Medroxyprogesterone acetate therapy for patients with adenocarcinoma of the endometrium who wish to preserve the uterus-usefulness and limitations

BACKGROUND: To determine the effectiveness of medroxyprogesterone acetate therapy for women with endometrial adenocarcinoma who wish to preserve their uterus. STUDY DESIGN: Fifteen patients with endometrial carcinoma (12 with grade 1 endometrioid adenocarcinoma. 2 with grade 2 adenocarcinoma and 1 with adenoacanthoma) were treated with high-dose medroxyprogesterone acetate alone as primary therapy and their clinical responses evaluated. RESULTS: Seven of the 12 cases (58%) with grade I adenocarcinoma and one of the two (50%) with grade 2 carcinoma responded initially to medroxyprogesterone acetate. The median length of treatment required for regression was 29 weeks. Three patients who initially responded relapsed. Thirteen patients are alive without evidence of disease as of December 1999 (10 to 146 months, median; 4 years and 11 months) and one is continuing medroxyprogesterone acetate therapy as a final follow-up. One patient was lost to follow-up. Two patients have conceived having three healthy infants. CONCLUSION: Treatment of endometrial carcinoma with high-dose medroxyprogesterone acetate could be an alternative to hysterectomy, although the successful rate is limited.     

Molecular weight variations in the diversity of phospholipase A2 forms in reptile venoms

Reptile venoms exhibit a wide diversity of phospholipase A2 forms when examined by electrophoretic and chromatographic techniques which separate on the basis of net charge. In principle, diversity in charge among the enzyme forms could result from two types of structural modifications: (i) pretranslational modifications, such as differences in amino acid sequences; (ii) post-translational modifications, such as partial proteolysis or hydrolysis of amide functions of asparagine and glutamine residues. Some types of modifications alter both charge and molecular weight. A radiolabeling technique has been developed which allows detection of phospholipase A2 enzymes after electrophoretic separation on the basis of molecular weight in polyacrylamide gels containing sodium dodecylsulfate. Venom preparations were radiolabeled by incubation with p-dodecylphenacylbromide, which was prepared radiolabeled to high specific activity with tritium. The labeling agent was dispersed in phosphatidylcholine liposomes and incubated with venom preparations under conditions of optimal enzyme activity. The preparations were then extracted with ether and hexane to remove substrate and unbound label and subjected to polyacrylamide gel electrophoresis under standard conditions. Protein-bound radiolabel was detected by fluorography and autoradiography. Patterns of labeled species obtained by gel electrophoresis of selected venoms using separation on the basis of charge were similar to the patterns of phospholipase A2 variants obtained under the same electrophoretic conditions using enzymatic detection in phosphatidylcholine-containing gels. Examination of a variety of snake and lizard venoms using this technique revealed the presence of multiple molecular weight forms of labeled enzymes, but the extent of diversity was less than that observed with the same venoms using separation of phospholipase electrophoretic variants on the basis of charge. The results are consistent with diversity in reptile venom phospholipase A2 forms being derived from differences in both molecular weight and charge.     

Simple and rapid analysis of aristolochic acid contained in crude drugs and Kampo formulations with solid-phase extraction and HPLC photodiode-array detection

