Maki Matoda

Detection of sentinel lymph node metastases in cervical cancer: Assessment of KRT19 mRNA in the one-step nucleic acid amplification (OSNA) method

OBJECTIVE The purpose of this study was to examine the utility of the one-step nucleic acid amplification (OSNA) assay using cytokeratin (CK) 19 (KRT19) messenger RNA (mRNA) for the detection of sentinel lymph node (SLN) metastases in cervical cancer patients. METHODS To determine a cutoff value, KRT19 mRNA was assessed by OSNA assay using 239 lymph nodes (LNs) (217 histopathologically negative LNs and 22 positive LNs). A cutoff value was determined by statistical analysis of the copy numbers obtained by OSNA assay. Subsequently, performance evaluation of the OSNA assay (applying the cutoff value above) on 130 SLNs (32 patients) was used to investigate (through concordance) whether the OSNA assay exhibited diagnostic performance equivalent to the two-mm interval histopathological examination. RESULTS Two hundred fifty copies/μL of KRT19 mRNA in the OSNA assay appeared to be an optimal cutoff value. In performance evaluation of the OSNA assay, we identified five positive SLNs and 125 negative SLNs by OSNA assay using KRT19 mRNA, exhibiting 96.2% agreement with two-mm interval histopathological examination. CONCLUSIONS Our results indicated that the KRT19 mRNA OSNA assay can detect LN metastases as accurately as two-mm interval histopathological examination and thus may be an effective additional or alternative method for a rapid intra-operative examination of SLNs in cervical cancer.

Clinicopathologic features and treatment outcomes of primary extramammary Paget disease of the vulva.

Objective The aim of this study was to identify the clinicopathologic features and treatment outcome of primary extramammary Paget disease of the vulva (EMPDV). Materials and Methods We performed a retrospective analysis of 14 patients who were treated at our center from April 1994 to November 2010. Results The mean age of patients in our sample was 64.4 years (range = 47–83 y). We observed intraepithelial and invasive EMPDV in 11 (78.6%) and 3 (21.4%) patients, respectively. Moreover, we observed a positive incision margin in 9 patients (64.3%). During a median follow-up period of 69.5 months (range = 32–221 mo), we observed recurrence in 3 patients (21.4%), 2 of whom had invasive EMPDV and 1 had intraepithelial EMPDV. Time to recurrence was 16 and 18 months for patients with invasive EMPDV and 98 months for patients with intraepithelial EMPDV. The recurrence rate of intraepithelial EMPDV and invasive EMPDV was significantly different (9.1% and 66.7%, respectively, p < .028). Local recurrence occurred in all 3 patients, necessitating further surgical resection. One patient with recurrence of invasive EMPDV received adjuvant radiotherapy but died 101 months after the initial treatment. The other 2 patients remained alive without recurrence. We did not observe distant recurrence. Conclusions The recurrence rate of invasive EMPDV was high. However, because distant metastasis is rare, repeat surgical excision for recurrent EMPDV and long-term observation are necessary for a good prognosis.

Recurrence patterns of advanced ovarian, fallopian tube, and peritoneal cancers after complete cytoreduction during interval debulking surgery.

Objectives Similar to primary debulking surgery, complete resection of all macroscopic diseases during interval debulking surgery (IDS) is the primary objective while using neoadjuvant chemotherapy followed by IDS for advanced ovarian, fallopian tube, and peritoneal cancers. However, most patients develop recurrent disease even after complete cytoreduction during IDS. This study aims to identify recurrence patterns of the ovarian, fallopian tube, and peritoneal cancers in patients who underwent complete cytoreduction during IDS. Methods We retrospectively reviewed data of patients with stage III or IV ovarian, fallopian tube, and peritoneal cancers who were treated at our hospital from January 1, 2005, to December 31, 2011. Results In this study, 105 patients underwent neoadjuvant chemotherapy followed by IDS and achieved complete cytoreduction. The median follow-up period was 42.1 months. Recurrence was documented in 70 patients (66.7%), and 35 (33.3%) showed no evidence of disease. Peritoneal dissemination was the most common recurrence (60.0%) observed. In multivariate analysis, positive peritoneal cytology (P = 0.0003) and elevated pre-IDS serum CA125 levels (P = 0.046) were independent risk factors for recurrence. Conclusions After complete cytoreduction during IDS in patients with stage III or IV ovarian, fallopian tube, and peritoneal cancers, positive peritoneal cytology at IDS and elevated pre-IDS CA125 levels are associated with an increased risk of cancer recurrence. Positive peritoneal cytology during IDS is a particularly strong predictive factor for poor outcomes in these patients.

Platinum-free interval in second-line chemotherapy for recurrent cervical cancer.

