A retrospective study of dose-dense paclitaxel and carboplatin plus bevacizumab as first-line treatment of advanced epithelial ovarian cancer.

OBJECTIVE: This study compared the effectiveness, safety, and tolerability of dose-dense paclitaxel and carboplatin plus bevacizumab (ddTC+Bev) with ddTC for advanced ovarian cancer. METHODS: We retrospectively analyzed the clinical records of 134 patients who received ddTC+Bev or ddTC as first-line chemotherapy for stage III-IV ovarian cancer. Progression-free survival as primary endpoint of this study was compared using the log-rank test. Cox proportional hazards model and propensity score matching (PSM) were used to analyze prognostic factors, and the frequency of adverse events was examined using the χ² test. RESULTS: We categorized 134 patients in the ddTC+Bev (n=57) and ddTC (n=77) groups who started treatment at four related institutions from November 2013 to December 2017. No patients used poly (ADP-ribose) polymerase inhibitors as the first line maintenance therapy. The progression-free survival (PFS) of the ddTC+Bev group had a significantly better prognosis than that of the ddTC group (hazard ratio [HR]=0.50; 95% confidence interval [CI]=0.32-0.79; p<0.003). Multivariate analysis showed that ddTC+Bev regimen was a prognostic factor. However, intergroup comparison using PSM revealed that the PFS of the ddTC+Bev group had a nonsignificantly better prognosis than that of the ddTC group (HR=0.70; 95% CI=0.41-1.20; p=0.189). Few adverse events above G3 were noted for ddTC+Bev, which were sufficiently tolerable. CONCLUSION: This study could not demonstrate that adding Bev to ddTC improves prognosis. Further studies with more cases are warranted.

Clinicopathological and endoscopic features of Helicobacter pylori infection-negative gastric cancer in Japan: a retrospective study.

Background/Aims: Helicobacter pylori infection-negative gastric cancer (HPNGC) has not been systematically investigated in consecutive patients. Hence, this study aimed to investigate the clinicopathological and endoscopic features of HPNGC. Methods: This single-center retrospective study selected participants from patients with gastric cancer who were treated at the Fukuoka University Chikushi Hospital between January 2013 and December 2021. Only patients diagnosed with HPNGC were enrolled, and their clinicopathological and endoscopic features were analyzed in detail. Results: The prevalence of HPNGC in the present study was 2.6% (54/2112). The types of HPNGC observed in each gastric region were as follows: advanced gastric cancer was observed in the cardia; gastric adenocarcinoma of fundic-gland differentiation, gastric adenocarcinoma of foveolar-type presenting with whitish elevation and raspberry-like foveolar-type gastric adenocarcinoma, gastric adenocarcinoma arising in polyposis, and gastric adenocarcinoma with autoimmune gastritis were observed in the fundic gland region ranging from the gastric fornix to the gastric body; signet-ring cell carcinoma was observed in the gastric-pyloric transition region ranging from the lower gastric body to the gastric angle; and well-differentiated tubular adenocarcinoma with low-grade atypia was observed in the antrum. Conclusions: This study revealed that tumors from each gastric region exhibited distinct macroscopic and histological types in HPNGC.

Association between occurrence of multiple white and flat elevated gastric lesions and oral proton pump inhibitor intake.

BACKGROUND/AIMS: Multiple white and flat elevated lesions (MWFL) that develop from the gastric corpus to the fornix may be strongly associated with oral antacid intake. Therefore, this study aimed to determine the association between the occurrence of MWFL and oral proton pump inhibitor (PPI) intake and clarify the endoscopic and clinicopathological characteristics of MWFL. METHODS: The study included 163 patients. The history of oral drug intake was collected, and serum gastrin levels and anti-Helicobacter pylori immunoglobulin G antibody titers were measured. Upper gastrointestinal endoscopy was performed. The primary study endpoint was the association between MWFL and oral PPI intake. RESULTS: In the univariate analyses, MWFL were observed in 35 (49.3%) of 71 patients who received oral PPIs and 10 (10.9%) of 92 patients who did not receive oral PPIs. The occurrence of MWFL was significantly higher among patients who received PPIs than in those who did not (p<0.001). Moreover, the occurrence of MWFL was significantly higher in patients with hypergastrinemia (p=0.005). In the multivariate analyses, oral PPI intake was the only significant independent factor associated with the presence of MWFL (p=0.001; odds ratio, 5.78; 95% confidence interval, 2.06-16.2). CONCLUSION: Our findings suggest that oral PPI intake is associated with the presence of MWFL (UMINCTR 000030144).