Simple and rapid analysis of aristolochic acid (AA) in crude drugs and Kampo extracts using a solid-phase extraction method and HPLC-PDA analysis was investigated. Extraction of AA from samples was accomplished by adding methanol containing 1% ammonia. The addition of ammonia ionized the AA of acidic substances so that they adhered to an acrylamide copolymer of a strong anion exchange resin (Sep-Pak QMA) coupled to diol silica easily. Furthermore, a mixture of acetonitrile–water–phosphoric acid (75:25:2, v/v) was effective in isolating AA from its carrier. Since almost all interfering peaks originating from contaminants in crude drugs and Kampo extract formulations could be removed, a satisfactory HPLC chromatogram of AA was obtained. A good result was also obtained when Aristolochiaceae and crude drugs containing AA were tested. Particularly in the case of the medicinal parts of Asarum, several interfering peaks and a ghost peak detected near the AA peak were eliminated. The AA contents of two Kampo extract formulations, tokishigyakukagoshuyushokyoto and ryutanshakanto, were calculated by HPLC analysis. The AA content (the sum of AA-I and AA-II) was 1.25–6.13 mg per daily dose. From an additional recovery experiment for Kampo formulations, high recovery rates of AA were obtained. Neither LC/MS nor special instrumentation was necessary. Our results suggest that this simple, quick, and sensitive analytical method to detect AA in crude drugs and Kampo extract formulations would be valuable in safety inspections of AA in crude drugs and their products.     

Safe Concurrent Use of Anti-tuberculosis Drugs and Pembrolizumab in a Patient with Non-small-cell Lung Cancer Who Was Infected with Mycobacterium tuberculosis

A 68-year-old Japanese man was diagnosed with lung adenocarcinoma stage IVB. We introduced a first-line chemotherapy of four cycles of carboplatin and pemetrexed and pembrolizumab, followed by pemetrexed and pembrolizumab maintenance therapy. Approximately four months after anticancer therapy, a small nodule appeared in the right peripheral S3 lesion. After five months, the nodule was confirmed as a Mycobacterium tuberculosis (TB) nodule. We initiated anti-TB therapy without stopping pembrolizumab, and the right S3 nodule shrank immediately. This report supports the concurrent use of anti-TB treatment with an immune checkpoint inhibitor when the TB infection area is limited.     

Risk Factors for Complications Associated with Peripherally Inserted Central Catheters During Induction Chemotherapy for Acute Myeloid Leukemia

Objective Peripherally inserted central catheters (PICCs) are widely used in patients with hematologic malignancies. However, the risks of PICC-related complications during chemotherapy for acute myeloid leukemia (AML) are not fully understood. Methods We conducted a retrospective review of 128 adult patients with AML who received induction therapy by way of PICC insertion between 2012 and 2019. Results The median duration of PICC insertion was 30 days. The incidence rate of catheter-related bloodstream infection (CRBSI) was 2.4% at 30 days, and women were more likely to suffer from CRBSI than men. Local reactions at the insertion site were observed in 56 patients; however, these events did not predict CRBSI. The incidence rates of catheter-related thrombosis (CRT) were 1.6% at 30 days. Obesity put patients at an increased risk for CRT. Unexpected PICC removal occurred in 59 patients, and women were at a higher risk of catheter removal than men. Conclusion Low PICC-related complication rates, possibly associated with high rates of catheter removal, were observed during intensive chemotherapy for AML. Women and obese patients require careful monitoring of their PICC. Procedures to achieve appropriate PICC removal without increasing the complication rate need to be considered.     

Erk pathways negatively regulate matrix mineralization

Skeletal mineralization is an important step regulating the mechanical properties of the calcified tissues, but molecular events underlying mineralization still remain elusive. We examined the role of extracellular signal-regulated kinase (Erk) pathways in matrix mineralization of osteogenic cells both in vitro and in vivo. Matrix mineralization by preosteocytic MLO-A5 cells and osteoblastic MC3T3-E1 cells was increased by either PD98059 Mek inhibitor treatment or adenovirus vector-mediated dominant negative Ras (Ras(DN)) expression and was suppressed by Erk activation by platelet-derived growth factor (PDGF) treatment or constitutively active Mek1 (Mek(CA)) expression. Administration of adenovirus vectors carrying Ras(DN) gene onto the calvaria of 1-day-old mice increased the mineralization of the tissues, while that of the Mek(CA) adenovirus suppressed it. These results suggest that the Erk pathway is a negative regulator of the matrix mineralization both in vitro and in vivo.     

Axial symptoms after en bloc cervical laminoplasty.

