Multiple primary malignancies in patients with head and neck cancer

From July, 1978 to December, 1985, 1,138 cases of malignancies of the head and neck were treated at the authors' hospital, and up to June, 1986, 132 patients with multiple primary malignancies were detected. In all cases, the incidence rate of a multiple primary malignancy was 11.6%. In 45 (33.0%) of these head and neck cancer cases, the multiple cancer was detected simultaneously, and as for the other cases (66.7%), they were discovered metachronously. In patients with a cancer of the mesopharynx, the incidence rate of a multiple primary malignancy was the highest (25.8%), whereas in those with a cancer of the parotid gland and in those with a cancer of the hypopharynx, the incidence rates were 20.0% and 14.9%, respectively. In most patients the second malignancy occurred in the same head and neck region, and in the rest, the second malignancy was a gastric cancer, a lung cancer, or an esophageal cancer in that descending order. Of the 45 synchronous cancer cases, ten were a thyroid cancer, most being latent. In head and neck malignancies, the authors stress the importance of a precise investigation prior to start of therapy and of maintaining follow-up investigations after therapy.     

Heredity and risk of cancer of the esophagus and gastric cardia.

The importance of genetic factors in the etiology of esophageal cancer is uncertain. We addressed the question of heredity in a population-based, nationwide case-control study conducted in Sweden during 1995 through 1997. The study involved 189 patients with esophageal adenocarcinoma, 262 with cardia adenocarcinoma, 167 with esophageal squamous cell carcinoma, and, for comparison, 820 control subjects. Familial occurrence of cancer was explored at face-to-face interviews. Logistic regression, with multivariate adjustment for potential confounders, was used to calculate odds ratios (ORs), which estimated relative risk. Occurrence of esophageal cancer among first-degree relatives did not increase the risk of adenocarcinoma or squamous cell carcinoma of the esophagus. Neither were there any significant associations with familial occurrence of gastric cancer or other gastrointestinal tumors. The risk of cardia adenocarcinoma was moderately increased among persons with first-degree relatives with gastric cancer (OR, 1.6; 95% confidence interval, 1.0-2.6). Familial occurrence of any cancer was not associated with increased risks of any of the three studied tumors. In conclusion, heredity does not seem to contribute importantly to the occurrence of esophageal cancer of any histological type. A weak association between familial gastric cancer and the risk of cardia cancer may represent a genetic link.     

MAL基因与肿瘤

MAL基因是一个在T细胞分化中晚期表达的基因。许多研究表明MAL基因在食管癌、胃癌、结肠癌、头颈部鳞癌等多种肿瘤组织中表达下调或缺失，与肿瘤的发生发展过程有关。MAL基因要作为临床诊断、判断预后及指导治疗的指标而得到应用，还需要进一步研究。     

MAL基因与肿瘤

MAL基因是一个在T细胞分化中晚期表达的基因.许多研究表明MAL基因在食管癌、胃癌、结肠癌、头颈部鳞癌等多种肿瘤组织中表达下调或缺失,与肿瘤的发生发展过程有关.MAL基因要作为临床诊断、判断预后及指导治疗的指标而得到应用,还需要进一步研究.     

Microsatellite instability associated with primary head and neck cancers and secondary esophageal cancers

BACKGROUND: It is common that patients with head and neck cancers have secondary malignant neoplasm of esophageal cancer. METHODS: To know the genetic background of the development of these secondary cancers, we performed microsatellite assay at six loci and immunohistochemical analysis on head and neck cancers of eight patients with esophageal cancer and on those of 19 patients without esophageal cancer. RESULTS: Replication error (RER) at more than two loci was observed in two (25%) of eight double cancer patients, whereas it was not observed in the patients without the secondary cancer. Immunohistochemically, overexpression of cyclin D1 was detected in two (25%) of eight double cancer cases and in two (11%) of 19 non-double cancer cases, respectively, the incidence showing a higher tendency in the former. CONCLUSIONS: The results suggest that microsatellite instability may be implicated in the development of head and neck double cancers and that RER (+) phenotype may serve as a biomarker to predict the development of secondary esophageal cancer in patients with head and neck cancer.      

