Robotic extended pyelolithotomy for complete staghorn calculus

Staghorn stones represent a therapeutic challenge to urologists. We present our experience with laparoscopic extended pyelolithotomy for treatment of staghorn and complex renal calculi in highly selected cases. This approach provides the principles of open surgery with the advantages of minimally invasive surgery. We describe our experience with robot-assisted extended pyelolithotomy for complex coralliform calculi. Since January 2007, robotic extended pyelolithotomy has been performed by transperitoneal approach in two patients with complete coralliform lithiasis (calculi average size 8 cm). One patient had history of percutaneous nephrolithotomy. Demographic and operative data were collected. All procedures were technically successful without need for open conversion. Mean estimated blood loss was 175 ml (range 50–300 ml), and mean operative time was 150 min (range 120–150 min). A perinephric drain was employed in one patient with duration of 5 days. Postoperative imaging confirmed complete stone clearance. Robotic extended pyelolithotomy is a feasible and reproducible procedure for removal of complete and partial staghorn calculi in selected patients with complex nephrolithiasis. This approach might limit the role of open surgery for these calculi, but further publications with more cases are necessary to further define its utility.     

Predictors of schizophrenia in patients with a first episode of psychosis

Early identification of schizophrenia in patients with a first episode of psychosis (FEP) may help to avoid inappropriate treatment and may enhance long-term outcome by addressing issues such as family network, treatment adherence and functional and symptomatic outcome. It was the aim of the study to determine baseline variables that significantly predicted a diagnosis of schizophrenia in patients with FEP. The sample consisted of 133 FEP patients hospitalized for at least 6 weeks, in whom a DSM-IV diagnosis was confirmed after 1 year follow-up. Patients were divided into two groups, those with a diagnosis of schizophrenia (Schizophrenia group, n = 63; 47.8%), and those with other psychosis, who were grouped under Non-Schizophrenic Psychosis (NSP, n = 70; 52.2%). Sociodemographic (marital status, educational level) and clinical variables were recorded for each patient. Substance use (alcohol, cannabis and cocaine) did not statistically differ between the two groups. Absence of characteristics defined as criteria for good prognosis, lack of ≥ 20% improvement in the total Positive and Negative Syndrome Scale score at 6 weeks, and a poor premorbid adjustment as determined by the Premorbid Adjustment Scale score significantly predicted the presence of schizophrenia. The regression model including these three variables achieved a predictive value of 76.3%, with a sensitivity of 74.6% and a specificity of 77.9%.     

Evaluation of the serum testosterone to prostate‐specific antigen ratio as a predictor of prostate cancer risk

Study Type – Diagnostic (exploratory cohort)
Level of Evidence 2b

OBJECTIVE

To analyse the ratio of serum testosterone (sT) to prostate‐specific antigen (PSA) as a predictor of prostate cancer risk, as low levels of sT have been related to a greater risk of prostate cancer, and its ratio with serum PSA level was recently proposed as a new tool to increase the specificity of PSA.

PATIENTS AND METHODS

In all, 439 consecutive men with a normal digital rectal examination and a serum PSA level of 4.1–20 ng/mL had a transrectal ultrasonography‐guided biopsy using a 10‐core scheme, with an additional 1–8 cores according to prostate volume and patient age. The sT level was determined before the procedure using a chemiluminescent assay, and the ratio of sT to PSA (sT/PSA) was calculated after transforming sT measurements from ng/dL to ng/mL. The percentage free PSA (%fPSA) and PSA density were also included in this analysis.

RESULTS

The overall cancer detection rate was 42.1%. The median sT level was 469 ng/dL in men with cancer and 499 ng/dL in those without (P = 0.521). The median sT/PSA was 0.68 and 0.74, respectively (P = 0.215). However, the median %fPSA was 14 in men with cancer and 17 in men without (P < 0.001) and the median PSA density was 0.22 and 0.16, respectively (P < 0.001). The multivariate analysis confirmed the independent predictive value only for %fPSA (odds ratio 0.94, 95% confidence interval 0.91–0.98) and PSA density (5.8, 3.42–19.8).

CONCLUSION

These results do not support the use of sT/PSA for predicting the risk of prostate cancer and to increase the specificity of PSA.     

The molecular genetics of Marfan syndrome and related disorders

Marfan syndrome (MFS), a relatively common autosomal dominant hereditary disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular systems, is caused by mutations in the gene for fibrillin-1 (FBN1). The leading cause of premature death in untreated individuals with MFS is acute aortic dissection, which often follows a period of progressive dilatation of the ascending aorta. Recent research on the molecular physiology of fibrillin and the pathophysiology of MFS and related disorders has changed our understanding of this disorder by demonstrating changes in growth factor signalling and in matrix-cell interactions. The purpose of this review is to provide a comprehensive overview of recent advances in the molecular biology of fibrillin and fibrillin-rich microfibrils. Mutations in FBN1 and other genes found in MFS and related disorders will be discussed, and novel concepts concerning the complex and multiple mechanisms of the pathogenesis of MFS will be explained.     

