Shared decision-making support program for older patients with advanced cancer using a question prompt list and geriatric assessment: A pilot randomized controlled trial.

INTRODUCTION: Older patients with cancer are less likely to express their treatment preferences than younger patients. Question prompt lists (QPLs) facilitate communication between patients and physicians. Geriatric assessment (GA) is recommended when older patients with cancer make treatment decisions. This study estimated the effect size of a shared decision-making (SDM) support program combining QPLs with GA in terms of patients' subjective evaluation of the SDM process for a future definitive randomized controlled trial. We also evaluated the number and quality of aging-related communication during consultations, and feasibility and acceptability of the study for exploratory purposes. MATERIALS AND METHODS: This is a pilot study with randomized allocation and blind evaluation. Patients aged 65 years or older at the National Cancer Center Hospital, Tokyo, Japan, scheduled to discuss the changes of their treatment, were randomly assigned in a 1:1 ratio to the SDM support program or usual care. This program consisted of 30-60 min of face-to-face coaching, with QPLs and GA provided before the coaching. As the primary endpoint, the decisional conflict scores given by the patients immediately after the consultation were compared between the two groups. For the secondary endpoints, the number and quality of aging-related communications during the consultations were assessed by evaluators (blinded) using audio-recordings. Adherence, burden, and usefulness were assessed for evaluating feasibility and acceptability of the SDM support program. RESULTS: Forty patients were enrolled. All patients completed the GA questionnaire, for which 70% did not require any individual assistance. Answering the questionnaires took approximately 11 min. The decisional conflict scores were mean [standard deviation (SD)]: 19.3 [10.8] vs. 18.0 [11.1] (effect size: Cohen's d = 0.12) for the SDM support program and usual care groups, respectively. The number of aging-related communications during the consultation for the new treatment was higher in the SDM support program group than the usual care (mean [SD]: 3.3 [1.2] vs. 2.2 [1.5], effect size: cohen's d = 1.32). Patients felt that the SDM support program was useful but not burdensome or difficult. DISCUSSION: The SDM support program was considered useful and feasible for older patients and able to facilitate communication regarding aging-related concerns. TRIAL REGISTRATION NUMBER: The study protocol was registered on September 23, 2020, in the UMIN Clinical Trials Registry (UMIN000041867).

Therapy-related myeloid neoplasms after treatment for ovarian cancer: A retrospective single-center case series.

OBJECTIVE: Therapy-related myeloid neoplasms (t-MNs) are often fatal and arise as late complications of previous anticancer drug treatment. No single-center case series has examined t-MNs in epithelial ovarian cancer (EOC). METHODS: All patients with EOC treated at Chiba University Hospital between 2000 and 2021 were included. We retrospectively analyzed the characteristics, clinical course, and outcomes of patients who developed t-MNs. RESULTS: Among 895 cases with EOC, 814 cases were treated with anticancer drugs. The median follow-up period was 45 months (interquartile range, 27-81) months. Ten patients (1.2%) developed t-MNs (FIGO IIIA in one case, IIIC in three, IVA in one, and IVB in five). Nine patients were diagnosed with myelodysplastic syndrome and one with acute leukemia. One patient with myelodysplastic syndrome developed acute leukemia. The median time from the first chemotherapy administration to t-MN onset was 42 months (range, 21-94 months), with t-MN diagnoses resulting from pancytopenia in four cases, thrombocytopenia in three, and blast or abnormal cell morphology in four. The median number of previous treatment regimens was four (range, 1-7). Paclitaxel + carboplatin therapy was administered to all patients, gemcitabine and irinotecan combination therapy to nine, bevacizumab to eight, and olaparib to four. Six patients received chemotherapy for t-MN. All patients died (eight cancer-related deaths and two t-MN-related deaths). None of the patients was able to restart cancer treatment. The median survival time from t-MN onset was 4 months. CONCLUSIONS: Patients with EOC who developed t-MN were unable to restart cancer treatment and had a significantly worse prognosis.

Prevalence of psychological distress and associated factors among patients undergoing comprehensive genomic profiling testing: protocol for a multicentre, prospective, observational study.

