(18)F-fluorodeoxyglucose positron-emission tomography-computed tomography to diagnose recurrent cancer.

BACKGROUND: Sometimes the diagnosis of recurrent cancer in patients with a previous malignancy can be challenging. This prospective cohort study assessed the clinical utility of (18)F-fluorodeoxyglucose positron-emission tomography-computed tomography ((18)F-FDG PET-CT) in the diagnosis of clinically suspected recurrence of cancer. METHODS: Patients were eligible if cancer recurrence (non-small-cell lung (NSCL), breast, head and neck, ovarian, oesophageal, Hodgkin's or non-Hodgkin's lymphoma) was suspected clinically, and if conventional imaging was non-diagnostic. Clinicians were asked to indicate their management plan before and after (18)F-FDG PET-CT scanning. The primary outcome was change in planned management after (18)F-FDG PET-CT. RESULTS: Between April 2009 and June 2011, 101 patients (age, median 65 years; 55% female) were enroled from four cancer centres in Ontario, Canada. Distribution by primary tumour type was: NSCL (55%), breast (19%), ovarian (10%), oesophageal (6%), lymphoma (6%), and head and neck (4%). Of the 99 subjects who underwent (18)F-FDG PET-CT, planned management changed after (18)F-FDG PET-CT in 52 subjects (53%, 95% confidence interval (CI), 42-63%); a major change in plan from no treatment to treatment was observed in 38 subjects (38%, 95% CI, 29-49%), and was typically associated with (18)F-FDG PET-CT findings that were positive for recurrent cancer (37 subjects). After 3 months, the stated post-(18)F-FDG PET-CT management plan was actually completed in 88 subjects (89%, 95% CI, 81-94%). CONCLUSION: In patients with suspected cancer recurrence and conventional imaging that is non-diagnostic, (18)F-FDG PET-CT often provides new information that leads to important changes in patient management.

Usefulness of Ki-67, Mitoses, and Tumor Size for Predicting Metastasis in Carcinoid Tumors of the Lung: A Study of 48 Cases at a Tertiary Care Centre in Canada.

Background. Evaluation of Ki-67 index in lung carcinoid tumors (LCTs) has been of interest in order to identify high risk subsets. Our objectives are (1) to evaluate the usefulness of Ki-67 index, mitoses, and tumor size in predicting metastasis and (2) to compare the Manual Conventional Method (MCM) and the Computer Assisted Image Analysis Method (CIAM) for Ki-67 calculation. Methods. We studied 48 patients with LCTs from two academic centres in Canada. For Ki-67 calculation, digital images of 5000 cells were counted using an image processing software and 2000 cells by MCM. Mitoses/10 HPF was counted. Results. We had 37 typical carcinoids (TCs) and 11 atypical carcinoids (ACs). 7/48 patients developed metastasis. There was a positive relationship between metastasis and carcinoid type (P = 0.039) and metastasis and mitoses (≥2) (P = 0.017). Although not statistically significant, the mean Ki-67 index for ACs was higher than for TCs (0.95% versus 0.72%, CIAM, P = 0.299). Similarly, although not statistically significant, the mean Ki-67 index for metastatic group (MG) was higher than for nonmetastatic group (NMG) (1.01% versus 0.71% by CIAM, P = 0.281). However when Ki-67 index data was categorized at various levels, there is suggestion of a useful cutoff (≥0.50%) to predict metastasis (P = 0.106, CIAM). A significantly higher proportion of patients with mitosis ≥2 and Ki-67 index ≥0.50% had metastasis (P = 0.033) compared to other patients. Similarly patients with tumor size ≥3 cm and Ki-67 ≥0.50% had a greater percentage of metastases than others (P = 0.039). Although there was a strong correlation between two (MCM versus CIAM) counting methods (r = 0.929, P = 0.001), overall the calculated Ki-67 index was slightly higher by MCM (range 0 to 6.4, mean 1.5) compared to CIAM (range 0 to 2.9, mean 0.75). Conclusion. This study confirms that mitoses ≥2 is a powerful predictor of metastasis in LCTs. Although this is a small sample size, there is suggestion that analysis of Ki-67 index along with mitoses and tumor size may be a useful adjunct for predicting metastasis in LCTs.

