A human mode of intestinal type gastric carcinoma.

Gastric cancer is a malignant tumor originating from the gastric mucosa epithelium. Intestinal type gastric cancer is frequently taken on elderly men, and there are many high incidence areas around the world. Intestinal type gastric cancer often is accompanied by gastric mucosal atrophy, intestinal metaplasia. The clinical manifestation involves hypergastrinemia, low stomach acid, PG I/II progressive decreasing, anemia, and protein energy malnutrition. The neck cells of gastric glands act as tissue stem cells to regenerate the gastric glands. In addition to secreting gastric acid and intrinsic factor, the parietal cells also have the function of inducing differentiation of themselves and gastric epithelial cells. When the function of parietal cells is normal, the neck cells differentiate into mature cells, and the glands regenerate intact. When the function of parietal cells is defective, the neck cells maybe differentiate into mature intestinal cells, and the gastric glands will regenerate in form of the intestinal metaplasia. When the function of parietal cells is lost, the neck cells can not differentiate into mature cells successfully, and the accumulation of immature cells in gastric mucosal tissue forms atypical hyperplasia of different degrees and cancers of various differentiation grades. Any factors that can reduce the function of parietal cell could result in intestinal type gastric carcinogenesis. Adrenal cortical hypofunction can make the parietal cell hypofunction, hypohematopoiesis, protein synthesis rates reducing and protein degradation rates increasing. The patients develop gastric cancer, and come with lack of gastric acid and intrinsic factor, anemia, protein energy malnutrition. Autoimmune gastritis can produce parietal cell antibodies to damage parietal cells. Patients with autoimmune gastritis gastric exhibit hypergastrinemia, lack of gastric acid and internal factor, higher incidence of gastric cancer. H. pylori can damage gastric parietal cells directly and indirectly. When declining in quantity of parietal cells, the patients exhibit hypergastrinemia, low gastric acid, mucosa atrophy, intestinal metaplasia and gastric cancer. Medicine that inhibits the function of parietal cells also could increase the risk of gastric cancer development. The distribution of mucosa atrophy, intestinal metaplasia and intestinal type gastric cancer is opposite with the distribution of parietal cells in stomach. With age the quantity of parietal cells decreases, the atrophy area of gastric mucosa extends upward from antrum to body and downward from cardia to body along lesser curvature, and the location of distal gastric cancer moves upward and the gastric cardiac cancer increase.

Cancer related fatigue and cancer cachexia are the consequence of endocrine failure caused by persistent stress.

This study researches the cause of tumor, cancer related fatigue (CRF) and cancer cachexia (CC), and the relationship among tumor and CRF and CC. Carcinogenesis is consequence of failure of tissue development. Tumor originates from tissue regeneration. The tumor cell is normal incomplete differentiated cell that stop in different phases of differentiation. Tumor promoter stimulates stem cell to proliferate. Carcinogen obstructs stem cell to differentiate. With tumor promoter and carcinogen, the tissue stem cells proliferate but cannot differentiate into mature cell, and form tumors. The disorder of biological signals cell proliferation and differentiation facilitates tumor development. CRF and CC are consequence of endocrine hypofunction and failure caused by persistent stress. Nature factors and psychological factors stimulate organic stress. The significant change of stress is the activation of endocrine system. The persistent stress exhausts the capacity of endocrine glands or hormone receptors of target cells, and leads to endocrine hypofunction even failure. CRF and CC are clinical manifestation of endocrine hypofunction and failure. Cancer is a local lesion, also is a systemic disease. As a local lesion, carcinogen obstructed stem cell to differentiate, developmental failure of local tissue forms tumor. As a systemic disease, cancer is related to natural physical, chemical, and biological factors, as well as negative spiritual factors. The material and spiritual factors induce persistent stress which eventually leads to endocrine hypofunction even failure and unbalance of homeostasis. The disorder of biological signals of cell proliferation and differentiation facilitates tumor development. CRF and CC, as clinical manifestation of endocrine hypofunction and failure, have nothing to do with tumor size and type, but facilitate tumor development. CRF and CC are through all the course of systemic cancerous disease, and commonly precede tumorigenesis. Many patients have been found tumors because of symptoms of CRF and CC. Even if no tumor be found at that time, various tumors would be found in the follow-up. For systemic cancerous disease, cachexia is the cause of death. Most cancer patients do not die of tumor, but of cancer cachexia. Eradicating tumor cell cannot cure systemic cancerous disease; on the contrary, the poisonous side effect of therapies usually speeds up the progress of CC and death. It is important for curing cancer cachexia and restoring the patient's constitution to prevent systemic cancer and improve the quality of life and prolong the survival.

