Watch and wait for Rectal Cancer: A 9 year Experience.

Background: Neoadjuvant long course chemoradiotherapy has become the standard treatment for locally advanced rectal cancer. It can reduce tumour bulk, downstage, reduce the risk of local recurrence, and increase the possibility of clear resection margins. The aim of our study is to evaluate all patients over a 9 year period who underwent neoadjuvant chemoradiotherapy for rectal cancer and entered our watch and wait programme. Methods: Data were analysed from a prospective database for all patients diagnosed with rectal cancer over a 9 year period (2011-2019 inclusive). Findings: Over a 9 year period, 532 patients were treated for rectal cancer, with 180 patients receiving long course chemoradiotherapy. 61 (11%) patients entered a watch and programme as they had a complete clinical and radiological response following chemoradiotherapy. Within this programme, 40 patients (65%) remain disease free over the follow-up period (mean 38 months); 12 (20%) patients had regrowth and proceeded to surgery; and 9 (15%) proceeded to palliation due to being unfit for surgery or had distant metastatic disease. Overall (all cause) mortality was 18% during follow-up period in the watch and wait group. Conclusions: Neoadjuvant long course chemoradiotherapy is the standard treatment for locally advanced rectal cancer. 34% of our patient group who received long course chemoradiotherapy entered a watch and wait programme with the majority avoiding major rectal surgery.

Re-Staging Following Long-Course Chemoradiotherapy For Rectal Cancer: Does It Influence Management?

BACKGROUND: In patients with locally advanced or low rectal cancers, long-course chemoradiotherapy (LCCRT) is recommended prior to surgical management.1 The need for restaging afterwards has been questioned as it may be difficult to interpret imaging due to local tissue effects of chemoradiotherapy. The purpose of this study was to determine if restaging affected the management of patients receiving long-course chemoradiotherapy for rectal cancer. METHODS: A retrospective review of patients with rectal cancer discussed at the South Eastern Health and Social Care Trust Lower Gastrointestinal Multi-Disciplinary Team Meeting (LGIMDT) in 2013 who had received long-course chemoradiotherapy was performed. Patients were identified from the Trust Audit Department, LGIMDT notes and patient records. Imaging results and outcomes from meetings were obtained through the Northern Ireland Picture Archiving and Communications System® (NIPACS) and Electronic Care Record® (ECR). Data including patient demographics, initial radiological staging and LGIMDT discussion, restaging modality and result, outcome from post-treatment LGIMDT discussion and recorded changes in management plans were documented using a proforma. RESULTS: Seventy-one patients with rectal cancer were identified as having LCCRT in 2013 (M:F 36:35; age range 31 - 85 years). Fifty-nine patients were restaged following long-course treatment with computed tomography (CT) and magnetic resonance imaging (MRI). Twelve patients did not undergo restaging. Data was not available for 6 patients, one patient underwent emergency surgery, two patients were not fit for treatment, one failed to attend for restaging and two patients died prior to completion of treatment. Of the 59 patients restaged, 19 patients (32%) had their management plan altered from that which had been proposed at the initial LGIMDT discussion. The most common change in plan was not to operate. Ten patients had a complete clinical and radiological response to treatment and have undergone intensive follow-up. Nine patients had disease progression, with 3 requiring palliative surgery and 6 referred for palliative care. CONCLUSION: Of those patients who were restaged, 32% had their management plan altered from that recorded at the initial LGIMDT discussion. Seventeen per cent of patients in this group had a complete clinical and radiological response to treatment. Fifteen percent demonstrated disease progression. We recommend, therefore, that patients with rectal cancer be restaged with CT and MRI following long-course chemoradiotherapy as surgery may be avoided in up to 27% of cases.

Intra-abdominal drain fracture following pancreatic necrosectomy.

We describe a rare case of iatrogenic fracture of an intra-abdominal tube drain (Portex Robinson drain, Smiths Medical, Kent, UK) in a 74-year-old man. The fracture occurred at the level of an additionally placed fenestration and was identified on CT scanning prior to retrieval at planned re-laparotomy. This case highlights the potential dangers of modifying pre-formed drains and recommends against this practice.

