Subjective Characterization of Nerve Sparing Predicts Recovery of Erectile Function after Radical Prostatectomy: Defining the Utility of a Nerve Sparing Grading System

IntroductionRadical prostatectomy (RP) is a common technique for managing prostate cancer. Concern regarding functional outcomes in patients prompted the development of nerve sparing to improve recovery of erectile function.AimTo assess if a cumulative nerve damage grading system is a more precise predictor of recovery of erectile function as compared to the current “all‐or‐none” grading system.MethodsBaseline demographic, medical history, and International Index of Erectile Function (IIEF)‐erectile function domain (EFD) scores were collected. At the time of RP, patients were assigned a nerve sparing score (NSS) by their surgeon for each neurovascular bundle (left and right) to assess the quality of intraoperative nerve sparing (1—complete preservation, 4—complete resection). Patients completed IIEF questionnaires at 24 months after RP.Main Outcome MeasuresGroup comparisons and multiple regression analyses were used to test the association between the NSS and IIEF‐EFD scores for patients with preoperative EFD scores ≥24.ResultsA total of 173 patients were included in this analysis. Mean age for patients was 59, and 62% of patients had at least one comorbidity. Baseline EFD scores were comparable between all NSS assignments. At 24 months, EFD scores were reduced by 7.2, 11.6, 13.9, and 15.4 points for patients with NSS grades of 2, 3, 4, and 5–8, respectively (P < 0.01). Multivariate analysis demonstrated lower NSS predicted recovery of erectile function at 24 months (P = 0.001), as did age (P = 0.001) and baseline EFD score (P = 0.02).ConclusionsOur data support the adoption of a subjectively assigned NSS to more precisely predict erectile function outcomes and suggest that even minor nerve trauma significantly impairs the recovery of erectile function after procedures classically regarded as having achieved bilateral nerve sparing. Further studies are needed to identify the optimal NSS system. Moskovic DJ, Alphs H, Nelson CJ, Rabbani F, Eastham J, Touijer K, Guillonneau B, Scardino PT, and Mulhall JP. Subjective characterization of nerve sparing predicts recovery of erectile function after radical prostatectomy: Defining the utility of a nerve sparing grading system.     

Evaluation of the correlation between tissue reaction and cytokines patterns induced by Alternaria alternate in mice

Alternaria alternata is well-known as a source of allergenic components in the cell wall and cytoplasm of conidia and hyphae that cause respiratory allergic disorders. The purpose of this study was to evaluate tissue reaction and Th₂ cytokines in mice exposed to A. alternata. A. alternata was cultured, and fungal extract was prepared by freeze–defreeze and sonication methods. BALB/c mice in one group were sensitized by two intraperitoneal injections of A. alternata extract and then intra-nasally challenged with spores suspended in sterile normal saline solution, and in another group, mice only received spores intra-nasally. Blood sampling and necropsy were performed at 1 and 72 h after spore inhalation. Histopathology demonstrated an inflammatory response with cells including lymphocytes, macrophages, neutrophils and eosinophils present and mucus hypersecretion in the lungs and airway epithelial cell hyperplasia and necrosis observed in sensitized and non-sensitized mice. Sera were analyzed by ELISA to determine serum levels of Interleukin (IL)-4 and IL-13 in immediate response and late-phase reaction, respectively. Increasing Th₂ cytokine (IL-4 and IL-13) levels in the sera was also observed in the sensitized and challenged mice. The results showed that exposure to extract and then spores of A. alternata induced rapid and highly elevated production of IL-4 and IL-3. These cytokines were associated with respiratory histopathological changes.     

Combined inhibition of the BMP pathway and the RANK-RANKL axis in a mixed lytic/blastic prostate cancer lesion

The purpose of this study was to investigate the influence of combined inhibition of receptor activator of nuclear factor kappa-B ligand (RANKL) and bone morphogenetic protein (BMP) activity in a mixed lytic/blastic prostate cancer lesion in bone. Human prostate cancer cells (C4 2b) were injected into immunocompromised mice using an intratibial injection model to create mixed lytic/blastic lesions. RANK-Fc, a recombinant RANKL antagonist, was injected subcutaneously three times a week (10mg/kg) to inhibit RANKL and subsequent formation, function and survival of osteoclasts. Inhibition of BMP activity was achieved by transducing prostate cancer cells ex vivo with a retroviral vector expressing noggin (retronoggin; RN). There were three treatment groups (RANK-Fc treatment, RN treatment and combined RN and RANK-Fc treatment) and two control groups (untreated control and empty vector control for the RN treatment group). The progression of bone lesion and tumor growth was evaluated using plain radiographs, hindlimb tumor size, (18)F-Fluorodeoxyglucose and (18)F-fluoride micro PET-CT, histology and histomorphometry. Treatment with RANK-Fc alone inhibited osteolysis and transformed a mixed lytic/blastic lesion into an osteoblastic phenotype. Treatment with RN alone inhibited the osteoblastic component in a mixed lytic/blastic lesion and resulted in formation of smaller osteolytic bone lesion with smaller soft tissue size. The animals treated with both RN and RANK-Fc demonstrated delayed development of bone lesions, inhibition of osteolysis, small soft tissue tumors and preservation of bone architecture with less tumor induced new bone formation. This study suggests that combined inhibition of the RANKL and the BMP pathway may be an effective biologic therapy to inhibit the progression of established mixed lytic/blastic prostate cancer lesions in bone.     

