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NCI CANCERLIT® Search: Esophageal Neoplasms - September 2001
Last Modified: November 1, 2001

Table of Contents

CancerMail from the National Cancer Institute

1
UI - 21183416
AU - Geshelin SA
TI - [TNM classification of the intestinal malignancies]
SO - Klin Khir 2000 May;(5):46-9

2
UI - 21227885
AU - Eksteen JA; Scott PA; Perry I; Jankowski JA
TI - Inflammation promotes Barrett's metaplasia and cancer: a unique role for TNFalpha.
SO - Eur J Cancer Prev 2001 Apr;10(2):163-6

AD - Epithelial Laboratory, Division of Medical Sciences, University of Birmingham, Edgbaston, UK.

3
UI - 21379547
AU - Roullet MH; Wind P; Zinzindohoue F; Laccourreye O; Berger A; Chevallier JM; Bonfils P; Brasnu D; Cugnenc PH
TI - [Esophagectomy for squamous cell carcinoma of the esophagus isolated or associated with head and neck cancer: long-term survival]
SO - Ann Chir 2001 Jul;126(6):526-34

AD - Service de chirurgie digestive, hopital europeen Georges-Pompidou, 20, rue Leblanc, 750015 Paris, France.
STUDY AIM: Esophageal squamous cell carcinomas are frequently associated with head and neck cancers. This retrospective study was conducted to compare the long-term outcome of the patients with a double cancer and of the patients with a solitary esophageal cancer after curative management. PATIENTS AND METHODS: From 1989 to 1999, 114 patients with an esophageal carcinoma were included in the study. Among them, 52 had an associated head and neck cancer (metachronous: n = 17 and synchronous: n = 35). Curative treatment was achieved in all patients. The patients were divided in "solitary" and "associated" group. RESULTS: Age, sex distribution, tumor location and histological findings were similar in the two groups. The esophageal resection was an esopharyngolaryngectomy (n = 13), a subtotal esophagectomy with cervical anastomosis (n = 92) and a Lewis-Santy esophagectomy with thoracic anastomosis (n = 9). Operative mortality (8 versus 7.7%), anastomotic leaks rate (14.5 versus 21%) and pneumonia rate (21 versus 9.6%) were not significantly different in the two groups. The mean hospital stay was 27 days. The mean follow-up was 85 +/- 50 months. Five-year survival rates were not significantly different in the two groups (p = 0.6411). In univariate survival analysis the only significant predictive factors were the depth of esophageal tumor invasion (p = 0.0002) and node involvement (p = 0.0373). The presence of head and neck cancer did not affect survival after esophagectomy. CONCLUSION: With an aggressive therapeutic plan, the survival of patients with an esophageal cancer associated to head and neck cancer was similar to the survival of patients with an isolated esophageal carcinoma. Long term esophageal survey seems to be useful to detect more superficial esophageal carcinomas in patients with head and neck cancer.

4
UI - 21385067
AU - Handra-Luca A; Terris B; Couvelard A; Molas G; Degott C; Flejou JF
TI - Spindle cell squamous carcinoma of the oesophagus: an analysis of 17 cases, with new immunohistochemical evidence for a clonal origin.
SO - Histopathology 2001 Aug;39(2):125-32

AD - Department of Pathology, Beaujon Hospital, Clichy, France.
AIMS: To study the morphological and immunohistochemical characteristics of spindle cell squamous carcinoma of the oesophagus, in order better to understand the histogenesis of this tumour. METHODS AND RESULTS: In this study we analysed the morphological and immunohistochemical characteristics of 17 cases of spindle cell squamous carcinoma of the oesophagus. Most tumours were polypoid, but tumours with an ulcerated and infiltrative pattern were also observed. Histologically, most tumours were of superficial type, with a characteristic morphological aspect consisting of two types of tumour cells, i.e. differentiated squamous cells, and spindle cells with transition zones between the two components. On immunohistochemistry, the squamous cells were positive for cytokeratin and the spindle cells showed variable expression of cytokeratin, vimentin and smooth muscle actin. p53 protein was over-expressed in 10 cases, both tumour cell types showing strong nuclear positivity. In most tumours, E-cadherin was expressed in the squamous cells and absent in the spindle cells. CONCLUSIONS: The similar pattern of p53 protein expression in the two tumour cell types of spindle cell squamous carcinoma of the oesophagus suggests their common origin. The change in adhesion molecule expression with loss of E-cadherin expression may be associated with the acquisition of spindle cell morphology by the squamous tumour cells.

5
UI - 21399392
AU - Voskuil JH; van Dijk MM; Wagenaar SS; van Vliet AC; Timmer R; van Hees PA
TI - Occurrence of esophageal granular cell tumors in The Netherlands between 1988 and 1994.
SO - Dig Dis Sci 2001 Aug;46(8):1610-4

AD - Department of Gastroenterology, De Tjongerschans Hospital, Heerenveen, The Netherlands.
Granular cell tumors (GCT) of the esophagus are rare. The tumor is generally beleived to be of neurogenic origin and shows a malignant course in 2-4% of cases. No unanimity has been reached regarding the management of this tumor. A national survey was conducted on the incidence of GCT of the esophagus, related symptoms, management, and follow-up. A national survey was performed on all newly registered esophageal GCTs in the PALGA system (Dutch register of all pathology diagnoses) for seven consecutive years (1988-1994). Fifty-two new cases (17 men, 35 women; median age 46 years, range 22-77 years) were registered. In 44 cases clinical data could be obtained (survey response 85%). The majority of the GCTs were solitary (42/44) and localized in the distal esophagus (33/44). At endoscopy the size of the tumor was estimated at <5 mm in 50%, 5-10 mm in 25%, and 10-30 mm in 18%. Most patients (40/44) presented with nonspecific gastrointestinal symptoms, only four had dysphagia (tumor size >1 cm). No malignancies were reported. Management of the tumor included excisional biopsy (1/44), endoscopic polypectomy (3/44), and surgical excision (1/44). Endoscopic follow up (1-60 months) in 16 out of 17 patients left untreated showed either a stable tumor size or regression of the tumor. In one case with multiple GCT's a slight tumor growth was seen after a follow-up period of 48 months. Esophageal GCTs in the Netherlands are rare, and mostly diagnosed incidentally. Most patients suffer from nonspecific symptoms; dysphagia occurs only with tumors >1 cm. The usual clinical course of esophageal GCTs is benign. Patients without dysphagia probably do not require routine endoscopic follow-up, provided they are instructed to contact their physician, once dysphagia develops.