Endoscopically assisted minimally invasive surgery for gallstones.

BACKGROUND: We present a case report of Bouveret syndrome followed by a review of the recent literature regarding the management of this condition. Bouveret syndrome is a form of gastric outlet obstruction secondary to a gallstone which has eroded through the gallbladder into the duodenum. It is an uncommon variant of gallstone ileus. Endoscopic methods have been described to extract the stone from the duodenum. METHODS: This is a case of an 85-year-old female patient who presented with a 1-week history of nausea, intermittent bilious vomiting and anorexia. Imaging confirmed the diagnosis of Bouveret syndrome caused by two large gallstones. Conventional endoscopic methods successfully extracted the impacted stones from the duodenum into the stomach but were unable to extract the stones from the stomach. A mini-transverse laparotomy and gastrotomy were performed to finally extract the stones.

Serous adenocarcinoma of the sigmoid mesentery arising in cystic endosalpingiosis.

This case report describes a Mullerian serous adenocarcinoma arising within a multoloculated cyst lined by ciliated serous-type epithelium located in the sigmoid mesentery. Twenty years previously the patient underwent a hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. The ovaries contained bilateral serous cystadenofibromas, and multiple cysts lined by ciliated serous-type epithelium were present in the omentum. The resection specimen 20 years later contained a 14 cm multiloculated cyst located in the sigmoid mesentery. This was lined largely by benign ciliated serous-type epithelium but a focus of well differentiated serous adenocarcinoma projected into the lumen. Two further peritoneal cysts were present, both of which were lined by ciliated serous-type epithelium. There was a coincidental renal cell carcinoma. This is a unique case of multiple omental, peritoneal, and retroperitoneal cysts (classified as cystic endosalpingiosis), one of which developed a focus of serous adenocarcinoma. Although rarely serous adenocarcinomas, similar to those occurring within the ovary, arise in the retroperitoneum, this is the first reported occurrence in association with a pre-existing benign lesion.

Efficacy of botulinum toxin in chronic anal fissure.

BACKGROUND: Chronic anal fissures (CAF) are caused by anal sphincter hypertonia leading to an ischaemic ulcer. By inducing temporary sphincter relaxation, botulinum toxin (Botox) injection has been shown to heal CAF in approximately 73-96% of cases in clinical trials. AIM: This study looks at the efficacy of Botox clinical practice. METHODS: The medical charts were reviewed of all patients with CAF treated with Botox (30iu injected into the sphincter complex in three 10iu aliquots) in the Ulster Hospital, Dundonald, Northern Ireland between March 1999 and November 2001. RESULTS: Fifty-one charts were identified. Four patients failed to attend for review and were excluded from the study. Of the remaining 47 patients, 37 (78.7%) were healed following Botox injection. 10 out of 37 (27.0%) developed a recurrent CAF after a median time of 16.0 months (IQR 3.8-20 months). Eight of these patients opted for repeat Botox injection, which was successful in 7 (87.5%) cases. No adverse effects were reported. CONCLUSION: Botox injection for the treatment of CAF is as effective in clinical practice as reported in clinical trials from specialist centres.

Management of severe acute pancreatitis.

BACKGROUND: Acute pancreatitis is still associated with significant morbidity and mortality. Current management guidelines are sometimes equivocal, particularly in relation to the surgical treatment of severe disease. This review assesses available investigative and treatment strategies to allow the development of a formalized management approach. METHODS: A literature review of diagnosis, staging and management of acute pancreatitis was performed. RESULTS AND CONCLUSION: Recent evidence has helped to clarify the roles of computed tomography, endoscopic retrograde cholangiopancreatography, prophylactic antibiotics, enteral feeding and fine-needle aspiration for bacteriology in the management of acute pancreatitis. Despite a relative shortage of prospective randomized trials there has been a significant change in the surgical management of acute pancreatitis over the past 20 years. This change has been away from early aggressive surgical intervention towards more conservative management, except when infected necrosis is confirmed. A formalized approach, with appropriate use of the various non-surgical and surgical options, is feasible in the management of severe acute pancreatitis.

