Detection of high-risk Human Papillomavirus in prostate cancer from a UK based population.

Human papillomavirus (HPV) infection is one of the sexually transmitted diseases which have been implicated in the etiology of multiple cancers. To date, several studies have been conducted to evaluate the incidence of high-risk (HR) HPV in prostate cancer (PCa) which have generated widely conflicting data. Hence, this leaves a lack of awareness on the causal role of persistent HPV infection in the development of PCa. Although this has been investigated in a handful of countries, to the best of our knowledge, no prior studies have been conducted in the UK. In this study, polymerase chain reaction (PCR) and Sanger sequencing were implemented to analyze a total of 49 fresh prostate specimens (35 benign and 14 malignant specimens) for the presence of viral DNA of 12 HR-HPV types. Data obtained confirmed the presence of HR-HPV in 32.7% of analyzed benign and malignant prostate tissues with HPV 35 being identified as the most frequent type. Moreover, HR-HPV positivity rate was found to be higher in abnormal prostate tissues (adenocarcinoma and benign with prostatitis) compared those with normal prostate condition. Using immunohistochemistry, we have confirmed the expression of HPV E7 protein in prostate tissues positive for HPV DNA. This observation, the first reported from a UK population, suggests that the presence of HPV in prostate tissue is likely to be a related factor in the progression of certain cases of prostate cancer.

Phase I Trial of an ICAM-1-Targeted Immunotherapeutic-Coxsackievirus A21 (CVA21) as an Oncolytic Agent Against Non Muscle-Invasive Bladder Cancer.

PURPOSE: The CANON [CAVATAK in NON-muscle-invasive bladder cancer (NMIBC)] study evaluated a novel ICAM-1-targeted immunotherapeutic-coxsackievirus A21 as a novel oncolytic agent against bladder cancer. PATIENTS AND METHODS: Fifteen patients enrolled in this "window of opportunity" phase I study, exposing primary bladder cancers to CAVATAK prior to surgery. The first 9 patients received intravesical administration of monotherapy CAVATAK; in the second stage, 6 patients received CAVATAK with a subtherapeutic dose of mitomycin C, known to enhance expression of ICAM-1 on bladder cancer cells. The primary endpoint was to determine patient safety and maximum tolerated dose (MTD). Secondary endpoints were evidence of viral replication, induction of inflammatory cytokines, antitumor activity, and viral-induced changes in resected tissue. RESULTS: Clinical activity of CAVATAK was demonstrated by induction of tumor inflammation and hemorrhage following either single or multiple administrations of CAVATAK in multiple patients, and a complete resolution of tumor in 1 patient. Whether used alone or in combination with mitomycin C, CAVATAK caused marked inflammatory changes within NMIBC tissue biopsies by upregulating IFN-inducible genes, including both immune checkpoint inhibitory genes (PD-L1 and LAG3) and Th1-associated chemokines, as well as the induction of the innate activator RIG-I, compared with bladder cancer tissue from untreated patients. No significant toxicities were reported in any patient, from either virus or combination therapy. CONCLUSIONS: The acceptable safety profile of CAVATAK, proof of viral targeting, replication, and tumor cell death together with the virus-mediated increases in "immunological heat" within the tumor microenvironment all indicate that CAVATAK may be potentially considered as a novel therapeutic for NMIBC.

Surgical excision of isolated renal-bed recurrence after radical nephrectomy for renal cell carcinoma.