6
UI - 21396379
AU - Kurabayashi A; Furihata M; Matsumoto M; Ohtsuki Y; Sasaguri S; Ogoshi S
TI - Expression of Bax and apoptosis-related proteins in human esophageal squamous cell carcinoma including dysplasia.
SO - Mod Pathol 2001 Aug;14(8):741-7

AD - Department of Pathology II, Kochi Medical School, Nankoku, Kochi, 783-8585, Japan.
The rate of tumor growth depends on the balance between proliferation and death of tumor cells. It is known that Bax, caspase-3, and p53 proteins are death-promoting factors, whereas Bcl-2 protein is a death antagonist. We immunohistochemically examined the expression of Bax and apoptosis-related proteins such as caspase-3, p53, and Bcl-2 in 76 patients with human esophageal squamous cell carcinoma (SCC) including dysplasia to determine the relationship of expression of each protein to tumor behavior and patients' prognosis. No significant relationships in immunopositivity were found among these proteins in SCCs. Cytoplasmic Bax expression was exhibited in 63 cases of SCCs (82.9%). The apoptotic index of caspase-3-positive lesions was significantly higher than that of caspase-3-negative lesions in both dysplasia and SCC (P =.016, P =.012). On the other hand, the apoptotic index (1.18%) was significantly correlated with Bax overexpression in dysplasia (P =.006), but not in SCC lesions (P =.129). The patients with Bax-positive SCCs were found to have a poor prognosis by the Kaplan-Meier method (P =.043). These findings suggested that Bax expressed in dysplasia may play a role as an apoptotic factor, but that it may be functionally inactive in some cancerous lesions and thus not contribute to suppression of the tumor progression in some cases of human esophageal SCCs.

7
UI - 21406683
AU - Dimick JB; Cattaneo SM; Lipsett PA; Pronovost PJ; Heitmiller RF
TI - Hospital volume is related to clinical and economic outcomes of esophageal resection in Maryland.
SO - Ann Thorac Surg 2001 Aug;72(2):334-9; discussion 339-41

AD - Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-4605, USA.
BACKGROUND: Previous studies have documented a relationship between hospital volume and perioperative and economic outcomes. Our objective was to determine the effect of hospital volume on outcomes of esophageal resection. METHODS: Statewide database was analyzed for patients who underwent esophageal resection in Maryland (n = 1,136 patients) from 1984 to 1999. Multivariate regression was used to determine the association of hospital volume with in-hospital mortality, length of stay, and charges after adjusting for case mix and time period. RESULTS: Unadjusted in-hospital mortality rates were lower in high volume hospitals (2.7%) than medium (12.7%) and low (16%) volume hospitals (p < 0.001). High hospital volume was associated with (1) fivefold reduction in the risk of death (odds ratio, 0.21; 95% confidence interval, 0.10 to 0.42; p < 0.001); (2) a 6-day (95% confidence interval, 5 to 7 days; p < 0.001) reduction in length of stay; and (3) $11,673 (95% confidence interval, $9,504 to $12,841; p < 0.001) decrease in hospital charges. Conclusions. Hospitals that perform high volumes of esophageal resection have superior clinical and economic outcomes. By referring these patients to high volume centers, we may improve quality and reduce costs.

8
UI - 21406759
AU - Pollock J
TI - Radiation-induced secondary malignancy of the esophagus.
SO - Ann Thorac Surg 2001 Aug;72(2):669

9
UI - 21379832
AU - Gallus S; Bosetti C; Franceschi S; Levi F; Simonato L; Negri E; Vecchia CL
TI - Oesophageal cancer in women: tobacco, alcohol, nutritional and hormonal factors.
SO - Br J Cancer 2001 Aug 3;85(3):341-5

AD - Istituto di Ricerche Farmacologiche "Mario Negri", Via Eritrea 62, Milan, 20157, Italy.
We analysed 3 case-control studies from Italy and Switzerland including 114 women with squamous cell oesophageal cancer and 425 controls. The multivariate odds ratio was 4.5 for heavy smoking and 5.4 for heavy alcohol drinking. Fruit intake, vegetable intake, oral contraceptive and HRT use were inversely related to oesophageal cancer. Copyright 2001 Cancer Research Campaign.

