A review of the use of biological mesh products in modern UK surgical practice: a religious and cultural perspective.

INTRODUCTION: The UK is an increasingly multicultural society. This change coincides with an increasing use of animal products in medicine and surgery and a change in the UK law of consent. The refusal of Jehovah's Witnesses to accept blood products is well known, but the use of animal products in surgery is a neglected topic. As society becomes more diverse and medicine becomes ever more advanced, there is increasing potential for a mismatch between what is medically possible and what is acceptable from a religious perspective. METHODS: Surgical products were identified by searching the literature and contacting manufacturing companies. Literature was identified by using PubMed and OVID (MEDLINE). Religious views were established by contacting national bodies for each group. FINDINGS: The views of common UK religious groups and the constituent parts of biological meshes are summarised in tables intended to be used as a reference during clinical practice. On an elective basis, the Islamic, Hindu. Sikh and Jain leaders contacted had strong views on avoiding animal derived products. The Christian and Jewish leaders contacted did not. All religious leaders contacted accepted the use of mesh derived from human tissue. All products, including those of porcine and bovine origin, were acceptable to all leaders contacted if the procedure was performed to save life. The highlighting of this issue should prompt earlier consideration and discussion in the surgical planning and the consenting process with all final decisions taken by both the surgeon and the individual patient.

Endoscopic Botulinum toxin as a treatment for delayed gastric emptying following oesophagogastrectomy.

INTRODUCTION: The incidence of delayed gastric emptying (DGE) following oesophagogastrectomy with gastric conduit reconstruction is reported to be between 1.7% and 50%. This variation is due to differing practices of intraoperative pylorus drainage procedures, which increase the risk of postoperative biliary reflux and dumping syndrome, resulting in significant morbidity. The aim of our study was to establish rates of DGE in people undergoing oesophagogastrectomy without routine intraoperative drainage procedures, and to evaluate outcomes of postoperative endoscopically administered Botulinum toxin into the pylorus (EBP) for people with DGE resistant to systemic pharmacological treatment. METHODS: All patients undergoing oesophagogastrectomy between 1 January 2016 and 31 March 2018 at our unit were included. No intraoperative pyloric drainage procedures were performed, and DGE resistant to systemic pharmacotherapy was managed with EBP. RESULTS: Ninety-seven patients were included. Postoperatively, 29 patients (30%) were diagnosed with DGE resistant to pharmacotherapy. Of these, 16 (16.5%) were diagnosed within 30 days of surgery. The median pre-procedure nasogastric tube aspirate was 780ml; following EBP, this fell to 125ml (p<0.001). Median delay from surgery to EBP in this cohort was 13 days (IQR 7-16 days). Six patients required a second course of EBP, with 100% successful resolution of DGE before discharge. There were no procedural complications. CONCLUSIONS: This is the largest series of patients without routine intraoperative drainage procedures. Only 30% of patients developed DGE resistant to pharmacotherapy, which was managed safely with EBP in the postoperative period, thus minimising the risk of biliary reflux in people who would otherwise be at risk following prophylactic pylorus drainage procedures.

Identification of Cystic Lesions by Secondary Screening of Familial Pancreatic Cancer (FPC) Kindreds Is Not Associated with the Stratified Risk of Cancer.

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) are associated with risk of pancreatic ductal adenocarcinoma (PDAC). It is unclear if an IPMN in individuals at high risk of PDAC should be considered as a positive screening result or as an incidental finding. Stratified familial pancreatic cancer (FPC) populations were used to determine if IPMN risk is linked to familial risk of PDAC. METHODS: This is a cohort study of 321 individuals from 258 kindreds suspected of being FPC and undergoing secondary screening for PDAC through the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC). Computerised tomography, endoscopic ultrasound of the pancreas and magnetic resonance imaging were used. The risk of being a carrier of a dominant mutation predisposing to pancreatic cancer was stratified into three even categories (low, medium and high) based on: Mendelian probability, the number of PDAC cases and the number of people at risk in a kindred. RESULTS: There was a median (interquartile range (IQR)) follow-up of 2 (0-5) years and a median (IQR) number of investigations per participant of 4 (2-6). One PDAC, two low-grade neuroendocrine tumours and 41 cystic lesions were identified, including 23 IPMN (22 branch-duct (BD)). The PDAC case occurred in the top 10% of risk, and the BD-IPMN cases were evenly distributed amongst risk categories: low (6/107), medium (10/107) and high (6/107) (P = 0.63). CONCLUSIONS: The risk of finding BD-IPMN was independent of genetic predisposition and so they should be managed according to guidelines for incidental finding of IPMN.