Objective The purpose of this study was to determine whether the platinum-free interval (PFI) was a predictive indicator in second-line treatment of cervical cancer in patients who had undergone prior platinum-based chemotherapy. The role of the PFI in selecting the second-line regimen in other gynecologic malignancies is also discussed. Methods In this retrospective study, we examined the clinical records of patients with recurrent or metastatic cervical cancer who had received platinum-containing combination regimens as second-line chemotherapy. All patients had received prior platinum-containing chemotherapy or concurrent chemoradiotherapy. Results The overall response rate to second-line chemotherapy was 25.8%; 7 patients achieved a complete response and 17 a partial response. The median progression-free survival (PFS) was 5.1 months and median overall survival (OS) was 13.5 months. The response rate was 12.5%, 14.2%, 20.0%, 22.2%, and 55.0%; median PFS was 4.0, 5.1, 4.4, 5.8, and 7.4 months; and median OS was 10.2, 14.4, 11.9, 16.3, and 19.7 months when PFI was within 3, 3 to 5, 6 to 11, 12 to 23, and more than 24 months, respectively. Age (>50 years), size (>3 cm), prior radiotherapy, and PFI (>24 months) were identified as prognostic factors in the multivariate analysis for PFS and OS. Conclusions The results indicate that a PFI of more than 24 months is the discriminating point between platinum-sensitive and platinum-resistance cervical cancer. This indicates that PFI offers a useful tool in selecting agents for second-line chemotherapy in a wide range of gynecologic malignancies.

Prognosis for endometrial cancer patients treated with systematic pelvic and para-aortic lymphadenectomy followed by platinum-based chemotherapy.

Objective The purpose of this study was to analyze the prognosis for endometrial cancer patients treated with systematic pelvic and para-aortic lymphadenectomy (PLA and PALA) followed by platinum-based chemotherapy. Materials and Methods From 1994 to 2004, in the Cancer Institute Hospital, 502 patients who were surgically treated with systematic PLA and PALA were enrolled in this study. Their prognosis and clinicopathological features were retrospectively reviewed. Results One hundred ninety-one (38.0%) patients received adjuvant platinum-based chemotherapy. Lymph node (LN) metastasis was observed in 80 (15.9%) patients, pelvic-only LN metastasis in 27 (5.4%), para-aortic-only LN metastasis in 15 (3.0%), and both pelvic and para-aortic LN metastasis in 38 (7.6%). The median number of metastatic LNs was 2 (range, 1–57), 1 (range, 1–4), and 6 (range, 2–50) in patients with pelvic-only, para-aortic-only, and both pelvic and para-aortic LN metastasis, respectively (P < 0.001). Only 2.6% (2/76) of patients with no myometrial invasion had LN metastasis, and no less than 8.9% (22/247) of patients with myometrial invasion (limited to the inner half) had LN metastasis. Five-year overall survival (OS) for LN metastasis–negative and –positive patients was 96.7% and 76% (P < 0.001), respectively. Five-year OS for patients with metastasis in 1 or 2 LNs was 84.8% and was significantly higher than that for patients with metastasis in 3 or more LNs (57.8%; P = 0.011). In patients with LN metastasis, 5-year OS of endometrioid adenocarcinoma and non–endometrioid adenocarcinoma cell types was 90.2% and 56.7% (P = 0.0016), respectively. Conclusions Under the settings of thorough PLA and PALA followed by intensive platinum-based chemotherapy for endometrial cancer, metastasis in 1 or 2 LNs seems to have little effect on survival, although para-aortic LNs are involved. This therapeutic strategy could not improve the prognosis of patients with metastasis in 3 or more LNs or patients with non–endometrioid adenocarcinoma cell types along with LN involvement.

Unexpected tumor progression after conization for carcinoma in situ of the uterine cervix.

Aim:  To determine the safety and usefulness of conization with an electrosurgical loop (the loop electrosurgical excision procedure [LEEP]) in young women with carcinoma in situ (CIS) of the uterine cervix.

Clinical characteristics of non-squamous cell carcinoma of the vagina.

Objective The prognosis and vaginal disease control rate after treatment with radiotherapy or concurrent chemoradiotherapy (CCRT) are reported to be worse for primary non–squamous cell carcinoma (non-SCC) of the vagina than for squamous cell carcinoma (SCC) of the vagina. Our objective was to examine the clinicopathological characteristics of primary non-SCC of the vagina and suggest an appropriate treatment strategy. Materials and Methods In a retrospective chart review, we identified patients with primary vaginal cancer who were treated in our hospital between 1990 and 2013. Twelve patients with histologically diagnosed non-SCC were identified. None of these cases was associated with in utero diethylstilbestrol exposure. Clinical data, including patient characteristics, stage, treatment outcome, and the site of recurrence, were recorded. Results The 12 identified cases included 5 of clear cell carcinoma, 3 of adenocarcinoma, 2 of adenosquamous carcinoma, 1 of carcinosarcoma, and 1 of mucinous adenocarcinoma. The most common location of the tumor was the upper one third of the vagina (56%). Initial treatment involved surgery in 8 patients. Among them, 4 received adjuvant chemotherapy, 3 received adjuvant radiotherapy, and 1 received neither. The initial treatment among the remaining 4 patients was CCRT in 1, neoadjuvant chemotherapy in 2 (followed by CCRT or surgery), and best supportive care in 1. The last 3 patients had lung metastasis. Six patients experienced recurrence, including vaginal recurrence in 2 patients and lymphatic spread in 4 patients. Five of these 6 patients experienced hematogenous metastasis. Conclusions Despite the absence of in utero diethylstilbestrol exposure in our cases, clear cell adenocarcinoma accounted for 41.7% (5/12) cases. A favorable local control rate was achieved in all 12 cases, but the incidence of distant metastasis, especially to the lung, was high. Prevention of distant metastasis may be the key to treating patients with non-SCC of the vagina.

