Real-World Experience of Endoscopic Submucosal Dissection for Ulcerative Colitis-Associated Neoplasia

Introduction: Patients with ulcerative colitis (UC) have an increased risk of colorectal cancer. Some studies have recently investigated endoscopic resection of UC-associated neoplasia (UCAN), but the indications for endoscopic resection of UCAN remain controversial. This study sought to clarify the problems encountered in endoscopic submucosal dissection (ESD) for UCAN. Methods: Seventeen lesions in 12 patients with UCAN (UCAN group) and 913 epithelial lesions in 824 control patients without UC (non-UC group) were evaluated. Both groups underwent ESD between January 2010 and December 2017 at Toranomon Hospital, Tokyo, Japan. Treatment outcomes of the 2 groups were compared retrospectively. Results: Univariate analysis showed that the mean tumor size was significantly smaller in the UCAN group than in the non-UC group (25.1 ± 26.7 mm vs. 31.9 ± 19.0; p = 0.0023); however, the R0 resection rate was significantly lower in the UCAN group (70.6 vs. 92.9%; p = 0.001). Multivariate analysis showed a significantly lower negative horizontal margin rate in the UCAN group (odds ratio 11.3, 95% confidence interval 3.588–34.525; p = 0.000). Discussion/Conclusion: ESD for UCAN is associated with a low-negative horizontal margin rate. When performing ESD for UCAN, it is important to evaluate the accuracy of the UCAN demarcation line, especially for flat lesions, using white-light imaging and chromoendoscopy as well as other modalities, including biopsy of surrounding tissues.

Perioperative risk factors of psychological distress in patients undergoing treatment for esophageal cancer

Background:Esophageal cancer patients often feel depressed and are fearful of metastasis and death. The objective of this study was to clarify the characteristics of patients with psychological distress at all 5time points compared with patients with no psychological distress especially from standpoints of personal coping styles and QOL.Methods:In total, 102 of 152 consecutive patients who attended the outpatient clinic at Toranomon Hospital between April 2017 and April 2019 met eligibility criteria for inclusion in this study. Questionnaires designed to identify psychological distress(HADS-scores) and assess QOL(EORTC QLQ C-30/OES18) were administered at 5 time points from the time of the first outpatient consultation to 3 months after esophagectomy. The questionnaire of coping strategies(MAC-scales) was administered at only Time1 point.Results:Based on the trends of HADS-scores, we defined two groups:“persistent high-HAD scores” and “persistent low-HADS scores”. There are strong relationships between psychological distress and coping strategy, and psychological distress and QOL. The possibility that there are relationships between stress coping strategies and some QOL status depending on some point of treatment.Conclusions:The psychological distress during treatment course of esophageal cancer is significantly associated with the coping strategies and QOL influenced by esophagectomy. This study can provide baseline information for identifying patients in need of psychological management and paves the way for larger clinical studies in the future.

Perioperative Risk Factors of Psychological Distress in Patients Undergoing Treatment for Esophageal Cancer

Background:Esophageal cancer patients often feel depressed and are fearful of metastasis and death. The objective of this study was to clarify the characteristics of patients with psychological distress at all 5time points compared with patients with no psychological distress especially from standpoints of personal coping styles and QOL.Methods:In total, 102 of 152 consecutive patients who attended the outpatient clinic at Toranomon Hospital between April 2017 and April 2019 met eligibility criteria for inclusion in this study. Questionnaires designed to identify psychological distress(HADS-scores) and assess QOL(EORTC QLQ C-30/OES18) were administered at 5 time points from the time of the first outpatient consultation to 3 months after esophagectomy. The questionnaire of coping strategies(MAC-scales) was administered at only Time1 point.Results:Based on the trends of HADS-scores, we defined two groups:“persistent high-HAD scores” and “persistent low-HADS scores”. There are strong relationships between psychological distress and coping strategy, and psychological distress and QOL. The possibility that there are relationships between stress coping strategies and some QOL status depending on some point of treatment.Conclusions:The psychological distress during treatment course of esophageal cancer is significantly associated with the coping strategies and QOL influenced by esophagectomy. This study can provide baseline information for identifying patients in need of psychological management and paves the way for larger clinical studies in the future.

