The mediastinal staging accuracy of 18F-Fluorodeoxyglycose positron emission tomography/computed tomography in non-small cell lung cancer with variable time intervals to surgery.

BACKGROUND: PET/CT scanning can determine suitability for curative therapy and inform decision making when considering radical therapy in patients with non-small cell lung cancer (NSCLC). Metastases to central mediastinal lymph nodes (N2) may alter such management decisions. We report a 2 year retrospective series assessing N2 lymph node staging accuracy with PET/CT compared to pathological analysis at surgery. METHODS: Patients with NSCLC attending our centre (excluding those who had induction chemotherapy) who had staging PET/CT scans and pathological nodal sampling between June 2006 and June 2008 were analysed. For each lymph node assessed pathologically, the corresponding PET/CT status was determined. 64 patients with 200 N2 lymph nodes were analysed. RESULTS: Sensitivity of PET/CT scans for indentifying involved N2 lymph nodes was 39%, specificity 96% and overall accuracy 90%. For individual lymph node analysis, logistic regression demonstrated a significant linear association between PET/CT sensitivity and time from scanning to surgery (p=0.031) but not for specificity and accuracy. Those scanned <9 weeks before pathological sampling were significantly more sensitive (64% >9 weeks, 0% ≥ 9 weeks, p=0.013) and more accurate (94% <9 weeks, 81% ≥ 9 weeks, p=0.007). Differences in specificity were not seen (97% <9 weeks, 91% ≥ 9 weeks, p=0.228). No significant difference in specificity was found at any time point. CONCLUSIONS: We recommend that if a PET/CT scan is older than 9 weeks, and management would be altered by the presence of N2 nodes, re-staging of the mediastinum should be undertaken.

Long-term follow-up of immunocytochemical analysis of vascular endothelial growth factor (VEGF), and its two receptors, VEGF-R1 (Flt-1) and VEGF-R2 (Flk-1/KDR), in oesophagogastric cancer.

BACKGROUND: The prognostic significance of immunocytochemical analysis of tumour vascular endothelial growth factor (VEGF) and its 2 receptors, VEGF-R1 and VEGF-R2, remains incompletely investigated in patients with oesophagogastric cancer.
 METHODS: Patients undergoing surgical resection were prospectively recruited between February 1999 and August 2000. Immunocytochemical analysis of VEGF, VEGF-R1 (Flt-1) and VEGF-R2 (Flk-1/KDR) was undertaken using validated techniques. Patients were followed up over a 10-year period using the Northern Ireland Cancer Registry.
 RESULTS: Sixty-one patients were recruited (male=45, 73.8%) with a median age of 66.0 years (range 39-83). Forty-seven (77.0%) adenocarcinomas and 14 (23.0%) squamous cell carcinomas were resected. UICC tumour staging was: stage I=14.7%, II=24.6%, III=54.1% and IV=6.6%. VEGF, VEGF-R1 and VEGF-R2 were over-expressed in tumour epithelial cells. VEGF-R2 expression was decreased in the presence of lymphovascular invasion and higher tumour grade. The 10-year survival rate was 19.7% (n=12) with a median follow-up of 808 (IQR 356-2313) days. On univariate analysis only lymphovascular invasion significantly predicted poor prognosis in this cohort (p=0.05). 
 CONCLUSION: VEGF, VEGF-R1 and VEGF-R2 were over-expressed in tumour epithelial cells. VEGF-R2 expression was decreased in the presence of more aggressive pathological variables. Larger studies are required to assess the prognostic significance of these biomarkers in oesophagogastric cancer.

Transection of the aerodigestive tract after blunt neck trauma.

Survival after blunt neck trauma resulting in combined tracheal and esophageal injury is uncommon. We present the case of a young boy who sustained complete transection of the trachea and subtotal transection of the esophagus after a clothes line type injury.

Impact of nutritional factors on survival in patients with inoperable oesophageal cancer undergoing self-expanding metal stent insertion.

