Nadine Ectors

Utility of Positron Emission Tomography for the Staging of Patients With Potentially Operable Esophageal Carcinoma

PURPOSE A prospective study of preoperative tumor-node-metastasis staging of patients with esophageal cancer (EC) was designed to compare the accuracy of 18-F-fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET) with conventional noninvasive modalities. PATIENTS AND METHODS Seventy-four patients with carcinomas of the esophagus (n = 43) or gastroesophageal junction (n = 31) were studied. All patients underwent attenuation-corrected FDG-PET imaging, a spiral computed tomography (CT) scan, and an endoscopic ultrasound (EUS). RESULTS FDG-PET demonstrated increased activity in the primary tumor in 70 of 74 patients (sensitivity: 95%). False-negative PET images were found in four patients with T1 lesions. Thirty-four patients (46%) had stage IV disease. FDG-PET had a higher accuracy for diagnosing stage IV disease compared with the combination of CT and EUS (82% v 64%, respectively; P: =.004). FDG-PET had additional diagnostic value in 16 (22%) of 74 patients by upstaging 11 (15%) and downstaging five (7%) patients. Thirty-nine (53%) of the 74 patients underwent a 2- or 3-field lymphadenectomy in conjunction with primary curative esophagectomy. In these patients, tumoral involvement was found in 21 local and 35 regional or distant lymph nodes (LN). For local LN, the sensitivity of FDG-PET was lower than EUS (33% v 81%, respectively; P: =.027), but the specificity may have been higher (89% v 67%, respectively; P: = not significant [NS]). For the assessment of regional and distant LN involvement, compared with the combined use of CT and EUS, FDG-PET had a higher specificity (90% v 98%, respectively; P: =. 025) and a similar sensitivity (46% v 43%, respectively; P: = NS). CONCLUSION PET significantly improves the detection of stage IV disease in EC compared with the conventional staging modalities. PET improves diagnostic specificity for LN staging.

Three-field lymphadenectomy for carcinoma of the esophagus and gastroesophageal junction in 174 R0 resections: impact on staging, disease-free survival, and outcome: a plea for adaptation of TNM classification in upper-half esophageal carcinoma

Objective:To determine the impact of esophagectomy with 3-field lymphadenectomy on staging, disease-free survival, and 5-year survival in patients with carcinoma of the esophagus and gastroesophageal junction (GEJ). Background:Esophagectomy with 3-field lymphadenectomy is mainly performed in Japan. Data from Western experience with 3-field lymphadenectomy are scarce and dealing with relatively small numbers. As a result, its role in the surgical practice of cancer of the esophagus and GEJ remains controversial. Methods:Between 1991 and 1999, primary surgery with 3-field lymphadenectomy was performed in 192 patients, of whom a cohort of 174 R0 resections was used for further analysis. Results:Hospital mortality of the whole series was 1.2%. Overall morbidity was 58%. Pulmonary complications occurred in 32.8%, cardiac dysrhythmias in 10.9%, and persistent recurrent nerve problems in 2.6%. pTNM staging was as follows: stage 0, 0.6%; stage I, 9.2%; stage II, 27.6%; stage III, 28.7%; and stage IV, 33.9%. Overall 3- and 5-year survival was 51% and 41.9%, respectively. The 3- and 5-year disease-free survival was 51.4% and 46.3%, respectively. Locoregional lymph node recurrence was 5.2%; no patient developed an isolated cervical lymph node recurrence. Five-year survival for node-negative patients was 80.2% versus 24.5% for node-positive patients. Five-year survival by stage was 100% in stages 0 and I, 59.1% in stage II, 36.8% in stage III, and 13.3% in stage IV. Twenty-three percent of the patients with adenocarcinoma (25.8% distal third and 17.6% GEJ) and 25% of the patients with squamous cell carcinoma (26.2% middle third) had positive cervical nodes resulting in a change of pTNM staging specifically related to the unforeseen cervical lymph node involvement in 12%. Cervical lymph node involvement was unforeseen in 75.6% of patients with cervical nodes at pathologic examinations. Five-year survival for patients with positive cervical nodes was 27.7% for middle third squamous cell carcinoma. For distal third adenocarcinomas, 4-year survival was 35.7% and 5-year survival 11.9%. No GEJ adenocarcinoma with positive cervical nodes survived for 5 years. Conclusions:Esophagectomy with 3-field lymph node dissection can be performed with low mortality and acceptable morbidity. The prevalence of involved cervical nodes is high, regardless of the type and location of tumor resulting in a change of final staging specifically related to the cervical field in 12% of this series. Overall 5-year and disease-free survival after R0 resection of 41.9% and 46.3%, respectively, may indicate a real survival benefit. A 5-year survival of 27.2% in patients with positive cervical nodes in middle third carcinomas indicates that these nodes should be considered as regional (N1) rather than distant metastasis (M1b) in middle third carcinomas. These patients seem to benefit from a 3-field lymphadenectomy. The role of 3-field lymphadenectomy in distal third adenocarcinoma remains investigational.

