Synchronous and metachronous primary malignancies in organs other than the stomach in patients with early gastric cancer

BACKGROUND/AIMS: We investigated the outcomes of patients with early gastric cancer, with special reference to the prognosis of patients with synchronous or metachronous primary malignancies in organs other than the stomach. PATIENTS AND METHODS: Among 890 patients with early gastric cancer, 97 (10.9%) had synchronous or metachronous primary malignancies in organs other than the stomach. Ten-year survival rates were compared between patients who had additional malignancies and patients who had early gastric cancer but no other malignant disease (control group). RESULTS: Synchronous primary malignancies were detected in 32 patients and metachronous primary malignancies were detected in 65 patients (17 had developed before gastrectomy and 48 developed after gastrectomy). Hepatic cell carcinoma, lung cancer and colorectal cancer were frequently detected between 2 and 24 years after gastrectomy. The 10-year survival rate was 80.8% for 769 patients in the control group but it was only 49.7% for the 92 patients with additional malignancies. Moreover, metachronous malignant disease was found more over 10 years after gastrectomy in 30 of the 48 cases (62.5%). CONCLUSIONS: These results suggest the importance of long-term follow-up for detection of metachronous carcinomas at sites other than the stomach for patients with early gastric cancer.     

Multiple primary colorectal and gastric carcinoma in Japan

We investigated the occurrence of multiple primary colorectal and gastric cancer (MPCGC) in 1277 colorectal cancer patients between 1972 and 1996. MPCGC was found in 65 (5.1%). In the 28 synchronous cases, gastric or colorectal cancer was accidentally detected by pre-, intra-, or postoperative examinations. In 23 of the 37 metachronous cases, colorectal cancer developed on average 83 months after the operation for gastric cancer. In the other 14 cases, gastric cancer developed on average 70 months after the operation for colorectal cancer. Therefore, careful pre-, intra-, or postoperative examinations are strongly called for in order to not overlook the presence of colorectal or gastric lesions in MPCGC cases.     

Outcome after multiple colorectal tumours

BACKGROUND: Patients with primary colorectal cancers have a higher risk of development of second tumours synchronously or metachronously. This special group of patients raise a particular interest in their characteristics and outcome. METHODS: The records of 1009 patients with colorectal cancer were scrutinized. A group with multiple cancers was identified. Perioperative investigations, patterns of follow-up, pathological variables and outcome were noted. RESULTS: There were 22 patients with metachronous tumours and 39 with synchronous tumours following 'curative' operations in 20 and 28 respectively. There was no difference in Dukes classification between the two groups: Polyps were associated with metachronous lesions in ten of 22 patients and synchronous lesions in 17 of 39 patients. Five-year survival was 75 per cent for patients with metachronous tumours and only 18 per cent for those with synchronous tumours. CONCLUSION: In this study patients with metachronous tumours seemed to do very well while those with synchronous lesions did very badly. There were no identifiable demographic or clinical characteristics to account for this. There is a need to study this group of patients and identify factors like tumour biology or host resistance which prevent spread of tumour.     

Prolonged survival follows resection of oesophageal SCC downstaged by prior chemoradiotherapy

BACKGROUND: The poor survival rate of surgically treated patients with oesophageal cancer has not improved substantially over the last 25 years, but combined modality therapy has shown early promising results. METHODS: A prospective study was undertaken to determine the effect of pre-operative synchronous chemoradiotherapy followed by oesophagectomy in 53 patients with squamous cell carcinoma (SCC) of the oesophagus. The patient group was unselected, other than by fitness for surgery. RESULTS: In 25% of patients, complete pathological regression of the tumour was achieved. All but one of the patients in this subgroup had T2 tumours on pre-operative clinical staging and two had evidence of lymph node involvement, but postoperative pathological examination revealed that pre-operative chemoradiotherapy had downstaged their disease to T0N0. There was no hospital mortality in this subgroup and the actuarial 7 year survival was 69%. CONCLUSIONS: For squamous oesophageal tumours deep to the submucosa this is an extremely good survival. For the present, this form of therapy for SCC of the oesophagus appears capable of achieving results comparable to, or better than, those reported for 3-field lymphadenectomy.     