Pedunculated gastric tube interposition in an esophageal cancer patient with prepyloric adenocarcinoma

Gastric carcinoma is one of the malignancies that are most frequently associated with esophageal carcinoma.We describe herein our device for advanced esophageal cancer associated with early gastric cancer in the antrum.A 57-year-old man presenting with dysphagia and upper abdominal pain was admitted to our hospital.Preoperative examinations revealed locally advanced squamous cell carcinoma (SCC) of the middle thoracic esophagus (T3N0M0 Stage ⅡA) and mucosal signetring cell carcinoma of the gastric antrum (T1N0M0 Stage ⅠA).Although the gastric tumor appeared to be an intramucosal carcinoma,its margin was obscure,so endoscopic en-bloc resection was considered inadequate.We chose surgical resection of the gastric tumor as well as the esophageal SCC after neoadjuvant chemotherapy with 5-fluorouracil and cisplatin for advanced esophageal cancer.Following transthoracic esophagectomy with three-field lymph node dissection,the gastric carcinoma was removed by gastric antrectomy,which preserved the right gastroepiploic vessels,and a pedunculated short gastric tube was used as the esophageal substitute.Twenty-eight months after the surgery,the patient is well with no evidence of cancer recurrence.Because it minimizes surgical stress and organ sacrifice,gastric tube interposition is a potentially useful technique for esophageal cancer associated with localized early gastric cancer.     

Clinicopathological and biological characteristics of esophageal squamous cell carcinoma associated with head and neck cancer

OBJECTIVE: Esophageal cancer has been reported to be frequently associated with cancer of the head and neck. The iodine dye method is reportedly useful to detect early esophageal cancer. The aim of this study was to clarify clinicopathological and biological characteristics of esophageal squamous cell carcinoma associated with head and neck cancer (HN group). METHODS: Thirty-seven patients of the HN group who underwent esophagectomy were examined clinicopathologically compared to 42 patients with esophageal cancer alone (SE group). All resected specimens were histologically studied after iodine dye staining, and p53 and cyclin D1 (CD1) expression were immunohistochemically examined in esophageal cancer. RESULTS: The HN group had more multiple iodine-unstained lesions and multiple primary cancers within the esophagus compared with the SE group (p = 0.0027, p = 0.067, respectively). There was no significant difference in smoking, drinking, family history and the other clinicopathological factors between the HN and SE groups. Coexpression of p53 and CD1 was found to be significant in the HN group (p = 0.03). CONCLUSIONS: The coexistence of multiple iodine-unstained lesions, multiple cancers in the esophagus and overexpression of p53 and CD1 is suggested as a risk factor for the HN group.     

Multiple primary cancers of the esophagus and thyroid gland.

The occurrence of multiple primary cancers in the aerodigestive tract is a well known phenomenon that has been explained by the concept of 'field carcinogenesis'. Metachronous or synchronous esophageal cancer has usually been identified in patients with head and neck cancer, gastric cancer or colon cancer. The incidence of multiple primary cancers of the esophagus and thyroid gland is very low. We treated four patients with synchronous cancers of the cervical esophagus and the thyroid gland. Histologically, all of the esophageal cancers were squamous cell carcinomas. Thyroid cancers were evaluated as papillary carcinoma or follicular carcinoma. Both the esophageal cancer and the thyroid cancer frequently metastasized to lymph nodes. All patients had multiple lymph nodes metastasis from the esophageal or the thyroid cancer. In one patient, both the esophageal and the thyroid cancers were detected in the same lymph node. Three of four patients died from recurrence of esophageal cancer. The prognosis of these patients was poor. In the treatment of esophageal carcinoma, cancers of other organs including the thyroid gland should be carefully investigated.     

Frequent microsatellite instability in primary esophageal carcinoma associated with extraesophageal primary carcinoma

Patients with esophageal squamous cell carcinoma (ESCC) frequently develop other primary cancers, such as gastric cancer and head and neck cancer. Details of carcinogenesis in patients with multiple primaries that include esophageal carcinoma with other primary carcinoma (ECOPC) remain uncertain. We examined microsatellite instability (MSI) status, frameshift mutation in target genes of MSI, mismatch repair protein expression and hypermethylation of the hMLH1 promoter region in ECOPC patients to better understand the underlying carcinogenic processes. High frequency MSI (MSI-H) was found in 15 (44.1%) of 34 patients with ECOPC, but in only 6 (14.3%) of 42 patients with esophageal cancer alone (p < 0.01). Frameshift mutations in TGFbetaRII, BAX, MSH3 and MSH6 genes respectively were present in 4, 1, 2 and 2 of 34 ECOPC patients. Immunohistochemical study showed that 12 (80.0%) of 15 MSI-H tumors showed loss of expression of either hMLH1 or hMSH2. In addition, 6 of 9 tumors (66.7%) that showed reduced hMLH1 expression also had hypermethylation of the hMLH1 promoter region. Our findings suggested that carcinogenesis in ECOPC was closely associated with the MSI pathway because of mismatch repair protein deficiency.     