Screening of high-risk families for pancreatic cancer.

PURPOSE OF REVIEW: To discuss how to recognise and manage high-risk individuals. RECENT FINDINGS: Publication of initial results of screening for pancreatic cancer from US centres. Several masses and premalignant lesions have been detected, but the detection of the first pancreatic cancer through an organised study of screening has yet to be published. There has been progress in risk stratification; the role of diabetes in predisposing for cancer has been characterised and molecular modalities have been published which could be used in conjunction with imaging in a screening programme. A mutation in the palladin gene was found to segregate with the disease in a family with a clear predisposition for pancreatic cancer, though this has yet to be found in other such kindreds. SUMMARY: Significant challenges remain to be solved in screening for early pancreatic cancer. Risk stratification needs to be improved and high-risk patients included in research-based screening programmes. It will be impossible to confirm that screening can detect cancers early enough for curative treatment until the results of these prospective studies become available.

Familial pancreatic cancer: a review and latest advances.

Familial Pancreatic Cancer (FPC) is the autosomal dominant inheritance of a genetic predisposition to pancreatic ductal adenocarcinoma, penetrance is assumed to be high but not complete. It was first described in 1987 and since then many families have been identified, but the candidate disease gene remains elusive and the very existence of the syndrome is sometimes questioned. FPC identifies a target group for secondary screening. As well as being potentially life saving for the subjects, screening offers researchers the opportunity to elucidate the early pathogenesis of pancreatic cancer. The scientific incentive for screening should not blind us to the challenges facing clinicians in managing high risk patients. Early surgical treatment may dramatically improve the five year survival for pancreatic cancer, but this must be balanced against the risks of false positives, where healthy individuals are subjected to the mortality and morbidity of major pancreatic surgery.

Ball bearing (BB) guns, ease of purchase and potential for significant injury.

INTRODUCTION: Ball bearing guns are used in the UK for war games, but they have the potential to cause severe injury if used incorrectly. MATERIALS AND METHODS: A search was made for availability of these weapons, the ease of purchase and the potential for tissue damage. RESULTS: These weapons are widely available on the Internet and are easy to purchase with no security checks. Once fully charged, an electric BB gun is capable of penetrating a cadaveric animal model at distances up to 5 m (1 m = 25 mm penetration, 3 m = 20 mm penetration, 5 m = 15 mm penetration). CONCLUSIONS: BB guns are not toys and have a significant potential to cause injury.

Suture anchors for treatment of sternoclavicular joint instability.

Instability of the sternoclavicular joint is a difficult problem to treat and can present with gross limitation in activities. Eight sternoclavicular joint stabilization procedures were performed over an 8-year period. The patients' ages ranged from 16 to 48 years (mean, 23.5 years). The indication for stabilization was pain associated with instability of the sternoclavicular joint. The joint was stabilized by use of suture anchors on the manubrium and capsular plication. The functional outcome was evaluated by use of the Constant score and patient-based Oxford Shoulder Questionnaire. At a mean follow-up of 4.5 years (range, 1-7.6 years), none of the patients had instability at the sternoclavicular joint, and all except one had returned to their previous employment. The Oxford score was 16 (range, 12-38). The mean Constant score was 74.88 (range, 33-87). We had only 1 poor result (Constant score of 33). Stabilization of the sternoclavicular joint can safely be performed by use of suture anchors. The technique is recommended for symptomatic sternoclavicular joint instability.

Effects of the gonadotrophin-releasing hormone agonist 'Zoladex' upon pituitary and gonadal function in hypogonadal (hpg) male mice: a comparison with normal male and testicular feminized (tfm) mice.

