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Background The DREAMtherapy (Dual REctal Angiogenesis MEK inhibition radiotherapy) trial is a novel intertwined design whereby two tyrosine kinase inhibitors (cediranib and selumetinib) were independently evaluated with rectal chemoradiotherapy (CRT) in an efficient manner to limit the extended follow-up period often required for radiotherapy studies. Patients and methods Cediranib or selumetinib was commenced 10 days before and then continued with RT (45 Gy/25#/5 wks) and capecitabine (825 mg/m2 twice a day (BID)). When three patients in the cediranib 15-mg once daily (OD) cohort were in the surveillance period, recruitment to the selumetinib cohort commenced. This alternating schedule was followed throughout. Three cediranib (15, 20 and 30 mg OD) and two selumetinib cohorts (50 and 75 mg BID) were planned. Circulating and imaging biomarkers of inflammation/angiogenesis were evaluated. Results In case of cediranib, dose-limiting diarrhoea, fatigue and skin reactions were seen in the 30-mg OD cohort, and therefore, 20 mg OD was defined as the maximum tolerated dose. Forty-one percent patients achieved a clinical or pathological complete response (7/17), and 53% (9/17) had an excellent clinical or pathological response (ECPR). Significantly lower level of pre-treatment plasma tumour necrosis factor alpha (TNFα) was found in patients who had an ECPR. In case of selumetinib, the 50-mg BID cohort was poorly tolerated (fatigue and diarrhoea); a reduced dose cohort of 75-mg OD was opened which was also poorly tolerated, and further recruitment was abandoned. Of the 12 patients treated, two attained an ECPR (17%). Conclusions This novel intertwined trial design is an effective way to independently investigate multiple agents with radiotherapy. The combination of cediranib with CRT was well tolerated with encouraging efficacy. TNFα emerged as a potential predictive biomarker of response and warrants further evaluation.

Purpose Cardiac dysfunction risk associated with intravenous trastuzumab (H IV) treatment may differ in real-world practice versus randomized trials. We investigated cardiac events in patients with HER2-positive early breast cancer (EBC) treated with H IV as adjuvant therapy in routine practice. Methods The observational study of cardiac events in patients with HER2-positive EBC treated with Herceptin (OHERA; NCT01152606) enrolled patients with stage I–IIIb disease eligible for H IV in the adjuvant setting per the European Summary of Product Characteristics (SmPC). Primary outcomes were symptomatic congestive heart failure incidence (CHF; New York Heart Association class II–IV) and cardiac death. Patient visits/assessments were per local practice. Results 3733 Patients received ≥ 1 H IV dose per local practice; 88.9% received H IV for > 300 days (median follow-up: ~ 5 years). Prior to disease recurrence (if any), symptomatic CHF occurred in 106 patients (2.8%); 6 (0.2%) cardiac deaths occurred (5 in patients with cardiac disease history). Median time to symptomatic CHF onset was 5.7 months (95% CI 5.3–6.5); 77/106 (72.6%) patients with symptomatic CHF achieved resolution. CHF incidence was higher in patients ≥ 65 years, and those with pre-existing cardiac conditions, hypertension, or left ventricular ejection fraction ≤ 55% at baseline. Conclusions OHERA is the largest prospective observational study to investigate the cardiac safety of H IV as adjuvant EBC therapy in a real-world setting. Symptomatic CHF and cardiac event incidences were consistent with randomized trials in this setting and baseline risk factors identified in the H IV European SmPC. Electronic supplementary material The online version of this article (10.1007/s10549-018-5058-6) contains supplementary material, which is available to authorized users.

The use of extracorporeal membrane oxygenation (ECMO) or extracorporeal life support (ECLS) has rapidly grown since the 1960s. Improvements in materials, device mechanics, the treatment of the underlying conditions, and provider proficiency, have resulted in better outcomes. The most common indication for ECLS in the pediatric population is viral pneumonia [ 1 ]. Complications secondary to ECLS are common with thromboembolic events (8%) and hemorrhage (27%) being amongst the most frequent [ 2 ]. We report a case of a 13-year-old female who presented to the Emergency Department with altered mental status and respiratory distress following a treatment course for influenza. She was diagnosed with multifocal pneumonia and developed fulminant respiratory failure requiring ECLS. The causative organism was later found to be Methicillin-Resistant Staphylococcus Aureus (MRSA). She was maintained on ECLS for 49 days and developed secondary complications of lung necrosis, an intrathoracic hematoma, and multiple bronchopleural fistulae. She was managed non-operatively for these complications until she stabilized enough to be weaned off ECMO. In this particular case, we resisted the urge to surgically intervene until she was decannulated. On day 86, she underwent a thoracotomy for evacuation of an intrathoracic hematoma and repair of a bronchopleural fistula. The patient survived and was discharged on hospital day 146. Currently, she is thriving and recovering well. We present this case due to its unusual duration of ECLS and to highlight the decision-making behind the initial non-operative management of the life-threatening complications that ensued.

