Kazuo Asanoma

Fibronectin mediates activation of stromal fibroblasts by SPARC in endometrial cancer cells

AbstractBackgroundMatricellular glycoprotein, SPARC is a secreted molecule, that mediates the interaction between cells and extracellular matrix. SPARC functions as a regulator of matrix organization and modulates cell behavior. In various kinds of cancer, strong SPARC expression was observed in stromal tissues as well as in cancer epithelial cells. The function of SPARC in cancer cells is somewhat controversial and its impact on peritumoral stromal cells remains to be resolved.MethodsWe investigated the effects of SPARC expression in endometrial cancer cells on the surrounding stromal fibroblasts using in vitro co-culture system. Changes in characteristics of fibroblasts were examined by analysis of fibroblast-specific markers and in vitro contraction assay.ResultsSPARC induced AKT phosphorylation and epithelial-to-mesenchymal transition, consistent with previous reports. Cancer-associated fibroblasts of endometrial cancer expressed higher levels of mesenchymal- and fibroblast-associated factors and had a stronger contraction ability. Unexpectedly, cancer-associated fibroblasts expressed comparable levels of SPARC compared with fibroblasts from normal endometrium. However, co-culture of normal fibroblasts with SPARC-expressing Ishikawa cells resulted in activation of the fibroblasts. Immunodepletion of SPARC did not affect the activation of fibroblasts.ConclusionsOur data indicated that SPARC activated fibroblasts only in the presence of fibronectin, which was abundantly secreted from SPARC-expressing endometrial cancer cells. These results suggested that a SPARC-fibronectin-mediated activation of fibroblasts might be involved in enhanced mobility and invasion of cancer cells.

Sentinel Lymph Node Detection Using SPECT and Gamma Probe in Low‐Risk Endometrial Cancer: Efficacy and Factors Associated With Detection Failure

ABSTRACT Introduction This study examined factors that affected sentinel lymph node (SLN) identification of patients with endometrial cancer having a preoperative estimation of low recurrent risk. Methods This study included 97 patients with endometrial cancer who attempted to identify SLN using a uterine cervical injection of technetium‐99 m phytate under laparoscopic or robotic‐assisted surgery at our institute. A preoperative single photon emission computed tomography (SPECT) and intraoperative gamma probe were used to detect hot nodes. Multiple clinical factors, including age, body mass index (BMI), and so on, were investigated for their association with SLN mapping failure. Results Among 97 cases, SPECT failed to detect SLN unilaterally in 38 cases (39%) and on both sides in 9 cases (9%). Meanwhile, the gamma probe failed to detect SLN unilaterally in 23 cases (24%) and on both sides in 3 cases (3%). While only age was significantly associated with SLN detection failure using the SPECT detection system, both age and BMI were significantly associated with SLN detection failure using the gamma probe detection system. When limiting to the preoperative SLN detection failure cohort of 47 cases, there was a strong association between intraoperative SLN detection failure and BMI, but not age. Conclusion The SLN biopsy system was effectively applied to patients with endometrial cancer who underwent minimally invasive surgery (MIS). Attempts to improve SLN identification in older patients and those with obesity are warranted to obtain maximum benefits of MIS for low‐ or medium‐risk cases.

Impact of obesity on robotic‐assisted surgery in patients with stage IA endometrial cancer and a low risk of recurrence: An institutional study

AbstractAimWesternization of lifestyle has increased the numbers of patients with endometrial cancer and obesity. This study aimed to compare the clinical outcomes of robotic‐assisted surgery according to whether patients are obese, morbidly obese, or nonobese.MethodsSixty‐three patients with endometrial cancer who underwent robotic‐assisted surgery between March 2014 and June 2022 were categorized according to whether they had a body mass index (BMI) <30 (group A, nonobese, n = 40), ≥30 and <35 (group B, obese, n = 13), or ≥35 (group C, morbidly obese, n = 10). Operation time, blood loss, perioperative complications, and recurrence rate were investigated.ResultsConversion to laparotomy was required in one case in group A and one in group C. There was no difference in total operation time, time for setting (including trocar installation and docking of the da Vinci robot), console time, or time for wound closure between the groups; however, there was a significant between‐group difference in the total time for setting and wound closure. There was no significant difference in blood loss or complications between the groups. Three patients in group A and two in group B received adjuvant treatment; none have shown evidence of recurrent disease during a mean observation time of 21 months (range, 2–29). Two cases in group A and one in group B had recurrence during a mean observation time of 38 months (range, 19–46).ConclusionPatients with endometrial cancer who are obese can be treated safely by robotic‐assisted surgery with a low risk of complications and few relapses.