What are the factors that predict outcome at relapse after previous esophagectomy and adjuvant therapy in high-risk esophageal cancer?

OBJECTIVES: The present study investigated factors affecting outcome at relapse after previous surgery and adjuvant chemoradiation (crt) in high-risk esophageal cancer patients. PATIENTS AND METHODS: From 1989 to 1999, we followed high-risk resected esophageal cancer patients who had completed postoperative crt therapy. Patients who relapsed with a disease-free interval of less than 3 months were treated with palliative crt when appropriate. Patients with a disease-free interval of 3 months or more were treated with best supportive care. Post-recurrence survival was estimated using the Kaplan-Meier technique, and statistical comparisons were made using log-rank chi-square tests and Cox regression. RESULTS: Of the 69 patients treated with adjuvant crt after esophagectomy, 46 experienced recurrence. Median time to relapse was 28 months (range: 0.1-40 months). Among the 46 relapsed patients, median age was 61 years (range: 37-82 years), and 42 were men. At the initial staging, 44 of 46 were node-positive; 31 of 46 had adenocarcinoma. In 33 of 46, post-esophagectomy resection margins were clear. Median follow-up after recurrence was 30.5 months (range: 1.3-100 months). Median overall survival after recurrence was 5.8 months, and the 12-month, 24-month, and 36-month survival rates were 20%, 10%, and 5% respectively. Of the prognostic factors analyzed, only resection margin status and interval to recurrence were statistically significant for patient outcome in univariate and multivariate analysis. Patients who had positive resection margins and who relapsed 12 or fewer months after surgery and adjuvant crt had a median post-recurrence overall survival of 0.85 months as compared with 6.0 months in other patients (more than 12 months to relapse, or negative resection margins, or both; log-rank p = 0.003). CONCLUSIONS: Resection margin status and interval to disease relapse are significant independent prognostic factors for patient outcome after adjuvant crt therapy.

Postoperative extended-volume external-beam radiation therapy in high-risk esophageal cancer patients: a prospective experience.

BACKGROUND AND PURPOSE: Extended-volume external-beam radiation therapy (RT) following esophagectomy is controversial. The present prospective study evaluates the feasibility of extended-volume RT treatment in high-risk esophagectomy patients with a cervical anastomosis receiving postoperative combined chemoradiation therapy. PATIENTS AND METHODS: From 2001 to 2006, 15 patients with resected esophageal cancer were prospectively accrued to this pilot study to evaluate the adverse effects of extended-volume RT. Postoperative management was carried out at London Regional Cancer Program. Eligibility criteria were pathology-proven esophageal malignancy (T3-4, N0-1), disease amenable to surgical resection, and esophagectomy with or without resection margin involvement. Patients with distant metastases (M1) and patients treated with previous RT were excluded. All 15 study patients received 4 cycles of 5-fluorouracil-based chemotherapy. External-beam RT was conducted using conformal computed tomography planning, with multi-field arrangement tailored to the pathology findings, with coverage of a clinical target volume encompassing the primary tumour bed and the anastomotic site in the neck. The radiation therapy dose was 50.40 Gy at 1.8 Gy per fraction. The RT was delivered concurrently with the third cycle of chemotherapy. The study outcomes-disease-free survival (DFS) and overall survival (OS)-were calculated by the Kaplan-Meier method. Treatment-related toxicities were assessed using the U.S. National Cancer Institute's Common Toxicity Criteria. RESULTS: The study accrued 10 men and 5 women of median age 64 years (range: 48-80 years) and TNM stages T3N0 (n = 1), T2N1 (n = 2), T3N1 (n = 11), and T4N1 (n = 1). Histopathology included 5 adenocarcinomas and 10 squamous-cell carcinomas. Resection margins were clear in 10 patients. The median follow-up time was 19 months (range: 3.5-53.4 months). Before radiation therapy commenced, delay in chemotherapy occurred in 20% of patients, and dose reduction was required in 13.3%. During the concurrent chemoradiation therapy phase, 20% of the patients experienced chemotherapy delay, and 6.6% experienced dose reduction. No patient experienced treatment-related acute and chronic esophagitis above grade 2. Disease recurred in 40% of the patients (6/15), and median time to relapse was 24 months. No tumour recurred at the anastomotic site. The median DFS was 23 months, and the median OS was 21 months. CONCLUSIONS: Extended-volume external-beam RT encompassing the tumour bed and the anastomotic site is feasible and safe for high-risk T3-4, N0-1 esophageal cancer patients after esophagectomy.

