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Background
Squamous cell carcinoma of the esophagus is a devastating disease. It is usually detected in the late stages when a cure is no longer possible. The most common presentation is dysphagia (difficulty swallowing). Weight loss and hypercalcemia may also ensue.
SYNONYMS Squamous cell carcinoma INCIDENCE 310,400 new cases per year AGE-RANGE AND MEDIAN 55-74 years SEX (MALE:FEMALE) 3:1 GEOGRAPHIC DISTRIBUTION Worldwide, more common in developing countries esp. China, northeast Iran, and temparate S. America
More common among blacks
EPIDEMIOLOGIC ASSOCIATIONS CHARACTERIZATION Alcohol abuse 25x increased risk Tobacco Not as great a risk as alcohol Nitrosamines May be produced by some fungi which can contaminate some grains Zinc and vitamin A deficiency May be carcinogenic cofactors
DISEASE ASSOCIATIONS CHARACTERIZATION Tylosis palmaris et plantaris Hereditary autosomal dominant with palmoplantar keratoderma Human papilloma virus (HPV) May be important in some geographic regions but not in US
HPV types 16 and 18 incidence ranged up to 20% of casesEsophagitis May be more important in high-risk populations Achalasia Low risk about 0.41/1000 patients in USA Plummer-Vincent (Patterson-Kelly) syndrome (Siderophagic dysphagia) Most common in postmenopausal women with:
Cervical esophageal webs
Iron deficiency anemia
Poor nutrition10% develop carcinoma, also in hypopharynx and mouth
Acid and lye burns CA occurs after long latency of 30 or more years
Strictures develop in the upper esophagus
PATHOGENESIS CHARACTERIZATION p53 oncogene Mutations vary from 50-80% ras oncogenes No ras mutations Experimental induction with nitrosamines Demonstrated in lab animals Expression of Bax and Apoptosis-Related Proteins in Human Esophageal Squamous Cell Carcinoma Including Dysplasia
Atsushi Kurabayashi, Mutsuo Furihata, Manabu Matsumoto, Yuji Ohtsuki, Shiro Sasaguri and Shohei Ogoshi
Departments of Pathology II (AKMF, MM, YO) and Surgery II (AK, SS), and Vice President (SO), Kochi Medical School, Nankoku, Kochi, Japan
Mod Pathol 2001;14:741-747 Abstract quote
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.
Expression of p53-related protein p63 in the gastrointestinal tract and in esophageal metaplastic and neoplastic disorders
Jonathan N. Glickman, MD, PhD
Annie Yang, BS
Aliakbar Shahsafaei, MSc
Frank McKeon, PhD
Robert D. Odze, MD, FRCPHum Pathol 2001;32:1157-116 Abstract quote
p63 is a p53-related DNA-binding protein that helps regulate differentiation and proliferation in epithelial progenitor cells. Its expression has never been evaluated in the human gastrointestinal tract.
The aim of this study was to evaluate the expression of p63 in the esophagus and related metaplastic and neoplastic disorders to gain insight into the pathogenesis of these processes. Of particular interest was the expression of p63 in Barrett esophagus (BE) and in BE-associated multilayered epithelium. Multilayered epithelium has been postulated to represent an early precursor to the development of BE primarily because it shares morphologic and immunophenotypic features of both squamous and columnar epithelium, and has been shown prospectively to be highly associated with BE. Routinely processed mucosal biopsy or resection specimens that contained normal esophageal squamous epithelium (n = 20), squamous dysplasia (n = 4), squamous cell carcinoma (n = 7), BE (n = 10), BE-associated multilayered epithelium (n = 13), esophageal mucosal gland ducts (n = 10), BE-associated dysplasia (n = 12), and BE-associated adenocarcinoma (n = 7) were immunostained for p63 to determine the extent and location of staining. p63 staining was compared with the staining patterns observed for p53, Ki 67 (proliferation marker), and cytokeratins (CKs) 13 (squamous marker), 14 (basal squamous marker), 8/18 (columnar marker), and 19 (basal/columnar marker). Expression of p63 messenger RNA (mRNA) isoforms was also analyzed by reverse-transcription polymerase chain reaction of freshly isolated tissues.
