Motoaki Saitou

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.

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.

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.

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

BackgroundThe 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.MethodsWe 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.ResultsThe 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).ConclusionThe 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.

Drug sensitivity associated mitochondrial (MT) ultrastructure in ovarian cancer

5122 Background: Morphological features found in ovarian carcinoma after chemotherapy have been reported (Silverberg SG; Int J Gynecol Pathol. 2000), however, there is no established correlation be...