Non-alcoholic duct destructive chronic pancreatitis

Background—The pathology of non-alcoholic chronic pancreatitis has not yet been sufficiently studied. Aims—To identify the major changes of pancreatic tissue in patients surgically treated for non-alcoholic chronic pancreatitis. Patients—Pancreatectomy specimens from 12 patients with non-alcoholic chronic pancreatitis, including four patients with autoimmune or related diseases (Sjögren’s syndrome, primary sclerosing cholangitis, ulcerative colitis, and Crohn’s disease), were reviewed. Methods—Morphological changes were studied histologically and immunohistochemically (to type inflammatory cells) and compared with the pancreatic alterations found in 12 patients with alcoholic chronic pancreatitis. Results—In patients with non-alcoholic chronic pancreatitis, with or without associated autoimmune or related diseases, pancreatic inflammation particularly involved the ducts, commonly resulting in duct obstruction and occasionally duct destruction. None of these features was seen in alcoholic chronic pancreatitis which, however, showed pseudocysts and calcifications. Conclusion—The pancreatic changes in patients with non-alcoholic chronic pancreatitis clearly differ from those with alcoholic chronic pancreatitis. The term chronic duct destructive pancreatitis is suggested for this type of pancreatic disease.

Inflammatory alterations in mesenteric adipose tissue in Crohn's disease

BACKGROUND & AIMS Abnormalities of fat in the mesentery including adipose tissue hypertrophy and fat wrapping have been long recognized on surgical specimens as characteristic features of Crohns disease. However, the importance, origin, and significance of the mesenteric fat hypertrophy in this chronic inflammatory disease are unknown. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a crucial factor involved in the homeostasis of adipose tissue, a major source of biologically active mediators. METHODS Intra-abdominal fat accumulation was quantified using a magnetic resonance imaging method in patients with Crohns disease and controls. PPARgamma and inflammatory cytokines synthesized by mesenteric adipose tissues were assessed by quantitative polymerase chain reaction, in situ hybridization, and immunohistochemistry. RESULTS In vivo, patients with Crohns disease have an important accumulation of intra-abdominal fat. This mesenteric obesity, present from the onset of the disease, is associated with overexpression of PPARgamma and tumor necrosis factor (TNF)-alpha, synthesized, at least in part, by adipocytes. CONCLUSIONS These results suggest that confined increased PPARgamma mesenteric concentrations could lead to the mesenteric fat hypertrophy, which could actively participate through the synthesis of TNF-alpha in the inflammatory response.