Direct Comparison of Long-Term Outcome of Allogeneic Transplantation for Myelofibrosis in Chronic and Leukemic Stage in a Single Institute

INTRODUCTION: Allogeneic hematopoietic cell transplantation provides an opportunity for a cure of myeloproliferative neoplasms (MPNs). Although several studies showed its efficacy even for leukemic transformation (LT) from MPNs, no direct evidence exists which compared the long-term outcome of patients in chronic phase (CP) and LT in a same cohort. METHODS: We retrospectively studied allogeneic hematopoietic cell transplantation for MPNs between 1999 and 2017 in Toranomon Hospital. LT was defined according to the WHO classification in 2016. Risk stratification was according to the dynamic international prognostic scoring system (DIPSS). The spleen index was defined as the measurement of spleen on CT scan. The day of neutrophil and platelet engraftment was defined as the first 3 consecutive days on which the patient's absolute neutrophil and platelet count was >0.5 x 109/L and >20 x 109/L without platelet transfusion, respectively. The study was approved by the ethics committee of Toranomon Hospital (research number #1796), and conducted in accordance with the Declaration of Helsinki. RESULTS: A total of 36 patients were extracted. At transplantation, the disease status of MPN was CP in 16 patients (44%) and LT in 20 (56%). Median spleen index was significantly lower in LT than CP (104 cm2 vs. 150 cm2, p < 0.01), and more CP patients received splenic irradiation before transplantation (p = 0.04). At the start of conditioning regimen, a half of the patients in LT was not in remission even after chemotherapy. Most patients in CP used bone marrow or peripheral blood stem cells, whereas umbilical cord blood (U-CB) was preferred for patients in LT (p < 0.001). Among these 2 cohorts, the cumulative incidence of neutrophil and platelet engraftment was comparable at day 60 and at 1 year after transplantation, respectively (neutrophil engraftment: 87.5% in CP vs. 80.0% in LT, p = 0.11; platelet engraftment: 68.8% in CP vs. 65.0% in LT, p = 0.70). Overall survival (OS) was significantly superior for patients in CP to ones in LT (p = 0.02) (Figure). OS rate at 5 and 10 years after transplantation for patients in CP and LT were 56.2% (95% confidence interval [CI], 1.0 - 35.4) vs. 11.2% (95% CI, 29.5 - 76.2), and 45.0% (95% CI, 17.8 - 69.1) vs. 0%, respectively. Median survival was 7.5 and 0.9 years for patients in CP and LT, respectively. Median follow up of survivors in CP and LT was 1652 days (range, 980 - 5395) and 906 days (range, 522 - 1014), respectively. At 10 years after transplantation, the cumulative incidence of relapse was significantly higher for patients in LT than ones in CP (6.2% in CP vs. 38.0% in LT, p = 0.04). In LT patients, disease recurrence occurred within 3 years after transplantation and 7 out of 17 patients (41%) died of relapse after transplantation. CONCLUSION: To achieve a long-term relapse-free survival, it is crucial for MPN patients to undergo transplantation in chronic phase, not after the development of LT. Delayed decision to transplant may be critical for patients who are at high risk for LT. Figure Disclosures No relevant conflicts of interest to declare.

Clinicopathological Analysis of "Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders" Reveals a Favorable Outcome Independent of the Effectiveness of Methotrexate Discontinuation in Autoimmune Disease Patients

[Background] Patients treated with immunosuppressive drugs for autoimmune diseases may suffer "other iatrogenic immunodeficiency-associated lymphoproliferative disorders" (OIIA-LPD). Some OIIA-LPDs regress after drug withdrawal but others need cytotoxic chemotherapy. However, the factors associated with a response to drug cessation remain unknown. [Methods] We collected clinical data on OIIA-LPD diagnosed between 2009 and 2018 at the University of Tsukuba Hospital and Toranomon Hospital in Japan. Clinicopathological features were retrospectively analyzed. The probability of overall survival (OS) and progression-free survival (PFS) was calculated using the Kaplan-Meier method. OS was defined as the time between the date of diagnosis of OIIA-LPD and the date of death or last follow-up. PFS was defined as the time from the date of diagnosis of OIIA-LPD to the date of commencing chemotherapy or the date of death or last follow up. [Results] Fifty-four cases of OIIA-LPD were identified, of which 25 were diagnosed at the University of Tsukuba Hospital and 29 at Toranomon Hospital. The male to female ratio was 1:3.5 and the median age at diagnosis was 70 years (range, 35-85). Thirty-four patients (63%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Most patients (n=50 [93%]) had rheumatoid arthritis (RA). The remaining 4 patients had systemic lupus erythematosus (SLE), myasthenia gravis (MG), polymyalgia rheumatica (PMR), and polymyositis (PM), respectively. Methotrexate (MTX), tacrolimus, and biological agents were used in 49, 17, and 16 cases, respectively. Histological diagnoses of OIIA-LPD type were diffuse large B-cell lymphoma (DLBCL) (n=24), composite lymphoma of DLBCL and follicular lymphoma (FL) (n=1), Hodgkin lymphoma (HL) (n=18), MALT lymphoma (n=2), peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) (n=2), angioimmunoblastic T-cell lymphoma (AITL) (n=1), B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic HL (n=1), extranodal NK/T-cell lymphoma (ENKTL) (n=1), Burkitt lymphoma (n=1), and not specified (n=3). Epstein-Barr virus (EBV) was detected in 61% of cases tested (31/51) by in situ hybridization for EBER. At diagnosis of OIIA-LPD, 44 cases (81%) were under MTX treatment. MTX was discontinued in all of these, after which spontaneous regression was observed in 27 (61%). There was no clinical response in 5 patients (11%) within 2 months of MTX cessation, and 12 patients (27%) received chemotherapy without confirming whether stopping MTX would have been sufficient intervention. In 27 cases with spontaneous regression after cessation of MTX, 18 achieved complete remission without chemotherapy, but 9 needed chemotherapy due to re-initiation of LPD. Regarding the histological diagnosis, spontaneous regression was observed in OIIA-LPD patients with DLBCL in 12 of 24 cases (50%) and those with HL in 8 of 18 (44%). After achieving spontaneous regression, patients with DLBCL (10/12 cases, 83%) did not require any form of chemotherapy more often than those with HL (4/8 cases, 50%). Neither EBV positivity nor histology were associated with spontaneous regression. With a median follow-up of 26.1 months (range, 1-120.7), 2-year OS and PFS was 91.9% and 30.1%, respectively. The 2-year PFS of DLBCL and HL was 33.1% and 17.5%, respectively (p=0.533). Only four patients died due to the progression of OIIA-LPD. [Conclusion] Fifty-four cases of OIIA-LPD were retrospectively analyzed. Spontaneous regression after MTX discontinuation was observed in approximately 60% of these patients. No factors associated with response to drug cessation were associated with histological features or EBV positivity, but patients with DLBCL remained in complete remission more frequently than those with HL. Despite the fact that 2-year PFS is low, our retrospective analyses revealed favorable OS of OIIA-LPD because chemotherapy resulted in a good response regardless of whether MTX discontinuation was effective. Disclosures No relevant conflicts of interest to declare.

