HER2 expression in oesophageal carcinoma and Barrett's oesophagus associated adenocarcinoma: An Australian study.

BACKGROUND: Several studies have evaluated the prognostic value of HER2 in oesophageal cancer, but the prognostic influence of HER2 overexpression in oesophageal cancer remains uncertain. The aim of this study was to assess the incidence of HER2 positivity and relationship with clinicopathological features in patients with oesophageal cancer. DESIGN: The study cohort consisted of 269 patients diagnosed with oesophageal carcinoma in a single institution. HER2 expression was analysed by immunohistochemistry (IHC) and silver in situ hybridization (SISH) in 152 archival oesophageal cancer specimens. Survival analysis was assessed using Hazard models. RESULTS: HER2 expression was IHC3+ in 14 (9.2%), IHC2+ in 14 (9.2%), IHC1+ in 57 (37.5%), and IHC0 in 67 (44.1%) cases. SISH results confirmed that 15 specimens (9.9%) were HER2 gene amplified. Among 27 squamous cell carcinomas (SCCs) only 3.7% were HER2 positive whereas 11.2% of 125 adenocarcinomas were HER2 positive. The HER2 positive tumours were more likely to occur in men (OR: 5.00, 95% CI: 1.69-14.29), smokers (OR: 10.00, 95% CI: 4.17-25) and in patients with Barrett's oesophagus (OR: 8.33, 95% CI: 3.71-20.00). There was no significant difference in survival between the (HER2 +ve, 14.3 months vs HER2 -ve, 24.6 months, p = 0.42) CONCLUSION: A HER2 prevalence rate of 9.9% was found among patients with oesophageal cancer and no correlation with survival was detected overall.

Folate intake and the risk of prostate cancer: a systematic review and meta-analysis.

There is conflicting evidence regarding the role of folate on the risk of developing prostate cancer. We performed a systematic review and quantitative meta-analysis of folate blood levels and folate intake, and the risk of prostate cancer. Four electronic databases (Medline, PubMed, Embase and Current Contents Connect) were searched to 11 October 2013, with no language restrictions for observational studies that measured folate intake or blood levels and the risk of prostate cancer. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a random effects model. The dietary folate meta-analysis comprising 11 studies with 15 336 cases and a total sample size of 146 782 found no statistically significant association with prostate cancer, with an OR of 0.97 (95% CI 0.89-1.06). The total folate meta-analysis comprising of 5 studies with 7114 cases and a total sample size of 93 781 also found no statistically significant association with prostate cancer, with an OR of 0.99 (95% CI 0.82-1.19). The blood folate meta-analysis comprising of seven studies with 6122 cases and a total sample size of 10 232 found an increased risk of prostate cancer with high blood folate levels, with an OR of 1.43 (95% CI 1.06-1.93). There was significant heterogeneity (I(2)=79.5%, P<0.01). Removal of an outlier study removed the heterogeneity (I(2)=0.0%, P=0.54) and the association remained significant with an OR of 1.14 (95% CI 1.02-1.28). Dietary and total folate intake do not appear to be significantly associated with the risk of prostate cancer. High blood folate levels are associated with an increased risk of prostate cancer. These conclusions are limited by the predominance of included studies originating from developed countries with mostly Caucasian populations. Further research in populations with a high prevalence of non-Caucasian backgrounds is needed.

Association between human papillomavirus (HPV) and oesophageal squamous cell carcinoma: a meta-analysis.

SUMMARY: The oncogenic potential of human papillomaviruses (HPV) is well known in the context of cervical carcinoma; however, their role in the development of oesophageal squamous cell carcinoma (OSCC) is less clear. We aimed to determine the extent of the association between HPV infection and OSCC. A comprehensive literature search found 132 studies addressing HPV and OSCC in human cases, and a meta-analysis was performed using a random-effects model. There was evidence of an increased risk of OSCC in patients with HPV infection [odds ratio (OR) 2·69, 95% confidence interval (CI) 2·05-3·54]. The prevalence of HPV in OSCC was found to be 24·8%. There was an increased risk associated with HPV-16 infection (OR 2·35, 95% CI 1·73-3·19). Subgroup analyses showed geographical variance, with Asia (OR 2·94, 95% CI 2·16-4·00), and particularly China (OR 2·85, 95% CI 2·05-3·96) being high-risk areas. Our results confirm an increase in HPV infection in OSCC cases.

