Eero Sihvo

Prospective Analysis of Accuracy of Positron Emission Tomography, Computed Tomography, and Endoscopic Ultrasonography in Staging of Adenocarcinoma of the Esophagus and the Esophagogastric Junction

AbstractBackground: Exact preoperative staging of esophageal cancer is essential for accurate prognosis and selection of appropriate treatment modalities. Methods: Forty-two patients with adenocarcinoma of the esophagus or the esophagogastric junction suitable for radical esophageal resection were staged with positron emission tomography (PET), spiral computed tomography (CT), and endoscopic ultrasonography (EUS). Results: Diagnostic sensitivity for the primary tumor was 83% for PET and 67% for CT; for local peritumoral lymph node metastasis, it was 37% for PET and 89% for EUS; and for distant metastasis, it was 47% for PET and 33% for CT. Diagnostic specificity for local lymph node metastasis was 100% with PET and 54% with EUS, and for distant metastasis, it was 89% for PET and 96% for CT. Accuracy for locoregional lymph node metastasis was 63% for PET, 66% for CT, and 75% for EUS, and for distant metastasis, it was 74% with PET and 74% with CT. Of the 10 patients who were considered inoperable during surgery, PET identified 7 and CT 4. The false-negative diagnoses of stage IV disease in PET were peritoneal carcinomatosis in two patients, abdominal para-aortic cancer growth in one, metastatic lymph nodes by the celiac artery in four, and metastases in the pancreas in one. PET showed false-positive lymph nodes at the jugulum in three patients. Conclusions: The diagnostic value of PET in the staging of adenocarcinoma of the esophagus and the esophagogastric junction is limited because of low accuracy in staging of paratumoral and distant lymph nodes. PET does, however, seem to detect organ metastases better than CT.

Incipient Angiogenesis in Barrett’s Epithelium and Lymphangiogenesis in Barrett’s Adenocarcinoma

PURPOSE Barretts esophagus (BE), a precancerous condition for Barretts adenocarcinoma, is classically characterized by flames of salmon-colored mucosa extending into normal pale esophageal mucosa. This flaming is thought to be a consequence of continuous erosis of mucosa caused by chronic reflux. Another characteristic feature of Barretts adenocarcinoma patients is the frequent development of lymph node metastases. We addressed whether onset of angiogenesis occurs in BE and if the lymphatic system might provide a route for Barretts adenocarcinoma cells to infiltrate regular lymph nodes. PATIENTS AND METHODS Fifteen surgically resected Barretts dysplasia or adenocarcinoma patients were included. Immunohistochemistry and a modified whole mount analysis were used. RESULTS The incipient angiogenesis originates from the pre-existing vascular network in the lamina propria and infiltrates Barretts epithelium, giving its ominous salmon-red color. Barretts epithelium-specific goblet cells express vascular endothelial growth factor (VEGF)-A. The immature blood vessels show a relative absence of smooth muscle actin (SMA)-positive mural cells and express VEGF receptor (VEGFR)-2 and matrix metalloproteinase (MMP)-9 on their exterior. Coexpression of VEGF-C and its receptor VEGFR-3 on lymphatic vessels is demonstrated. CONCLUSION BE is strongly neovascularized not eroded. This novel concept of a molecular mechanism of the origin of BE might emphasize why precancerous BE can give rise to the more cancerous dysplasia and Barretts adenocarcinoma stages. In addition, adenocarcinoma cells induce lymphangiogenesis. The new lymphangiogenic vessels might provide a systemic route for adenocarcinoma cells to invade circulation and induce lymph node metastasis.

