John M. Fitzpatrick

Early prediction of severity in acute pancreatitis by urinary trypsinogen activation peptide: a multicentre study.

BACKGROUND There is a pressing clinical requirement for an early simple test of severity in acute pancreatitis. We investigated the use of an assay of trypsinogen activation peptide (TAP). METHODS We undertook a multicentre study in 246 patients (172 with acute pancreatitis [35 with severe disease], 74 controls). We assessed the predictive value of urinary TAP concentrations measured by a validated competitive immunoassay. We compared the results with those for plasma C-reactive protein and three clinicobiochemical scoring systems. TAP and C-reactive protein concentrations were analysed at set times after symptom onset and compared with the clinicobiochemical systems scores at key times during hospital stay. FINDINGS At 24 h after symptom onset, the median urinary TAP concentration was 37 nmol/L (IQR 17-110) for severe and 15 nmol/L (5-35) for mild disease (p<0.001). The respective values for plasma C-reactive protein were 24 mg/L (3-34) and 25 mg/L (6-75; p=0.208). The sensitivity, specificity, positive predictive, and negative predictive values of the test to show severe acute pancreatitis compared with mild acute pancreatitis at 24 h were: for TAP (>35 nmol/L), 58%, 73%, 39%, and 86%, respectively, and for C-reactive protein (>150 mg/L), 0%, 90%, 0%, and 75%. 48 h after admission the values for the clinicobiochemical scoring systems were: APACHE II (> or =8), 56%, 64%, 30%, and 85%; Ranson score (> or =3), 89%, 64%, 38%, and 96%; and Glasgow score (> or =3), 77%, 75%, 44%, and 93%. At 48 h, the values for C-reactive protein were 86%, 61%, 37%, and 94% and for TAP were 83%, 72%, 44%, and 94%. Combined testing of C-reactive protein and TAP was not superior to TAP alone for accuracy. INTERPRETATION Urinary TAP provided accurate severity prediction 24 h after onset of symptoms. This single marker of severity in acute pancreatitis deserves routine clinical application.

Intervertebral discs which cause low back pain secrete high levels of proinflammatory mediators

Herniated intervertebral disc tissue has been shown to produce a number of proinflammatory mediators and cytokines, but there have been no similar studies using discs from patients with discogenic low back pain. We have compared the levels of production of interleukin-6 (IL-6), interleukin-8 (IL-8) and prostaglandin E2 (PGE2) in disc tissue from patients undergoing discectomy for sciatica (63) with that from patients undergoing fusion for discogenic low back pain (20) using an enzyme-linked immunoabsorbent assay. There was a statistically significant difference between levels of production of IL-6 and IL-8 in the sciatica and low back pain groups (p < 0.006 and p < 0.003, respectively). The high levels of proinflammatory mediator found in disc tissue from patients undergoing fusion suggest that production of proinflammatory mediators within the nucleus pulposus may be a major factor in the genesis of a painful lumbar disc.

Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: a retrospective analysis.

Background:Regional anesthesia and analgesia attenuate or prevent perioperative factors that favor minimal residual disease after removal of the primary carcinoma. Therefore, the authors evaluated prostate cancer recurrence in patients who received either general anesthesia with epidural anesthesia/analgesia or general anesthesia with postoperative opioid analgesia. Methods:In a retrospective review of medical records, patients with invasive prostatic carcinoma who underwent open radical prostatectomy between January 1994 and December 2003 and had either general anesthesia–epidural analgesia or general anesthesia–opioid analgesia were evaluated through October 2006. The endpoint was an increase in postoperative prostate-specific antigen. Results:After adjusting for tumor size, Gleason score, preoperative prostate-specific antigen, margin, and date of surgery, the epidural plus general anesthesia group had an estimated 57% (95% confidence interval, 17–78%) lower risk of recurrence compared with the general anesthesia plus opioids group, with a corresponding hazard ratio of 0.43 (95% confidence interval, 0.22–0.83; P = 0.012) in a multivariable Cox regression model. Gleason score and tumor size (percent of prostate involved) were also independent predictors of recurrence (hazards ratios of 1.19 [1.08, 1.52], P = 0.004, and 1.17 [1.03, 1.34] for 10% size difference, P = 0.01, respectively). A similar association between epidural use and recurrence was obtained by comparing patients matched on the propensity to receive epidural versus general anesthesia. Conclusions:Open prostatectomy surgery with general anesthesia, substituting epidural analgesia for postoperative opioids, was associated with substantially less risk of biochemical cancer recurrence. Prospective randomized trials to evaluate this association seem warranted.