Peroral endoscopic myotomy for a pediatric case of suspected congenital esophageal stenosis.

Video 1Peroral endoscopic myotomy for a pediatric case of suspected congenital esophageal stenosis.

A Case of Tinea Corporis Caused by Trichophyton benhamiae var. luteum from a Degu and Evolution of the Pathogen's Taxonomy.

BACKGROUND: Trichophyton benhamiae, an anthropophilic dermatophyte, can cause dermatophytosis in humans and animals with rising zoonotic infections through pets, primarily in Europe. Dermatophytosis from T. benhamiae is often misdiagnosed due to its inflammatory symptoms. We report a case of tinea corporis from T. benhamiae var. luteum in a Japanese woman, contracted from pet Czech degus. CASE: The 40-year-old patient developed neck papules resembling acne. Initial treatment with topical antibiotics and steroids exacerbated the rash. Fungal elements were not detected by direct potassium hydroxide examination. Skin biopsy confirmed fungal elements in the stratum corneum and hair follicles, and tinea corporis was diagnosed. Oral terbinafine 125 mg was initiated without topical agents. Erythematous papules appeared on her limbs, determined as a trichophytid reaction. After two months, her skin improved significantly. Fungal culture identified T. benhamiae var. luteum colonies with a yellowish hue. Mating tests classified the strain as Americano-European race (-) with MAT1-1 genotype. This was diagnosed as tinea corporis from T. benhamiae var. luteum, likely transmitted from pet Czech degus. CONCLUSIONS: The incidence rate of pet-transmitted cutaneous fungal infections may increase in Japan with the trend to keep exotic pets. Dermatologists must recognize dermatophytosis clinical features from anthropophilic dermatophytes to prevent misdiagnosis and understand evolving nomenclature and pathogenesis.

Short- and long-term morbidity of total parietal peritonectomy for advanced ovarian cancer.

OBJECTIVE: Total parietal peritonectomy is gradually being recognized as a surgical option for advanced ovarian cancer; however, evidence regarding its efficacy and safety remains insufficient. Herein, we aimed to assess the short- and long-term post-operative safety profiles of total parietal peritonectomy. METHODS: We reviewed the medical records of post-operative morbidity and mortality of patients who underwent cytoreductive surgery with total parietal peritonectomy for stage III and IV ovarian cancer between April 2018 and January 2023. RESULTS: Fifty patients were enrolled in the study: 31 who underwent primary cytoreductive surgery and 19 who underwent interval cytoreductive surgery. The median age of all patients was 57 (range, 23-74) years. The median follow-up period was 22 (range, 3-59) months. Of 44 patients (88%) with stage IIIC/IV, 38 patients (76%) had high-grade serous carcinoma. The complete resection rates were 94%, 91%, and 100% in all patients, the primary cytoreductive surgery group, and the interval cytoreductive surgery group, respectively. There were 63 post-operative complication events overall, including 17 (27%) major complication events in 15 patients within 1 year post-operatively. Ten major complications occurred within 30 days of surgery, mainly in the primary cytoreductive surgery group (9 cases). Regarding complication type, the most frequent major event was pleural effusion (3 cases, 7%). After 30 days, there were a total of 17 all-grade complication events, of which ileus and hydronephrosis were major complications in 3 cases each (18%). There were no mortalities related to cytoreductive surgery. The scheduled adjuvant chemotherapy could be completed in 96% of patients. CONCLUSIONS: Total parietal peritonectomy is a feasible procedure for managing advanced ovarian cancer. Short- and long-term complications may include pleural effusion and ileus/hydronephrosis, respectively.

Numerous lesions of gastric adenocarcinoma of fundic-gland and fundic gland-mucosa type in a patient.