D2 receptor binding in dopa-responsive dystonia

OBJECTIVES: Synchronous gastric tumors (including benign and secondary tumors) associated with esophageal cancer present diagnostic and therapeutic issues. We investigated this synchronous association, and retrospectively determined the frequency of the gastric tumors and the clinical characteristics. METHODS: In a series of 208 patients with esophageal cancer, we investigated the synchronous gastric tumors, as well as the frequency of association, clinicopathological characteristics, diagnosis, treatment, and the clinical outcome after surgery. RESULTS: Twenty-eight gastric tumors were found in 24 patients. Adenocarcinoma was most frequent. Most of these tumors were located at the upper or middle third of the stomach. Eight gastric tumors in six patients could not be detected preoperatively. Six of these tumors including a gastric remnant cancer were detected in the resected stomach, and two leiomyomas were detected during the operation. In one patient in which an endoscope could not pass through the esophagus, a leiomyoma was detected in the resected stomach. For the gastric cancers, total gastrectomy or proximal gastrectomy with lymph node dissections was performed. For the benign tumors, partial resection of the stomach was performed, and endoscopic resection was performed preoperatively for an adenoma. In both the postoperative hospital mortality rate and the survival rate after surgery, there were no significant differences between the patients with and without gastric tumors. CONCLUSIONS: Synchronous gastric tumors associated with esophageal cancer are not rare. When an endoscope cannot pass through the esophagus before surgery, other techniques must be performed to explore the stomach. For these patients, surgical treatment should be adapted positively.     

A sensitive assay for studying dopaminergic activity in cultures of rat pituitary cells

Nine male patients with separate primary cancers of the esophagus and head and neck (pharynx, larynx) presented with a mean age of 56 years (41-69). They included 7 pharyngeal cancer patients and 2 laryngeal ones. Esophageal cancer was discovered synchronously in 6 patients and metachronously in 3 (1, 4, and 11 years later, respectively). The head and neck cancer was stage-I in one patient, stage-II in 4 and stage-IV in 4. The esophageal cancer was cervical in 2, thoracic in 6 and abdominal in 1. It was early cancer (stage-0) in 6 patients and advanced (stage-IV) in 3. The esophageal cancer was more advanced in the metachronous group, while it was early in the synchronous group. Since the head and neck cancer was advanced, all patients underwent a total laryngectomy for their head and neck cancers. As for esophageal surgery, a transhiatal esophagectomy was, in principle, performed for early cancers while a total thoracic esophagectomy was done for advanced cancers. For the reconstruction of the esophagus, a gastric tube was used. Four patients are still alive with a mean survival time of 25 months, whereas five died of cancer recurrence of either type a mean of 19 months after surgery. As compared with the survival rates of the patients with esophageal cancer alone, the 5-year survival rate was 18.2% for patients with double cancers in this series and 27.9% for those with esophageal cancer alone.     

A specific conformation of the territory of chromosome 17 locates ERBB-2 sequences to a DNase-hypersensitive domain at the nuclear periphery

Oesophageal and gastric cancers are common tumors that represent a number of challenges for oncologists, gastroenterologists and surgeons. The prognosis remains poor with the majority of patients presenting with advanced disease. Combined chemotherapy and radiotherapy has demonstrated a survival benefit in patients with loco-regional oesophageal cancer compared to radiotherapy alone. In an interim analysis we have observed a 62% response rate using a chemoradiation regimen based on protracted venous infusion of 5-fluorouracil and cisplatin combined with radiotherapy in patients with inoperable oesophageal cancer. Improved outcomes with loco-regional disease has rekindled interest in preoperative therapy. In a trial comparing preoperative chemoradiation to surgery alone in patients with operable oesophageal adenocarcinoma, survival was improved with multimodality treatment. In addition, a study including both adeno- and squamous carcinomas demonstrated a trend towards improved survival. A complete pathological response to chemoradiation was associated with significantly improved survival. Gastric cancer is one of the most chemosensitive solid tumors of the gastrointestinal tract with the majority of patients being suitable for palliative chemotherapy. The ECF (epirubicin, cisplatin, protracted venous infusion 5-fluorouracil) regimen was developed in the Gastrointestinal unit of the Royal Marsden Hospital and first reported in 1991. In a prospective randomised trial including 274 patients ECF has been compared with the standard combination of 5-fluorouracil, adriamycin and methotrexate (FAMTX) in patients with previously untreated gastric cancer. Overall response rate, failure-free and overall survival were significantly improved with ECE, ECF also demonstrated improved quality of life and cost effectiveness when compared to the FAMTX regimen. ECF should now be regarded as the standard treatment for advanced oesophago-gastric cancer against which new therapies should be compared. In addition the Medical Research Council are conducting a trial randomising patients between surgery alone and perioperative chemotherapy using the ECF regimen in operable gastric cancer.     

