Detection of clinical progression through plasma ctDNA in metastatic melanoma patients: a comparison to radiological progression

Background The validity of circulating tumour DNA (ctDNA) as an indicator of disease progression compared to medical imaging in patients with metastatic melanoma requires detailed evaluation.Methods Here, we carried out a retrospective ctDNA analysis of 108 plasma samples collected at the time of disease progression. We also analysed a validation cohort of 66 metastatic melanoma patients monitored prospectively after response to systemic therapy.Results ctDNA was detected in 62% of patients at the time of disease progression. For 67 patients that responded to treatment, the mean ctDNA level at progressive disease was significantly higher than at the time of response (P < 0.0001). However, only 30 of these 67 (45%) patients had a statistically significant increase in ctDNA by Poisson test. A validation cohort of 66 metastatic melanoma patients monitored prospectively indicated a 56% detection rate of ctDNA at progression, with only two cases showing increased ctDNA prior to radiological progression. Finally, a correlation between ctDNA levels and metabolic tumour burden was only observed in treatment naïve patients but not at the time of progression in a subgroup of patients failing BRAF inhibition (N = 15).Conclusions These results highlight the low efficacy of ctDNA to detect disease progression in melanoma when compared mainly to standard positron emission tomography imaging.Subject terms: Tumour biomarkers, Biomarkers     

Mitomycin C application after photorefractive keratectomy in high,moderate, or low myopia: Systematic review and meta-analysis

Photorefractive keratectomy (PRK) is considered a safe approach laser procedure with a clinical significance in correcting myopia results. PRK requires removing the whole superficial epithelium. The integrity of the epithelial basement membrane and the deposition of abnormal extracellular matrix can put the cornea in a probable situation for corneal haze formation. Mitomycin C (MMC) is applied after excimer laser ablation as a primary modulator for wound healing, limiting corneal haze formation. We aim to summarize the outcomes of MMC application after laser ablation. We searched Scopus, PubMed, Cochrane CENTRAL, and Web of Science till December 2020 using relevant keywords. The data were extracted and pooled as mean difference (MD) or risk ratio (RR) with a 95% confidence interval (CI), using Review Manager software (version 5.4). Our analysis demonstrated a statistically significant result for MMC application over the control group in terms of corneal haze formation postoperatively (RR = 0.29, 95% CI: [0.19, 0.45], P < 0.00001). Regarding corrected distance visual acuity (CDVA), no significant difference was observed between the MMC group and the control group (MD = 0.02; 95% CI: [-0.04, 0.07]; P = 0.56). Regarding the uncorrected distance visual acuity (UDVA), the analysis favored the MMC application with (MD -0.03, 95% CI: [-0.06, -0.00]; P = 0.05). There was no statistically significant increase in complications with MMC. In conclusion, MMC application after PRK is associated with a lower incidence of corneal haze formation with no statistically significant side effects. The long term effect can show improvement regarding UDVA favoring MMC. However, there is no significant effect of MMCs application regarding CDVA, and SE.     

The nature of intrauterine adhesions following reproductive hysteroscopic surgery as determined by early and late follow-up hysteroscopy: clinical implications

Objective To evaluate the rate and characteristics of postoperative intrauterine adhesions (IUA) that might be formed following hysteroscopic reproductive surgery from both a gross and a histologic perspective as determined by early and late follow-up diagnostic hysteroscopy. Methods Retrospective analysis of 61 women wishing a pregnancy and suffering from a significant intrauterine pathology affecting their reproductive outcome were reviewed. All patients were treated hysteroscopically. Subsequently, they were randomly assigned to perform a follow-up diagnostic hysteroscopy at a variable intervals from their initial surgery. Multiple hysteroscopic-guided biopsies from IUA, when present, were obtained in several cases. Twenty patients were in the early group and had follow-up hysteroscopy performed 2–4 weeks after the initial operation. The late diagnostic group consisted of 41 patients with follow-up hysteroscopy at about 12 months (8–16 months). The two groups were similar to composition. Postoperatively, none of the early diagnostic group underwent hysterosalpingography (HSG) whereas all of the late group performed HSG 4 months following the initial surgery, which showed at least one-third of the cavity free of adhesions. When adhesions were present, no effort was made to lyse them. Results At follow-up hysteroscopy, 25% of both groups had no significant adhesions. Grade I adhesions (thin, filmy) occurred in 60% of the early hysteroscopy patients and in only 12% of the late group (P < 0.05). Grade II adhesions were present in 10% of the early group and in up to 41% in the late group (P < 0.05), whereas Grade III adhesions were present in only 5% of the early hysteroscopy group, but in 22% of the late one (P < 0.05). Correlation between hysteroscopic and histologic findings were good in most of cases in both groups. Follow-up to determine the subsequent reproductive outcome revealed similar conception rates in both groups. Conclusion The IUA that might be formed immediately following hysteroscopic reproductive surgery are histologically different from those appearing a longer time after the original operation. Routine early follow-up hysteroscopy can influence the prognosis resulting from the original surgery.     

