cancer stem cells (CSCs) have been reported to be correlated with chemoresistance and may also be enriched in side populations (SPs). In this study, the relationship between resistance to paclitaxel (PTX) and cisplatin (CDDP) and side populations was examined in three parental PTX- and CDDP-sensitive ovarian cancer cell lines (2008, KF28, and TU-OM-1) and several other cell lines derived from these as well as the additional effects of interferon-alpha (INF-α). METHODS: SP of three different parental cell lines and PTX- and/or CDDP-resistant cell lines derived from these was analyzed with flow cytometry. The expression of ABCB1 and ABCG2 in KF28 and its derived cell lines was examined. Additional cell-death effect of INF-α with PTX was also examined. RESULTS: In the three parental cell lines and the PTX-sensitive cell lines derived from these lines, SP was very low. Conversely, in PTX-resistant cell lines, regardless of CDDP resistance, SP increased. ABCB1 was strongly expressed in the PTX-resistant cells, but not in their parental lines, which are sensitive to PTX. While INF-α showed only slight enhancement of the cell-death effect of PTX in PTX-sensitive cells, INF-α itself strongly induced apoptosis in PTX-resistant cells regardless of PTX concentration. CONCLUSIONS: The SP could be correlated with resistance to PTX. SP could be a target of INF-α, and resistance to PTX might be overcome by INF-α.

Ovarian carcinoma complicated by sigmoid colon fistula formation: a case report and review of the literature.

Formation of a fistula to a digestive organ is an extremely rare phenomenon in cases of ovarian carcinoma. We report a case of ovarian clear-cell carcinoma complicated by formation of a sigmoid colon fistula, and review the related literature. A 61-year-old woman, who had undergone hysterectomy and right salpingo-oophorectomy due to myoma and an ovarian tumor, developed bloody bowel discharge and abdominal distention. Computed tomography revealed a huge pelvic tumor with a thickened wall and internal gas. As the patient also had severe anemia and peritonitis, emergency laparotomy was performed, and intraoperatively it was noted that the tumor was tightly attached to the sigmoid colon, and contained bloody pus. Left salpingo-oophorectomy was performed and pathological examination of the specimen revealed fistula formation between the ovarian tumor and the sigmoid colon. The tumor was diagnosed as left ovarian clear-cell carcinoma, but no diverticulum or direct tumor invasion was evident around the fistula. The patient was given chemotherapy with paclitaxel and carboplatin, and she is now doing well after 9 months with no evidence of tumor recurrence. Although fistulation to the digestive tract is very rare in cases of ovarian cancer, it must be diagnosed and treated promptly because severe inflammation can make it potentially life-threatening.

Risk factors for perioperative venous thromboembolism: A retrospective study in Japanese women with gynecologic diseases.

BACKGROUND: Patients with gynecologic cancer have a high risk of venous thromboembolism (VTE) like patients with other cancers. However, there is little information on risk factors for VTE during gynecologic surgery and no uniform preventive strategy. Our objectives were to identify risk factors for perioperative VTE in gynecologic patients and establish methods for prevention. METHODS: We analyzed 1,232 patients who underwent surgery at the Department of Obstetrics and Gynecology of St. Marianna University School of Medicine between January 2005 and June 2008. We investigated (1) risk factors for preoperative VTE, (2) use of an inferior vena cava (IVC) filter, and (3) risk factors for postoperative VTE. RESULTS: There were 39 confirmed cases of perioperative VTE (3.17%), including 25 patients with preoperative VTE and 14 with postoperative VTE. Thirty-two patients had cancer and seven patients had benign diseases. Twenty-two of the 32 cancer patients (68.7%) had preoperative VTE, while postoperative VTE occurred in 10 cancer patients. Multivariate analysis indicated that ovarian cancer, tumor diameter ≥10 cm, and previous of VTE were independent risk factors for preoperative VTE. Among ovarian cancer patients, multivariate analysis showed that an age ≥50 years, the presence of heart disease, clear cell adenocarcinoma, and tumor diameter ≥20 cm were independent risk factors for preoperative VTE. The factors significantly related to preoperative VTE in patients with benign disease included previous VTE, age ≥55 years, tumor diameter ≥20 cm, and a history of allergic-immunologic disease. Thirteen of the 25 patients (52%) with preoperative VTE had an IVC filter inserted preoperatively. Postoperative screening (interview and D-dimer measurement) revealed VTE in 14/1,232 patients (1.14%). Multivariate analysis indicated that cancer surgery, a history of allergic-immunologic disease, and blood transfusion ≥2,000 ml were independent risk factors for postoperative VTE. CONCLUSIONS: Perioperative VTE is often fatal and preventive measures should be taken in the gynecologic field, especially when patients have the risk factors identified in this study. Since VTE is often present before surgery, preoperative screening is important and use of an IVC filter should be considered.

