Miho Muraji

Squamous cell carcinoma of the uterine cervix producing granulocyte colony-stimulating factor: a report of 4 cases and a review of the literature.

Granulocyte colony-stimulating factor (G-CSF)-producing malignant tumor has been reported to occur in various organs, and most of which has been associated with poor clinical outcome. However, because of the rarity of the reported cases, information regarding the G-CSF-producing gynecological malignancies is limited. We report 4 cases of G-CSF-producing cervical cancers. At initial diagnosis, all of the 4 patients exhibited marked leukocytosis without an obvious sign of infection. Of the 4 patients, 3 had their disease initially treated with definitive radiotherapy, and one was treated with radical surgery. Despite the aggressive treatments, all of these patients experienced recurrences within 6 months. In all cases, the white blood cell count returned to the normal range in response to the initial treatment and then increased again with recurrences. Based on the facts that the tumor cells were positive for G-CSF, the serum level of G-CSF was elevated, and their clinical course correlated well with the white blood cell count, we concluded that these tumors were G-CSF-producing cancers. All patients died from disease progression in less than 15 months. These cases strongly indicate the aggressive nature of the G-CSF-producing cervical cancer.

Histopathology predicts clinical outcome in advanced epithelial ovarian cancer patients treated with neoadjuvant chemotherapy and debulking surgery

OBJECTIVE To analyze the factors prognostic of survival in patients with advanced epithelial ovarian cancer (EOC) treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery. METHODS Outcomes were retrospectively in patients with advanced EOC or peritoneal cancer who received neoadjuvant paclitaxel and carboplatin chemotherapy every 3 weeks for three to four cycles, followed by interval debulking surgery and three additional cycles of the same regimens from January 2001 to November 2010. Therapeutic response was assessed histopathologically as grade 0 to 3, based on the degree of disappearance of cancer cells, displacement by necrotic and fibrotic tissue, and tumor-induced inflammation. Factors prognostic of progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS The 124 enrolled patients had a median age of 62 years (range, 35-79 years). Viable cancer cells were observed in specimens resected from 72 patients (58%) at interval debulking surgery after NAC. Multivariate analysis using the Cox proportional hazard model showed that advanced (stage IV) disease (hazard ratio [HR]=1.94, p=0.003), residual cancer at the end of surgery ≥1cm (HR=3.78, p<0.001), and histological grade 0-1 (HR=1.65, p=0.03) were independent predictors of decreased OS. Grade 0-1 was also an independent predictor of increased risk of relapse within 6 months (odds ratio=8.42, p=0.003). CONCLUSIONS Residual disease of ≥1cm, advanced stage, and the presence of more viable disease in resected specimens are prognostic factors for survival in advanced EOC patients receiving NAC followed by interval debulking surgery.

Type II versus type III fertility-sparing abdominal radical trachelectomy for early-stage cervical cancer: a comparison of feasibility of surgical outcomes.

Objective The purpose of this study was to compare surgical outcomes using modified (type II) and traditional (type III) abdominal radical trachelectomy (ART) for fertility-sparing surgery in early cervical cancer. Methods A prospectively maintained database of ART procedures was analyzed. Data were collected regarding age, stage, histology, operative outcome, surgical complication, and fertility outcome. Results We performed 23 fertility-sparing ARTs for patients with International Federation of Gynecology and Obstetrics stages IA to IB1 tumors of less than 2 cm between 2006 and 2010. Type III ART was attempted in 8 patients and modified ART in 15 patients. The median operating time was greater in the type III group compared with that in the type II group (305 vs 247 minutes; P < 0.02). The median surgical blood loss was greater in the type III ART group (580 mL; range, 250–988 mL) compared with that in the modified type II group (366 mL; range, 200–850 mL; P < 0.05). The median time to recovery of bladder dysfunction was less in the type II group (9 days; range, 3–10 days) than that in the type III group (13 days; range, 10–23 days; P < 0.01). There were no recurrences at the time of this report. Conclusions Type II ART provides surgical and pathological outcomes with better recovery of bladder function similar to those in type III ART. For patients with early cervical cancer who wish to preserve reproductive function, type II ART is a feasible and safe operation.

Cesarean scar pregnancies successfully treated with methotrexate.

Three cases of cesarean scar pregnancy successfully treated with methotrexate are described. The diagnosis was confirmed by transvaginal sonographic examinations showing a well‐formed gestational sac in the myometrium of the lower uterine segment. Initial treatment with a systemic injection of 50 mg of methotrexate was not sufficient, and multiple doses were required to obtain a complete remission in two cases. In a case with a β‐hCG level of more than 20,000 mIU/mL with a viable embryo in a gestational sac, a combination of systemic and local treatment with methotrexate was required. It took 7–11 weeks for the β‐hCG level to become undetectable and 12–17 weeks for the cesarean scar pregnancy mass to disappear completely.