A man in his 60 s underwent upper gastrointestinal endoscopy at our hospital, which revealed a 30-mm elevated lesion in the upper stomach (main lesion). There were several discolored, flat mucosal lesions and slightly elevated, reddish, subepithelial mass-like lesions (multiple secondary lesions) in the gastric fornix and body. Histopathological examination of several biopsied secondary lesions revealed gastric adenocarcinoma of fundic-gland type (GA-FG) or gastric adenocarcinoma of fundic gland-mucosa type (GA-FGM). The main lesion was suspected to be GA-FGM on magnifying endoscopy with narrow-band imaging. It was removed using endoscopic submucosal dissection for therapeutic and diagnostic purposes. The histopathological diagnosis of the resected lesion was GA-FGM, which was surrounded by two GA-FGM and > 30 GA-FG lesions. Total gastrectomy was considered; however, the patient declined further surgical treatment. Therefore, he was followed up with biannual endoscopy and computed tomography. At five years postoperatively, no tumor growth or metastasis has been observed.

Genetic characteristics of platinum-sensitive ovarian clear cell carcinoma.

OBJECTIVE: Most ovarian clear cell carcinomas are resistant to platinum-based chemotherapy, while a small subset shows a positive response. The aim of this study was to clarify the clinical, pathological and genetic characteristics of platinum-sensitive ovarian clear cell carcinomas. METHODS: The study included 53 patients with stage III-IV ovarian clear cell carcinoma who had residual tumours after primary surgery and received platinum-based therapy between 2009 and 2018. A retrospective examination of platinum sensitivity was performed using the criterion of ≥6 months from the last day of first-line platinum therapy until recurrence/progression. Cases determined to be platinum-sensitive were subjected to immunohistochemical staining, genomic analyses using target sequencing (i.e. NCC Oncopanel) and homologous recombination deficiency (myChoice® HRD Plus) assays. RESULTS: Of the 53 stage III-IV ovarian clear cell carcinoma cases, 11 (21%) were platinum-sensitive. These cases showed better progression-free and overall survival than platinum-resistant cases (hazard ratio = 0.16, P < 0.001). Among the seven sensitive cases whose tumour tissues were available for molecular profiling, five were pure ovarian clear cell carcinoma based on pathological and genetic features, whereas the remaining two cases were re-diagnosed as high-grade serous ovarian carcinoma. The pure ovarian clear cell carcinomas lacked BRCA1 and BRCA2 mutations, consistent with the absence of the homologous recombination deficiency phenotype, whereas two cases (40%) had ATM mutations. By contrast, the two high-grade serous ovarian carcinoma cases had BRCA1 or BRCA2 mutations associated with the homologous recombination deficiency phenotype. CONCLUSION: The subset of platinum-sensitive ovarian clear cell carcinomas includes a majority with pure ovarian clear cell carcinoma features that lack the homologous recombination deficiency phenotype.

A case report of simultaneous robot-assisted nephroureterectomy and robot-assisted total laparoscopic hysterectomy.

Introduction: Robot-assisted surgery is spreading across surgical specialities as a less invasive alternative to conventional laparoscopic and open surgery. Case presentation: In this report, robot-assisted total laparoscopic hysterectomy and robot-assisted nephroureterectomy were performed simultaneously for a 69-year-old Japanese female with giant cervical polyp and ureteral cancer. All specimens could be removed from the vagina. The operative time was 379 min, the estimated intraoperative blood loss was 29 mL, and the patient was discharged on the sixth postoperative day without complications. Conclusion: We reported our experience with simultaneous robot-assisted nephroureterectomy and robot-assisted total laparoscopic hysterectomy. To our knowledge, this is the first report of simultaneous robot-assisted nephroureterectomy and robot-assisted total laparoscopic hysterectomy surgery.

A new endoscopic scoring system corresponding to histological healing using linked color imaging in ulcerative colitis: the SOUL study.