Superficial Bladder Tumors (Stage pTa, Grades 1 and 2): The Importance of Recurrence Pattern Following Initial Resection

We treated 414 new patients with stage pTa, grades 1 and 2 bladder tumors by transurethral resection between 1970 and 1982. All of the patients with grade 3 or previous upper tract tumors, or who had been treated at some stage with intravesical chemotherapy were excluded. Followup for 5 or more years was available in 188 of the patients. There was a low increase in T stage (6 per cent). Of the patients followed for 5 or more years 46 per cent remained free of tumor. Only 16 per cent of the patients had multiple tumors at presentation and 20 per cent had tumors of 10 gm. or more. These factors were associated with a worse prognosis. Patients free of tumor at 3 months had an 80 per cent chance of having no further recurrences and this rate remained the same up to 2 years from the start of the disease. Patients with a recurrence at 3 months were much less likely to remain free of tumor, and had a higher chance of recurrence at every future visit.

Management of prostate cancer in older men: recommendations of a working group of the International Society of Geriatric Oncology

Prostate cancer is the most prevalent cancer in men and predominantly affects older men (aged ≥70 years). The median age at diagnosis is 68 years; overall, two‐thirds of prostate cancer‐related deaths occur in men aged ≥75 years. With the exponential ageing of the population and the increasing life‐expectancy in developed countries, the burden of prostate cancer is expected to increase dramatically in the future. To date, no specific guidelines on the management of prostate cancer in older men have been published. The International Society of Geriatric Oncology (SIOG) conducted a systematic bibliographic search based on screening, diagnostic procedures and treatment options for localized and advanced prostate cancer, to develop a proposal for recommendations that should provide the highest standard of care for older men with prostate cancer. The consensus of the SIOG Prostate Cancer Task Force is that older men with prostate cancer should be managed according to their individual health status, which is mainly driven by the severity of associated comorbid conditions, and not according to chronological age. Existing international recommendations (European Association of Urology, National Comprehensive Cancer Network, and American Urological Association) are the backbone for localized and advanced prostate cancer treatment, but need to be adapted to patient health status. Based on a rapid and simple evaluation, patients can be classified into four different groups: 1, ‘Healthy’ patients (controlled comorbidity, fully independent in daily living activities, no malnutrition) should receive the same treatment as younger patients; 2, ‘Vulnerable’ patients (reversible impairment) should receive standard treatment after medical intervention; 3, ‘Frail’ patients (irreversible impairment) should receive adapted treatment; 4, Patients who are ‘too sick’ with ‘terminal illness’ should receive only symptomatic palliative treatment.

Neutrophil apoptosis is delayed in patients with inflammatory bowel disease.

Delayed neutrophil apoptosis is a feature of persistent acute inflammation. Neutrophil-mediated damage has been shown to be associated with the development of inflammatory bowel disease (IBD). Persistence of these cells both at the colonic site and circulation may further contribute to IBD. The aims of this study were to determine whether neutrophils isolated from IBD patients delay apoptosis and to investigate possible mechanisms involved in this delay. We studied 20 patients with IBD, 13 with Crohns disease, and 7 with ulcerative colitis, all of whom were undergoing intestinal resection for symptomatic disease. Seventeen patients undergoing elective resection of colon cancer acted as operative controls. Systemic, mesenteric arterial, and mesenteric venous blood was harvested. Neutrophils isolated from patients with IBD showed decreased spontaneous apoptosis compared to cancer patients. Mesenteric venous serum of IBD patients contributed to this delay, which contained higher concentrations of interleukin-8 (IL-8). Pro-caspase 3 expression was also reduced in IBD neutrophils, which may contribute to decreased spontaneous and Fas antibody-induced apoptosis. Neutrophil apoptosis may be altered in Crohns disease and ulcerative colitis through release of anti-apoptotic cytokines and altered caspase expression. The alterations in cell death mechanisms may lead to persistence of the inflammatory response associated with IBD.