Histopathologic validation of lymph node staging with FDG-PET scan in cancer of the esophagus and gastroesophageal junction : a prospective study based on primary surgery with extensive lymphadenectomy

ObjectiveTo assess the value of positron emission tomography with 18fluorodeoxyglucose (FDG-PET) for preoperative lymph node staging of patients with primary cancer of the esophagus and gastroesophageal junction. Summary Background DataFDG-PET appears to be a promising tool in the preoperative staging of cancer of the esophagus and gastroesophageal junction. Recent reports indicate a higher sensitivity and specificity for detection of stage IV disease and a higher specificity for diagnosis of lymph node involvement compared with the standard use of computed tomography and endoscopic ultrasound. MethodsForty-two patients entered the prospective study. All underwent attenuation-corrected FDG-PET imaging of the neck, thorax, and upper abdomen, a spiral computed tomography scan, and an endoscopic ultrasound. The gold standard consisted exclusively of the histology of sampled nodes obtained by extensive two-field or three-field lymphadenectomies (n = 39) or from guided biopsies of suspicious distant nodes indicated by imaging (n = 3). ResultsThe FDG-PET scan had lower accuracy for the diagnosis of locoregional nodes (N1–2) than combined computed tomography and endoscopic ultrasound (48% vs. 69%) because of a significant lack of sensitivity (22% vs. 83%). The accuracy for distant nodal metastasis (M+Ly), however, was significantly higher for FDG-PET than the combined use of computed tomography and endoscopic ultrasound (86% vs. 62%). Sensitivity was not significantly different, but specificity was greater (90% vs. 69%). The FDG-PET scan correctly upstaged five patients (12%) from N1–2 stage to M+Ly stage. One patient was falsely downstaged by FDG-PET scanning. ConclusionsFDG-PET scanning improves the clinical staging of lymph node involvement based on the increased detection of distant nodal metastases and on the superior specificity compared with conventional imaging modalities.

Patterns of recurrence after curative resection of pancreatic ductal adenocarcinoma

AIMS Despite curative surgery for pancreatic ductal adenocarcinoma (PDAC), most patients develop cancer recurrence and die from metastatic disease. Understanding of the patterns of failure after surgery can lead to new insights for novel therapeutic modalities. The aim of the present study is to describe the patterns of recurrence after curative resection of PDAC. METHODS A retrospective analysis was performed of 145 consecutive resections for PDAC between 1998 and 2005 (M/F 75/70; median (range) age 67 years (32-85 y)). The location of the first and consecutive recurrences, and the time interval to cancer recurrence after surgical resection was studied. The magnitude of tumour-free margin was less than a millimetre in 48 patients, whereas a positive surgical margin was observed in 27 patients. The median duration of follow-up was 18.5 (range 0.3-116.8) months. RESULTS Cancer recurrence was observed in 110 patients. The first location of recurrence was locoregional in 19, extra-pancreatic in 66, and combined locoregional and extra-pancreatic in 25 patients. Extra-pancreatic recurrence developed in the liver in 57, peritoneal in 35, pulmonary in 15, and retroperitoneal in 5 patients. The median (95% CI) overall (OS) and disease-free (DFS) survival was 18.7 (15.7-23.5) and 9.8 (7.5-12.4) months, respectively. The type of cancer recurrence did not significantly influence OS, while the resection margin status had a prognostic effect. CONCLUSION The vast majority of patients who undergo potentially curative surgery for PDAC develop cancer recurrence located in the abdominal cavity. Surgical resection margins with tumour involvement and tumour-free margins of less then 1mm are negative prognostic factors. Further research on better local surgical control, peri-operative locoregional treatment, and more effective adjuvant systemic therapy is necessary to improve long-term survival of patients with curable PDAC.

The future of the TNM staging system in colorectal cancer: time for a debate?

TNM staging has made a major contribution to the clinical management of patients with cancer over the past 50 years, but are we sure it delivers what is needed to provide adequate advice in the 21st century, and are there ways in which the system can be improved? This article, by pathologists with a special interest in colorectal cancer, is intended to offer constructive criticism towards the TNM classification of colorectal cancer, make suggestions for improvement, and recommend the adoption of a robust evidence base for this system.