BACKGROUND: Undernutrition has been shown to be predictive of 30-day mortality in patients undergoing self-expanding metal stent (SEMS) insertion for inoperable oesophageal cancer. The aim of this study was to assess the relationship between nutritional factors and 30-day mortality in patients undergoing SEMS insertion for palliation of oesophageal cancer. METHODS: A retrospective cohort study was conducted from April 2007 to June 2009. BMI, swallowing ability, calorific intake and nature of nutritional support were recorded. ICD-10 causes of death were obtained from the Department of Health and Social Services. RESULTS: Fifty-six stents were inserted into 53 patients (mean age 70 years, male n=35). Median (interquartile range) BMI was 21.0 kg/m (18.7-24.0). Median pre-SEMS swallowing grade was 3. Median calorific intake as a percentage of estimated daily requirements was 94.0% (75.6-100.0%). Thirty (56.6%) patients tolerated an oral diet enhanced with supplement drinks whereas 23 (43.4%) patients required more invasive forms of enteral and parenteral support. The 30-day mortality rate was 11.3% (n=6) and cumulative median survival was 84 (interquartile range 38-156) days. BMI, calorific intake and swallowing capacity were not predictors of survival. Although there was a nonsignificant trend for reduced survival in those patients who did (n=23) receive invasive nutritional support compared with those who did not (n=30) (83.9 vs. 151.3 days, P=0.053), invasive nutritional support itself was not predictive of 30-day mortality (P=0.74). CONCLUSION: The requirement for invasive nutritional support before SEMS insertion is associated with a poor prognosis and possibly represents more aggressive tumour pathology. Further prospective assessment of prognostic factors, including nutritional parameters, to facilitate reliable selection of appropriate palliative modalities in oesophageal cancer is required.

Does pre-operative estimation of oesophageal tumour metabolic length using 18F-fluorodeoxyglucose PET/CT images compare with surgical pathology length?

PURPOSE: The aim of the study was to compare the pre-operative metabolic tumour length on FDG PET/CT with the resected pathological specimen in patients with oesophageal cancer. METHODS: All patients diagnosed with oesophageal carcinoma who had undergone staging PET/CT imaging between the period of June 2002 and May 2008 who were then suitable for curative surgery, either with or without neo-adjuvant chemotherapy, were included in this study. Metabolic tumour length was assessed using both visual analysis and a maximum standardised uptake value (SUV(max)) cutoff of 2.5. RESULTS: Thirty-nine patients proceeded directly to curative surgical resection, whereas 48 patients received neo-adjuvant chemotherapy, followed by curative surgery. The 95% limits of agreement in the surgical arm were more accurate when the metabolic tumour length was visually assessed with a mean difference of -0.05 cm (SD 2.16 cm) compared to a mean difference of +2.42 cm (SD 3.46 cm) when assessed with an SUV(max) cutoff of 2.5. In the neo-adjuvant group, the 95% limits of agreement were once again more accurate when assessed visually with a mean difference of -0.6 cm (SD 1.84 cm) compared to a mean difference of +1.58 cm (SD 3.1 cm) when assessed with an SUV(max) cutoff of 2.5. CONCLUSION: This study confirms the high accuracy of PET/CT in measuring gross target volume (GTV) length. A visual method for GTV length measurement was demonstrated to be superior and more accurate than when using an SUV(max) cutoff of 2.5. This has the potential of reducing the planning target volume with dose escalation to the tumour with a corresponding reduction in normal tissue complication probability.

The relationship between the prevalence of nighttime gastroesophageal reflux disease and disease severity.

BACKGROUND: Nighttime gastrointestinal reflux disease (GERD) prevalence and severity estimates vary substantially across studies. METHODS: We assessed nighttime GERD (NTG) prevalence and symptom frequency and severity through a web survey of US adults, using the GERD Symptom and Medication Questionnaire (GERD-SMQ), a validated symptom questionnaire. NTG was based on episodes of nighttime heartburn per week and time of occurrence. Symptom severity and impact were assessed and compared for GERD cases with and without NTG. RESULTS: GERD prevalence among respondents (n = 2,603) was 27%. Forty-five percent of symptomatic GERD respondents had NTG. Among respondents with both daytime and nighttime symptoms, 51% reported that nighttime symptoms were more bothersome. NTG respondents reported greater disease severity compared with those without (P < 0.0001). CONCLUSIONS: NTG symptoms are very common among those identified with GERD. People with nighttime symptoms have greater disease severity than those with exclusively or primarily daytime symptoms.

Long-term results of a selective surgical approach to management of Zollinger-Ellison syndrome in patients with MEN-1.

