Prognostic factors for survival after curative resection of Dukes' B colonic cancer.

AIM: Data on the prognostic factors for survival in patients with locally advanced, node-negative colon cancer are limited. This study aimed to determine which factors might predict survival in patients with Dukes' B (T3 or T4, N0) colon cancer. METHOD: One hundred and eighty (93 male; median age 75 [range, 38-96] years) consecutive patients who had resection of a primary Dukes' B (on final histopathological analysis) colonic cancer between 1998 and 2003 were studied. No patient received neoadjuvant chemotherapy. Multivariate Cox regression modelling was used to assess the prognostic value of variables. Median follow up was 85 (60-125) months. RESULTS: Thirteen (7%) patients had a perforation at presentation. The median distance from tumour to the nearest longitudinal resection margin was 6 (0.3-27) cm. One hundred and twenty-four (69%) patients had a lymph node yield of 12 or more nodes. Actual 5-year survival was 59%. On multivariate regression analysis, tumour perforation (perforation vs no perforation, 5-year survival, 23%vs 61%; hazard ratio (HR), 3.7; 95% confidence interval (CI), 1.6-8.4; P = 0.002), tumour-to-margin distance (< 5 cm vs ≥ 5 cm, 48%vs 65%; HR, 1.7; 95% CI, 1.1-2.7; P = 0.039) and older age (≥ 75 years vs < 75 years, 45%vs 72%; HR, 3; 95% CI, 1.8-5; P < 0.001) were independent significant variables. CONCLUSION: A lymph node yield of 12 or more nodes is not a significant prognostic factor for survival after resection of Dukes' B colonic cancer. Patients with tumour perforation or limited resection have worse prognosis.

Morbidity and mortality after closure of loop ileostomy.

BACKGROUND: A temporary loop ileostomy is commonly used to protect low pelvic anastomoses. Closure is associated with morbidity and mortality. This study investigated patterns of complications after loop ileostomy closure and factors associated with morbidity and mortality. METHOD: A review was performed of patients who underwent loop ileostomy closure between 1999 and 2005. RESULTS: Three hundred and twenty-five patients underwent closure of loop ileostomy. Reasons for primary surgery were: anterior resection for cancer (n = 160, 49%), ileal pouch-anal anastomosis (n = 114, 35%), diverticular disease (n = 25, 8%), Crohn's colitis (n = 4, 1%) and other conditions (n = 22, 7%). Overall mortality was 2.5% (n = 8) and morbidity was 22.8% (n = 74). Thirty-two patients (10%) developed small bowel obstruction, of whom seven required operative intervention. Overall, the re-operation rate in this series was 28 patients (8.6%). Thirteen (4%) patients had an anastomotic leak of whom 12 patients had re-operation. Preoperative anaemia was significantly associated with leakage (Hb < 11 g/dl; n = 65, P = 0.033). The leakage rate was lower after a stapled anastomosis than a hand-sutured anastomosis (4/203 vs 9/122; P = 0.039). Hypo-albuminaemia (albumin < 34 g/l) was significantly associated with mortality (n = 46, P < 0.001). CONCLUSIONS: Loop ileostomy closure is associated with morbidity and mortality. Anaemia and hypo-albuminaemia may be associated with poor outcome.

Minimally invasive management of chylous fistula after esophagectomy.

Chyle leak is an unwelcome complication of esophagectomy that is associated with a high mortality. The diagnosis of this condition may be difficult or delayed and requires a high index of suspicion. Management varies from conservative treatment with drainage, intravenous nutrition, treatment and prevention of septic complications, to re-operation, either by thoracotomy or laparotomy to control the fistula. To reduce the mortality, early surgical intervention is advised and a minimally invasive approach has recently been reported in several cases. From June 2002 through August 2005 we have used video-assisted thoracoscopic surgery to diagnose and treat chyle fistulas from 6/129 (5%) patients who underwent esophagectomy for resectable carcinoma of the esophagus or high-grade dysplasia. The fistula was successfully controlled in 5/6 cases by direct thoracoscopic application of a suture, clips or fibrin glue. One patient required a laparotomy and ligation of the cysterna chyli after thoracoscopy failed to identify an intrathoracic source of the leak. An early minimally invasive approach can be safely and effectively applied to the diagnosis and management of post-esophagectomy chylous fistula in the majority of cases. Open surgery may be appropriate where minimally invasive approaches fail or where the availability of such skills is limited.

