Prediction of Prostate Cancer Biochemical and Clinical Recurrence Is Improved by IHC-Assisted Grading Using Appl1, Sortilin and Syndecan-1.

Gleason scoring is used within a five-tier risk stratification system to guide therapeutic decisions for patients with prostate cancer. This study aimed to compare the predictive performance of routine H&E or biomarker-assisted ISUP (International Society of Urological Pathology) grade grouping for assessing the risk of biochemical recurrence (BCR) and clinical recurrence (CR) in patients with prostate cancer. This retrospective study was an assessment of 114 men with prostate cancer who provided radical prostatectomy samples to the Australian Prostate Cancer Bioresource between 2006 and 2014. The prediction of CR was the primary outcome (median time to CR 79.8 months), and BCR was assessed as a secondary outcome (median time to BCR 41.7 months). The associations of (1) H&E ISUP grade groups and (2) modified ISUP grade groups informed by the Appl1, Sortilin and Syndecan-1 immunohistochemistry (IHC) labelling were modelled with BCR and CR using Cox proportional hazard approaches. IHC-assisted grading was more predictive than H&E for BCR (C-statistic 0.63 vs. 0.59) and CR (C-statistic 0.71 vs. 0.66). On adjusted analysis, IHC-assisted ISUP grading was independently associated with both outcome measures. IHC-assisted ISUP grading using the biomarker panel was an independent predictor of individual BCR and CR. Prospective studies are needed to further validate this biomarker technology and to define BCR and CR associations in real-world cohorts.

Aberrant protein expression of Appl1, Sortilin and Syndecan-1 during the biological progression of prostate cancer.

Diagnosis and assessment of patients with prostate cancer is dependent on accurate interpretation and grading of histopathology. However, morphology does not necessarily reflect the complex biological changes occurring in prostate cancer disease progression, and current biomarkers have demonstrated limited clinical utility in patient assessment. This study aimed to develop biomarkers that accurately define prostate cancer biology by distinguishing specific pathological features that enable reliable interpretation of pathology for accurate Gleason grading of patients. Online gene expression databases were interrogated and a pathogenic pathway for prostate cancer was identified. The protein expression of key genes in the pathway, including adaptor protein containing a pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif 1 (Appl1), Sortilin and Syndecan-1, was examined by immunohistochemistry (IHC) in a pilot study of 29 patients with prostate cancer, using monoclonal antibodies designed against unique epitopes. Appl1, Sortilin, and Syndecan-1 expression was first assessed in a tissue microarray cohort of 112 patient samples, demonstrating that the monoclonal antibodies clearly illustrate gland morphologies. To determine the impact of a novel IHC-assisted interpretation (the utility of Appl1, Sortilin, and Syndecan-1 labelling as a panel) of Gleason grading, versus standard haematoxylin and eosin (H&E) Gleason grade assignment, a radical prostatectomy sample cohort comprising 114 patients was assessed. In comparison to H&E, the utility of the biomarker panel reduced subjectivity in interpretation of prostate cancer tissue morphology and improved the reliability of pathology assessment, resulting in Gleason grade redistribution for 41% of patient samples. Importantly, for equivocal IHC-assisted labelling and H&E staining results, the cancer morphology interpretation could be more accurately applied upon re-review of the H&E tissue sections. This study addresses a key issue in the field of prostate cancer pathology by presenting a novel combination of three biomarkers and has the potential to transform clinical pathology practice by standardising the interpretation of the tissue morphology.

Maxillary Odontogenic Keratocyst.

The Odontogenic Keratocyst (OKC) is one of the most aggressive odontogenic cysts. OKCs of the maxilla are particularly rare with less than 1% of cases reported in the literature. A 29-year-old female patient presented with pain and loose upper molars. Imaging confirmed an ectopic tooth at the osteomeatal complex and a maxillary OKC. These were endoscopically surgically removed and two teeth were encountered at the maxillary antrum. Histopathology confirmed the diagnosis of OKC of the maxilla. Surveillance with CT imaging and clinical assessment at 6 months shows no evidence of recurrence.

Prophylactic Negative Pressure Dressing Use in Closed Laparotomy Wounds Following Abdominal Operations: A Randomized, Controlled, Open-label Trial: The P.I.C.O. Trial.

OBJECTIVE: A randomized controlled trial was undertaken to investigate the effect of prophylactic negative pressure dressings on postoperative surgical site infection (SSI) rates in closed laparotomy wounds. SUMMARY OF BACKGROUND DATA: Laparotomy wounds are associated with high rates of SSI. The effect of prophylactic negative pressure dressing of closed incisional wounds on SSI rate is unknown. METHODS: A randomized, controlled, open-label trial was conducted (clinicaltrials.gov registration number NCT02780453). Fifty patients undergoing open abdominal surgery were included, with 25 patients randomized to the negative pressure dressing group and 25 to the standard dressing group. The primary endpoint was SSI incidence at 30 days postoperatively. Secondary endpoints included SSI incidence at 4 days, length of stay, cosmetic outcome, and patient satisfaction. Statistical analysis was performed on a per-protocol basis using SPSS version 23.0. RESULTS: The incidence of SSI at 30 days postoperatively was significantly reduced in the treatment group compared with the control group [8.3% vs 32.0%, P = 0.043 (1-sided), P = 0.074 (2-sided)]. There was no difference in SSIs at 4 days postoperatively [4.1% vs 8.0%, P = 0.516 (1-sided), P = 1.0 (2-sided)]. Analysis of predictors of wound infection identified standard wound dressings as the only significant predictor of SSI development. Length of stay was significantly reduced in the negative pressure dressing group [6.1 vs 14.7 days, P = 0.019 (2-sided)]. Cosmetic outcome and patient satisfaction did not show any difference between the 2 groups. CONCLUSIONS: Prophylactic use of negative pressure dressings for closed laparotomy wounds significantly reduces the incidence of SSI at 30 days postoperatively.

Epidural abscess secondary to acute appendicitis.

A 62-year-old man presented via the emergency department with a 1-week history of back pain, on a background of non-insulin-dependent diabetes mellitus and rectal carcinoma for which he had undergone abdominoperineal resection, chemotherapy and radiotherapy. He exhibited signs of sepsis, midline lumbar spine tenderness and reduced hip flexion. CT of the abdomen and pelvis showed a presacral collection contiguous with the tip of the appendix, and MRI lumbar spine revealed abscess invation into the epidural space extending to T9. He underwent a laparotomy with washout of the presacral abscess and appendicectomy and prolonged course intravenous antibiotic therapy. At 3 months after initial presentation he had made a full clinical recovery with progressive radiological resolution of the epidural abscess. The objective of the case report is to highlight a unique and clinically significant complication of a very common pathology (appendicitis) and to briefly discuss other intra-abdominal sources of epidural abscess.