In the normal esophagus, p63 was expressed in the basal and suprabasal layers of the squamous epithelium and in basal cells that line the mucosal gland ducts but was negative in all other epithelia of the gastrointestinal tract, including the stomach, small intestine, and colon. Similarly, p63 was not expressed in BE, but it, was present in the basal layer of multilayered epithelium in 9 of 13 cases (69%). p63-positive cells in multilayered epithelium and in the mucosal gland duct epithelium were positive for CK8/18 (100%) and CK13 (67% and 30%, respectively) and negative for CK14 (0%), in contrast to p63-positive cells in squamous epithelium, which were positive for CK14 and CK13 (100%) but negative for CK8/18.
In neoplastic tissues, p63 was diffusely expressed in all cases of esophageal squamous cell dysplasia and carcinoma but was negative in all cases of esophageal and colorectal adenocarcinoma. The N isoform of p63 mRNA predominated in all benign and neoplastic squamous tissues examined. p63 may represent a marker of 2 distinct epithelial progenitor cells (basal squamous epithelium and gland duct epithelium) in the esophagus. P63 is upregulated in squamous neoplastic conditions and in this manner may play a role in squamous carcinogenesis.
These data also indicate that multilayered epithelium is phenotypically similar to, and may share a lineage relationship with, mucosal gland duct epithelium.
LABORATORY/RADIOLOGIC/OTHER TESTS CHARACTERIZATION Hypercalcemia Hypercalcemia of malignancy
GROSS APPEARANCE/CLINICAL VARIANTS CHARACTERIZATION Superficial squamous cell carcinoma Polypoid
Plateau-like
Flat (erosive, ulcerative, and mixed)Deeply invasive squamous cell carcinoma Fungating
Ulcerative
InfiltrativeOften present in the middle and lower portions of the thoracic esophagus
HISTOLOGICAL TYPES CHARACTERIZATION Squamous epithelial dysplasia and carcinoma in situ Preinvasive histological change, may be 8x more common in high risk areas
More likely to be found when cancer is low stage and small
Some advocate dividing into low and high grade dysplasia though reproducibility is poor
Architectural and cytologic abnormalities with enlarged and hyperchromatic nuclei and increased mitotic figures, confined to the mucosaSuperficial squamous cell carcinoma Carcinoma limited to the submucosa Deeply invasive squamous cell carcinoma Invasion of the submucosa and deeper, often with deep and circumferential expansion Sarcomatoid squamous cell carcinoma (spindle cell carcinoma, carcinosarcoma) Squamous cell carcinoma mixed with a sarcomatous-like stroma
Same profile as deeply invasive squamous cell carcinomas
May be very large, 10 cm or more, usually polypoid mass
Better prognosis since most are polypoid and remain at low stageBasaloid squamous cell carcinoma Aggressive deeply invasive and rapidly fats
Large basaloid cells with high grade nuclei and numerous mitosesAdenoid cystic carcinoma Uniform basaloid cells with smal nuclei and rare mitoses
Grows in cords, cribriform, tubules, and solid nests surrounded by hyalinized basement membrane
Recurrence frequent
Metastases in 50%, usually to lungsVerrucous squamous cell carcinoma Malignant papillay tumor with well-differentiated squamous epithelium with minimal cytologic atypia growing with a pushing margin
Locally aggressive but usually do not metastasize
SPECIAL STAINS/IMMUNOPEROXIDASE/OTHER CHARACTERIZATION Cytokeratin positive
DIFFERENTIAL DIAGNOSIS CHARACTERIZATION Hyperplastic Polyps of the Esophagus and Esophagogastric Junction Histologic and Clinicopathologic Findings
Susan C. Abraham, M.D.; Vikesh K. Singh, M.D.; John H. Yardley, M.D.; Tsung-Teh Wu, M.D., Ph.D.
From the Division of Gastrointestinal/Liver Pathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
Am J Surg Pathol 2001;25:1180-1187 Abstract quote
Hyperplastic polyps of the esophagus and esophagogastric junction region (EGJ) are uncommon lesions characterized by hyperplastic epithelium (foveolar-type, squamous, or both) with variable amounts of inflamed stroma. They have been reported almost exclusively in the radiologic and clinical literature as occurring predominantly in association with gastroesophageal reflux disease (GERD). Comprehensive histologic and clinicopathologic evaluation of these polyps, their association with background mucosal pathology, and their association with Barrett's esophagus has not been previously performed.