Carcinogenesis is consequence of failure of tissue development.

Cancer has become a public health problem. The exploration of pathogenesis and therapy of cancer is mainly under the guidance of gene mutation theory. But the therapeutic effect of cancer is not satisfactory, and many predictions of gene mutation theory do not conform actual phenomena of cancer. The research results of mechanism of genetic molecular mutation trap us in an intricate molecular maze hopelessly. The dilemma compels us to doubt about the correctness of gene mutation theory and re-understand the nature of tumor. This study explores the nature of cancer by the method of theoretical analysis by the view of tissue regeneration, and draws a conclusion that the carcinogenesis is consequence of failure of tissue development. Tumors originate from tissue regeneration, tumor cells originate from normal tissue stem cells. The tumor cells are only normal immature cells. Tumor promoters stimulate stem cells to proliferate. Carcinogens obstruct the inducers from inducing tissue stem cells differentiation outside of cells. With tumor promoters and carcinogens, the tissue stem cells proliferate, but cannot differentiate into mature cells, and stop in different phases of differentiation forming atypical hyperplasia of different degrees and tumors of various differentiation grades in tissue. The tumor cells can differentiate into normal mature cells with suitable inducers. The normal stem cells will develop into tumor stem cells without suitable inducers. The ultimate solution of tumor is differentiation therapy. Stem cell transplantation should be cautious.

[Clinical characteristics of multiple primary cancer associated with esophageal squamous carcinoma].

OBJECTIVE: To examine the characteristics of esophageal squamous cancers with multiple primary cancers in another organ. METHODS: Between January 2012 and December 2014, 3 104 patients with esophageal squamous cell carcinoma treated in Cancer Institute and Hospital, Chinese Academy of Medical Sciences, were reviewed for the presence of an additional primary cancer retrospectively. The patients were divided into two groups according to whether they had multiple primary cancer. RESULTS: Totally 369 (11.9%) patients were found multiple primary cancer in the other organs. Among these patients, 72.4% was found synchronously, another primary cancer was found in the head and neck region in 211 (6.8%), in the stomach in 140 (4.2%), and in the lung, colon, breast, and other locations in the remaining patients. Of the 211 patients with another primary cancer in the head and neck region, 156 (73.2%) had hypopharyngeal cancer. Furthermore, the incidence of intraesophageal multiple cancerous lesion in the patients with primary cancer in the head and neck region was significantly higher than that in those whose other primary cancers were gastric cancer or in those with non-multiple primary cancer (P<0.01). CONCLUSION: There is a high incidence of multiple primary cancers in patients with esophageal squamous carcinoma, mostly found synchronously. The leading multiple primary cancers were head and neck cancer and stomach cancer. Intraesophageal multiple cancerous lesion is an indicator for a second primary cancer in head and neck. A better knowledge of the relationships between esophageal carcinoma and cancers in other organs may lead to earlier detection of other primary cancers and improved therapeutic results.

[Value of narrow band imaging endoscopy in the detection of unknown primary site with cervical lymph node metastasis of squamous cell carcinoma].

