Perioperative optimization of patients undergoing bariatric surgery.

Bariatric surgery is fast becoming an efficient and safe method of weight reduction, especially for patients in whom conservative measures have failed. As the obese population of the world increases, so will the number of patients requesting or requiring surgical weight loss methods. Bariatric patients however have numerous co-morbidities that make their operative course more difficult, and therefore is important to have a good understanding of the important issues surrounding their pre, peri and post operative management. This article aims to educate the reader about optimal management of the bariatric surgical patient.

Aortic thrombus after bariatric surgery.

Laparoscopic gastric bypass is becoming a frequently performed bariatric operation for patients with obesity. However, bariatric surgery has inherent risks and complications, which are further potentiated by the high risk nature of bariatric patients. These complications can be either site specific i.e. anastomotic leaks, or systemic i.e. venous thromboembolism, however they can intimately related. We present the case of one patient undergoing routine gastric bypass complicated postoperatively by recurrent intra-abdominal collections and sepsis, and aortic thrombosis with distal embolisation.

Metastatic malignant melanoma causing ileo-ileal intussusception.

We report here a rare case of metastatic malignant melanoma presenting as ileo-ileal intussusception. A 66-year-old man revealed a past medical history of excision of malignant melanoma, followed by axillary lymph node spread treated with block dissection and radiotherapy. He presented with symptoms of small bowel obstruction and subsequent CT revealed a likely nodular intussusception. Resection confirmed the intussusception and histological analysis confirmed the lead point as metastatic malignant melanoma. It has been reported that up to 5% of those with malignant melanoma will present with bowel metastases before death, yet autopsy studies estimate approximately 60% of those with melanomas have GI metastases. Intussusceptions themselves account for only 1-5% of intestinal obstructions in adults. The magnitude of silent metastases highlights the need to take those with a previous malignant melanoma presenting with GI symptoms seriously as surgery can affect survival.

The pharmacokinetics and safety of porfimer after repeated administration 30-45 days apart to patients undergoing photodynamic therapy.

BACKGROUND: Porfimer is an intravenous (i.v.) injectable photosensitizing agent used in the photodynamic treatment of tumours and of high-grade dysplasia in Barrett's oesophagus. AIM: To assess the pharmacokinetics as well as the safety profiles of porfimer after a first and a second dose administered 30-45 days apart in patients undergoing photodynamic therapy. METHODS: Nineteen patients (16 with cholangiocarcinoma) were enrolled. Porfimer sodium was administered by i.v. injection over 3-5 min. Blood samples were collected prior to starting i.v. drug injection and postdose at different time points after the first and second administrations. RESULTS: Porfimer exposure values after the second administration were statistically higher than those observed after the first administration, suggesting a slight accumulation of porfimer following repeated administration. The apparent mean elimination half-life of porfimer increased from 410 h after the first administration to 725 h after the second administration. The safety profiles of porfimer after a first and a second administration were similar and did not raise additional concern. Eight patients experienced nine serious adverse events. Only photosensitivity was deemed study-drug related. CONCLUSION: Porfimer appears to display a safe and tolerable profile when used in patients requiring a second photodynamic therapy within 45 days.

The effect of argon plasma coagulation ablation on esophageal motility and chemoreceptor sensitivity in Barrett's esophagus patients.

Patients with Barrett's esophagus usually demonstrate impaired esophageal motility, which affects acid clearance, together with reduced chemo-receptor sensitivity and symptom severity. Ablative endoscopic techniques are now used to eliminate Barrett's cells. The hypothesis for this study was that ablation with argon plasma coagulation (APC) may affect esophageal sensitivity and motility in patients with Barrett's esophagus, and the aim of this study was to assess differences in these parameters before and after APC treatment. Twenty patients with Barrett's esophagus were investigated before and after APC therapy. After standard pull through manometry, water bolus aliquots were given to assess primary peristalsis and rapid water and air bolus injections to assess secondary peristalsis. Sensitivity studies were carried out using weak solutions of either hydrochloric acid or sodium hydroxide, together with saline washouts. Onset time for typical symptoms (t), sensory intensity rating (I), and a sensory score (SS) = (t) x (I)/100 was observed. There were no significant differences in the lower esophageal sphincter pressures (13.6 mm Hg versus 12.6 mm Hg, P= 0.8) and successful test swallows (3 mm Hg versus 5 mm Hg, P= 0.5) before and after treatment, but there was a trend for secondary peristalsis to improve (air bolus 0 versus 2, P= 0.05, water bolus 0 versus 1, P= 0.07). Sensitivity studies showed a smaller sensitivity intensity rating to both acid (61 versus 31, P= 0.02) and alkaline (91 versus 64, P= 0.03) after treatment. In conclusion, we have shown no substantive changes in esophageal motility after ablation of Barrett's esophagus cells, but have demonstrated reduced sensitivity to reflux type solutions.