INTRODUCTION: Since May 2019, comprehensive genomic profiling (CGP) has been covered by Japan's health insurance system for patients with solid tumours that have progressed on standard chemotherapy, rare tumours or tumours of unknown primary origin. Although CGP has the potential to identify actionable mutations that can guide the selection of genomically matched therapies for patients with advanced cancer and limited treatment options, less than 10% of patients benefit from CGP testing, which may have a negative impact on patients' mental status. The aim of this study is to investigate the prevalence of psychological distress and associated factors among patients with advanced cancer who are undergoing CGP testing across Japan. METHODS AND ANALYSIS: This multicentre, prospective cohort study will enrol a total of 700 patients with advanced cancer undergoing CGP testing. Participants will be asked to complete questionnaires at three timepoints: at the time of consenting to CGP testing (T1), at the time of receiving the CGP results (T2; 2-3 months after T1) and 4-5 months after T2 (T3). Primary outcome is the prevalence of depression as measured by the Patient Health Questionnaire-9 at the three timepoints. Secondary outcomes are the prevalence of anxiety and Quality of Life Score. Associated factors with psychological distress will also be examined, including knowledge about CGP, attitudes, values and preferences towards CGP, satisfaction with oncologists' communication and patient characteristics as well as medical information including CGP test results and genomically matched therapies if provided. The prevalence of depression and anxiety will be estimated using the unadjusted raw rates observed in the total sample. Longitudinal changes in measures will be explored by calculating differences between the timepoints. Multivariate associations between variables will be examined using multiple or logistic regression analysis depending on the outcomes to adjust for confounders and to identify outcome predictors. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of the National Cancer Center Japan on 5 January 2023 (ID: 2022-228). Study findings will be disseminated through peer-reviewed journals and conference presentations. TRIAL STATUS: The study is currently recruiting participants and the enrolment period will end on 31 March 2025, with an expected follow-up date of 31 March 2026. TRIAL REGISTRATION NUMBER: UMIN000049964.

Computer-aided diagnosis for screening of lower extremity lymphedema in pelvic computed tomography images using deep learning.

Lower extremity lymphedema (LEL) is a common complication after gynecological cancer treatment, which significantly reduces the quality of life. While early diagnosis and intervention can prevent severe complications, there is currently no consensus on the optimal screening strategy for postoperative LEL. In this study, we developed a computer-aided diagnosis (CAD) software for LEL screening in pelvic computed tomography (CT) images using deep learning. A total of 431 pelvic CT scans from 154 gynecological cancer patients were used for this study. We employed ResNet-18, ResNet-34, and ResNet-50 models as the convolutional neural network (CNN) architecture. The input image for the CNN model used a single CT image at the greater trochanter level. Fat-enhanced images were created and used as input to improve classification performance. Receiver operating characteristic analysis was used to evaluate our method. The ResNet-34 model with fat-enhanced images achieved the highest area under the curve of 0.967 and an accuracy of 92.9%. Our CAD software enables LEL diagnosis from a single CT image, demonstrating the feasibility of LEL screening only on CT images after gynecologic cancer treatment. To increase the usefulness of our CAD software, we plan to validate it using external datasets.

Barriers and facilitators to implementing geriatric assessment in daily oncology practice in Japan: A qualitative study using an implementation framework.

INTRODUCTION: Various guidelines recommend geriatric assessment (GA) for older adults with cancer, but it is not widely implemented in daily practice. This study uses an implementation framework to comprehensively and systematically identify multi-level barriers and facilitators to implementing GA in daily oncology practice. MATERIALS AND METHODS: We conducted 16 semi-structured interviews with healthcare providers in 10 designated cancer hospitals in Japan, using purposive and convenience sampling. The Consolidated Framework for Implementation Research (CFIR) was used to guide collection and analysis of interview data following a deductive content analysis approach with consensual qualitative research methods. After coding the interview data, ratings were assigned to each CFIR construct for each case, reflecting the valence and strength of each construct relative to implementation success. Then, those constructs that appeared to distinguish between high-implementation hospitals (HI) where GA is routinely performed in daily practice and low-implementation hospitals (LI) where GA is performed only for research purposes or not at all were explored. RESULTS: Of the 24 CFIR constructs assessed in the interviews, 15 strongly distinguished between HI and LI. In HI, GA was self-administered (Adaptability), or administered via a mobile app with interpretation (Design Quality and Packaging). In HI, healthcare providers were strongly aware of the urgent need to change practice for older adults (Tension for Change) and recognized that GA was compatible with existing workflow as part of their jobs (Compatibility), whereas in LI, they did not realize the need to change practice, and dismissed GA as an extra burden on their heavy workload. In HI, usefulness of GA was widely recognized by healthcare providers (Knowledge & Beliefs about the Intervention), GA had a high priority (Relative Priority) and had strong support from hospital directors, managers, and nursing chiefs (Leadership Engagement), and multiple stakeholders were successfully engaged, including nurses (Key Stakeholders), peer doctors (Opinion Leaders), and those who drive implementation of GA (Champions). DISCUSSION: These findings suggest that successful implementation of GA should focus on not only individual beliefs about the usefulness of GA and the complexity of GA itself, but also organizational factors related to hospitals and the engagement of multiple stakeholders.