10
UI - 21379840
AU - Salmela MT; Karjalainen-Lindsberg ML; Puolakkainen P; Saarialho-Kere U
TI - Upregulation and differential expression of matrilysin (MMP-7) and metalloelastase (MMP-12) and their inhibitors TIMP-1 and TIMP-3 in Barrett's oesophageal adenocarcinoma.
SO - Br J Cancer 2001 Aug 3;85(3):383-92

AD - Department of Dermatology, University of Helsinki, Finland.
Oesophageal adenocarcinoma is believed to arise from metaplastic mucosa in the distal oesophagus, a condition also known as Barrett's oesophagus (BE). BE develops as a result of injury caused by refluxing gastric and duodenal contents and is associated with increased risk of malignant transformation. Matrix metalloproteinases (MMPs) have been implicated in all aspects of tumour progression; tumour growth, basement membrane degradation, invasion and metastatic spread. Using in situ hybridization, we investigated the expression patterns of collagenases-1 and -3, stromelysin-2, matrilysin, metalloelastase and TIMPs-1 and -3 in BE, adenocarcinoma and lymph-node metastases. Matrilysin was expressed abundantly in 12/15 tumours and in 4/6 lymph-node metastases and its expression correlated with the histological aggressiveness of tumour. Matrilysin and metalloelastase were upregulated already in BE. Stromelysin-2 and collagenase-3 expression was detected only in a few tumours. Collagenase-1 was expressed by cancer and stromal cells in 9/15 tumours. Tumour-infiltrating macrophages expressed metalloelastase in 13/15 cancers. TIMPs-1 and -3 were expressed in 12/15 and 11/15 tumours, respectively. Laminin-5 and tenascin were abundantly expressed at the invasive front of poorly differentiated tumours, but not in BE. Our results indicate that matrilysin is the principal MMP expressed by tumour cells in oesophageal adenocarcinoma, and further studies are needed to investigate whether matrilysin or tenascin-C could be used as a predictive marker for progression of BE to cancer. Copyright 2001 Cancer Research Campaign.

11
UI - 21379844
AU - Nishioka K; Doki Y; Shiozaki H; Yamamoto H; Tamura S; Yasuda T; Fujiwara Y; Yano M; Miyata H; Kishi K; Nakagawa H; Shamma A; Monden M
TI - Clinical significance of CDC25A and CDC25B expression in squamous cell carcinomas of the oesophagus.
SO - Br J Cancer 2001 Aug 3;85(3):412-21

AD - Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, 2-2-E2, Yamadaoka Suita, Osaka, 565-0871, Japan.
CDC25A, CDC25B and CDC25C belong to a family of protein phosphatases which activate the cyclin-dependent kinase at different points of the cell cycle. According to accumulating evidence, CDC25A and CDC25B seem to possess oncogenic properties. We have analysed these expressions by immunohistochemistry, western blot and RT-PCR in a series of 100 patients with squamous cell carcinoma of the oesophagus. When compared with non-cancerous cells, CDC25A and CDC25B were strongly expressed in the cytoplasm of cancer cells, with positive (+) classification in 46% (46 cases) and 48% (48 cases), respectively. There was no significant correlation between CDC25A and CDC25B expression, nor was there any association with the expression of other cell cycle-regulating molecules, including cyclin D1, Rb, p16(INK4), p27(KIP1)and PCNA (proliferating cell nuclear antigen). CDC25A (+), as well as CDC25B (+), was more frequently found in patients with deeper tumour invasion and lymph node metastasis, while tumour size was correlated only with CDC25A expression. Postoperative survival was significantly poorer for CDC25A (+) patients than CDC25A (-) patients, but was not affected by the CDC25B status. Nuclear localization of CDC25A was observed in 51 cases (51%), regardless of its cytoplasmic expression, and was not associated with clinico-pathological factors or prognosis. Multivariate analysis revealed only the CDC25A status to be an independent significant prognostic factor among these biological and clinico-pathological factors. CDC25A but not CDC25B may be a new prognostic factor for squamous cell carcinoma of the oesophagus. Thus, regulation of the G1 checkpoint in the cell cycle may be important in oesophageal carcinogenesis, which may also involve many other oncogenes. Copyright 2001 Cancer Research Campaign.

12
UI - 21255258
AU - Messmann H
TI - Squamous cell cancer of the oesophagus.
SO - Best Pract Res Clin Gastroenterol 2001 Apr;15(2):249-65

AD - Department of Internal Medicine I, University of Regensburg, Germany.
Squamous cell cancer is the most common neoplasm of the oesophagus worldwide, with an enormous variation in its global incidence. Several risk factors, such as achalasia, Plummer-Vinson syndrome, coeliac disease and nutritional factors, have been identified. The surveillance of patients, especially those with tylosis or caustic ingestion, has been recommended. Vital staining with iodine may improve the diagnosis of early cancer. The endoscopic management of early cancer and dysplasia by minimal invasive techniques such as photodynamic therapy or mucosal resection has become attractive for many of these patients with co-morbidity. Copyright 2001 Harcourt Publishers Ltd.

13
UI - 21255259
AU - Pech O; Gossner L; May A; Ell C
TI - Management of Barrett's oesophagus, dysplasia and early adenocarcinoma.
SO - Best Pract Res Clin Gastroenterol 2001 Apr;15(2):267-84

AD - Department of Internal Medicine II, Horst Schmidt Hospital, Wiesbaden, Germany.
There has been a dramatic increase in recent years in the incidence of Barrett's oesophagus and the oesophageal adenocarcinoma associated with it. Adequate monitoring strategies and improved diagnostic procedures are therefore essential. Alongside conventional video-endoscopy with four-quadrant biopsies, many additional diagnostic procedures are now available to improve monitoring. These allow the early diagnosis of dysplastic areas and early carcinomas. Both thermal procedures (argon plasma coagulation, multipolar electrocoagulation and KTP laser and Nd∶YAG laser treatment) and non-thermal ablation procedures (photodynamic therapy) are used for the endoscopic ablation of Barrett's mucosa without dysplasia, being employed in addition to acid suppression treatment. On the basis of the data currently available, it is, however, not yet possible to offer a general recommendation in favour of endoscopic ablation. Alongside surgical treatment for high-grade dysplasia and early carcinoma, endoscopic treatment procedures, which have a much lower complication and mortality rate, will probably play an important role in the future. Endoscopic mucosal resection and photodynamic therapy are particularly promising. Long-term results with these procedures are, however, still awaited. Copyright 2001 Harcourt Publishers Ltd.

