Factors influencing patient's perception of long-term treatment with low-molecular-weight heparins for cancer-associated thrombosis: an updated analysis of TROPIQUE, a prospective observational study.

PURPOSE: Our objective was to compare patient's expectations to their experience and to identify factors predictive of patient's perception of long-term LMWH for the treatment of cancer-associated thrombosis (CAT). METHODS: Results from the validated Perception Anticoagulant Treatment Questionnaires (PACTQ) completed before inclusion (PACTQ1 for expectations) and at the end (PACTQ2 for convenience and satisfaction) of the 6-month TROPIQUE study were studied with principal component analysis. Possible predictive factors of improved perception of LMWH treatment were analyzed with the Kruskall-Wallis test. RESULTS: Among 409 included patients treated with LMWH, 269 PACT-Q1 and 139 PACT-Q2 were evaluable for treatment perception. Patients had high expectations (A1-A7 score of 26.7 ± 3.5, max = 35). Treatment cost (A7 = 1.90 ± 1.31) and concern about a mistake in anticoagulation (A5 = 1.93 ± 1.12) had little importance while LMWH treatment was considered easy to use (A4 = 4.20 ± 0.93). Six-month treatment with LMWH was associated with a high rate of convenience (B1-B11, C1-C2 = 55.1 ± 8.38, max = 65) and a high satisfaction score (D1-D7 = 25.1 ± 4.32, max = 35). Patients' confidence in treatment and perception of possible LMWH side effects were moderate while perception of autonomy and independence significantly improved at the end of the study compared to inclusion. PACT-Q2 satisfaction score was low in patients who experienced bleeding (PACT-Q2 24.1 ± 3.3 vs. 25.1 ± 4.3). LMWH twice daily tended to be found less convenient compared than once daily (53.3 ± 7.2 vs. 55.0 ± 8.3). CONCLUSION: CAT patients had a good perception of the 6-month LMWH treatment when comparing expectations and experience. Using a quantitative scale validated in the general population for VTE and subcutaneous injection and including a large number of patients, bleeding complications and LMWH twice daily were associated with a nonsignificant trend towards a worsen perception.

Infiltration of wounds and extraperitoneal space with local anesthetic in patients undergoing laparoscopic totally extraperitoneal repair of unilateral inguinal hernias: a randomized double-blind placebo-controlled trial.

BACKGROUND: The potential analgesic benefit of infiltration of the wounds and extraperitoneal space with local anesthetic in patients undergoing laparoscopic totally extraperitoneal (TEP) repair of inguinal hernias remains unclear. METHODS: Consenting adults scheduled to undergo laparoscopic TEP repair of unilateral inguinal hernias were recruited to this randomized double-blind placebo-controlled clinical trial of 0.25% bupivacaine (Group I) versus saline (Group II) infiltration of abdominal wounds and the extraperitoneal space. Pain scores were assessed at 4 and 24 hours postoperatively using the short-form McGill pain questionnaire (SF-MPQ), the Present Pain Index (PPI) score and the visual analogue scale (VAS). The intravenous and oral analgesic requirements were recorded. Each patient completed questionnaire to assess their satisfaction with the postoperative analgesia. RESULTS: 40 patients were randomized (Group I, n = 20; Group II, n = 20). The two groups were comparable for age, gender, body mass index, and operating time. Minor complications occurred in one patient in each group. There were no significant differences in the postoperative SF-MPQ scores, PPI and VAS at 4 hours (p = 0.413, p = 0.631, p = 0.615 respectively) and 24 hours (p = 0.116, p = 0.310, p = 0.100 respectively) post-operatively. The parenteral and oral analgesics consumed post-surgery were comparable (p = 0.605, p = 0.235). No difference was ob-served in the patient satisfaction scores. CONCLUSIONS: Infiltration of abdominal wounds and extraperitoneal space with bupivacaine in patients undergoing laparoscopic TEP repair of unilateral inguinal hernias does not appear to offer analgesic benefits.Key words: Laparoscopic; extraperitoneal; inguinal hernia; repair; pain; bupivacaine; analgesia; satisfaction; day case; randomized.

Breath testing for intra-abdominal infection: appendicitis, a preliminary study.

