MRI findings for primary fallopian tube cancer: correlation with pathological findings.

PURPOSE: To clarify the MRI findings for primary fallopian tube cancer (PFTC). MATERIALS AND METHODS: MRI findings for 11 patients who were pathologically diagnosed with PFTC at our institute were retrospectively reviewed. MRI findings (shape, appearance, signal intensity, ADC value, enhancement patterns, and location of the primary tumor, the morphologic appearance of the ipsilateral ovary, and intrauterine fluid collection) were evaluated and compared with pathological findings including histological subtype and PFTC location. RESULTS: On MRI, PFTCs with a tubal component (n = 8) exhibited a sausage-like shape in five cases and a nodular or irregular shape in three cases. PFTCs located at the fimbria (n = 3) presented a nodular shape. The PFTC was solid in nine cases (82%), and the solid portion showed high intensity on diffusion-weighted images in all cases. The mean ADC value was 0.86 × 10-3 mm2/s. Rim enhancement of the tumor was seen in six of nine cases (67%), all with a tubal component. CONCLUSION: PFTCs with a tubal component are sausage-shaped and PFTCs located at the fimbria have a nodular shape. Rim enhancement is frequently seen in PFTCs with a tubal component, which may suggest a tubal origin.

The concept of platinum sensitivity could be applied to recurrent cervical cancer: a multi-institutional retrospective study from the Japanese Gynecologic Oncology Group.

PURPOSE: This study aimed at evaluating the applicability of the concept of platinum sensitivity to recurrent cervical cancer. METHODS: The clinical information of patients with recurrent cervical cancer, who were initially treated with platinum-based chemotherapy and received second-line platinum-based chemotherapy at the time of recurrence between January 2008 and December 2012, was retrospectively reviewed. RESULTS: A total of 677 patients from 71 medical centers were analyzed. The median overall survival (OS) for patients with platinum-free interval (PFI) of <6, 6-11, 12-17, and ≥18 months was 12.1 (95% CI 11.0-14.1) months, 17.4 (15.5-20.4) months, 20.2 (17.9-27.6) months, and 29.9 (26.7-36.0) months, respectively (P < 0.0001, log-rank). The best cut-off value of PFI that affected OS was 7 months, analyzed by the minimum P value method. The median progression-free survival (PFS) for patients with less than and more than PFI of 7 months was 6.2 months (95% CI 4.8-9.3) and 21.0 months (18.9-24.8) (P < 0.0001, log-rank), respectively, and the median OS for patients with less than and more than PFI of 7 months was 12.3 months (11.2-14.1) and 24.2 months (20.8-25.8) (P < 0.0001, log-rank). Multivariate analysis revealed that PFI (P < 0.0001, HR 0.449, 95% CI 0.369-0.548) alone had a statistically significant association with OS. CONCLUSIONS: This study showed that the concept of platinum sensitivity could be applied to recurrent cervical cancer and PFI could be one of the independent prognostic factors for patients with recurrent cervical cancer who have previously been treated with platinum-based chemotherapy.

Feasibility of reduced port surgery applying Higuchi's transverse incision.

OBJECTIVE: Higuchi's transverse incision is made at a lower position than the Pfannenstiel transverse incision and is superior in terms of cosmetic outcomes. The purpose of this study was to examine the safety and efficacy of novel forms of reduced port surgery for ovarian cysts and uterine fibroids applying Higuchi's transverse incision. METHODS: In 33 patients with ovarian cysts who underwent low-position single-incision laparoscopic surgery (L-SILS)-modified single-port laparoscopy placed in the 2-3-cm Higuchi's incision above the pubis, patient's characteristics and perioperative outcomes were compared with those of patients who underwent multiport laparoscopy (n = 53). In addition, 18 patients with uterine fibroids who underwent dual-port laparoscopically assisted myomectomy without using power morcellators and conventional four-port laparoscopically assisted myomectomy were investigated. RESULTS: There were no significant differences between L-SILS and multiport laparoscopy in tumor diameter, bleeding, hospital stay, or postoperative pain. However, the L-SILS group demonstrated significantly shorter operative and pneumoperitoneum times (p < 0.01 and p < 0.01). In comparison with cases of uterine fibroids, no significant differences were found in maximum fibroid diameter, operative time, pneumoperitoneum time, or bleeding. However, the dual-port laparoscopically assisted myomectomy group demonstrated a significantly shorter length of hospital stay than the conventional laparoscopically assisted myomectomy group (p < 0.05). CONCLUSION: We reported novel forms of reduced port surgery applying Higuchi's transverse incision. It was suggested that these procedures are relatively simple, but ensure the same safety and efficacy as conventional methods. We intend to increase the number of cases and examine safety, efficacy, and patient satisfaction for these procedures.