Oxidative stress has a role in malignant transformation in Barrett's oesophagus

Mechanisms underlying the development of oesophageal adenocarcinoma are poorly understood. To discover the role of oxidative stress and radical scavenger capacity in the malignant transformation of Barretts oesophagus, we measured myeloperoxidase activity, superoxide dismutase activity, glutathione content and total aromatic DNA adducts. Mucosal specimens came from 52 patients in 6 groups: symptomatic gastro‐oesophageal reflux disease (GORD) without and with endoscopic oesophagitis, Barretts epithelium without and with dysplasia, adenocarcinoma in the oesophagus and controls. In the GORD‐oesophagitis‐metaplasia‐dysplasia‐adenocarcinoma sequence, glutathione content was progressively lower and myeloperoxidase activity higher than in controls, plateauing at Barretts epithelium without dysplasia. Only in Barretts epithelium with dysplasia was SOD activity significantly increased. In all patient groups, DNA adduct levels were significantly higher than the control level. Though these levels between patient groups did not differ significantly, the level was highest in Barretts epithelium without dysplasia and progressively lower in Barretts with dysplasia and adenocarcinoma. Pooled data showed a negative correlation between glutathione content and DNA adducts (−0.28, p = 0.05). Simultaneous formation of DNA adducts, increased myeloperoxidase‐related oxidative stress, decreased antioxidant capacity (glutathione content) and the negative correlation between glutathione content and DNA adducts in the GORD–oesophagitis–metaplasia–dysplasia–adenocarcinoma sequence of Barretts oesophagus indicate a role in the pathogenesis and malignant transformation related to oxidative stress.

Fatal complications of adult paraesophageal hernia: A population-based study

OBJECTIVES Data on mortality from paraesophageal hernia are scarce. This study focused on mortality associated with its natural history or conservative treatment. METHODS For this population-based retrospective study, Finlands administrative databases provided preliminary data. Among 333 patients who died from benign esophageal diseases or hiatal hernias, analysis of medical records led us to include 32. RESULTS From 1987 through 2001 in Finnish hospitals, 563 patients underwent surgical intervention and 67 underwent conservative treatment for paraesophageal hernia. This hernia caused death (mortality, 0.6/1,000,000 of the adult population; 95% confidence interval, 0-1.8/1,000,000) in 32 patients, 29 (91%) with concomitant diseases. The overall mortality rate for the 563 having surgical treatment was 2.7% (15 patients). Three died after elective repair. Of 67 patients hospitalized for symptomatic paraesophageal hernia and treated conservatively, 11 (16.4%) died in the hospital within a mean of 42 months (range, 2-96 months) from onset of symptoms. Four (13%) deaths might have been prevented by elective surgical intervention. Of the 32 deceased patients, 4 (12.5%) had type II, 16 (50%) had type III, and 9 (28.1%) had type IV hiatal hernias. In 3 (9.4%) patients type remained unknown. Death resulted from incarceration in 24 (75%), complications of surgical intervention in 6 (18.8%), and bleeding ulcer in 2 (6.2%). CONCLUSIONS Overall, most deaths were related to type III or IV hernias in aged patients with concomitant diseases, with those with severe symptoms requiring hospitalization at significant risk. Except for those at high surgical risk, we recommend repair of the paraesophageal hernia, at least in symptomatic patients.

Long-term indwelling pleural catheter (PleurX) for malignant pleural effusion unsuitable for talc pleurodesis

AIMS Talc pleurodesis using talc slurry via chest tube is a primary option in malignant pleural effusion, since life expectancy is short and surgical decortication is hazardous. Incomplete lung expansion after fluid evacuation, and/or excessive fluid secretion predicts failure of pleurodesis. A mini-invasive alternative was investigated. METHODS Between March 2004 and September 2005, 51 consecutive patients with malignant pleural effusion, and clinically considered unsuitable for talc pleurodesis, received an indwelling pleural catheter (Denver PleurX). In 47, implantation was done bedside using local anaesthesia. There were 24 men and 27 women, median age 63 (range 36-85) years, receiving 39 right side, 10 left side, and 2 bilateral catheters. There were 19 non-small cell lung cancer cases, 7 mesothelioma, and 25 with other malignancy. Chemotherapy was being given to 18 patients and was not interrupted. RESULTS Discharge to home was possible in 71% (36 of 71 patients) on the following day. At 2 years follow-up in September 2007, one patient was alive. Mean survival was 3 months (range 5 days to 37+months) for all patients, with best median survivals of 5.5-6 months in breast and ovarian cancer. Catheter was removed or replaced in 15% (8 of 51 patients) due to infection, air leak, or blockage. One patient requested decortication for excessive fluid secretion. None required surgery or died due to catheter-related complications. Pleural fusion with subsequent catheter removal was achieved in 21% (11 of 51 patients). CONCLUSIONS An indwelling pleural catheter is a safe alternative for patients with malignant pleural effusion unsuitable for talc pleurodesis. In some, pleural fusion may be achieved.

