Objective: Signal transducer and activator of transcription 3 (STAT3) plays key roles in regulating cancer cell proliferation, survival, and metastasis. We aimed to determine the effects of YHO-1701, an oral STAT3 inhibitor, in ovarian cancer (OC). Methods: We evaluated the impact of YHO-1701 on cell growth in patient-derived cells (PDCs) and OC cell lines using standard cell proliferation assays. Spheroid models derived from PDCs were assessed using three-dimensional (3D) cell viability assays. Antitumor activity was performed in SKOV3 xenograft mice treated orally administrated YHO-1701 with 20 mg/kg.Changes in STAT3 signaling were analyzed by western blotting. The molecular mechanisms of STAT3 inhibition were investigated by sequencing RNA and analyzing pathways in the SKOV3 using a small interfering RNA targeting STAT3 (STAT3 siRNA) and YHO-1701. Results: YHO-1701 inhibited the growth of OC cell lines by preventing STAT3 dimerization and decreasing the expression of its downstream signaling molecule, survivin. The growth of PDCs and spheroids obtained from patients with primary and recurrent OCs was significantly inhibited. Antitumor effect was observed in the SKOV3 xenograft mice with YHO-1701. YHO-1701 induced apoptosis in OC cells. Additionally, p53 and/or MAPK signaling pathways were upregulated in SKOV3 cells incubated with YHO-1701 and in those with STAT3 siRNA. Conclusion Our results showed that YHO-1701 suppressed cell growth in PDCs of OC, accompanied by survivin inhibition, and a decrease in the number of peritoneal metastasis in the mice by YHO-1701, compared with those treated with control. Therefore, YHO-1701 could be a promising candidate agent for treating OC

Purpose: Determination of optimal treatment strategies for HER2-positive advanced gastric cancer (AGC) in randomized trials is necessary despite difficulties in direct comparison between trastuzumab deruxtecan (T-DXd) and nivolumab as third or later-line treatments. Materials and Methods: This single-institution, retrospective study aimed to describe the real-world efficacy and safety of T-DXd and nivolumab as ≥ third line treatments for HER2-positive AGC between March 2016 and May 2022. Overall, 58 patients (median age, 64 years;69% male) were eligible for the study (T-DXd group, n=20; nivolumab group, n=38). Results: Most patients exhibited a HER2 3+ status (72%) and presented metastatic disease at diagnosis (66%). The response rates of 41 patients with measurable lesions in the T-DXd and nivolumab groups were 50% and 15%, respectively. The T-DXd and nivolumab groups had a median progression-free survival of 4.8 months (95% confidence interval [CI], 3.3, 7.0) and 2.3 months (95% CI, 1.5, 3.5), median overall survival (OS) of 10.8 months (95% CI, 6.9, 23.8) and 11.7 months (95% CI, 7.6, 17.1), and grade 3 or greater adverse event rates of 50% and 2%, respectively. Overall, 64% patients received subsequent treatment. Among 23 patients who received both regimens, the T-DXd–nivolumab and nivolumab–T-DXd groups had a median OS of 14.0 months (95% CI, 5.0, not reached) and 19.3 months (95% CI, 9.5, 25.1), respectively. Conclusions T-DXd and nivolumab showed distinct efficacy and toxicity profiles as ≥ third line treatments for HER2-positive AGC. Considering the distinct features of each regimen, they may help clinicians personalize optimal treatment approaches for these patients.

Although palliative sedation therapy (PST) is considered to alleviate intolerable and refractory symptoms in dying patients with advanced cancer, there have been few studies regarding the situation of tertiary cancer center. We conducted a retrospective survey of the medical records of the patients who died between April 2015 and March 2016 at the National Cancer Center Hospital in Japan. PST was conducted in 75 out of 431 patients (17.4%). The patient demographics were as follows: sex (male/female), 48/27; median age, 61 years (range 5-83; 11 patients (14.7%) were aged under 39 years); and primary sites were lung, 18 (24.7%)/ pancreas, 11 (14.7%)/ hematopoietic organs, 11 (14.7%)/ bones and soft tissues, 8 (10.7%)/ and the others, 27 (36.0%). The main target symptoms for PST were dyspnea (38, 50.7%) and delirium (30, 40.0%). The most commonly used sedative agent was midazolam (72, 96.0%). Continuous deep sedation was intended in 61 patients (81.3%) at the death. Median survival from the start of PST were 2 days (range 0-54). The differences between palliative care team (PCT) intervention group and control group were lower age (58 vs. 62.5, P=0.048) and uniformity of initial midazolam dose (5-12 vs. 9.6-25.2 mg/day). Distinctive feature in this study was large proportion of adolescent and young adult patients with rare cancers. PCT might have different approaches to sedation in comparison to non-PCT medical staffs.