Development and validation of a disease-specific quality of life questionnaire (EQOL) for potentially curable patients with carcinoma of the esophagus.

The objective was to develop, pretest and validate a disease-specific quality of life questionnaire for potentially curable patients with esophageal carcinoma, for use with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) in order to assess the quality of life associated with the various treatment modalities available for this disease. Questionnaire development phase Patients were enrolled in three centres. Literature reviews, patients, family members, and health care professionals generated 195 items: symptoms (55); emotions (53); physical functioning (17); activities of daily living (ADL) (48); and leisure/social (22). Thirty-eight patients identified items of importance and assigned importance ratings on a 5-point Likert scale. Impact scores were calculated as frequency times mean item importance. Item impact scores<20/100 were excluded. Pearson's correlation co-efficients compared domains with the Medical Outcomes Study SF-20 (MOS SF-20). Fifteen items remained. Questionnaire validation phase EORTC QLQ-C30, Esophageal Quality of Life Questionnaire (EQOL), MOS SF-36 and a Global Rating of Change Questionnaire were completed at baseline, 1 week after baseline but prior to any treatment, 1 month, 3 months, and 6 months after treatment began. Reliability was assessed using paired samples correlations. Responsiveness was assessed between mean scores of changed and unchanged patients, and a responsiveness index was calculated. The MOS SF-36 was used for criterion validity. Construct validity included four a priori predictions. Sixty-five patients were enrolled in four centres in the validation phase. Paired samples correlations were high for all domains (0.749-0.889) indicating good reliability. Symptom, physical function and social domains were responsive to change at all time intervals (P<0.05). Emotional function was responsive at 1 and 3 months, activities of daily living (ADLs) at 1 and 6 months. Magnitude of change was significant when direction of change was stated. Between better and worse, magnitude of change was significant in all domains except at 6 months in symptoms, emotional and physical domains. The minimal clinically important difference was consistently around 0.5 for all domains. Minimal, moderate and large effect ranges were established. Only 2/16 time intervals had poor correlations with the SF-36, establishing criterion validity. Of the four a priori predictions for construct validity, only the second part of one prediction, in the emotional function domain, was not confirmed. We have developed a 15-item questionnaire (EQOL) which has good reliability, responsiveness and validity and is now in use in studies in Canadian centres with the EORTC QLQ-C30.

Pulmonary sclerosing hemangioma with lymph node metastases.

Pulmonary sclerosing hemangioma is an unusual benign tumour of uncertain histogenesis. In the past 50 years, hundreds of cases have been described. A case of sclerosing hemangioma with some unusual features, including a false-positive fine needle aspiration biopsy and histological evidence of lymph node metastases, is described.

The role of surgery and postoperative chemoradiation therapy in patients with lymph node positive esophageal carcinoma.

