Iain Tait

Liver cell adenoma and liver cell adenomatosis

During the last three decades liver cell adenoma and liver cell adenomatosis have emerged as new clinical entities in hepato-logical practice due to the widespread use of oral contraceptives and increased imaging of the liver. On review of published series there is evidence that 10% of liver cell adenomas progress to hepatocellular carcinoma, diagnosis is best made by open or laparoscopic excision biopsy, and the preferred treatment modality is resection of the liver cell adenoma to prevent bleeding and malignant transformation. In liver cell adenomatosis, the association with oral contraceptive use is not as high as in solitary liver cell adenomas. The risk of malignant transformation is not increased compared with solitary liver cell adenomas. Treatment consists of close monitoring and imaging, resection of superficially located, large (>4 cm) or growing liver cell adenomas. Liver transplantation is the last resort in case of substantive concern about malignant transformation or for large, painful adenomas in liver cell adenomatosis after treatment attempts by liver resection.

Socioeconomic status and stage at presentation of colorectal cancer

The stage at which colorectal cancer presents varies by district of residence 1 , but the reasons for this are not clear. We correlated stage at presentation with socioeconomic status in a stable UK population. The pathology reports of 905 consecutive patients with colorectal cancer who had undergone transabdominal resection in Tayside between Jan 1, 1991, and Sept 30, 1997, were reviewed. Dukes’ staging was derived from the reports. Socioeconomic status was determined with the Carstairs score, a deprivation index based on the postal-code areas from the 1991 census. 2 Of the 905 patients, 128 were excluded due to absence of pathology reports on lymph-node involvement, and/or no record of postal code. 15% (n=120) of cases were stage A at diagnosis, 43% (n=330) stage B, and 42% (n=327) stage C. Patients with distant metastases were not considered because local registry data could not be relied upon to identify the primary lesion in all patients presenting with advanced cancer. Patients were stratified in ascending order of social deprivation into four groups, according to the quartiles of Carstairs score. Group 4 was the highest score, and comprised people with the greatest socioeconomic disadvantage. The distribution of Dukes’ stages in each of these four groups is shown in the table. From group 1 to group 4, there was a diminishing proportion of stage A, and an increasing proportion of stages B and C; the only exception was in group 2, where there was a slightly higher percentage of stage A, and a lower percentage of stage C than in group 1. The differences were significant (

Photodynamic therapy is associated with an improvement in survival in patients with irresectable hilar cholangiocarcinoma

BACKGROUND The majority of patients with hilar cholangiocarcinoma have irresectable disease and require palliation with biliary stenting to alleviate symptoms and prevent biliary sepsis. Chemotherapy and radiotherapy have proved ineffective, but recent studies suggest photodynamic therapy (PDT) may improve the outlook for these patients. This prospective clinical cohort study has evaluated the efficacy of radical curative surgery, standard palliative therapy (stent +/- chemotherapy) and a novel palliative therapy (stent +/- Photofrin-PDT) in 50 consecutive patients treated for hilar cholangiocarcinoma over a 5-year period. METHODS Between January 2002 and December 2006, 50 patients with hilar cholangiocarcinoma were evaluated for treatment. Ten patients were considered suitable for curative resection (Cohort 1). Forty patients with irresectable disease were stratified into Cohort 2 - Stent +/- chemotherapy (n= 17); and Cohort 3 - Stent +/- PDT (n= 23). Prospective follow-up in all patients and data collected for morbidity, mortality and overall patient survival. RESULTS The median age was 68 years [range 44-83]. Positive cytology/histology was obtained in 28/50 (56%). One death in Cohort 1 occurred at 145 days after surgical resection. No treatment related-deaths occurred in Cohort 2 or 3, chemotherapy-induced morbidity in three patients in cohort 2, PDT-induced morbidity in 11 patients in cohort 3. Actual 1-year survival was 80%, 12% and 75% in Cohorts 1, 2 and 3, respectively. Mean survival after resection was 1278 days (median survival not reached). Mean and median survival was 173 and 169 days, respectively, in Cohort 2; and 512 and 425 days in Cohort 3. Patient survival was significantly longer in cohorts 1 and 3 (P < 0.0001; Log rank test). CONCLUSION This prospective clinical cohort study has demonstrated that radical surgery and palliative Photofrin-PDT are associated with an increased survival in patients with hilar cholangiocarcinoma.

