Tomohito Tanaka

Clinical utility and characteristics of comprehensive genomic profiling tests in patients with gynecologic cancer: a multi-institutional survey in Kinki District, Japan

Robot‐assisted modified radical hysterectomy with removal of lymphatic vessel using indocyanine green: A new method

AbstractBackgroundThe sentinel lymph node (SLN) procedures using indocyanine green (ICG) have recently been performed worldwide. The aim of this study was to emphasise the safety of robot‐assisted modified radical hysterectomy (RAMRH) with removal of the lymphatic vessels (RLV) using ICG in endometrial cancer according to a single surgeon's experience.MethodsRobot‐assisted modified radical hysterectomy with RLV using ICG was performed in patients with endometrial cancer. We compared 34 cases of RAMRH with RLV, with 54 patients without RLV.ResultsThe median (interquartile range) time for the procedure did not differ between the RAMRH with and without RLV groups (88 [80–114] vs. 88 [79–104] min, p = 0.7). The success rate of RLV was 100% when SLNs were detected.ConclusionRobot‐assisted modified radical hysterectomy with RLV using ICG can completely dissect tissue from the uterus, including lymphatic vessels. This procedure using a robotic system with ICG, is simple and does not require additional time.

Oncologic outcomes in elderly patients who underwent hysterectomy for endometrial cancer: a multi-institutional survey in Kinki District, Japan

The goal of this study is to assess the oncologic outcomes of elderly patients who underwent hysterectomy for endometrial cancer across three variables: hysterectomy approach, lymph node resection, and adjuvant therapy. Hospital records of patients aged ≥ 70 years who underwent hysterectomy for endometrial cancer were obtained from 19 institutions. Patients were categorized into three risk groups: low, intermediate, and high. In each group, disease-free survival and overall survival were compared according to hysterectomy approach, lymph node resection, and adjuvant therapy using Kaplan-Meier method. Cox regression analysis with a 95% confidence interval was performed to estimate relative risk (RR) of death. A total of 1246 patients were included. In the low-risk group, the adjusted RR for death for minimally invasive surgery (MIS) versus laparotomy and lymph node resection versus no lymph node resection were 0.64 (0.24-1.72) and 0.52 (0.24-1.12), respectively. In the intermediate-risk group, the adjusted RR for death for MIS versus laparotomy, lymph node resection versus no lymph node resection, and adjuvant therapy versus no adjuvant therapy were 0.80 (0.36-1.77), 0.60 (0.37-0.98), and 0.89 (0.55-1.46), respectively. In the high-risk group, the adjusted RRs for death for lymph node resection versus no lymph node resection and adjuvant therapy versus no adjuvant therapy were 0.56 (0.37-0.86) and 0.60 (0.38-0.96), respectively. MIS is not inferior to laparotomy in uterine-confined diseases. Lymph node resection improved the outcome for all disease stages and histological types. In contrast, adjuvant therapy improved the outcomes only in high-risk patients.

Oncologic outcomes for patients with endometrial cancer who received minimally invasive surgery: a retrospective observational study

Laparoscopic hysterectomy has been performed for patients with endometrial cancer as minimally invasive surgery; however, the long-term outcomes of high-risk disease compared to open surgery remain unclear. Eight hundred and eighty-three patients with endometrial cancer who underwent laparoscopic or abdominal hysterectomy were categorized into three groups. Low-risk disease was defined as stage IA disease with endometrioid carcinoma of grade 1 or 2. Uterine-confined disease was defined as stage IA disease with high-grade tumors or stage IB and II disease. Advanced disease was defined as stage III or IV disease. The progression-free survival (PFS) and overall survival (OS) rates were compared between laparoscopic and laparotomic hysterectomy. Among 478 patients with low-risk disease, including 226 with laparoscopy and 252 with laparotomy, the prognosis was not significantly different between the groups (3-year PFS rate, 97.4% vs. 97.1%, p = 0.8; 3-year OS rate, 98.6% vs. 98.3%, p = 0.9). Among the 229 patients with uterine-confined disease, including 51 with laparoscopy and 178 with laparotomy, the prognosis was not significantly different between the groups (3-year PFS rate, 90.5% vs. 85.5%, p = 0.7; 3-year OS rate, 91.3% vs. 92.5%, p = 0.8). Among the 176 patients with advanced disease, including 24 with laparoscopy and 152 with laparotomy, laparoscopic hysterectomy had a higher PFS rate and OS rate than laparotomic hysterectomy (3-year PFS rate, 74.5% vs. 51.5%, p = 0.01; 3-year OS rate, 92.3% vs. 75.1%, p = 0.03). Laparoscopic procedures are not associated with a poorer outcome than laparotomy in patients with advanced endometrial cancer or uterine-confined endometrial cancer.