Background/Purpose Laparoscopic gastrostomy (LG) and percutaneous endoscopic gastrostomy (PEG) are two common methods for gastrostomy feeding tube placement in children. There have been limited studies evaluating these surgical interventions in infants under 12 months of age. Methods This study is a retrospective review of 186 patients who underwent either LG or PEG placement over a 5-year period at a single institution. The primary outcome for this study was the complication rate between the two groups. Results Of 186 patients who underwent gastrostomy tube placements, n = 130 patients comprised the PEG cohort, and n = 56 made up the LG cohort. The demographics of the two cohorts were comparable in weight, age, and co-morbidities. The overall complication rate was 29.6% The breakdown of 31.5% complications in the PEG group vs. 25% in the laparoscopic group was not statistically different. However, the PEG group did have significantly more patients who required general anesthetic for additional procedures related to G tube placement. Conclusion Laparoscopy and endoscopy are both acceptable options for gastrostomy tube placements in infants. However, this study identifies that PEG placements are associated with significantly increased risk for the need of additional procedures requiring general anesthesia in this patient population. Level of Evidence

Background\ud Postmastectomy radiotherapy in patients with four or more positive axillary nodes reduces breast cancer mortality, but its role in patients with one to three involved nodes is controversial. We assessed the effects of postmastectomy radiotherapy on quality of life (QOL) in women with intermediate-risk breast cancer.\ud \ud Methods\ud SUPREMO is an open-label, international, parallel-group, randomised, controlled trial. Women aged 18 years or older with intermediate-risk breast cancer (defined as pT1–2N1; pT3N0; or pT2N0 if also grade III or with lymphovascular invasion) who had undergone mastectomy and, if node positive, axillary surgery, were randomly assigned (1:1) to receive chest wall radiotherapy (50 Gy in 25 fractions or a radiobiologically equivalent dose of 45 Gy in 20 fractions or 40 Gy in 15 fractions) or no radiotherapy. Randomisation was done with permuted blocks of varying block length, and stratified by centre, without masking of patients or investigators. The primary endpoint is 10-year overall survival. Here, we present 2-year results of QOL (a prespecified secondary endpoint). The QOL substudy, open to all UK patients, consists of questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23, Body Image Scale, Hospital Anxiety and Depression Scale [HADS], and EQ-5D-3L) completed before randomisation, and at 1, 2, 5, and 10 years. The prespecified primary outcomes within this QOL substudy were global QOL, fatigue, physical function, chest wall symptoms, shoulder and arm symptoms, body image, and anxiety and depression. Data were analysed by intention to treat, using repeated mixed-effects methods. This trial is registered with the ISRCTN registry, number ISRCTN61145589.\ud \ud Findings\ud Between Aug 4, 2006, and April 29, 2013, 1688 patients were enrolled internationally and randomly assigned to receive chest wall radiotherapy (n=853) or not (n=835). 989 (79%) of 1258 patients from 111 UK centres consented to participate in the QOL substudy (487 in the radiotherapy group and 502 in the no radiotherapy group), of whom 947 (96%) returned the baseline questionnaires and were included in the analysis (radiotherapy, n=471; no radiotherapy, n=476). At up to 2 years, chest wall symptoms were worse in the radiotherapy group than in the no radiotherapy group (mean score 14·1 [SD 15·8] in the radiotherapy group vs 11·6 [14·6] in the no radiotherapy group; effect estimate 2·17, 95% CI 0·40–3·94; p=0·016); however, there was an improvement in both groups between years 1 and 2 (visit effect −1·34, 95% CI −2·36 to −0·31; p=0·010). No differences were seen between treatment groups in arm and shoulder symptoms, body image, fatigue, overall QOL, physical function, or anxiety or depression scores.\ud \ud Interpretation\ud Postmastectomy radiotherapy led to more local (chest wall) symptoms up to 2 years postrandomisation compared with no radiotherapy, but the difference between groups was small. These data will inform shared decision making while we await survival (trial primary endpoint) results.\ud \ud Funding\ud Medical Research Council, European Organisation for Research and Treatment of Cancer, Cancer Australia, Dutch Cancer Society, Trustees of Hong Kong and Shanghai Banking Corporation.

Pectus excavatum is a common chest wall anomaly. Achieving optimal pain control is a priority for adolescents undergoing surgical correction of this condition. Options for pain control include the use of subcutaneous catheters (On-QWe identified patients who underwent pectus excavatum repair at our institution between January 2010 and August 2016. Patients were divided into two cohorts (epidural or On-Q pump). Patient charts were reviewed for length of stay, pain scores, pain medications, and complications.A total of 124 patients were included. Forty percent of patients used an epidural (n = 50), and 60% had the On-Q pump (n = 74). The average patient age was 15.6 years. The average Haller index was 4.3. The On-Q pump population had a significant decrease in postoperative length of stay (mean [M] = 4.86, standard deviation [SD] = 0.85) compared with the epidural population (M = 5.60, SD = 0.97); P ≤ .001. There was a significant difference observed in pain scores for patients on the epidural (M = 2.91, SD = 1.13) and On-Q pump (M = 3.81, SD = 1.19; P ≤ .001). There was n = 1 wound infection in each group.The use of bilateral subcutaneous infusion catheters is a safe and effective method for pain control in patients undergoing surgical correction of pectus excavatum. Even though the degree of pain control is not necessarily superior to epidurals, in this study, the catheters were associated with a shorter postoperative length of stay in this patient population and did not increase the incidence of complications.