Meta-analysis: Barrett's oesophagus and the risk of colonic tumours.

BACKGROUND: Barrett's oesophagus (BO) is a premalignant condition associated with oesophageal adenocarcinoma. Although speculation exists, it is currently unclear if BO is associated with an increased risk of colonic tumours. AIM: To conduct a meta-analysis of studies reporting the prevalence of colonic tumours in patients with BO vs. controls and thus quantify the risk of colonic tumours associated with BO. METHODS: A search was conducted through Medline, PubMed, Embase, and Current Contents Connect to 7 October 2012. We calculated pooled odds ratios (OR) and 95% confidence intervals (CI) using a random-effects model for the risk of all colonic tumours associated with BO, as well as for the subgroups of colorectal cancer (CRC) and benign adenomatous tumours. RESULTS: In total, 11 studies, with 2580 BO cases, met our inclusion criteria. BO was associated with an increased risk of any colonic tumours (OR: 1.96; 95% CI: 1.56-2.46). BO was associated with an increased risk of benign adenomatous tumours (OR: 1.69; 95% CI: 1.20-2.39), as well as an increased risk of CRC (OR: 1.90; 95% CI: 1.35-2.67). No statistically significant heterogeneity was observed. Publication bias was not present. CONCLUSIONS: Barrett's oesophagus was associated with an increased risk of both benign adenomatous colonic tumours and colorectal cancer. Barrett's oesophagus had a stronger association with colorectal cancer than with benign colonic tumours. Further prospective cohort studies are needed to confirm the relationship.

Meta-analysis: coeliac disease and the risk of all-cause mortality, any malignancy and lymphoid malignancy.

BACKGROUND: Coeliac disease has been associated with an increased risk of mortality and malignancy. However, the strength of this association is conflicting among different studies. AIM: To perform a systematic review and quantitative meta-analysis to determine the risk of all-cause mortality, any malignancy and lymphoid malignancy in coeliac disease patients. METHODS: Four electronic databases (Medline, PubMed, Embase and Current Contents Connect) were searched to 4 January 2012, with no language restrictions. From 8698 citations identified, a total of 17 studies met our inclusion criteria. RESULTS: The all-cause mortality meta-analysis showed an increased risk for all-cause mortality in coeliac patients [odds ratio (OR) 1.24; 95% confidence interval (CI) 1.19-1.30]. A subgroup analysis showed that patients identified by positive serology alone were also at an increased risk of all-cause mortality (OR 1.16; 95% CI 1.02-1.31). The non-Hodgkin lymphoma (NHL) meta-analysis showed an increased risk for NHL in coeliac patients (OR 2.61; 95% CI 2.04-3.33). A subgroup analysis showed that patients identified by positive serology alone were also at an increased risk of NHL (OR 2.55; 95% CI 1.02-6.36). The T-cell non-Hodgkin lymphoma (TNHL) meta-analysis showed an increased risk of TNHL (OR 15.84; 95% CI 7.85-31.94). The any malignancy meta-analysis showed no increased risk (OR 1.07; 95% CI 0.89-1.29). CONCLUSIONS: Patients with coeliac disease are at an increased risk of mortality and non-Hodgkin lymphoma, particularly T-cell non-Hodgkin lymphoma; they do not have an increased risk of any malignancy overall. Serologically defined patients with coeliac disease have an elevated risk of mortality and non-Hodgkin lymphoma.

Grasper trauma during laparoscopic cholecystectomy.