14
UI - 21364841
AU - Launois B; Raoul JL; Leprise E; Meunier B
TI - [Neoadjuvant treatment in surgery of esophageal cancer]
SO - Bull Acad Natl Med 2000;184(8):1703-13; discussion 1714

AD - Departement de Chirurgie, l'Universite de Rennes.
We conducted a prospective study on neoadjuvant treatment for squamous cell carcinoma of the esophagus, modifying the chemotherapy protocol by adding l-folinic acid and giving bifractionated radiotherapy with a cis-diaminedichloroplatinum (CDDP) injection before each fraction. Thirty-two patients, 30 men, 2 women, mean age 56.2-8.9 years, with resectable squamous celi carcinoma of the esophagus (TNM stage I = 4, IIA = 4, IIB = 13, III = 11) were included. Chemotherapy, CDDP (80 mg/m2: D2), 5-fluorouracil (5-FU; 600 mg/m2, D1-4), and 1-folinic acid (200 mg/m2, DI-4), was given in two sessions with a 3-week interval during which the patients received radiotherapy (45 Gy), two fractions per day (150 cGy/fraction). A 3-mg Injection of CDDP was given prior to each fraction. Patients underwent surgery 4 to 7 weeks after neoadjuvant therapy. No severe side effects were observed in 12 patients. Grade 3 effects (WBC, platelests, mucosite's) occurred in 16 patients and grade 4 effects (platelets, mucositis) in four including 1 death due to septicemia with an infected catheter. Surgery was performed in 29 patients; 26 had resectable tumors (81%). Operative mortality was 10%. The 26 surgical specimens showed complete response (n = 18), persistent microscopic residues (n = 4), or not significant modification (n = 4). Survival at 1, 3, and 5 years was 82, 47, and 47% and disease-free survival was 77, 47, and 47% respectively. This new therapeutic combination is aggressive and associated with a high postoperative mortality but has a remarkable histological effect since complete response was achieved in 56% (95% CI: 39-73%) of the patients and 5-year survival reached 47%, a very high rate in our experience.

15
UI - 21364843
AU - Etienne J; Dorme N; Bourg-Heckly G; Raimbert P; Fekete F
TI - [Local curative treatment of superficial adenocarcinoma in Barrett's esophagus. First results of photodynamic therapy with a new photosensitizer]
SO - Bull Acad Natl Med 2000;184(8):1731-44; discussion 1744-7

AD - Centre de Therapie photodynamique pluridisciplinaire, Clinique Les Martinets, 97 avenue Albert Ier-92500 Rueil-Malmaison.
Pre-cancerous lesions and mucosally confined superficial cancers can benefit from local therapy given with curative intent due to the absence of near metastatic lymph nodes. Photodynamic therapy (PDT) which acts by laser irradiation with an appropriate wave-length after administration of a photosensitiser retained preferentially by the cancerous tissue can destroy tumour cells selectively, but its efficiency depends upon the photosensitiser. The results presented concern 10 sites on Barrett's mucosa (BO). They consisted of either an association of intramucosal cancer (IMC) with high-grade dysplasia (HGD) or of high-grade dysplasia alone. The method consisted of intravenous injection of Temoporfin 0,15 mg/kg 4 days before irradiation of the lesion with a green laser light emitting 514 nm through a windowed diffuser. The light fluence was 75 J per cm2 and irradiation 100 mW per cm2. Irradiation time was 12,5 mn. Omeprazole was routinely prescribed after treatment at a dose of 40 mg daily. The follow-up protocol was 2 years with endoscopic surveillance at 2, 3, 6, 12, 18 and 24 months. Biopsies obligatory at 2 and 3 months were in fact carried out at all the other delays. Efficacy was judged on the absence of high-grade dysplasia or intra mucosal carcinoma on biopsies at treated sites. Undesirable side effects noted have been moderate for the most part. No stenosis appeared. Treatment has been 100% successful for the 10 lesion after 15 treatments with PDT. The follow up varies from 6-36 months and was more than 18 months for 6 lesions on 5 patients. Our series has demonstrated a great heterogeneity in lesions which were sometimes visible and highly localised, but more often invisible, multi-focal and diagnosable only by biopsy at different levels. In keeping with the literature and our experience, PDT has several advantages over the other locally curative therapies, mucosectomy and thermocoagulation. These are the possible treatments without general anaesthesia, selectively for cancer cells, an action on more extensive areas with eradication of non visible lesions. Temoporfin has contributed notably to the field of photodynamic therapy compared to previously used sensitisers. It is a pure, synthetic product which guarantees more reproducible results. Compared with Photofrin, Temoporfin has many advantages with smaller doses of drugs and less energy, better selectivity and rapid elimination which reduce the risk period for photosensitisation. The frequency of important undesirable side effects is diminished. Finally, it produces a consistent effect on the surface and in depth producing a complete reepithelialisation of the treated zones. Subject to validation of the method on a greater number of patients, the first results obtained on superficial cancer in Barrett's aesophagus allow us to propose green light Temoporfin PDT as an alternative first line therapy with curative intent.