Successful colonoscopy; completion rates and reasons for incompletion.

Factors such as poor bowel preparation or obstructing colonic disease may confound the reporting of colonoscopy completion rates, as these factors are outside of the control of the endoscopist performing the procedure. By adjusting for these factors when calculating a colonoscopy completion rate, it may be possible to make a more accurate assessment of a unit's or individuals' competence. Details of two thousand two hundred and sixteen colonoscopies performed by four consultants and their trainees between 1993-2000 were analysed retrospectively from a prospective endoscopy database. Crude (all cases) and adjusted (excluding poor bowel preparation and disease as causes of incompletion) rates were recorded for each sex, and by age according to cause. Overall crude and adjusted completion rates were 77.9% and 85.0% respectively. There was a significant difference between male and female completion rates due to a difference in the incidence of excess looping and intolerance of the procedure (adjusted rate 88.9% in males vs. 81.6% in females, p<0.05). There was a non-significant trend to lower completion rates in patients over 75 years of age compared to younger patients. Completion rates were significantly higher following bowel resection (adjusted rates 93.5% vs. 82.8%, p<0.05). There was no significant difference between completion rates for inpatient and outpatient referrals (P=0.36). Reporting colonoscopy completion rates by adjusting for factors such as poor bowel preparation and obstructing colonic disease allows for direct comparisons of completion rates reported by different units. Reporting completion rates in this way also highlights the effect of inadequate bowel preparation on successful colonoscopy.

Progress in the understanding and treatment of chronic anal fissure.

BACKGROUND: Chronic anal fissure is a common and painful condition associated with internal anal sphincter hypertonia. Reduction of this hypertonia improves the local blood supply, encouraging fissure healing. Surgical sphincterotomy is very successful at healing these fissures but requires an operation with associated morbidity. Temporary reduction in sphincter tone can be achieved on an outpatient basis by applying a topical nitric oxide donor (for example, glyceryl trinitrate) or injecting botulinum toxin into the anal sphincter. METHODS: A Medline database was used to perform a literature search for articles relating to the non-surgical treatment of chronic anal fissure. RESULTS: Review of the literature shows botulinum toxin injection to be more effective at healing chronic anal fissures than topical glyceryl trinitrate. Topical isosorbide dinitrate has not been directly compared with either of these two agents but has a healing rate approaching that of botulinum toxin injection. The main side effect of botulinum toxin injection is temporary faecal incontinence in approximately 2% of cases, whereas topical nitrates cause headaches in 20%-100% of cases. No long term side effects were identified with any of the medical treatments. CONCLUSION: Chemical sphincterotomy is an effective treatment for chronic anal fissure and has the advantages over surgical treatment of avoiding long term complications (notably incontinence) and not requiring hospitalisation.

Bactericidal/permeability-increasing protein attenuates systemic inflammation and acute lung injury in porcine lower limb ischemia-reperfusion injury.