Postpartum Outcome of Cervical Intraepithelial Neoplasia in Pregnant Women Determined by Route of Delivery

Cervical intraepithelial neoplasia (CIN) has its highest incidence during women’s reproductive years. During 2 sequential 7-year periods, 1994 to 2000 and 2001 to 2007, 3695 and 3894 deliveries were performed, respectively, at Osaka University Hospital. CIN was detected in 21 cases (0.57%) during 1994-2000 and in 43 cases (1.1%) during 2001-2007. By comparison, cervical intraepithelial neoplasia—complicated pregnancies increased significantly in the latter period (P = .015 by Fisher exact test, Odds ratio = 1.95; 95%CI: 1.16-3.30). We observed CIN regression in 34 (76%) of 45 cases of vaginal delivery and in 6 (50%) of 12 cases of cesarean delivery, indicating that the outcome of an initially diagnosed CIN and the delivery routes appeared not to be significantly related. However, a different result was obtained when only those patients whose CIN lesions persisted until the delivery were analyzed. Among the 35 such cases in the vaginal delivery group, 24 cases (69%) regressed after the delivery; in 8 such cases from the cesarean delivery group, only 2 cases (25%) regressed afterward. Our study clearly shows that pregnancy complicated with CIN is increasing rapidly in Japan. We also find that there is a significantly more frequent postpartum regression of biopsy-proven CIN lesions following a vaginal delivery compared to cesarean section (P = .042 by Fisher exact test, Odds ratio = 6.55; 95% CI: 1.13-37.8).

A case of recurrent cesarean scar pregnancy

We thank Professor Dan Hellberg for his interest in our study. The main message of our study was that women with cervical cell changes (suggestive for HPV) had higher levels of nitric oxide metabolites (NOx) in cervical fluid compared to women with normal cytology. We made subgroup analyses by age, parity, use of oral contraceptives, and history of miscarriage or termination of early pregnancy and found that these variables did not affect the result. In another study we compared the level of cervical fluid NOx in women with or without of high-risk HPV DNA, and found that women showing the presence of high-risk HPV DNA had a higher level of cervical fluid NOx compared to women without high-risk HPV DNA (1). Smoking is an independent risk factor for cervical cancer and it worsens the prognosis of mild abnormalities in cervical cytology (2). In Finland, 15% of women smoke and that would have been 45 smoking women in our study. However, the majority of the women had low-grade cell changes, most of which are known to regress spontaneously (3). In addition, the progression from low-grade changes to cancer takes years (3). Thus, even if we would have controlled for smoking, we think that from our study population we cannot conclude on a straight link between cervical carcinogenesis and NOx or between smoking and carcinogenesis. On the other hand, the effect of NO is dual; it may even suppress or promote tumor growth depending on the microenvironment and concentration and duration of NO exposure (4). Therefore, more studies need to be performed to clarify whether NO associated to cell changes is beneficial or deleterious to the host.

The effect of abdominal radical trachelectomy on ovarian reserve: serial changes in serum anti-müllerian hormone levels.

Aim: To evaluate the effect of abdominal radical trachelectomy on ovarian reserve and compare it with abdominal radical hysterectomy and a control group that did not have surgery. Method: We enrolled eighteen women who had abdominal radical trachelectomy with pelvic lymphadenectomy and sixteen patients who had abdominal radical hysterectomy for this study. Ten thousand one hundred eighty-six women were also included as a control group for comparison. The Mann-Whitney U test was used for comparison of patient characteristics and comparison of serum anti-Müllerian hormone levels between the three groups. Results: Serum anti-Müllerian hormone levels in patients with abdominal radical trachelectomy were significantly higher than those of patients with abdominal radical hysterectomy (P<0.05). Serum anti-Müllerian hormone levels in the abdominal radical hysterectomy group were significantly lower than those in the control group (P=0.02), with no significant difference between the abdominal radical trachelectomy and control groups. These data indicated that abdominal radical trachelectomy did not affect ovarian function with respect to ovarian reserve and the response to ovarian stimulation. Conclusions: Serum anti-Müllerian hormone levels could be useful as a marker of ovarian reserve after abdominal radical trachelectomy. It is important to avoid postoperative complications causing a reduction in ovarian function to accomplish fertility-sparing surgery.