16
UI - 21225880
AU - Delcambre C; Jacob JH; Pottier D; Gignoux M; Ollivier JM; Vie B; Roussel A; Segol P
TI - Localized squamous-cell cancer of the esophagus: retrospective analysis of three treatment schedules.
SO - Radiother Oncol 2001 May;59(2):195-201

AD - Centre Francois Baclesse, Route de Lion sur Mer, 14076, Caen, France.
BACKGROUND AND PURPOSE: A retrospective study comparing chemotherapy and radiation, esophagectomy alone versus preoperative radiochemotherapy and surgery in localized squamous-cell esophageal carcinoma. MATERIALS AND METHODS: Between 1989 and 1995, 139 patients (40 stage I, 77 stage IIA and 22 stage IIB according to the UICC 78 TNM classification) were treated in two different institutions. They were divided into three groups according to the treatment proposed: E group (treatment by esophagectomy; n = 30), RCT+E group (treatment by preoperative radiochemotherapy and esophagectomy; n = 46), RCT group (treatment by radiochemotherapy; n = 63). Factors like age, tumor localization and stage were similar in all groups. An intention to treat analysis was made. RESULTS: The E group showed no postoperative mortality, while in the RCT+E group, the surgery mortality was 12.8%. The mortality after RCT was 1.7%. After preoperative radiochemotherapy, a pathological complete response was observed in 25% of cases and the curative resection rate was higher (82% after RCT + E versus 60% after E). The 5-year survival difference between the three groups was not relevant (E group, 12.6%; RCT group, 25.8%; RCT + E group, 38.7%). The median survival was 29, 24 and 28.5 months, respectively. The event-free survival was identical for the E group and the RCT group. For patients treated by radiochemotherapy, local and/or distant relapses were significantly reduced by esophagectomy (relapses occurred in 51% of patients in the RCT + E group versus 75% in the RCT group, P = 0.017). Palliative care (dilatations, prosthesis, gastrostomy or jejunostomy) to improve dysphagia was necessary for 38% of patients treated by exclusive radiochemotherapy versus 11% of patients treated by surgery (P = 0.001). CONCLUSIONS: Treatments by esophagectomy or radiochemotherapy were not significantly different. Preoperative radiochemotherapy and surgery lead to a higher survival rate than exclusive radiochemotherapy, however, with a high postoperative mortality rate. This study suggests the relevance of a prospective randomized trial to compare RCT+E and RCT alone.

17
UI - 21356471
AU - Liedman B; Johnsson E; Merke C; Ruth M; Lundell L
TI - Preoperative adjuvant radiochemotherapy may increase the risk in patients undergoing thoracoabdominal esophageal resections.
SO - Dig Surg 2001;18(3):169-75

AD - Department of Surgery, Sahlgrenska University Hospital, Goteborg, Sweden. liedman@sahlgrenska.se
BACKGROUND/AIM: Fatigue and malaise are common symptoms after radiochemotherapy which could affect patients' working capacity and add to the subsequent postoperative risk. The aim of the study was to investigate whether neoadjuvant radiochemotherapy in patients scheduled for a thoracoabdominal resection impairs their working capacity and adds to the postoperative risk. PATIENTS AND METHODS: 29 patients with resectable tumors (T(3) or N(1)) and a working capacity of > or =80 W on a bicycle test were included into the study. The tumor stage was determined by endoscopic ultrasound and computed tomography scan. The patients were given neoadjuvant radiochemotherapy during 38 days, consisting of two cycles of 5-fluorouracil (1,000 mg/m(2)) daily during 5 days and cisplatinum (100 mg/m(2)) on two occasions. Accelerated radiochemotherapy to a total dose of 40.8 Gy was given. Surgery was planned 4-6 weeks after completion of therapy. The patients had a bicycle test before induction of neoadjuvant treatment and 2-5 days prior to the operation. RESULTS: Three patients died already during the course of neoadjuvant treatment. The 26 remaining patients who had a bicycle test decreased their working capacity by a mean of 30 W (p < 0.0001). Ten patients had a decrease of their working capacity to < or = 90 W, of whom 6 died within 3 months postoperatively, and of the patients who had the working capacity decreased to < or = 80 W, 4 out of 5 died during the corresponding postoperative period. None of the patients, who performed >100 W at the second preoperative bicycle test died. CONCLUSIONS: Preoperative adjuvant radiochemotherapy, according to the present schedule, clearly exerts a detrimental effect on the patients' working capacity. A physical performance, at the time of the operation, < or = 80-90 W strongly predicts the subsequent postoperative risk. Similar adjuvant therapies may, therefore, in fact be harmful to some patients scheduled for a thoracoabdominal resection. Copyright 2001 S. Karger AG, Basel

18
UI - 21411754
AU - Mariette C; Maurel A; Fabre S; Balon JM; Triboulet JP
TI - [Preoperative prognostic factors for squamous cell carcinomas of the thoracic esophagus]
SO - Gastroenterol Clin Biol 2001 May;25(5):468-72

AD - Service de Chirurgie Digestive et Generale, Hopital Claude-Huriez, CHRU, Lille.
AIM OF THE STUDY: To identify preoperative survival prognostic factors in patients with resectable squamous cell carcinoma of the thoracic esophagus. POPULATION: From January 1982 to September 1999, 868 patients underwent surgery for esophageal carcinoma in our department, including 493 for squamous cell carcinoma of the thoracic esophagus. The following parameters were retrospectively included in univariate and multivariate analysis: age, sex, undernutrition, dysphagia, tumor diameter and nodal involvement on the CT-scan, preoperative treatment, surgical technique, curative resection, pTNM classification, histologic type and postoperative complications. The actuarial survival was determined. RESULTS: Survival prognostic factors were dysphagia, nodal involvement on CT-scan and depth of tumor invasion at pathological examination. Three groups of patients were identified on the two preoperative variables: group 1: patients without dysphagia (n=102), group 2: patients with dysphagia but without nodal involvement on the CT- scan (n=244), group 3: patients with dysphagia and with nodal involvement on the CT- scan (n=147). The median survivals were 62.4, 19.1 and 14.4 months in groups 1, 2 and 3, respectively, and 5-year actuarial survivals were 50%, 21% and 11% (P<0.009). CONCLUSION: Our study confirms that dysphagia and nodal involvement on the CT-scan are simple preoperative prognostic factors in patients with resectable squamous cell carcinoma of the thoracic esophagus.