Surgical and nonsurgical management of primary and metastatic liver tumors

The medical records of 267 patients who had liver tumors, primary and metastatic, from 1988 to 1995 were retrospectively reviewed. Two hundred thirteen patients (80%) had metastatic disease, and 54 patients (20%) had primary liver disease. Their clinical manifestations and laboratory values were evaluated as factors predictive of diagnosis and survival. There was a significant increase in the occurrence of upper abdominal pain, weight loss, extrahepatic symptoms due to the metastatic origin, and hepatomegaly. Metastases from colorectal primary lesions were synchronous in 34 patients and metachronous in 31 patients. Stomach, lung, and pancreatic primaries were more commonly synchronous. Breast metastases were more commonly metachronous. Elevated serum glutamic-oxaloecetic transaminase and alkaline phosphatase and decreased albumin were the most common liver test abnormalities at diagnosis. Carcinoembryonic antigen values were elevated in the majority of colon cancer patients. Eighty-one percent of patients with primary liver cancer had elevated levels of alpha-fetoprotein, 40 per cent were seropositive for hepatitis B, and 23 per cent were seropositive for hepatitis C. Seventy-nine patients (30%) underwent surgery for their cancer, 37 (47%) had resections, 38 (48%) were unresectable, and 4 (5%) underwent liver transplantation. The patients who underwent surgery had a 32 per cent 5-year survival rate compared to a 0 per cent 5-year survival in the patients who did not have surgery (p = 0.0001). The patients who had resections had a better survival rate than those deemed unresectable at surgery (62% versus 0% at 5-years with p = 0.0008). The perioperative morbidity rate was 16 per cent, with lobectomies having the best rate and trisegmentectomies having the worst. Perioperative mortality rate was zero for all liver resections. Hepatic resection and, in selected patients, liver transplantation are the only two available therapeutic modalities that produce long-term survival with a possible cure in patients with primary and metastatic liver tumor.     

Four multiple primary malignant neoplasms of the aerodigestive tract

Multiple primary cancers of the head, neck, and upper aerodigestive tract have been documented in patients previously treated for oropharyngeal cancer. There generally is no causal relationship established between the different tumors. Two synchronous or metachronous cancers are common, three are unusual, and four are very unusual. We describe the treatment of a patient with tonsillar and synchronous esophageal and pulmonary cancers followed by a tongue cancer over a 6-year period.     

Characteristics and clinical outcome of proximal-third gastric cancer

BACKGROUND: It is generally accepted that the prognosis of patients with proximal gastric cancer (PGC) is worse than that of patients with more distal gastric cancer. STUDY DESIGN: The aim of this study was to compare the clinical features and outcomes of PGC with those of middle- and distal-third gastric cancers. A total of 646 primary gastric cancers was analyzed as a retrospective study. RESULTS: Proximal gastric cancer occurred in 21.8% of the 646 cancers analyzed, and approximately 21% of PGCs had esophageal invasion. The 5-year survival rate for patients with PGC was significantly lower than that of patients with more distal tumors. When the PGC group was divided into patients with esophageal invasion and without esophageal invasion, patients with esophageal invasion had significantly worse outcomes. When corrected for depth of invasion, lesions with esophageal invasion had significantly worse outcomes than those of other sites in T2 curative cancers. Proximal gastric cancer with esophageal invasion was characterized by a larger tumor, deeper penetration, and a higher incidence of lymph node metastasis compared with tumors in other sites, and in multivariate analysis of all curative cases, these variables were independent prognostic factors for survival. The frequency of positive proximal margins of PGC was higher than those of other sites. CONCLUSIONS: The relatively poor prognosis associated with PGC is mainly from advanced tumor stages of esophageal invasion. Early detection is the most important strategy to improve the survival of patients with PGC. In addition, aggressive lymph node dissection and chemotherapy for esophageal invasion should be considered even if the tumor invasion is moderate (T2 tumor), and a tumor-free margin is important.     