Seasonal palmar keratoderma in erythropoietic protoporphyria indicates autosomal recessive inheritance.

Erythropoietic protoporphyria (EPP) is an inherited disorder that results from partial deficiency of ferrochelatase (FECH). It is characterized clinically by acute photosensitivity and, in 2% of patients, liver disease. Inheritance is usually autosomal dominant with low penetrance but is recessive in about 4% of families. A cross-sectional study of 223 patients with EPP in the United Kingdom identified six individuals with palmar keratoderma. We now show that these and three additional patients, from six families, have an inherited subtype of EPP which is characterized by seasonal palmar keratoderma, relatively low erythrocyte protoporphyrin concentrations, and recessive inheritance. No patient had evidence of liver dysfunction; four patients had neurological abnormalities. Patients were hetero- or homoallelic for nine different FECH mutations; four of which were previously unreported. Prokaryotic expression predicted that FECH activities were 2.7-25% (mean 10.6%) of normal. Neither mutation type nor FECH activity provided an explanation for the unusual phenotype. Our findings show that palmar keratoderma is a clinical indicator of recessive EPP, identify a phenotype that occurs in 38% of reported families with recessive EPP that to our knowledge is previously unreported, and suggest that patients with this phenotype may carry a lower risk of liver disease than other patients with recessive EPP.

A brief overview of photodynamic therapy in Europe.

Photodynamic effect was a chance discovery early in the 1900s, demonstrating the lethal effects of light activated chemicals on living cells. Although the application of the principles of photodynamic effect to patients' treatment and what became photodynamic therapy (PDT) was practiced in 1960s and 1970s, clinical trials were only started in the 1980s, following successful synthesis of clinically usable photosensitisers (drugs) and the manufacturing of light sources. We briefly review and highlight some of the landmarks of the development of clinical PDT in Europe.

Preoperative shuttle walking testing and outcome after oesophagogastrectomy.

BACKGROUND: Objective assessment of cardiorespiratory reserve has been recommended before major surgery to identify patients with impaired oxygen delivery who may be at increased operative risk. Access to formal cardiopulmonary exercise (CPX) testing is limited outside larger centres. Following a previous audit of morbidity and mortality after oesophagectomy, we decided to add a simpler form of exercise test to our preoperative screen and review the outcomes. METHODS: Fifty-one patients who had surgical resection of an oesophageal cancer in our unit between April 2002 and April 2005 carried out an incremental shuttle walk exercise test before operation. Thirty-day outcome data were collected for each patient. RESULTS: Overall mortality in the group was 10%. No patient who walked 350 m or more died within 30 days. Five of the eight patients who could not achieve this distance died and two others remained in the critical care unit at 30 days. CONCLUSION: Preoperative shuttle walk testing using a standard protocol appears to be a sensitive indicator of operative risk in this group of patients. The apparent threshold value of 350 m is consistent with previously reported measures of functional capacity obtained using formal CPX testing.

Laparoscopic gastric bypass in a patient with malrotation of the intestine.

The increased prevalence of morbid obesity is associated with an increased prevalence of obesity co-morbidities. Bariatric surgery is generally the only effective treatment. Gastric bypasses are the most common bariatric operation in many countries, and more than half are performed laparoscopically. We discuss the challenges encountered in performing laparoscopic gastric bypass and cholecystectomy in a morbidly obese patient who was found to have malrotated small and large bowel when the procedure started. In the absence of past gastrointestinal symptoms and investigations, there is no way of diagnosing this anomaly preoperatively. However, when such a problem is posed at the time of surgery, it is safe to perform the planned operation if the surgeon has experience and skills in advanced laparoscopic techniques.

The effect of photodynamic therapy (PDT) on oesophageal motility and acid clearance in patients with Barrett's oesophagus.

