2.Proof-of-concept study of the caninized anti-canine programmed death 1antibody in dogs with advanced non-oral malignant melanoma solid tumors
Masaya IGASE ; Sakuya INANAGA ; Shoma NISHIBORI ; Kazuhito ITAMOTO ; Hiroshi SUNAHARA ; Yuki NEMOTO ; Kenji TANI ; Hiro HORIKIRIZONO ; Munekazu NAKAICHI ; Kenji BABA ; Satoshi KAMBAYASHI ; Masaru OKUDA ; Yusuke SAKAI ; Masashi SAKURAI ; Masahiro KATO ; Toshihiro TSUKUI ; Takuya MIZUNO
Journal of Veterinary Science 2024;25(1):e15-
Background:
The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear.
Objective:
The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM.
Methods:
Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group.
Results:
One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%).Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively.
Conclusions
The present study demonstrated that ca-4F12-E6 was well-tolerated in nonOMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs.
3.Usefulness of Endoscopic Transpapillary Tissue Sampling for Malignant Biliary Strictures and Predictive Factors of Diagnostic Accuracy.
Hiroki TANAKA ; Shimpei MATSUSAKI ; Youichirou BABA ; Yoshiaki ISONO ; Tomohiro SASE ; Hiroshi OKANO ; Tomonori SAITO ; Katsumi MUKAI ; Tetsuya MURATA ; Hiroki TAOKA
Clinical Endoscopy 2018;51(2):174-180
BACKGROUND/AIMS: It is sometimes difficult to distinguish between malignant and benign biliary strictures using imaging studies alone, and pathological diagnosis is necessary. The aim of this study was to determine the usefulness of endoscopic transpapillary tissue sampling and factors predictive of diagnostic accuracy. METHODS: From April 2008 to December 2014, 136 patients underwent endoscopic transpapillary tissue sampling for malignant biliary strictures. The cytological and histological findings were reported as negative, suspicious, or positive. Suspicious and positive findings were defined as pathologically positive. RESULTS: The sensitivity was 65.0% for forceps biopsy, 49.5% for brush cytology, 46.2% for bile aspiration cytology, and 21.9% for endoscopic nasobiliary drainage cytology. The combination of these procedures improved the sensitivity (72.8%). Endoscopic transpapillary tissue sampling was more sensitive for lesions of biliary origin (91.4%) than for extrabiliary lesions (66.3%). In surgical cases, the sensitivity for tumors with an infiltrative growth pattern (53.3%) was significantly lower than for a tumor with an expanding or intermediate growth pattern (87.5%). CONCLUSIONS: Combining procedures can improve diagnostic accuracy. It may be possible to predict the sensitivity of endoscopic transpapillary tissue sampling by evaluating the etiology and tumor growth pattern using preoperative imaging studies.
Bile
;
Biliary Tract Neoplasms
;
Biopsy
;
Constriction, Pathologic*
;
Diagnosis
;
Drainage
;
Humans
;
Pancreatic Neoplasms
;
Surgical Instruments
4.Two advanced cancer patients in whom escitalopram was useful for depression
Shinichiro Nakajima ; Hitoshi Tanimukai ; Mika Baba ; Koji Amano ; Muneyoshi Kawasaki ; Hiroshi Wakayama
Palliative Care Research 2013;8(2):548-553
Purpose: Escitalopram has been inadequately evaluated in cancer patients. Here, we report two patients with advanced cancer who benefited from escitalopram for depression. Case 1: A man aged in his 50s had postoperative recurrence of rectal cancer. He was diagnosed with a major depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). The score of the Hamilton Rating Scale for Depression (HAMD-17) was 20 points. He began treatment with 10 mg/day of escitalopram. His symptoms began to improve at about 14 days, and the HAMD-17 score was 4 points at 23 days, suggesting a marked improvement. Case 2: A woman aged in her 50s had cancer of the external auditory canal. She was diagnosed with a major depressive episode according to DSM-IV-TR. The score of HAMD-17 was 26 points. She began treatment with 10 mg/day of escitalopram. Her symptoms began to improve at 15 days, and the HAMD-17 score at 28 days was 13 points, suggesting a marked improvement. In both cases, serious side effects, clear exacerbation of depression, and withdrawal syndrome due to acute drug deprivation associated with worsening of the symptoms were not noted. Conclusion: Escitalopram is considered a useful drug for depression in patients with advanced cancer.
