Clinical characteristics, medical service utilization, and expenditure for colorectal cancer in China, 2005 to 2014: Overall design and results from a multicenter retrospective epidemiologic survey.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in China, however, publicly available, descriptive information on the clinical epidemiology of CRC is limited. METHODS: Patients diagnosed with primary CRC during 2005 through 2014 were sampled from 13 tertiary hospitals in 9 provinces across China. Data related to sociodemographic characteristics, the use of diagnostic technology, treatment adoption, and expenditure were extracted from individual medical records. RESULTS: In the full cohort of 8465 patients, the mean ± SD age at diagnosis was 59.3 ± 12.8 years, 57.2% were men, and 58.7% had rectal cancer. On average, 14.4% of patients were diagnosed with stage IV disease, and this proportion increased from 13.5% in 2005 to 20.5% in 2014 (P value for trend < .05). For diagnostic techniques, along with less use of x-rays (average, 81.6%; decreased from 90.0% to 65.7%), there were increases in the use of computed tomography (average, 70.4%; increased from 4.5% to 90.5%) and magnetic resonance imaging (average, 8.8%; increased from 0.1% to 20.4%) over the study period from 2005 to 2014. With regard to treatment, surgery alone was the most common (average, 50.1%), but its use decreased from 51.3% to 39.8% during 2005 through 2014; and the use of other treatments increased simultaneously, such as chemotherapy alone (average, 4.1%; increased from 4.1% to 11.9%). The average medical expenditure per patient was 66,291 Chinese Yuan (2014 value) and increased from 47,259 to 86,709 Chinese Yuan. CONCLUSIONS: The increasing proportion of late-stage diagnoses presents a challenge for CRC control in China. Changes in diagnostic and treatment options and increased expenditures are clearly illustrated in this study. Coupled with the recent introduction of screening initiatives, these data provide an understanding of changes over time and may form a benchmark for future related evaluations of CRC interventions in China.

B7-H3 immune checkpoint expression is a poor prognostic factor in colorectal carcinoma.

Although PD-1/PD-L1 immunotherapy has been used successfully in treating many cancers, metastatic colorectal cancer (CRC) patients are not as responsive. B7-H3 is a promising target for immunotherapy and we found it to have the highest expression among B7-CD28 family members in CRC. Thus, the aim of the present study was to investigate B7-H3 expression in a large CRC cohort. B7-H3, B7-H4, and PD-L1 protein levels and differential lymphocyte infiltration were evaluated in tissue microarrays from 805 primary tumors and matched metastases. The relationships between immune markers, patient characteristics, and survival outcomes were determined. B7-H3 (50.9%) was detected in more primary tumors than B7-H4 (29.1%) or PD-L1 (29.2%), and elevated B7-H3 expression was associated with advanced overall stage. Co-expression of B7-H3 only with B7-H4 or PD-L1 was infrequent in primary tumors (6.3%, 5.7%, respectively). Moreover, B7-H3 in primary tumors was positively correlated with their respective expression at metastatic sites (ρ = 0.631; p < 0.001). No significant relationships between B7-H4 and PD-L1 and survival were observed; however, B7-H3 overexpression in primary tumors was significantly related to decreased disease-free survival. A positive relationship between B7-H3 expression and high density CD45RO T cell was observed in primary tumors, whereas B7-H4 and PD-L1 overexpression were related to CD3 T-cell infiltration. In conclusion, compared with B7-H4 and PD-L1, B7-H3 expression exhibited a higher prevalence and was significantly related to aggressiveness, worse prognosis and CD45RO T-cell infiltration in primary tumors. Further exploration of this potential target of immunotherapy in CRC patients is warranted.

Is adjuvant chemotherapy necessary for patients with ypT0-2N0 rectal cancer treated with neoadjuvant chemoradiotherapy and curative surgery?

BACKGROUND AND OBJECTIVE: The benefit from adjuvant chemotherapy for patients treated with neoadjuvant chemoradiotherapy (NCRT) and curative surgery remains controversial, particularly among those responding well to NCRT. This retrospective study aimed to clarify the benefits of adjuvant chemotherapy in terms of the oncological outcomes of patients with ypT0-2N0 rectal cancer after NCRT and curative surgery. METHODS: All patients with ypT0-2N0 rectal cancer after NCRT and curative resection between 2005 and 2014 were examined. The oncological outcomes between patients treated with adjuvant chemotherapy and those without any chemotherapy were compared. RESULTS: The clinicopathological characteristics of 110 patients were reviewed in this study; one patient was excluded due to lack of follow-up. Of the 109 patients included, 58 (53.2%) underwent adjuvant chemotherapy (chemo group), whereas the remaining 51 (46.8%) did not receive any chemotherapy (non-chemo group). After a median follow-up of 50 months, there were no significant differences in the 5-year overall survival (OS) or recurrence-free survival (RFS) rates between the groups (OS: 92.1 vs 86.3%, P = 0.375; RFS: 80.9 vs 74.7%, P = 0.534). Subgroup analysis also demonstrated no significant differences in 5-year OS and RFS rates between patients with ypT0N0 rectal cancer (P = 0.712 and P = 0.599, respectively) and those with ypT1-2N0 disease (P = 0.255 and P = 0.278, respectively). CONCLUSIONS: These results indicate that patients with ypT0-2N0 rectal cancer after NCRT followed by curative surgery may not derive significant benefit from adjuvant chemotherapy. However, further prospective randomized trials, with larger sample sizes, are warranted to confirm this conclusion.