The Diagnostic Accuracy of an Intraoperative Frozen Section Analysis and Imprint Cytology of Sentinel Node Biopsy Specimens from Patients with Uterine Cervical and Endometrial Cancer: a Retrospective Observational Study

Sentinel node biopsy (SNB) may be a decision-making tool for function preservation surgery, including radical trachelectomy and ovary preservation in the treatment of cervical and endometrial cancer. The intraoperative diagnosis is important for guiding treatment decisions for patients with these conditions. Three hundred seventy-one patients with cervical and endometrial cancer received SNB with an intraoperative frozen section analysis and imprint cytology. The sentinel node was cut in half, parallel to the longest axis, to obtain the maximum section area. After performing imprint cytology, one half was used to create a frozen section. The specimen was cut at 2-mm intervals into 5-μm-thick sections, which were subjected to hematoxylin and eosin staining. The diagnostic accuracy of intraoperative frozen section analyses and imprint cytology was compared to the final pathological diagnosis. Among 951 detected sentinel nodes, 51 nodes were found to be positive in the final pathological diagnosis. The sensitivity of a frozen section analysis, imprint cytology and the combination of the two modalities was 76.5%, 72.6%, and 92.2%, respectively. The specificity of a frozen section analysis and imprint cytology was 100%. The negative predictive value of a frozen section analysis and imprint cytology was 98.7% and 98.5%, respectively. In these settings, the accuracy of the frozen section analysis and imprint cytology in the evaluation of SNB specimens was considered acceptable; however, the sensitivity of the combined approach was higher in comparison to when a frozen section analysis or imprint cytology was performed alone.

Consistency between Primary Uterine Corpus Malignancies and Their Corresponding Patient-Derived Xenograft Models

Patient-derived xenograft (PDX) models retain the characteristics of tumors and are useful tools for personalized therapy and translational research. In this study, we aimed to establish PDX models for uterine corpus malignancies (UC-PDX) and analyze their similarities. Tissue fragments obtained from 92 patients with uterine corpus malignancies were transplanted subcutaneously into immunodeficient mice. Histological and immunohistochemical analyses were performed to compare tumors of patients with PDX tumors. DNA and RNA sequencing were performed to validate the genetic profile. Furthermore, the RNA in extracellular vesicles (EVs) extracted from primary and PDX tumors was analyzed. Among the 92 cases, 52 UC-PDX models were established, with a success rate of 56.5%. The success rate depended on tumor histology and staging. The pathological and immunohistochemical features of primary and PDX tumors were similar. DNA sequencing revealed similarities in gene mutations between the primary and PDX tumors. RNA sequencing showed similarities in gene expressions between primary and PDX tumors. Furthermore, the RNA profiles of the EVs obtained from primary and PDX tumors were similar. As UC-PDX retained the pathological and immunohistochemical features and gene profiles of primary tumors, they may provide a platform for developing personalized medicine and translational research.