Effect of surveillance of Barrett's oesophagus on the clinical outcome of oesophageal cancer.

BACKGROUND: Surveillance programmes for Barrett's oesophagus have been implemented in an effort to detect oesophageal adenocarcinoma at an earlier and potentially curable stage. The aim of this study was to examine the impact of endoscopic surveillance on the clinical outcome of patients with adenocarcinoma complicating Barrett's oesophagus. METHOD: Consecutive patients who underwent oesophageal resection for high-grade dysplasia or adenocarcinoma arising from Barrett's oesophagus were studied retrospectively. The pathological stage and survival of patients identified as part of a surveillance programme were compared with those of patients presenting with symptomatic adenocarcinoma. RESULTS: Seventeen patients in the surveillance group and 74 in the non-surveillance group underwent oesophagectomy. Disease detected in the surveillance programme was at a significantly earlier stage: 13 of 17 versus 11 of 74 stage 0 or I, three versus 26 stage II, and one versus 37 stage III or IV (P < 0.001). Lymphatic metastases were seen in three of 17 patients in the surveillance group and 42 of 74 who were not under surveillance (P = 0.004). Three-year survival was 80 and 31 per cent respectively (P = 0.008). CONCLUSION: Patients with surveillance-detected adenocarcinoma of the oesophagus are diagnosed at an earlier stage and have a better prognosis than those who present with symptomatic tumours.

Plasma and esophageal mucosal levels of vitamin C: role in the pathogenesis and neoplastic progression of Barrett's esophagus.

Antioxidants may protect against the development of esophageal adenocarcinoma. Blood samples and endoscopic biopsies (squamous, Barrett's, and gastric mucosa) were obtained from 48 Barrett's esophagus (BE) patients, while 48 age- and sex-matched controls provided blood samples only. Plasma concentrations of vitamins A, C, and E were measured in all subjects, while vitamin C was measured in relation to the type of mucosa. Plasma total vitamin C level, but not vitamin A or E, was lower in BE patients compared to controls (P = 0.014). Tissue levels of total vitamin C were significantly lower in Barrett's compared with squamous mucosa (P = 0.047). A positive association was observed between plasma vitamin C and dietary intake of vitamin C, while there was an inverse association with alcohol consumption. The lower levels of vitamin C in plasma of BE patients and in Barrett's mucosa compared with squamous mucosa are consistent with oxidative stress being of importance in the pathogenesis and neoplastic progression of BE.

Multivariate analysis of clinical, operative and pathologic features of esophageal cancer: who needs adjuvant therapy?

The failure of adjuvant therapy to significantly improve the prognosis of patients undergoing esophago-gastrectomy for cancer may be because of poor patient selection. We sought prognostic factors that would identify those patients who could benefit from adjuvant therapy. Data on 15 possible prognostic factors were prospectively collected on 225 patients undergoing esophago-gastrectomy at a single institution, and univariate and multivariate analyzes performed. T, N, M and overall UICC stage, differentiation, involvement of the circumferential resection margin and number of metastatic of lymph nodes were identified as significant prognostic factors by univariate analysis. Multivariate analysis revealed that the completeness of resection (R-category), ratio of metastatic to total nodes resected and the presence of vascular invasion were independently significant prognostic factors. Following R0 or R1 resection, patients with a metastatic to total lymph node ratio > 0.2 and /or the presence of vascular invasion have a poor prognosis, and the effects of adjuvant therapy in these patients should be studied.

Effects of the Magenstrasse and Mill operation for obesity on plasma plasminogen activator inhibitor type 1, tissue plasminogen activator, fibrinogen and insulin.

Plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (t-PA), fibrinogen and insulin were measured in 43 patients 3 years after they had undergone the Magenstrasse and Mill (MM) procedure and in 43 morbidly obese (MO) patients. Mean plasma PAI-1 was 61 ng/ml in the MO group compared to 30 ng/ml in the MM group (p < 0.0001); mean plasma t-PA was 10 ng/ml in the MO group compared to 7 ng/ml in the MM group (p < 0.001). Mean fibrinogen was 3.6 g/l in the MO group compared to 3.2 g/l in the MM group (p < 0.05). Mean plasma insulin levels were 32 U/ml in the MO group compared to 15 U/ml in the MM group. These changes suggest that use of the MM procedure may reduce mortality and morbidity from coronary heart disease in these high-risk obese patients.

Evaluation of POSSUM in patients with oesophageal cancer undergoing resection.

BACKGROUND: The Physiogical and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) has been used to produce a numerical estimate of expected mortality and morbidity after a variety of general surgical procedures. The aim of this study was to evaluate the ability of POSSUM to predict mortality and morbidity in patients undergoing oesophagectomy. METHODS: POSSUM predictor equations for morbidity and mortality were applied retrospectively to 204 patients who had undergone oesophagectomy for cancer. Observed morbidity and mortality rates were compared with rates predicted by POSSUM using the Hosmer-Lemeshow goodness-of-fit test. Evaluation of the discriminative capability of POSSUM predictor equations was performed using receiver-operator characteristic (ROC) curve analysis. RESULTS: The observed and predicted mortality rates were 12.7 and 19.1 per cent respectively, and the respective morbidity rates were 53.4 and 62.3 per cent. However, the POSSUM model showed a poor fit with the data both for the observed 30-day mortality (chi2 = 16.26, P = 0.002) and morbidity (chi2 = 63.14, P < 0.001) using the Hosmer-Lemeshow test. ROC curve analysis revealed that POSSUM had poor predictive accuracy both for mortality (area under curve 0.62) and morbidity (area under curve 0.55). CONCLUSION: These data suggest that POSSUM does not accurately predict mortality and morbidity in patients undergoing oesophagectomy and must be modified.

Gastric emptying after a new, more physiological anti-obesity operation: the Magenstrasse and Mill procedure.

The Magenstrasse and Mill (M&M) procedure for obesity is designed to preserve normal gastric emptying mechanisms. The hypothesis investigated in this study was that gastric emptying would be normal after the M&M gastroplasty. Gastric emptying studies were performed using both liquid and solid test meals, in ten morbidly obese patients (MO group) and in 13 patients after the M&M procedure (MM group). Seven people of normal weight served as controls and were matched for age, sex and height to the M&M and MO groups. Three years after the M&M procedure, mean (SD) weight loss was 42 (19) kg, with a mean loss of excess weight of 58% (20%). Gastric emptying half-times (t 1/2) are expressed in minutes, as median values (25th and 75th percentiles). The t 1/2 for solids was 97 (85-110) min in the control group, 140 (86-220) min in the MO group and 79 (46-150) min in the MM group. Median gastric emptying for solids was 0.7% (0.6%-0.8%) per minute in the control group, 0.5% (0.3%-0.8%) in the MO group and 0.9% (0.4%-1.4%) in the M&M group. There were no statistically significant differences in the emptying times of the three groups. It is concluded that the M&M procedure achieves acceptable weight loss, while preserving gastric emptying mechanisms and thus minimising possible side-effects such as vomiting, dumping and diarrhoea, which are common complications of gastric bypass procedures.

Circumferential resection margin involvement: an independent predictor of survival following surgery for oesophageal cancer.

