Kyoko Nishikimi

ARID1A expression in ovarian clear cell carcinoma with an adenofibromatous component

The carcinogenesis of ovarian clear cell carcinoma (CCC) has been hypothesized to comprise two different pathways: an adenofibroma–carcinoma sequence and an endometriosis–carcinoma sequence. However, the difference in the genetic basis of these two pathways remains unclear. Recent studies have suggested that an ARID1A mutation and the loss of the corresponding protein, BAF250a, are frequent events in CCC. Herein, we investigated the difference in the loss of BAF250a expression in adenofibroma‐related CCC and endometriosis‐related CCC.

Surgical anatomy of the common iliac veins during para-aortic and pelvic lymphadenectomy for gynecologic cancer

Objective Compression of the left common iliac vein between the right common iliac artery and the vertebrae is known to be associated with the occurrence of left iliofemoral deep vein thrombosis (DVT). In this study, we described the variability in vascular anatomy of the common iliac veins and evaluated the relationship between the degree of iliac vein compression and the presence of DVT using the data from surgeries for gynecologic cancer. Methods The anatomical variations and the degrees of iliac vein compression were determined in 119 patients who underwent systematic para-aortic and pelvic lymphadenectomy during surgery for primary gynecologic cancer. Their medical records were reviewed with respect to patient-, disease-, and surgery-related data. Results The degrees of common iliac vein compression were classified into three grades: grade A (n=28, 23.5%), with a calculated percentage of 0%-25% compression; grade B (n=47, 39.5%), with a calculated percentage of 26%-50% compression; and grade C (n=44, 37%), with a calculated percentage of more than 50% compression. Seven patients (5.9%) had common iliac veins with anomalous anatomies; three were divided into small caliber vessels, two with a flattened structure, and two had double inferior vena cavae. The presence of DVT was associated with the elevated D-dimer levels but not with the degree of iliac vein compression in this series. Conclusion Although severe compression of the common iliac veins was frequently observed, the degree of compression might not be associated with DVT in surgical patients with gynecologic cancer. Anomalous anatomies of common iliac veins should be considered during systematic para-aortic and pelvic lymphadenectomy in the gynecologic cancer patients.

Daily low-dose cisplatin-based concurrent chemoradiotherapy in patients with uterine cervical cancer with emphasis on elderly patients: a phase 2 trial.

Objective We evaluated the usefulness of daily low-dose cisplatin-based concurrent chemoradiotherapy (daily CCRT) in patients with cervical cancer with an emphasis on elderly patients. Methods Between January 2003 and December 2008, a total of 65 patients with untreated stage IIA to IIIB cervical cancer were enrolled and 54 were selected for this nonrandomized prospective study. The daily CCRT comprised pelvic external beam radiotherapy (2 Gy/d × 25) with daily low-dose cisplatin (8.0 mg/m2 per day) and either low- or high-dose rate intracavitary brachytherapy. Results The median age of the patients was 62 years (range, 29–85 years), and 21 patients (39%) were 70 years or older. The median follow-up period was 47 months (range, 4–107 months). Daily CCRT was successfully completed in 91% (49/54) of the patients. The mean total cisplatin dose was 191 mg/m2 (range, 128–224 mg/m2), and a neutropenia grade higher than 3 was observed in 24% of the patients. Of the 21 patients 70 years or older, 17 (81%) completed daily CCRT with acceptable toxicity. The 3-year overall survival (OS) rate for all the patients was 82.9%. No statistically significant differences in the OS rate and toxicity were observed between patients 70 years or older and those younger than 70 years. Conclusions Daily CCRT showed acceptable toxicity and compliance, leading to the use of a high total dosage of cisplatin. The OS rate for daily CCRT was comparable to that for previously reported weekly CCRT. Daily CCRT could be an alternate choice for the CCRT treatment in elderly patients with cervical cancer.

Bladder function after modified posterior exenteration for primary gynecological cancer

OBJECTIVE Bladder dysfunction caused by autonomic nerve injury is a well-recognized complication of pelvic surgery. Modified posterior exenteration with or without nerve preservation was performed in patients with primary ovarian, tubal, peritoneal, and endometrial cancer. The aim of this retrospective study was to evaluate the impact of this surgical technique on bladder function. METHODS Among the 60 consecutive patients in whom modified posterior exenteration was performed, bilateral and unilateral nerve-sparing surgeries were performed in 43 (72%) and 15 (25%) patients, respectively. In the remaining 2 patients (3%), the pelvic autonomic nerves on both sides were sacrificed. Symptoms and bladder function after bilateral or unilateral nerve-sparing surgery were analyzed using standardized questionnaires before and 3 and 6 months after surgery. RESULTS All patients with bilateral nerve-sparing surgery had sufficient micturition from the early postoperative period. Though 40% of the patients with unilateral nerve-sparing surgery had difficulty in spontaneous voiding and needed intermittent catheterization, voiding ability of them improved and no self-catheterization was required 3 months after surgery. The assessment of patient questionnaires suggested that bladder function was acceptable in both groups at 6 months. Patients with bilateral nerve-sacrificing surgery complained of neurogenic bladder requiring self-catheterization even 6 months after surgery. CONCLUSIONS This preliminary study showed that preservation of bladder function after modified posterior exenteration was feasible with a nerve sparing approach and that standardized outcome measures could be used to monitor this. However, careful follow-up is required. Future larger studies are needed to investigate pelvic autonomic nerve function.