We studied 30 hyperplastic polyps from 27 patients and characterized the histologic, endoscopic, and clinical features of both the polyps and the background esophagus. Hyperplastic polyps were most common in the region of the EGJ (67%), followed by the distal esophagus (30%) and mid-esophagus (3%). Most (80%) were composed of predominantly cardiac-type mucosa, predominantly squamous mucosa (17%), or an admixture (3%). Intestinal metaplasia of the polyp was present in only 7% and low-grade dysplasia in only 3%. In the majority of cases (67%) hyperplastic polyps were associated with concurrent or recent ulcers or erosive esophagitis. In most cases (48%) esophageal injury was associated with GERD, but other potential etiologies included medications, infection, anastomotic or polypectomy sites, vomiting, and photodynamic therapy. Four patients (15%) had Barrett's esophagus, three of whom had or developed dysplastic Barrett's mucosa.
These results underscore the pathogenesis of esophageal/EGJ region hyperplastic polyps as a mucosal regenerative response to surrounding mucosal injury. Careful clinical history and biopsy of the nonpolypoid mucosa are essential for determining the clinicopathologic context in which the polyps have developed.
PROGNOSIS CHARACTERIZATION Prognostic Factors Stage is most important
Lymph node inolvement regardless of the size of primary tumor is poor prognosis5 Year Survival Overall 6-9% survival
If tumor extends to adventitia, 10-20%
Early superficial carcinoma is potentially curable with 86% survivalPrognosis of early esophageal cancer. Comparison between adeno- and squamous cell carcinoma.
Holscher AH, Bollschweiler E, Schneider PM, Siewert JR.
Department of Surgery, Technische Universitat Munchen, Germany.
Cancer 1995 Jul 15;76(2):178-86 Abstract quote
BACKGROUND. The purpose of this study was to compare the prognosis of patients with T1 squamous cell carcinoma (SCC) with those with T1 adenocarcinoma of the esophagus and to explain prognostic differences by an analysis of clinicopathologic characteristics.
METHODS. Seventy-seven patients with early esophageal cancer who underwent esophagectomy and lymphadenectomy from 1982 to 1993 were included in the study. Clinical and histopathologic characteristics, patterns of lymph node metastasis, results of surgery, and long term prognosis of 47 patients with SCC were compared with 30 patients with adenocarcinoma; a multivariate analysis of various prognostic factors was performed.
RESULTS. The groups with adenocarcinoma and SCC were comparable regarding age, postoperative 90-day mortality (6.6% vs. 8.5%), infiltration of submucosa (74.5% vs. 80%), and rate of lymph node metastasis (17% vs. 16.6%). Cancer limited to the mucosa was not associated with lymph node metastasis in either group, whereas submucosal spread showed lymph node involvement in 21% of patients with adenocarcinoma and 26% of those with SCC. The 5-year survival rate of patients with complete tumor removal was superior for those with adenocarcinoma (82.5%) compared with those with SCC (59.2%) (P < 0.03). Multivariate analysis indicated that the histopathologic type (adenocarcinoma vs. SCC) was the only independent prognostic factor. The unfavorable prognosis of patients with T1 SCC was due to a higher recurrence rate and the more frequent development of second primary tumors (21% vs. 0%).
CONCLUSIONS. The prognosis of patients with early esophageal cancer depends on the histologic tumor type. Patients with T1 SCC should be examined for another primary cancer before surgery and during follow-up.
Metastasis Regional lymph nodes most common site
Liver and lung most common visceral organ
Local recurrences in 35% without adjuvant therapyMucosal squamous cell carcinoma of the esophagus: a clinicopathologic study of 30 cases.
Natsugoe S, Baba M, Yoshinaka H, Kijima F, Shimada M, Shirao K, Kusano C, Fukumoto T, Mueller J, Aikou T.
First Department of Surgery, Kagoshima University School of Medicine, Japan.
Oncology 1998 May-Jun;55(3):235-41 Abstract quote
A clinicopathologic study was carried out on 30 patients with mucosal esophageal cancer (MEC).
The depth of cancer invasion was subdivided histologically into three categories: m1 = carcinoma in situ (intraepithelial carcinoma) or carcinoma with questionable invasion beyond the basal membrane; m2 = cancer invasion confined to the lamina propria, and m3 = cancer reaching to or infiltrating into the muscularis mucosae. Lymph node metastases and lymphatic invasion were found only in the tumors reaching or infiltrating the muscularis mucosae (m3). The maximum histologic vertical extent of the tumors was more than 1 mm in 4 of 5 patients with lymph node metastasis or lymphatic invasion. None of the patients died of recurrent esophageal disease, and 3 of the 6 patients who had a second primary tumor died of this other malignancy.