BACKGROUND: Barrett's oesophagus is the major risk factor for oesophageal adenocarcinoma. It is proposed that long-term re-epithelialisation, which has been achieved following ablation using 5-aminolaevulinic acid (5-ALA) photodynamic therapy (PDT) may reduce the risk of malignant change. However, it is not known whether PDT modifies oesophageal motility. AIM: To assess oesophageal pH and motility before and after PDT ablation in treated and untreated areas of the oesophagus. METHODS: Twelve patients (10 male) with Barrett's oesophagus, median segment length 4 cm, were treated with PDT ablation. Twenty-four hours pH assessment and oesophageal manometry were performed before and 4-6 weeks after ablation. PDT was carried out using 635 nm red light, 4-6h after administration of 30 mg/kg 5-ALA. Proximal (untreated) and distal (treated) oesophageal resting pressure, wave amplitude, percentage peristalsis and percentage study time oesophageal pH<4, were assessed. Proton pump inhibitors (PPI) were administered throughout the study. RESULTS: There were no significant differences in oesophageal motility in treated or untreated areas of the oesophagus after PDT compared to pre-treatment values. Patients who continued to experience oesophageal acid exposure required more treatments to achieve complete Barrett's ablation. CONCLUSIONS: Oesophageal motility following ALA-PDT suggests a trend toward enhanced wave propagation however continued oesophageal acid exposure may affect PDT efficacy.

Loss of human leucocyte antigen class I and gain of class II expression are early events in carcinogenesis: clues from a study of Barrett's oesophagus.

BACKGROUND: Human leucocyte antigen (HLA) expression is altered in oesophageal carcinomas compared with normal tissue. It is unclear, however, whether this phenotype precedes malignant transformation or results as a consequence of it. AIM: To investigate HLA class I and II expression in Barrett's oesophagus and normal squamous oesophageal tissue. METHODS: Asian patients with Barrett's oesophagus (n = 64) and a control group (n = 60) with a normal oesophagus but without reflux symptoms were recruited using endoscopic and histopathological criteria. Tissue samples were stained with monoclonal antibodies specific for HLA-ABC, HLA-DR alpha chain or HLA-DP/DQ/DR, and scored semiquantitatively. The results of immunohistochemical staining were correlated with clinical and histopathological characteristics of patients. RESULTS: Marked expression of HLA-ABC was observed in 50% of Barrett's oesophagus sections as compared with 68.3% of controls (p = 0.038). HLA-DR staining was seen in 51.6% of Barrett's oesophagus samples versus 11.7% of controls (p<0.001). Expression of HLA-DP/DQ/DR was evident in 73.4% of oesophageal intestinal metaplasia tissue as opposed to 18.3% of controls (p<0.001). Importantly, a total loss of HLA-ABC and a concomitant gain of HLA-DP/DQ/DR expression were seen in 37.5% of patients with Barrett's oesophagus but in none of the controls (p<0.001). Interestingly, this phenotype was associated positively with dysplasia (adjusted p, p* = 0.031) but negatively with non-steroidal anti-inflammatory drug use (p* = 0.004). CONCLUSIONS: HLA class I expression is down regulated and class II expression is up regulated in Barrett's oesophagus. As these changes predate malignant transformation, altered major histocompatibility complex expression may be a key event in disease progression, possibly in facilitating evasion from immune surveillance.

Photodynamic therapy for Barrett's oesophagus and oesophageal carcinoma-How I do it.

We have considerable experience in the use of both ALA and Photofrin-induced photodynamic therapy in the treatment of Barrett's oesophagus (with and without dysplasia) and both early and advanced oesophageal carcinoma. The drugs used and the techniques vary depending on the condition being treated. The techniques and doses used for the various conditions are outlined here.

Human leucocyte antigen determinants of susceptibility to Barrett's oesophagus in Asians--a preliminary study.

BACKGROUND: Characteristic immune profiles have been demonstrated in gastro-oesophageal reflux disease. However, the genetic basis of gastro-oesophageal reflux disease remains unclear. AIM: To investigate whether certain human leucocyte antigen genes are associated with Barrett's oesophagus. METHODS: Asian patients of Malay, Chinese and Indian descent with Barrett's oesophagus (n = 59) and those without reflux symptoms and a normal oesophagus (n =60) were recruited prospectively using endoscopic and histopathological criteria. Human leucocyte antigen class I and II typing was performed using a polymerase chain reaction sequence-specific primers method. RESULTS: The HLA-B7 allele was present in 17% (10 of 59) of patients with Barrett's oesophagus when compared with 0% (zero of 60) of controls [P = 0.0006, corrected P = 0.0171, OR = 25.67]. Subgroup analysis revealed that the HLA-B7 allele was confined almost exclusively to Indians with Barrett's oesophagus, 43% (nine of 21) vs. 0% (zero of 19) Indian controls (P = 0.0014, corrected P = 0.0406, OR = 29.64). No class II associations, protective human leucocyte antigens or extended haplotypes for disease susceptibility were identified. CONCLUSIONS: Barrett's oesophagus in Asians, particularly Indians, is strongly positively associated with HLA-B7; reinforcing a genetic component to gastro-oesophageal reflux disease. A larger sample size and different ethnic populations should be genotyped to further confirm this association and identify possible additional risk factors in the human leucocyte antigen locus.