The de-ubiquitinase UCHL1 promotes gastric cancer metastasis via the Akt and Erk1/2 pathways.

Ubiquitin C-terminal hydrolase-L1 (UCHL1) is a de-ubiquitinating enzyme, which enzymatic activity relies on the C90 site. The function of UCHL1 is controversial in different types of cancer, and its role in gastric cancer progression remains unclear. In this study, immunohistochemistry staining was applied to detect the expression of UCHL1 in primary gastric cancer and liver metastases from gastric cancer. MKN45 and BGC823 cell lines with stable expression of de-ubiquitinase active UCHL1 or inactive UCHL1-variant C90S were established by lentiviral infection. The effect of UCHL1 on cell proliferation was evaluated by MTT and colony formation assays. The abilities of cell migration and invasion were determined by transwell assay. Protein expression levels were determined by Western blot. The results indicated that UCHL1 had a significantly higher positive expression rate in liver metastases from gastric cancer compared with primary gastric cancer. Overexpression of UCHL1 in MKN45 and BGC823 cells promoted cell proliferation, migration, and invasion depending on its de-ubiquitinase activity. UCHL1 activated Akt and Erk1/2, which process also required enzymatic activity and was necessary for mediating cell migration and invasion. These findings demonstrated that UCHL1 promoted cell proliferation, migration, and invasion depending on its de-ubiquitinase activity by activating Akt and Erk1/2, which may account for its higher positive expression rate in liver metastases from gastric cancer. UCHL1 could be a candidate biomarker and a therapeutic target for gastric cancer metastasis.

Outcome after simultaneous resection of gastric primary tumour and synchronous liver metastases: survival analysis of a single-center experience in China.

BACKGROUND: The optimal surgical strategy for the treatment of synchronous resectable gastric cancer liver metastases remains controversial. The aims of this study were to analyze the outcome and overall survival of patients presenting with gastric cancer and liver metastases treated by simultaneous resection. MATERIALS AND METHODS: Between January 1990 and June 2009, 35 patients diagnosed with synchronous hepatic metastases from gastric carcinoma received simultaneous resection of both primary gastric cancer and synchronous hepatic metastases. The clinicopathologic features and the surgical results of the 35 patients were retrospectively analyzed. RESULTS: The 5-year overall survival rate after surgery was 14.3%. Five patients survived for more than 5 years after surgery. No mortality has occurred within 30 days after resection, although two patients (5.7%) developed complications during the peri-operative course. Univariate analysis revealed that patients with the presence of lymphovascular invasion of the primary tumor, bilateral liver metastasis and multiple liver metastases suffered poor survival. Lymphovascular invasion by the primary lesion and multiple liver metastases were significant prognostic factors that influenced survival in the multivariate analysis (p=0.02, p=0.001, respectively). CONCLUSIONS: The presence of lymphovascular invasion of the primary tumor and multiple liver metastases are significant prognostic determinants of survival. Gastric cancer patients without lymphovascular invasion and with a solitary synchronous liver metastasis may be good candidates for hepatic resection. Simultaneous resection of both primary gastric cancer and synchronous hepatic metastases may effectively prolong survival in strictly selected patients.

Colorectal cancer incidence and mortality in China, 2010.

BACKGROUND: The National Central Cancer Registry of China (NCCR) affiliated to the Bureau of Disease Control, National Health and Family Planning Commission of China is responsible for cancer surveillance in the entire country. Cancer registration data from each local registry located in each province are collected by NCCR annually to be analyzed and published to provide useful information for policy makers and cancer researchers. MATERIALS AND METHODS: Until 1st June, 2013, 219 population-based cancer registries submitted data of 2010 to the National Central Cancer Registry of China covering about 207,229,403 population, and 145 cancer registries were selected after quality evaluation for this study. Colorectal cancer cases were selected from the database according to ICD-10 coded as "C18-C20". We calculated the crude incidence and mortality rates by sex, age groups and location (urban/rural). The China population in 2000 and Segi's population were used as standardized populations for the calculation of age-standardized rates. The 6th National Population Census data of China was used to combined with the cancer registries' data to estimate the colorectal cancer burden in China in 2010. RESULTS: Colorectal cancer was the sixth most common cancer in China. It was estimated that there were 274,841 new cases diagnosed in 2010 (157,355 in males and 117,486 in females), with the crude incidence rate of 20.1/100,000, highest in males in urban areas. Age-standardized rates by China standard population of 2000 (ASRcn) and World standard population (Segi's population, ASRwld) for incidence were 16.1/100,000 and 15.9/100,000 respectively. There were 132,110 cases estimated to have died from colorectal cancer in China in 2010 (76,646 men and 55,464 women) with the crude mortality rate of 10.1/100,000. The ASRcn and ASRwld for mortality were 7.55/100,000 and 7.44/100,000 respectively, higher in males and urban areas than in females and rural areas. The incidence and mortality rates increased with age, reaching peaksin the 80-84 year old, and oldest age groups, respectively. CONCLUSIONS: Colorectal cancer is one of the most common incident cancers and cause of cancer death in China. Primary and secondary prevention, with attention to a health lifestyle, physical activity and screening should be enhanced in the general population.