In the current pilot study we aimed to determine whether breath analysis could be used to help recognise intra-abdominal infection, using acute appendicitis as an exemplar condition. Our study included 53 patients (aged 18-88 years) divided into three groups: appendix group, 26 (13 male) patients suffering from acute appendicitis; control group 20 (seven male) patients undergoing elective abdominal surgery; normal group, seven patients who were clinically diagnosed with appendicitis, but whose appendix was normal on histological examination. Samples of breath were analysed using ion molecule reaction mass spectroscopy measuring the concentration of volatile compounds (VCs) with molecular masses 27-123. Intraperitoneal gas samples were collected from a subset of 23 patients (nine diagnosed with acute appendicitis). Statistically significant differences in the concentration of VCs in breath were found between the three groups. Acetone, isopropanol, propanol, butyric acid, and further unassigned VCs with molecular mass/charge ratio (m/z) 56, 61 and 87 were all identified with significant endogenous contributions. Principle component analysis was able to separate the control and appendicitis groups for seven variables: m/z = 56, 58, 59, 60, 61, 87 and 88. Comparing breath and intraperitoneal samples showed significant relationships for acetone and the VC with m/z = 61. Our data suggest that it may be possible to help diagnose acute appendicitis by breath analysis; however, factors such as length of starvation remain to be properly accounted for and the management or mitigation of background levels needs to be properly addressed, and larger studies relating breath VCs to the causative organisms may help to highlight the relative importance of individual VCs.

Fixity of ports to the abdominal wall during laparoscopic surgery: a randomized comparison of cutting versus blunt trocars.

BACKGROUND: Dislodgement of ports from the abdominal wall is a common problem during laparoscopic surgery. The aim of this study was to evaluate port stability using either cutting or blunt-tipped trocars. METHODS: Patients undergoing laparoscopic surgery were randomized to have the secondary ports inserted using either cutting or blunt-tipped trocars. The fixity of ports to the abdominal wall was evaluated at the start and completion of surgery by measuring the total traction force required to displace the ports. Similarly, the friction forces required to displace instruments within the ports were measured. RESULTS: Thirty patients were randomized into two groups (15 patients in each group), and a total of 114 ports (cutting, n = 51; blunt, n = 63) were evaluated. The groups were comparable in age, gender, body mass index, and operating time. The total traction forces needed to displace the 5-mm and 10-mm ports were significantly lower when cutting trocars were used at both the beginning (2.6 vs. 11.8 N, p < 0.001, and 6.3 vs. 15.5 N, p = 0.014, respectively) and completion of surgery (1.3 vs. 6.7 N, p < 0.001, and 1.1 vs. 12.0 N, p = 0.001, respectively). The declines in the total traction forces from the start to the completion of surgery were significant for the 5-mm and 10-mm cutting-trocar ports (p = 0.031 and p = 0.043, respectively) but not for the blunt-trocar ports (p = 0.088 and p = 0.152, respectively). While no significant differences between the instruments' friction forces and the traction forces of the cutting-trocar ports were observed, the former were significantly lower than the traction force needed to displace the blunt-trocar ports. This explains the significantly greater frequency of spontaneous port dislodgements when cutting ports were employed (25.5% vs. 1.6%, p < 0.001). Port-site bleeding was encountered only in patients (n = 2, 13%) where cutting trocars were used. CONCLUSIONS: Port fixity to the abdominal wall during laparoscopic surgery declines with time. The insertion of ports using a blunt-tipped trocar is associated with significantly greater stability and fixity of the port to the abdominal wall. The use of blunt-tipped trocars is recommended for routine practice in laparoscopic surgery.

[Why screening for a renal artery stenosis?]. / Pourquoi dépister une sténose artérielle rénale?

Diagnosis of renal artery stenosis (RAS) should be discussed in numerous clinical situations including refractory high blood pressure (HBP), HBP in a polyvascular patient, degradation of renal function following renin angiotensin inhibitor or flash pulmonary edema. Ultrasound-doppler coupled with gadolinium-enhanced MR or CT angiography has proven adequate for most patients with RAS. Digital subtraction angiography should be limited to revascularisation procedures. Functional testing are not sensitive or specific enough because the degree of renin activation differs widely among patients with RAS. Renal percutaneous angioplasty induces a light to moderate decrease in blood pressure, has no effect on renal function but allows to reduce the number of anti-hypertensive drugs. Stenting completed angioplasty is worthwhile in most patients with atherosclerotic RAS. ACE inhibitors decrease mortality and increase renal function in patients with RAS.