The epidemiology of oesophageal adenocarcinoma: has the cancer of gastric cardia an influence on the rising incidence of oesophageal adenocarcinoma?

Background: Owing to overgrowth and definitional problems in classification, the cancer of gastric cardia may affect significantly the epidemiological analysis of oesophageal adenocarcinoma. The purpose of the present study was to evaluate the changes in the incidence of all the adenocarcinomas near the gastro-oesophageal junction. Methods: Trends in the incidence rates of adenocarcinoma of the oesophagus and the gastric cardia were described through the Finnish Cancer Registry. The annual age-standardized incidence rates during 1976-95 were analysed by a linear regression technique. Results: The total incidence of oesophageal carcinoma remained around 3.5/100,000 in men, and decreased from 2.8 to 1.3/100,000 in women. The incidence of oesophageal adenocarcinoma increased from 0.28 to 0.77/100,000 (nearly 300%) in males, and from 0.08 to 0.11 per 100,000 in females. There were no significant changes with time in the incidence rate of gastric cardia cancer in either sex. Combined gastric cardia and oesophageal adenocarcinoma incidence rates remained stable in women, and increased slightly, but significantly, from 2.4 to 2.9/100,000 in men. Conclusion: Oesophageal adenocarcinoma has increased significantly in men in Finland, but the combined incidence of cancers of the gastro-oesophageal junction has increased only slightly. To overcome the difficulties in classification of oesophageal adenocarcinoma and the cancer of gastric cardia in the epidemiological studies, the focus should be on all adenocarcinomas at or near the oesophagogastric junction.BACKGROUND Owing to overgrowth and definitional problems in classification, the cancer of gastric cardia may affect significantly the epidemiological analysis of oesophageal adenocarcinoma. The purpose of the present study was to evaluate the changes in the incidence of all the adenocarcinomas near the gastrooesophageal junction. METHODS Trends in the incidence rates of adenocarcinoma of the oesophagus and the gastric cardia were described through the Finnish Cancer Registry. The annual age-standardized incidence rates during 1976-95 were analysed by a linear regression technique. RESULTS The total incidence of oesophageal carcinoma remained around 3.5/100,000 in men, and decreased from 2.8 to 1.3/100,000 in women. The incidence of oesophageal adenocarcinoma increased from 0.28 to 0.77/100,000 (nearly 300%) in males, and from 0.08 to 0.11 per 100,000 in females. There were no significant changes with time in the incidence rate of gastric cardia cancer in either sex. Combined gastric cardia and oesophageal adenocarcinoma incidence rates remained stable in women, and increased slightly, but significantly, from 2.4 to 2.9/100,000 in men. CONCLUSION Oesophageal adenocarcinoma has increased significantly in men in Finland, but the combined incidence of cancers of the gastro-oesophageal junction has increased only slightly. To overcome the difficulties in classification of oesophageal adenocarcinoma and the cancer of gastric cardia in the epidemiological studies, the focus should be on all adenocarcinomas at or near the oesophagogastric junction.

Adenocarcinoma of the esophagus and the esophagogastric junction: positron emission tomography improves staging and prediction of survival in distant but not in locoregional disease.

In adenocarcinoma of the esophagus and esophagogastric junction for prognostication and treatment allocation, one prerequisite is accurate pretreatment staging. This staging, we hypothesized, would be improved by the use of positron emission tomography (PET). After 55 patients suitable for radical esophageal resection were staged with PET, spiral computed tomography (CT), and endoscopic ultrasonography (EUS), results were compared with histopathology and with survival. Accuracy in detecting locoregional lymph node metastasis did not differ significantly between EUS (72%), PET (60%), and CT (58%). Adding PET to standard staging failed to improve the accuracy of N staging (P = 0.250). In M staging, accuracy between CT (75%) and PET (76%) did not differ. The accuracy of combined studies of CT and PET and of EUS, CT, and PET were 87% (P = 0.016 versus CT) and 91% (P = 0.031 versus EUS and CT), respectively. Of the 55 patients, 19 (35%) had metastatic lesions. By combined use of CT and EUS and by combined use of CT, EUS, and PET, 8 and 14 (P = 0.031), respectively, could be detected. In nodal disease without distant metastases, PET did not improve the prediction of survival. However, positive PET for distant metastasis by either positive EUS or CT predicts well the poor survival of these patients. The staging value of PET by itself in adenocarcinoma of the esophagus is limited because of low accuracy for nodal and the lack of specificity for distant disease prognosis. Adding PET to standard staging does, however, improve detection of stage IV disease and its associated poor survival.