[Usefulness of clinical study of irinotecan and cisplatin for recurrent ovarian cancer].

So far, there is no recommended evidence-based chemotherapeutic regimen for recurrent or refractory ovarian carcinoma in the guideline. In our institute, combination chemotherapy of CPT-11 and CDDP (CPT-P) was administered for recurrent or refractory ovarian carcinoma patients previously treated with regimens including taxane. In fourteen cases treated with CPT-P, there were 2 cases of CR, 2 of PR, 3 of SD, and 7 of PD. Overall response rate was 28. 5%, and the median progression-free interval was 5.5 months. No severe side effect was observed except in one patient in whom chemotherapy was discontinued due to grade 4 neutropenia and grade 3 diarrhea. Thus CPT-P seemed to be effective and safe for the recurrent or refractory ovarian carcinoma previously treated with taxane-included regimen.

Concurrent chemoradiotherapy with nedaplatin after radical hysterectomy in patients with stage IB and II cervical cancer.

Although radical hysterectomy is the standard surgical treatment for patients with stage IB and II cervical cancer, it does not improve the prognosis of high-risk patients even if postoperative radiotherapy is added. There is therefore a need to establish some other therapeutic regimen. In the present retrospective study, the efficacy of concurrent nedaplatin after radical hysterectomy in high-risk stage IB to II cervical cancer was analyzed. From 1995 through 2005, patients with an International Federation of Gynecology and Obstetrics stage of IB2 and II cervical cancer who were given only radiotherapy (RT; n = 17) or postoperative concurrent chemoradiotherapy with biweekly nedaplatin at 70 mg/m(2) (p-CCRT; n = 13) were entered. All of the patients had at least one of the following risk factors: lymphovascular space infiltration, positive lymph nodes, or parametrial invasion. There was no significant difference between the RT and p-CCRT groups with regard to mean age and risk factors, except that more patients in the p-CCRT group had positive lymph nodes (P < 0.05). Five-year progression-free survival and overall survival after RT versus p-CCRT were 76.0% versus 83.3%, and 81.9% versus 83.3%, respectively. Although many patients in the p-CCRT group had positive lymph nodes, there was no significant difference in either PFS or OS. No grade 4 myelosuppression or other severe side effects were seen in the p-CCRT group. As CCRT with nedaplatin might have some benefit, a randomized control trial should be conducted in the future.

Enzymatic activities of uridine and thymidine phosphorylase in normal and cancerous uterine cervical tissues.

In this study, the preliminary analyses were conducted of enzymatic activities of uridine phosphorylase (UP) and thymidine phosphorylase (TP) in normal tissues and cancer tissues of the uterine cervix. The study was performed on 27 patients of cervical cancer, treated first in our hospital. Normal cervical tissues obtained from 15 patients undergoing hysterectomy for benign diseases were used as controls. The supernatant of the homogenated cervical tissues and the stroma (5-FU and ribose-1-P or deoxyribose-1-P) were analyzed by high performance liquid chromatography, and then the UP and TP activities calculated. TP activity was significantly greater than UP activity (P < 0.0001). Both UP and TP showed significantly greater activity in cancer tissues than in normal tissues (P < 0.0001). In the TP activity of the cancer tissues, there was no significant difference among the histological types, while the TP activity tended to be significantly higher in the cases with lymph node metastasis. These results showed that the TP-mediated route seemed important as the 5FU metabolic pathway in the uterine cervical tissues, and TP enzymatic activity might be associated with lymph node metastasis.