Obstetric Outcome After Trachelectomy for Cervical Cancer Without Uterine Artery Preservation

ABSTRACT Aim A trachelectomy is a fertility‐preserving surgery that is performed for cervical cancer. Transecting the uterine arteries (UAs) during abdominal radical trachelectomy (ART) or abdominal modified radical trachelectomy (AmRT) has the advantage of simplifying other surgical procedures. However, the effect of UA transection on subsequent pregnancy outcome is unknown. The purpose of this study was to clarify the pregnancy outcomes in post‐RT pregnancies in which the UAs were not preserved. Methods This was a retrospective cohort study of electronic case records involving pregnant women after ART and AmRT, which were managed at Kyushu University Hospital from January 2008 to July 2024. Results Complications that often occur in pregnancies after ART and AmRT, such as antepartum bleeding, premature birth, and preterm premature rupture of membranes, were noted to the same degree after UA‐sparing ART. In contrast, abnormalities related to placental attachment, such as placenta previa and adherent placenta, occurred at a high rate after UA transection. Furthermore, compared to pregnancies with normal placentation, pregnancies with abnormal placentation had more blood loss during cesarean section (1150 g vs. 2289 g; p  = 0.0004) and required blood transfusion more frequently (5.7% vs. 64.2%; p  < 0.0001). Conclusions Although ART and AmRT with UA transection may increase the risk of abnormal placentation and bleeding‐related complications during cesarean section, UA transection may not increase the risk of major obstetric complications after ART and AmRT. Therefore, UA transection should be considered during ART and AmRT due technical advantages.

Retrospective analysis of treatment and prognosis for clear cell carcinoma of the uterine cervix: 15‐year experience at a single institution

AbstractAimClear cell carcinoma of the uterine cervix (CCCUC) is a rare disease, accounting for 4% to 9% of cervical adenocarcinomas. Because it is so rare, its pathogenesis is largely unknown, and the standard treatment is unclear due to a lack of prospective studies. Our aim is to investigate the clinical features, treatment, and prognosis of CCCUC.MethodsWe retrospectively evaluated the clinical characteristics, treatment choices, and outcomes of 12 patients with CCCUC treated at our institution between January 2009 and July 2024.ResultsThe median patient age was 62.5 years (range, 14–90 years). The most common stage was IB (IA, n = 3; IB, n = 4; IIB, n = 1; IIIC, n = 2; IVB, n = 2). Ten patients underwent surgery as initial treatment: 6 underwent radical hysterectomy plus pelvic lymphadenectomy (PLD) or sentinel lymph node biopsy (SLNB), with or without para‐aortic lymphadenectomy (PALD); 3 underwent modified radical hysterectomy plus PLD with or without PALD; and 1 underwent radical trachelectomy with SLNB as fertility‐preserving surgery. All patients underwent bilateral salpingo‐oophorectomy except for the patient who opted for radical trachelectomy. Five patients received adjuvant treatment: 3 received platinum‐based systemic chemotherapy (2 of whom had combination therapy with bevacizumab), and 2 received concurrent chemoradiotherapy. The median follow‐up was 43.5 months (range, 1–123 months). The 5‐year progression‐free survival rate was 64.5%.ConclusionSystemic platinum‐based chemotherapy with bevacizumab may be more effective than concurrent chemoradiotherapy as adjuvant therapy for CCCUC.