BACKGROUND: For rectal carcinoma, the presence of tumour within 1 mm of the circumferential margin is an important independent prognostic factor for both local recurrence and survival. Similar prospective data have not been reported for oesophageal carcinoma and we wished to ascertain the prognostic importance of this variable following potentially curative resection for oesophageal carcinoma. AIM: To prospectively assess the impact of circumferential margin involvement (tumour within 1 mm) following potentially curative resection for oesophageal carcinoma. PATIENTS AND METHODS: In a prospective study, resection specimens of 135 patients treated with potentially curative oesophageal resection alone were studied for the presence of tumour within 1 mm of the circumferential margin (margin positive), using inked margins and cross sectional slicing of the specimen. All tumours were also staged using the 1987 UICC TNM classification. Patients were followed for a mean of 19 months, and overall and cancer specific survival analysed. RESULTS: The finding of tumour cells within 1 mm of the circumferential margin (CRM+) was a significant and independent predictor of survival following potentially curative oesophageal resection. Overall, 64 (47%) patients were CRM+. Median survival in this group was 21 months compared with 39 months in the CRM- group (p=0.015). The impact of CRM status on survival was only seen in patients with a low nodal metastatic burden (<25% nodes positive). The odds ratio for the risk of dying from oesophageal cancer was 2.08 when the CRM was involved (p=0.013). CONCLUSIONS: The presence of tumour within 1 mm of the circumferential margin following potentially curative resection for oesophageal carcinoma is an important independent prognostic variable and should be reported routinely.

Effects of the Magenstrasse and Mill operation for obesity on plasma leptin and insulin resistance.

BACKGROUND: We evaluated the effect of the Magenstrasse and Mill (M & M) operation--a new form of non-banded vertical gastroplasty-on weight loss, plasma leptin levels and insulin resistance. METHODS: Fasting plasma glucose, leptin and insulin levels were measured in 12 normal controls, 39 morbidly obese patients and 39 patients a median 3 years after the M & M procedure. Insulin resistance was calculated by the homeostasis model insulin resistance index. RESULTS: Body mass index mean (s.d.) decreased significantly (p < 0.0001), from 48(7) to 33(5) kg/m2, after the M & M procedure. Fasting plasma leptin concentration in the morbidly obese group was 37.9(15.4) ng/ml, significantly (p < 0.0001) higher than the control group (12.2(8.4)) and the M & M group (19.1(12.7)) ng/ml. Fasting plasma insulin concentrations were also significantly (p < 0.0001) higher in the morbidly obese group compared with than in the M & M group or in the control group: 35.5(22.3) mU/l, 15.5(7.1) mU/l and 13.6(3.4) mU/l, respectively. Insulin resistance was 9.6(7.2) in the morbidly obese group and 3.5(1.9) in the M & M group (p < 0.0001). CONCLUSION: This is one of the first studies to show that the decrease in insulin resistance after weight loss achieved by anti-obesity surgery is associated with significantly lower levels of plasma leptin.

Quality of life after the Magenstrasse and Mill procedure for morbid obesity.

BACKGROUND: The authors assessed the quality of life (QOL) of patients after the Magenstrasse and Mill (M-M) procedure for morbid obesity (MO) and compared this with the QOL of MO patients and non-obese controls. METHODS: Personal, postal and telephone questionnaire survey was completed by 82 patients after the M-M procedure, 35 MO patients and 20 normal controls. QOL was assessed by Short Form 36 (SF-36), Hospital Anxiety and Depression (HAD) scale, and obesity surgery related questionnaire. RESULTS: Physical, social and psychological well-being of patients was substantially better after the M-M compared with their MO counterparts. After the M-M procedure, patients were significantly less depressed but remained anxious when compared with morbidly obese patients. The majority of patients (88%) were pleased with the result of surgery. CONCLUSION: This study provides empirical evidence that the M-M procedure for MO leads to a substantially better QOL.

Relaparoscopy for the detection and treatment of complications of laparoscopic cholecystectomy.

BACKGROUND: Laparotomy remains the commonest intervention in patients with abdominal complications of laparoscopic surgery. Our own policy is to employ relaparoscopy to avoid diagnostic delay and unnecessary laparotomy. The results of using this policy in patients with suspected intra-abdominal complications following laparoscopic cholecystectomy are reviewed. METHODS: Data were collected from laparoscopic cholecystectomies carried out by five consultant surgeons in one center. Details of relaparoscopy for complications were analyzed. RESULTS: Thirteen patients underwent relaparoscopy within 7 days of laparoscopic cholecystectomy for intra-abdominal bleeding (2 patients) or abdominal pain (11 patients). The causes of pain were subhepatic haematoma (1), acute pancreatitis (1), small bowel injury (1), and minor bile leakage (6). In 2 patients no cause was identified. Twelve patients were managed laparoscopically and 1 patient required laparotomy. Median stay after relaparoscopy was 7 days (range 2 to 19). CONCLUSIONS: Exploratory laparotomy can be avoided by prompt relaparoscopy in the majority of patients with abdominal complications of laparoscopic cholecystectomy.