Phase II trial of oral etoposide plus intravenous irinotecan in patients with platinum-resistant and taxane-pretreated ovarian cancer (JCOG0503).

OBJECTIVE: To assess the safety and efficacy of the combination of oral etoposide and intravenous irinotecan in patients with platinum-resistant and taxane-pretreated ovarian cancer. METHODS: Eligible patients (age, 20-75years; platinum-free interval, ≤28weeks) with an adequate organ function received oral etoposide (50mg/m(2) once a day) from day 1 to day 21 and intravenous irinotecan (70mg/m(2)) on days 1 and 15. The regimen was repeated every 28days up to 6cycles. The primary endpoint was the response rate (RR) with a threshold of 20%. The response was evaluated according to RECIST 1.0 and Gynecologic Cancer Intergroup CA-125 Response Definition, and toxicities were evaluated according to CTCAE version 3.0. This trial was registered at UMIN-CTR as UMIN000001837. RESULTS: Between April 1, 2009 and January 20, 2012, 61 patients were enrolled. Sixty patients were eligible. 1 CR and 12 PRs were confirmed; RR was 21.7% (p=0.42, the exact binomial test). PFS and OS were 4.1 and 11.9months, respectively. Major toxicities of ≥grade 3 were neutropenia (60%), anemia (36.7%), thrombocytopenia (11.7%), febrile neutropenia (18.3%), fatigue (13.3%), anorexia (11.7%), and nausea (11.7%). Three patients died from treatment related death (interstitial pneumonia, a pulmonary embolism, and DIC due to infection). Two of these patients were aged ≥65years. CONCLUSIONS: Oral etoposide and intravenous irinotecan had a moderate RR but did not meet the primary endpoint. Because of toxicity, we do not recommend this regimen outside of clinical trials. In particular, when considering this regimen for elderly patients, extreme caution is advised.

Success rate and safety of tumor debulking with diaphragmatic surgery for advanced epithelial ovarian cancer and peritoneal cancer.

PURPOSE: In advanced epithelial ovarian and peritoneal cancer, residual tumor diameter correlates with prognosis; therefore, maximum debulking and optimal surgery (OS) for residual tumors <1 cm is warranted. Here, we clarified the efficacy of tumor debulking with diaphragmatic surgery (DS). METHODS: In 45 patients with epithelial ovarian or peritoneal cancer who underwent DS (ten, full-thickness resection; 35, stripping) between January 2010 and December 2013 at two related institutions, we retrospectively evaluated OS safety and success by surgical duration, blood loss, complications, hospitalization stay, and residual tumor diameter and site. RESULTS: Blood loss was 4,090.8 and 2,847.9 mL; surgical duration was 485.2 and 479.5 min; hospitalization stay was 21.7 and 24.8 days; and complications included intraoperative thoracotomy in 17 and 7 patients, unexpected thoracotomy in 11 and 3, chest drain insertion in one and three, and pleural effusion in 14 and 7, in the primary debulking surgery (PDS) and interval debulking surgery (IDS) groups, respectively. OS was successful in all patients with complete surgery (CS: no residual tumor) achieved in 16 (50.0%) and 9 (69.2%), residual tumor diameter < 5 mm in 11 (34.4%) and 2 (15.4%), and residual tumor diameter < 1 cm in 5 (15.6%) and 2 (15.4%) in the PDS and IDS groups, respectively. CONCLUSIONS: Tumor debulking surgery with DS resulted in controllable blood loss, and OS was successful in all patients without severe complications or postoperative treatment delay. Currently, OS is considered to have very few benefits over CS; thus, the success rate of CS rate should be improved while maintaining safety.