Hypogonadal (hpg) mutant mice, with a congenital deficiency of hypothalamic gonadotrophin-releasing hormone (GnRH), and testicular feminized (tfm) mice, which lack a functional androgen receptor, were used to study the effects of the potent GnRH agonist 'Zoladex' (ICI 118630; D-Ser (Bu(t))6, Azgly10-GnRH) on pituitary and gonadal function. Zoladex (0.5 mg) in a sustained-release lactide-glycolide copolymer depot was administered subcutaneously under anaesthesia and was left in place for 7 days, after which time the effects of the drug upon pituitary and serum gonadotrophin concentrations, glycoprotein hormone subunit mRNAs and testicular morphology were investigated. At the pituitary level, Zoladex treatment resulted in a substantial reduction in LH content in normal males, and LH content was depressed in hpg mice even below the basal levels normally found in these mutants. Pituitary LH content in the Zoladex-treated animals was depressed in the tfm groups, but not to the same levels as those found in the normal and castrated normal mice. Zoladex treatment at the time of castration prevented the post-operative elevation in serum LH associated with castration alone. In the androgen-deficient tfm mouse, Zoladex did not depress the normally elevated serum LH levels. Serum LH in the hpg animals was, in all cases, below the limit of detection of the assay. Pituitary FSH content was depressed into the hpg range in both the normal and castrated animals, but there was no further depression in the hpg mice. The pituitary content was reduced in the tfm mice, again the effects not being as dramatic as in the normal and castrated animals. Serum FSH content, as measured by radioimmunoassay, was depressed by 50% in normal mice; there was no reduction in the hpg mice, however. With regard to pituitary gonadotrophic hormone gene expression, Zoladex administration to normal mice caused a dramatic reduction in LH beta mRNA content, to a level approximating that found in untreated hpg mice. The drug also depressed LH beta mRNA in the castrated group to the hpg range when given at the time of castration, whereas in untreated castrated mice there was a significant increase in LH beta mRNA. In the tfm mouse, which can be considered as a model for long-term failure of androgen feedback, Zoladex again induced a fall in LH beta mRNA, but not to the same extent as in the normal and normal castrated group. Zoladex had no effect on the already low levels of LH beta mRNA found in hpg mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of LH injections on testicular steroidogenesis, cholesterol side-chain cleavage P450 mRNA content and Leydig cell morphology in hypogonadal mice.

Hypogonadal (hpg) mice have a congenital deficiency of hypothalamic gonadotrophin-releasing hormone (GnRH) and the gonads consequently lack exposure to gonadotrophins during development. We injected male hpg mice with LH for 10 days to investigate whether LH alone can stimulate normal steroidogenesis in these animals. Control animals had an inactive interstitium and very few germ cells. Testicular content of androgens was undetectable by radioimmunoassay in control animals unless a single injection of LH was given 1 h before death, when androgens were just detectable. Control testes incubated in vitro with [3H]pregnenolone demonstrated that without gonadotrophin stimulation pregnenolone was metabolized only to progesterone in significant amounts. Assay for cholesterol side-chain cleavage cytochrome P450 (P450scc) mRNA showed basal expression in saline-treated hpg mouse testis. LH treatment induced hypertrophy and hyperplasia of Leydig cells and division of germ cells. Testicular androgen content increased significantly, with testosterone and androstenedione as the major androgens. LH-treated testes incubated with [3H]pregnenolone in vitro had a greater synthetic capacity for testosterone, suggesting an increase in 17 alpha-hydroxylase/C17-20-lyase activity. Basal and human chorionic gonadotrophin-stimulated androgen production in vitro increased markedly following LH treatment to levels previously described in the normal adult animal. LH treatment caused a rapid and transient increase in the hybridization of P450scc mRNA which was sevenfold greater than that of saline-treated controls when the animals were killed 1 h after the last injection but fell to control levels within 24 h of cessation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of the fetal pituitary in cryptorchidism induced by exogenous maternal oestrogen during pregnancy in mice.