Clinicopathological characteristics of gastric cancer in the elderly

The clinicopathological features of 380 elderly patients 70 years of age or older with gastric cancer were reviewed retrospectively from hospital records between 1969 and 1993. They were then compared with 1134 middle-aged patients between 40 and 69 years. The elderly constituted 18.4% of all gastric cancer patients 20 years ago but now comprise 24.4% of all patients in the most recent decade, despite the overall decrease in the rate of gastric cancer. The distinguishing histological features of gastric cancer in the elderly were an intestinal type of cancer, expansive tumour growth and synchronous multiplicity of the lesions. Elderly patients had a similar rate of tumour extension but had poorer survival as compared with the middle-aged patients. Post-operative death within 30 days after surgery was also higher in the elderly than in the middle-aged patients.     

Development of synchronous bilateral lung cancers after esophagectomy for esophageal cancer: report of a case

It is well known that squamous cell carcinoma of the esophagus can be associated with carcinoma of other organs. We report herein the rare case of a 60-year-old man who developed synchronous bilateral lung cancers after undergoing esophagectomy for esophageal cancer. Staged bilateral lobectomy was successfully performed to minimize respiratory complications 3 years after his esophagectomy. This case report serves to demonstrate that aggressive and careful surgical approach with adequate followup offers the chance of long-term survival for patients with multiple primary cancers.     

The correlation between microscopical examination and erythrocyte band 3 (AE1) gene deletion in South-east Asian ovalocytosis

Seventy-five patients with brain metastases from solid tumours were treated with whole-brain irradiation at our institution between 1990 and 1993. The primary cancers included 35 cases of lung cancer, 19 cases of breast cancer, nine cases of renal-cell cancer, six cases of melanoma and six cases of other primary sites. In each case the total dose to the whole brain was at least 25 gray (Gy). The primary site, age, performance status, number of brain metastases and the presence of extracranial disease were studied as prognostic factors for survival. The median survival for the whole population was 4 months (range 1-62 months). The patients with the brain as the only metastatic site had significantly better survival (P = 0.019) than those with both intracranial and extracranial metastatic sites. Poor performance status at the time of diagnosis of brain metastases was also related to short survival (P = 0.001). None of the other studied variables had prognostic significance. Four of the 75 patients with primary tumour sites in the breast (two patients) and the kidney (two patients) survived for more than 2 years. In general, patients with breast cancer had better survival than patients with other primary cancers. Our study confirms the generally poor prognosis of cancer with brain metastases, although individual patients may survive several years after whole-brain irradiation. Approximately two-thirds of the patients experienced a relief in symptoms allowing a reduction in the dose of corticosteroid medication, which clearly supports the use of whole-brain radiotherapy as a palliative treatment.     

Synchronous hepatocellular carcinoma or metastatic hepatic tumor with primary gastric cancer

BACKGROUND/AIMS: When a solitary hepatic tumor occurs synchronously with gastric cancer, it is usually presumed to be metastatic. However, this may not be true in a place like Taiwan, where hepatocellular carcinoma (HCC) is prevalent. This study was conducted to examine the clinicopathological factors of both conditions. METHODOLOGY: A retrospective analysis of 14 patients who underwent a synchronous hepatectomy in combination with radical gastrectomy over the past 15 years was performed. RESULTS: Seven patients had metastatic gastric cancer, and seven had concomitant gastric and hepatic cancer. Serosal invasion and lymph node metastasis were the major features in the patients with metastatic gastric cancer. Early gastric cancer was found in three of the patients with the coexisting primary cancers. No patient with solitary metastatic cancer survived more than one year, but long-term survival of more than two years was achieved in two patients with the two forms of cancer. CONCLUSIONS: Double cancer of the stomach and liver should be kept in mind in patients with gastric cancer concomitant with a solitary hepatic tumor, in order to provide optimal treatment.     