5.A study of the significance of death conferences in the palliative care unit : through the experience of coping with the death of a liver cancer patient who died of necrotizing fasciitis resulted from bedsore
Koji Amano ; Mika Baba ; Takashi Sugiura ; Muneyoshi Kawasaki ; Shinichiro Nakajima ; Hiroshi Wakayama ; Akiko Watakabe ; Hiromi Kunimoto ; Miwako Uemori
Palliative Care Research 2012;7(2):568-574
When patients hospitalized in a palliative care unit die, particularly when their deaths were not peaceful ones, we, as health professionals, feel distressed, senses of helplessness and defeat, and even regret. However, busy daily clinical practice usually does not allow us to express these feelings. After going through such an experience repeatedly, your self-efficacy may be reduced and you could feel burned out. In this study, through the experience of coping with the death of a liver cancer patient who died of necrotizing fasciitis resulted from bedsore, a death conference was organized for us, health professionals who had been directly concerned with the patient, to discuss questions, conflicts, and dilemmas that arose when we provided care and express feelings that had been repressed. And other participants in the conference, who had not been directly concerned with the patient, gave their affirmative views. The conferences served to: (1) promote mutual understanding, trustful relationships, and teamwork among us, (2) increase our awareness of palliative care, and (3) allow us to cope with stress and prevent us from feeling burned out. These effects are considered to help implement improved health care. In the former part of the conference remarks were divided into three categories, (1) regret, (2) questions, conflicts, and dilemmas, and (3) senses of helplessness and defeat, and in the latter part affirmative views were mainly stated.
6.Validation of Hospital Anxiety and Depression Scale as a screening tool for psychological distress in advanced cancer patients undergoing chemotherapy
Keita Uchino ; Hitoshi Kusaba ; Junji Kishimoto ; Hiroshi Mitsuyasu ; Hiroaki Kawasaki ; Eishi Baba ; Koichi Akashi
Palliative Care Research 2011;6(2):150-157
Advanced cancer patients experience stress and are at risk for developing psychological problems. Early diagnosis and suitable intervention are very important for their quality of life and compliance with chemotherapy. The Hospital Anxiety and Depression Scale (HADS) is one of the most commonly used mood scales; however, HADS has not been validated for use with cancer patients undergoing chemotherapy. The purpose of this study was to validate HADS as a screening tool for psychological distress among cancer patients undergoing chemotherapy. We also identified possible factors contributing to psychological distress and explored the development of original screening tools. Fifty subjects agreed to complete HADS and consult with psychiatric specialists. Possible contributing factors to psychological distress were identified by HADS and logistic regression analysis. The mean score for patients with psychological distress was 20.0 ± 8.93, and for patients without distress was 9.67 ± 6.11; scores for patients with psychological distress were significantly higher. The optimal cutoff point of psychological distress appeared to be 17. This cutoff point was associated with 72.7% sensitivity and 82.1% specificity. The factor “recurrent cancer” (p=0.043) had an odds ratio of 7.24 (1.21-61.2). We verified that HADS is a useful screening tool for cancer patients undergoing chemotherapy. The factor “recurrent cancer” was shown to contribute to psychological distress. Palliat Care Res 2011; 6(2): 150-157
7.A Stent Graft Infection after Abdominal Aortic Aneurysm Repair
Masakazu Aoki ; Kenichi Kamiya ; Shinji Ogawa ; Hiroshi Baba ; Yasuhide Okawa
Japanese Journal of Cardiovascular Surgery 2011;40(3):125-129
We present a rare case of stent graft infection. A 69-year-old man, who had undergone endovascular repair of an abdominal aortic aneurysm with an Inoue stent graft 5 years previously, was admitted with high-grade fever. An abscess around an abdominal aortic aneurysm was found on abdominal computed tomography (CT) and he was given a diagnosis of stent graft infection. The stent graft was removed and vascular reconstruction was performed using a Gelweave graft bonded with rifampicin. The graft was then covered with the greater omentum, and he was discharged on the 27th postoperative day.
8.The Long-Term Survival and Predictors of Heart Failure after Endoventricular Circular Patch Plasty
Yoshiyuki Nishimura ; Yasuhide Ookawa ; Hiroshi Baba ; Syunsuke Fukaya ; Masakazu Aoki ; Shinji Ogawa ; Masashi Komeda
Japanese Journal of Cardiovascular Surgery 2009;38(1):1-6
Endoventricular circular patch plasty (the Dor procedure) has been demonstrated to improve outcome in patients with ischemic cardiomyopathy. However, in some of them congestive heart failure (CHF) occurred during follow-up. This study examined the effects of the Dor procedure on the long-term survival and predictors of CHF after this procedure. Hemodynamic and clinical results were analyzed and predictors of CHF were examined. Postoperative ESVI in the CHF group was larger than that in the non-CHF group. The delayed MR rate was greater following the CHF group (82.4%) compared to the non-CHF group (19.2%). Despite mitral valve repair (N=8), 3 patients had delayed MR. All of them were greater than MR3. Hemodynamic and clinical results were improved by the Dor procedure. However, cardiac events were usually occurred during the follow-up. The predictor of CHF was delayed MR. Therefore, patients with preoperative MR should be treated. If preoperative MR is greater than 3, there will be MR recurrence cases after MVP only. Therefore, patients with preoperative MR (3 or 4) should be treated by alternative surgical procedures.