Usefulness of intraoperative imprint cytology in ovarian germ cell tumors.

Objective: This study retrospectively investigated the usefulness of intraoperative diagnosis based on imprint cytology and frozen sections for ovarian germ cell tumor. Study Design: Intraoperative studies were reviewed for 23 cases with ovarian germ cell tumor treatment for which both frozen sections and imprint cytology were available. Final histopathologic diagnoses were compared with those based on intraoperative examinations. Results: Underlying pathologies included dysgerminoma (n = 6), yolk sac tumor (n = 1), non-gestational choriocarcinoma (n = 1), mature cystic teratoma with malignant transformation (n = 1), immature teratoma (n = 11), and mixed germ cell tumor (n = 3). Discrepancies between intraoperative imprint cytology and definitive histologic diagnosis were seen in 6 of the 23 cases. Accuracy was 54.5% (6/11) for immature teratoma and 91.7% (11/12) for other tumors. Cytologic examination facilitated accurate diagnosis in both of our cases, and intraoperative diagnosis by frozen section proved inaccurate. Conclusion: These results demonstrate that intraoperative assessment based on imprint cytology for immature teratoma has a relatively lower sensitivity, but an acceptable sensitivity for other germ cell tumors. Diagnostic approaches combining frozen sections and imprint cytology are advisable to improve the yield for intraoperative diagnosis.

Analysis of A Single Para-Aortic Lymph Node Metastasis in Endometrial Cancer

Objective: To determine the indication for lymph node dissection in patients with endometrial cancer, we investigated the incidence and distribution of single metastatic lymph nodes in patients who underwent systematic pelvic and para-aortic lymph node dissection.Methods: This study involved 910 patients with endometrial cancer who were treated at the Cancer Institute Hospital, Japan, between January 1994 and December 2015. All patients underwent an open hysterectomy with bilateral salpingo-oophorectomy and pelvic and para-aortic lymph nodes dissection.Results: Lymph node metastasis was observed in 199 patients (21.9%), 45 (5%) of whom had single lymph node metastasis. Single lymph node metastasis accounted for 22.6% of all metastatic cases. Myometrial invasion >50% was observed in 30 patients, whereas 15 patients had <50% myometrial invasion. When mapping single lymph node metastatic sites, the para-aortic area had a frequency of 31.1% (14 cases). The distribution of single metastatic lymph nodes spanned a wide area between the pelvic and para-aortic regions. Considering single metastatic nodes and myometrial invasion, 8 patients (53.3%) who had myometrial invasion <50% had a single metastatic node in the para-aortic region. Four of 9 patients (45%) considered low-risk (endometrioid Grade 1-2, invasion depth <50%, no lymphovascular space invasion) showed metastasis to the para-aortic areas.Conclusion: Single metastatic lymph nodes were widely distributed between the pelvic and para-aortic regions, suggesting that detection of a sentinel lymph node in patients with endometrial cancer could be problematic.

Review of Treatment and Prognosis of Stage IVB Cervical Carcinoma.

Objectives In most patients, stage IVB cervical cancer is incurable, and the outcomes are poor. There is significant individual variation in patients with stage IVB cervical cancer, in whom standard treatment has not been well defined. This study aims to review the outcomes and discuss treatment strategies in patients with stage IVB cervical cancer. Methods From January 1, 1992, to December 31, 2011, we retrospectively reviewed the data of patients with stage IVB cervical cancer who were given a diagnosis at the Department of Gynecology of the Cancer Institute Hospital. Results A total of 111 patients were enrolled. At the time of analysis, the median overall survival (OS) was 16.6 months (range, 0.2–120.9 months), and the 5-year OS rate was 20.2%. The 5-year OS rate was 59.4% for those with only para-aortic lymph node metastases; 24.8% for those with lymphogenous metastases, excluding those with only para-aortic lymph node metastases; 6.1% for those with hematogenous metastases; and 0% for those with disseminated metastases. The OS in patients with lymphogenous metastases was better compared with that of those with either hematogenous or disseminated metastases (P < 0.0001). In multivariate analysis, the performance status, site of metastases (only lymph node or other metastases), and local stage were all independent prognostic factors. Conclusions We determined performance status, site of metastases (only lymph node or other metastases), and local stage as independent prognostic factors in patients with stage IVB cervical cancer. Regarding treatment, we confirmed that the effectiveness of chemotherapy was also of significance.