Behçet’s disease (BD) is a multisystem inflammatory disease of unknown origin. Rarely, BD occurs together with myelodysplastic syndrome (MDS). Interestingly, it is speculated that these are not simple coexistence but that the etiology of intestinal BD is at least partly derived from MDS itself. Furthermore, there is a relationship between MDS in patients with intestinal BD and trisomy 8. Immunosuppressive agents alone are insufficient to control MDS-associated BD, and many of these patients die of infection or hemorrhage. Surgery is considered for intestinal BD patients who are unresponsive to medical treatment or those with bowel complications such as perforation or persistent bleeding. We report a case of intestinal BD associated with MDS and trisomy 8. The patient was unresponsive to oral steroids and immunosuppressive treatment; the patient improved by surgical repair of a bowel perforation. Five years after the surgery, the patient is free of recurrence and not on medication. Our experience suggests that surgery may provide an effective therapeutic option for the treatment of MDS-related BD.

Treatment of perianal and vulvar extramammary Paget disease (EMPD), rare intraepithelial malignancies, is often challenging because of its potential to spread into the anal canal. However, there is still no consensus regarding the optimal resection margin within the anal canal. Between 2004 and 2014, six patients (three with perianal EMPD and three with vulvar EMPD) in which the spread of Paget cells into the anal canal was highly suspected were referred to our department. To evaluate the disease extent within the anal canal, preoperative mapping biopsy of the anal canal was performed in five out of six patients. Two patients were positive for Paget cells within the anal canal (one at the dentate line and the other at 0.5 cm above the dentate line), whereas in three patients, Paget cell were present only in the skin of the anal verge. Using 1 cm margin within the anal canal from the positive biopsy sites, we performed anal-preserving wide local excision (WLE), and negative resection margins within the anal canal were confirmed in all five patients. The remaining one patient with perianal EMPD did not undergo mapping biopsy of the anal canal because preoperative colonoscopy revealed that the Paget cells had spread into the lower rectum. Therefore, WLE with abdominoperineal resection was performed. During the median follow-up period of 37.3 months, no local recurrence was observed in all patients. Our small case series suggest the usefulness of mapping biopsy of the anal canal for the treatment of perianal and vulvar EMPD.
Anal Canal* ; Biopsy* ; Colonoscopy ; Consensus ; Follow-Up Studies ; Humans ; Paget Disease, Extramammary* ; Rectum ; Recurrence ; Skin

Treatment of perianal and vulvar extramammary Paget disease (EMPD), rare intraepithelial malignancies, is often challenging because of its potential to spread into the anal canal. However, there is still no consensus regarding the optimal resection margin within the anal canal. Between 2004 and 2014, six patients (three with perianal EMPD and three with vulvar EMPD) in which the spread of Paget cells into the anal canal was highly suspected were referred to our department. To evaluate the disease extent within the anal canal, preoperative mapping biopsy of the anal canal was performed in five out of six patients. Two patients were positive for Paget cells within the anal canal (one at the dentate line and the other at 0.5 cm above the dentate line), whereas in three patients, Paget cell were present only in the skin of the anal verge. Using 1 cm margin within the anal canal from the positive biopsy sites, we performed anal-preserving wide local excision (WLE), and negative resection margins within the anal canal were confirmed in all five patients. The remaining one patient with perianal EMPD did not undergo mapping biopsy of the anal canal because preoperative colonoscopy revealed that the Paget cells had spread into the lower rectum. Therefore, WLE with abdominoperineal resection was performed. During the median follow-up period of 37.3 months, no local recurrence was observed in all patients. Our small case series suggest the usefulness of mapping biopsy of the anal canal for the treatment of perianal and vulvar EMPD.
Anal Canal* ; Biopsy* ; Colonoscopy ; Consensus ; Follow-Up Studies ; Humans ; Paget Disease, Extramammary* ; Rectum ; Recurrence ; Skin