EXTENDING THE INDICATIONS AND ANATOMICAL LIMITS OF PELVIC LYMPH NODE DISSECTION FOR PROSTATE CANCER: IMPROVED STAGING OR INCREASED MORBIDITY?

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

• ? To assess, in a risk/benefit analysis, the additional risk for complications and benefits of extending the indications and anatomical limits of pelvic lymph node dissection (PLND).

PATIENTS AND METHODS

• ? In total, 971 consecutive patients with clinically localized prostate cancer underwent laparoscopic radical prostatectomy from 2003–2007.
• ? Before 1 February 2005, patients with a nomogram probability of lymph node invasion (LNI) <2% did not undergo PLND (No PLND group), whereas those with a LNI ≥2% had a PLND limited to the external iliac nodal group (limited PLND group).
• ? After 1 February 2005, all patients underwent a standard PLND including the external iliac, hypogastric and obturator fossa nodal groups (standard PLND group).
• ? The risk parameters were PLND‐related complications and operating time. Complications were graded using a modified Clavien classification. The benefit was the detection of nodal metastases.

RESULTS

• ? In the subgroup of patients with a LNI ≥2%, standard PLND was a superior operation than the limited PLND in detecting nodal metastases (14.3% vs 4.5%, respectively; P = 0.003).
• ? The risk/benefit of standard vs limited PLND would be one additional grade 3 complication per 20 additional patients with nodal metastases. In the subgroup of patients with LNI <2%, three patients (1.0%) had positive nodes after a standard PLND.
• ? The risk/benefit of standard PLND vs no PLND would be one additional grade 3 complication per three or four additional patients with nodal metastasis. The no PLND group was associated with the lowest risk of grade 1, 2 and 3 complications compared to either the limited or standard PLND groups (P < 0.001).

CONCLUSIONS

• ? In patients with LNI ≥2%, standard PLND detects more nodal metastasis. PLND is associated with higher but non‐prohibitive complications rate.
• ? The present study found no evidence that the incidence of complications would be reduced by a limited PLND.

     

Grape Seed Extract to Improve Liver Function in Patients with Nonalcoholic Fatty Liver Change

Background/Aim:

Therapeutic interventions in nonalcoholic fatty liver disease are limited, while antioxidative materials have shown benefi ts in animal models. This study aimed to evaluate grape seed extract as an anti-oxidative material in this process. Therapeutic effects of grape seed extract were evaluated in comparison to vitamin C in a double-blind setting.

Materials and Methods:

Fifteen patients were enrolled in each group. Liver function tests were done; also, grade of steatosis and pattern of echogenicity of the liver were determined. Patients were followed up by the same evaluation repeated in first, second and third months.

Results:

Mean age ± standard deviation was 43.2 ± 10.3 years. Grape seed extract (GSE) significantly improved the grade of fatty liver change; and resulted in significant decrease in alanine aminotransferase in patients receiving the concentrate compared to those receiving vitamin C independently, from the initial grade of steatosis.

Conclusions:

This study describes the beneficial effect of using grape seed extract for three months in patients with nonalcoholic fatty liver disease. These results may improve with a longer period of follow-up.     

Personality factors and profiles in variants of irritable bowel syndrome

AIM: To study the association between irritable bowel syndrome (IBS) variants (constipation,diarrhea,or both) and personality traits in non-psychiatric patients. METHODS: IBS was diagnosed using the Rome Ⅱ diagnostic criteria after exclusion of organic bowel pathology. The entry of each patient was confirmed following a psychiatric interview. Personality traits and the score of each factor were evaluated using the NEO Five Factor Inventory. RESULTS: One hundred and fifty patients were studied. The mean age (± SD) was 33.4 (± 11.0) year (62% female). Subjects scored higher in neuroticism (26.25 ± 7.80 vs 22.92 ± 9.54,P < 0.0005),openness (26.25 ± 5.22 vs 27.94 ± 4.87,P < 0.0005) and conscientiousness (32.90 ± 7.80 vs 31.62 ± 5.64,P < 0.01) compared to our general population derived from universities of Iran. Our studied population consisted of 71 patients with Diarrhea dominant-IBS,33 with Constipation dominant-IBS and 46 with Altering type-IBS. Scores of conscientiousness and neuroticism were significantly higher in C-IBS compared to D-IBS and A-IBS (35.79 ± 5.65 vs 31.95 ± 6.80,P = 0.035 and 31.97 ± 9.87,P = 0.043,respectively). Conscientiousness was the highest dimension of personality in each of the variants. Patients with C-IBS had almost similar personality profiles,composed of higher scores for neuroticism and conscientiousness,with low levels of agreeableness,openness and extraversion that were close to those of the general population. CONCLUSION: Differences were observed between IBS patients and the general population,as well as between IBS subtypes,in terms of personality factors. Patients with constipation-predominant IBS showed similar personality profiles. Patients with each subtype of IBS may benefit from psychological interventions,which can be focused considering the characteristics of each subtype.