Barrett's oesophagus: results from a 13-year surveillance programme.

OBJECTIVES: To review the results of a 13-year surveillance programme of patients with Barrett's oesophagus to determine the incidence of adenocarcinoma. Although the risk of cancer in Barrett's oesophagus is well established, the magnitude of this risk is still controversial. DESIGN: Records of all patients with histologically confirmed Barrett's oesophagus in our 13-year surveillance programme were examined retrospectively. SETTING: Integrated gastroenterology and gastrointestinal surgical service in a large teaching hospital. PARTICIPANTS: During the study period, 597 patients had a diagnosis of Barrett's oesophagus; of these, 357 entered a yearly endoscopy and biopsy surveillance programme. MAIN OUTCOME MEASURES: The development of oesophageal adenocarcinoma. RESULTS: After a mean follow-up of 43 months, 12 patients, all with specialized epithelium, developed adenocarcinoma (11 men), an incidence for men of one cancer per 69 patient-years; and for women, one cancer per 537 patient-years follow-up (P < 0.01). If only patients with specialized mucosa were included the incidence of cancer was one per 95 patient-years of follow-up (men, one per 61 patient-years; women, one per 468 patient-years). CONCLUSIONS: Whilst the role of screening patients with Barrett's oesophagus remains controversial, this study supports the routine surveillance of male patients with specialized epithelium.

Total or subtotal gastrectomy for gastric carcinoma? A study of quality of life.

The aim of this study was to compare quality of life after total gastrectomy (TG) with that after subtotal gastrectomy (STG) for gastric carcinoma. The value of the routine use of TG de principe in the treatment of gastric carcinoma, wherever the tumor may be sited in the stomach, remains controversial. The advocates of TG contend that when it can be performed safely, with relatively low operative mortality and morbidity, it yields better long-term survival than STG. Most surgeons, however, believe that the routine use of TG increases both operative mortality and morbidity and the risk of nutritional deficiency in the long term, without improving survival. TG may also be associated with poorer outcome in terms of quality of life (QOL), but the evidence for this is tenuous. Forty-seven consecutive patients who had undergone potentially curative (R0) gastric resection for carcinoma were studied: 26 had undergone TG and 21 STG. A radical D2 lymph node dissection had been performed in each, and all patients were free from recurrence at the time of the study. QOL was measured before operation and 1, 3, 6, and 12 months after operation by means of five questionnaires to measure functional outcome: the Rotterdam symptom checklist (RSCL), the Troidl index, the hospital anxiety and depression (HAD) scale, activities of daily living score, and Visick grades. Before operation there was no significant difference in QOL between the two groups of patients. At 1 year after operation, however, patients who had undergone STG had a significantly better QOL than patients who had undergone TG: Their median RSCL score was lower (10 versus 19 respectively, p < 0.05), and their Troidl index was higher (11 versus 9 respectively, p < 0.05). The QOL of patients who underwent STG was also significantly better after operation than it had been before operation, whereas the QOL of the TG group was not significantly better after operation than before operation. The QOL of patients was found to be significantly better after STG than after TG for gastric carcinoma. Because operative mortality is greater and long-term survival is no better after TG than after STG, the latter is recommended as the treatment of choice for tumors of the distal stomach.

Assessment of microsatellite alterations in young patients with gastric adenocarcinoma.

BACKGROUND: Genetic factors are probably important in the development of gastric carcinoma in young patients (younger than 40 years). The authors investigated early onset primary gastric adenocarcinomas for the presence of microsatellite instability, which is a phenotypic marker for the hereditary nonpolyposis colon carcinoma syndrome. METHODS: DNA was extracted from archival microdissected carcinoma and corresponding normal tissue from 10 British gastric carcinoma patients age 19 to 39 years at the time of diagnosis. A panel of 12 microsatellite loci were amplified by fluorescent polymerase chain reaction and analyzed using an automated DNA sequencer. RESULTS: There was no evidence of microsatellite instability. In contrast, allelic imbalance was recorded at D3S966, D3S1076, D10S197, D11S904, P53, NM23, and DCC microsatellite loci. CONCLUSIONS: The authors reported ten cases of early onset gastric carcinoma that demonstrated allelic imbalance but no evidence of instability at microsatellite loci. It is unlikely that defective DNA mismatch repair is important in this group of young patients.