Family history of cancer is a risk factor for squamous cell carcinoma of the head and neck in Brazil: A case-control study

To determine the role of familial factors in head and neck cancer, we analysed data from a hospital-based case-control study of squamous cell carcinoma of the head and neck in Brazil. There were 754 cases of squamous cell carcinoma of the head and neck (SCCHN) and 1,507 age- and gender-matched hospital-based controls with non-malignant diseases. Subjects provided information on the occurrence of cancer in first-degree relatives, as well as about other risk factors, including tobacco and alcohol consumption. Relative risks (RRs) were estimated for developing mouth, pharynx and larynx cancer when cancers in relatives were observed. RRs were adjusted for age, sex, city of admission and alcohol and tobacco consumption. The RR for developing SCCHN if a first-degree relative had cancer at any site was significantly elevated at 1.97. The RR was 3.65 (95% Cl: 1.97–6.76) if the relative had head and neck cancer. Significantly elevated risks for developing head and neck cancer were associated with siblings with head and neck cancer (RR = 8.57) and, to a lesser extent, with fathers with head and neck cancer (RR = 2.49). There was no significantly increased risk associated with mothers with head and neck cancer, but these tumours were rare among mothers. Our data show that familial, possibly genetic, factors are important in the aetiology of head and neck cancer. © 1995 Wiley-Liss, Inc.     

小野寺预后营养指数与食管鳞癌同步放化疗不良反应的相关性研究

背景与目的：小野寺预后营养指数是由血清白蛋白和外周血淋巴细胞总数计算得出，可以预测晚期肿瘤患者的预后，包括肺癌、食管癌、胃癌、肾癌、结直肠癌和肝癌等，但其与食管鳞癌同步放化疗不良反应的相关性研究较少。探讨小野寺指数对食管鳞癌同步放化疗患者不良反应的预测作用。方法：选取2017年1月—2019年12月于山东大学齐鲁医院放疗科接受同步放化疗的食管鳞癌患者80例，根据小野寺指数将患者分为营养良好组（小野寺指数≥45）和营养不良组（小野寺指数＜45），比较两组患者的白细胞减少、血小板减少、恶心呕吐、食管炎、腹泻和肺炎6种急性不良反应。结果：营养不良组食管炎（68.4% vs 45.2%，P=0.045）、腹泻（15.8% vs 2.4%，P=0.034）的发生率高于营养良好组。进一步分析重度不良反应在两组中的差别，发现营养不良组的重度食管炎的发生率显著高于营养良好组（34.2% vs 16.7%，P=0.070），但差异无统计学意义。结论：小野寺指数对食管鳞癌同步放化疗患者的不良反应有较好的预测作用。     

Superselective intra-arterial chemoradiotherapy with docetaxel-nedaplatin for advanced oral cancer

Cisplatin-based, superselective, intra-arterial chemotherapy concurrent with radiotherapy (SSIACRT) has gained wide acceptance as a common/curative treatment for advanced head and neck cancer. We combined nedaplatin (CDGP) with docetaxel (DOC) as a new combination in SSIACRT for advanced oral squamous cell carcinoma in 2003. Twenty-two patients with advanced oral cancer were treated by radiotherapy (66 Gy) concurrent with superselective intra-arterial DOC (40 mg/body) and CDGP (80 mg/m2) infusion between 2003 and 2009. Complete response was achieved in 18 (81.8%) of the 22 patients. Of the 17 patients with positive neck disease, 16 (94%) were assessed as disease-free. The 5-year overall survival rate was 78.5%, and the major adverse effects were leukocytopenia and mucositis. Five patients (22.7%) developed distant metastases post-treatment. These results indicate that intra-arterial docetaxel-nedaplatin infusion concurrent with radiotherapy is efficacious for advanced oral cancer. The side effects are easily manageable, and the most important outcome of the treatment is the preservation of patients' quality of life (QOL) and improved prognosis.     