19
UI - 21402380
AU - Fuwa N; Nomoto Y; Shouji K; Kodaira T; Kamata M; Ito Y
TI - Therapeutic effects of simultaneous intraluminal irradiation and intraluminal hyperthermia on oesophageal carcinoma.
SO - Br J Radiol 2001 Aug;74(884):709-14

AD - Department of Radiation Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusaku, Nagoya 464-0021, Japan.
An applicator enabling simultaneous intraluminal radiotherapy and intraluminal hyperthermia delivery was developed to improve the treatment results for locally advanced oesophageal carcinoma. Eight inoperable cases were treated by this method. Six cases received 40 Gy external irradiation followed by simultaneous intraluminal hyperthermia and radiotherapy (3 Gy and 4 Gy in three cases each) once weekly for 3 weeks; the remaining two cases received 50 Gy external irradiation followed by simultaneous intraluminal hyperthermia and radiotherapy (4 Gy) once weekly for 2 weeks. Hyperthermia was delivered by a radiofrequency current thermotherapy instrument for 30 min at an output that raised the oesophageal mucosal surface temperature to 42-43 degrees C. Intraluminal radiotherapy was delivered with a microSelectron to a submucosal depth of 5 mm after the first 15 min of hyperthermia. Four cases achieved complete response, with all demonstrating local control. Partial response was obtained in four cases, and three of these patients died of local recurrence. There were no significant adverse side effects apart from fistula in one case. In conclusion, simultaneous intraluminal radiotherapy and hyperthermia may improve the current treatment results for locally advanced oesophageal carcinoma.

20
UI - 21404882
AU - Gupta NM; Gupta R; Rao MS; Gupta V
TI - Minimizing cervical esophageal anastomotic complications by a modified technique.
SO - Am J Surg 2001 Jun;181(6):534-9

AD - Department of Surgery, Postgraduate Institute of Medical Education and Research, 160012, Chandigarh, India. medinst@pgi.chd.nic.in
BACKGROUND: The anastomotic leak and stricture formation after esophagectomy and cervical esophagogastric anastomosis deny patients with esophageal carcinoma the benefits of surgery. The present study was designed to ascertain whether a wide cross-sectional area at the site of anastomosis leads to lesser anastomotic complications. METHODS: One hundred patients with resectable carcinoma of the esophagus were randomly distributed into two groups of 50 each. All patients underwent one-stage transhiatal esophagectomy. In group A, 3 x 2 cm gastric crescent was excised from the anterior wall of the gastric tube before constructing the cervical esophagogastric anastomosis. No such intervention was done in group B, which acted as control. All patients were followed up for at least 3 months for detection of anastomotic complications. RESULTS: The incidence of anastomotic leak in the study group was significantly less in comparison with the control group (4.3% versus 20.8%; P = 0.03). Similarly, anastomotic stricture formation was significantly lower in the study group (8.5% versus 29.2%; P = 0.02). CONCLUSIONS: A wide cross-sectional area achieved at the anastomotic site by removal of gastric crescent resulted in significantly lower anastomotic complications.

21
UI - 21413554
AU - Kihara C; Tsunoda T; Tanaka T; Yamana H; Furukawa Y; Ono K; Kitahara O; Zembutsu H; Yanagawa R; Hirata K; Takagi T; Nakamura Y
TI - Prediction of sensitivity of esophageal tumors to adjuvant chemotherapy by cDNA microarray analysis of gene-expression profiles.
SO - Cancer Res 2001 Sep 1;61(17):6474-9

AD - Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
We applied cDNA microarray analyses of 9216 genes to establish a genetic method for predicting the outcome of adjuvant chemotherapy to esophageal cancers. We analyzed expression profiles of 20 esophageal cancer tissues from patients who were treated with the same adjuvant chemotherapy after removal of tumor by operation, and we attempted to find genes associated with the duration of survival after surgery. By comparing expression profiles of those cancer tissues, we identified by statistical analysis 52 genes that were likely to be correlated with prognosis and possibly with sensitivity/resistance to the anticancer drugs. We also developed a drug response score based on the differential expression of these genes, and we found a significant correlation between the drug response score and individual patients' prognoses. Our results indicated that this scoring system, based on microarray analysis of selected genes, is likely to have great potential for predicting the prognosis of individual cancer patients with the adjuvant chemotherapy.

22
UI - 21230825
AU - Bosetti C; Franceschi S; Negri E; Talamini R; Tomei F; La Vecchia C
TI - Changing socioeconomic correlates for cancers of the upper digestive tract.
SO - Ann Oncol 2001 Mar;12(3):327-30

AD - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. bosetti@marionegri.it
BACKGROUND: Cancers of the upper digestive tract have long been associated with low socio-economic levels. It has however been suggested that in recent times the social gradient for these cancers is leveling off. PATIENTS AND METHODS: Data from three case-control studies on oral, pharyngeal and oesophageal cancer conducted in Northern Italy during the periods 1984-1992 and 1992-1997 were combined and re-analyzed. Cases were subjects admitted to the major teaching and general hospitals in the areas under study with incident, histologically confirmed cancer of the oral cavity and pharynx (n = 1126) and oesophagus (n = 714). Controls were subjects admitted to the same hospitals for a wide spectrum of acute, non-neoplastic conditions, not related to smoking or alcohol consumption (n = 4642). RESULTS: In the 1980s a significant association was observed with low education and social class level. The multivariate odds ratios for oral, pharyngeal and oesophageal cancers combined was 1.78 for the lowest versus the highest educational level, and 1.75 for the lowest versus the highest social class. No consistent pattern of risk was observed with any of the socio-economic indicators considered in the studies conducted in the 1990s. CONCLUSIONS: The present study indicates that the socio-economic correlates of cancers of the upper digestive tract have changed over the last few years in Italy, with a disappearance of the social gradient.

