Prediction of early (4-week) mortality in acute myeloid leukemia with intensive chemotherapy

The progress with intensive chemotherapy and supportive care measures has improved survival in patients with newly diagnosed acute myeloid leukemia (AML). Given the recent development of effective low intensity therapies, an optimal decision on the therapy intensity may improve survival through the avoidance of early mortality. We reviewed the outcome of 3728 patients with newly diagnosed AML who received intensive chemotherapy between August 1980 and May 2020. Intensive chemotherapy was defined as a cumulative cytarabine dose ≥ 700 mg/m² during induction therapy. We divided the whole cohort into a training and validation group at a 3:1 ratio. The population was divided into a training (2790 patients) and a validation cohort (938 patients). The median age was 55 years (range, 15-99). Among them, 442 patients (12%) had core-binding factor AML. Binary logistic regression identified older age, worse performance status, hyperbilirubinemia, elevated creatinine, hyperuricemia, cytogenetic abnormalities other than CBF and -Y, and pneumonia as adverse prognostic factors for an early 4-week mortality. This risk classification for early mortality was verified in the validation cohort of patients. In the validation cohort of more recently treated patients from 2000 to 2017, the 4-week mortality rates with intensive chemotherapy were 2%, 14%, and 50% in the low-, high-, and very high-risk group, respectively. The mortality rates with low intensity therapies were 3%, 9%, and 20%, respectively. The risk classification guides treatment intensity by the assessment of age, frailty, organ dysfunction, cytogenetic abnormality, and infection to avoid early mortality.     

Association of kidney function with cancer incidence and its influence on cancer risk of smoking: The Japan Multi-Institutional Collaborative Cohort Study

The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m², the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m² were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m² were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m² revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m², with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.     

Human papillomavirus genotype contribution to cervical cancer and precancer: Implications for screening and vaccination in Japan

To obtain baseline data for cervical cancer prevention in Japan, we analyzed human papillomavirus (HPV) data from 5045 Japanese women aged less than 40 years and diagnosed with cervical abnormalities at 21 hospitals during 2012‐2017. These included cervical intraepithelial neoplasia grade 1 (CIN1, n = 573), CIN2‐3 (n = 3219), adenocarcinoma in situ (AIS, n = 123), and invasive cervical cancer (ICC, n = 1130). The Roche Linear Array was used for HPV genotyping. The HPV type‐specific relative contributions (RCs) were estimated by adding multiple infections to single types in accordance with proportional weighting attributions. Based on the comparison of type‐specific RCs between CIN1 and CIN2‐3/AIS/ICC (CIN2+), RC ratios were calculated to estimate type‐specific risks for progression to CIN2+. Human papillomavirus DNA was detected in 85.5% of CIN1, 95.7% of CIN2‐3/AIS, and 91.2% of ICC. Multiple infections decreased with disease severity: 42.9% in CIN1, 40.4% in CIN2‐3/AIS, and 23.7% in ICC (P < .0001). The relative risk for progression to CIN2+ was highest for HPV16 (RC ratio 3.78, 95% confidence interval [CI] 3.01‐4.98), followed by HPV31 (2.51, 1.54‐5.24), HPV18 (2.43, 1.59‐4.32), HPV35 (1.56, 0.43‐8.36), HPV33 (1.01, 0.49‐3.31), HPV52 (0.99, 0.76‐1.33), and HPV58 (0.97, 0.75‐1.32). The relative risk of disease progression was 1.87 (95% CI, 1.71‐2.05) for HPV16/18/31/33/35/45/52/58, but only 0.17 (95% CI, 0.14‐0.22) for HPV39/51/56/59/66/68. Human papillomavirus 16/18/31/33/45/52/58/6/11 included in a 9‐valent vaccine contributed to 89.7% (95% CI, 88.7‐90.7) of CIN2‐3/AIS and 93.8% (95% CI, 92.4‐95.3) of ICC. In conclusion, our data support the Japanese guidelines that recommend discriminating HPV16/18/31/33/35/45/52/58 genotypes for CIN management. The 9‐valent vaccine is estimated to provide over 90% protection against ICC in young Japanese women.     

Signet‐ring cell/histiocytoid carcinoma in the axilla: A case report with genetic analysis using next‐generation sequencing

Signet‐ring cell/histiocytoid carcinoma (SRCHC) is a very rare skin appendage cancer, with an extremely rare occurrence in the axilla. This study describes the 11th case of SRCHC occurring in the axilla and reports the first gene alteration analysis performed for SRCHC. An 85‐year‐old Japanese male presented with a tumor in the left axilla. Biopsy of the axilla nodule demonstrated diffuse proliferation of histiocytoid neoplastic cells and signet‐ring cells in the dermis and subcutis. Immunohistochemistry revealed loss of E‐cadherin expression in these neoplastic cells. Accordingly, SRCHC of the axilla was diagnosed. Genetic analysis using next‐generation sequencing demonstrated missense mutation of PIK3CA (c1633G>A, pGlu545Lys) and no CDH1 gene mutation.SRCHC of the axilla is considered equivalent to a histiocytoid variant of invasive lobular breast carcinoma. The present SRCHC case demonstrated a pathogenic PIK3CA mutation, which is observed in invasive lobular carcinoma. Additional large case studies are required to clarify the clinicopathological features and gene alterations in SRCHC of the axilla.     