HHT is an autosomal dominant vascular dysplasia, in which abnormalities of endothelial cells cause patients to develop mucocutaneous telangiectasias, and AVMs of the pulmonary, hepatic, and cerebral circulations. Pulmonary AVMs occur in more than 20% of patients with HHT, and presentation varies from simple diffuse telangiectasias to large complex structures. Surgical management is usually indicated for large pulmonary AVMs. Treatment options for pulmonary AVMs include therapeutic embolization, segmental or lobar resection of the affected lung, and less commonly lung transplantation. Here we report the first successful case of a bilateral lung transplant for a four-yr-old girl with HHT.

Background: The antenatal health-care given to pregnant women has great influence on the rates of perinatal death and morbidity. Amongst the different causes of perinatal mortality, low birth weight (LBW) is the single most significant factor therefore placenta from all the LBW babies (LBWB) should be examined routinely to find out the likely cause. Aims: The aims of this study were to assess the pathological changes in the placenta in association with LBWB.Materials and Methods: This is a Case control study performed at Medical College Allahabad,( MLN) India. In this study, 90 placentae were included. 30 placentae from full-term vaginally delivered babies, weighing more than 2500 g were included as the control group. 60 placentae belonged to babies whose birth weight was less than 2500 g (LBW). Weight of the baby was taken within the 1st h of birth and Apgar score was noted. Gross and microscopic examination of placentae was done. Statistical correlation of was carried out between them by using SPSS 18 version. Chi-square test with or without yate’s correction was used as and when required. P < 0.05 was taken as critical level of significance. Results: Placenta was circum-marginal in both groups. Attachment of cord was mainly central in the control group 90% (27/30), whereas eccentric attachment was prominent in patient group 66.67% (40/60). The difference was statistically significant (P < 0.001). Calcification and sub-chorionic fibrin deposition was seen in significantly higher numbers of placentae from patients than controls (P < 0.01) infarction and meconium staining were seen in placentae from patients only. Histologically placental ischemia, infarction and calcification were seen in significantly higher number of patients (P < 0.001, P < 0.001 and < 0.01 respectively). Fibrinoid necrosis, stromal fibrosis, placental dysmaturity and obstructive vasculopathy were seen in placentae from patients only. Conclusion: Placental pathology among LBW infants was high in comparison to control group. The findings suggest that chronic ischemia and associated secondary changes probably lead to improper perfusion and LBWB.Keywords: Calcification, Fibrinoid necrosis, Infarction, Intrauterine growth restriction, Low birth weight, Stromal fibrosis

BACKGROUND AND STUDY AIMS Figures for the prevalence of anorectal varices and portal hypertensive colopathy have varied considerably in the available studies of patients with cirrhosis, and few studies have observed these changes in patients with extrahepatic portal vein obstruction (EHPVO). Our aim was to investigate the colonic changes, if any, in patients with EHPVO and to compare them with those seen in patients with cirrhosis of the liver. PATIENTS AND METHODS A total of 50 patients with cirrhosis and 35 patients with EHPVO, all of whom had a history of at least one episode of bleeding from esophageal varices, underwent both upper gastrointestinal endoscopy and colonoscopy. RESULTS Anorectal varices were seen more commonly in patients with EHPVO than in patients with cirrhosis (63 % vs. 38 %, P < 0.03). Of the patients with anorectal varices, large anorectal varices were also more common in patients with EHPVO than in patients with cirrhosis (73 % vs. 32 %, P < 0.01). Colopathy was noted in 40 % of patients with EHPVO and in 62 % of patients with cirrhosis (P < 0.05). Of the patients with EHPVO, colopathy was noted in 27 % of patients who also had anorectal varices and in 61.5 % of patients without anorectal varices (P < 0.05). Similarly, patients with both cirrhosis and anorectal varices were found to have a lower prevalence of colopathy than cirrhotic patients without anorectal varices (42 % vs. 74 %, P < 0.03). CONCLUSIONS Anorectal varices are more common in patients with EHPVO, while portal hypertensive colopathy is more common in patients with cirrhosis. Large anorectal varices are also more common in patients with EHPVO than in patients with cirrhosis and there is an inverse relationship between anorectal varices and colopathy in both cirrhotic patients and patients with EHPVO.

Background and study aims Although it is known that obliteration of esophageal varices following endoscopic variceal band ligation results in an increase in the incidence of portal hypertensive gastropathy, the effect of variceal ligation on hemorrhoids, anorectal/colonic varices and portal hypertensive colopathy is not known. The aim of this study was to investigate the effect of endoscopic variceal band ligation on hemorrhoids, anorectal/colonic varices and portal hypertensive colopathy. Patients and methods A total of 60 consecutive patients with cirrhosis of the liver and portal hypertension were prospectively studied. Upper gastrointestinal endoscopy and full-length colonoscopy were carried out before the patients underwent endoscopic variceal band ligation for esophageal varices and after obliteration of the varices following band ligation. Results Obliteration of esophageal varices by endoscopic variceal band ligation did not affect the incidence of hemorrhoids (37 % before and after), anorectal varices (40 % before and after), and portal hypertensive colopathy (57 % before and after). Conclusions It is concluded that esophageal variceal band ligation does not affect the incidence of hemorrhoids, anorectal varices or portal hypertensive colopathy in patients with cirrhosis of the liver.