OBJECTIVE: To present our results on managing loco-regional recurrence of renal cell carcinoma (RCC) with surgical excision, as local recurrence at the site of a previous nephrectomy is resistant to both systemic therapy and radiotherapy. PATIENTS AND METHODS: In all, 16 patients were operated on between 1994 and 2003 for local recurrence of RCC. The median (mean, range) age at the time of local recurrence was 57.9 (57.4, 28.9-71.7) years, and the median interval from primary surgery 2.22 (3.88, 0.27-14.46) years. Before surgery eight patients had been given systemic immunotherapy, with no response of their local recurrence. RESULTS: Two patients were deemed inoperable because of direct invasion of the great vessels and the liver by tumour. The remaining 14 patients had recurrence in residual adrenal tissue (two), para-aortic nodes (three), para-caval nodes (two), retrocaval nodes (one), renal bed (six), liver, spleen and stomach (one each), and diaphragm (two). Although complete macroscopic en-bloc clearance was achieved in these patients, only eight had tumour-free margins on histological examination. The histology was consistent with RCC recurrence in all cases. All of the patients were followed with computed tomography at regular intervals. At a median follow-up of 1.0 (1.65, 0.25-6.5) years, five patients remain disease-free, four have local and distant relapse, and five developed distant metastasis only. The presence of tumour at the resection margin was a significant factor in predicting local and distant disease-free survival (P < 0.05). CONCLUSIONS: En bloc excision of isolated locally recurrent RCC is possible, and complete surgical extirpation can lead to prolonged disease-free survival.

Laparoscopic radical prostatectomy: the learning curve.

PURPOSE OF REVIEW: Laparoscopic radical prostatectomy is now an accepted treatment option for the management of localized prostate cancer. Numerous studies have demonstrated the feasibility and the reproducibility of this procedure. Expert teams in high-volume centres routinely carry out laparoscopic radical prostatectomy but for the novice the obstacle to success is how to learn and gain proficiency in this procedure. In this review, we will present our views on how this can be done. RECENT FINDINGS: A learning curve includes the necessity for continuous self-evaluation in terms of cancer control, continence and potency. Many different methods can be used to acquire the technique: dry lab, animal live lab, cadaveric laparoscopic dissection or mentoring with an expert. All of these steps may not be essential as laparoscopic radical prostatectomy is not too dissimilar to open prostatectomy. However, one must understand that the physiological consequences of anaesthesia during laparoscopy and basic laparoscopic suturing technique should be perfected prior to taking on laparoscopic radical prostatectomy. The training then must continue under the supervision of a mentor. The opportunity for discussion with an expert allows the novice to learn the pitfalls and the tips and tricks of laparoscopic radical prostatectomy, thus reducing the length of the learning curve and negating the need to reinvent the wheel. SUMMARY: Laparoscopic radical prostatectomy is similar to any other new surgical procedure and as with open surgery we learn and gain experience with each procedure; the learning curve is never completely finished.

The management of haemorrhagic cystitis with sodium pentosan polysulphate.

OBJECTIVE: To assess the use of sodium pentosan polysulphate (SPP) for haemorrhagic cystitis (HC), a potentially life-threatening side-effect in patients treated with pelvic radiotherapy or cyclophosphamide, and which can be difficult to manage as patients often have significant comorbidity. PATIENTS AND METHODS: Between September 1991 and December 2000, 60 consecutive patients (24 women and 36 men) with haemorrhagic cystitis were primarily treated with SPP; 53 patients had had radical radiotherapy for pelvic malignancy and seven systemic cyclophosphamide. All patients were screened for blood dyscrasia and residual/primary urothelial malignancy with imaging, urine cytology and cystoscopy. RESULTS: In all, 51 patients were available for follow-up; the median (range) interval between completing treatment and developing haematuria was 4.5 (0.08-39.4) years, the duration of treatment 180 (21-1745) days and patients were followed for 450 (19-4526) days from the onset of haematuria. All patients were started on SPP at an initial dose of 100 mg three times daily. In 21 patients the dose was gradually reduced to a maintenance dose of 100 mg and in 10 further patients SPP was stopped because the haematuria stopped completely. Twenty patients died while on treatment from causes not directly related to their haematuria. CONCLUSION: We recommend the use of SPP as the primary method of managing haemorrhagic cystitis associated with pelvic radiotherapy or systemic chemotherapy.