Novel nomogram developed for determining suitability of metastatic castration-resistant prostate cancer patients to receive maximum benefit from radium-223 dichloride treatment-Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial.

PURPOSE: To develop a novel nomogram for determining radium-223 dichloride (Ra-223) treatment suitability for metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: This Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial was a retrospective multicenter investigation enrolled 258 mCRPC patients in Japan with Ra-223 treatment between June 2016 and August 2020, with bone scintigraphy findings before treatment, clinical data, and survival outcome available. A nomogram was constructed using prognostic factors for overall survival (OS) based on a least absolute shrinkage and selection operator Cox regression model. A sub-analysis was also conducted for patients meeting European Medicines Agency (EMA) guidelines. RESULTS: Within a median of 17.4 months after initial Ra-223 treatment, 124 patients (48.1%) died from prostate cancer. Predictive factors included (1) sum of prior treatment history (score 0, never prior novel androgen receptor-targeted agents (ARTA) therapy, never prior taxane-based chemotherapy, and ever prior bisphosphonate/denosumab treatment), (2) Eastern Cooperative Oncology Group (ECOG) performance status, (3) prostate-specific antigen doubling time (PSADT), (4) hemoglobin, (5) lactate dehydrogenase (LDH), and (6) alkaline phosphatase (ALP) levels, and (7) automated bone scan index (aBSI) value based on bone scintigraphy. The nomogram using those factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.748 and 0.734, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.771, 0.818, and 0.771, respectively. In 227 patients meeting EMA recommendation, the nomogram with seven factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.722 and 0.704, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.747, 0.790, and 0.759, respectively. CONCLUSION: This novel nomogram including aBSI to select mCRPC patients to receive Ra-223 with significantly prolonged OS possibility was found suitable for assisting therapeutic decision-making, regardless of EMA recommendation.

Successful para-aortic lymph node dissection for endometrial cancer with horseshoe kidney: A case report and review of the literature.

Horseshoe kidney (HSK) is considered to impede para-aortic lymph node dissection. We report the case of a 54-year-old female patient with endometrial cancer and HSK, treated successfully with para-aortic lymph node dissection, and present literature review regarding vascular abnormalities associated with HSK affecting para-aortic lymph node dissection. Three-dimensional computed tomography reconstruction revealed the accessory renal artery, supernumerary renal vein and ventral displacement of the renal pelvis and ureter. Abdominal modified radical hysterectomy, bilateral salpingo-oophorec'tomy, pelvic and para-aortic lymph node dissection and omentectomy were then performed. Lymphadenectomy behind the isthmus of the kidney was performed without separation of the isthmus by lifting the kidneys with vessel tape. There were no intraoperative or postoperative complications. Grasping shifted ureter and complicated vascular network of HSK and securing the operative field without division of the isthmus were key to reducing complications and hemorrhage. This case report can serve as a guide for performing para-aortic lymph node dissection safely and effectively in patients with HSK.

Impact of hysteroscopic surgery for isthmocele associated with cesarean scar syndrome.

AIM: Cesarean scar syndrome (CSS) is characterized by increased risk of postmenstrual abnormal uterine bleeding, dysmenorrhea, and infertility, due to a post-cesarean scar defect known as an isthmocele. This study aimed to assess the impact of hysteroscopic surgery on isthmocele associated with CSS. METHODS: Eighteen patients with CSS were enrolled. Surgical methods included resection of the inferior edge and superficial cauterization of the isthmocele via hysteroscopic surgery. We evaluated the residual myometrial thickness and isthmocele volume using magnetic resonance imaging, before and after hysteroscopic surgery. RESULTS: All patients underwent surgery without any complications. The residual myometrium was thicker after hysteroscopic surgery (median: 2.1 mm and 4.2 mm, before and after surgery, respectively; P = 0.0001). Isthmocele volume was significantly reduced after hysteroscopic surgery (median: 494.9 mm3 and 282.8 mm3 , before and after surgery, respectively; P = 0.0016). CONCLUSION: This study demonstrated that hysteroscopic surgery is effective in increasing the residual myometrial thickness and reducing the size of isthmocele.

Assessing Therapeutic Response to Radium-223 with an Automated Bone Scan Index among Metastatic Castration-Resistant Prostate Cancer Patients: Data from Patients in the J-RAP-BSI Trial.