Phase II study: concurrent chemo-radiotherapy in advanced nasopharyngeal carcinoma

Oesophageal carcinoma is a major cause of cancer death in certain parts of the world. Early detection provides the only chance of cure. In this study, one female and nine male patients with superficial oesophageal carcinoma were investigated to determine the pertinent clinical and pathological features. All male patients were smokers and six patients drank various amounts of alcohol on a daily basis. Histologically, five cases were confined within the mucosal layer and five within the submucosal layer. All five mucosal cancer cases and two of the five submucosal cancer cases were asymptomatic. Endoscopically, all five mucosal cancer patients had flat lesions, whereas the five submucosal cancer tumours appeared either protruding or depressed. Barium oesophagography failed to demonstrate the lesions in four of five mucosal cancer and one of five submucosal cancer cases. Endoscopic ultrasonography correctly detected the depth of cancer invasion in six out of eight superficial oesophageal carcinoma cases. All patients received a one-stage operation that included oesophagectomy and lymph node dissection. All five mucosal cancer patients had no lymph node involvement and have experienced no tumour recurrence. Among them, one who had concomitant hepatocellular carcinoma died early. Of the five submucosal cancer cases, four died 1-5 years after the operation. It is concluded that oesophageal carcinoma is curable in its early stage. Physicians should be alert while performing endoscopic examination. We believe that the dyeing technique is a useful adjunct to endoscopic examination.     

Establishment of a hereditary nonpolyposis colorectal cancer registry

INTRODUCTION: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant condition characterized by early age of onset colorectal cancer, right-sided predominance, excess of synchronous and metachronous colonic neoplasms, and extracolonic cancers. The purpose of this study is to report clinical characteristics of HNPCC families in our registry. METHODS: This is a retrospective review of medical records of patients with a significant history of colorectal cancer and interviews with their families. RESULTS: Three hundred one people with cancer in 40 HNPCC families were identified. In 284 of 301 (94 percent) people, 363 cancers were identified. Colorectal cancer only was identified in 182 people (64 percent) and, in conjunction with extracolonic tumors, in another 31 people (11 percent). Extracolonic cancer alone was noted in 71 people (25 percent). Median age at diagnosis of colorectal cancer was 48 (range, 17-92) years. In patients with documented pathology, right-sided tumors predominated (55 percent), synchronous and metachronous tumors were noted in 53 percent, and synchronous of metachronous adenomas were documented in 51 percent of people. Generational anticipation was also noted. CONCLUSION: This study demonstrates and confirms characteristics that have been described in HNPCC. Namely, early age of onset of colorectal cancer, right-sided predominance, multiple synchronous and metachronous neoplasms, increased extracolonic cancers, and generational anticipation.     

DNA repair capacity and cisplatin sensitivity of human testis tumour cells

To identify characteristics of gastric cancer associated with hereditary non-polyposis colorectal cancer (HNPCC), we gathered clinical data and tumor samples relating to patients recorded in the Finnish HNPCC registry. Our series included 51 families with a characterized mutation and/or that met the Amsterdam criteria. Of 570 members affected by malignancy, gastric cancer occurred in 62. Adequate clinical data were obtained for 45 patients. Tumor samples from 24 patients were re-examined. The mean age of diagnosis of gastric cancer was 56 years. The average percentage of all cancers within a family was 11 (range 0-40). Nineteen were of the intestinal type. Only 3 were of the diffuse type. Helicobacter pylori infection was demonstrated in 3 of 15 cases. Replication error (RER) phenotype was present clearly in 7 cases and at least fairly clearly in 11. The overall 5-year survival rate was 15%. The 5-year survival rate was 48% in cases in whom radical surgery had been undertaken. Our results support the view that gastric cancer belongs to the tumor spectrum of HNPCC. The intestinal type of histology is characteristic, as is the RER+ phenotype, but H. pylori infection was rare.     