The Efficacy of Palonosetron Plus Dexamethasone in Preventing Chemoradiotherapy-induced Nausea and Emesis in Patients Receiving Daily Low-dose Cisplatin-based Concurrent Chemoradiotherapy for Uterine Cervical Cancer: A Phase II Study.

Objectives: The prevention of chemotherapy-induced and radiotherapy-induced emesis is recommended by several guidelines; however, there are no evidence-based recommendations for the use of antiemetics in concurrent chemoradiotherapy (CCRT). The aim of the present study was to evaluate the efficacy and safety of antiemetic therapy comprising palonosetron and dexamethasone during CCRT. Methods: This is a nonrandomized, prospective, single-center, open phase II study. Twenty-six consecutive patients with cervical carcinoma were treated with daily low-dose cisplatin (8 mg/m2/d)-based CCRT (2 Gy/d, 25 fractions, 5 times a week). All patients received 0.75 mg of palonosetron on day 1 of each week and 4 mg of oral dexamethasone daily. The primary endpoint was the percentage of patients achieving a complete response, which was defined as no emetic episodes and no antiemetic rescue medication during treatment. Results: Planned daily low-dose cisplatin-based CCRT was successful without delay or interruption in 46% (12/26) of the patients. The mean dose of total cisplatin was 184 (range, 136 to 200) mg/m2. No patient vomited during the treatment period. The complete response rate during CCRT was 100%. A total of 81% patients were completely free from nausea. All patients tolerated the combination of palonosetron and dexamethasone and completed the scheduled regimen. Five patients exhibited grade 1 Cushingoid features that resolved after treatment. Conclusions: Antiemetic therapy comprising palonosetron and dexamethasone provided complete protection from nausea and vomiting in patients with cervical cancer receiving daily low-dose cisplatin-based CCRT.

Daily low-dose Cisplatin-based concurrent chemoradiotherapy for the treatment of cervical cancer in patients 70 years or older.

Objectives It has been established that concurrent chemoradiotherapy (CCRT) is efficacious for cervical cancer, but adherence is unsatisfactory among elderly patients. To improve adherence, we have developed and initiated a daily low-dose cisplatin-based CCRT regimen. Here, we retrospectively evaluated the use of CCRT, especially for elderly patients. Methods The study included a total of 53 patients who were 70 years or older, had stage IB-IVA cervical cancer, and were initially treated with daily CCRT. The daily CCRT comprised pelvic external beam radiotherapy (2 Gy/d × 25) with daily low-dose cisplatin (8.0 mg/m2 per day) and either low- or high-dose-rate intracavitary brachytherapy. Results The median age was 72 years (range, 70–85 years). The median follow-up duration was 32 months (range, 2–104 months). The 3-year overall survival rate was 79.0%. Daily cisplatin chemotherapy was successfully completed in 32 (60.4%) of the 53 patients. Grade 3 or 4 neutropenia was observed in 19 patients (36%). A late complication of grade 3 rectal hemorrhage occurred in 3 patients who received high-dose-rate brachytherapy. All primary tumors responded to daily CCRT; complete response was observed in 43 patients (91.5%) and partial response was observed in 4 patients (8.5%). Conclusions Daily CCRT in patients 70 years and older had acceptable compliance and safety. Daily CCRT is suggested to be a good treatment option for elderly patients who have advanced cervical cancer and require concurrent cisplatin.

Cytologic findings of low grade endometrial stromal sarcoma with sex cord-like differentiation: a case report.

BACKGROUND To report the cytologic characteristics of low grade endometrial stromal sarcoma with sex cord-like differentiation. CASE A 49-year-old woman presented with hypermenorrhea, menorrhalgia and anemia. With a diagnosis of degenerated leiomyoma of the uterus, simple total hysterectomy was conducted. Histologic examination revealed cells with ovoid to short, spindle-shaped nuclei resembling endometrial stromal cells proliferating in a space-occupying manner and compressing and partially infiltrating the myometrium. Some tumor cells were arranged in sex cord-like form, and hyalinization was observed in the center of the cord. Low grade endometrial stromal sarcoma with sex cord-like differentiation was diagnosed. Touch imprint cytologic examination of the tumor showed cells containing scanty cytoplasm and ovoid to spindle-shaped nuclei with little atypia; they were scattered individually, aggregated in clusters, or arranged in cord or glandular form. Hyaline-like substance was present in abundance. The histologic characteristics of the endometrial stromal sarcoma with sex cord-like differentiation were confirmed by touch imprint cytology of the tumor. CONCLUSION In this case of low grade endometrial stromal sarcoma with sex cord-like differentiation, cytologic examination revealed hyaline substance and tumor cells aligned in cord or glandular form.