OBJECTIVE: To investigate the role of recombinant bactericidal/permeability-increasing protein (rBPI21) in the attenuation of the sepsis syndrome and acute lung injury associated with lower limb ischemia-reperfusion (I/R) injury. SUMMARY BACKGROUND DATA: Gut-derived endotoxin has been implicated in the conversion of the sterile inflammatory response to a lethal sepsis syndrome after lower torso I/R injury. rBPI21 is a novel antiendotoxin therapy with proven benefit in sepsis. METHODS: Anesthetized ventilated swine underwent midline laparotomy and bilateral external iliac artery occlusion for 2 hours followed by 2.5 hours of reperfusion. Two groups (n = 6 per group) were randomized to receive, by intravenous infusion over 30 minutes, at the start of reperfusion, either thaumatin, a control-protein preparation, at 2 mg/kg body weight, or rBPI21 at 2 mg/kg body weight. A control group (n = 6) underwent laparotomy without further treatment and was administered thaumatin at 2 mg/kg body weight after 2 hours of anesthesia. Blood from a carotid artery cannula was taken every half-hour for arterial blood gas analysis. Plasma was separated and stored at -70 degrees C for later determination of plasma tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 by bioassay, and IL-8 by enzyme-linked immunosorbent assay (ELISA), as a markers of systemic inflammation. Plasma endotoxin concentration was measured using ELISA. Lung tissue wet-to-dry weight ratio and myeloperoxidase concentration were used as markers of edema and neutrophil sequestration, respectively. Bronchoalveolar lavage protein concentration was measured by the bicinclinoic acid method as a measure of capillary-alveolar protein leak. The alveolar-arterial gradient was measured; a large gradient indicated impaired oxygen transport and hence lung injury. RESULTS: Bilateral hind limb I/R injury increased significantly intestinal mucosal acidosis, intestinal permeability, portal endotoxemia, plasma IL-6 concentrations, circulating phagocytic cell priming and pulmonary leukosequestration, edema, capillary-alveolar protein leak, and impaired gas exchange. Conversely, pigs treated with rBPI21 2 mg/kg at the onset of reperfusion had significantly reduced intestinal mucosal acidosis, portal endotoxin concentrations, and circulating phagocytic cell priming and had significantly less pulmonary edema, leukosequestration, and respiratory failure. CONCLUSIONS: Endotoxin transmigration across a hyperpermeable gut barrier, phagocytic cell priming, and cytokinemia are key events of I/R injury, sepsis, and pulmonary dysfunction. This study shows that rBPI21 ameliorates these adverse effects and may provide a novel therapeutic approach for prevention of I/R-associated sepsis syndrome.

Circulating neutrophil priming and systemic inflammation in limb ischaemia-reperfusion injury.

BACKGROUND: Recruitment and activation of neutrophils is a key step in the development of local and systemic injury in lower limb ischaemia-reperfusion. We hypothesis that increased circulating neutrophil priming is responsible for systemic inflammation. METHODS: Anaesthetised ventilated swine (n = 6 per group) underwent mid-line laparotomy and were randomised to control group or bilateral external iliac artery occlusion for two hours followed by two and a half hours reperfusion (I/R group). Using luminol, respiratory burst activity was assayed with a BioOrbit Luminometer to detect whole blood chemiluminescence (CL) by stimulation with phorbol 1,2-myristate 1,3-acetate (PMA) in the absence or presence of tumour necrosis factor (TNF) respectively. PMN priming is expressed as the ratio of whole blood CL in the presence of TNF to that without. We measured plasma interleukin(IL)-6 and tumour necrosis factor alpha by bioassay as a measure of systemic inflammation. The alveolar-arterial (A-a) gradient was measured using the formula [(A-a)gradient = fraction inspired O2 x 710-(arterial pCO2/0.8)-arterial pO2], it is a measure of lung function, a large gradient being indicative of impaired oxygen transport and hence lung injury. RESULTS: Lower limb I/R caused significantly greater PMN priming, 0.83 +/- 0.14, compared to control group, 0.22 +/- 0.04, (p < 0.001). Plasma IL-6, a reliable indicator of systemic inflammation, was significantly increased in I/R group after two and a half hours of reperfusion, 1295.0 (833.9-2073.0) pg/L, compared to control, 382.9 (367.4-568.3) pg/L, (p < 0.005). Plasma tumour necrosis factor alpha was significantly elevated after one hour of reperfusion in the I/R group, 86.8 (48.7-106.6) pg/ml, compared to the control group, 32.7 (0.9-42.8) pg/ml, (p < 0.01). (A-a) gradient was significantly increased after IRI, 407.97 +/- 53.13, compared to the control, 183.19 +/- 45.75, (p < 0.005). Mean pulmonary artery pressure was significantly greater after IRI, 38.80 +/- 4.87 mmHg, compared to control, 27.86 +/- 1.92 mmHg, (p < 0.005). Data represents mean +/- standard error mean or median (interquartile range), statistical comparisons using one-way Anova with Student's "t"-test and Kruskall-Wallis Anova with the Mann-Whitney U test. CONCLUSIONS: Priming of neutrophils increases their circulating respiratory burst activity and ability to induce tissue injury. Systemic PMN priming during hind limb ischaemia-reperfusion injury is associated with the systemic inflammatory response syndrome.