Delayed postrenal failure due to progression of asymptomatic hydronephrosis following hysterectomy.

Asymptomatic hydronephrosis following hysterectomy is generally transient. Here, we present the case of a 52-year-old woman who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for benign indications. Computed tomography (CT) to examine bleeding on the second postoperative day incidentally revealed bilateral grade II hydronephrosis. Asymptomatic hydronephrosis was not reevaluated, and gynecological outpatient follow-up was terminated with a normal creatinine level on postoperative day 43. On postoperative day 107, the patient noticed weight gain of 10 kg, decreased urine output, and generalized edema. The serum creatinine level was elevated to 5.4 mg/dL, and CT revealed bilateral grade III hydronephrosis. Urgent bilateral ureteral stenting was performed to treat stenosis of the distal ureters that caused postrenal failure. Ureteroneocystostomy was performed for strict stenosis of the right ureter at 10 months postoperatively. Histological examination of the resected distal ureter showed inflammation and fibrosis. Asymptomatic hydronephrosis developing after hysterectomy progress to delayed postrenal failure.

Suppressor-type TERT mutations associated with recurrence in ovarian clear cell carcinoma.

Several cancers harbor "enhancer-type" mutations of the telomerase reverse transcriptase (TERT) promoter for immortalization. Here, we report that 8.6% (8/93) of ovarian clear cell carcinomas (OCCCs) possess the "suppressor-type" TERT promoter mutation. The recurrence rate of OCCCs with "suppressor-type" TERT promoter mutations was 62.5% (5/8) and was significantly higher than that of the "unaffected-type" with no mutation (20.8%, 15/72) or "enhancer-type" TERT promoter mutations (7.7%, 1/13). Our findings show that the acquired suppression of TERT is closely associated with OCCC development and recurrence, indicating the need for further research on telomerase suppression in cancers.

A nationwide, cross-sectional, web-based survey on healthcare providers' knowledge about, attitudes toward, and perceived barriers to adherence to clinical practice guidelines for anticancer drug therapy for older patients with cancer in Japan.

INTRODUCTION: In July 2019, in accordance with the Medical Information Distribution Service Manual for Guideline Development 2014, which was based on the Grading of Recommendations Assessment, Development and Evaluation approach, the Japanese Society of Medical Oncology (JSMO) and the Japan Society of Clinical Oncology (JSCO) published clinical practice guidelines (CPGs) on chemotherapy and other drug therapies for older patients with cancer (JSMO-JSCO CPGs). In September 2020, at one year after the publication of these guidelines, a survey was conducted to determine the extent to which they had been disseminated to JSMO and JSCO members and implemented in daily practice. MATERIALS AND METHODS: This nationwide, cross-sectional, web-based survey was conducted with JSMO and JSCO members. We surveyed the participants' overall awareness of the JSMO-JSCO CPGs, and their knowledge about, attitudes toward, and perceived barriers to adherence to each recommendation using validated questionnaires based on theoretical frameworks used in previous studies (Awareness to Adherence Model, Clinicians' Assessments of Practice Guidelines in Oncology questionnaires, and Knowledge-Attitudes-Behavior Framework). RESULTS: Among JSMO and JSCO members who had been informed of the survey, 1230 responded (response rate: 8.6% and 4.8%, respectively). From these respondents, 107 were excluded because they did not practice anticancer drug therapy at the time of the survey. Of the remaining 1123 eligible participants, 674 (60.0%) were aware of the JSMO-JSCO CPGs before the survey, 492 (73.0%) of whom had read all or part of the guidelines (publications 57.1%, JSMO website 34.8%, and JSCO website 14.0%). Knowledge about, attitudes toward, and barriers to adherence to each recommendation differed widely according to the clinical questions. The most commonly cited barriers were lack of awareness, lack of agreement, lack of evidence, lack of outcome expectancy, patient values and preferences, and patient factors. DISCUSSION: This survey identified different barriers to guideline adherence, including providers' knowledge, attitudes, and external factors, depending on each recommendation. Effective strategies to overcome these barriers can be expected to improve the implementation of the guideline recommendations. Based on the results of this survey, efforts should be made to promote further the use of the clinical guidelines in daily practice.