History of photodynamic therapy in Great Britain.

Although the concept photodynamic therapy has been recognised for over a century, it is only over the last 25 years that it has been used in Great Britain. The first applications in the UK were in 1981 by John Carruth, who treated patients with advanced ENT and skin cancers. The following year, he and Stephen Bown set up the British Medical Laser Association (BMLA). Since that time, the use of PDT in the UK has slowly expanded in all fields of medicine and surgery. In 1986, Bown set up the National Medical Laser Centre (NMLC) and later collaborated with Liverpool gastroenterologist, Neville Krasner, in animal studies on rat colon. In 1997, Keyvan Moghissi founded the Yorkshire Laser Centre (YLC) and began treating patients with advanced inoperable bronchial and oesophageal cancers. Stan Brown in Leeds set up the Centre for Photobiology and Photodynamic Therapy at the University of Leeds, working in close collaboration with the Yorkshire Cancer Research Centre. Other pioneers include Hugh Barr in Gloucester, Colin Hopper in London, Grant Fullarton in Glasgow and Roger Ackroyd, Malcolm Reed and Nicky Brown in Sheffield. PDT has now been used in the UK in the treatment of skin, oral, ENT, oesophageal, lung, bladder and gynaecological malignancies.

Endoscopic ablation of Barrett's oesophagus: a randomized-controlled trial of photodynamic therapy vs. argon plasma coagulation.

BACKGROUND: Barrett's oesophagus is the major risk factor for oesophageal adenocarcinoma. 5-Aminlevulinic acid-induced photodynamic therapy and argon plasma coagulation have been shown to be effective for ablating Barrett's oesophagus, but a comparative trial of these two modalities has not been reported. AIMS: To compare photodynamic therapy and argon plasma coagulation for the ablation of Barrett's oesophagus. METHODS: A total of 68 patients (54 male, 14 female; median age 61) with Barrett's oesophagus were randomized to photodynamic therapy (n = 34) or argon plasma coagulation (n = 34). Photodynamic therapy was performed using 5-aminlevulinic acid (30 mg/kg) and red light. Argon plasma coagulation was administered at a power setting of 65 W. Multiple treatment sessions were performed, with follow-up to 24 months. RESULTS: All patients showed a macroscopic reduction in the area of Barrett's oesophagus. This was greatest in the argon plasma coagulation group with 33 of 34 (97%) ablated, compared with 17 of 34 (50%) in the photodynamic therapy group; in the remainder, there was a reduction in the length of Barrett's oesophagus (median 50%, range: 5-90). Buried glands were found in 24% of photodynamic therapy patients, and in 21% of argon plasma coagulation patients. The median follow-up is 12 months (range: 6-24). CONCLUSIONS: Photodynamic therapy and argon plasma coagulation are both effective for ablating Barrett's oesophagus. Argon plasma coagulation appears more effective than photodynamic therapy, but the impact of both on carcinoma development requires larger studies with long-term follow-up.

5-Aminolaevulinic acid-induced photodynamic therapy and photodetection in Barrett's esophagus.

Barrett's esophagus is a precursor of adenocarcinoma of the esophagus. This cancer has the fastest growing incidence of any solid tumor in the Western world. Surveillance of Barrett's esophagus is routinely undertaken to detect early malignant transformation. However, ablative endoscopic treatments are available and these can obliterate the abnormal epithelium, allowing neosquamous regrowth. Photodynamic therapy using 5-aminolaevulinic acid (ALA) is such a technique. In this non-thermal method of ablation, ALA is metabolized to produce the photosensitizer protoprophyrin IX. This, together with light and oxygen, produces local tissue destruction. Fluorescence detection using ALA has also been used to identify areas of dysplasia and thus enhance positive biopsy yield. The use of ALA in photodynamic therapy and photodetection is reviewed.