BACKGROUND: Patients who have undergone resection for lymph node positive esophageal carcinoma are at high risk of disease recurrence and early death. The role of postoperative adjuvant therapy in this population needs to be determined. METHODS: A retrospective review of all patients with resected esophageal carcinoma between 1991 and 1997 was performed. Lymph node positive (N1) patients who received concurrent or sequential postoperative radiotherapy (50 grays) and chemotherapy (cisplatin, 5-fluorouracil with or without epirubicin) were compared with N1 patients who underwent surgery alone. The disease free and overall survival rates were calculated using the Kaplan-Meier method, and groups were compared with the log-rank test. Prognostic variables were entered into a Cox regression model controlling for age, weight loss, T status, Eastern Cooperative Oncology Group (ECOG) score, and treatment received. RESULTS: A total of 165 patients were reviewed: Twenty-eight N1 patients underwent surgery alone (S group), and 38 N1 patients underwent surgery and received postoperative chemoradiation therapy (CRT group). Preoperative risk factors, tumor characteristics, ECOG scores, and lengths of hospital stay were similar. The disease free survival rates were similar (S group, 10.6 months; CRT group, 10.2 months), although the S group had more local disease recurrences (S group, 35%; CRT group, 13%; P = 0.09). The overall survival rate according to the Kaplan-Meier analysis showed a significant survival advantage with postoperative CRT radiation (log-rank test; P = 0.001). The median overall survival for the CRT group was 47.5 months, which was significantly longer than that of the S group (14.1 months). The ECOG score, T status, and treatment received all were found to influence survival significantly on univariate analysis. In the multivariate model, postoperative CRT was a predictor of survival (P = 0.007; risk ratio for mortality, 0.35; 95% confidence interval, 0.16-0.76) and was correlated with a significantly decreased risk of death in patients with lymph node positive, resected esophageal carcinoma. CONCLUSIONS: Postoperative CRT appears to prolong survival in patients with lymph node positive, resected esophageal carcinoma.

Oropharyngeal dysphagia in esophageal cancer before and after transhiatal esophagectomy.

Although dysphagia is the predominant symptom of esophageal cancer, the nature of the swallowing deficit remains unclear, particularly regarding an oropharyngeal motor component. The present study examined the oropharyngeal swallow in patients with esophageal cancer before and following transhiatal esophagectomy. Videofluoroscopic data were obtained from ten patients with esophageal cancer before and following transhiatal esophagectomy as they swallowed 2-, 5-, and 10-cc aliquots of liquid and puree, and 0.5 and 1 tsp of solid. Each swallow was rated on 36 parameters by three independent judges. Swallow-related hyoid bone movement, computed from digitized segments of the videofluoroscopic data, was compared pre- and postsurgically. All patients showed at least mild abnormality of the oropharyngeal swallow preoperatively. Abnormalities involved all stages of swallowing in nine of the ten patients; however, the oral preparatory/oral stage was relatively more impaired than the pharyngeal stage in the majority of patients. Postsurgically, all patients exhibited at least a mild oropharyngeal swallowing impairment. New or increased postoperative deficits involved the pharyngeal stage of swallowing, whereas oral stage abnormalities were generally improved or unchanged following surgery. Swallow-related hyoid kinematics were highly variable both before and following surgery. Anterior hyoid bone excursion was significantly reduced postoperatively in one patient and significantly increased in one patient. Patients with esophageal cancer exhibit oropharyngeal dysphagia, with different profiles of abnormality before and following esophagectomy.

Acute airway obstruction secondary to bilateral broncholithiasis.

We report a case of acute airway obstruction secondary to bilateral broncholiths. Successful management was achieved with rigid bronchoscopy.

Surgeons' assessment of symptoms suggesting extrathoracic metastases in patients with lung cancer. Canadian Lung Oncology Group.