BACKGROUND: The present study characterized the histopathological nature of laparoscopic grasper trauma during laparoscopic cholecystectomy in a prospective, blinded trial in order to establish a model for laparoscopic grasper trauma. The null hypothesis that graspers cause no histologically distinct tissue injury was tested. METHODS: The gall bladders of 19 patients undergoing laparoscopic cholecystectomy were examined. The area of gall bladder that had been grasped by Debakey laparoscopic forceps was excised (sample), along with an area of gall bladder that had not been grasped (control). Paired specimens were examined by a pathologist (blinded) to identify which was 'sample' and which was 'control' and to assess for histological markers of crushed tissue injury. The data were analysed by chi-squared or Fisher's exact tests. RESULTS: The pathologist was able to identify the sample (gripped) specimen in 13 of the 19 cases. In the remaining six cases the pathologist was unable to determine the specimen that had been gripped due to either absence of damage (four cases), or severe inflammation precluding assessment (two cases). The ability of the pathologist to distinguish the sample from the control specimen was significant (chi-squared test, P = 0.003). Of the histological markers of crushed tissue injury, focal thinning of the gall bladder wall and epithelial loss were present in significantly more sample (gripped) specimens than control specimens (chi-squared test, P = 0.0002 and P < 0.0001, respectively). CONCLUSIONS: Laparoscopic graspers cause tissue trauma that can be assessed histologically. The current study presents a relevant, reproducible, ethically acceptable human model for assessing the interaction between laparoscopic graspers and soft tissues.

Selective vascular occlusion with staged hemihepatectomy for blunt liver trauma.

BACKGROUND: A 23-year-old man with extensive blunt trauma to the right lobe of the liver in whom adequate haemostasis could not be achieved by selective suturing and packing was encountered. Contributing factors to poor haemostasis included massive transfusion, hypothermia and acidosis. METHODS: Hepatic haemostasis was achieved by selective intrahepatic ligation of the right hepatic pedicle and packing. RESULTS: After resuscitation and stabilization in the intensive care unit, a right hemihepatectomy was performed 14 h later. CONCLUSIONS: The present case describes a modification of the Pringle manoeuvre, termed 'selective Pringle manoeuvre'. This technique is a useful additional strategy for the management of uncontrollable bleeding in massive hepatic trauma.

The effect of fundoplication on the motility of the canine lower oesophageal sphincter.

BACKGROUND: A canine model was used to define whether Nissen fundoplication inhibits gastro-oesophageal reflux by inhibiting transient lower oesophageal sphincter relaxations (TLOSR) or by creating a pressure barrier at the gastro-oesophageal junction. METHODS: Four surgical models were studied pre-operatively and postoperatively. These were: (i) the surgical mobilization required for fundoplication (sham fundoplication, n = 5); (ii) a standard fundoplication (n = 4); (iii) anterior and posterior myotomy of the lower oesophageal sphincter (LOS; cardiomyotomy, n = 4); and (iv) combined cardiomyotomy and fundoplication (n = 4). Each operative procedure was assessed for its effect on the incidence of TLOSR and gas reflux events, the mean LOS pressure and the LOS pressure profile during swallow events. RESULTS: Sham fundoplication reduced the rate of evoked TLOSR in response to gaseous gastric insufflation from 9.8+/-1.6/h (mean +/- SEM) to 5.4 +/-1.5/h. The mean LOS pressure was reduced from 25.1+/-2.6 to 18.5+/-2.1 mm Hg but nadir LOS pressure during swallowing was not altered. Nissen fundoplication virtually abolished evoked TLOSR from 10.4+/-1.2/h to 0.4+/-0.4/h, increased mean basal LOS pressure from 19.8+/-2.1 to 27.0+/-1.1 mm Hg and increased the nadir pressure on swallowing from 3.4+/-1.0 mm Hg to 14.4+/-1.0 mm Hg. Cardiomyotomy was associated with a near continuous leakage of gas across a chronically hypotensive LOS. Cardiomyotomy reduced the resting LOS pressure from 14.7+/-1.2 mm Hg to 2.3+/-1.0 mm Hg. Cardiomyotomy with fundoplication was associated with no loss of LOS competence. No gas venting episodes occurred either by passive leakage or by TLOSR. Cardiomyotomy with fundoplication was associated with a fall in mean LOS pressure from 14.3+/-1.5 mm Hg to 7.1+/-1.8 mm Hg but no LOS relaxation occurred during swallowing. CONCLUSION: Nissen fundoplication is highly effective in preventing reflux across a normal or chronically hypotensive LOS. Fundoplication results in a constant, measurable pressure barrier at the lower end of the oesophagus that is not due to a change in intrinsic LOS tone. Following fundoplication TLOSR are prevented by the constant low-pressure barrier.

Transhiatal versus Ivor-Lewis oesophagectomy: is there a difference?