Background and study aims An important therapeutic aim in ulcerative colitis (UC) is endoscopic remission. Although an endoscopic score with white light imaging (WLI) is mainly used to evaluate endoscopic findings, the usefulness of linked color imaging (LCI) has been reported. We evaluated the relationship between LCI and histopathological findings and attempted to establish a new LCI endoscopic evaluation index for UC. Patients and methods This study was conducted at Kyorin University, Kyoto Prefectural University, and Fukuoka University Chikushi Hospital. Ninety-two patients with a Mayo endoscopic subscore (MES) ≤ 1 who underwent colonoscopy for UC in clinical remission were included. LCI index was defined as redness (R) (Grade 0-2), area of inflammation (A) (Grade 0-3), and lymphoid follicles (L) (Grade 0-3). Histological healing was defined as Geboes score < 2B.1. Endoscopic and histopathological scores were determined by central judgment. Results In 92 patients, 85 biopsies from the sigmoid colon and 84 biopsies from the rectum (total 169 biopsies) were evaluated. There were 22, 117, and 30 cases of Grades 0, 1, and 2, respectively in LCI index-R; 113, 34, 17, and five cases of Grades 0, 1, 2, and 3, respectively, in LCI index-A; and 124, 27, 14, and four cases of Grades 0, 1, 2, and 3, respectively, in LCI index-L. Histological healing was achieved in 84.0 % of the cases (142 of 169), and there were significant associations with histological healing or non-healing in LCI index-R ( P  = 0.013) and A ( P  = 0.0014). Conclusions A new LCI index is useful for predicting histological healing in UC patients with MES ≤ 1 and clinical remission.

An attempt to establish real-world databases of poly(ADP-ribose) polymerase inhibitors for advanced or recurrent epithelial ovarian cancer: the Japanese Gynecologic Oncology Group.

The development of new treatments for gynecological malignancies has been conducted mainly through collaborative international phase III trials led by the United States and Europe. The survival outcomes of many gynecological malignancies have greatly improved as a result. Recent large-scale genome-wide association studies have revealed that drug efficacy and adverse event profiles are not always uniform. Thus, it is important to validate new treatment options in each country to safely and efficiently provide newly developed treatment options to patients with gynecological malignancies. The Japanese Gynecologic Oncology Group (JGOG) is conducting 5 cohort studies (JGOG 3026, 3027, 3028, 3030, and 3031) to establish real-world data (RWD) of poly(ADP-ribose) polymerase (PARP) inhibitor use in patients with advanced or recurrent epithelial ovarian cancer. The RWD constructed will be used to provide newly developed PARP inhibitors for women with advanced or recurrent ovarian cancer in a safer and more efficient manner as well as to develop further treatment options. In 2022, The JGOG, Korean Gynecologic Oncology Group, Chinese Gynecologic Cancer Society, and Taiwanese Gynecologic Oncology Group established the East Asian Gynecologic Oncology Trial Group to collaborate with East Asian countries in clinical research on gynecologic malignancies and disseminate new knowledge on gynecologic malignancies from Asia. The JGOG will conduct a collaborative integrated analysis of the RWD generated from Asian countries and disseminate real-world clinical knowledge regarding new treatment options that have been clinically implemented.

Evaluation of non-hematologic toxicity in patients with cervical cancer after Type 3 radical hysterectomy followed by concurrent chemoradiotherapy: a retrospective study.

OBJECTIVE: To investigate the safety of concurrent chemoradiotherapy after Type 3 radical hysterectomy, focusing on non-hematologic toxicity. METHODS: Between January 2010 and December 2017, 236 patients diagnosed with cervical cancer Stages IB1-II (FIGO2008) and who had undergone Type 3 radical hysterectomy at the Jikei Medical University School-related four hospitals were included. Of these 236 patients, 134 had undergone adjuvant concurrent chemoradiotherapy after Type 3 radical hysterectomy (radical hysterectomy + concurrent chemoradiotherapy group), and 102 received no adjuvant therapy after Type 3 radical hysterectomy (radical hysterectomy group). The frequency of non-hematologic toxicities, especially lymphedema, pelvic infection, renal dysfunction, ileus and diarrhea, was investigated in the radical hysterectomy + concurrent chemoradiotherapy and radical hysterectomy groups using univariate and multivariate analyses. In these analyses, age, extent of lymph node dissection and preoperative clinical stage were included as risk factors for five complications. The risk factors for grade ≤ 2 adverse events were statistically evaluated. RESULTS: The frequency of lower extremity lymphedema (22 vs. 10%), renal dysfunction (13 vs. 3%), and diarrhea (13 vs. 0%) was significantly higher in the radical hysterectomy + CRRT group than that in the radical hysterectomy group. Logistic regression analysis revealed that adjuvant concurrent chemoradiotherapy significantly affected the occurrence of grade ≥ 2 lymphedema (P < 0.01) and renal dysfunction (P < 0.01). CONCLUSIONS: Concurrent chemoradiotherapy after Type 3 radical hysterectomy is associated with a higher incidence of renal dysfunction, lower extremity lymphedema and diarrhea. A more appropriate adjuvant therapy needs to be established.