BACKGROUND: In patients with apparently operable non-small cell lung cancer (NSCLC), clinicians often omit investigation for M disease in asymptomatic patients. Previous investigations have not specified in detail what is meant by "symptomatic," and this could differ between surgeons. We have investigated the extent to which surgeons' criteria differ for presence of symptoms. METHODS: Participating surgeons from seven centers, enrolled patients they judged "asymptomatic" in a randomized trial of investigational strategies for NSCLC. Patients completed a structured questionnaire describing symptoms of the central nervous system (CNS). In 685 patients, we documented CNS symptom recurrence after resectional surgery over 1 year of follow-up. RESULTS: Two centers enrolled only patients without even the mildest symptoms. Three centers took an intermediate approach, occasionally classifying patients with mild symptoms as "asymptomatic" and thus enrolling them in the trial. Two centers classified an appreciable number of patients with minimal symptoms, and occasionally with more than minimal symptoms, as "asymptomatic." Patients with even mild CNS symptoms were more likely to subsequently present with CNS metastases. CONCLUSIONS: Thoracic surgeons differ in their ideas of what may constitute the symptoms of M disease. Patients with structured questionnaire results that suggest symptoms of CNS disease are more likely to have CNS symptom recurrence after resectional surgery.

Thoracoscopic versus laparoscopic modified Heller Myotomy for achalasia: efficacy and safety in 87 patients.

BACKGROUND: The ideal treatment for achalasia permanently eliminates the dysfunctional lower esophageal sphincter, relieving dysphagia and regurgitation; prevents gastroesophageal reflux; and has an acceptable morbidity rate. Controversy exists concerning whether the thoracoscopic Heller Myotomy (THM) or laparoscopic Heller myotomy (LHM) technique is the best approach to a modified Heller myotomy for achalasia. STUDY DESIGN: We performed a retrospective comparison of the patient characteristics, operative results, postoperative symptoms, and the learning curves for the procedures of 24 patients undergoing THM and 63 patients undergoing LHM between 1991 and 1998. RESULTS: Preoperative patient variables in each group revealed similar distributions for age, gender, and prevalence of previous pneumatic dilation. Mean operating room (OR) times were 4.3 hours (range 2.9 to 5.6 hours) for THM and 3.0 hours (range 1.5 to 6.5 hours) for LHM (p = 0.01). Three esophageal perforations occurred in the THM group and two in the LHM group. Conversion to an open procedure took place in five THM operations (21%) and one LHM operation (2%) (p = 0.005). There were no postoperative esophageal leaks. Mean postoperative length of stay (LOS) for THM was 6.1 days (range 1 to 17 days) and for LHM was 4.0 days (range 1 to 12 days) (p = 0.03). Learning-curve analysis of the first 24 LHM patients compared with the most recent 24 revealed greater OR time in the first 24 mean 3.6 hours, (range 2.0 to 6.5 hours) versus mean 2.3 hours, (range 1.5 to 3.7 hours; p = 0.01), and greater LOS mean 5.5 days, (range 3 to 12 days) versus mean 3.1 days, (range 1 to 8 days; p < 0.01). One esophageal perforation occurred in each subgroup. A similar analysis in the first 12 THM patients compared with the most recent 12 revealed no significant improvement in OR times or LOS. Three esophageal perforations occurred in the latter subgroup only. All patients had preoperative daily dysphagia to solids. Followup data for LHM (n = 49) (median 17 months, range 1 to 39 months) and THM (n = 15) (median 42 months, range 1 to 69 months) revealed no or minimal dysphagia in 90% (44 of 49) after LHM and 31% (4 of 13) after THM (p < 0.01). No or minimal heartburn was present in 89% (41 of 46) after LHM and 67% (8 of 12) after THM (p < 0.05). Regurgitation was absent or minimal in 94% (46 of 49) after LHM and 86% (12 of 14) after THM (p = 0.3). CONCLUSIONS: LHM was associated with decreased OR time, decreased rate of conversion to an open procedure, and shorter LOS compared with THM. LHM was superior to THM in relieving dysphagia and preventing heartburn. LHM may be the preferred surgical treatment of achalasia in some patients.

Propranolol for the prevention of postoperative arrhythmias in general thoracic surgery.