Mitochondrial ultrastructure-associated chemotherapy response in ovarian cancer.

We developed mitochondrial (MT) scoring system based on MT ultrastructural findings in association with response to chemotherapy in ovarian cancer (OC). Ultrathin sections of MT prepared from 28 OC patients before chemotherapy were examined by electron microscopy. Platinum-sensitive ovarian carcinoma cell line 2008 and its resistant variant C13 were used as control cells. Seven independent MT features including, diameter, pattern of cresta structure, electron density, distribution-density and -pattern, ratio of minimal/maximal diameter and MT architecture were examined and were assigned a score between 0 and 2. Twenty-eight cases were primary advanced OC, including 4 recurrent cases. Nine cases were chemosensitive while 19 were resistant. Univariate and multivariate analysis in each factor showed good correlation to chemosensitivity for 2 factors of electron density, distribution pattern. Total score of these 2 factors in 9 sensitive cells was 1.44+/-0.41 (M +/- SE) and was 3.58+/-0.18 in 19 resistant cells (P<0.001). Receptor operative characteristics (ROC) analysis revealed that total 'cut-off' score was 3 point (P<0.05; AUC=0.84). In conclusion, this MT scoring system was excellently correlated to response regardless of histopathologic findings and this strongly suggests that the system is deemed to be of great value as biomarker for the chemosensitivity in OC.

Small cell carcinoma of the ovary: clinical and biological study.

Ovarian small cell carcinoma of hypercalcemic type is a rare neoplasm that typically occurs in young females. We describe three cases of ovarian small cell carcinoma of hypercalcemic type occurring in patients aged 24, 37, and 25 years. The first patient had stage IIc disease and had primary surgery with a left salpingo-oophorectomy and omentectomy, followed by chemotherapy with cisplatin and etoposide. Upon a second relapse, pelvic lymphadenectomy was performed, followed by chemotherapy with docetaxel. She is alive for 4 years without any recurrence after the initial treatment. In vitro drug-sensitivity assay revealed the tumor cells were sensitive to taxane and resistant to irinotecan. The second patient had stage III disease and had primary debulking surgery with bilateral salpingo-oophorectomy, simple hysterectomy, omentectomy, low-anterior resection, and lymphadenectomy, followed by chemotherapy with paclitaxel and carboplatin. Four months after the initial treatment she relapsed and died. The tumor cells were sensitive to platinum, taxane, and doxorubicin, but resistant to irinotecan. The third patient had stage III disease and had right salpingo-oophorectomy, omentectomy, and lymphadenectomy, followed by chemotherapy with cisplatin, cyclophosphamide, and doxorubicin. She relapsed 4 months after completing the chemotherapy and died 5 months after secondary debulking surgery. The tumor cells were sensitive to platinum, taxane, and doxorubicin, but resistant to irinotecan. The drug-sensitivity assays suggested that a non-irinotecan, taxane-containing combination might have been suitable as first-line chemotherapy for these patients. However, an effect of such a regimen was seen in only one patient with early-stage disease, and this questions the validity of chemosensitivity testing.

Differential regulation of the cytotoxicity activity of paclitaxel by orobol and platelet derived growth factor in human ovarian carcinoma cells.