Is Calcifying Fibrous Pseudotumor a Late Sclerosing Stage of Inflammatory Myofibroblastic Tumor

Calcifying fibrous pseudotumor is a recently described distinctive lesion, characterized by the presence of abundant hyalinized collagen with psammomatous or dystrophic calcifications and a lymphoplasmacytic infiltrate. The cause and pathogenesis are unclear, but a possible relationship with other pseudotumors, like nodular fasciitis or inflammatory myofibroblastic tumor, has been proposed by some authors. However, cases with overlapping histologic features have not been reported. A 17-year-old girl with multiple peritoneal calcifying fibrous pseudotumors and inflammatory myofibroblastic tumors (inflammatory pseudotumors) is described. Some multinodular lesions showed calcifying fibrous pseudotumors next to inflammatory myofibroblastic tumors. Transitional stages between calcifying fibrous pseudotumor and inflammatory myofibroblastic tumor were also present. This case clearly illustrates a histogenetic relationship between calcifying fibrous pseudotumor and inflammatory myofibroblastic tumor, and it suggests that calcifying fibrous pseudotumor is a late sclerosing stage of inflammatory myofibroblastic tumor, at least in some cases.

Expression of Carbonic Anhydrase IX (CA IX), a Hypoxia- Related Protein, Rather Than Vascular-Endothelial Growth Factor (VEGF), a Pro-Angiogenic Factor, Correlates With an Extremely Poor Prognosis in Esophageal and Gastric Adenocarcinomas

Objective:To evaluate the expression of carbonic anhydrase IX (CA IX) and vascular-endothelial growth factor (VEGF) in esophageal and gastric adenocarcinomas and in turn with the histologic subtype. Summary Background Data:Tumor hypoxia is an important factor in therapy resistance. A low oxygen concentration in tumors stimulates a.o. the expression of CA IX, a marker of hypoxia, and VEGF, a pro-angiogenic factor. Methods:We evaluated the immunohistochemical expression of CA IX and VEGF on paraffin-embedded material of 154 resection specimens: 39 esophageal, 73 cardiac, and 42 distal gastric adenocarcinomas (UICC classification). The adenocarcinomas were subtyped according to the Lauren classification (intestinal- and diffuse-type). Statistical Analysis:&khgr;2 test, Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazards model. Results:CA IX and VEGF expression were independent of the localization of the tumor. However, intestinal-type adenocarcinomas showed a significantly higher expression of CA IX as well as VEGF than diffuse-type tumors. VEGF expression was associated with a high microvessel density. Although survival analysis showed that CA IX expression (P = 0.008) as well as the coexpression of CA IX and VEGF (P = 0.008) correlate with a poor outcome, only CA IX expression is an independent prognostic factor for overall survival and metastasis-free survival. Conclusion:The difference in expression of CA IX and VEGF between intestinal- and diffuse-type adenocarcinomas may possibly explain the different clinical behavior of these tumors. CA IX expression, rather than VEGF positivity in tumors, enables the identification of a subpopulation, characterized by a more aggressive behavior and a poorer prognosis.

On the existence and location of cardiac mucosa: an autopsy study in embryos, fetuses, and infants

Background: The incidence of gastric cardiac adenocarcinoma has increased in the last decades. Gaining insight into the pathogenesis of this lesion is hampered by the limited knowledge of the origin and histology of cardiac mucosa (CM). Currently, the location, extent, and even the existence of CM are controversial. Aims: We studied the development of the gastro-oesophageal junction (GOJ) in embryos, fetuses, and infants to clarify if CM is a normal structure at birth and where it is located. Subjects: Twenty one autopsy cases were evaluated ranging in age from 13 weeks’ gestational age (GA) to seven months. Methods: The distal oesophagus and proximal part of the stomach were embedded entirely. Serial sections were stained with haematoxylin-eosin and alcian blue/periodic acid-Schiff. The following parameters were measured: length of abdominal oesophagus; length of columnar lined oesophagus; length of CM; and distance from CM to angle of His. Results: CM was present in all evaluated sections. Its mean length varied throughout gestation. A maximum value was reached at a GA of 16 weeks (1.2 mm). After term delivery it was very short (0.3–0.6 mm). CM was proximal to, or straddled, the angle of His in all cases. During gestation, the mucin staining pattern of the CM was to a high degree similar to that of the developing pyloric mucosa. Conclusions: CM develops during pregnancy and is present at birth as a normal structure. If the angle of His is taken as a landmark for the GOJ, CM is located in the distal oesophagus.