Optimal surgical technique, use of intra-operative cholangiography (IOC), and management of acute gallbladder disease: the results of a nation-wide survey in the UK and Ireland

INTRODUCTION There is debate on optimal techniques that reduce bile duct injury during laparoscopic cholecystectomy (LC). A national survey of Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS) members was carried out to determine current surgical practice for gallstones, including the use of intra-operative cholangiography (IOC) or critical view of safety to reduce the risk of bile duct injury. SUBJECTS AND METHODS An anonymous postal survey was sent to all 417 AUGIS members. Data on grade of surgeon, place of work (district general hospital, teaching), subspecialty, number LC per year, use of IOC, critical view of safety, and management of stones detected during surgery were collated. RESULTS There was a 36% (152/417) response - 134 (88%) from consultant surgeons (36, HPB; 106,OG; 64, DGH; 88, teaching hospital). Of these, 38% performed > 100 LC per year, 36% 50-100 LC per year, and 22% 25-50 LC per year. IOC was routine for 24%; and selective for 72%. Critical view of Calots triangle was advocated by 82%. Overall, 55% first clip and divide the cystic artery, whereas 41% first clip and divide the cystic duct. Some 39% recommend IOC and 23% pre-operative MRCP if dilated common bile duct (CBD) is noted on pre-operative ultrasound. When bile duct stones are identified on IOC, 61% perform laparoscopic CBD exploration (LCBDE), 25% advise postoperative ERCP, and 13% perform either LCBDE or ERCP. Overall, 88% (n = 134) recommend index cholecystectomy for acute pathology, and this is more likely in a teaching hospital setting (P = 0.003). Laparoscopic CBD exploration was more likely to be performed in university hospitals (P < 0.05). CONCLUSIONS A wide dissection of Calots triangle to provide a critical view of safety is the technique most commonly recommended by AUGIS surgeons (83%) to minimise risk of bile duct injury, in contrast to 24% that recommend routine IOC. The majority (88%) of AUGIS surgeons advise index admission cholecystectomy for acute gallbladder disease.

Treatment of grade III anal intraepithelial neoplasia with photodynamic therapy: report of a case.

AbstractPURPOSE: We report the use of photodynamic therapy to treat a 53-year-old female with Grade III anal intraepithelial neoplasia. METHODS: Topical 5-aminolevulinic acid cream was applied to the affected area five hours before light treatment. The distribution of 5-aminolevulinic acid–induced protoporphyrin IX was identified by its characteristic red fluorescence. The lesion was treated by illumination with a 630-nm red laser light that used a total energy of 125 J/cm2 for approximately 17 minutes. RESULTS: Complete symptomatic relief was achieved after the first photodynamic therapy session, and macroscopic and microscopic ablation of dysplasia was achieved after a second session of photodynamic therapy. Healing was excellent, with no residual scarring or functional loss. CONCLUSION: Photodynamic therapy offers a simple, noninvasive method for treatment of anal intraepithelial neoplasia.

In vivo measurement of 5‐aminolaevulinic acid‐induced protoporphyrin IX photobleaching: a comparison of red and blue light of various intensities

Background: In recent years, 5‐aminolaevulinic acid (ALA) has become an increasingly popular photosensitizing drug for use in both photodynamic therapy (PDT) and photodetection (PD) of cancers. ALA metabolizes within tissue to form the photosensitizer protoporphyrin IX (PpIX). Like most photosensitizers, PpIX is fluorescent, and this fluorescence progressively decreases during PDT. This phenomenon is referred to as photobleaching.