Outpatient hysteroscopy and subsequent IVF cycle outcome: a systematic review and meta-analysis

A systematic review of studies evaluating the influence of outpatient (office) hysteroscopy on the outcome of the subsequent IVF cycle was conducted. MEDLINE, EMBASE, the Cochrane Library, National Research Register, ISI Conference Proceedings, ISRCTN Register and Meta-register were searched for randomized controlled trials (up to July 2007). All trials comparing the outcome of IVF treatment performed in patients who had outpatient hysteroscopy in the cycle preceding their IVF treatment with a control group in which hysteroscopy was not performed were included. Study selection, quality appraisal and data extraction were performed independently and in duplicate. Study authors were contacted for additional information. The main outcome measure was pregnancy rate. In total, 1691 participants were included in two randomized (n = 941) and three non-randomized controlled studies (n = 750). The quality of the studies was variable. Meta-analyses of the results of five studies showed evidence of benefit from outpatient hysteroscopy in improving the pregnancy rate in the subsequent IVF cycle (pooled relative risk = 1.75, 95% CI 1.51-2.03). The evidence from randomized trials was consistent with that from non-randomized controlled studies. Future robust randomized trials comparing outpatient hysteroscopy or mini-hysteroscopy with no intervention before IVF treatment would be a useful addition to further guide clinical practice.     

Contrast enhanced spiral computerized tomography in patients with chronic obstructive uropathy and normal serum creatinine: a single session for anatomical and functional assessment

PURPOSE: We evaluated contrast enhanced spiral computerized tomography (CT) as a single session for the anatomical and functional assessment of patients with chronic obstructive uropathy and normal serum creatinine. MATERIALS AND METHODS: The study included 65 patients with unilateral or bilateral chronic renal obstruction and normal serum creatinine. Five patients had bilateral obstruction and the remaining 60 had unilateral obstruction and a normal contralateral kidney. Therefore, the total number of renal units was 130, that is 70 obstructed and 60 normal. All patients underwent contrast enhanced spiral CT together with excretory urography (IVP) and Tc-mercaptoacetyltriglycine renal scan. CT was used to identify the cause of obstruction and selectively determine the glomerular filtration rate (GFR) of the 2 kidneys. The diagnostic accuracy of CT for identifying the cause of hydronephrosis was compared with that of IVP. Moreover, a correlation was made between CT GFR and isotope GFR. RESULTS: Obstruction was caused by ureteropelvic junction narrowing in 25 cases, ureteral stones in 21, ureteral stricture in 20 and extrinsic ureteral obstruction in 4. Contrast enhanced spiral CT identified the cause of hydronephrosis in all obstructed kidneys (100% sensitivity), while IVP identified the cause in 52 (74% sensitivity), which was a significant difference (p <0.05). CT and IVP excluded obstruction in all normal kidneys (100% specificity). A comparison between the isotope GFR of obstructed kidneys with the corresponding CT GFR showed a perfect correlation (r = 0.78, p <0.0001). Moreover, a similar comparison between isotope GFR and CT GFR of normal kidneys showed an excellent correlation (r = 0.73, p <0.0001). In obstructed and normal kidneys mean isotope clearance was not significantly different from that of mean CT clearance. CONCLUSIONS: Contrast enhanced spiral CT is more sensitive than IVP for identifying the cause of chronic obstructive uropathy. Moreover, it is as accurate as radioisotope renal scan for calculating the total and separate kidney function. We recommend spiral CT with contrast medium as a single radiological diagnostic modality for the assessment of patients with chronic renal obstruction and normal serum creatinine.     