Cancer-Specific miRNAs Extracted from Tissue-Exudative Extracellular Vesicles in Ovarian Clear Cell Carcinoma

Ovarian clear cell carcinomas (OCCs) arise from endometriotic cysts that many women develop. Biomarkers for early OCC detection need to be identified. Extracellular vesicles have attracted attention as biomarker carriers. This study aims to identify cancer-specific miRNAs as novel OCC biomarkers using tissue-exudative extracellular vesicles (Te-EVs). Te-EVs were collected from four patients with OCC on one side and a normal ovary on the other side. Microarray analysis was performed to identify cancer-specific miRNAs in Te-EVs. Serum samples obtained before and after surgery from patients with OCC and atypical endometrial hyperplasia (AEH) (controls) were compared using real-time PCR to examine changes in the detected EV miRNA levels. Thirty-seven miRNAs were >2-fold upregulated on the OCC side compared with the normal ovarian side. We selected 17 miRNAs and created specific primers for 12 of these miRNAs. The levels of six EV miRNAs were significantly decreased in postoperative OCC serum compared to those in preoperative OCC serum. In contrast, no significant change was observed between the pre and postoperative values in the control group. We identified OCC tissue-specific miRNAs in the EVs secreted by OCC tissues. These EV miRNAs have potential for use as biomarkers for the early diagnosis and detection of OCC.

Postsurgical urodynamic study of total laparoscopic nerve‐sparing radical hysterectomy for uterine cervical cancer

AbstractAimTo evaluate the impact on urodynamic results between the laparoscopic nerve‐sparing radical hysterectomy (LRH) following a step‐by‐step procedure and abdominal nerve‐sparing radical hysterectomy (ARH) for patients with uterine cervical cancer.MethodsThis retrospective study enrolled 76 patients with cervical cancer: 35 in the LRH group and 41 in the ARH group. We analyzed their postoperative bladder function in a urodynamics study and examined the volume of resected pelvic nerves contained in parametrial sections using S‐100 antibody staining.ResultsEstimated blood loss and hospital stay after operation for the LRH group were significantly better than those in the ARH group (p < 0.0001). As well, the number of harvested lymph nodes was significantly higher in the LRH group (p = 0.044). There was no difference in perioperative complications between the two groups in this study. The 5‐year disease‐free survival rates and overall survival rates were 91.2% and 94.0% in the LRH group and 87.8% and 95.1% in the ARH group, both respectively. Although the median residual urine volume were no statistical differences between the LRH group and the ARH group, the recovery of postoperative bladder function (uroflowmetry) in the LRH group rapidly reached presurgery levels at 1 month, and the LRH group had a smaller number of s‐100 antibody stained nerves contained the parametrial sections.ConclusionWe demonstrated that LRH following a step‐by‐step procedure could achieve a higher level of prevention of damage to the bladder branch of the pelvic splanchnic nerve plexus and thus restore bladder function more rapidly.

Comparison of Prognosis between Minimally Invasive and Abdominal Radical Hysterectomy for Patients with Early-Stage Cervical Cancer

Minimally invasive surgery (MIS) is performed to treat cervical cancer patients; however, a recent study showed that MIS was associated with higher recurrence and death rate compared with abdominal radical hysterectomy (ARH). In the current study, the prognosis of patients with early-stage cervical cancer who underwent MIS with vaginal closure or ARH was evaluated. One hundred and eighty-two patients underwent radical hysterectomy for cervical cancer with stage of IA2, IB1, and IIA1. MIS was performed by laparoscopy or a robot using the vaginal closure method. Disease-free survival (DFS) and overall survival (OS) were evaluated between the groups. Among the patients, 67 underwent MIS and 115 underwent ARH. The recurrence rate was 4.5% in MIS patients and 3.5% in ARH patients with a median follow-up (interquartile range) of 36 (18–60) and 78 (48–102) months, respectively. DFS and OS were not different between the groups (3y-DFS, 95.3% vs. 96.1%, p = 0.6; 3y-OS, 100% vs. 100%, p = 0.06). In early-stage cervical cancer patients, MIS with vaginal closure did not increase the risk for recurrence or death. Surgical techniques and procedures to avoid spillage of tumor cells could be important for a better prognosis.

Laparoscopic Approach to Cervical Cancer

The goal of this clinical research study is to compare the long-term outcomes of different surgical methods for the treatment of cervical cancer. The long-term outcome of a total abdominal radical hysterectomy (TARH) will be compared against laparoscopy. In this study, the laparoscopy will be done with or without robotic technology.