Serum FSH as a Useful Marker for the Differential Diagnosis of Ovarian Granulosa Cell Tumors.

Background: We evaluated whether the serum hormone levels are useful in the differential diagnosis of granulosa cell tumors (GCTs), regardless of menopausal status. Methods: Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol, and progesterone were measured preoperatively in all patients (n = 471) who underwent surgery for ovarian tumors at Chiba University Hospital between 2009 and 2021. These were compared in two groups, a GCT group (n = 13) and a group with other histological types (non-GCT) (n = 458). Results: The GCT group had significantly lower serum LH and FSH (p = 0.03 and p < 0.001, respectively) and significantly higher testosterone, estradiol, and progesterone (p < 0.001, p < 0.001, and p = 0.045, respectively) than the non-GCT group. Multivariate analysis revealed that serum FSH and estradiol were significantly associated with GCT (FSH, odds ratio (OR) = 0.0046, 95% confidence interval (CI) = 0.0026−0.22, p = 0.004; estradiol, OR = 0.98, 95% CI = 0.96−0.998, p = 0.046). Receiver-operating characteristic curve analysis for GCTs showed that the area under the curve of serum FSH was 0.99, with a sensitivity of 100% and a specificity of 98%, when the cutoff level was set at 2.0 IU/L. Conclusions: Preoperative serum FSH level is an extremely useful marker for differentiating GCTs from all ovarian tumors.

Validity of the 2014 FIGO Stage IIIA1 Subclassification for Ovarian, Fallopian Tube, and Peritoneal Cancers.

BACKGROUND/AIM: The 2014 International Federation of Gynecology and Obstetrics (FIGO) classification subdivides patients with stage IIIA1 ovarian, fallopian tube, and peritoneal cancers by the greatest dimension of metastatic lymph node without supporting evidence. This study aimed to assess the validity of this subdivision. PATIENTS AND METHODS: A retrospective single-institution cohort study was performed in patients with ovarian, fallopian tube, or peritoneal cancer from 2009 to 2020. We compared outcomes between patients diagnosed with IIIA1(i) (metastasis ≤10 mm in the greatest dimension) and IIIA1(ii) (metastasis >10 mm in the greatest dimension). RESULTS: Of the 895 patients, 46 (5.1%) were classified as stage IIIA1, 20 as IIIA1(i), and 26 as IIIA1(ii). In stage IIIA1(ii), there were significantly more cases of serous carcinoma (p<0.001), and the number of positive nodes and lymph node ratio were significantly higher than those in stage IIIA1(i) (p=0.001, p=0.002). Five-year progression-free survival was 68.7% in patients with stage IIIA1(i) cancer and 58.1% in those with stage IIIA1(ii) (p=0.58). Five-year overall survival was 83.1% in patients with stage IIIA1(i) cancer and 80.2% in those with stage IIIA1(ii) (p=0.44). Among other patient characteristics and pathologic findings, there were no prognostic factors for patients with stage IIIA1 cancer. CONCLUSION: In this retrospective cohort study, further classification of FIGO stage IIIA1 cancer was not significantly associated with patient outcomes.

Geriatric assessment and management with question prompt list using a web-based application for elderly patients with cancer (MAPLE) to communicate ageing-related concerns: J-SUPPORT 2101 study protocol for a multicentre, parallel group, randomised controlled trial.