Quality of life following lobectomy or bilobectomy for non-small cell lung cancer, a two-year prospective follow-up study

Surgery for non-small cell lung cancer (NSCLC) is associated with a significant negative impact on health-related quality of life (HRQoL), but only a few published studies evaluate the long-term HRQoL and its association with preoperative pulmonary function tests (PFTs). We conducted a prospective study, with 53 patients undergoing lobectomy (n=49) or bilobectomy (n=4) for NSCLC, between May 2002 and September 2005. The 15D HRQoL instrument was administered preoperatively, and 3, 12, and 24 months postoperatively. Preoperative PFTs were recorded. We also compared the preoperative HRQoL results to an age-standardized general population. The two-year survival was 81%, 43/53 patients. Sustained impairment of HRQoL was noted two years after the surgery. No correlation emerged between preoperative PFTs and postoperative HRQoL. No differences were observed between stages I-II and stage III patients. Thus, lobectomy and bilobectomy are associated with significant sustained decrease especially in breathing, sleeping, usual activities, mental function, vitality and sexual activity, and in the overall HRQoL. These findings maybe used as preoperative patient information to emphasize the long-term consequences of lung cancer surgery.

Anatomic thoracoscopic lung resection for non-small cell lung cancer in stage I is associated with less morbidity and shorter hospitalization than thoracotomy

Abstract Background. Patients undergoing surgery for non-small cell lung cancer (NSCLC) are often elderly with co-morbid conditions and decreased performance status. Thus, the morbidity of lung resection via thoracotomy may be unacceptable for some patients. This is the reason why video-assisted thoracoscopic surgery (VATS) instead of open thoracotomy has gained more use and acceptance, especially in patients with stage I disease. The aim of this study was to evaluate the difference between VATS and open thoracotomy in treatment outcomes of stage I NSCLC patients. Methods. A total of 328 stage I NSCLC patients underwent lobectomy, bilobectomy or segmentectomy between January 2000 and February 2010. VATS was implemented in 116 patients, of which 16 were converted to thoracotomy. Muscle-sparing anterolateral thoracotomy was performed in 212. Propensity-matched groups were analyzed based on preoperative variables and stage. Results. VATS was associated with lower postoperative morbidity in both overall (p = 0.020) and propensity-matched analysis (p = 0.026) and shorter hospitalization (both p < 0.001). Patients selected for VATS were older (p = 0.001) with a significantly higher Charlson comorbidity index (p = 0.007) and poorer diffusion capacity (p < 0.001). The conversion rate was 14%. Between the two groups, no significant difference was observable in two-year overall and progression-free survival. Conclusions. Despite the VATS lobectomy and segmentectomy patients’ being older, with more comorbid condition and poorer pulmonary function, the incidence of major complications was lower and hospitalization shorter than for open thoracotomy patients. For stage I NSCLC, VATS should be considered the primary surgical approach.

Novel additive manufactured scaffolds for tissue engineered trachea research

Abstract Conclusions: This study demonstrates proof of concept for controlled manufacturing methods that utilize novel tailored biopolymers (3D photocuring technology) or conventional bioresorbable polymers (fused deposition modeling, FDM) for macroscopic and microscopic geometry control. The manufactured scaffolds could be suitable for tissue engineering research. Objectives: To design novel trachea scaffold prototypes for tissue engineering purposes, and to fabricate them by additive manufacturing. Methods: A commercial 3D model and CT scans of a middle-aged man were obtained for geometrical observations and measurements of human trachea. Model trachea scaffolds with variable wall thickness, interconnected pores, and various degrees of porosity were designed. Photocurable polycaprolactone (PCL) polymer was used with 3D photocuring technology. Thermoplastic polylactide (PLA) and PCL were used with FDM. Cell cultivations were performed for biocompatibility studies. Results: Scaffolds of various sizes and porosities were successfully produced. Both thermoplastic PLA and PCL and photocurable PCL could be used effectively with additive manufacturing technologies to print high-quality tubular porous biodegradable structures. Optical microscopic and SEM images showed the viability of cells. The cells were growing in multiple layers, and biocompatibility of the structures was shown.