McGuire MM, Jones BA, Hull MA, Misra MV, Smithers CJ, Feins NR, Jenkins RL, Lillehei CW, Harmon WE, Jonas MM, Kim HB. Combined en bloc liver–double kidney transplantation in an infant with IVC thrombosis. Pediatr Transplantation 2011: 15: E142–E144. © 2010 John Wiley & Sons A/S. Abstract: We report a case of a pediatric en bloc liver-double kidney transplant in a patient with IVC thrombosis below the renal veins. The patient is an 11-month-old girl diagnosed with congenital nephrotic syndrome at two months of age. Multifocal liver masses were identified on routine ultrasound at eight months of age. Alpha fetoprotein level was 55 319. Biopsy confirmed hepatoblastoma. CT scan confirmed multiple lesions in both lobes, which would require liver transplantation for resection. She was also found to have thrombosis of her infrarenal IVC secondary to multiple central lines. She was listed for combined liver–kidney transplant and began chemotherapy. After four cycles of chemotherapy, she underwent bilateral nephrectomies followed by a combined en bloc liver-double kidney transplant from a size matched donor. In order to provide adequate venous outflow from the kidneys in the absence of a recipient infrarenal IVC, the donor liver and kidneys were procured en bloc with a common arterial inflow via the infrarenal aorta and common outflow via the suprahepatic IVC. Kidney transplantation in the absence of adequate recipient venous drainage may require unusual vascular reconstruction techniques. This case demonstrates a novel approach in patients who may require combined liver–kidney transplantation.

DT-diaphorase, a cytosolic reductase, has been implicated as an activator of chemotherapeutic prodrugs and a detoxifier of certain potentially carcinogenic xenobiotics. A common C to T nucleotide 609 substitution in DT-diaphorase cDNA has been associated with protein instability and reduced catalytic activity. The degree to which the allelic status of the substitution correlates with enzymatic activity was assessed in 45 normal human skin fibroblast strains using a PCR-RFLP assay. Included in this study was the 3437T strain, which is unique in that it is heterozygous for the polymorphism yet contains undetectable enzymatic activity. An allele-specific RT-PCR-RFLP technique attributed this phenomenon to exclusive DT-diaphorase mRNA expression from the variant allele. Overlap in activities was observed between individual strains homozygous for the wild-type allele and heterozygotes, but the former group displayed enzymatic activity that was on average 2-fold higher. Western blot analysis of the two strains in this panel that are homozygous for the variant allele revealed that they express relatively low amounts of DT-diaphorase protein, consistent with the role of the substitution in protein instability. This work confirms that genotypic status is a reliable initial estimate of DT-diaphorase activity. © 2000 Cancer Research Campaign

Patients on cardiac assist devices are often considered to be high-risk solid organ donors. We report the first case of a reduced size liver transplant performed using the left lateral segment of a pediatric donor whose cardiac function was supported by a Berlin Heart. The recipient was a 22-day-old boy with neonatal hemochromatosis who developed fulminant liver failure shortly after birth. The transplant was complicated by mild delayed graft function, which required delayed biliary reconstruction and abdominal wall closure, as well as a bile leak. However, the graft function improved quickly over the first week and the patient was discharged home with normal liver function 8 weeks after transplant. The presence of a cardiac assist device should not be considered an absolute contraindication for abdominal organ donation. Normal organ procurement procedures may require alteration due to the unusual technical obstacles that are encountered when the donor has a cardiac assist device.

Purpose: Bioreductively activated drugs have been used as antimicrobials, chemotherapeutic agents, and radiation sensitizers. The present paper is an overview of their mechanism of action and application in the treatment of cancer. Materials and Methods: Drugs such as nitroimidazoles, mitomycins, and benzotriazine di-N-oxides were a focus of this research. Studies have ranged from the chemistry of the reductive process of activation to in vitro and in vivo studies in rodent and human cells, through to clinical testing. The variety of techniques and test systems brought to bear on these compounds is a strength of this field of research. Results: A detailed chemical understanding of the mechanism of action of a variety of bioreductives is now available. The enzymatic processes by which these drugs are activated and the cofactors involved in this activation are becoming well understood. Recent advances have been made in the design and use of dual-function bioreductives, bioreductive triggers of drug activation, and DNA-targeted bioreductives. Significant success has been demonstrated clinically with bioreductive drugs, used in combination with radiation and front-line chemotherapeutic agents. The areas of antibody-directed enzyme prodrug therapy (ADEPT) and gene-directed enzyme prodrug therapy (GDEPT) are identified as new directions for bioreductive therapy. Conclusion: The use of bioreductively-activated drugs for the treatment of cancer has made steady progress. The success obtained clinically and the new molecular approaches currently being implemented promise significant advances in the future.