Pheochromocytoma: A Cause of Anemia.

Patients with a Pheochromocytoma usually present with intractable hypertension, postural hypotension, headaches and palpitations, with intractable hypertension being the predominant symptom. When the tumor is located in the urinary bladder, symptoms may be induced by micturition. Herein, we report a young patient with a urinary bladder Pheochromocytoma without hypertension or symptoms induced by micturition. Instead, she presented with anemia.

A case report on a left sided gallbladder: A rare finding during cholecystectomy.

INTRODUCTION: Cholecystectomy is the surgical removal of gallbladder for symptomatic gallstones disease or where exist the risk of gallbladder malignancy. Its performed routinely across the globe often as day surgery. In this case report, we describe an incidental intra operative finding of a left sided gallbladder creating a technical challenge for the surgeon. CASE: We describe the case of 35 year old female who presented with RUQ pain. Ultrasound examination revealed gallstones. Intraoperative findings during routine cholecystectomy were of a left sided gallbladder. The surgical procedure in performing laparoscopic surgery required an extra port placement for safe and effective dissection. DISCUSSION: The finding of left sided gallbladder is a rare congenital anomaly and has a prevalence of 0.1-0.7%. A true left sided gallbladder is one that is found to the left of the ligamentum teres and falciform ligament and the cystic artery always crosses in front of the CBD from right to left. There are various abnormalities associated this anatomical variant from abnormality of the biliary tree to the porto-venous anatomy. Failure to recognise these variations can lead to serious complications especially in hepatobiliary surgery. CONCLUSION: The finding of left sided gallbladder is an abnormality which is often discovered intraoperatively. It may provide the surgeon with operative challenges in performing the surgery safely and increase the incidence of morbidity. If there is any clinical suspicion of the presence of a left sided gallbladder, pre-operative CT angiography and/or intraoperative cholangiography should be performed to minimise the risk of intraoperative complications.

Therapeutic, prophylactic, and preresection applications of laparoscopic gastric and biliary bypass for patients with periampullary malignancy.

BACKGROUND: Laparoscopic bypass surgery for the palliation of gastric and biliary obstruction is associated with a rapid recovery. This study aimed to extend its application to other aspects in the management of patients with periampullary cancer. METHODS: Between 2001 and 2004, 21 patients (median age, 68 years) underwent laparoscopic gastric (n = 8), biliary (n = 5), and combined gastric and biliary (n = 8) bypass. In addition to its therapeutic role (n = 12), indications included a concomitant prophylactic gastric (n = 3) and biliary (n = 2) bypass as well as pre- 1 Whipple's relief of deep jaundice at the time of staging laparoscopy (n = 3). Construction of the biliary bypass to the gallbladder (n = 11) or bile duct (n = 2) was based on preoperative imaging. RESULTS: All procedures were completed laparoscopically. The median operating times for gastric, biliary, and combined bypass were 75, 60, and 130 min, respectively. The addition of a prophylactic bypass did not significantly prolong the operating time, as compared with a single therapeutic bypass. One patient died postoperatively of aspiration pneumonia. The postoperative hospital stay (median, 4 days) was not significantly influenced by the type of bypass. No recurrence of or new obstructive symptoms developed during the follow-up period after a therapeutic or prophylactic bypass. CONCLUSIONS: Applications of laparoscopic gastric and biliary bypass can safely be expanded to include a prophylactic role and preresection relief of obstructive jaundice. Prophylactic bypass surgery does not prolong operating time or hospital stay significantly and prevents future onset of obstructive symptoms.

A new HLA allocation procedure of kidneys from deceased donors in the current era of immunosuppression.

INTRODUCTION: It has recently been proposed to replace the current Eurotransplant kidney allocation based primarily on mismatches (MM) at the 3 HLA loci by a simpler system based on full HLA-DR compatibility. The present study analyzes this system in the current era of immunosuppression. METHODS: From 1999 to 2012, 723 renal grafts were performed on 586 patients who were treated with a calcineurin inhibitor, mycophenolate mofetil, and in most cases antilymphocyte globulins. Four groups of HLA MM were compared: (A) A+B 2-4/DR 1-2 MM (n = 397), (B) A+B 2-4 MM/DR 0 MM (n = 106), (C) A+B 0-1 MM/DR 1-2 MM (n = 138), and (D) A+B 0-1/DR 0 MM (n = 82). RESULTS: Acute rejection episodes were less frequent during the first post-transplantation year in group D than in the other groups (P = .018). Patient survival was lower in group A than in the other groups (P = .008). Immunologic graft survival was higher in group D than in the other groups in univariate (P = .015) and multivariate analyses (P = .033; 96.4% vs 90.1% at 10 years). CONCLUSIONS: In the current era of immunosuppression, allocation of kidneys from deceased donors could be performed primarily according to full DR compatibility then to the best A+B matching, affording excellent graft outcome to most recipients.