Survival and safety associated with aggressive surgery for stage III/IV epithelial ovarian cancer: A single institution observation study

OBJECTIVE We evaluated the efficacy and safety of aggressive surgery for advanced ovarian cancer at a non-high-volume center. MATERIALS AND METHODS We evaluated consecutive patients with stage III/IV ovarian, fallopian, and peritoneal cancer undergoing elective aggressive surgery from January 2008 to December 2012, which encompassed the first 5years after implementing an aggressive surgery protocol. After receiving appropriate training for 9months, a gynecological surgical team began performing multi-visceral resections. Primary debulking surgery was chosen when the team considered that optimal surgery was achievable on the initial laparotomy, otherwise interval debulking surgery was chosen (the protocol treatments). Analysis was performed on an intention-to-treat basis (full-set analysis), and outcomes were compared to those of patients who underwent standard surgery between 2000 and 2007. RESULTS Of 106 consecutive patients studied, 87 (82%) underwent aggressive surgery per protocol and 19 were excluded. Serous carcinoma was the most common disease (78%), followed by clear cell carcinoma (7%), and 32% of the patients had stage IV disease. The respective median progression-free and overall survival rates increased from 14.6 and 38.1months before implementation, respectively, to 25.0 and 68.5months after implementation, respectively. Complete resection was achieved in 83 of the 106 patients (78%), and the surgical complexity score was high (>8) in 61 patients (58%); although there was no mortality within 12weeks of surgery, major complications occurred in 8 patients. CONCLUSIONS We confirmed that outcomes improved after implementing aggressive surgery for advanced ovarian cancer, without causing a significant increase in mortality. Factors enhancing survival outcomes are discussed.

Management of pancreatic fistulas after a splenectomy as part of cytoreductive surgery for ovarian cancer.

Objective This study evaluated the incidence of postoperative morbidities, focusing specifically on pancreatic fistulas, after a splenectomy performed as part of cytoreductive surgery for the treatment of ovarian cancer. Methods A retrospective chart review was performed for all the patients with ovarian, tubal, or peritoneal cancer who underwent splenectomy during a 5-year period. Patient-, disease-, and surgery-related data were collected. Pancreatic fistulas were identified when the drainage fluid obtained via a surgically placed drain had an amylase content greater than 3 times the normal serum value after postoperative day 3. Results A splenectomy was performed in 21 patients. Postoperative pancreatic fistulas developed in 6 patients (29%). Of these 6 patients, 2 had no symptoms and did not require specific treatment for their pancreatic fistulas. Therapeutic intervention was required in the remaining 4 patients. The durations of oral feeding prohibition and the use of a peripancreatic drain were longer in the patients with a pancreatic fistula than in those without a pancreatic fistula. Overall, the pancreatic fistulas were managed conservatively or using minimally invasive procedures. Staple-line reinforcement seemed to be an effective means of closing the transected stump during the splenectomy, compared with the standard stapling technique. Conclusions Elevated amylase levels in the drainage fluid reflect the patient’s actual condition better than serum amylase levels. We recommend the intraoperative placement of a peripancreatic drain and postoperative measurement of amylase concentrations in the drainage fluid to identify the development of pancreatic fistulas and to facilitate the management of this complication.

Retroperitoneal lymphadenectomy for ovarian cancer with double inferior vena cava

Objective Double inferior vena cava (IVC) is present in 1.0%–3.0% of the general population and can create clinical problems [1,2]. This anomaly is classified according to the presence and pattern of an interiliac vein; 23% of double-IVC cases do not have an interiliac vein, and variations exist in those with one [3]. Fewreports on retroperitoneal lymphadenectomy in patients with a double IVC exist. Herein, we show retroperitoneal lymphadenectomies in two patients with different double IVC classifications. Methods We performed an interval debulking surgery, including retroperitoneal lymphadenectomy, in two cases of advanced ovarian cancer with double IVC. The retroperitoneal lymphadenectomy procedure was the same as that for patients with normal IVC. Case 1 involved a 53-year-old female having a double IVC without an interiliac vein. Case 2 involved a 51-year-old female having a double IVC with an interiliac vein from the right common iliac vein to the left IVC. Preoperative enhanced computed tomography revealed double IVC flow pattern in both cases; however, the presence of the interiliac vein in case 2 remained unrecognized. Results Lymphadenectomy in case 1 was without complications. In case 2, major bleeding from the interiliac vein occurred during lymphatic tissue removal from the front of the sacral region. The bleeding was difficult to stop, and was finally stopped using Tacho Sil®. We then completed lymphadenectomy. Conclusions During retroperitoneal lymphadenectomy in patients with a double IVC, it is important to determine the presence of an interiliac vein. Furthermore, its flow pattern should be considered with care.