It is critical to distinguish between m1, m2 and m3 tumors to plan a treatment strategy, including an endoscopic mucosal resection.
Prognostic factors after extended esophagectomy for squamous cell carcinoma of the thoracic esophagus.
Tachibana M, Kinugasa S, Dhar DK, Kotoh T, Shibakita M, Ohno S, Masunaga R, Kubota H, Kohno H, Nagasue N.
Second Department of Surgery, Shimane Medical University, Shimane, Japan.
J Surg Oncol 1999 Oct;72(2):88-93 Abstract quote
BACKGROUNDS AND OBJECTIVES: In Japan, extended esophagectomy with extensive lymphadenectomy has become the standard surgical procedure for carcinoma of the thoracic esophagus. Although mortality and morbidity rates after such extensive esophagectomy have been acceptable, the long-term outcomes are not necessarily satisfactory.
METHODS: Among 235 patients with primary squamous cell carcinoma of the thoracic esophagus between June 1981 and March 1998, 143 patients (60.9%) underwent extended esophagectomy with extensive lymphadenectomy. To exclude the effects of surgery-related postoperative complications, 14 patients who died within 90 days after operation were excluded. Thus, clinicopathological characteristics and prognostic factors of 129 patients were retrospectively investigated.
RESULTS: Sixty-three patients were alive and free of cancer. Sixty-six patients died: 37 of recurrence of the esophageal cancer and 29 of other causes. The 1-, 3-, 5-, and 10-year overall survival rates in the 129 patients were 78.8%, 53.5%, 45.8%, and 30.9%, respectively, and the disease-specific survival rates were 85.7%, 69.1%, 67.9%, and 56.2%, respectively. The factors influencing the disease-specific survival rate were tumor location (upper third vs. non-upper third), Borrmann classification (0, 1 vs. 2, 3), size of tumor (3.0 cm), depth of invasion (T1, 2 vs. T3, 4), number of lymph node metastases (0 or 1 vs. >/=2), time of operation (420 min), amount of blood transfused (/=3 U), lymph vessel invasion (marked vs. not marked), and blood vessel invasion (marked vs. not marked). Among those significant variables, independent prognostic factors for survival determined by multivariate analysis were number of lymph node metastases (P < 0.001), amount of blood transfusions (P = 0.0016), and tumor location (P = 0.0382).
CONCLUSIONS: Patients with a single metastatic node after extended esophagectomy should be considered to have excellent prognosis, like patients with pN0 tumors. Patients with multiple involved nodes should receive aggressive postoperative adjuvant treatments. Reduced blood loss during extended esophagectomy and minimal blood transfusions might improve the outcome of curative esophageal resections.
Prognostic factors in T1 and T2 squamous cell carcinoma of the thoracic esophagus.
Tachibana M, Kinugasa S, Dhar DK, Tabara H, Masunaga R, Kotoh T, Kubota H, Nagasue N.
Second Department of Surgery, Shimane Medical University, Izumo, Japan.
Arch Surg 1999 Jan;134(1):50-4 Abstract quote
BACKGROUND: Prognostic indicators in patients with T2 tumor have not been fully understood.
OBJECTIVE: To clarify the clinicopathologic characteristics and long-term results of T1 and T2 squamous cell carcinomas of the thoracic esophagus.
DESIGN: Consecutive case series.
SETTING: Department of surgery in a university hospital.
PATIENTS: Of 234 patients with primary squamous cell carcinoma of the thoracic esophagus, 142 patients underwent esophagectomy with curative intent: 97 patients had pT1 and pT2 tumors.
INTERVENTIONS: Investigated were clinicopathologic characteristics of 65 of 97 patients with pT1 and pT2 tumors; excluded were 7 patients who died of postoperative complications and another 25 patients who died of causes other than esophageal cancer.
MAIN OUTCOME MEASURES: Clinicopathologic characteristics and long-term results.