OBJECTIVE: To investigate the value of narrow band imaging (NBI) endoscopy in the detection of unknown primary tumor site with cervical lymph node metastases of squamous cell carcinoma. METHODS: Fifty-three patients with cervical lymph node metastases of squamous cell carcinoma treated in our department between June 2009 and December 2011 were enrolled in this study. Their primary tumor site was not detected by routine computed tomography, magnetic resonance imaging and laryngoscopy. The nasopharyngolarynx was examined by NBI endoscopy to explore the primary tumor site. RESULTS: A total of 53 cases with cervical lymph node metastasis of squamous cell carcinoma from an unknown primary were examined under NBI endoscopy. The primary tumor site was confirmed by NBI examination in 47.2% (25/53) of patients, significantly better than routine radiology and endoscopy (0, P < 0.001). These primary tumors were small and superficial, with characteristic mucosal vascular morphologies. The superficial nasopharyngeal carcinomas under NBI examination showed the superficial thin branch-like or torturous line microvessels. The notable characteristics of the squamous cell carcinoma of oropharynx, hypopharynx and larynx was the well demarcated brownish area and scattered brown dots. CONCLUSION: The NBI endoscopy can provide better visualization of the morphology of superficial mucosal vasculature and improve the ability to detect possible primary cancer in patients with primary unknown cervical lymph node metastasis.

[Comparative study of endoscopic mucous resection with transparent cap and endoscopic multi-band mucosectomy for early esophageal cancer and precancerous lesion].

OBJECTIVE: To evaluate the efficacy and safety of endoscopic mucous resection with transparent cap (EMR-Cap) and endoscopic multi-band mucosectomy (MBM) in the treatment of early esophageal cancer and precancerous lesion. METHODS: A retrospective study was performed to review 30 EMR-Cap cases from December 2008 to December 2009 and 32 MBM cases from January 2010 to January 2011 of early esophageal cancer and precancerous lesions. The differences between these two techniques in efficacy, safety, and cost were compared. RESULTS: In EMR-Cap group, the median resection time was 26(10-56) min and median procedure time was 43(22-81) min, significantly longer than those in MBM group [10(7-18) min and 32(28-45) min, P=0.036 and 0.038, respectively]. There were no significant differences between the two groups in total thickness and depth of resected lesions (P>0.05). In EMR-Cap group, the median cost was significantly higher than that of MBM group [(5466±354) vs. (4014±368) RMB, P=0.008)]. CONCLUSIONS: EMR-Cap and MBM are minimally invasive, safe and effective methods in the treatment of early esophageal cancer and precancerous lesions. Compared to the EMR-Cap, MBM is simple with shorter treatment time and lower cost.

[Display of esophageal entrance by injecting gas through the laryngoscopic biopsy channel in hypopharyngeal cancer].

OBJECTIVE: To investigate the method displaying the hypopharynx and esophageal entrance under laryngoscopy to determine the invasion range of hypopharyngeal cancer. METHODS: A total of 113 patients with hypopharyngeal cancer was enrolled in this study and they previously underwent conventional laryngoscopic and radiologic examinations. The esophageal entrance was exposed by injecting gas through the biopsy channel of laryngoscope. The invasion of esophageal entrance in hypopharyngeal cancers was evaluated by this method and compared with that evaluated with radiology. RESULTS: Conventional laryngoscopy was unable to evaluate appreciably esophageal entrance involvement in the 113 patients with hypopharyngeal cancer. After injecting gas through the laryngoscopic biopsy channel, the esophageal entrance was clearly displayed in 96.5% (109/113) patients, showing the presence (33 cases) and absence (76 cases) of esophageal entrance invasion. Imaging examinations only showed the invasion of the esophageal entrance in 25 patients of these patients,but did not in other 8 patients. Laryngoscopy with injecting gas through the biopsy channel was superior to radiological imaging examinations in determining the invasion of the esophageal entrance (χ² = 9.103, P = 0.003). CONCLUSION: Laryngoscopy with injecting gas through the biopsy channel is a useful method for determining the presence or absence of esophageal entrance invasion in hypopharyngeal cancer prior to surgery.

[Value of endobronchial ultrasound-guided transbronchial needle aspiration in hilar and mediastinal lesions].