Family history of cancer, mutagen sensitivity, and increased risk of head and neck cancer

To evaluate individual cancer susceptibility, 170 previously untreated patients with pathologically-confirmed squamous cell carcinoma of the oral cavity, pharynx, and larynx, and 175 age- and sex-matched health controls were investigated for the occurrence of cancer in first-degree relatives along with other established risk factors for head and neck cancer. More than 54% of these subjects were assayed for mutagen sensitivity by quantifying in-vitro bleomycin-induced chromosomal breaks within peripheral blood lymphocytes. After adjusting for age, gender, education, family income, tobacco and alcohol consumption, the odds ratio associated with three or more first-degree relatives with cancer at any site was 3.79 (95% CI 0.9-15.9) with a linearly-increased trend in risk (P = 0.040). Significantly elevated risk was found to be associated with a history of cancer within siblings (OR = 2.61, 1.2-5.6, P = 0.014). Patients with a family cancer history and mutagen sensitivity were at greatest risk (OR = 7.88, 2.5-25.3, P = 0.005), indicating an additive interactive effect. The findings suggested that genetic familial influence is important in the causation of head and neck cancer.     

Esophageal squamous cell cancer in patients with head and neck cancer: Prevalence of human papillomavirus DNA sequences

An etiologic role for human papillomavirus (HPV) infections in either head and neck (HNC) or esophageal carcinogenesis remains debatable. Patients with head and neck cancer are at high risk for developing a second esophageal squamous cell cancer (ESCC). The aim of our study was to determine whether HPV infections play a role in this multifocal carcinogenesis. Samples from 2 groups of HNC patients were studied: Random esophageal biopsies were collected from the first group of 60 patients who had been screened for asymptomatic ESCC. The second group consisted of 21 patients with pairs of HNC and ESCC. Both the fresh frozen biopsy samples of the first group and the paraffin-embedded specimens of the second group were evaluated for the presence of HPV DNA sequences by PCR amplification, cloning and sequencing. HPV DNA sequences were detected in 66.7% of normal/inflammatory (34/51) and dysplastic and malignant (6/9) esophageal tissues from HNC patients being screened endoscopically. Similarly, in the second group of 21 patients with both HNC and ESCC, HPV DNA sequences were demonstrated in 13 (61.9%) of the HNC biopsies and in 14 (66.7%) of the ESCC biopsies. The prevalence of high-risk-type HPV 16 was low (5/51, 9.8%) in normal/inflammatory esophageal mucosa but higher (10/24, 47.6%) in ESCC. The low-risk HPV 11 was present in 37.3% (19/51) of normal/inflammatory, 66.7% (4/6) of dysplastic and 28.9% (13/45) of the carcinoma samples. The same HPV type was present in only 3/21 pairs of HNC and ESCC samples, suggesting that a clonal expansion from the HNC to a subsequent ESCC, or visa versa, is unlikely. The high prevalence of "low-risk" HPV infections points to the need for studies on possible interactions of these infections with the use of alcohol and tobacco in the pathogenesis of these tumors.     

胃镜检查在下咽癌共病食管癌中的重要性评价及其临床特点分析

背景与目的：食管癌是常见的消化道恶性肿瘤,而当作为头颈部鳞癌中最常见的下咽癌与食管癌共病存在时预后很差,因此早期诊断对该病生存率的提高至关重要。探讨胃镜检查在下咽癌共病食管癌早期诊断中的重要性及其临床特点。方法：在2013年2月—2019年9月广西医科大学附属肿瘤医院收治的226例下咽癌患者中,回顾性分析40例进行了胃镜检查患者的临床资料及确诊为下咽癌共病食管癌患者的临床特点,比较分析进行或未进行胃镜检查下咽癌患者的生存率。结果：226例下咽癌患者中,有40例（17.7%）进行了胃镜检查,其中检出下咽癌共病食管癌36例（90.0%）,其中同时性癌29例（80.6%）,异时性癌7例（19.4%）。36例下咽癌共病食管癌患者中位年龄56.5（47.3~62.5）岁,男性32例（88.9%）,有吸烟史25例（69.4%）,有饮酒史24例（66.7%）,下咽癌生长的主体部位在梨状窝区的23例（63.9%）,呈结节样肿块型25例（69.4%）,食管癌呈隆起型病变31例（86.1%）,非隆起型病变5例,其中3例为食管鳞癌,2例为原位癌。156例未进行胃镜检查及32例进行胃镜检查的下咽癌患者生存曲线比较差异无统计学意义（P＞0.05）。186例未进行胃镜检查及40例进行胃镜检查的下咽癌患者下咽癌病理学分化程度比较差异无统计学意义（P＞0.05）。结论：胃镜检查在下咽癌共病食管癌的早期诊断中具有重要意义,建议对下咽癌患者常规开展胃镜检查并作为定期随访项目;中年、男性、吸烟、饮酒是下咽癌共病食管癌患者的重要临床特点。     

Elevated serum gastrin levels in patients with gastric cancer

Elevated plasma gastrin levels have been found in patients with colorectal cancer. We measured fasting serum gastrin levels in control subjects (n = 12), patients with gastric cancer (n = 43), and patients with carcinoma of the esophagus (n = 55). Serum gastrin levels were significantly higher in patients with gastric cancer compared to normal controls (P less than 0.005) and those with esophageal cancer (P less than 0.05). This information may add to our understanding of the pathogenesis of gastric cancer.     