To evaluate the usefulness of change in the automated bone scan index (aBSI) value derived from bone scintigraphy findings as an imaging biomarker for the assessment of treatment response and survival prediction in metastatic castration-resistant prostate cancer (mCRPC) patients treated with Ra-223. This study was a retrospective investigation of a Japanese cohort of 205 mCRPC patients who received Ra-223 in 14 hospitals between July 2016 and August 2020 and for whom bone scintigraphy before and after radium-223 treatment was available. Correlations of aBSI change, with changes in the serum markers alkaline phosphatase (ALP) and prostate-specific antigen (PSA) were evaluated. Additionally, the association of those changes with overall survival (OS) was assessed using the Cox proportional-hazards model and Kaplan-Meier curve results. Of the 205 patients enrolled, 165 (80.5%) completed six cycles of Ra-223. Following treatment, ALP decline (%ALP < 0%) was noted in 72.2% (148/205), aBSI decline (%aBSI < 0%) in 52.7% (108/205), and PSA decline (%PSA < 0%) in 27.8% (57/205). Furthermore, a reduction in both aBSI and ALP was seen in 87 (42.4%), a reduction in only ALP was seen in 61 (29.8%), a reduction in only aBSI was seen in 21 (10.2%), and in both aBSI and ALP increasing/stable (≥0%) was seen in 36 (17.6%) patients. Multiparametric analysis showed changes in PSA [hazard ratio (HR) 4.30, 95% confidence interval (CI) 2.32-8.77, p < 0.0001], aBSI (HR 2.22, 95%CI 1.43-3.59, p = 0.0003), and ALP (HR 2.06, 95%CI 1.35-3.14, p = 0.0008) as significant prognostic factors for OS. For mCRPC patients treated with Ra-223, aBSI change is useful as an imaging biomarker for treatment response assessment and survival prediction.

18F-fluorodeoxyglucose uptake in advanced gastric cancer correlates with histopathological subtypes and volume of tumor stroma.

PURPOSE: The aim of this study was to investigate the correlation between preoperative 18F-fluorodeoxyglucose (FDG) uptake and histological subtypes, amount of tumor stroma in advanced gastric cancer (GC), and clinical outcomes. METHODS: We evaluated 56 patients (male/female, 42:14; mean age, 69 years) with advanced GC who underwent surgical resection at our institution and positron emission tomography-computed tomography with 18F-FDG prior to surgery. We used the maximum standardized uptake value (SUVmax) of the tumor and the tumor-to-liver ratio (TLR) of the SUVmax for the analysis. The SUVmax and TLR correlated with histological subtypes, immunohistochemistry (IHC) for CD34, and recurrence-free survival (RFS). Tumor stroma in GC was evaluated by CD34 expression. GCs were classified according to the Lauren and World Health Organization (WHO) classifications. RESULTS: The average FDG uptakes (SUVmax) were 4.17% and 14.04% in diffuse and intestinal type GCs, respectively, according to the Lauren classification, and 4.17%, 13.87%, 7.70%, 9.71%, and 19.45% in the poorly cohesive, tubular, mucinous, and papillary adenocarcinomas, respectively, according to the WHO classification. The FDG uptake in diffuse type was significantly lower than that in the intestinal type (p = 0.000). The SUVmax and TLR of the CD34(+) group (mean SUVmax, 5.50; TLR, 1.56) were significantly lower than those of the CD34(-) group (mean SUVmax, 14.09; TLR, 4.09). RFS was not associated with TLR or CD34 expression. CONCLUSION: GC, which has abundant tumor stroma characterized by high CD34 expression on IHC, shows low FDG uptake.

Pregnancy outcomes after hysteroscopic surgery in women with cesarean scar syndrome.

Cesarean scar defect often causes postmenstrual abnormal uterine bleeding, dysmenorrhea, chronic pelvic pain, and infertility, which are collectively known as cesarean scar syndrome (CSS). Several studies have reported that hysteroscopic surgery can restore fertility in women with CSS. The study aimed to identify factors that influence subsequent pregnancy following hysteroscopic surgery. Therefore, we studied 38 women with secondary infertility due to CSS who underwent hysteroscopic surgery at Shiga University of Medical Hospital between July 2014 and July 2019. Our hysteroscopic procedure included inferior edge resection and superficial cauterization of the cesarean scar defect under laparoscopic guidance. Patients were followed up for 3 to 40 months after surgery. Surgery was successful in all cases and no complications were observed. Twenty-seven patients (71%) became pregnant (pregnant group), while 11 (29%) did not (non-pregnant group). Baseline characteristics of age, body mass index, gravidity, parity, previous cesarean section, presence of endometriosis, retroflex uterus, and preoperative residual myometrial thickness were not significantly different between the groups. However, the median residual myometrium thickness was significantly higher after surgery than before surgery in the pregnant group (1.9 [1.1-3.6] vs 4.9 [3.4-6.6] mm, P<0.0001), whereas this difference was not significant in the non-pregnant group. Of those who became pregnant, 85% conceived within 2 years of surgery. Although three pregnancies resulted in abortion and one is ongoing at the time of writing, 23 pregnancies resulted in healthy babies at 35-38 gestational weeks by scheduled cesarean sections with no obstetrical complications due to hysteroscopic surgery. The average birth weight was 3,076 g. Our findings support that hysteroscopic surgery is a safe and effective treatment for secondary infertility due to CSS. The thickness of the residual myometrium may be a key factor that influences subsequent pregnancy in women with CSS.