Clinicopathological presentations and surgical outcomes of esophageal melanoma

Background Primary malignant melanoma of the esophagus is a rare tumor with a poor prognosis; the optimal treatment strategy has yet to be established. This study aimed to clarify clinical features, courses, and outcomes of patients undergoing surgical resection of primary malignant melanoma of the esophagus. Methods Six patients with primary malignant melanoma of the esophagus, in whom the absence of other primary melanomas had been confirmed, were selected from the medical database maintained in Toranomon Hospital. Their clinicopathological characteristics and long-term outcomes were retrospectively reviewed and analyzed. Results All 6 patients (five males and one female) underwent radical esophagectomy with three-field regional lymphadenectomy, and none received neoadjuvant therapy. Tumor invasion was classified into T1 in 5 (83%) cases and T3 in one (17%). Four (67%) patients had nodal metastases (one N1, one N2 and two N3). No distant metastatic lesions were detected preoperatively in any of our cases. Postoperative surveillance revealed recurrence in all 6 patients, and 5 (83%) died of the disease. The median overall survival was 24 months. One patient with a T3N3M0 tumor was treated after surgery with a dacarbazine-nimustine-vincristine regimen followed by irradiation for bone recurrence and survived for 87 months postoperatively. Another patient with a T1N3M0 tumor who survived for 27 months after liver and bone recurrence was treated with nivolumab, ipilimumab, and dacarbazine. Conclusion Although the courses of patients with primary malignant melanoma of the esophagus were consistently unfavorable, surgical resection with multidisciplinary therapeutic modalities may prolong survival in some cases.

High-Dose Intravenous Immunoglobulin and Immunosuppressive Therapy Have Therapeutic Potential for Non-Infectious Myelopathy and Peripheral Neuropathy Following Cord Blood Transplantation