Preoperative scoring system for predicting early adjacent vertebral fractures after Balloon Kyphoplasty

BackgroundAdjacent vertebral fracture (AVF) is a major complication following Balloon Kyphoplasty (BKP). There is no scoring system for predicting AVF using only preoperative elements. The purposes of this study were to develop a scoring system for predicting early AVF after BKP based on preoperative factors and to investigate the appropriate surgical indication for BKP.MethodsOf 220 patients who underwent BKP at a single institution since 2011, 65 patients over the age of 60 who had undergone a standing whole spine X-ray preoperatively were enrolled. Factors affecting the occurrence of early AVF were examined. A scoring system was created consisting of the factors exhibiting significant differences, and the correlation between the total score and the incidence of early AVF was investigated.ResultsTwenty of the 65 patients (30.8%) had early AVF. In a univariate analysis, age, previous vertebral fracture, pelvic tilt, and Local kyphosis significantly influenced early AVF. In a multivariate logistic regression analysis, age had an odds ratio of 1.136 (95% CI 1.001–1.289), previous vertebral fractures 4.181 (1.01–17.309), and Local kyphosis 1.103 (1.021–1.191). The scoring system was set as follows: ①Age (<75 years: 0 points(P), 75years≦: 1P), ②The number of previous vertebral fractures (0: 0 P, 1: 1P, 2: 2P, 3 or more: 3P), and ③Local kyphosis (<10°: 0P, 10°≦: 1P). There was a correlation between the total score and the incidence of early AVF (r = 0.812, 1P = 0.05). The incidence of early AVF was 6.4% (2 cases/31 cases) for a score of ≦1P and 54.5% (18 cases/33 cases) for a score of ≧2P.ConclusionsThere was a correlation between the total score and the incidence of early AVF. A score of 1 point or less may represent the appropriate surgical indication for BKP.     

Laparoscopic surgery for familial multiple gastrointestinal stromal tumors with germ line c-kit gene mutation

Familial gastrointestinal stromal tumor (GIST) is an exceedingly rare disease characterized by mutations in the c-kit and platelet-derived growth factor receptor alpha genes. We report the case of a 73-year-old woman with multiple submucosal tumors (SMTs) in the stomach and small intestine. Her elder sister had previously presented with multiple SMTs on examination and underwent surgery to remove the tumors because they showed a tendency to increase in size during follow-up. The sister's tumors were pathologically diagnosed as GISTs, and a germ line mutation was recognized in exon 17 of c-kit. Subsequently, the patient presented with multiple SMTs and the same germ line mutation as her sister. After 9 years of follow-up, a single tumor was found to have grown in size, and SILS was performed for this SMT, which was also pathologically diagnosed as a GIST. To our knowledge, this is the first report of laparoscopic surgery for a case of familial GIST.     

CT and MRI characteristics of ovarian mature teratoma in patients with anti-N-methyl-D-aspartate receptor encephalitis

PurposeThe purpose of this study was to determine the computed tomography (CT) and magnetic resonance imaging (MRI) characteristics of ovarian mature teratoma in patients with anti-N-methyl-d-aspartate receptor encephalitis (NMDAR-E).Materials and MethodsA total of 125 women (mean age, 40.9 ± 17.8 [SD] years; age range: 12–85 years) with 146 histopathologically or radiologically proven ovarian mature teratomas who underwent preoperative CT and MRI examinations were retrospectively included. Eight patients with 11 teratomas had NMDAR-E, whereas 117 patients with 135 teratomas did not have NMDAR-E. CT and MRI examinations were retrospectively reviewed and teratomas in patients with NMDAR-E were compared to those in patients without NMDAR-E. Comparisons were performed using Mann-Whitney U test or Fisher exact test.ResultsIn patients with NMDAR-E, maximum diameter of teratomas (26.1 ± 9.3 [SD] mm), prevalence of teeth/calcification (36%) and rate of occupation by fat components (26%) were lower than those in patients without NMDAR-E (67.0 ± 37.6 [SD] mm [P < 0.01]; 75% [P < 0.05]; and 65%[P < 0.01], respectively). More than 75% of space was occupied by fat components in 76/135 teratomas (56%) in patients without NMDAR-E, whereas this was not observed in any teratoma in patients without NMDAR-E.ConclusionBy comparison with teratomas in patients without NMDAR-E, teratomas in patients with NMDAR-E are smaller, have few teeth/calcification, and the amount of space occupied by fat components is smaller.