INTRODUCTION: Curative oesophageal resection for carcinoma may be carried out by either the transhiatal or the Ivor-Lewis transthoracic technique. The aims of this study were to compare the morbidity, 30-day mortality and long-term survival of the two techniques in the treatment of oesophageal carcinoma and to provide data to calculate the sample sizes for a prospective randomized trial. METHODS: Results from 44 series published between January 1986 and December 1996 were reviewed. Thirty-three papers reported results on 2675 patients having transhiatal (THO) and 29 papers reported results on 2808 patients having Ivor-Lewis oesophagectomy (ILO). RESULTS: The two groups were comparable in terms of age, sex and stage of the disease. There was no apparent difference in postoperative morbidity between the two groups with respect to respiratory complications (24% for THO, 25% for ILO), cardiovascular complications (12.4% for THO, 10.5% for ILO), wound infection (8.8% for THO, 6.2% for ILO) and chylothorax (2.1% for THO, 3.4% for ILO). The transhiatal group appeared to have a higher incidence of anastomotic leaks (16% for THO, 10% for ILO), anastomotic strictures (28% for THO, 16% for ILO) and recurrent laryngeal nerve injuries (11.2% for THO, 4.8% for ILO). The 30-day mortality was 6.3% for transhiatal and 9.5% for Ivor-Lewis oesophagectomy. Overall long-term survival at 5 years was similar (24% for THO, 26% for ILO). CONCLUSIONS: The surgical approach to oesophagectomy was not an important determinant of morbidity and long-term survival in patients with oesophageal carcinoma. Transhiatal oesophagectomy was associated with a higher incidence of anastomotic complications and recurrent laryngeal nerve injury. Ivor-Lewis oesophagectomy had a higher mortality. In order to demonstrate a significant difference in morbidity or long-term survival between the two techniques 3100 patients would be required in each arm of a prospective randomized trial.

Somatostatin stimulates the brush-tailed possum sphincter of Oddi in vitro and in vivo.

BACKGROUND & AIMS: Somatostatin, a neuropeptide and hormone, is found in the biliary tract of several species. The aim of this study was to map the distribution of somatostatin-like immunoreactive nerve fibers in the extrahepatic biliary tract of the Australian possum and to determine the pharmacological effects of somatostatin 1-14 on sphincter of Oddi activity in vitro and in vivo. METHODS: Tissue was harvested for immunohistochemistry and sphincter of Oddi for circular or longitudinal muscle contractility. In anesthetized possums, sphincter of Oddi motility was measured by manometry, and transsphincteric flow was measured gravimetrically. RESULTS: Somatostatin immunoreactivity was evident in gallbladder ganglia nerve cell bodies and in nerve fibers of the common bile duct and sphincter of Oddi. Somatostatin 1-14 increased circular and longitudinal muscle contraction amplitude 3-4-fold (P < 0.05), but only the longitudinal muscle contraction amplitude was tetrodotoxin sensitive. Somatostatin 1-14 stimulated spontaneous sphincter of Oddi motility in a tetrodotoxin-insensitive manner, increasing basal pressure, contraction frequency, and amplitude 2-4-fold (P < 0.05) and reducing transsphincteric flow to 25% of control (P < 0.0001). CONCLUSIONS: Somatostatin-like immunoreactivity is present in the extrahepatic biliary tree, and somatostatin 1-14 stimulates sphincter of Oddi smooth muscle and nerves. The major action is direct stimulation of sphincter of Oddi circular muscle, which reduces transsphincteric flow.

Gastrin-releasing peptide stimulates gallbladder motility but not sphincter of Oddi motility in Australian brush-tailed possum.

The neural distribution and action of gastrin-releasing peptide in the extrahepatic biliary tree of the Australian brush-tailed possum was investigated. Immunohistochemical staining of fixed specimens demonstrated gastrin-releasing peptide-containing nerves throughout the neural plexuses of the gallbladder, sphincter of Oddi, and mucosa of the common bile duct. Gastrin-releasing peptide (5-2000 ng/kg) increased gallbladder tone to a level equivalent to that produced by cholecystokinin octapeptide (160 ng/kg). This action was tetrodotoxin-insensitive. Sphincter of Oddi motility and transsphincteric flow were not altered. Possible mediation of the gallbladder response by gastrin was examined. Gastrin (50-2500 ng/kg) stimulated gastric acid secretion, elevated gallbladder motility to 64% of that produced by gastrin-releasing peptide, and did not alter sphincter of Oddi motility. In conclusion, gastrin-releasing peptide-containing nerves are found in the neural plexus of the possum extrahepatic biliary tree. Gastrin-releasing peptide induces gallbladder contraction in part by a direct action on gallbladder smooth muscle and also via release of gastrin.