Paclitaxel (PX) binds to and stabilizes tubulin, preventing depolymerization, and resulting in cell death. Based on a previous report showing the activity of phosphatidylinositol kinase (PIK) on tubulin, we investigated the effect of the PI4K inhibitor orobol and the PI3K activator platelet derived growth factor (PDGF) on PX sensitivity. Drug sensitivity was examined by classical colony forming assay. Tubulin isotype expression was determined by semi-quantitative RT-PCR. Microtubule texture was observed by laser confocal microscope using anti-beta-tubulin antibody. Apoptotic activity was estimated by frequency of condensed nuclear chromatin with Hoechst 33342 stain. Orobol enhanced PX sensitivity of human ovarian carcinoma 2008 cells by 18.9+/-1.2-fold (N=3; P<0.01). In contrast, pretreatment with PDGF rendered cells resistant to PX by 2.3+/-0.4-fold (N=3; P<0.01). Neither orobol nor PDGF showed any effect on cell growth. Orobol produced a 2.5-fold sensitization in cisplatin-resistant 2008/C13*5.25 (C13) cells, and PDGF rendered the cells 2.3-fold resistant to PX. Orobol suppressed the beta 4a-tubulin isotype expression by 85% and other isotypes by 20%. In contrast, PDGF induced beta 4a-tubulin isotype expression by 1.3-fold, while it supressed all the other isotypes by 20-40%. Orobol produced thick microtubules and PDGF generated ring condensed microtubules. Orobol promoted PX-induced apoptosis, while PDGF caused 50% reduction of apoptosis. These results indicate that orobol and PDGF regulate PX sensitivity by reciprocally altering the proportion of tubulin isotype expression and PX-induced apoptotic signaling.

Primary chemotherapy-associated effect of second-line chemotherapy on survival of patients with advanced ovarian cancer.

BACKGROUND: The current treatment of patients with recurrent ovarian cancer who have received initial platinum- or taxane-based chemotherapy depends on the results of the initial chemotherapy. The purpose of this study was to evaluate how to make the selection of second-line agents for patients with recurrent ovarian carcinoma initially diagnosed as stage II to IV. METHODS: We conducted a retrospective crossover study in patients who received second-line chemotherapy at Jikei University School of Medicine. We evaluated the responses, progression-free survivals, survivals of second-line chemotherapy, and overall survivals after primary surgery for 51 patients. The treatment cohorts were defined as follows: TC1, patients who were given paclitaxel and carboplatin as first-line chemotherapy and who, upon recurrence, were treated with a platinum-based combination as second-line; and TC2, patients who were given a non-taxane-based platinum combination as first-line chemotherapy, followed, at the time of recurrence, with paclitaxel and carboplatin. RESULTS: The response rates of the second-line chemotherapy for the TC1 and TC2 groups were 44% and 25% (P=0.09). The median progression-free survivals of TC1 and TC2 were 12.9 and 6.4 months (P=0.018; hazard ratio [HR], 2.42; 95% confidence interval [CI], 1.16-5.04). The median survivals after second-line chemotherapy for the two groups were 16.8 and 10.4 months (P=0.007; HR, 2.78; 95% CI, 1.33-5.84) and overall survivals after primary surgery were 36.6 and 27.9 months (P=0.007; HR, 2.36; 95% CI, 1.07-5.21). CONCLUSION: The TC1 group demonstrated a significantly better response and extension of progression-free survival, as well as significantly better survival after crossover and overall survival after primary surgery. As this was a retrospective analysis, this effect should be considered as hypothesis-generating and assessed prospectively in other trials comparing these two chemotherapy schedules.

[Docetaxel and carboplatin for epithelial ovarian cancer].

We report herein on the efficacy and toxicity of docetaxel and carboplatin in patients with epithelial ovarian cancer. Fifteen patients with FIGO stage I c-IV epithelial ovarian cancer were administered docetaxel (70 mg/m2) and carboplatin (AUC 5) every 3 weeks as 1 course. Eleven patients received this regimen as a first-time chemotherapy, and the other 4 as therapy for recurrence. Seven patients were evaluated for response. Of these, 6 achieved complete response and the other a partial response. CA 125 response was seen in 2 of 8 patients who did not have visible tumors. Our toxicity findings include the following: grade 3 and 4 neutropenia (86.7%), hypersensitive reaction (13.3%), grade 2 alopecia (13.3%), and no edema. Docetaxel and carboplatin are actively used in ovarian cancer, with the major toxicity being bone marrow suppression. But we were able to control myelosuppression with G-CSF. Hypersensitivity reactions were frequent, we thought pre-medication. This chemotherapy combination appears effective for epithelial ovarian cancer.