Flexible sigmoidoscopy and the changing distribution of colorectal cancer: implications for screening.

BACKGROUND AND AIMS: There has been a significant proximal shift in the distribution of colorectal cancer (CRC) in Northern Ireland over recent decades. The aim of this study was to investigate the potential implications of this proximal shift in CRC distribution on the efficacy of flexible sigmoidoscopy (FS) as a screening tool. PATIENTS AND METHODS: The site distribution of 5153 CRCs was available from the Northern Ireland Colorectal Cancer Register for the period 1990-1997. Similar data on 1241 CRCs between 1976 and 1978 were available from a previous study. Data on the site reached by FS were obtained from a prospectively collected endoscopy database at one of Northern Ireland's main teaching hospitals for the period 1993-1998. RESULTS: There was a significant proximal shift in CRC distribution between the two periods (23.5% proximal to the splenic flexure between 1976 and 1978 v 36.7% between 1990 and 1997; p<0.001). The descending colon was visualised during 74.4% of FS examinations. By combining the observed extent of FS examination with CRC site distribution, it was calculated that FS could have visualised 68.8% of CRCs between 1976 and 1978 but only 56.0% between 1990 and 1997. Extrapolating these data to a Northern Ireland screening programme involving FS and faecal occult blood testing suggests that significantly more CRCs could have been detected between 1976 and 1978 than between 1990 and 1997 (51.7% v 48.2%, respectively; p=0.03). CONCLUSIONS: This study confirms the previously documented left to right shift in CRC distribution in Northern Ireland and demonstrates that if this shift continues, FS will become less successful as a screening tool than is currently predicted.

Antisense Bcl-2 oligonucleotide uptake in human transitional cell carcinoma.

OBJECTIVES: Antisense oligonucleotides (AO) downregulate Bcl-2 protein expression in various tumours if good target cell uptake is achieved. In this study, uptake of FITC labelled AO (FITC-AO) directed at Bcl-2 was examined in: (1) the RT4 bladder tumour cell line; (2) normal pig urothelium, and (3) human superficial bladder tumours. METHODS: In the RT4 cell line, uptake of FITC-AO, FITC-scrambled and FITC-sense oligonucleotides were quantified by flow cytometry at 4-hour intervals over 24 h. Uptake of FITC-AO was assessed in normal pig urothelium by flow cytometry after FITC-AO was infused for 1 h. Uptake of FITC AO was assessed in samples from 14 human superficial bladder tumours which were maintained in an ex vivo model. In samples from 6 tumours, uptake at 4 h was assessed using fluorescence microscopy. In samples from 8 separate tumours uptake every 4 h within the first 24-hour incubation period was assessed by flow cytometry. RESULTS: In the RT4 cell line the FITC-AO, FITC-scrambled and FITC-sense oligonucleotide uptake was similar. Disaggregated cells from the normal urothelium of the 3 pigs exhibited 33, 46 and 51% of cells staining positively for FITC-AO as determined by flow cytometry. All 6 tumour samples had detectable intracellular FITC-AO by fluorescence microscopy at 4 h. In the 8 tumours examined over the 24-hour incubation period, there was a range of percentages of positively staining cells. However, most tumours had a monotonic increase in intracellular fluorescence intensity that plateaued 16 h post-infusion. CONCLUSION: Antisense Bcl-2 oligonucleotides were readily taken up by superficial bladder cancer cells but the heterogeneous uptake in tumour samples needs to be considered when assessing the bioavailability of these drugs.

Ischemic preconditioning ameliorates ischemia- and reperfusion-induced intestinal epithelial hyperpermeability in rats.