Expression of blood group A, B and H iso-antigens in oral mucosae was demonstrated by specific red cell adherence test in forty seven mucosal biopsies from oral cavity (14 normal, 10 leucoplakia and 23 squamous cell carcinomas). All normal mucosae gave a positive reaction whereas in malignancy only 6 cases of well differentiated squamous cell carcinomas were either weekly positive or showed a patchy reaction. Remaining cases were negative irrespective of their grading. In leucoplakia though the test was positive in all the cases, the intensity of adherence was less as compared to normal mucosa. The intensity of adherence was found to be directly related to the degree of cellular differentiation. Study of A, B and H isoantigens might help in deciding the prognosis in leukoplakia and/or early detection of malignancy.

Ascitic fluid total protein, albumin, cholesterol, their ascites/serum ratios, serum-ascites albumin and cholesterol gradients were measured for their ability to differentiate cirrhotic, malignant and tuberculous ascites in 76 patients. The mean +/- s.d. ascitic fluid total protein, albumin, cholesterol, their respective ascitic fluid/serum ratios in cirrhotic ascites were lower than malignant and tuberculous groups (P < 0.001 for each). The difference between malignant and tuberculous groups was significant for ascitic fluid/serum total protein (P < 0.05) and ascitic fluid/serum albumin (P < 0.01) only. Mean serum-ascites albumin gradient in cirrhotics was higher than in the malignant and tuberculous groups (P < 0.001 for each). The difference between malignant and tuberculous groups was significant (P < 0.01). Mean +/- s.d. serum-ascites cholesterol gradient in cirrhotics was higher than that in malignant and tuberculous groups (P < 0.001 for each). The difference between malignant and tuberculous groups was also significant (P < 0.01). Both serum/ascitic fluid total protein less than 0.5 and ascitic fluid cholesterol less than 55 mg/dL had 94% diagnostic accuracy for differentiating cirrhotic from malignant and tuberculous differentiating cirrhotic from malignant and tuberculous ascites. Serum ascitic fluid albumin gradient greater than 1.1 g/dL, ascitic fluid/serum albumin less than 0.65 and ascitic fluid albumin less than 2 g/dL had diagnostic accuracy of 92, 92 and 91%, respectively. Ascitic fluid total protein had diagnostic accuracy of 88%. None of the tests was able to differentiate between malignant and tuberculous ascites. Measurement of ascitic fluid cholesterol concentration is a simple method of differentiating cirrhotic from non-cirrhotic ascites.

Transversus abdominis plane (TAP) block is a new regional anaesthetic technique that blocks abdominal neural afferents by introducing local anaesthetic into the neuro-fascial plane between the internal oblique and the transversus abdominis muscles. We evaluated its analgesic efficacy in patients undergoing open appendicectomy in a randomized controlled double-blinded clinical trial.Fifty-two adult patients undergoing open appendicectomy were randomized to undergo standard care (n=26) or to undergo a right-sided TAP block with bupivacaine (n=26). In addition, all patients received patient-controlled i.v. morphine analgesia, regular acetaminophen, and non-steroidal anti-inflammatory drug, as required, in the postoperative period. All patients received standard anaesthetic, and after induction of anaesthesia, the TAP group received an ultrasound-guided unilateral TAP block. Each patient was assessed after operation by a blinded investigator at 30 min and 24 h after surgery.Ultrasound-guided TAP block significantly reduced postoperative morphine consumption in the first 24 h [mean (sd) 28 (18) vs 50 (19) mg, P0.002]. Postoperative visual analogue scale pain scores were also reduced in the TAP block group soon after surgery [median (IQR) 4.5 (3-5.3) vs 8.5 (7.5-10), P0.001] and at 24 h [5.2 (4-6.2) vs 8 (7-8.5), P0.001]. There were no complications attributable to the TAP block.Ultrasound-guided TAP block holds considerable promise as a part of a balanced postoperative analgesic regimen for patients undergoing open appendicectomy.

Background Despite aggressive chemotherapy, recurrence of disease remains the leading cause of death after liver transplantation (LTx) for hepatoblastoma (HB). Unfortunately, little is known about the effects of immunosuppression on recurrence and posttransplant outcomes. We hypothesized that minimal immunosuppression can be safely used in these recipients. Methods In 2004, we adopted a minimal immunosuppression regimen using daclizumab induction and tacrolimus monotherapy. Kaplan-Meier survival curves were generated. Results From 2004 to 2006, 6 children underwent primary LTx for HB with neoadjuvant and adjuvant chemotherapy. Patient survival was 100% at 12 months and at 24 months, without graft loss. One patient died 28 months after transplantation. Recurrence-free survival was 83% at 12 months and at 24 months. Despite minimal immunosuppression (IS), 4 of 6 HB recipients remained rejection-free. When compared to other LTx recipients receiving minimal IS, HB recipients trended to have better rejection-free survival (HB, 83% at 12 months and 62.5% at 24 months vs all others, 36% and 36%, respectively; P = .19). Conclusion Our short-term patient and graft survival rates are comparable to those reported for all HB recipients in the United Network for Organ Sharing database. Although not statistically significant, our rejection-free survival data suggest that HB recipients may be less likely to reject than other recipients.