A single subcutaneous injection of 5 or 1 mg oestradiol given to pregnant female mice on Day 14 of pregnancy resulted in all male offspring being cryptorchid. Pituitary LH content, testicular weights and structure, seminal vesicle weights and the structure of the reproductive tract as a whole were monitored on the day of birth and at 2, 4, 8 and 14 weeks of age. Apart from an initial significant reduction in pituitary LH at the time of birth, no other marked differences were seen between control and treated animals except that all oestrogen-treated males lacked a gubernaculum and the testes were freely mobile within the abdomen. Hypogonadal (hpg) male mice lacking GnRH are cryptorchid but have a normal gubernaculum and their testes develop and descend normally if treated with gonadotrophins. When the mothers of hpg mice were treated with oestradiol the male offspring lacked a gubernaculum. These results indicate that perturbations of the fetal hypothalamic/pituitary axis play no significant part in oestrogen-induced cryptorchidism in mice.

Effect of different photoperiods on testicular weight changes in the vole, Microtus agrestis.

The testicular weight response of 2-week-old male voles exposed to 10, 12, 14, 15 or 16 h light (L) per day for 4 weeks and of 5-week-old males exposed from birth to 12, 13, 13.5, 14, 14.25, 14.5, 14.75, or 15 h light per day was proportional to the photoperiod: 13L or less produced little growth but 13.5L or more produced progressively heavier testes. Only 14.5L and 15L gave full spermatogenesis. 'Night-break' schedules produced a marked testicular response with 7L :8D :1L :8D and 7L :6D :1L :10D, intermediate effects with 7L :4D :1L :12D and none with 7L :2D :1L :14D. Of various skeleton photoperiods with 0.75L only 0.75L : 12.5D :0.75L :10D and 0.75L :10.5D :0.75L :12D produced marked increases in testicular weight. The peak of photosensitivity appeared to be phase-shifted towards 'dawn' by reducing the initial light phase. Its position appeared to move from 16 h after 'dawn' in block photoperiods to 14 h after 'dawn' in the 'night-break' and 12 h after 'dawn' in the skeleton photoperiod experiments. Previous experience of 16L :8D or 8L :16D had little effect on the subsequent response to skeleton photoperiods (0.5L :9D :0.5L :14D, 0.5L :13D :0.5L :10D, 0.5L :15D :0.5L :8D). Animals reared in these photoperiods only showed a positive testicular response to 0.5L : 13D :0.5L :10D. The lack of response to constant darkness indicated that voles were capable of perceiving these skeleton photoperiods.

Testis development in the vole, Microtus agrestis, subjected to long or short photoperiods from birth.

Voles exposed to long photoperiods (16L:8D) from birth became sexually mature at 40-45 days and remained so up to the end of the experiment at 6 months of age. In short photoperiods development was inhibited up to 60 days but the majority of males became sexually mature between 4 and 6 months of age.

The effects of pinealectomy and superior cervical ganglionectomy on the testis of the vole, Microtus agrestic.

PIP: The effects of pinealectomy and superior cervical ganglionectomy on the testis of the vole (Microtus agrestis) were studied. Testicular weight at 4 and 8 weeks was significantly (p less than .001) greater in pinealectomized and ganglionectomized than in controls animals. Similar results were found in the weights of the seminal vesicles. Seminiferous tubule diameters were also increased, and spermatogenesis was stimulated. Spermatogenic development in controls had preceeded only to the meiotic phase. The results indicate that the pineal gland is involved in light-induced gonadal changes in this species, and that an intact sympathetic nerve supply from the superior cervical ganglion is required for this aspect of pineal function.^ieng

Spermatogenesis in mature and regressed testes of the vole (Microtus agrestis).

Eight stages of spermatogenesis, each with a characteristic frequency and germ cell association could be recognized in the vole. There was no difference between laboratory bred and field animals in the frequency of the stages. Counts of the different types of germ cell showed that there was considerable cell loss during spermatogonial mitotic and spermatocytic meiotic divisions. Only 60% of germ cells became spermatozoa in sexually mature animals, and 19% in the regressing testes of voles exposed to short photoperiods. Animals with regressed testes probably have lowered circulating levels of gonadotrophins and testicular hormones, so that the greater germ loss suggests the importance of these hormones in the regulation of germ cell wastage. From the cell counts in mature animals, a scheme of cell divisions has been suggested by which spermatogonia produce progressively more highly differentiated germ cells while continuing to perpetuate stem cells.