Objective: The aim of this study was to establish the proper definitions of venous thromboembolism (VTE) and bleeding events for a healthcare database in Japan.
Study Design: Validation study.
Methods: The study comprised patients with VTE or who had undergone orthopedic surgery of the lower extremities and whose outpatient or inpatient medical information from April 1, 2008 to September 30, 2013 was available.  The source population of the database was derived from 100 acute-care hospitals.  The endpoints were VTE events (deep venous thrombosis [DVT], pulmonary thromboembolism [PE]) and bleeding events (bleeding requiring blood transfusion, intracranial hemorrhage, intraocular hemorrhage, upper gastrointestinal [GI] bleeding, and lower GI bleeding).  The frequent events with laboratory data were randomly extracted and evaluated, while all the infrequent events with laboratory data were extracted and evaluated.  Positive predictive value (PPV) was defined as the proportion of events judged to be clinical by medical experts of all the extracted events.  First, we conducted a test with a small number of cases and then revised the definitions of events.  Second, we extracted and evaluated data in 50 patients for VTE and bleeding events patients, based on which we defined the target PPV level between 60 and 70%.
Results: Of the 5,044,743 patients in the database, 36,947 patients underwent orthopedic surgeries of the lower extremities and 3,578 patients experienced a VTE event.  The PPV at the first evaluation was 80.0% (8/10) for DVT, 57.1% (4/7) for PE, and 27.3% (6/22) for bleeding events.  At the second evaluation using the revised definitions, the PPV were 75.0% (42/56) for VTE and 73.3% (33/45) for bleeding events.  Overall, the PPVs for VTE and bleeding events were over 70%.  The PPV of the VTE events were 76.9% (30/39) for DVT and 70.6% (12/17) for PE.  The PPVs of each type of bleeding event were over 70% except for intracranial hemorrhage (44.4%, 4/9).
Conclusion: The PPV was high for VTE events (75.0%) and bleeding events (73.3%).  The definitions used in this study are rational for the identification of VTE, DVT, PE, and bleeding events in the healthcare database in Japan.  The definition for each type of bleeding event should be investigated in further studies.

Purpose: A report of effective occupational therapy for delirium patients with cancer is uncommon. We report a patient of carcinomatous meningitis, in whom her daily activity is improved by occupational therapy. Case: Firstly, we supported her meals and then started occupational therapy accepting her interest. Although degree of confusion and her performance status was not varied from beginning to end, she could concentrate our programmed works and change her way of feelings. Also occupational therapy promotes reminiscence about her life review and friendship among other patients even in delirium condition. Conclusion: Occupational therapy can reduce cancer patients' impatience, anxiety and solitary feelings and improve quality of life.

Alpha-fetoprotein-Producing gastric cancer is associated with poor prognosis because of frequent liver and lymph node metastasis. We present a case with synchronous liver metastasis who survived for 5 years. A 69-year-old man with upper abdominal pain was referred to our hospital. Gastrointestinal endoscopy revealed a Borrmann II-like tumor in the lower part of the stomach. Computed tomography revealed a tumor in the left lobe of the liver. Serum alpha-fetoprotein levels were markedly increased. We performed distal gastrectomy after administering oral tegafur/gimeracil/oteracil potassium and administered hepatic intra-arterial cisplatin injection. Liver metastasis showed partial response on computed tomography. Despite left hepatic lobectomy, further metastases to the liver and mediastinal lymph nodes became difficult to control. After sorafenib tosylate administration, stabilization of the disease was observed for 4 months. We conclude that hepatic intra-arterial chemotherapy and oral administration of sorafenib tosylate may potentially improve the prognosis in such cases.
Abdominal Pain ; Administration, Oral ; alpha-Fetoproteins ; Cisplatin ; Endoscopy, Gastrointestinal ; Gastrectomy ; Liver ; Lymph Nodes ; Neoplasm Metastasis ; Niacinamide ; Phenylurea Compounds ; Potassium ; Prognosis ; Stomach ; Stomach Neoplasms