Discovery and preliminary confirmation of novel early detection biomarkers for triple-negative breast cancer using preclinical plasma samples from the Women’s Health Initiative observational study

Triple-negative breast cancer is a particularly aggressive and lethal breast cancer subtype that is more likely to be interval-detected rather than screen-detected. The purpose of this study is to discover and initially validate novel early detection biomarkers for triple-negative breast cancer using preclinical samples. Plasma samples collected up to 17 months before diagnosis from 28 triple-negative cases and 28 matched controls from the Women’s Health Initiative Observational Study were equally divided into a training set and a test set and interrogated by a customized antibody array. Data were available on 889 antibodies; in the training set, statistically significant differences in case versus control signals were observed for 93 (10.5 %) antibodies at p < 0.05. Of these 93 candidates, 29 were confirmed in the test set at p < 0.05. Areas under the curve for these candidates ranged from 0.58 to 0.79. With specificity set at 98 %, sensitivity ranged from 4 to 68 % with 20 candidates having a sensitivity ≥20 % and 6 having a sensitivity ≥40 %. In an analysis of KEGG gene sets, the pyrimidine metabolism gene set was upregulated in cases compared to controls (p = 0.004 in the testing set) and the JAK/Stat signaling pathway gene set was downregulated (p = 0.003 in the testing set). Numerous potential early detection biomarkers specific to triple-negative breast cancer in multiple pathways were identified. Further research is required to followup on promising candidates in larger sample sizes and to better understand their potential biologic importance as our understanding of the etiology of triple-negative breast cancer continues to grow.     

Uterine serous carcinoma: increased familial risk for lynch-associated malignancies

Serous uterine cancer is not a feature of any known hereditary cancer syndrome. This study evaluated familial risk of cancers for patients with serous uterine carcinoma, focusing on Lynch syndrome malignancies. Fifty serous or mixed serous endometrial carcinoma cases were prospectively enrolled. Pedigrees were developed for 29 probands and tumors were assessed for DNA mismatch repair (MMR) abnormalities. Standardized incidence ratios for cancers in relatives were estimated. A second-stage analysis was undertaken using data from Gynecologic Oncology Group (GOG)-210. Incidence data for cancers reported in relatives of 348 patients with serous and mixed epithelial and 624 patients with endometrioid carcinoma were compared. Nineteen of 29 (65.5%) patients in the single-institution series reported a Lynch-related cancer in relatives. Endometrial and ovarian cancers were significantly overrepresented and a high number of probands (6 of 29, 20.7%) reported pancreatic cancers. None of the probands' tumors had DNA MMR abnormalities. There was no difference in endometrial or ovarian cancer incidence in relatives of serous and endometrioid cancer probands in the case-control study. Pancreatic cancers were, however, significantly more common in relatives of patients with serous cancer [OR, 2.39; 95% confidence interval (CI), 1.06-5.38]. We identified an excess of endometrial, ovarian, and pancreatic cancers in relatives of patients with serous cancer in a single-institution study. Follow-up studies suggest that only pancreatic cancers are overrepresented in relatives. DNA MMR defects in familial clustering of pancreatic and other Lynch-associated malignancies are unlikely. The excess of pancreatic cancers in relatives may reflect an as yet unidentified hereditary syndrome that includes uterine serous cancers.     

Expression of cyclooxygenase-2 and peroxisome proliferator-activated receptor gamma during malignant melanoma progression

Background: Cancer chemoprevention using nonsteroidal anti‐inflammatory drugs is frequently attributed to cyclooxygenase‐2 (COX‐2) inhibition, although recent studies suggest that peroxisome proliferator‐activated receptor gamma (PPARγ) may also be involved. While surgical excision remains the treatment mainstay for localized malignant melanoma, certain high‐risk patients may benefit from adjunctive chemotherapy. In this study, we compared COX‐2 and PPARγ immunohistological staining in benign nevi, primary melanomas and metastatic melanomas to help predict the effectiveness of compounds targeting these markers. Methods: COX‐2 and PPARγ immunohistological staining was performed and reviewed in 99 melanocytic lesions, including 38 benign nevi, 32 primary melanomas and 29 metastatic melanomas. Results: There was a significant increase in both COX‐2 and PPARγ immunostaining in melanomas compared with benign nevi. Metastatic melanomas were more likely to have a higher number of PPARγ‐immunopositive cells. They were also more likely to express COX‐2 than primary melanomas. Neither COX‐2 nor PPARγ expression was associated with a specific pathologic subtype. Conclusions: COX‐2 and PPARγ may help modulate the progression of melanocytic precursor lesions to disseminated malignant melanoma. As such, they may serve as candidate substrates for targeted cancer therapies and may be particularly useful as adjuncts to surgery.