OBJECTIVE: To evaluate the diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in cases of undiagnosed intrapulmonary lesions. METHODS: A total of 89 patients with intrathoracic lesions underwent EBUS-TBNA, including 56 pulmonary lesions, 7 lymph node staging in lung cancer patients, 21 unknown hilar and/or mediastinal lymphadenopathies and 5 mediastinal tumors. All samples were evaluated for cytological and pathological examinations. RESULTS: No complication of EBUS-TBNA was observed. Among 89 cases, 76 had positive results, 5 negative and 5 cases excluded as unsatisfied samples. In 56 patients with pulmonary lesions, EBUS-TBNA demonstrated 45 malignant tumors, 5 benign diseases, 3 suspicious cancers, 1 negative and 2 unsatisfied samples. In 7 lung cancer patients staged by EBUS-TBNA, 5 showed metastasis and 2 showed no metastasis. In 21 cases with mediastinal and/or hilar lymphadenopathy, EBUS-TBNA demonstrated 3 malignant tumors, 13 benign diseases, 2 negative and 3 unsatisfied samples. All 5 mediastinal lesions were malignant. Three suspicious cancers were confirmed, 1 by CT-guided percutaneous transthoracic needle biopsy and 2 by clinical follow-ups. In 2 lung cancer patients EBUS-TBNA showed negative, 1 surgical sample showed metastasis and another no metastasis by PET-CT. Three negative cases were diagnosed as benign by clinical follow-ups. The diagnostic sensitivity, specificity, positive predictive value and negative predictive value of EBUS-TBNA were 95%, 100%, 100% and 20% respectively. CONCLUSION: EBUS-TBNA is both effective and safe in making a diagnosis of intrathoracic lesions.

[Application of narrow band imaging endoscopy in the diagnosis of laryngeal cancer].

OBJECTIVE: To investigate the value of narrow band imaging (NBI) endoscopy in the detection of laryngeal cancer and its precursor lesions. METHODS: Between December 2008 and July 2009, a total of 122 consecutive patients with suspected precancerous or cancerous lesions of the larynx were enrolled in this study. High performance endoscopic system equipped with the white light mode and NBI mode was introduced in the examination of larynx. Full pharyngeal and laryngeal examination was performed first under white light endoscope and then under NBI. Each lesion was observed by NBI endoscopy and classified according to the detailed morphologic findings of epithelial microvessels. Histological results were then compared to the corresponding white light and NBI images. RESULTS: Among the 122 patients, a total of 149 lesions were detected by white light and NBI modes. The histological diagnoses of these lesions were as follows: 16 laryngeal polyp, 7 laryngitis, 24 simple hyperplasia, 17 mild dysplasia, 6 moderate dysplasia, 6 severe dysplasia, 9 carcinoma in situ, 64 invasive cancer. The diagnostic accuracy by NBI for the laryngeal lesions was 90.6% (135/149), which was significantly higher than that of white light (75.2%, 112/149, chi² = 12.514, P < 0.001). The sensitivity of NBI and white light to detect laryngeal carcinoma was 93.2% (68/73) and 68.5% (50/73), respectively (chi² = 14.317, P < 0.001). CONCLUSIONS: NBI endoscopy was a promising tool for the differentiation of non-malignant from malignant laryngeal lesions in vivo by detection of the morphology of mucosal capillary vessels. NBI endoscopy was easy to application in the routine pharyngolaryngeal examination with high sensitivity, and facilitated to improve the abilities of preoperative diagnosis and postoperative surveillance.

[Diagnostic value of transbronchial needle aspiration combined with transesophageal endoscopic ultrasound-guided fine needle aspiration in mediastinal and pulmonary hilar lesions].

OBJECTIVE: To evaluate the value of transbronchial needle aspiration (TBNA) combined with transesophageal endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the diagnosis of mediastinal and pulmonary hilar lesions as well as in the lymph node staging (N staging) of lung cancer. METHODS: 129 patients with mediastinal and pulmonary hilar lesions underwent either TBNA or EUS-FNA with cytological needle aspiration. The samples obtained from TBNA or EUS-FNA were examined by both cytologiy and histopathology. RESULTS: Of the 129 patients, 59 underwent TBNA and 70 EUS-FNA. The diagnostic rate were 84.7% (50/59) by TBNA and 94.3% (66/70) by EUS-FNA, resepectively. The diagnosis of 116 (89.9%) patients were confirmed by either TBNA or EUS-FNA. The pathological and cytological diagnostic rates were 92.2% (107/116) and 88.0% (102/116), resepectively. The diagnostic rate was elevated by 8.4% (9/107) through pathological examination. The histological classification rates by cytological and pathological examination were 73.8% (76/116) and 89.3% (92/103), respectively. The diagnostic rate of histological classification was elevated by 35.5% (27/76) through pathological examination. CONCLUSION: The combination of TBNA and EUS-FNA can improve the diagnostic rate for wider mediastinal and pulmlonary hilar lesions. Pathological examination of the samples obtained from the TBNA and EUS-FNA can elevate not only the rate of diagnosis but also the rate of histological classification.