Patient and graft outcome in current era of immunosuppression: a single centre pilot study.

OBJECTIVES: The present single centre study aims at analyzing the impact on renal allograft outcome of the important changes which occurred in the transplant population and immunosuppressive therapy during the last two decades. METHODS: From 2000 to 2013, 779 single kidney transplantations were performed on 635 patients who all received on an intent-to-treat basis steroids, a calcineurin inhibitor, mycophenolate mofetil and an induction therapy with either antithymocyte globulin or an antagonist directed to the interleukin (IL)-2 receptor. Uni- and multivariate analyses of patient and immunologic graft survival were conducted. RESULTS: The sole factor predicting patient survival is recipient's age: 10-year survival rates are 94·7, 81·6 and 57·9% for the <45, 45-60 and >60 years age groups, respectively (P<0·001). Peak (>50% panel reactive antibodies) anti-human leucocyte antigens (HLA) sensitization, cold ischaemia time and HLA-B and -DR mismatches (MM) influence graft outcome: at 10 years, the difference in 10-year survival rates is 5·9% between grafts from sensitized and not sensitized patients (90·9 vs 96·8%, P = 0·002), 3·8% between grafts with <18 and ≧18 hours cold ischaemia (96·6 vs 92·8%, P = 0·003), 7·3% between grafts with no MM and either B or DR MM versus those with B and DR MM (96·8 vs 89·5%, P = 0·002). CONCLUSION: In our single centre experience, graft survival was most strongly determined by HLA matching, offering excellent long term graft outcome to most patients.

DNA-damaging effects of genotoxins in mixture: nonadditive effects of aflatoxin B1 and N-acetylaminofluorene on their mutagenicity in Salmonella typhimurium.

Most animal genotoxicity studies have used exposures to single chemicals; humans, however, are potentially exposed to mixtures of genotoxins. Cancer and developmental toxicity risks associated with genotoxins in mixture are generally estimated by assuming additivity of the components. Two or more genotoxins acting sequentially or simultaneously may present a greater or lesser hazard than that predicted by simple addition of their potencies. Previously, we studied the effect of one genotoxin on the binding of a second genotoxin to DNA in an in vitro system and demonstrated that consecutive binding of the two toxins was not additive. In the present study, the effect of one genotoxin on the mutagenicity of another was evaluated for two well-known genotoxins using the Salmonella assay. Pretreatment of frameshift strains TA98 and TA1538 with AFB1-8,9-epoxide (17.3 ng/plate) enhanced the mutagenicity induced by subsequent exposure to N-acetoxy-acetylaminofluorene (N-AcO-AAF) approximately 2-3 times above theoretical values for additivity. Pretreatment of base-substitution strain TA100 with N-AcO-AAF (0.1 microg/plate) inhibited the mutagenicity following subsequent exposure to AFB1-8,9-epoxide by 3 times below the theoretical additive value. Concentration-response relationships for these enhancing or inhibitory effects were demonstrated using increasing concentrations of the first genotoxin during pretreatment. These results demonstrate effects, other than additive, of sequential exposures to two genotoxins on the induction of mutations in a bacterial system.

Mucin lakes or perforation?

We are reporting two cases with similar appearances on post chemo radiotherapy MRI scan of the mucinous adenocarcinoma. There was high signal on T2-weighted sequences of the mucin pools within and beyond the rectal wall. Does this imply that wall tissues become less resistant to cancer pools intrusion after chemo radiation? Does the high intramural pressure have an impact on the protrusion of the cancer pools beyond the muscularis propria? Final histology reports differ from predicted MRI staging. It highlights the difficulty of the final MRI staging and outcome for mucinous adenocarcinomas. The presence of acellular mesothelial reaction, acellular mucin pools and inflammation extending to the serosal surface causes considerable confusion and may result in over staging or under staging of mucinous adenocarcinoma. Pathogenesis and prediction of the mucin lakes behaviour prior and post chemoradiotherapy is unclear and requires future study but may impact surgical management.