23
UI - 21236677
AU - Whyte RI
TI - Advances in the staging of intrathoracic malignancies.
SO - World J Surg 2001 Feb;25(2):167-73

AD - Department of Cardiothoracic Surgery, Division of Thoracic Surgery, Stanford University, CVRB 205, 300 Pasteur Drive, Stanford, California 94305, USA. riwhyte@leland.stanford.edu
Conventional staging of lung and esophageal tumors has consisted of a thorough history and physical examination, screening laboratory studies, computed tomography, and radionuclide imaging. Newer modalities including positron emission scanning, endoscopic ultrasonography, minimally invasive surgery (laparoscopy and thoracoscopy), and immunohistochemical staining of lymph node tissue. The role of these techniques are subject to much current debate, and they may ultimately add information that is valuable for staging and optimally treating patients with intrathoracic malignancies.

24
UI - 21236680
AU - Law S; Wong J
TI - What is appropriate treatment for carcinoma of the thoracic esophagus?
SO - World J Surg 2001 Feb;25(2):189-95

AD - Department of Surgery, Division of Esophageal Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong, China.
Recent advances in the treatment of esophageal cancer have yielded a variety of new options for management of this highly lethal disease. Various approaches to surgical resection have been proposed. Chemotherapy and radiotherapy with or without surgery have been tested in numerous trials, the results of which are often conflicting and confusing for clinicians. The changing epidemiology of the disease between East and West adds to the controversy. In this review, the authors address some of the more controversial debates. The following questions are asked: What is the appropriate approach for surgical resection? What is the appropriate extent of resection? Is multimodality treatment appropriate for esophageal cancer?

25
UI - 21236681
AU - Orringer MB; Marshall B; Iannettoni MD
TI - Transhiatal esophagectomy for treatment of benign and malignant esophageal disease.
SO - World J Surg 2001 Feb;25(2):196-203

AD - Section of General Thoracic Surgery, Department of Surgery, University of Michigan Medical Center, 2120 Taubman Health Care Center, 1500 E. Medical Center Drive, Box 0344, Ann Arbor, Michigan 48109, USA. morrin@umich.edu
Since our initial 1978 report, we have performed transhiatal esophagectomy (THE) in 1085 patients with intrathoracic esophageal disease: 285 (26%) benign lesions and 800 (74%) malignant lesions (4.5% upper, 22% middle, and 73.5% lower third/cardia). THE was possible in 97% of patients in whom it was attempted; reconstruction was performed at the same operation in all but six patients. The esophageal substitute was positioned in the original esophageal bed in 98%, stomach being used in 782 patients (96%) and colon in those with a prior gastric resection. Hospital mortality was 4%, with three deaths due to uncontrollable intraoperative hemorrhage. Major complications included anastomotic leak (13%), atelectasis/pneumonia prolonging hospitalization (2%), recurrent laryngeal nerve paralysis, chylothorax, and tracheal laceration (< 1% each). There were five reoperations for mediastinal bleeding within 24 hours of THE. Intraoperative blood loss averaged 689 ml. Altogether, 78% of the patients had no postoperative complications. Actuarial survival of the cancer patients mirrors that reported after transthoracic esophagectomy. Late functional results are good or excellent in 80%. Approximately 50% have required one or more anastomotic dilatations. With intensive preadmission pulmonary and physical conditioning, use of a side-to-side staple technique (which has reduced the cervical esophagogastric anastomotic leak rate to less than 3%), and postoperative epidural anesthesia, the need for an intensive care unit stay has been eliminated and the length of hospital stay was reduced to 7 days. We concluded that THE can be achieved in most patients requiring esophageal resection for benign and malignant disease and with greater safety and less morbidity than the traditional transthoracic approaches.

26
UI - 21253232
AU - Stein HJ; Feussner H
TI - Comment on "The role of laparoscopy in preoperative staging of esophageal cancer".
SO - Surg Endosc 2001 May;15(5):528-9

27
UI - 21297118
AU - Jiao X; Krasna MJ; Sonett J; Gamliel Z; Suntharalingam M; Doyle A; Greenwald B
TI - Pretreatment surgical lymph node staging predicts results of trimodality therapy in esophageal cancer.
SO - Eur J Cardiothorac Surg 2001 Jun;19(6):880-6

AD - Department of Thoracic Surgery, University of Maryland Medical System, 22 South Greene Street, 21201, Baltimore, MD, USA.
OBJECTIVE: Prediction of responders to induction therapy in esophageal cancer (EC) patients is important. In this study, we evaluated the role of thoracoscopic/laparoscopic (Ts/Ls) staging in prediction of treatment response and survival in EC patients with trimodality treatment. METHODS: Retrospective study of EC patients who had undergone Ts/Ls staging and received trimodality treatment at the University of Maryland Medical Center and the Baltimore Veterans Administration Hospitals from July, 1991 to December, 1999. Preoperative therapy consisted of concurrent chemotherapy (5-FU + cisplatinum) and radiotherapy. RESULTS: Forty-four EC patients who underwent pretreatment Ts/Ls staging during the study period were able to complete concurrent chemoradiotherapy followed by surgical resection. There were 36 men and 8 women aged 40 to 77 (median age 62). Twenty-seven (61.4%) patients were found to have lymph node metastasis by surgical staging. Fourteen patients (31.8%) had a pathologic complete response. Patients with positive lymph nodes had a lower response rate than those with negative lymph nodes (14.8% vs. 58.8%, P=0.006). Other clinicopathologic features including gender, weight loss, clinical TNM stage, surgical T stage, and histology did not correlate with treatment response. Univariate analysis showed that weight loss and treatment response were important prognostic factors for disease-free survival (P=0.01 and P=0.02, respectively). Histology, surgical N stage and surgical TNM stage appeared to be associated with prognosis (P=0.067-0.097). Multivariate analysis revealed that only surgical N status and weight loss were significant prognostic factors (P=0.05, and P=0.006, respectively). CONCLUSIONS: Surgical Ts/Ls staging provides accurate evaluation of tumor spread in EC patients. Pretreatment N status was the single most important predictor of response to induction treatment as well as a reliable prognosticator of survival.