Substance P stimulates sphincter of Oddi motility and inhibits trans-sphincteric flow in the Australian brush-tailed possum.

Substance P containing nerves are widely distributed throughout the gastrointestinal tract. The aims of this study were to determine the distribution of substance P containing nerves in the extrahepatic biliary tree of the Australian brush-tailed possum and to characterize the effect of exogenous substance P on the sphincter of Oddi (SO) motility and transphincteric flow in vivo. Immunohistochemical staining of fixed specimens (n = 8) found moderate numbers of substance P containing nerve cell bodies and fibres throughout the neural plexuses of the SO, in particular in the serosal and intraluminal nerve trunks of the SO and gallbladder. Synthetic porcine substance P (1-2000 ng kg-1), administered by close intra-arterial injection (i.a.; n = 7), produced a dose-dependent elevation in basal pressure [P < 0.01] and an associated dose-dependent reduction in trans-sphincteric flow [P < 0.0001]. Substance P had no significant dose-dependent effect on SO phasic contraction amplitude or frequency. Tetrodotoxin (9 micrograms kg-1, i.a.) did not inhibit the effect of substance P on SO motility and trans-sphincteric flow (n = 5). In conclusion, substance P containing nerves are found throughout the possum extrahepatic biliary tree. Exogenous substance P stimulates SO motility and reduces trans-sphincteric flow in vivo by acting directly on the sphincter smooth muscle.

An intervention on discharge polypharmacy.

OBJECTIVE: To determine if providing a way to cancel pre-admission prescriptions would reduce the number of active drug prescriptions (RXs) at discharge. DESIGN: A randomized non-blinded clinical trial. SETTING: Inpatient acute medical service of a university affiliated Veterans Administration medical center. PARTICIPANTS: Twelve medicine ward teams were randomized to control and intervention groups. Patients controlled had been discharged from these teams during 12 weeks and were receiving outpatient medications from this facility at hospital admission; control = 180, intervention = 168. INTERVENTION: At discharge, intervention teams used a computer-generated drug list to cancel or renew previous outpatient RXs or to prescribe new medications. Control teams could not cancel outpatient drugs and wrote all medications on individual prescriptions. MEASUREMENTS: The difference between admission and discharge RXs. RESULTS: There were no significant differences in patients' age, sex, race, Charlson Index (CI), or LOS between patient groups at discharge. The intervention group had fewer RXs on admission (5.4 vs 6.2, P < .05) and at discharge was not significantly different (2.9 vs 2.9, P = .87) from the control group. CONCLUSIONS: Providing a method for canceling pre-admission medications did not reduce the number of RXs at discharge. Further research is needed to evaluate the appropriateness of the large increase in RXs from admission to discharge for patients in acute hospital settings.

Laparoscopic common bile duct exploration: evolution of a new technique.

Laparoscopic exploration of the common bile duct (CBD) with a choledochoscope or a stone basket during laparoscopic cholecystectomy was attempted in 60 patients and was successful in 56. The cystic duct was used for entry to the CBD in 46 patients and in 14 a choledochotomy was performed. Of 51 patients with confirmed common duct stones, 38 had complete laparoscopic clearance (75 per cent). In 13 patients the duct was not cleared or was only partially cleared, of whom four went on to have clearance by postoperative percutaneous choledochoscopy down a cystic duct or T-tube track. Two patients with cystic duct tubes passed their remaining stones spontaneously. One patient had open exploration and six required endoscopic retrograde cholangiopancreatography. Of nine patients without stones, choledochoscopy was impossible in three patients whose cholangiogram was later considered to be normal. In five patients stones were excluded by choledochoscopy and in one patient laparoscopic choledochoscopy was undertaken to better define abnormal biliary anatomy; this helped to avoid major bile duct injury. Choledochoscopy was easier with the smaller 3.6-mm ureteroscope but stone removal was more difficult when the basket was too small for the stones, the cystic duct too small relative to stone size or the number of stones was too great. Successful stone clearance was proportional to the level of effort expended, and was limited by operating time and equipment.