Establishment and characterization of a cell line derived from a human serous surface papillary carcinoma of the ovary.

A novel serous surface papillary carcinoma of the ovary (SSPC) cell line, HYKSSPC, was established successfully. Carcinoma cells were obtained from ascitic fluid of a 60-year-old Japanese woman. The population doubling time was 51.4 h. A phase contrast micrograph showed a pavement stone-like arrangement without contact inhibition. The chromosome number showed a wide distribution of aneuploidy, and the mode was in 46-47. An immunocytochemical study showed that CA125, BerER4 and cytokeratin were positive and that CEA, calretinin and thrombomodulin were negative. This cell line preserved some characters of the adenocarcinoma while growing in vitro. A chemosensitivity test revealed that HYKSSPC cells were sensitive to CDDP (cis-platinum), 5-fluorouracil, mitomycin C, paclitaxel and irinotecan. To our knowledge, HYKSSPC is the first established cell line derived from SSPC, and it may offer some useful information for investigating this disease.

Establishment and characterization of a human liposarcoma cell line (HTLS) from the retroperitoneal liposarcoma.

A cell line designated HTLS was established from the retroperitoneal liposarcoma. The HTLS line showed stable proliferation without interruption for 2 years and subcultivated over 35 times. The cells were elongated fibrous and spindle in shape, and neoplastic and pleomorphic features. The multinucleated giant cells with fine cytoplasm were seen. The cells proliferated slowly and the population doubling time was about 90 hours. The chromosome number showed a wide distribution of aneuploidy, the mode was hyperdiploid range (51-52), and many marker chromosomes were observed. The cells were transplantable into the submucosa of immunesuppressed hamster's cheek pouch and produced liposarcoma, while were not transplantable into subcutis of nude mice

New chemosensitivity test using a thermo-reversible gelation polymer for recurrent gynecologic cancer patients and a preliminary study of mechanisms of anticancer drug resistance.

OBJECTIVES: TGP (thermo-reversible gelation polymer) is a high molecular compound that has so-gel transmitting temperature of 221C Since solid cancer tissue grows in this polymer three-dimensionally, and fibroblasts scarcely grow in it, TGP is suitable for chemosensitivity assays for solid tumors. In this study, a chemosensitivity test using TGP was applied to recurrent gynecologic cancer patients in order to evaluate its utility and efficacy. In some ovarian cancer cases, expression of anticancer drug resistance-related proteins was also analyzed. METHODS: Recurrent tumor tissues were surgically obtained with informed consent. After these tissues were minced and incubated for 4 days with CDDP, mitomycin C, 5-fluorouracil, paclitaxel, and CPT-11, the sensitivity against these drugs was estimated. Western blotting was performed in 8 recurrent ovarian cancer tissues in order to analyze the expression of Bcl-2, MRP2, BCRP, and GST-pi. RESULTS: The total evaluability rate of this assay was 90.6% (29/32). Sensitive drugs could be determined in 5 of 7 ascites samples (71.4%) and in 2 of 3 intra-tumoral fluid samples (66.7%). The overall clinical response rate of chemotherapy determined by these results was 50.0%. There were significant correlations between the IC50 of CDDP and Bcl-2, BCRP, GST-pi, and between that of 5-FU and MRP 2. CONCLUSIONS: Although this was a preliminary study, the chemosensitivity test using this new material appears to be useful for designing 'made-to order' salvage chemotherapy for pretreated recurrent gynecologic patients. In order to overcome multidrug resistance, the mechanisms of multidrug resistance should be further investigated.