We hypothesized that ischemic preconditioning (IPC) would ameliorate ischemia (I) and reperfusion (R)-induced intestinal mucosal hyperpermeability and that this effect would be diminished by lowering local adenosine concentrations using adenosine deaminase (ADA). The small intestine of anesthetized rats (group 1; n = 6) was divided into six 10-cm segments (A1-F1) each perfused by a different set of mesenteric branches. Segments D1-F1 were subjected to 3 cycles of IPC (2 min I/5 min R). Segments A1, B1, and C1 were excised at baseline, after 60 min of I (160), and after 60 min of I followed by 60 min of R (160/R60), respectively. Segment D1 was excised immediately after the last cycle of IPC, E1 was excised at 160 after IPC, and F1 was excised at 160/R60 after IPC. In group 2 (n = 6), the intestine was divided into five 10-cm vascularly isolated segments (A2-E2). Segment A2 was resected at baseline. The lumen of the remaining segments was filled with ADA (32 U/50 cm). Segment B2 was removed at the end of the experiment having been exposed to ADA for 150 min (ADA150). Segments C2, D2, and E2 were subjected to IPC. Segment C2 was excised immediately thereafter. Segments D2 and E2 were excised at 160 and 160/R60, respectively. Intestinal permeability to fluorescein isothiocyanate-labeled dextran (molecular weight 4000 D) was assessed ex vivo by using an everted gut sac method. IPC ameliorated intestinal hyperpermeability induced by 160 (43.0+/-7.6 vs. 70.4+/-8.3 nLmin/cm2; P = 0.024) and 160/R60 (20.2+/-3.7 vs. 69.5+/-10.8 nL/min/cm2; P= 0.003). IPC prevented ischemia-induced reduction in villus height. Treatment with ADA partially reversed the protective effect of IPC on the changes in permeability and villus height induced by I/R. We conclude that IPC partially protects against mucosal barrier dysfunction in rats subjected to mesenteric I/R. Adenosine is a mediator of IPC in the gut mucosa, but other factors also may be important.

Influence of hospital and clinician workload on survival from colorectal cancer: cohort study.

OBJECTIVE: To determine whether clinician or hospital caseload affects mortality from colorectal cancer. DESIGN: Cohort study of cases ascertained between 1990 and 1994 by a region-wide colorectal cancer register. OUTCOME MEASURES: Mortality within a median follow up period of 54 months after diagnosis. RESULTS: Of the 3217 new patients registered over the period, 1512 (48%) died before 31 December 1996. Strong predictors of survival both in a logistic regression (fixed follow up) and in a Cox's proportional hazards model (variable follow up) were Duke's stage, the degree of tumour differentiation, whether the liver was deemed clear of cancer by the surgeon at operation, and the type of intervention (elective or emergency and curative or palliative intent). In a multilevel model, surgeon's caseload had no significant effect on mortality at 2 years. Hospital workload, however, had a significant impact on survival. The odds ratio for death within 2 years for cases managed in a hospital with a caseload of between 33 and 46 cases per year, 47 and 54 cases per year, and >/=55 cases per year (compared to one with

A prospective randomised study comparing polyethylene glycol and sodium phosphate bowel cleansing solutions for colonoscopy.

Polyethylene glycol (Klean-Prep, Norgine) is widely used for bowel cleansing in the United Kingdom. This study compares the efficacy, acceptability and adverse effects of a polyethylene glycol (PEG) solution with sodium phosphate (Fleet Phospho-soda, De Witt) for bowel preparation prior to colonoscopy. Two hundred and nine consecutive patients were prospectively randomised to either PEG or sodium phosphate (SP) preparation. The endoscopist was blinded to the randomisation process. Fifty patients were excluded from the study because of previous colectomies or incomplete data. Of the remaining 159 patients, 88 had been randomised to the PEG group and 71 to the SP group. There was no difference in sex distribution between the groups. There were no significant differences between groups in terms of patient acceptability, side effects (nausea/vomiting and abdominal cramps), adequacy of bowel preparation and colonoscopy completion rates. 74% of the PEG and 70.4% of the SP group were rated by the endoscopist as having good or excellent bowel preparation. Sodium phosphate is well tolerated without additional side effects when compared with PEG solution. Both solutions were found to be equally effective in bowel cleansing.