BACKGROUND: Prevention of postoperative arrhythmias in patients undergoing general thoracic surgery is desirable to prevent morbidity. METHODS: A randomized, double-blind, placebo controlled trial of propranolol (10 mg every 6 hours) for 5 days was undertaken in patients undergoing major thoracic operations to determine whether arrhythmias requiring treatment could be reduced. Secondary outcomes included overall arrhythmia rate, adverse events, and length of stay. Arrhythmias were assessed by 72-hour Holter monitoring. Patients with a history of heart failure, asthma, advanced heart block, preexisting arrhythmias, sensitivity to propranolol, or use of antiarrhythmic drugs were excluded. RESULTS: Using the intention-to-treat principle there was a 70% relative risk reduction from 20% to 6% in the rate of treated arrhythmias with propranolol (p = 0.071, 95% confidence interval 0.6% to 27.2%). Overall arrhythmias were common but usually benign. Adverse effects were common, although generally mild with hypotension and bradycardia being reported more often in the propranolol group. Length of stay was not different. CONCLUSIONS: There was a trend to a reduction in the risk of perioperative arrhythmias with propranolol. Moreover, propranolol was well tolerated showing a slight increase in minor adverse events.

Small-bowel necrosis associated with jejunal tube feeding.

OBJECTIVES: To report 3 cases of small-bowel necrosis after jejunal tube feeding and to review the literature concerning this condition. DESIGN: A 5-year retrospective review. SETTING: A 560-bed university-affiliated tertiary-care teaching hospital. PATIENTS: Three patients who had bowel necrosis out of 386 who received jejunal tube feedings. RESULTS: The patients experienced small-bowel necrosis as a consequence of jejunal feeding. The ischemic necrosis was preceded by progressive abdominal pain, distension and high nasogastric output. All 3 patients required extensive small-bowel resection. Although survival was rare in previous reports, our 3 patients survived after prompt surgical intervention and small-bowel resection. CONCLUSIONS: Although the death rate for this condition approaches 70%, timely recognition and surgical intervention can save the patient's life.

Minithoracoscopy for pleural effusions.

The current management of pleural disease often requires direct visualization and biopsy of the pleural space using thoracoscopy. A diagnostic and therapeutic approach to pleural disease is described that uses a new 2 mm rigid thorascope. The technique allows complete visualization, biopsy and drainage of the pleural space with rapid recovery and minimal pain.

The Second Canadian Consensus Conference on the Management of Patients with Gastroesophageal Reflux Disease.

The Second Canadian Consensus Conference on the Management of Patients with Gastroesophageal Reflux Disease (GERD) was organized by the Canadian Association of Gastroenterology to address major advances in the understanding of the pathophysiology of GERD, to review the new methods of investigation and therapy introduced since the first conference in 1992 and to examine the issue of relevant health economics. The changes that have taken place over the past four years have been sufficiently dramatic to necessitate reassessment of the recommendations made following the first conference. The second conference dealt with the investigation and treatment of uncomplicated GERD and the complex issues of esophageal and extraesophageal complications such as chest pain, Barrett's esophagus, and reflux-related pulmonary and laryngeal disorders. The role of laparoscopic surgery was also discussed. A decision tree for investigation and treatment of patients with GERD was developed. The 38 participants represented a broad spectrum of experience, location of practice and special interests. The distribution of participants conformed to the recommendations of the Canadian Medical Association guidelines for consensus documents in that there should be input from all possible interested parties. A list of the state-of-the-art lectures presented during the conference, the small group sessions, the session chairpersons and participants are appended to this document. CONCLUSIONS. UNCOMPLICATED GERD: GERD with alarm symptoms must be investigated immediately. There was no consensus about when to investigate uncomplicated GERD, ie, whether to perform endoscopy immediately or after initial therapy fails. There was controversy regarding 'step up' (H2 receptor antagonist [H2RA] or prokinetic [PK] first therapy) versus 'step down' therapy (proton pump inhibitor [PPI] first therapy). The majority decision was for short term 'step up' therapy and investigation if symptoms do not improve or recur. Maintenance therapy should be carried out with the initial therapy that was effective. H2RAs and PKs may suffice for maintenance therapy in milder GERD; however, for severe esophagitis, PPIs should be used. SURGERY: Indications for laparoscopic surgery should be the same as for conventional antireflux operations. NONCARDIAC ANGINA-LIKE CHEST PAIN: After exclusion of nonesophageal causes, the majority decided that eight weeks of therapy with a PPI should be performed, while some suggested work-up before a therapeutic test. In the absence of response or recurrence, esophagogastroduodenoscopy (EGD) and, depending on the circumstances, 24 h ambulatory pH/motility may be indicated. BARRETT'S ESOPHAGUS: Only patients who, in case of future discovery of cancer or dysplasia, are able or willing to undergo therapy should have surveillance. In the absence of dysplasia EGD should be performed every two years, and in the presence of mild dysplasia every three to six months. All agreed that for severe dysplasia, esophagectomy or poor risk patients, esophageal mucosal ablation is indicated. ESTRAESOPHAGEAL COMPLICATONS (EECs): Asthma, chronic cough and posterior laryngitis were considered EECs. Although PPIs may decrease symptoms, improvement alone is not diagnostic of the presence of EEC. Ambulatory pH studies with two pH probes or ambulatory pH/motility may be useful in establishing causation. HEALTH ECONOMICS: There are limited data for an economic comparison among the different drugs or between medical and surgical therapy.