RESULTS: Pathologic tumor stages were pT1 N0 in 23 patients, pT1 N(+) in 7 patients, pT2 N0 in 15 patients, and pT2 N(+) in 20 patients. Fifty patients are alive and free of cancer and 15 patients died of tumor recurrence (1 patient with pT1 N0 tumor, 1 patient with pT1 N[+][+] tumor, 1 patient with pT2 N0 tumor, and 12 patients with pT2 N[+] tumor). The sites of metastatic nodes in 6 survivors with pT1 N(+) tumor were a solitary perigastric node in 4 patients, a solitary mediastinal node in 1 patient, and 2 mediastinal nodes in 1 patient. The 5-year survival rates of patients with pT1 N0, pT1 N(+), and pT2 N0 tumors all exceeded 85%, and the rate of those with pT2 N(+) tumor was 33.9% (pT2 N[+] vs. others: pT1 N0, pT1 N[+], and pT2 N0; P = .003). The factors affecting survival rate by univariate analysis were Borrmann classification (0, 1 vs. 2, 3, 4), tumor size (<4.0 vs. > or =4.0 cm), combined T, N factor (pT2 N[+] vs. others), time of operation (< or =420 vs. >420 minutes), estimated blood loss (<1000 vs. > or =1000 mL), and lymph vessel invasion (marked vs. not marked). Stage pT2 N(+) tumor became a single independent prognostic factor for survival as determined by multivariate analysis (pT2 N[+] vs. others; P = .008).
CONCLUSIONS: Stage pT1 N(+) tumors with a few diseased nodes and pT2 N0 tumors are considered to be a group with an excellent prognosis, similar to pT1 N0 tumors. Patients with pT2 N(+) diseases had worse prognoses and thus should have meticulous lymph node dissection and extensive adjuvant therapy.
Prognostic significance of perioperative blood transfusions in resectable thoracic esophageal cancer.
Tachibana M, Tabara H, Kotoh T, Kinugasa S, Dhar DK, Hishikawa Y, Masunaga R, Kubota H, Nagasue N.
Second Department of Surgery, Shimane Medical University, Izumo, Japan.
Am J Gastroenterol 1999 Mar;94(3):757-65 Abstract quote
OBJECTIVE: The perioperative blood transfusions have been associated with tumor recurrence and decreased survival in various types of alimentary tract cancer. There exist, however, contradictory studies showing no relationship between blood transfusions and survival. For patients with esophageal cancer, only one report suggested that blood transfusions did not by itself decrease the chance of cure after esophagectomy.
METHODS: Among 235 patients with primary squamous cell carcinoma of the thoracic esophagus between December 1979 and March 1998, 143 patients (60.9%) underwent esophagectomy with curative intent (RO). To exclude the effects of surgery-related postoperative complications, 14 patients who died within 90 days during the hospital stay were excluded. Thus, clinicopathological characteristics and prognostic factors were retrospectively investigated between patients with no or few transfusions (< or = 2 units) (n = 58), and much transfused patients (> or = 3 units) (n = 71).
RESULTS: Sixty-three patients are alive and free of cancer, and 66 patients are dead. A total of 98 patients (76%) received blood transfusions, whereas 31 patients (24%) had no transfusion. The amount of blood transfused was 1 or 2 units in 27 patients (27.6%), 3 or 4 units in 33 (33.7%), 5 or 6 units in 20 (20.4%), and > or = 7 units in 18 (18.4%). The 5-yr survival rate for patients with no or few transfusions was 69%, whereas that for much transfused patients was 31.7% (p < 0.0001). The much transfused patients had more prominent ulcerative tumor, longer time of operation, more estimated blood loss, and more marked blood vessel invasion than the group with no or few transfusions. The factors influencing survival rate were tumor location, Borrmann classification, size of tumor, depth of invasion, number of lymph node metastases, time of operation, amount of blood transfusions, lymph vessel invasion, and blood vessel invasion. Among those nine significant variables verified by univariate analysis, independent prognostic factors for survival determined by multivariate analysis were number of lymph node metastasis (0 or 1 vs > or = 2, p < 0.0001), amount of blood transfusions (< or = 2 units vs > or = 3 units, p < 0.0001), and blood vessel invasion (marked vs non-marked, p = 0.0207).
CONCLUSIONS: There is an association between high amount of blood transfusions and decreased survival for patients with resectable esophageal cancer. To improve the prognosis, surgeons must be careful to reduce blood loss during esophagectomy with extensive lymph node dissection and subsequently must minimize blood transfusions.