28
UI - 21297119
AU - Igaki H; Kato H; Tachimori Y; Sato H; Daiko H; Nakanishi Y
TI - Prognostic evaluation for squamous cell carcinomas of the lower thoracic esophagus treated with three-field lymph node dissection.
SO - Eur J Cardiothorac Surg 2001 Jun;19(6):887-93

AD - Department of Surgery, National Cancer Center Hospital and Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, 104-0045, Tokyo, Japan. hiigaki@gan2.res.ncc.go.jp
OBJECTIVE: The efficacy of esophagectomy with three-field lymph node dissection in surgical treatment for patients with squamous cell carcinomas of the lower thoracic esophagus remains controversial. This report documents the outcomes of this surgical procedure for a large series. METHODS: From February 1986 to November 1998, 437 patients with squamous cell carcinomas of the thoracic esophagus underwent transthoracic esophagectomy with three-field lymph node dissection. One hundred and sixteen of these had cancer of the lower thoracic esophagus. To avoid the influence of adjuvant therapy on survival, 20 who also received radiation and/or chemotherapy were excluded, leaving 96 patients who were retrospectively analyzed. RESULTS: The operative morbidity, and 30-day and in-hospital mortality rates were 62, 0, and 3%, respectively. The overall 1-, 3-, and 5-year survival rates were 89, 65, and 59%, with a median survival of 76 months. In those with lymph node metastases (66% of cases), the values were 87, 56, and 48%, as compared with 94, 84, and 79%, respectively (P=0.005) for patients without lymph node metastasis. Factors significantly influencing the overall survival rates were patient age (> or = 65 vs. <65), clinical N status (cN1 vs. cN0), clinical M status (cM1 vs. cM0), longitudinal tumor length of resected specimen (> or =5 vs. <5 cm), pathologic T status (pT3 vs. pT1, 2), pathologic N status (pN1 vs. pN0), lymphatic invasion (positive vs. negative), vascular invasion (positive vs. negative) and intramural metastasis (present vs. absent). Independent prognostic factors for survival determined by multivariate analysis were pathologic T status (P=0.02), pathologic N status (P=0.03), and presence of intramural metastasis (P=0.04). Additional pathologic M1 status, cervical or celiac lymph node metastasis, was without significant influence. CONCLUSIONS: Patients with pathologic T3 tumors with both pathologic N1 status and the presence of intramural metastasis in the lower thoracic esophagus had a poor prognosis. Cervical or celiac lymph node metastasis in patients with carcinomas of the lower thoracic esophagus should be distinguished from pathologic M1 status in the UICC-TNM staging system.

29
UI - 21303172
AU - Tang JC; Lam KY; Law S; Wong J; Srivastava G
TI - Detection of genetic alterations in esophageal squamous cell carcinomas and adjacent normal epithelia by comparative DNA fingerprinting using inter-simple sequence repeat PCR.
SO - Clin Cancer Res 2001 Jun;7(6):1539-45

AD - Department of Pathology, The University of Hong Kong, Hong Kong.
In this study, we screened 19 esophageal squamous cell carcinomas (ESCCs) for the detection of genetic alterations using inter-simple sequence repeat PCR, a DNA fingerprinting approach. Three simple repetitive unanchored primers representing tri- and tetranucleotide repeats [(GTG)(5), (GACA)(4), and (GATA)(4)] were used, and evidence of gains and losses of chromosomal sequences were detected in all tumors (19 of 19 cases) for at least one of the primers. In 13 of these cases, apparently normal marginal epithelia adjacent to the tumors were also collected and examined. Eight of the 13 (62%) patients showed matching somatic mutations in the marginal epithelia adjacent to the tumors. Five of these 8 (63%) marginal epithelial samples were histologically normal, two were dysplastic, and one had extremely rare tumor cells. In 3 of these 13 (23%) cases, the profile bands were also seen to quantitatively increase in intensity, progressing from normal epithelia to marginal epithelia to tumors. Ten profile bands showing gains and one profile band showing loss in tumors compared with the corresponding normal epithelia were cloned, and their origins were determined by sequencing. The DNA sequence of one of the profile bands showing gain in the tumor could be matched to an expressed sequence tag sequence that has been mapped to the 7q22 region, a genomic amplification novel to ESCC. The sequence of the other profile band showing gain in the tumor could be matched to a nonexonic sequence of chromosome 20, whereas the sequences of the remaining profile bands could not be matched with any known sequences after comparison with the genomic sequence data in the European Molecular Biology Laboratory and GenBank databases. The bona fide nature of the gains or losses of 11 profile bands in the original cases was confirmed by direct genomic PCR amplification. The frequencies of these specific gene alterations in tumors were then analyzed in a total of 60 ESCCs, which included 41 additional cases of ESCC. Significantly, 26 of 60 (43%) tumors showed the DNA amplification for the expressed sequence tag sequence of chromosome 7, whereas the frequency of other individual gene alterations ranged from 7% to 15%. It is concluded that the inter-simple sequence repeat PCR strategy is adequate for the detection of somatic mutations in tumors, most of which are quantitative alterations in anonymous genomic sequences. This approach is also suitable for detection of somatic mutations preceding the onset of morphologically detectable neoplasia in ESCC.

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