Clinical significance of telomerase activity in peripheral blood of patients with esophageal squamous cell carcinoma

BACKGROUND: The presence of tumor cells in the blood stream is considered evidence of a high risk of distant organ metastasis. We examined the usefulness of telomerase activity in peripheral blood polymorphonuclear cells as an indicator of distant metastasis in patients with esophageal squamous cell carcinoma. METHODS: Telomerase activity was measured in the peripheral blood mononuclear cell and polymorphonuclear cell fractions obtained from blood samples of healthy volunteers mixed with squamous cell carcinoma cell lines, and cell distribution was analyzed by flow cytometry. Then telomerase activity of forty-two polymorphonuclear cell fractions obtained from esophageal squamous cell carcinoma patients was measured. RESULTS: Telomerase activity was detected in polymorphonuclear cell fractions and cell distribution analysis revealed the presence of esophageal squamous cell carcinoma cells. Organ metastasis was detected in 7 (78%) of the 9 patients with telomerase-positive polymorphonuclear cell fractions as opposed to only five (15%) of the 33 with telomerase-negative cases, and there was a significant positive correlation between telomerase activity and organ metastasis (p < 0.0008). CONCLUSIONS: Measurement of telomerase activity in the polymorphonuclear cell fractions is useful for identifying a high risk group for distant organ metastasis in patients with esophageal squamous cell carcinoma.     

Clinical effects of L-threo-3,4-dihydroxyphenylserine on orthostatic hypotension in hemodialysis patients

Orthostatic hypotension is one of the major factors interfering with everyday activities in hemodialysis patients, but there has been no effective agent for treating it. In order to clarify the clinical effects of L-threo-3,4-dihydroxyphenylserine (L-DOPS) on orthostatic hypotension of hemodialysis patients, we conducted a randomized, double-blind comparative trial. 149 regular hemodialysis patients with orthostatic hypotension were randomly allocated to three groups and L-DOPS at doses of 400 mg, 200 mg or placebo was orally administrated to each group 30 min before starting every hemodialysis for 4 weeks. Changes of blood pressure (BP) in orthostatic hypotension immediately after completion of hemodialysis and symptoms related to orthostatic hypotension were compared between the three groups. In the 400-mg group, systolic and diastolic BP after standing increased significantly and the drop of mean BP after standing was also reduced compared with pretreatment levels. No such changes were observed in the placebo group. Fatiguability, malaise/weakness, dizziness and light-headed feeling, the interdialytic symptoms commonly observed in hemodialysis patients who developed orthostatic hypotension, were improved to a significant extent in the L-DOPS group compared with the placebo group. In particular, the improvement was more remarkable for the L-DOPS 400-mg group than the placebo group in patients with diabetic nephropathy, lower systolic BP after standing, and the long duration type of orthostatic hypotension. The incidence of adverse events was comparable between the three groups, and all recovered after discontinuation of L-DOPS or concomitantly administered drugs, or without any treatment. These findings indicate that L-DOPS taken before hemodialysis prevents orthostatic hypotension in patients undergoing hemodialysis, and is also effective for the interdialytic symptoms related to orthostatic hypotension.     

Evidence for two distinct Fc receptors on guinea pig peritoneal macrophages

Fcreceptors of guinea pig peritoneal macrophages for homologous IgG1 and IgG2 antibodies were found to be solubilized by treatment of the cells with Nonidet P-40, since the soluble fraction obtained inhibited the binding reactions of complexes of IgG1 and IgG2 antibodies with ovalbumin to the intact cells. The solubilized Fc receptors for IgG1 and IgG2 antibodies were indistinguishable from one another by means of gel filtration on a column of Sepharose 6B in the presence or absence of the detergent. Both of the Fc receptors were almost completely removed by affinity chromatography on a column of IgG2-bound Sepharose 6B. Affinity chromatography on a column of IgG1-bound Sepharose 6B, however, showed that the Fc receptor for IgG1 antibody was also almost completely adsorbed, though about 50% of the Fc receptor for IgG2 antibody remained unbound. These results demonstrate the existence of two distinct Fc receptors on guinea pig macrophages; one binds to IgG2 antibody alone and the other bind IgG2 as well as IgG1 antibodies.     

Laparoscopic repair of an irreducible femoral hernia containing an epiploic appendage of the sigmoid colon

Here we present the first report of laparoscopic repair of an irreducible femoral hernia containing an epiploic appendage of the sigmoid colon. A 73‐year‐old woman presented with a 1‐week history of a left groin mass below the inguinal ligament with no abdominal symptoms. Abdominal CT demonstrated a 21 × 18‐mm oval‐shaped, fat‐dense structure in the left groin area. The hernia contents were considered potentially associated with the omentum; thus, a left irreducible femoral hernia was diagnosed. Elective laparoscopic surgery revealed an irreducible femoral hernia containing an epiploic appendage of the sigmoid colon, which was then reduced. The reduced epiploic appendage showed no ischemic changes, inflammation, torsion, or swelling, obviating the need for resection. The femoral hernia was laparoscopically repaired via a transabdominal preperitoneal approach with mesh. The patient's postoperative recovery was uneventful, and no recurrence of the femoral hernia was noted at the 6‐month follow‐up.     