Why wait for a colonoscopy? An easy cure.

OBJECTIVE: Three thousand five hundred and forty-nine patients are waiting for a colonoscopy in the Kent and Medway cancer network. New guidelines identify those who require surveillance for polyp, cancer, IBD and family history. Our hypothesis was that most of the patients on the waiting list would no longer need a colonoscopy if the new guidelines were applied. PATIENTS AND METHODS: We compared the ACPGBI guidelines for screening/surveillance colonoscopy with the indications in 411 notes of one hospital's waiting list and removed patients as appropriate. In the second part of study we analysed 192 patients attending colonoscopy in seven hospitals in the region and calculated the potential impact of the guidelines on our waiting lists. RESULTS: Of 411 patients on the waiting list in one hospital, only 98 (24%) needed to remain on the list. 142 (34%) were cancelled completely. One hundred and seventy-one (42%) were taken off the 'waiting' list and rebooked for a later date since according to the new guidelines the colonoscopy was not due yet. Of 192 colonoscopies actually performed during the study period in 7 hospitals of Kent and Medway cancer network, 72 (38%) were for surveillance. Two thirds of those were not in line with the guidelines. As a result of implementing the guidelines, waiting times for diagnostic colonoscopy fell from 12 to 4 weeks for urgent, and from 40 to 15 weeks for routine referrals. CONCLUSION: A quarter of the 8000 colonoscopies performed annually in our region are unnecessary when compared to the guidelines. More than three quarters of our waiting list could be removed by reviewing the notes. Implementing the guidelines in one cancer network would save pounds 1 million per year even on conservative estimates of pounds 500 per colonoscopy. It would also reduce the waiting times for diagnostic colonoscopy.

Acute pancreatitis: an under-recognized risk of percutaneous transhepatic distal biliary intervention.

OBJECTIVE: Percutaneous transhepatic biliary intervention (PTBI) plays an important role in the management of biliary obstruction, and this may be complicated by acute pancreatitis. The aim of this study was to assess the incidence of acute pancreatitis following PTBI. PATIENTS AND METHODS: Patients who underwent PTBI between January 1992 and December 2003 in a tertiary referral centre were identified from the hospital database. Patients who did not have their amylase measured post-procedure were excluded, as acute pancreatitis might have been missed. Acute pancreatitis was defined as hyperamylasaemia of three times or more above normal in association with abdominal pain. RESULTS: Over a 12-year period, 331 patients underwent 613 procedures. Serum amylase was measured after 134 procedures (21.9%) and was elevated in 26 of those (19.4%). There was no difference in the frequency of hyperamylasaemia between proximal and distal PTBI (14/73 [19.2%] vs 12/61 [19.7%] procedures, p=NS). However, acute pancreatitis developed after 4 of 61 (6.6%) distal PTBI (stent, n=3; internal-external catheter insertion, n=1) but not after proximal PTBI (cholangiography or external drainage) (p=0.041). The attacks were mild in three of the four patients. No pancreatitis-related deaths occurred. CONCLUSION: The risk of acute pancreatitis after distal PTBI is under-recognized and should be considered as a consent issue in patients scheduled for distal PTBI and when post-procedure abdominal pain ensues.

Mutagenic activity and DNA adduct formation by 1, 2-epoxy-3-(p-nitrophenoxy)propane, an HIV-1 protease inhibitor and GST substrate.

Acid protease inhibitor 1,2-epoxy-3-(p-nitrophenoxy)propane (ENPP) is commonly used in research as a substrate for glutathione-S-transferase activity (GST) and recently was found to inhibit human immunodeficiency virus 1 (HIV-1) protease. The question of DNA-adduct formation and mutagenicity was investigated and found that ENPP causes DNA damage and acts directly to induce mutagenicity in Salmonella. Using HPLC analysis, ENPP was shown to bind covalently to guanine residues. The Salmonella mutagenicity assay indicated that ENPP enhanced the mutation frequencies in the base-substitution strain TA00 by more than 20 times above the background. Its mutagenic potency was comparable to that of well-known carcinogens, N-methyl-N-nitrosourea (MNU) and aflatoxin B(1)-8,9-epoxide (AFB(1)-8,9-epoxide). The results suggest that ENPP should be classified as a mutagenic compound and a potential carcinogen.