Delays in the diagnosis of oesophagogastric cancer: a consecutive case series.

OBJECTIVES: To examine the time taken to diagnose oesophageal or gastric cancer, identify the source of delay, and assess its clinical importance. DESIGN: Study of all new patients presenting to one surgical unit with carcinoma of the oesophagus or stomach. SETTING: University department of surgery in a large teaching hospital. SUBJECTS: 115 consecutive patients (70 men, mean age 66 years) with carcinoma of the oesophagus (27) or stomach (88). MAIN OUTCOME MEASURES: Interval from the onset of symptoms to histological diagnosis, final pathological stage of the tumour, and whether potentially curative resection was possible. RESULTS: The median delay from first symptoms to histological diagnosis was 17 weeks (range 1 to 168 weeks). 25% (29/115) of patients had a delay of over 28 weeks (median 39 weeks). Total delay was made up of the following components: delay in consulting a doctor (29%), delay in referral (23%), delay in being seen at hospital (16%), and delay in establishing the diagnosis at the hospital (32%). No relation was found between delay in diagnosis and tumour stage in patients with gastric cancer, but for oesophageal cancer those with stage I and II disease were diagnosed within 7 weeks compared with 21 weeks (P < 0.02) for those with stage III and IV disease. CONCLUSIONS: Long delays still occur in the diagnosis of patients with cancer of the stomach or oesophagus. Streamlined referral and investigation pathways are needed if patients with gastric and oesophageal carcinomas are to be diagnosed early in the course of the disease.

Spiral computed tomography and operative staging of gastric carcinoma: a comparison with histopathological staging.

BACKGROUND: Much controversy exists as to the value of computed tomography (CT) in the preoperative staging of gastric cancer, because of its limited ability to identify correctly lymph node (LN) metastases, invasion of adjacent organs, or hepatic and peritoneal metastases. Spiral CT scanners have a number of potential advantages over conventional scanners, including the absence of respiratory misregistration, image reconstruction smaller than scan collimation permitting overlapping slices and optimisation of intravenous contrast enhancement. AIM: To compare the performance of spiral CT and operative assessment against formal (TNM) pathological staging. PATIENTS AND METHODS: A study of 105 consecutive patients who underwent both spiral CT and operative staging was performed. All CT scans were reviewed by a radiologist who commented on tumour location and size, evidence of adjacent organ invasion, lymph node metastases to both N1 and N2 nodes, and evidence of hepatic and peritoneal metastases. All patients underwent careful operative assessment at the time of surgery, along the lines suggested by Rohde and colleagues. RESULTS: Spiral CT remained poor at identifying LN metastases to both N1 and N2 lymph nodes, with sensitivity ranging from 24 to 43%; specificity, however, was 100%. Operative staging was superior, with sensitivities between 84 and 94%, but specificity was much lower (63-74%). Spiral CT correctly detected 13 of 17 cases of invasion of either the colon or the mesocolon (sensitivity 76%) compared with 16 of 17 cases at operative staging (sensitivity 94%). Spiral CT correctly identified three of six cases with invasion of the pancreas (sensitivity 50%) compared with six of six cases on operative staging (sensitivity 100%). Spiral CT correctly identified 12 of 17 cases of peritoneal metastases (sensitivity 71%) and four of seven cases of hepatic metastases (sensitivity 57%). CONCLUSION: Whilst spiral CT remains poor at identifying lymph node metastases, it correctly identified most cases with invasion of either the colon or the mesocolon and half the cases of pancreatic invasion. It was of value in detecting peritoneal metastases and some cases with hepatic metastases. At present, at Leeds General Infirmary spiral CT is performed routinely on all patients with gastric cancer and a selective staging laparoscopy policy is adopted in those patients in whom the status of the peritoneal cavity and liver is in doubt.