INTRODUCTION: Elderly cancer patients often have ageing-related physical and psychosocial problems that should be fully shared with their oncologists. Geriatric assessment (GA) can assess these ageing-related problems and guide management. Communication support might also facilitate implementation of GA-guided management. We will conduct a multicentre, randomised controlled trial to examine the efficacy of a programme that combines a GA summary, management recommendations and communication support to facilitate ageing-related communications between elderly Japanese patients with cancer and their oncologists, and thus to implement programme-guided management. METHODS AND ANALYSIS: We plan to recruit a total of 210 patients aged ≥70 years, diagnosed with incurable cancers of gastrointestinal origin, and referred for first-line or second-line chemotherapy. In the intervention arm, a summary of management recommendations based on a GA and question prompt list (QPL) will be provided to patients and shared with their oncologists at the first outpatient visit after randomisation by trained intervention providers. For 5 months after the initial intervention, implementation of GA-guided management recommendations will be reviewed monthly with the patients and their oncologists to implement management as needed. The GA and QPL will be re-evaluated at 3 months, with a summary provided to patients and their oncologists. Those participants allocated to the usual care arm will receive usual oncology care. The primary endpoint is the number of conversations about ageing-related concerns at the first outpatient visit after randomisation. ETHICS AND DISSEMINATION: This study was approved by the institutional review board of the National Cancer Center Japan on 15 April 2021 (ID: 2020-592). Study findings will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: UMIN000045428.

Highly Aggressive Surgery Benefits in Patients With Advanced Ovarian Cancer.

BACKGROUND/AIM: We investigated whether highly aggressive surgery has survival and perioperative complication benefit in patients with advanced ovarian cancer. PATIENTS AND METHODS: This retrospective study included 209 patients with stage III/IV ovarian cancer who underwent aggressive surgery [surgical complexity score (SCS) ≥8] between January 2008 and December 2018. Patients were categorized into the SCS 8-12 (less aggressive surgery, 83 patients) and SCS ≥13 (highly aggressive surgery, 126 patients) groups. Survival outcomes and perioperative complications between the groups were compared. Patient suitability for primary debulking surgery or neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) was based on the evaluation of performance status, tumor load, and ascites. If patients were suitable for NACT/IDS, the residual tumor margins were marked at the initial laparotomy. The previously marked lesions were removed during IDS, even in patients with macroscopic tumor resolution. RESULTS: Prevalence rates of stage IV disease, poor performance status, presence of omental cake, peritoneal cancer index ≥15, and IDS performed were significantly higher in the highly aggressive surgery group than in the less aggressive surgery group. The median progression-free survival (PFS) and overall survival (OS) were not significantly different between the groups (PFS, 32 and 31 months, respectively; p=0.622; OS, 99 and 75 months, respectively; p=0.390). The incidence of severe perioperative complications was not significantly different between the less aggressive group (4.8%) and the highly aggressive surgery group (6.4%) (p=0.767). CONCLUSION: Highly aggressive surgery with appropriate selection regardless of the timing of cytoreduction benefits patients with advanced ovarian cancer.

Factors affecting the implementation of guideline-based prophylactic antiemetic therapy for chemotherapy-induced nausea and vomiting in Japan: a protocol for a hospital-based qualitative study.

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) decrease patients' quality of life and negatively impact treatment outcomes. Although standard prophylactic antiemetic therapy for acute CINV recommended by guidelines is effective, poor guideline implementation is a worldwide problem. In Japan, prophylactic antiemetic therapy is relatively well implemented for chemotherapy associated with high emetogenic risk, while implementation gaps are observed for that with low emetogenic risk.Although most reports on factors influencing appropriate antiemetic prescription focus on physicians' attitudes and behaviours, a more comprehensive exploration is needed since chemotherapy is expected to involve pharmacists, nurses and eventually hospital directors. The purpose of this qualitative study is to comprehensively explore the factors that influence the implementation of appropriate prophylactic antiemetic procedures at cancer care hospitals in Japan. METHODS AND ANALYSIS: This study is a hospital-based qualitative study using semistructured individual interviews. The target population will be hospital directors, and chiefs (including proxies) of departments of oncology and/or chemotherapy, pharmacy and nursing, working in the hospitals, selected by purposive sampling. We will obtain information on antiemetics in chemotherapy regimens, antiemetic routine use and awareness of guidelines using prequestionnaires. Interviews will then be conducted online using an interview guide. The Consolidated Framework for Implementation Research will be used to collect and analyse the interview data. We will also create new codes inductively, as required. In addition, we will refer to the aggregate results of the Quality Indicator survey to determine the implementation of recommended antiemetic prescriptions for each hospital and discuss the relationship with influencing factors. ETHICS AND DISSEMINATION: This study has been approved by the National Cancer Centre Ethics Approval Committee (approval number: 2020-305). The study findings will be disseminated via peer-reviewed journal publications and presentations to academics, policy-makers, and clinicians at scientific conferences.