Prognostic factors in node-negative squamous cell carcinoma of the thoracic esophagus.
Tachibana M, Kinugasa S, Dhar DK, Shibakita M, Ohno S, Masunaga R, Kotoh T, Kubota H, Nagasue N.
Second Department of Surgery, Shimane Medical University, Izumo, Japan.
Int J Surg Investig 2000;1(5):389-95 Abstract quote
BACKGROUNDS: Among several clinicopathological factors influencing the outcome of patients with esophageal carcinoma, the presence or absence of lymph node metastasis is the most important. Prognostic indicators, however, in patients without lymph node involvement have not been fully understood.
MATERIALS AND METHODS: Out of 247 patients with primary squamous cell carcinoma of the thoracic esophagus between February 1981 and December 1998, 154 patients (62.3%) underwent esophagectomy with curative intent; 78 patients (50.6%) had no lymph node metastasis. Clinicopathological characteristics of those node-negative 78 patients were investigated.
RESULTS: Pathological tumor stages (pT) were pT1 in 44 patients, pT2 in 24 patients, pT3 in 9 patients, and pT4 in one patient. Forty-six patients are alive free of cancer and another one with pT2N0 tumor is alive with recurrence. Four patients died of recurrence; one in pT1 and three in pT3. The remaining 27 patients died of miscellaneous causes other than esophageal cancer. The 1-, 3-, 5-, and 10-year overall survival rates of all 78 patients including in-hospital mortality were 86.3%, 73%, 66.5%, and 34.6%, respectively. The 3- and 5-year survival rates were 75.4% and 67.7% for those with pT1, T2 tumor (n = 68) and 57.1% and 57.1% for those with pT3, T4 tumor (n = 10) (p = 0.0151). The factors influencing overall survival rate were patient age (< 65 vs. > or = 65), depth of invasion (pT1,T2 vs. pT3, T4), time of operation (< or = 420 min vs. > 420 min), and estimated blood loss (< or = 810 ml vs. > 810 ml). More elderly patients died of unrelated causes to esophageal cancer than younger patients. Among those four variables, the patient age (p = 0.0114) and depth of invasion (p = 0.0443) were independent prognosticators for survival determined by multivariate analysis.
CONCLUSION: For follow-up of elderly patients with node-negative esophageal cancer, evaluation of medical problems is more important than detection of recurrence. pT2N0 stage tumors should be considered a group with an excellent prognosis like pT1N0 tumors.
Prediction of prognosis by the extent of lymph node involvement in squamous cell carcinoma of the thoracic esophagus.
Hsu CP, Chen CY, Hsia JY, Shai SE.
Division of Thoracic Surgery, Department of Surgery, Taichung Veterans General Hospital, #160, Section 3, Taichung-Kang Road, Taichung, Taiwan.
Eur J Cardiothorac Surg 2001 Jan;19(1):10-3 Abstract quote
OBJECTIVES: Current criteria of the N-category in the TNM staging system for carcinoma of the esophagus needs further subgrouping due to its simplicity in mixing together patients with different prognosis.
METHOD: A retrospective cohort study of 186 patients (176 men and ten women; mean age, 59.9 years) with squamous cell carcinoma (SCC) of the thoracic esophagus who underwent esophagectomy followed by two-field lymphadenectomy and cervical lymph node sampling between 1992 and 1999 was conducted. A proposed N-category which involved dividing the nodal status into N0 (no nodal involvement), N1 (< or =4 nodes or < or =20% nodal involvement), and N2 (>4 nodes, or >20%, or non-regional nodal involvement) subgroups was used for survival analysis.
RESULTS: The overall 5-year cumulative survival rate was 27%. Lymph node metastases were identified in 101 (54.3%) patients. Cumulative survival rates were 46% at 4 years in the N0 group and 21% at 4 years in the N1 group, whereas no patients in N2 group survived longer than 3 years (P<0.01). A multivariable analysis revealed that independent prognostic factors included the depth of tumor invasion (P<0.01), nodal involvement (P<0.01), and organ metastasis (P<0.01).
CONCLUSION: In addition to the location of nodes, the extent of nodal involvement in SCC of the thoracic esophagus also plays an important role in prognosis prediction.
TREATMENT A clinical study of surgical treatment of patients with carcinoma of the cervical esophagus extending to the thoracic esophagus.