Background Acute cellular rejection (ACR) is a common complication of small bowel transplantation (SBTx) and the major cause of graft loss. However, little is known regarding the genetic graft response to ACR in clinical transplants. In this study, we have determined a genetic expression profile of intestinal graft response to ACR after living related (LR) SBTx. Results By identifying the expression profiles of reported markers of rejection we were able to identify 57 genes that had significantly increased (more than twofold) expression in response to ACR. Known markers of rejection identified: MMP-9, MMP-2, VIP, IFNγ, IL-2R, MADCAM-1, HSP-60 , and HSP-70 all had greater than twofold increased expression after ACR diagnosed (week 3 to week 6). The newly identified genes were: IFI27, EPST11, APAF1, LAP3, STK6 , and MDK. Conclusion Newly identified up-regulated genes in response to ACR in small bowel graft are involved in the immune response, cell adhesion, neurogenesis, cell division and proliferation, DNA replication/repair, protein ubiqutin/proteolysis, and apoptosis. TNF α up-regulated early at week 2 biopsy may be an early genetic marker of ACR in SBTx.

Disseminated invasive aspergillosis is a serious and potentially lethal infectious complication of immunosuppressed individuals, including transplant recipients. We report here a successfully treated case of disseminated Aspergillus fumigatus infection involving the lungs, brain, and endocardium in a multivisceral transplant recipient. In addition to supportive measures, the patient was aggressively treated with a combination of three antifungal agents, and all immunosuppression was significantly lowered with close observation for rejection. After 3 months of therapy, the patient cleared the fungal infection, made a full recovery of his cerebral function, and was discharged to a rehabilitation facility.

Background and study aim Endoscopic band ligation has recently been used to control bleeding from a variety of nonvariceal upper gastrointestinal sources. However, it has not been used as salvage therapy in patients with peptic ulcer in whom injection therapy has failed to control bleeding. The objective was to study the role of band ligation in patients with bleeding peptic ulcer where injection therapy had failed. Patients and methods Endoscopic band ligation was attempted in patients with upper gastrointestinal bleeding from peptic ulcers in whom at least two attempts to control bleeding by injection therapy failed. Anti- Helicobacter pylori therapy was given to patients who were infected with the bacteria. Results Endoscopic band ligation could be performed in all the 11 patients in whom it was attempted. It was successful in controlling the bleeding in all patients. Over a mean (SD) follow-up of 23.1 (14.8) months none of the patients had recurrence of ulcer or bleeding. Conclusions Endoscopic band ligation is an effective means of controlling bleeding in patients with bleeding peptic ulcer in whom injection therapy is not successful. Band ligation followed by anti- H. pylori therapy is useful in preventing recurrence of ulcer and bleeding in such patients.

Primary gastric lymphoma is a rare tumour. It is thought that low grade gastric mucosa associated lymphoid tissue lymphoma has not been previously reported to occur in a patient with gastrojejunostomy. This report describes such a case. The patient presented with bleeding from non-healing stomal ulcers. The ulcers healed and there was regression of the tumour after eradication of Helicobacter pylori.

Background and study aim Colonic strictures are commonly encountered in patients with colonic tuberculosis. If the colonoscope cannot be negotiated past the stricture the procedure is abandoned, the colonic mucosa proximal to the stricture cannot be inspected, and therefore lesions in these locations may be missed. Patients and methods 130 patients with colonic tuberculosis were studied. Of these 22 (17 %) had impassable colonic strictures. These strictures were dilated, the colonic mucosa proximal to the strictures was then inspected, and biopsies were obtained from lesions of suspicious appearance. Results All strictures could be dilated. No abnormality was found in 11 patients. In the other 11 patients one or more additional findings were noted on colonoscopy after dilation. A second stricture was found in three patients. Nodularity and/or ulceration was observed in the colon proximal to the site of the primary stricture in ten patients. Dilation of the strictures and histological examination of the biopsy from target lesions of the proximal colon contributed to making the definitive diagnosis in five patients. The diagnosis was not altered in the remaining six patients. Conclusion Dilation of colonic strictures facilitates inspection of the colonic mucosa proximal to the strictures, enabling biopsy of target lesions. This approach offers important diagnostic clues and confirmation of the diagnosis in several patients in whom lesions might be missed if strictures are not dilated.

Background and study aims Colonic tuberculosis is generally diagnosed by colonoscopy and targeted biopsy of lesions. However, the diagnostic yield of colonic biopsies is not very good. So far as we are aware, there have been no studies investigating the role of biopsies from endoscopically normal-appearing cecum and terminal ileum in diagnosing colonic or ileal tuberculosis, or both. Patients and methods Patients with a clinical suspicion of colonic tuberculosis, in whom no endoscopic abnormalities were found on colonoscopy or ileoscopy, were included in the study. Multiple biopsies were obtained from the cecum and ileum. Results Fifty patients were studied. Intubation of the terminal ileum was possible in 43 patients (86 %). Histological examination of biopsies obtained from the cecum and terminal ileum showed noncaseating granuloma in two patients. Both of these biopsies were from the terminal ileum. In two other patients, collections of loosely arranged epithelioid cells were observed. This established the diagnosis in these four patients (8 %). In the remaining 46 patients, histology showed nonspecific inflammation in 18 patients (in the cecum in 15 and in the terminal ileum in seven). The other biopsies did not show any abnormalities (33 from the cecum, 34 from the terminal ileum). Conclusions Histological examination of biopsies from the normal-appearing cecum and terminal ileum is useful in a small but significant number of patients with colonic tuberculosis.