Influence of Estradiol-Producing Ovarian Tumors on the Maturation Index of Cervical Cytology in Postmenopausal Women.

INTRODUCTION: The aim of the study was to evaluate the influence of estradiol-producing ovarian tumors, including surface epithelial-stromal tumors, on the cervical cytology of postmenopausal women. METHODS: This case-controlled study included 160 postmenopausal women who underwent a gynecological surgery between January 2009 and December 2016. The relationship between serum estradiol levels and the maturation index of cervical cytology was examined. Patients with ovarian tumors and a high estradiol level (≥28 pg/mL) constituted the estradiol-producing ovarian tumor group (30 women, including 23 with surface epithelial-stromal tumors). The maturation index of this group was compared with that of the control group (130 women with normal estradiol levels [<28 pg/mL] with either ovarian tumors or uterine tumors). RESULTS: For all patients, the serum estradiol levels were significantly correlated with the maturation index (p < 0.001, r = 0.65). The maturation index of the estradiol-producing ovarian tumor group was significantly higher than that of the control group (0.67 ± 0.21 vs. 0.075 ± 0.16, p < 0.001). The area under the receiver operating characteristic curve for the maturation index was 0.94. The best maturation index cut-off level for estradiol-producing ovarian tumors was 0.20. Using this cut-off, the sensitivity and specificity were 94% and 82%, respectively. CONCLUSION: Estradiol-producing ovarian tumors influence cervical epithelial maturation in postmenopausal women. An increased maturation index may trigger the early detection of asymptomatic ovarian tumors.

Bevacizumab-based Salvage Chemotherapy Improves Survival Outcomes for Patients With Brain Metastasis from Ovarian Cancer.

BACKGROUND/AIM: Brain metastases from ovarian cancer remain rare and the appropriate treatment is unknown. We investigated survival outcomes following salvage chemotherapy before and after bevacizumab approval to evaluate the efficacy of bevacizumab in patients with brain metastasis from ovarian cancer. PATIENTS AND METHODS: We investigated 23 consecutive patients with brain metastasis from ovarian cancer at our hospital between 2001 and 2020. Bevacizumab was administered for treating ovarian cancer after approval in Japan in November 2013. Survival after brain metastasis was compared between 9 patients treated before bevacizumab approval (2000-2013) and 14 patients treated after approval (2014-2020). Seven patients treated in the latter period received bevacizumab-salvage chemotherapy for brain metastasis. RESULTS: Median survival in all patients was 9.1 months [95% confidence interval (CI)=4.2-33.5]. In addition, patients treated during the latter period presented better survival outcomes than those treated in the former period (former, 2.9 months vs latter, 33.5 months, log-rank test, p=0.015; Wilcoxon test, p=0.009). Multivariate analysis revealed that bevacizumab addition (p=0.020), interval to brain metastasis (p=0.005), number of brain lesions (p=0.001), number of recurrences (p=0.001), and platinum sensitivity (p=0.028) were independently associated with survival in all cohorts. CONCLUSION: Bevacizumab-based salvage chemotherapy may improve survival outcomes in patients with brain metastasis.

Predictors of postoperative pancreatic fistula after splenectomy with or without distal pancreatectomy performed as a component of cytoreductive surgery for advanced ovarian cancer.