Management of prostate cancer in older patients: updated recommendations of a working group of the International Society of Geriatric Oncology

In 2010, the International Society of Geriatric Oncology (SIOG) developed treatment guidelines for men with prostate cancer who are older than 70 years old. In 2013, a new multidisciplinary SIOG working group was formed to update these recommendations. The consensus of the task force is that older men with prostate cancer should be managed according to their individual health status, not according to age. On the basis of a validated rapid health status screening instrument and simple assessment, the task force recommends that patients are classed into three groups for treatment: healthy or fit patients who should have the same treatment options as younger patients; vulnerable patients with reversible impairment who should receive standard treatment after medical intervention; and frail patients with non-reversible impairment who should receive adapted treatment.

Heat shock proteins HSP27, HSP60, HSP70, and HSP90: expression in bladder carcinoma.

Heat shock proteins (HSPs) are synthesized by cells in response to various stress conditions, including carcinogenesis. The expression of HSPs in neoplasia has been implicated in the regulation of apoptosis, and HSPs also can act by increasing immunity. In the current study, the authors attempted to clarify the significance of HSPs in bladder carcinoma and their effect on tumor behavior.

The natural history of benign prostatic hyperplasia.

The progression of benign prostatic hyperplasia (BPH) can be defined as a deterioration of clinical variables such as lower urinary tract symptoms (LUTS), health‐related quality of life and peak flow rate, increased prostate size, or unfavourable outcomes such as acute urinary retention (AUR) and BPH‐related surgery. The natural history of BPH is best analysed from longitudinal studies of community‐dwelling men. In the Olmsted county study, which followed for 12 years a randomly selected cohort of 2115 men aged 40–79 years, there was an average increase in the International Prostate Symptom Score (IPSS) of 0.18 points per year, ranging from 0.05 for men in their fifties to 0.44 for those in their seventies. There was also a decrease in peak flow rate of 2% per year and a median prostate growth of 1.9% per year. The cumulative incidence of AUR was low (2.7% over 4 years). Information can also be collected from the placebo arms of controlled studies of men with symptomatic BPH, although the strict trial inclusion criteria and indeed the taking of a placebo itself introduce biases which limit the analysis of the natural history of the disease in this way, and its applicability to the general population. Hence, in the Medical Therapy of Prostatic Symptoms study, there is clear evidence that symptom deterioration, defined by a worsening of the IPSS of ≥ 4 points, was by far the most prevalent progression event (79.5%), with a cumulative incidence of 14% over a mean follow‐up of 4.5 years. As in the longitudinal community‐based studies, AUR was rather uncommon (14.8% of overall progression events) with a cumulative incidence of 2%. BPH‐related surgery, which was a secondary criterion in the study, was required in 5% of men. Similar conclusions can be drawn from a 2‐year placebo‐controlled study (ALTESS) assessing the impact of alfuzosin 10 mg once daily on LUTS/BPH progression in 1522 men with symptomatic BPH at high risk of developing AUR. Symptom deterioration was clearly the main progression event, with a cumulative incidence of 16.8%, compared to BPH‐related surgery (6.5%) and AUR (2.2%). Thus, there is evidence from longitudinal studies, and to a lesser extent from the placebo arms of large controlled studies, that BPH is a progressive disease. Symptom worsening is by far the most frequently occurring progression event. Identifying those patients at risk of BPH progression is crucial to optimize their management.

Laparoscopic versus open appendicectomy: A prospective evaluation

A prospective evaluation of laparoscopic surgery for acute appendicitis over a 6-month period is reported. Sixty-five patients with signs and symptoms of appendicitis necessitating surgery were assigned to open (n = 36) or laparoscopic (n = 29) appendicectomy. Thirty-seven patients were female (22 open) and 28 were male (14 open). The median age was 24 (range 14-64) years for open appendicectomy and 18 (range 14-60) years for the laparoscopic procedure. The mean postoperative stay for open operation was 4.8 (range 1-21) days and for the laparoscopic route 2.2 (range 1-11) days (P < 0.05). Inflammation was confirmed histologically in 72 per cent of the open cases and in 74 per cent of the laparoscopic cases (P not significant). The wound infection rate was 11 per cent (n = 4) for open and 4 per cent (n = 1) for laparoscopic appendicectomy (P < 0.05). The median anaesthesia time was 52 (range 15-90) min for open appendicectomy and 48 (range 20-120) min for laparoscopic surgery (P not significant). After open appendicectomy patients had a median of 5 (range 2-12) intramuscular injections of analgesia compared with a median of 1 (range 0-5) in the laparoscopic group (P < 0.05). Two laparoscopic operations were converted to an open procedure. The results suggest that emergency laparoscopic appendicectomy should be explored further as an alternative to open surgery for acute appendicitis.