A phase II study of nedaplatin and 5-fluorouracil in metastatic squamous cell carcinoma of the esophagus: The Japan Clinical Oncology Group (JCOG) Trial (JCOG 9905-DI)

Background

This phase II study evaluated the efficacy and toxicity of combination chemotherapy with nedaplatin and 5-fluorouracil (5-FU) for metastatic esophageal squamous cell carcinoma.

Methods

Eligibility criteria included squamous cell carcinoma with organ metastasis, ECOG performance status (PS) 0–2, ≤ 75 years, measurable disease, and adequate organ function. Chemotherapy consisted of 5-FU (800 mg/m²/day) on days 1–5 and a 2-h infusion of nedaplatin (90 mg/m²) on day 1, repeated every 4 weeks. Therapy was continued until disease progression or intolerable adverse events. The primary end point was response rate. Secondary end points included overall survival, progression-free survival, and toxicities.

Results

Forty-two patients (39 men, 3 women; median age 59 years; range 44–70 years) were enrolled. Twenty-one, 21, and 0 patients had PS 0, 1, and 2, respectively. 23, 6, 3, and 18 patients had a history of surgical resection, radiotherapy, adjuvant chemotherapy, and no therapy, respectively. Among the 38 eligible patients, 1 and 14 complete and partial responses were observed, respectively; the overall response rate was 39.5 % (90 % confidence interval: 26.1–54.1 %). The median survival time was 8.8 months. The one-year survival rate was 32.9 %. Grade 4 neutropenia and thrombocytopenia were observed in 7 and 2 % of 41 patients, respectively. Grade 3 nausea, diarrhea, and stomatitis were observed in 12, 2, and 2 %, respectively.

Conclusion

Combination therapy with nedaplatin and 5-FU is highly active and well tolerated in metastatic or recurrent esophageal squamous cell cancer and is therefore a chemotherapy option for esophageal squamous cell carcinoma.     

Laparoscopic repair of an incarcerated inguinal hernia containing the sigmoid colon with a colonoscope

Here, we report the first case of laparoscopic surgery to repair an incarcerated colonoscope in an inguinal hernia containing the sigmoid colon. After colonoscopy was performed on a 74-year-old man with positive fecal occult blood test results, the colonoscope could not be withdrawn. A bulge consistent with an incarcerated colonoscope was found on examination of the patient's left inguinal area. Computed tomography revealed and led to the diagnosis of an incarcerated colonoscope in the sigmoid colon within the inguinal hernia. After confirmation during emergency laparoscopic surgery, the incarcerated sigmoid colon was reduced, and the colonoscope was removed under radiographic and laparoscopic guidance. No ischemic changes or serosal injuries were observed, averting the need for resection. A transabdominal preperitoneal approach with a mesh was then used to repair the inguinal hernia laparoscopically. The patient's postoperative recovery was uneventful, and no recurrence was observed at the 1-year follow-up.     

Effectiveness of remdesivir with corticosteroids for COVID-19 patients in intensive care unit: A hospital-based observational study

The effectiveness of remdesivir on survival in coronavirus disease 2019 (COVID-19), especially in cases treated in the intensive care unit (ICU), is controversial. We investigated the effectiveness of remdesivir with corticosteroids on the survival of COVID-19 patients in a real ICU clinical practice. For laboratory-confirmed COVID-19 patients admitted to the ICU of a tertiary hospital in Tokyo (April 2020–November 2021) and who received corticosteroids, the effectiveness of remdesivir for survival, stratified by interval length (within 9 or 10+ days), was retrospectively analyzed using Cox regression model. A total of 168 patients were included: 35 with no remdesivir use (control), 96 with remdesivir use within 9 days, and 37 with remdesivir use with an interval of 10+ days. In-hospital mortality was 45.7%, 10.4%, and 16.2%, respectively. After adjusting for possible covariates including comorbidities, laboratory data, oxygen demand, or level of pneumonia, remdesivir use within 9 days from symptom onset reduced mortality risk (hazard ratio [HR]: 0.10; 95% confidence interval (CI): 0.025–0.428) compared to the control group. However, remdesivir use with an interval of 10+ days showed no significant association with mortality (HR: 0.42; 95% CI: 0.117–1.524). Among COVID-19 patients who received corticosteroids in ICU, remdesivir use within 9 days from symptom onset was associated with reduced in-hospital mortality risk.