Role of surgery in the management of gastroesophageal reflux disease.

Surgical management of gastroesophageal reflux disease (GERD) can provide good long term control of symptoms. The introduction and increasing use of laparoscopic antireflux procedures may provide an early surgical alternative to long term medical control of GERD. Indications for surgery, preoperative investigations, surgical options, and results and complications are discussed.

Boerhaave's syndrome and children: a rare and unexpected combination.

Boerhaave's syndrome, or the spontaneous rupture of the esophagus, appears most commonly in males between the ages of 40 and 60. Severe vomiting followed by excruciating chest pain are the classic clinical signs, often in conjunction with a history of over indulgence in food and alcohol. The authors describe a case of Boerhaave's syndrome in a child, the result of missed appendicitis.

Early detection of cancer cachexia in the rat using 31P magnetic resonance spectroscopy of the liver and a fructose stress test.

The dynamic metabolic effects of a fructose infusion challenge on hepatic intracellular levels of adenosine 5'-triphosphate (ATP), inorganic phosphate (Pi) and phosphomonoesters (PME) were monitored noninvasively by 31P MRS in a remote tumour-bearing rat model. Fisher male rats were inoculated with a methylcholanthrene-induced sarcoma. Seventeen rats were randomized into three groups: control (n = 6), low tumour burden (LTB, n = 6), or moderate tumour burden (MTB, n = 5). The LTB group had tumour burdens of 0.2-2.0% while the MTB group had tumour burdens of 2.6-5.7%. All rats were in the pre-clinical phase of cancer cachexia as determined by food intake and body weight. Rats were infused with 1.2 g/kg of fructose i.v. and the metabolic response of the liver was monitored with time over 1 h via 31P MRS. In all groups an immediate increase in hepatic levels of PME was noted, which returned to baseline values over the course of the experiment, reflecting the phosphorylation of fructose to fructose 1-phosphate. For the MTB rats, the return to baseline levels was more rapid than in the control or LTB group. All groups experienced a 20% decrease in hepatic ATP levels which did not return to baseline over the 1 h observation period. As well, all groups experienced an initial fall in Pi, which recovered to prefructose levels or greater. MTB rats demonstrated a 30-40% increase in Pi concentration and a 60-70% increase in Pi/ATP ratio after infusion with fructose as compared to LTB and control rats (ANOVA;p<0.05). This is consistent with cachexia-induced enhancement of hepatic gluconeogenic activity, and hence more rapid release of Pi from the phosphorylated metabolites in the MTB rats. Thus fructose infusion and hepatic 31P MRS permit pre-clinical detection of cancer cachexia as reflected by increased Pi generation and more rapid removal of PME.