Eighty-two patients were evaluated after cervical laminoplasty to explore measures that could minimize future postoperative axial complaints. Patients were divided into two groups: Group A--severe postoperative axial symptoms, and Group B--mild axial complaints. Japanese Orthopaedic Association outcomes scores were similar for the two groups. Radiologic studies demonstrated greater restriction of range of motion in Group A patients who had undergone longer and more extensive surgical procedures.     

Adjacent segment disease after anterior cervical interbody fusion

BACKGROUND CONTEXT: There have been many follow-up studies on anterior interbody fusion for cervical nerve root and spinal cord compression, and excellent neurological outcomes have been reported. However, postoperative degenerative changes at adjacent discs may lead to the development of new radiculopathy or myelopathy. In the previous reports, the incidence of symptomatic adjacent segment disease has ranged from 7% to 15%. PURPOSE: The present study was undertaken to investigate the incidence of symptomatic adjacent segment disease after anterior cervical interbody fusion (ACIF) and to identify the factors that are related to the development of this disease. STUDY DESIGN/SETTING: This is a retrospective cohort study. PATIENT SAMPLE: A total of 112 patients were followed up clinically and radiologically for more than 2 years. OUTCOME MEASURES: Follow-up evaluation was primarily by means of clinical visits. The postoperative course of any symptoms, the findings of neurological examination and serial follow-up radiographs were performed in all patients. METHODS: The diagnosis of symptomatic adjacent segment disease was based on the presence of new radiculopathy or myelopathy symptoms referable to an adjacent level, and the presence of a compressive lesion at an adjacent level by magnetic resonance imaging or myelography. We evaluated the correlation between the incidence of symptomatic adjacent segment disease and the following clinical parameters (age at operation, sex, number of the levels fused) and radiological parameters (preoperative cervical spine alignment, preoperative range of motion of C2-C7 cervical spine, anteroposterior spinal canal diameter, preoperative existence of an adjacent segment degeneration on plain radiograph, myelography and magnetic resonance imaging [MRI]). RESULTS: Symptomatic adjacent segment disease developed in 19 of 112 patients (19%) followed. A Kaplan-Meier survival analysis was performed in order to follow the disease-free survival of the entire series of patients. The disease-free survival rates were 89% at 5 years, 84% at 10 years and 67% at 17 years. The incidences of indentation of dura matter on preoperative myelography or disc protrusion on MRI at the adjacent level were significantly higher in disease cases (p=.0087, .0299, respectively; chi-squared test). However, the other parameters did not show a statistically significant difference. There were seven cases (37%) who had failure of nonoperative treatment and additional operations were performed. CONCLUSIONS: The incidence of symptomatic adjacent segment disease after ACIF was higher when preoperative myelography or MRI revealed asymptomatic disc degeneration at that level regardless of the number of the levels fused, preoperative alignment, spinal canal diameter or fusion alignment.     

Tongue reconstruction with minimal donor site morbidity using a deep inferior epigastric perforator (DIEP) free flap in a 6‐year‐old girl

Tongue reconstruction was performed using a deep inferior epigastric perforator (DIEP) free flap in a 6‐year‐old girl with undifferentiated sarcoma of the tongue. After hemi‐glossectomy with upper neck dissection, a 3‐lobed DIEP free flap was used for the reconstruction. Donor site was closed primarily with suturing umbilicus in proper position. No flap loss, leakage, or infection occurred. Postoperatively, the patient was able to consume a normal diet without difficulty or aspiration and displayed good speech function. No donor site morbidity, e.g., herniation or bulging, was observed, and the patient was able to perform their normal daily activities. DIEP flaps provide a pliable skin paddle, an adequate amount of adipose tissue, and reduced donor site morbidity, even in children. We did not have any difficulty harvesting the DIEP flap or with the microvascular anastomosis. We consider DIEP free flaps to be the ideal option for pediatric tongue reconstruction. © 2013 Wiley Periodicals, Inc. Microsurgery 33:487–490, 2013.