[Public screening for early carcinoma of gastric cardia: rule of carcinogenetic development observed by endoscopy].

OBJECTIVE: To study the rule of development of early cancer of gastric cardia in vivo in public screening. METHODS: A prospective cohort study on gastric cardiac cancer was held in the high incidence area of cancer of esophagus and stomach in China. 106 subjects had been examined regularly by endoscopy to observe the change of mucosa in high incidence area of gastric cardiac carcinoma developing at the root of gastric cardiac ridge by taking serial biopsy specimens. All specimens were diagnosed through the normal pathological processes to study the prognosis of pre-cancerous lesion of gastric cardia. RESULTS: The result of 106 subjects who had been observed for four years were: 1. Of 8 normal persons, 3 stayed normal, 4 turned to chronic gastritis, 1 developed early gastric cardiac cancer. 2. Of 61 persons chronic gastritis, 11 was observed to have glandular atrophy, 4 with mild atypical hyperplasia, and 2 with highly atypical hyperplasia. 3. Of 9 subjects showing atrophic chronic gastritis, 5 revealed no change, and 4 became chronic gastritis. 4. Of 22 subjects who revealed mild atypical hyperplasia, 17 resolved, 4 showed no change, and 1 advanced to highly atypical hyperplasia. 5. One person with highly atypical hyperplasia reverted to mild atypical hyperplasia. 6. Of 5 subjects with early gastric cardiac cancer without any treatment, 1 became advanced cancer, 1 still stayed in early stage, and 3 turned to atypical hyperplasia. CONCLUSION: 1. The development of early cancer of gastric cardia would proceed through the stages of chronic gastritis, glandular atrophy, and atypical hyperplasia. 2. The early cancer and pre-cancerous lesion of gastric cardia is reversible, though possessing malignant possibility.

[A comparative study of endoscopic image stained by iodine and histopathology in early esophageal cancer and precancerous lesions (dysplasia)].

OBJECTIVE: The aim of this study is to evaluate the relationship between the imaging patterns of endoscopy aided by iodine stain and histological diagnosis. METHODS: A balloon cytological screening was conducted in 4000 participants in high-risk area of esophageal cancer in 1997-1998, 1050 out of these 4000 participants were confirmed as abnormal by cytology. Among them, 867 were given endoscopy examination during which mucosal stain with 1.2% iodine solution was used. The stain images were graded as four categories: Grade 1, dark yellow, protruding inlay-like with clear borders and showing pink after discoloration; Grade 2, between grade 1 and grade 3; Grade 3, light yellow, flat lesion with clear but not sharp borders and Grade 4, dark-brown color. According to the above criteria, the lesions were recorded and graded after the examination. The biopsies were taken from the unstained lesions and underwent pathologic evaluation. A comparison between the imaging patterns of endoscopy aided by iodine stain and histological diagnosis was evaluated. The correlation coefficient was estimated using Spearman's Rank Correlation. RESULTS: 94.4% (68/72) of the superficial carcinoma and severe dysplasia, 61.8% (73/118) of moderate dysplasia and 27.7% (35/126) of mild dysplasia were distributed in the grade 1 and grade 2 of iodine stain images of which the patterns conforming to the principle and rule of formation of the image by iodine stain. CONCLUSION: There is close relationship between the imaging patterns of endoscopy aided by iodine stain and histological diagnosis. The magnitude of exposure of the malignant tissue is the pathologic basis of formation of various images by iodine stain. Iodine stain greatly helps of early detection of esophageal cancer.

[Minimal invasive treatment of early esophageal cancer and its precancerous lesion: endoscopic mucosal resection using transparent cap-fitted endoscope].