9.Evaluation of Graft Selection and Design to Improve Long-Term Results of Coronary Artery Bypass Grafting
Hiroshi Baba ; Shinji Ogawa ; Syunsuke Fukaya ; Hideki Kitamura ; Masakazu Aoki ; Masashi Komeda ; Yasuhide Ookawa
Japanese Journal of Cardiovascular Surgery 2009;38(6):355-360
To improve the long-term clinical results of coronary artery bypass grafting, we evaluated our graft selections and the designs that were used, in relation to the quality of the anastomoses and patient backgrounds. We retrospectively reviewed the records of 505 patients who underwent isolated coronary artery bypass grafting involving more than 3 vessel reconstructions between May 1999 and March 2007. Neither the selection of a saphenous vein graft nor that of an internal thoracic artery graft was a statistically significant cardiac event factor. The cardiac event-free rates (at 1 and 5 years) according to anastomotic site were as follows : a) 92.9% and 76.6% for a radial artery graft and 93.2% and 83.9% for a saphenous vein graft at the right coronary artery ; b) 93.0% and 70.3% for a radial artery graft and 95.1% and 80.4% for a saphenous vein graft at the distal right coronary artery ; c) 94.5% and 77.8% for a left internal thoracic artery graft and 93.0% and available for a right internal thoracic artery graft at the left anterior descending artery ; d) 96.5% and 79.8% for a radial artery graft, 93.0% and 78.0% for a saphenous vein graft, and 91.3% and 75.6% for an internal thoracic artery graft at the left circumflex artery. Significant cardiac event factors were dialysis (risk ratio, 5.28 ; p<0.001), the use of a right gastroepiploic artery graft as the inflow blood vessel of a radial artery graft (risk ratio, 5.75 ; p=0.02), and off-pump coronary artery bypass grafting (risk ratio, 1.62 ; p=0.03). As a tendency toward more frequent early-stage cardiac events among patients with radial artery grafts was confirmed, careful follow-up is important for this group of patients. Right gastroepiploic artery grafts should be chosen carefully with full consideration of the anastomotic site quality and the flow demand, as the blood supply capability of such grafts is limited. For dialysis patients, although the mid-term clinical results are still being evaluated, a saphenous vein grafts have bwer early-stage of cardiac events. In younger patients, off-pump bypass is not the only treatment method available, and revascularization with extracorporeal circulation can reliably achieve good long-term results. To improve the long-term clinical results for coronary artery bypass grafts, graft selection and design should be carefully considered on a case-by-case basis. The quality of the anastomotic site and the patient background are important factors, especially with regard to the selection of a saphenous vein graft or a right gastroepiploic artery graft. A radial artery graft should be selected for use in relatively young patients because of its superior patency. Off-pump bypass may not necessarily be the treatment of choice in some cases because revascularization using extracorporeal circulation can reliably achieve better long-term results.
10.Valve Replacement in Hemodialysis Patients in Japan
Masakazu Aoki ; Yoshiyuki Nishimura ; Hiroshi Baba ; Masanori Hashimoto ; Yasuhide Ohkawa ; Yoshitaka Kumada
Japanese Journal of Cardiovascular Surgery 2007;36(1):1-7
A retrospective review was performed on 43 patients on hemodialysis undergoing valve surgery between May 1999 and August 2004. Ages ranged from 36 to 80 years (mean, 63.8 years). Twenty aortic, 9 mitral, 8 aortic and mitral and 6 valvuloplasties were performed. Twenty-three aortic mechanical valves, 5 aortic bioprosthetic valves, 13 mitral mechanical valves and 4 mitral bioprosthetic valves were implanted. Twenty-five of the 28 aortic valve replacement were hypoplasia of the aortic valve ring. There were 3 hospital deaths (heart failure, pneumonia and sepsis). There were 10 late deaths (2 heart failure, 2 pneumonia, wound infection, cerebral infarction, 2 cancer, arteriosclerosis obliterans and unknown death). Survival at 1, 3 and 5 years was 81%, 74% and 47%. There were three documented major bleedings or thromboembolisms in the 29 patients with mechanical valves (10%) and none in the 9 patients with bioprosthetic valves (0% no significance). Three reoperations were performed for premature degeneration of bioprosthetic valve (19, 24 and 50 months) due to accelerated calcification. These results demonstrate that the prosthetic valve-related major bleedings and strokes in hemodialysis patients are similar for both mechanical and bioprosthetic valves, and that bioprosthetic valves will undergo premature degeneration. Therefore, preference should be given to mechanical valve prostheses in hemodialysis patients.


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