Background and Study Aims: Endoscopic sclerotherapy (EST) results in an increase in the prevalence of portal hypertensive gastropathy (PHG). However, the effects of sclerotherapy on hemorrhoids, anorectal or colonic varices and portal hypertensive colopathy are not known. The aim of this study was to investigate these effects. Patients and Methods: A total of 39 patients with portal hypertension were studied. Upper gastrointestinal endoscopy and full-length colonoscopy were carried out before the patients underwent EST for esophageal varices, and after obliteration of the varices following sclerotherapy. Results: The obliteration of esophageal varices by EST did not significantly affect the prevalence of hemorrhoids (32 % before and after), anorectal varices (45 % before and after) or portal hypertensive colopathy (60.5 % before and 66% after, P > 0.05). Conclusion: Obliteration of esophageal varices does not affect the prevalence of hemorrhoids, anorectal varices, or portal hypertensive colopathy.

Summary Fifty-five patients with oral submucosal fibrosis and an equal number of patients with no evidence of the disease were studied. All patients underwent upper gastrointestinal endoscopy and any abnormality was noted. Multiple oesophageal biopsies were obtained from the upper end of the oesophagus and from any endoscopically observed abnormality. The histological changes in the two groups were assessed blindly by an experienced histopathologist. Histological abnormalities were noted in the oesophageal mucosa in 2% of controls and 66% of patients with oral submucosal fibrosis (p < 0.0001). In the control group, acanthosis was seen in one patient, while in the patient group atrophy of the squamous epithelium was evident in 52%, hyperkeratosis in 52%, parakeratosis in 30%, dyskeratosis in 14%, acanthosis in 14%, and papillomatosis and mild dysplasia in 2% patients. Subepithelial collagenization was seen in 32 (64%) patients. The oesophageal abnormalities were seen more frequently in patients who had consumed Pan masala, Gutka, betel nut, tobacco or a combination of some or all of these, with or without betel leaf, for > or = 5 years compared to those consuming them for a shorter period of time (91% vs 46%, p < 0.001). It is concluded that oral submucosal fibrosis is not a disease confined to the oral cavity; the oesophagus may also be involved in about two-thirds of patients.

BACKGROUND AND STUDY AIMS It has recently been reported that in developed countries gastric outlet obstruction now predicts gastric malignancy. The aim of this study was to find out if this is the case in a developing country like India. PATIENTS AND METHODS Seventy-four patients with gastric outlet obstruction underwent upper gastrointestinal endoscopy and biopsy specimens were obtained from any suspicious looking lesions or from the most distal point at which the endoscope could be positioned. RESULTS In 56 patients (76%) the cause of the gastric outlet obstruction was malignant. On clinical and endoscopic appearance three patients were wrongly diagnosed as having malignancy when the cause, on endoscopic biopsy, was benign (tuberculosis n = 2, and immunoproliferative small intestinal disease n = 1). Twelve of the 18 patients with benign gastric outlet obstruction were managed conservatively with drugs and endoscopic balloon dilatation. CONCLUSION Even in a developing country like India, malignancy is the commonest cause of gastric outlet obstruction and endoscopic biopsy specimens should be obtained in all patients with gastric outlet obstruction because the occasional benign lesions can be managed conservatively.

The purpose was to determine whether magnification endoscopy (ME) accurately diagnosed rejection in living related small bowel transplants (LRSBTx) during initial morphological adaptation of segmental intestinal grafts. The small bowel recipient was a 44-year-old woman with short gut syndrome following multiple bowel surgeries for familial adenomatous polyposis. ME was enhanced by chromoendoscopy staining. Bowel mucosa was washed with acetic acid and stained with methylene blue for optimal visualization of mucosal villi and to improve the diagnostic yield of biopsies. The recipient underwent surveillance ME with biopsy 16 times through the ileostomy in the first 9 months following transplantation. The recipient developed diarrhea in the postoperative course, which led to the suspicion of rejection. ME findings of patchy villus blunting were consistent with biopsy samples that showed mild acute cellular rejection. Episodes of rejection were treated with high-dose immunosuppressants and steroids. Reversal of rejection was monitored by follow-up ME, which showed increased length of villi and normalization of morphology. Biopsy confirmed these findings. The first endoscopy, at 5 days posttransplant, showed no evidence of intestinal ischemia. LRSBTx involves early morphological adaptation of the recipient small bowel mucosa, characterized by an increased length of villi. ME is a reliable technique to follow adaptation and detect early rejection. The superior imaging of small bowel mucosa created by ME chromoendoscopy enables early diagnosis and delivery of more prompt antirejection therapy to prevent progression of rejection. ME also confirmed that segmental LRSBTx caused minimal ischemic injury to the recipient.