OBJECTIVE: To explore the effect of endoscopic esophageal mucosal resection using transparent cap-fitted endoscope to treat early esophageal cancer and severe hyperplasia, precancerous lesion of esophageal cancer. METHODS: Endoscopic esophageal mucosal resection were performed with transparent-cap technique on 29 cases of early esophageal cancer and 42 cases of severe hyperplasia, and the residual lesions were treated by Argon plasma coagulation (APC). All patients were followed up by endoscopic examination one month, 4 months, and 12 months after the therapy. RESULTS: (1) Local esophageal mucosa with the size of 21.8 mm +/- 1.02 mm x 18.2 mm +/- 1.02 mm on average was resected from 71 cases, with 88 lesions, using transparent cap-fitted endoscope. 1:1,000 saline-epinephrine at an average dose of 18 ml was injected submucosally for each lesion. (2) After the mucosectomy 5 cases had bleeding which was controlled successfully by compression, local injection of saline-epinephrine, and APC. None case suffered from perforation. Stenosis was found in 4 cases after mucosal resection, in three of which the extent of resected mucosa exceeded 3/4 of the esophageal circumference. Water-balloon dilator was used once a month for 3 - 4 times since one month after mucosal resection. All cases were cured. (3) The lesions of 58 cases (81.2%) were completely resected, and the remaining cases had residual lesions that were treated by APC. Three cases of early cancer and 2 cases of severe atypical hyperplasia were discovered endoscopically 4 months after resection and were cured by APC. (4) All cases survived without any discomfort after a follow-up of 4.6 months on average. CONCLUSION: Safe, simple, minimally invasive and effective on early esophageal cancer and precancerous lesion, endoscopic esophageal mucosal resection (EEMR) is promising clinically.

Endoscopic study on cancer of gastric cardia in the high incidence areas of China.

OBJECTIVE: Endoscopy was used to study the high incidence area of cancer of gastric cardia. METHODS: 417 patients with early cardiac cancer and 451 patients with advanced lesions were analyzed to the high incidence point of cardiac cancer. Verifying endoscopic screening of 205 subjects was performed later in the high incidence area of esophageal cancer. RESULTS: 327 of 417 (78.4%) of early cardiac cancer patients and 336 of 451 (74.5%) of advanced lesions were proved to have developed their origin at the root of the mucosal fold in the gastric cardia. Eleven cardiac cancer patients were found by the verifying endoscopic screening, among whom 9 patients (81.8%) developed the primary focus at the root of mucosal fold in the cardia. CONCLUSION: The root of mucosal fold in the gastric cardia is proved to be the high incidence point of cancer of gastric cardia, which is very important clinically.

Serial public cancer screening in China.

Screening of hollow-organ cancers has been carried out for 16 years using the occult blood test. We are currently assessing the result of serial public cancer screening in China. Human cancers can be divided into 3 types: 1) surface cancer (15%), 2) hollow-organ cancer (65%), and 3) deep-seated solid-organ cancer (20%). Through an education program, the general population was taught to self-examine the body surface and to use a self-examination kit to detect any occult blood discharged from the hollow organs. On discovering positive or doubtful results, these subjects were referred to the hospital for a complete clinical checkup. A total of 10,000 people ages 40 to 70 years chosen from the university areas in Beijing were divided in a test group (5,000) and a control group (5,000). This study, which was carried out for 4 years, showed that 79 cancers were discovered in the test group, with an annual cancer detection rate of 482.5/10,000 population and a cancer mortality rate of 36.6/10,000. The control group showed an annual cancer mortality rate of 206/10,000 population. The difference has very marked statistical significance ( p< 0.001). During the same interval, an extensive cancer screening was carried out in the high-incidence areas. The Cancer Institute in Sihui city of Guangdong province discovered, by screening 758 persons in the outpatient department during a 2-year period, 16 cancers with 15 as nasopharyngeal cancer. From 1999 to 2000, another extensive public cancer screening in the high-incidence areas in Jiangsu province discovered 480 cancers from an 80,000 population. Together with the screening test carried out by Qin's self-examination kit before the National Supported Cancer Research Project on a population of 431,000, 1,272 cancers and more than 10,000 precancerous lesions have been detected. The self-examination kit and public cancer screening are highly important in the practice of public cancer screening.