Saito R, Suzuki H, Motoyama S, Sasaki S, Okuyama M, Ogawa J, Kitamura M.
Second Department of Surgery, Akita University School of Medicine, Japan.
Jpn J Thorac Cardiovasc Surg 2000 Jul;48(7):417-23 Abstract quote
OBJECTIVE: We studied optimum surgery for carcinoma of the cervical esophagus extending to the thoracic esophagus (Ce-Ut carcinoma).
METHODS: Subjects were 13 patients diagnosed with Ce-Ut carcinoma treated at our institute from January 1989 to December 1998. Clinicopathologic information such as surgical procedures, pathologic findings, and postoperative complications were analyzed.
RESULTS: In 10, laryngoesophagectomy was conducted due to tracheal invasion by the tumor. In 7, mediastinal tracheostomy was done because of the extended resection of the proximal trachea. In 3, the larynx was preserved and, in 2, cricopharyngeal myotomy was added. Lymph node metastasis was found only in the neck and the upper mediastinum at surgery and recurrences were all lung metastasis. The incidence of postoperative complications was very high (76.9%), and 1 patient died due to widespread tracheal necrosis. The cumulative 5-year survival rate for the group was 33.3% and that for the 9 curative cases was 50%, but most of the cases who underwent noncurative resection and/or who received preoperative therapy for widespread invasion to surrounding organs died within a year.
CONCLUSION: The prognosis of patients who undergoing curative extended resection of the proximal trachea and suitable lymph node dissection in the neck and upper mediastinum may improve, and larynx-preserving surgery is recommended for patients without tracheal invasion. Despite preoperative chemoradiotherapy, the prognosis of patients with widespread invasion to surrounding organs was very poor, and clinical studies on new therapeutic strategies for these advanced cases are needed to improve the prognosis of Ce-Ut carcinoma patients.
Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction.
Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA.
St Vincent's Comprehensive Cancer Center, New York, USA.
N Engl J Med 2001 Sep 6;345(10):725-30 Abstract quote
BACKGROUND: Surgical resection of adenocarcinoma of the stomach is curative in less than 40 percent of cases. We investigated the effect of surgery plus postoperative (adjuvant) chemoradiotherapy on the survival of patients with resectable adenocarcinoma of the stomach or gastroesophageal junction.
METHODS: A total of 556 patients with resected adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to surgery plus postoperative chemoradiotherapy or surgery alone. The adjuvant treatment consisted of 425 mg of fluorouracil per square meter of body-surface area per day, plus 20 mg of leucovorin per square meter per day, for five days, followed by 4500 cGy of radiation at 180 cGy per day, given five days per week for five weeks, with modified doses of fluorouracil and leucovorin on the first four and the last three days of radiotherapy. One month after the completion of radiotherapy, two five-day cycles of fluorouracil (425 mg per square meter per day) plus leucovorin (20 mg per square meter per day) were given one month apart.
RESULTS: The median overall survival in the surgery-only group was 27 months, as compared with 36 months in the chemoradiotherapy group; the hazard ratio for death was 1.35 (95 percent confidence interval, 1.09 to 1.66; P=0.005). The hazard ratio for relapse was 1.52 (95 percent confidence interval, 1.23 to 1.86; P<0.001). Three patients (1 percent) died from toxic effects of the chemoradiotherapy; grade 3 toxic effects occurred in 41 percent of the patients in the chemoradiotherapy group, and grade 4 toxic effects occurred in 32 percent.
CONCLUSIONS: Postoperative chemoradiotherapy should be considered for all patients at high risk for recurrence of adenocarcinoma of the stomach or gastroesophageal junction who have undergone curative resection.
Long-term survival following induction chemoradiotherapy and esophagectomy for esophageal carcinoma.
Lew JI, Gooding WE, Ribeiro U Jr, Safatle-Ribeiro AV, Posner MC.
Department of Surgery, The University of Chicago Hospitals, and the Pritzker School of Medicine, 5841 S Maryland Ave, MC 5031, Chicago, IL 60637, USA.
Arch Surg 2001 Jul;136(7):737-42; Abstract quote
HYPOTHESIS: Long-term survival is rare in patients treated for esophageal carcinoma. Several clinical trials suggest the possibility of prolonged survival in patients who undergo induction chemoradiotherapy plus esophagectomy.
DESIGN: Prospective uncontrolled study.
SETTING: University hospital.