Background and Study Aims : Little is known about the colon in patients with portal hypertension. The present study was carried out in order to assess the prevalence of, and factors influencing, hemorrhoids, anorectal varices, and colopathy in these patients. Patients and Methods : Seventy patients with cirrhosis and portal hypertension, and seventy controls, were prospectively studied. Full-length colonoscopy was carried out in all cases, and the presence of hemorrhoids, anorectal varices, and colopathy was noted. Results : Hemorrhoids and anorectal varices were seen in 36% and 40% of patients, compared to 40 % and 0 % in the controls. The difference was statistically significant only for anorectal varices (p

It is well known that the vascular pathology leading to a myocardial infarction involves both the long term formation of an atherosclerotic plaque and a thrombus, which often leads to final closure of a coronary vessel. Numerous cells types, including the platelet, contribute to the development of an atherosclerotic lesion. Of considerable importance is the observation that various cardiovascular risk factor conditions, such as hypertension (HTN) and hyperlipidemia, alter the physiology of the platelets and, therefore, increase their activity level. For example, we have previously demonstrated that hypertriglyceridemia-producing infusions of parenteral lipid emulsions into rats induce 1) myofibroelastic changes indicative of early aortic atherogenesisl and 2) significant platelet hyperaggregability.2–4 Regarding hypertension, in general, the literature indicates an enhanced risk of thromboembolic disease in hypertensives, due to an increase in platelet function and a decrease in fibrinolytic activity. For example, Hoffmann et al.5 have shown that intraplatelet levels of cAMP are significantly lower in an untreated essential hypertension group, compared to that of healthy control subjects. Gleerup et al.6 have shown that the threshold for irreversible platelet aggregation is reduced in hypertensives, while tPA activity is significantly lower vs. that of normal patients.

Summary To compare the efficacy of imprint cytology, histology and CLO-test (for biopsy urease) in detecting Helicobacter pylori infection, antral biopsies were taken from 239 patients undergoing upper gastrointestinal endoscopy. Both imprint cytology and histology showed the presence of H. pylori in 215 (90%) patients. The sensitivity and specificity of imprint cytology vis-à-vis histology was noted to be 100%. The CLO-test was performed in 165 patients and was positive in 130 (79%) patients. The sensitivity and specificity of the CLO-test were 89% and 95%, respectively. The median time required for the CLO-test to become positive and for imprint was 60 minutes for each. The sensitivity of the CLO-test was reduced further in patients receiving colloidal bismuth subcitrate. Of the 27 patients receiving the drug the sensitivity of the CLO-test was only 9% after 4 weeks of therapy. However, the specificity was 100%. The sensitivity and specificity of imprint cytology were unaffected by the antimicrobial therapy and after 4 weeks of treatment were still 100%. It is concluded that the CLO-test has a lower sensitivity and specificity for diagnosing H. pylori infection compared to imprint cytology, which had a sensitivity and specificity equal to that of histology. Imprint cytology may be prepared as an adjunct to histology in patients in whom antral biopsies are taken as it offers a relatively quick diagnosis of H. pylori infection, is considerably cheaper than the CLO-test and does not require additional biopsy material.

To assess whether gallbladder motility is altered in patients with irritable bowel syndrome (IBS) or essential dyspepsia (ED), we studied gallbladder function in 25 healthy volunteers, 20 patients with IBS, and 22 with ED. By real time ultrasonography, we studied the following parameters: (a) fasting gallbladder volume, (b) maximum percent of gallbladder emptied, (c) time required for maximal contraction, (d) residual volume after maximal contraction, and (e) percent fasting volume at 2 h. All parameters, except fasting gallbladder volume, were measured after a high-fat meal. The fasting gallbladder volume, maximum percent of gallbladder emptied, time required for maximal contraction, residual volume after maximal contraction, and percent fasting volume at 2 h in controls and patients with IBS was 19.3 +/- 8.8 ml and 24.4 +/- 9.7 ml, 67.1 +/- 10.7% and 67.6 +/- 13.5%, 41 +/- 20.6 min and 49.7 +/- 25.3 min, 6.2 +/- 3.3 ml and 7.6 +/- 5.3 ml, and 38.1 +/- 12.2% and 40.7 +/- 14.5%, respectively. The differences between the two groups were statistically not significant. The corresponding values in patients with ED were 15.5 +/- 6.3 ml, 57.6 +/- 16.5%, 51.8 +/- 29.3 min, 6.1 +/- 3.2 ml, 44.1 +/- 17%, respectively. Compared with controls there was no statistically significant difference in these parameters, except the maximum percent of gallbladder emptied, which was significantly less than that in controls (57.6 +/- 16.5% vs. 67.1 +/- 10.7%; p less than 0.05). Therefore, we could not find that patients with IBS have any abnormality of gallbladder function; postprandially, patients with ED have submaximal contraction of the gallbladder.

Malignant mesothelioma of tunica vaginalis testis is a rare tumour usually associated with hydrocele. Until now only one case has been documented, where a pre-operative diagnosis was made by cytological examination of hydrocele fluid. We report one more case with pre-operative diagnosis using hydrocele fluid cytology.