Renal cell carcinoma (RCC) and telomerase activity: relationship to stage

Limited information is available on the correlation of telomerase activity and the clinical and pathological characteristics, in patients with renal cell carcinoma (RCC). Telomerase repeat amplification protocol (TRAP) was used to measure telomerase activity in frozen RCC specimens from partial/radical nephrectomies performed between 1987 and 1991. Presence of tumor tissue was verified by a pathologist using hematoxylin and eosin stained sections. RNA was measured to ensure the presence of intact protein necessary for telomerase expression. Data on demographics, tumor type, and stage at presentation, local recurrence, distant metastasis, disease-free survival (DFS), and overall survival (OS) was collected, and telomerase activity was correlated with each of these variables. Forty-nine of 67 patients (73%) were telomerase positive (+ve). Gender and stage were the only variables that appeared to be associated with telomerase positivity. Tumors were telomerase +ve in 12/21 females (57 %) vs. 37/46 males (80%) (P = 0.07). Tumors were telomerase +ve in 85% of Stage IV, 76% of Stage III, and 70% of Stage I/II patients (P = 0.12). Five-year survival was 0% for Stage IV, 57% for Stage III, and 77% for Stage I/II patients (P < 0.001), DFS 54% for stage III and 84% for Stage I/II patients (P = 0.05). Telomerase activity, however, was not related to survival in either univariate or multivariate analysis. In patients with telomerase +ve tumors 5-year survival was 55%, and with telomerase −ve tumors 58% (P = 0.56). Stage was the only variable associated with OS or DFS in clear cell RCC patients. In patients with advanced disease, there is a high incidence of telomerase positivity was found, within this limited sample, however, no correlation with survival was found.     

Vascular Risk Factors as Predictors of Sexual Function Following Coronary Artery Bypass Graft

IntroductionA strong association between cardiovascular risk factors and erectile dysfunction (ED) was suggested. Coronary artery bypass grafting (CABG) is the gold standard for surgical myocardial revascularization.AimWe herein evaluate the impact of vascular risk factors on postoperative sexual functions in patients undergo CABG.Main Outcome MeasuresED severity by the International Index of Erectile Function (IIEF-5) and penile duplex study.MethodsThe present study included 100 patients who underwent CABG. The patients were evaluated by an abridged form of the IIEF-5 questionnaire, followed by CABG. Six months after surgery the erectile function of all patients was revaluated utilizing the IIEF-5.ResultsNumber of risk factors was significantly associated with postoperative change in IIEF-5 score (P = 0.02). A post hoc analysis of the association revealed that patients with one risk factor were significantly more likely to have increased IIEF-5 scores (N = 18), whereas those with two or more risk factors were significantly more likely to have decreased IIEF-5 scores (N = 21, P < 0.05). Furthermore, those with no risk factors were significantly more likely to be stable (N = 8) compared with those with more than two risk factors, who were more likely to have decreased scores (P < 0.05). The hierarchical logistic regression results showed that when examining all risk factors simultaneously, because of multicollinearity, only hyperlipidemia was significantly associated with postoperative ED (odds ratio [OR] = 11.33, confirdence interval [CI] = 1.25, 102.82). Frequency of intercourse was also significantly associated with postoperative ED after controlling for risk factors (OR = 0.71, CI = 0.52, 0.97).ConclusionsThis data clearly shows that the number of cardiovascular risk factors is an essential predictive factor for sexual function following surgery. Only hyperlipidemia may play a predictive role for the future sexual function of patients undergo CABG. Mohamed OA, Hamed HA, Roaiah MF, Helmy T, Mahran A, and Bennett CJ. Vascular risk factors as predictors of sexual function following coronary artery bypass graft. J Sex Med 2009;6:2017–2023.