PATIENTS AND METHODS: Forty-four patients with carcinoma of the esophagus or gastroesophageal junction were prospectively entered into a phase II trial of preoperative 5-fluorouracil, cisplatin, and interferon alfa with concurrent external beam radiotherapy before esophagectomy. Curative resection was performed on 36 of 41 patients who completed the induction chemoradiotherapy.
RESULTS: Of the 44 patients, 17 are alive at a median follow-up of 50 months. Of these 17 patients, 15 show no evidence of recurrent disease. Of the 14 patients with long-term survival (> or =3 years), 1 patient died of disease, and another patient is alive with disease. The remaining 12 patients are alive and disease-free (median follow-up, 54 months). Six patients have survived longer than 4 years and 3 patients longer than 5 years. Subsequent primary tumors have developed in 2 patients. One patient had a recurrence at 11 months following initiation of treatment and remains disease-free 43 months postresection of a single brain metastasis. Standard clinicopathologic parameters (age, sex, histologic findings, chemoradiotherapy regimen, and clinical and pathologic stages) were not significantly associated with a survival time of 3 years or longer (Fisher exact test, 2-tailed). Although not significant, p 53 mutational status suggested long-term survival. In 11 of 14 patients who are alive with no history of recurrence, p53 genotyping demonstrated no point mutations in 10 patients. Median survival time for the long-term survivors has not been reached.
CONCLUSIONS: Long-term survival can be achieved in patients with esophageal carcinoma who undergo induction chemoradiotherapy and esophagectomy. Recurrence is unlikely in patients who survive for 3 years or longer after undergoing this multimodality treatment.
A three-step strategy of induction chemotherapy then chemoradiation followed by surgery in patients with potentially resectable carcinoma of the esophagus or gastroesophageal junction.
Ajani JA, Komaki R, Putnam JB, Walsh G, Nesbitt J, Pisters PW, Lynch PM, Vaporciyan A, Smythe R, Lahoti S, Raijman I, Swisher S, Martin FD, Roth JA.
Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer 2001 Jul 15;92(2):279-86 Abstract quote
BACKGROUND: Patients with locoregional carcinoma of the esophagus or gastroesophageal junction have a poor survival rate after surgery. Preoperative chemotherapy or chemoradiotherapy has not improved the outcome for these patients. Our study was designed to assess the feasibility of preoperative induction combination chemotherapy in addition to chemoradiotherapy to improve the curative resection rate, local control, and survival.
PATIENTS AND METHODS Patients having histologic proof of localized carcinoma (either squamous cell carcinoma or adenocarcinoma) of the esophagus or gastroesophageal junction underwent full classification including endoscopic ultrasonography (EUS). Patients first received up to two courses of induction chemotherapy consisting of 5-fluorouracil at 750 mg/m(2)/day as continuous infusion on Days 1--5, cisplatin at 15 mg/m(2)/day as an intravenous bolus on Days 1--5, and paclitaxel at 200 mg/m(2) as a 24-hour intravenous infusion on Day 1. The second course was repeated on Day 29. This was followed by radiotherapy (45 grays in 25 fractions) and concurrent admission of 5-fluorouracil (300 mg/m(2)/day as a continuous infusion 5 days/week) and cisplatin (20 mg/m(2) on Days 1--5 of radiotherapy). After chemoradiotherapy, patients underwent surgery. The feasibility of this approach, curative resection rates, patient survival, and patterns of failure were assessed.
RESULTS: Thirty-seven of 38 patients enrolled were evaluable for toxicity and survival. Adenocarcinoma and distal esophageal location of carcinoma were observed frequently. Thirty-five (95%) of the 37 patients underwent surgery, all of whom had an R0 (curative) resection. A pathologic complete response was noted in 11 (30%) of the 37 total patients. In addition, 5 patients (14%) had only microscopic carcinoma. According to EUS classification, 31 (89%) of the 35 patients who underwent surgery had a T3 carcinoma whereas according to pathologic classification only 3 (9%) had a T3 carcinoma (P
CONCLUSIONS: These data show that the three-step strategy of preoperative paclitaxel-based induction chemotherapy then chemoradiotherapy followed by surgery is feasible and appears quite active in patients having locoregional carcinoma of the esophagus or gastroesophageal junction. Future investigations should focus on substituting cisplatin with less toxic agents and including more systemic therapy with newer classes of agents.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
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