Enhanced immunoglobulin levels correlate with infectious complications after surgery in esophageal cancer

Severe septic complications account for the high mortality of patients with esophageal cancer. We examined the levels of immunoglobulins and complements together with infection-related complications in a large number of patients. Enhancements of IgG, IgA, C3, C4, and CH50 were evident in patients with esophageal cancer and were more predominant compared to findings in cases of gastric cancer. Average levels of IgG and IgA immediately before surgery were significantly higher in esophageal cancer patients with postoperative septic complications than in those without such problems. Preoperative radiation therapy and total parenteral nutrition did not significantly alter the levels of immunoglobulins and complements. It would thus appear that the enhancement of IgG and IgA is associated with the occurrence of infectious complications following surgery for patients with esophageal cancer.     

Nutrient intake and risk of subtypes of esophageal and gastric cancer.

Incidence rates for adenocarcinoma of the esophagus and gastric cardia have been rising rapidly. We examined nutrient intake as a risk factor for esophageal and gastric cancers in a population-based case-control study in Connecticut, New Jersey, and western Washington state. Interviews were completed for cases with histologically confirmed esophageal adenocarcinoma (n = 282), adenocarcinoma of the gastric cardia (n = 255), esophageal squamous cell carcinoma (n = 206), and noncardia gastric adenocarcinoma (n = 352), along with population controls (n = 687). Associations between nutrient intake and risk of cancer were estimated by adjusted odds ratios (ORs), comparing the 75th versus the 25th percentile of intake. The following nutrients were significantly inversely associated with risk of all four tumor types: fiber, beta-carotene, folate, and vitamins C and B6. In contrast, dietary cholesterol, animal protein, and vitamin B12 were significantly positively associated with risk of all four tumor types. Dietary fat [OR, 2.18; 95% confidence interval (CI), 1.27-3.76] was significantly associated with risk of esophageal adenocarcinoma only. Dietary nitrite (OR, 1.65; 95% CI, 1.26-2.16) was associated with noncardia gastric cancer only. Vitamin C supplement use was associated with a significantly lower risk for noncardia gastric cancer (OR, 0.60; 95% CI, 0.41-0.88). Higher intake of nutrients found primarily in plant-based foods was associated with a reduced risk of adenocarcinomas of the esophagus and gastric cardia, whereas higher intake of nutrients found primarily in foods of animal origin was associated with an increased risk.     

Occurrence of esophageal carcinoma after gastrectomy

A review of data on 548 patients with primary squamous cell carcinoma revealed that 24 (4.4%) had had gastrectomy. Although the interval of the gastrectomy due to peptic ulcer or gastric cancer and esophageal cancer was 13.4 +/- 7.9 and 5.8 +/- 4.2 years, respectively, this difference was thought to be due only to the occurrence of each disease. The incidence of the occurrence of the lower esophageal cancer after gastrectomy was 29.2%, not significantly higher than the 22.4% incidence of lower esophageal cancer in overall cases. Histopathological investigation of the 13 resected esophageal cancer tissues from gastrectomized patients revealed a mild esophagitis in some cases, with no significant histologic characteristics. Thus esophageal squamous cell carcinoma and previous gastrectomy may be incidentally related.     

Endoscopic screening of early esophageal cancer with the Lugol dye method in patients with head and neck cancers.

The poor prognosis for esophageal cancer could be improved if lesions were detected at an early stage. To detect early esophageal cancer, endoscopic screening of the esophagus with the Lugol dye method was performed in patients with head and neck cancers who were asymptomatic but regarded as being at high risk for synchronous or metachronous esophageal cancer. Of 178 patients screened, 9 had esophageal cancer (5.1%). Eight of these patients (89%) were at early stages with no lymph node metastasis. Most of the lesions (9 of 13 lesions) were not detectable by barium studies or ordinary endoscopic study. The epidemiologic statistical analysis of the patients confirmed that they had a significantly high observed and expected number (O/E) ratio (39.7; P less than 0.001). These results demonstrate the value of endoscopic screening of the esophagus with the Lugol dye method in patients with head and neck cancers and imply that endoscopic screening with the Lugol dye method may be useful for detecting early esophageal cancer in individuals at risk for other causes.