The role of operation in patients with Multiple Endocrine Neoplasia Type 1 (MEN-1) and Zollinger-Ellison Syndrome (ZES) is controversial. Our institutional bias for this disease has, in general, been towards aggressive imaging and operative removal of localized gastrinomas. Few studies have reported long-term outcomes in patients with MEN-1 and ZES. A single institution retrospective review of all patients with MEN-1 and ZES from 1970 to present was performed. Twelve patients were identified (median age = 37 years at diagnosis). The median follow-up was 18 years from diagnosis of ZES. Common symptoms associated with gastrinoma in these patients were diarrhea (n = 6), abdominal pain (n = 4), and nausea/vomiting (n = 4). Most commonly identified sites of gastrinoma were: pancreas (n = 10), duodenum (n = 4), lymph nodes (n = 3), and liver (n = 1). Fifteen celiotomies were performed in total (median = 1; range 0-3). Operative procedures performed included: distal pancreatectomy (n = 4), acid reducing procedure (n = 4), enucleation of pancreatic gastrinoma (n = 3), duodenal resection (n = 3), pancreaticoduodenectomy (n = 1), and other (n = 7). One patient had a transient biochemical cure after operation lasting 3 years. Only one patient in this series had documented liver metastases of gastrinoma and no patients expired of metastatic gastrinoma. There was one postoperative patient death, secondary to respiratory arrest thought to be a result of aspiration or pulmonary embolus. Three patients died of nondisease related causes, and seven patients were alive at the time of last follow-up. Operations rarely result in biochemical cures in patients with MEN-1 and ZES. In our experience, resection of localized gastrinomas often did not require extended surgical resection and were associated with excellent long-term outcomes.

Reoperative surgery in sporadic Zollinger-Ellison Syndrome: longterm results.

BACKGROUND: Most patients with Zollinger-Ellison Syndrome (ZES), even those in whom gastrinoma is found and resected at initial operation, will suffer from persistent or recurrent disease in longterm followup. There is currently no consensus about managing patients with recurrent or persistent ZES. Our unit has historically maintained an aggressive approach toward monitoring and reoperation for patients with sporadic ZES. STUDY DESIGN: We performed a review of a consecutive series of patients evaluated and managed at our institution between 1970 and 2007 for ZES. "Biochemical cure" was defined as normal serum gastrin assays and negative imaging studies. Reoperations were performed for elevations in serum gastrin assays and positive findings on imaging studies. RESULTS: Fifty-two patients with sporadic ZES were analyzed. Median followup was 14 years. Among patients with sporadic ZES, 37 patients underwent operative management. The most common operations were resection of duodenal gastrinoma (n=8) and total gastrectomy (n=7). Nine patients underwent 15 reoperations for recurrent or persistent disease. "Biochemical cure" was obtained in four patients (44%) undergoing reoperation for ZES. Three of these patients remained without evidence of recurrence at 4, 9, and 12 years after their curative re-resection. Only one of nine patients who underwent reoperation died of metastatic gastrinoma. CONCLUSIONS: Primary and reoperative surgery in patients with sporadic ZES results in a significant rate of "biochemical cure." In selected patients with recurrent or persistent disease, reoperation for resection of gastrinoma is associated with excellent longterm survival and is warranted.

Cytochrome P450 1B1 expression in rat esophageal tumorigenesis promoted by gastric and duodenal reflux.

Cytochrome P450 1B1 (CYP1B1) mRNA is constitutively expressed in most normal extra-hepatic tissues; however the protein is not detectable in these tissues but is expressed in a wide variety of tumors. CYP1B1 is responsible for the activation of a number of carcinogens present in tobacco smoke and food. A surgical model of rat esophageal tumorigenesis, promoted by gastric or duodenal reflux was used to determine CYP1B1 expression in premalignant esophageal tissue. Immunohistochemistry was performed using a modified amplified fluorescein tyramide protocol. CYP1B1 was not observed in normal esophageal mucosa, submucosa, or muscularis mucosa. Animals exposed to gastric reflux developed mild hyperplasia. Varying degrees of hyperplasia were observed in the duodenal reflux group. All regions of hyperplasia showed moderate or strong CYP1B1 immunoreactivity. Duodenal reflux induced a small number of premalignant changes: immunoreactivity was absent from the epithelium of squamous dysplasia (0/10), Barrett's esophagus (0/7), and majority of dysplastic Barrett's esophagus (1/4). Moderate or strong immunoreactivity was observed in the majority (7/8) of squamous cell carcinomas (SCCs) in situ. Immunoreactivity was also observed in the lamina propria and submucosa in association with inflammation, regardless of the severity of inflammation. The expression of CYP1B1 in hyperplasia, SCCs in situ, or in association with inflammation may increase the production of carcinogenic metabolites, which may promote esophageal tumorigenesis.