Efficacy of endoscopy under general anesthesia for the detection of synchronous lesions in oro-hypopharyngeal cancer.

BACKGROUND/AIMS: Image-enhanced endoscopy can detect superficial oro-hypopharyngeal squamous cell carcinoma; however, reliable endoscopy of the pharyngeal region is challenging. Endoscopy under general anesthesia during transoral surgery occasionally reveals multiple synchronous lesions that remained undetected on preoperative endoscopy. Therefore, we aimed to determine the lesion detection capability of endoscopy under general anesthesia for superficial oro-hypopharyngeal squamous cell carcinoma. METHODS: This retrospective study included 63 patients who underwent transoral surgery for superficial oropharyngeal squamous cell carcinoma between April 2005 and December 2020. The primary endpoint was to compare the lesion detection capabilities of preoperative endoscopy and endoscopy under general anesthesia. Other endpoints included the comparison of clinicopathological findings between lesions detected using preoperative endoscopy and those newly detected using endoscopy under general anesthesia. RESULTS: Fifty-eight patients (85 lesions) were analyzed. The mean number of lesions per patient detected was 1.17 for preoperative endoscopy and 1.47 for endoscopy under general anesthesia. Endoscopy under general anesthesia helped detect more lesions than preoperative endoscopy did (p<0.001). The lesions that were newly detected on endoscopy under general anesthesia were small and characterized by few changes in color and surface ruggedness. CONCLUSION: Endoscopy under general anesthesia for superficial squamous cell carcinoma is helpful for detecting multiple synchronous lesions.

Magnifying endoscopy with narrow-band imaging for diagnosis of subtype of gastric intestinal metaplasia.

BACKGROUND AND AIM: Patients with incomplete gastric intestinal metaplasia (GIM) have a higher risk of gastric cancer (GC) than those with complete GIM. We aimed to clarify whether micromucosal patterns of GIM in magnifying endoscopy with narrow-band imaging (M-NBI) were useful for diagnosis of incomplete GIM. METHODS: We enrolled patients with a history of endoscopic resection of GC or detailed inspection for suspicious or definite GC. The antrum greater curvature and corpus lesser curvature were regions of interest. Areas with endoscopic findings of light blue crest and/or white opaque substance (WOS) were defined as endoscopic GIM, and subsequent M-NBI was applied. Micromucosal patterns were classified into Foveola and Groove types, and targeted biopsies were performed on GIM with each pattern. GIM was classified into complete and incomplete types using mucin (MUC)2, MUC5AC, MUC6, and CD10 immunohistochemical staining. The primary endpoint was the association between micromucosal pattern and histological subtype. The secondary endpoint was endoscopic findings associated with incomplete GIM. RESULTS: We analyzed 98 patients with 156 GIMs. Univariate analysis (odds ratio [OR] 3.4, P = 0.004), but not multivariate analysis (OR 0.87, P = 0.822), demonstrated a significant association between micromucosal pattern and subtype. The antrum (OR 3.7, P = 0.006) and WOS (OR 43, P = 0.002) were independent predictors for incomplete GIM. The WOS had 69% sensitivity and 93% specificity. CONCLUSIONS: The M-NBI micromucosal pattern is not useful for diagnosis of GIM subtype. WOS is a promising endoscopic indicator for diagnosis of incomplete GIM. (UMIN-CTR000041119).

Intraperitoneal Carboplatin for Ovarian Cancer - A Phase 2/3 Trial.

Intraperitoneal Carboplatin for Ovarian CancerThis trial compared intravenous weekly paclitaxel administered with intraperitoneal or intravenous carboplatin. There was a statistically significant increase in progression-free survival in patients with ovarian cancer treated with intraperitoneal versus intravenous carboplatin and paclitaxel, with no difference in overall survival between groups.

Effectiveness of an online support program to help female cancer patients manage their health and illness: Protocol for a randomized controlled trial.