OBJECTIVE: Splenectomy with or without distal pancreatectomy is occasionally performed during cytoreductive surgery for advanced ovarian cancer. We investigated pre-, intra-, postoperative risk factors and predictors of clinically relevant postoperative pancreatic fistula (CR-POPF) in patients who underwent cytoreductive surgery for advanced ovarian cancer. METHODS: We investigated 165 consecutive patients with ovarian, fallopian tube, and peritoneal carcinoma categorized as stage III/IV disease, who underwent splenectomy with or without distal pancreatectomy as a component of cytoreductive surgery performed as initial treatment at Chiba University Hospital. Patient characteristics, clinical factors, and surgical outcomes were compared between those with and without CR-POPF. RESULTS: CR-POPF occurred in 20 patients (12%). There were no significant intergroup differences in the characteristics between patients with CR-POPF and patients without CR-POPF except for operative time, intraoperative blood loss, amylase (AMY) levels in drain fluid on postoperative day (POD)1 and POD3, and pancreatic stump thickness. Multivariate analysis showed that the POD3 drain fluid AMY level was the only significant risk factor and predictor of CR-POPF in patients who underwent cytoreductive surgery for advanced ovarian cancer. The receiver operating characteristic curve of the POD3 drain fluid AMY level, which predicted development of CR-POPF showed an area under the curve of 0.77, and the optimal cut-off value of AMY was 808 U/L. A pancreatic fistula did not occur in patients with POD3 drain fluid AMY levels <130 U/L. CONCLUSION: The POD3 drain fluid AMY level can be early diagnostic predictor CR-POPF after splenectomy with or without distal pancreatectomy for advanced ovarian cancer.

Surgical Techniques and Outcomes of Colorectal Anastomosis after Left Hemicolectomy with Low Anterior Rectal Resection for Advanced Ovarian Cancer.

Extended colon resection is often performed in advanced ovarian cancer. Restoring intestinal continuity and avoiding stoma creation improve patients' quality of life postoperatively. We tried to minimize the number of anastomoses, restore intestinal continuity, and avoid stoma creation for 295 patients with stage III/IV ovarian cancer who underwent low anterior rectal resection (LAR) with or without colon resection during cytoreductive surgery. When the remaining colon could not reach the rectal stump after left hemicolectomy with LAR, we used the following techniques for tension-free anastomosis: right colonic transposition, retro-ileal anastomosis through an ileal mesenteric defect, or an additional colic artery division. Rates of stoma creation and rectal anastomotic were 3% (9/295) and 6.6% (19/286), respectively. Among 21 patients in whom the remaining colon did not reach the rectal stump after left hemicolectomy with LAR, 20 underwent tension-free anastomosis, including eight, six, and six patients undergoing right colonic transposition, retro-ileal anastomosis through an ileal mesenteric defect, and an additional colic artery division, respectively. Colorectal anastomosis is feasible for patients with extended colonic resection. Low anastomotic leakage and stoma rates can be achieved with careful attention to colonic mobilization and tension-free anastomosis.

Bevacizumab in First-Line Chemotherapy Improves Progression-Free Survival for Advanced Ovarian Clear Cell Carcinoma.

(1) Background: We investigated survival outcomes following first-line chemotherapy before and after approval of bevacizumab (Bev) for ovarian cancer in Japan to evaluate the efficacy of Bev for advanced clear cell carcinoma (CCC). (2) Methods: We investigated 28 consecutive patients diagnosed with CCC (stages III/IV) at our hospital between 2008 and 2018. Bev was administered for treatment of advanced CCC after approval in Japan in November 2013. Progression-free survival (PFS) was compared between 10 patients treated before Bev approval (2008-2013, Bev- group) and 18 patients treated after Bev approval (2014-2018, Bev+ group) for first-line chemotherapy. (3) Results: No intergroup difference was observed in patient characteristics. The rate of completeness of resection was higher in the Bev - group (9/10, 90%) than in the Bev+ group (15/18, 83%) (p = 0.044). Eleven (61%) patients in the Bev + group received ≥ 21 cycles of Bev. The median PFS increased from 12.0 months before Bev approval to 29.8 months after Bev approval (Wilcoxon test, p = 0.026). Multivariate analysis showed that performance status (p = 0.049), Bev administration (p = 0.023) and completeness of resection (p = 0.023) were independent prognostic factors for PFS. (4) Conclusions: Bev incorporated into first-line chemotherapy might improve PFS in patients with advanced CCC. We hope that our findings will be confirmed in adequate clinical trials.