Mutation and Lineage Analysis of DNMT3A in BCR-ABL1-negative Chronic Myeloproliferative Neoplasms

SummaryIn addition to the JAK2 V617F mutation, somatic mutation in DNMT3A has been described in BCL-ABL1-negative myeloproliferative neoplasms (MPNs). We have screened for DNMT3A exon 23 mutations in 130 adult Taiwanese patients with chronic phase myeloproliferative neoplasms. Only one somatic DNMT3A R882H mutation was identified in one JAK2 V617F mutation-positive essential thrombocythemia patient (1/91, 1%). Both mutations were detected in the CD34+-, CD19+-, peripheral blood mononuclear cell- and granulocyte-enriched fractions, but were not detected in the CD3+-enriched fraction by lineage analysis. Our findings suggest that DNMT3A mutation is not prevalent in MPNs, and further study is needed to clarify its role in the molecular pathogenesis of myeloproliferative neoplasms

Role of Transperitoneal Laparoscopic Para-aortic Lymph Node Dissection for the Treatment of Elderly Patients with Locally Advanced Squamous Cell Carcinoma of the Uterine Cervix

Background: Surgical staging using transperitoneal laparoscopic para-aortic lymph node dissection is an option for the pretreatment evaluation of locally advanced cervical cancer; however, its role for elderly patients (≥ 65 years) remains unclear. Methods: Elderly patients with stage IIB–IVA cervical squamous cell carcinoma who underwent transperitoneal laparoscopic para-aortic lymph node dissection (TLSPAD) before radiation therapy (RT) or concurrent chemoradiation therapy (CCRT) during 1993–2001 were included in this retrospective study. The control group included elderly patients with the same clinical conditions, except they did not undergo TLSPAD. Survival and major bowel complications were compared between these two groups. Results: The TLSPAD group consisted of 19 patients (median age: 72 years; range: 65–78 years), and the control group consisted of 37 patients (median age: 73 years; range: 65–86 years). In the TLSPAD group, para-aortic lymph node metastasis was noted in 15.8% of patients and another 15.8% were unable to have their lymph node laparoscopically retrieved. Although patients in the TLSPAD group demonstrated a higher rate of receiving CCRT than the control group, neither failure-free survival nor overall survival were statistically different between these two groups. Subsequent major bowel complications (e.g., fistula, bowel obstruction) were more frequent in the TLSPAD group (36.8%) than the control group (10.8%; p=0.032). Conclusion: In elderly patients with locally advanced cervical squamous cell carcinoma, pretreatment TLSPAD might not improve survival and might be associated with an increased risk of subsequent major bowel complications. Extraperitoneal laparoscopic para-aortic lymphadenectomy might be a better method for the pretreatment surgical staging of elderly patients because it could potentially result in fewer bowel complications

Outcomes in Advanced Stage Epithelial Ovarian, Fallopian Tubal, and Peritoneal Cancer after Primary Surgery and Adjuvant Chemotherapies: A Single-Institute Real-World Experience

Debulking surgery followed by systemic chemotherapy—including three-weekly intravenous paclitaxel and carboplatin (GOG-158)—is the cornerstone for advanced epithelial ovarian, fallopian tubal, and peritoneal cancer (EOC) treatment. In this scenario, Federation of Gynecology and Obstetrics (FIGO) stage, cell types, completeness of surgery, lymph nodes (LN) status, adjuvant chemotherapy regimens, survival status, progression-free survival (PFS), and overall survival (OS) of 192 patients diagnosed as having stage IIIA1–IVB EOC over January 2008–December 2017 were analyzed retrospectively. Of them, 100 (52.1%) patients had been debulked optimally. Of all cases, 64.1% and 10.9% demonstrated serous and clear-cell carcinoma. Moreover, the FIGO stage, surgery completeness, and LN status affected recurrence/persistence and mortality (all p < 0.001). Clear cell carcinoma led to shorter survival than serous carcinoma (p = 0.002). Adjuvant chemotherapy regimens were divided into five main groups according to previous clinical trials. However, choice of chemotherapy failed to demonstrate significant differences in patient outcomes. Similar results were found in the sub-analysis of optimally debulked cases, except that intraperitoneal chemotherapy could reduce mortality risk when compared with GOG-158 (p = 0.042). Notably, retroperitoneal LN dissection in all cases or optimally debulked cases reduced risks of recurrence/persistence and mortality, and prolonged PFS and OS significantly (all p < 0.05). Without optimal debulking, LN dissection led to little improvement in outcomes. Various modified chemotherapy regimens did not prolong PFS and OS or reduce recurrence/persistence and mortality risks. LN dissection is strongly recommended to improve the completeness of surgery and patient outcome. Clear cell type has a poorer outcome than serous type, which requires more aggressive treatment and follow-up