Background: The aim of the trial is to evaluate the effectiveness of interventions provided by online support program apps, adopting health-related quality of life (HR-QOL) scores as indicators. Methods: The design is as an open, randomized, parallel-group trial with longitudinal data collection. The subjects will be female cancer patients receiving treatment in a Japanese National Cancer Hospital. Patients assigned to the experimental group will use three apps: an app for them to monitor their own health (monitoring app), an app to assess their understanding of their diagnosis and treatment and their readiness to receive treatment (confirmation app), and an app to address mental health issues (writing app); patients assigned to the control group will use only the monitoring app. At baseline (before patients undergo cancer treatment) and three other times during the study, evaluation indicators will be obtained from three different standardized HR-QOL scales that are incorporated in the monitoring app. The study hypothesis is that at 6 months after patients' baseline health monitoring, patients in the experimental group will have improved HR-QOL as compared with patients in the control group. Conclusion: This study is based on self-regulation theory, so it is important that the online support program works in an efficient way with respect to patients finding and setting their own health-related goals and adapting their behaviors to achieve those goals. Verifying the effectiveness of the combination of the three apps will show that it is a scientifically valid approach to maintaining or improving the HR-QOL of cancer patients.

A case of early gastric cancer in a patient with gastric juvenile polyposis diagnosed by magnifying endoscopy and resected by endoscopic submucosal dissection.

Gastric juvenile polyposis (GJP) is frequently associated with the development of gastric cancer. However, there are no reports of gastric cancer in patients with GJP diagnosed using magnifying endoscopy with narrow-band imaging (M-NBI) and successfully treated by endoscopic submucosal dissection (ESD). A 50-year-old woman was referred to our hospital. Conventional white-light endoscopy revealed numerous aggregated polyps with reddish and whitish areas in the gastric cardia. M-NBI revealed a regular microvascular pattern (MVP) and regular microsurface pattern (MSP) in the reddish area of the lesion, and they were diagnosed as non-cancerous polyps. There was a clear demarcation line between the reddish and whitish areas, with irregular MVP plus irregular MSP in the whitish area, which was diagnosed as early gastric cancer. The horizontal extent of the cancer was precisely identified using M-NBI, and the en bloc resection of cancerous lesions was performed using ESD. Histopathological examination of the resected specimen showed that the reddish area comprised a hyperplastic foveolar epithelium. Conversely, the whitish area was diagnosed as a well-differentiated adenocarcinoma. The cancer was limited to the mucosa, lymphovascular invasion was negative, and horizontal and vertical margins were free from cancerous tissue. According to surveillance endoscopy, there has been no recurrence 11 years after ESD. This is the first report demonstrating that M-NBI is useful for making a precise diagnosis of cancer in juvenile polyposis and that ESD can be an option for the treatment of such a cancer.

Retrospective Analysis of Total Parietal Peritonectomy Without Systematic Lymphadenectomy for Advanced Epithelial Ovarian Cancer.

BACKGROUND/AIM: Total parietal peritonectomy (TPP) is a surgical procedure used for complete resection of microscopic peritoneal dissemination. This study analyzed the perioperative complications that developed when omitting systematic lymphadenectomy from TPP. PATIENTS AND METHODS: We retrospectively analyzed perioperative complications in epithelial ovarian cancer patients with stage IIIB-IVB who underwent TPP during primary and interval cytoreductive surgeries between April 2018 and October 2021. RESULTS: Thirty-three patients were enrolled in the study. The median patient age was 62 years. Of 31 patients (94%) with stage IIIC/IV disease, 24 (73%) had high-grade serous carcinoma. The median operative time and blood loss were 447 min and 2,831 ml, respectively. Complete tumor resection was performed in 30 patients (91%). Only five patients underwent partial lymphadenectomy for clinical metastatic lymph nodes. Further, grade 3 complications were observed in seven (21%) patients, and there were no fatal events in this study. Three patients (9%) had ureteric injuries, which was the most frequent complication in this study. Only one patient developed an intra-abdominal infection due to ascites. In this case, partial para-aortic and pelvic lymphadenectomies were performed. CONCLUSION: TPP without systematic lymphadenectomy reduces the frequency of perioperative complications associated with ascites.