Event-related correlates of response suppression as indicators of novelty seeking in alcoholics

We examined amplification of the c-met, c-erbB-2, and epidermal growth factor receptor (EGFR) gene in the patients with primary gastric cancer, and compared the data with clinical features in order to clarify the relationship between oncogenic abnormality and clinical features. Oncogene amplifications were examined by slot blot hybridization using DNAs extracted from formalin-fixed and paraffin-embedded tissues of primary gastric cancers. Seven of the seventy cancers (10.0%) had c-met gene amplification, nine (12.9%) had c-erbB-2 gene amplification, and six (8.6%) had EGFR gene amplification, respectively. Eighteen cases (25.7%) exhibited one or multiple oncogene amplification, and two cases (2.9%) exhibited simultaneous amplification of the three genes. The cases with c-met gene amplification tend to show invasive character and were related to peritoneal dissemination. The cases with c-erbB-2 gene amplification were related to lymph node metastasis. The cases with EGFR gene amplification had large tumors and were in highly advanced stage. The survival rate in patients with oncogene amplification was significantly lower than that in patients without amplification. Our data indicated that these genes were related to growth and metastasis of gastric cancer. Furthermore, this study about the three genes suggested that the type of activated gene might decide on the type of metastasis and clinical features.     

Characterization of two Chinese hamster ovary cell lines expressing the COOH-terminal domains of sterol regulatory element-binding protein (SREBP)-1

BACKGROUND: To assess surgical outcome after oesophagectomy, we reviewed operative techniques and postoperative course among 90 patients who underwent oesophageal resection for malignancies from January 1989 to December 1995. METHODS: There were 73 males and 17 females; mean age was 64.2 years. Indications were squamous cell carcinoma in 49 patients and adenocarcinoma in 41. Preoperatively 7 patients had chemotherapy and 18 benefited from radiochemotherapy. There were 56 total thoracic oesophagectomies, with anastomosis in the neck in 34 patients and at the thoracic inlet in 22. In 34 cases operation was limited to distal oesophageal resections. Digestive continuity was restored with the stomach in 62 patients, with the colon in 24, and with a jejunal loop in 4. A feeding jejunostomy was constructed in 48 patients with a gastric transplant. RESULTS: Mortality was 10% (9 patients), decreasing from 18.5% (before 1993) to 3.8% (since 1993). One patient died in the colonic graft group and 8 in the gastric pull-up group. Postoperative complications occurred in 9 patients after colonic interposition and in 23 after gastric pull-up; they consisted in pulmonary infection or insufficiency in 26 patients, cerebrovascular accident in one, renal insufficiency in 2, recurrent nerve palsy in 4, and anastomotic leakage in 6. Transhiatal approach was not associated with a decreased incidence of postoperative deaths or complications. Eighteen patients (72%) developed postoperative pulmonary complications after preoperative chemotherapy. CONCLUSION: Oesophagectomy can be performed with low mortality. A colonic graft is not associated with an increased incidence of perioperative deaths or complications and is the substitute of choice when there is any question regarding gastric vascularization, or in young patients with long life expectancy. Preoperative neoadjuvant treatment significantly increases postoperative pulmonary complications.     

Recent arguments in advanced gastric cancer treatment]

In advanced inoperable gastric cancer patients, survival was significantly prolonged for the group receiving antineoplastic treatment against only the best supportive care group by some randomized controlled studies. Greater prolongation of survival is expected from surgery in CR and PR cases because of the change from inoperable to operable. One problem is that the evaluation of response to the primary site is different between Japan and other countries. Outside of Japan, it is considered that barium contrast studies and routine endoscopy are not sufficient for tumor response assessment at the primary site. I think this is not true evaluation of the response to gastric cancer chemotherapy to exclude primary site assessment. We must generalize the Japanese criteria of gastric cancer chemotherapy throughout the world.