The role of interventional radiology in the management of surgical complications after pancreatoduodenectomy

OBJECTIVES This study evaluates the role of interventional radiology (IR) in the management of postoperative complications after pancreatoduodenectomy (PD). METHODS A total of 120 consecutive patients were reviewed to identify IR procedures performed for early complications after PD. RESULTS Findings showed that 24 patients (20.0%) required urgent radiological or surgical re-intervention for early complications, including 11 instances of post-pancreatectomy haemorrhage (PPH), six intra-abdominal abscesses, two bile leaks, one pancreatic fistula and one bowel ischaemia. Three of 24 complications were managed by surgery and 21 were managed by IR. Two of 11 PPHs involved intraluminal haemorrhage (ILH) and nine involved intra-abdominal haemorrhage (IAH). One ILH was managed conservatively and one required surgical intervention. In eight of nine patients with IAH, the bleeding site was identified on computed tomography angiography, and endovascular stenting or coil embolization were performed. No patient required a re-look laparotomy following IR for haemorrhage or intra-abdominal abscess. Overall, three of 120 patients required an urgent re-look laparotomy for early complications. CONCLUSIONS Rates of major morbidity after PD remain high. However, many significant complications (PPH, pancreatic fistula, intra-abdominal abscess) can be managed by IR, reducing the need for reoperation. Re-look surgery is still required in a small percentage (2.5%) of patients.

Influence of cell interactions in a novel model of postnatal mucosal regeneration.

BACKGROUND AND AIMS--Conventional models of postnatal mucosal regeneration are cumbersome and limited: a novel model is described here. In addition, the influence of cell interactions on mucosal regeneration is examined within the model. METHODS--Postnatal rat small intestinal mucosa was digested by enzymes to yield heterotypic cell aggregates (CA). CA colony forming ability, growth, and limited cytodifferentiation were assessed in vitro. CA were transplanted subcutaneously and retrieved for histological examination at staggered intervals to assess neomucosal morphogenesis and cytodifferentiation in vivo. Cell interactions in CA were disrupted by enzymes, thus producing cell suspensions (CS). Regeneration by CA and CS were compared. RESULTS--CA produced proliferative colonies in vitro and showed a temporal sequence of neomucosal morphogenesis and differentiation in vivo. CA colonies were more numerous within 24 hours of primary culture and had greater cellularity by 96 hours than CS colonies. Alkaline phosphatase was expressed only by 258 of 696 CA colonies (37%). CA subcutaneous grafts (48 of 56 (87%)) regenerated small intestinal neomucosa while CS were unsuccessful. CONCLUSION--These methods provide a model of mucosal regeneration which includes constituent processes of colony formation, growth, neomucosal morphogenesis, and cytodifferentiation. Preservation of cell interactions within CA seems advantageous to regeneration within the model.

Does neomucosa induced by small bowel stem cell transplantation have adequate function

Small intestinal epithelium digests and absorbs nutrients. Crypt stem cell transplantation can generate neomucosa with normal morphology, but the digestive and absorptive capacities of this neomucosa are unknown. This study evaluates stem cell induced neomucosal brush border digestive enzyme activity and nutrient transport function. Rodent small intestinal epithelial stem cells were isolated by enzymatic digestion, then grafted to inbred recipients. Grafts were retrieved at 25 days, and apical brush border membrane vesicles prepared for quantitative assays. Neomucosal lactase, sucrase, aminopeptidase N, and alkaline phosphatase activity was determined by incubation with enzyme specific substrate. Neomucosal sodium dependent D-glucose transport was evaluated by incubation with D-[U-14C] glucose. Comparative assays were performed in age-matched control intestine. Neomucosal digestive enzyme activities and D-glucose transport were all similar in neomucosa and control small intestine.

Endoscopic fluorescence imaging and point spectroscopy system for the detection of gastro-intestinal cancers

We describe a combined endoscopic fluorescence imaging and spectroscopy system for the detection of gastro-intestinal cancers, utilizing the fluorescence from aminolaevulinic acid-induced protoporphyrin IX. Both the imaging and spectroscopy systems are controlled by a single desktop PC, which also carries out image processing and stores spectral data, enabling real-time display of images and spectra on one monitor. These systems have been tested in vivo and the results illustrate the potential of both systems in the detection of early cancers. Preliminary testing of the combined system using a foam model has shown that the combined system may better facilitate cancer detection than the use of either system individually.