BACKGROUND: We previously reported higher incidence of central nervous system complications (CNSCs) after cord blood (CB) than after bone marrow or peripheral blood transplantation (Kageyama K, et al. ASH 2016). Infectious complications such as human herpes virus type 6 (HHV-6) associated limbic encephalitis and/or myelitis have been the major cause of CNSCs. In this study, we now focused on non-infectious myelopathy and peripheral neuropathy (NIMPN) for which the main diseased focus located outside of cerebrum or cerebellum, since there has been little information available about them. The aim of the study is to clarify the incidence and the outcome of NIMPN after CBT. METHODS: We retrospectively studied medical records of 459 patients who underwent CBT as the first transplantation at Toranomon Hospital between July 2012 and March 2018. NIMPNs were diagnosed when the patients developed myelopathy or peripheral neuropathy without detection of pathogens tested in cerebrospinal fluid (CSF) or without radiological findings indicating hemorrhage, ischemia, or focal lesions suggestive of infections. We excluded the patients whose ECOG performance status scale was 3 or 4, and who had neurological symptoms before transplantation. Institutional review board of Toranomon Hospital approved the study (research number #1205-H) RESULTS: NIMPNs developed in 8 patients within 2 years after transplantation (2 myelopathies and 6 peripheral neuropathies [PN]). Their characteristics are as follows: the median age, 53 years (range, 37 - 62); 5 males and 3 females; AML-NOS (n = 5), AML with MRC (n = 1), therapy-related MDS or AML (n = 2). All except one were not in remission before transplantation. The combination of fludarabine, busulfan, and melphalan with or without high-dose cytarabine was used as conditioning regimen. Tacrolimus (Tac) alone (n = 2), Tac and mycophenolate mofetil (n = 5), and Tac and methotrexate (n = 1) were used as GVHD prophylaxis. The cumulative incidence of NIMPNs was 1.74% at 2 years after transplantation (95% confidence interval, 0.54 - 3.93). The median onset day of NIMPNs was 90 days after transplantation for all patients (range, 25 - 255); 40 days for myelopathy, and 100 days for PN. All had varying degree of hypesthesia or paresis and were unable to walk by themselves at diagnosis. All developed neurological symptoms after engraftment. Grade 2 - 3 of acute GVHD preceded NIMPNs in all patients. At diagnosis, the following pathogens were confirmed to be negative by PCR in CSF; HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, BKV, toxoplasma. CSF cell count and protein level did not increase in all of them. Myelin basic protein level in CSF was elevated in 3 out of 6 patients (519 ng/L and 1358 ng/L for myelopathies, 1321 ng/L for PN), which suggested demyelinating changes. Oligoclonal bands were not detected. Spinal MRI study performed in 4 patients showed no abnormality. In line with previous reports, axonal degeneration was confirmed by nerve biopsy in 2 patients with PN. After the diagnosis of NIMPNs, all patients were treated with high dose intravenous immunoglobulin (IVIG) (400 mg/kg for 5 days). The median interval from diagnosis to treatment was 28 days (range, 5 - 71). IVIG was administered monthly for the median of 2 courses (range, 2 - 5). In 2 patients, rituximab or steroid pulse therapy was added on IVIG, respectively. After these treatments, symptoms improved in 6 out of 8 patients and they finally were able to walk by themselves (1/2 of myelopathy and 5/6 of PN). The remaining one died of severe liver acute GVHD and another one is hospitalized until now without recovery. The median follow-up days of survivors was 498 days (range, 74 - 2190). Seven out of 8 patients are currently alive. CONCLUSION: NIMPNs were observed after CBT with low incidence. Although all patients presented severe neurological symptoms at diagnosis, IVIG and immunosuppressive therapy had a therapeutic benefit, and their prognosis with respect to neurological symptoms and survival was not dismal. Disclosures Yamamoto: Bristol-Myers Squibb: Honoraria.

PS02.223: EFFECTIVENESS OF ETILEFRINE REGIMEN FOR CHYLOTHORAX AFTER ESOPHAGECTOMY WITH THORACIC DUCT RESECTION

Background Management of postoperative chylothorax generally involves nutritional regimens as well as pharmacological and surgical therapies, but a clear consensus has yet to be reached. The aim of this study was to clarify the usefulness of an etilefrine regimen to broaden the medical treatment options for postoperative chylothorax after esophagectomy with resection of the thoracic duct. Methods A total of 371 consecutive patients with esophageal cancer were identified from a prospectively constructed database at the Department of Gastroenterological Surgery, Toranomon Hospital between January 2011 and February 2017. They were patients with squamous cell carcinoma or adenocarcinoma of the esophagus including Siewert type I, II tumor of the esophagogastric junction who underwent subtotal esophagectomy. Of these 371 patients, 19 patients who were diagnosed with chylothorax as a postoperative complication were enrolled in this study. Results Conservative treatment achieved cure in 16 patients among 19 patients. The duration of chylothorax tended to be longer in the no-etilefrine group (n = 5) than in the etilefrine group (n = 11) (27.8 vs. 11.6 days; P = 0.078). The 14 patients among 19 patients was resected the thoracic duct. Etilefrine was used in 12 of these 14 patients. Among these 12 patients, 3 required surgical treatment and the remaining 9 patients were cured with conservative treatment. The duration of chylothorax was shorter in the conservative treatment group than in the surgical treatment group (11.9 vs. 36.3 days; P = 0.052). And also, with the use of etilefrine as adjuvant therapy, cure was achieved in 9 patients (75%) without surgical intervention. Conclusion The findings of this study suggest the effectiveness of etilefrine in patients with chylothorax following esophagectomy. The drug was effective even in post-TDR chylothorax, an often intractable condition that is difficult to treat conservatively. However, when the effectiveness of etilefrine regimen is unexpectedly poor, it is important to switch from drug therapy to surgical treatment in the early stage of this complication. Disclosure All authors have declared no conflicts of interest.