An objective assessment of the sudomotor response after thoracoscopic sympathectomy.

OBJECTIVE: Thoracoscopic sympathectomy has become an accepted therapeutic option for palmar hyperhidrosis. Objective assessment of sweat output after sympathectomy, however, has not been reported to date. We report for the first time sweat output measurements after sympathectomy during a 3-year postoperative period. METHODS: Thoracoscopic sympathectomy was performed by division of T2 and T3 sympathetic ganglia in 17 healthy adult patients with no comorbidities. Preoperative and postoperative sweat measurements were done at 29 degrees C (below sweat threshold, at baseline, after conversation, and after a mental arithmetic challenge) and at 40 degrees C (baseline and after exercise) with the ventilated capsule technique in left palm, sole, and chest wall. Serial postoperative measurements were conducted at 1 and 6 months and 1, 2, and 3 years. RESULTS: Sweat output fell significantly after sympathectomy relative to preoperative levels under all experimental conditions (P < .001, analysis of variance) in the left palm. Differences in sweat outputs in the left palm were statistically significant between groups at baseline and postoperatively after mental arithmetic challenge and exercise at 40 degrees C (P < .05, analysis of variance). Compensatory increases in the sweat outputs from the left sole and chest were observed after sympathectomy. No patients had recurrence of preoperative sweat output values at follow-up. CONCLUSION: According to objective sweat output measurements, thoracoscopic sympathectomy results in long-term control of palmar hyperhidrosis. This evaluation method is valuable in investigating recurrence of symptoms or compensatory hyperhidrosis after sympathectomy, providing a robust and objective criterion for planning intervention.

Primary mediastinal synovial sarcoma.

Synovial sarcoma occurs predominantly in the soft tissues of the extremities, but is exceedingly rare in the mediastinum. It has overlapping histological and immunophenotypic features with other tumours in the differential diagnosis. We report a case of a patient who had an incidental finding of such a tumour. Because of the rarity of this tumour in the mediastinum, optimal therapy is unknown and the prognosis remains guarded.

Zollinger-Ellison phenotype in the absence of hypergastrinemia and islet-cell tumor.

Patients with the Zollinger-Ellison syndrome are characterized by islet-cell tumors, striking gastric acid hypersecretion, and peptic ulcer disease. They often experience severe abdominal pain, diarrhea, and gastrointestinal bleeding with potentially life-threatening consequences. It is a rare syndrome caused by non-beta cell islet-cell tumors (gastrinomas) located in or in proximity to the pancreas. These tumors freely secrete gastrin, a peptide hormone that serves as a powerful stimulant of gastric acid secretion. Exuberant secretion of gastrin from the gastrinomas produces severe gastric acid hypersecretion that often leads to impressive peptic ulcer disease and the constellation of symptoms listed above. We describe a patient presenting with clinical manifestations characteristic of the ZES with strikingly elevated gastric acid secretion,multiple ulcers in the first and second portions of the duodenum and diarrhea, but in absence of islet-cell tumor and/or hypergastrinemia.

Bone marrow micrometastases and markers of angiogenesis in esophageal cancer.