Percutaneous cystogastrostomy with a new catheter for drainage of pancreatic pseudocysts and fluid collections.

We describe a new catheter for the initial percutaneous drainage of large symptomatic pancreatic fluid collections and abscesses using a transgastric approach to allow fluid drainage into the gastric lumen. A double-mushroom stent is placed secondarily for long-term internal drainage to the stomach, avoiding the need for an extended period of external catheter drainage. This technique, termed percutaneous cystogastrostomy (PCG), has been used in 19 consecutive patients with one recurrent symptomatic pseudocyst in the follow-up period fo 9-43 months. There was one death within 30 days of PCG and 1 patient proceeded to surgical necrosectomy. After evidence of resolution of the pseudocysts, the internal stent was retrieved in 17 patients by endoscopic snare.

Prospective randomized comparison of open versus laparoscopic appendectomy in men.

A prospective, randomized trial was performed to compare open appendectomy with laparoscopic appendectomy in men with a clinical diagnosis of acute appendicitis. Sixty-four patients with a median age of 25 years (range 18-84 years) were randomized to open appendectomy (n = 31) or laparoscopic (n = 33) appendectomy. Of the 64 men, 56 (87.5%) had appendicitis (27 open, 29 laparoscopic procedures). The mean operating times were 50.6 +/- 3.7 minutes (+/- SEM) for open and 58.9 +/- 4.0 minutes for laparoscopic appendectomy (p = 0.13). Five (15%) patients randomized to laparoscopic appendectomy had an open operation. The mean postoperative hospital stay was significantly longer for open appendectomy (3.8 +/- 0.4 days) than for laparoscopic appendectomy (2.9 +/- 0.3 days) (t = 2. 05,df = 62,p = 0.045). The complication rate after open appendectomy (25.8%) was not significantly different from that after laparoscopic appendectomy (12.1%). There was a single postoperative death due to a pulmonary embolus in the laparoscopic group and a single death due to cardiac and renal failure in the open group. The mean time to return to normal activities was significantly longer following open appendectomy (19.7 +/- 2.4 days) than after laparoscopic appendectomy (10.4 +/- 0.9 days), (t = 3.75,df = 49,p = 0.001). In conclusion, laparoscopic appendectomy in men has significant advantages in terms of a more rapid recovery compared to open appendectomy. There were no significant disadvantages to laparoscopic appendectomy compared to open appendectomy.

Minimal access surgery of the gastrointestinal tract.

In the last 5 years, surgery of the gastrointestinal tract has been revolutionized by the application of minimal access techniques. Following initial enthusiasm, which suggested that most abdominal surgery would ultimately be done via this approach, there is now need for appraisal and evaluation of the role of a number of these minimal access techniques when compared with open surgery. Undoubtedly, the most convincing and total application of minimal access techniques has been in the treatment of gallstone disease. Laparoscopic cholecystectomy is now standard therapy for cholelithiasis and endoscopic sphincterotomy with stone extraction is standard therapy for choledocholithiasis. Where the two conditions co-exist, operative cholangiography allows for the recognition of stones in the bile duct at the time of laparoscopic cholecystectomy and provides the potential avenue for treatment. Most major centres also would recommend routine operative cholangiography during laparoscopic cholecystectomy for the detection of unsuspected stones and as an extra safety procedure in the early identification of potential bile duct injuries. The efficacy of laparoscopic appendicectomy and laparoscopic or thoracoscopic treatment of achalasia of the oesophagus also is supported by data from well conducted prospective studies. Doubt remains regarding the advantage of laparoscopic surgery over other approaches in the treatment of gastro-oesophageal reflux, inguinal hernias and jaundice due to non-resectable cancer. For all three of these conditions, prospective trials are underway and the results of these trials should be assessed prior to widespread adoption of the laparoscopic techniques.(ABSTRACT TRUNCATED AT 250 WORDS)