BACKGROUND: Tumor angiogenesis is critical for metastasis development. The detection of bone marrow micrometastases may indicate a metastatic phenotype. We aim to establish if the detection of bone marrow micrometastases associates with elevated markers of angiogenesis and adverse histopathologic features of esophageal cancer. METHODS: Bone marrow aspirates from 49 patients with esophageal cancer were assessed and assigned to be positive or negative for micrometastases. Routine histologic assessment of the primary tumor was also undertaken. Circulating and tumor levels of the angiogenic cytokine vascular endothelial growth factor were determined in plasma and tumor homogenate. Intratumor microvessel density was evaluated by counting anti-CD34 positive neovessels. RESULTS: Twenty-two patients were positive for bone marrow micrometastases (44.9%). The detection of micrometastases was associated with advanced T stage (T3/4 vs T1/2; p = 0.023), circumferential margin involvement (p = 0.002) and lymphovascular invasion (p = 0.024). Plasma vascular endothelial growth factor was significantly more elevated in micrometastatic-positive patients than in those without micrometastases (p = 0.018). No difference was noted in tumor vascular endothelial growth factor expression. For adenocarcinomas alone, intratumor microvessel density was significantly higher in micrometastatic positive cases (p = 0.03). This was not the case for squamous cell carcinomas. CONCLUSIONS: The detection of bone marrow micrometastases is associated with esophageal tumors of advanced T stage and specifically for adenocarcinomas with tumor vascularity. Plasma vascular endothelial growth factor is elevated in micrometastatic positive cases and might be derived from sources other than the primary tumor.

Traumatic aortic rupture during pregnancy.

A 29-year-old woman, in her third trimester of pregnancy, underwent emergency Caesarian section for placental abruption following a road traffic accident. Following transfer, an abrupt change in the diameter of the aorta was noted on CT scan. Aortography confirmed aortic rupture distal to the left subclavian artery and Dacron graft replacement of this segment was carried out, utilizing a left atrial to descending aorta partial bypass through a centrifugal pump. The mother is alive and well at 4 months follow-up.

Erdheim-Chester disease with prominent pericardial involvement: clinical, radiologic, and histologic findings.

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis. Herein we describe documented skeletal and pericardial involvement by ECD producing cardiac tamponade in a 30-year-old woman. The diagnosis of ECD was established by histopathology, immunocytochemistry, and by radiologic studies demonstrating diffuse, bilateral, symmetrical osteosclerosis of the long bones, sparing the epiphyses and axial skeleton. Scintography using methyl diphosphonate showed increased uptake in involved bone. The patient presented with jaundice and hepatic congestion produced by cardiac tamponade. Pericardial biopsy revealed xanthogranulomatous lesions comprised of foamy and lipid-laden macrophages, multinucleated giant cells, monocytes, and lymphocytes in a mesh of fibrosis. Immunohistochemical staining was positive for CD68 and negative for CD1a, consistent with ECD rather than with the much more common Langerhans cell form of histiocytosis.

Sputum retention after lung operation: prospective, randomized trial shows superiority of prophylactic minitracheostomy in high-risk patients.

BACKGROUND: Sputum retention after lung operation is a potentially life-threatening condition. The minitracheostomy (Minitrach II, SIMS Portex, Hythe, Kent, UK) is a 4-mm percutaneous cricothyroidotomy device, which allows immediate and repeated aspiration of the tracheobronchial tree by minimally trained staff, and can effectively treat sputum retention. This trial was designed to test the hypothesis that prophylactic minitracheostomy could prevent sputum retention in a high-risk group. METHODS: Between March 1997 and October 1999, 102 patients undergoing lung procedures and considered to be at high risk were prospectively randomized to postoperative, prophylactic minitracheostomy insertion in the recovery room with regular aspiration, or to standard postoperative respiratory therapy. RESULTS: Sputum retention developed in 15 patients (30%) in the standard group (n = 52) compared to 1 patient (2%) in the minitracheostomy group (n = 50) (p < 0.005). There were three deaths related to sputum retention in the standard group compared to none in minitracheostomy group during the perioperative period. CONCLUSIONS: It is possible to identify a group of patients at high risk for sputum retention who will benefit from prophylactic therapy. Minitracheostomy is effective as prophylaxis and treatment.

Pulmonary infarct cytologically mimicking adenocarcinoma of the lung.

We describe a patient who underwent a right lower lobectomy for a lung lesion with a preoperative diagnosis of adenocarcinoma made on sputum cytology. Pathologic assessment of the resected specimen revealed a pulmonary infarct with no evidence of malignancy. All thoracic surgeons should be aware of this diagnostic pitfall. A positive sputum specimen should not always be regarded as definitive evidence of malignancy. Instead a full assessment of all available information should be made if unnecessary surgery is to be avoided.