Optimization of reference genes for normalization of the quantitative polymerase chain reaction in tissue samples of gastric cancer.

For an exact comparison of mRNA transcription in different samples or tissues with real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), it is crucial to select a suitable internal reference gene. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and beta-actin (ACTB) have been frequently considered as house-keeping genes to normalize for changes in specific gene expression. However, it has been reported that these genes are unsuitable references in some cases, because their transcription is significantly variable under particular experimental conditions and among tissues. The present study was aimed to investigate which reference genes are most suitable for the study of gastric cancer tissues using qRT-PCR. 50 pairs of gastric cancer and corresponding peritumoral tissues were obtained from patients with gastric cancer. Absolute qRT-PCR was employed to detect the expression of GAPDH, ACTB, RPII and 18sRNA in the gastric cancer samples. Comparing gastric cancer with corresponding peritumoral tissues, GAPDH, ACTB and RPII were obviously up-regulated 6.49, 5.0 and 3.68 fold, respectively. Yet 18sRNA had no obvious expression change in gastric cancer tissues and the corresponding peritumoral tissues. The expression of GAPDH, ß-actin, RPII and 18sRNA showed no obvious changes in normal gastric epithelial cells compared with gastric cancer cell lines. The carcinoembryonic antigen (CEA), a widely used clinical tumor marker, was used as a validation gene. Only when 18sRNA was used as the normalizing gene was CEA obviously elevated in gastric cancer tissues compared with peritumoral tissues. Our data show that 18sRNA is stably expressed in gastric cancer samples and corresponding peritumoral tissues. These observations confirm that there is no universal reference gene and underline the importance of specific optimization of potential reference genes for any experimental condition.

[Diagnosis and treatment of primary colorectal non-Hodgkin's lymphoma: analysis of 52 cases].

OBJECTIVE: To summarize and analyze the diagnosis, clinical features and therapy of primary colorectal non-Hodgkin's lymphoma (NHL). METHODS: The clinicopathological data of 52 patients with primary colorectal NHL diagnosed and treated in our department from January 2000 to January 2010 were reviewed and analyzed retrospectively in this study. RESULTS: This group of patients was composed of 45 cases of B cell and 7 T cell lymphomas, including 33 males and 19 females, with a male to female ratio of 1.7:1, and the age at diagnosis was 16 - 74 years old, with a median age of 50 years. The ileocecal region was most frequently involved site, acounted for 48.1%. The common symptoms encountered were abdominal pain (66.7%), diarrhea (15.6%), blood stool (24.4%), and body weight loss (8.9%). All patients were eventually diagnosed by histopathology, and the DLBCL subtype took up 64.4%. Among the 45 cases of B cell subtype, 33 cases (73.3%) were of early stage (IE and IIE confirmed), and the 5-year survival rate was 78.1%, while those of stage IIIE and IVE comprised 26.7%, with a 5-year survival rate of 45.5% (P < 0.05). The 5-year survival rate of all patients was 71.1%. Surgery was employed in 36 cases, and 9 patients received chemotherapy alone. Radical surgery could significantly increase the patients' overall survival rate, as compared with the chemotherapy alone group and palliative surgery group (P < 0.05). CONCLUSIONS: Colorectal non-Hodgkin's lymphoma is a rare malignancy of the gastrointestinal tract. B cell type, male predominance and DLBCL subtype are most encountered manifestations in clinics. Multi-modality management with radical surgical resection of the primary lesion followed by standard chemotherapy, affords better local disease control, and a better survival outcome. Early detection and tailored immunotherapy can obviously prolong the long-term survival time.

[The diagnosis, treatment and prognosis evaluation of gastric small cell carcinoma: analysis of 41 cases].

OBJECTIVE: To summarize and analyze the clinical feature, therapeutic methods and prognosis of gastric small cell carcinoma (SCC). METHODS: The clinical and pathological data of 41 patients diagnosed of gastric SCC were analyzed in this research. Also, the factors which may potentially affect the patients' survival outcome were evaluated. There were 35 male and 6 female patients. The age at diagnosis was 39-84 years, median age was 62 years. The 31 cases (75.6%) of gastric SCC patients were involved in the upper third of the stomach, 3 cases (7.3%) in the middle, 7 cases (17.1%) in the lower third. RESULTS: The time from the event of symptoms to final confirmation was 1 to 13 months, the median time was 3 months. The longest diameter of tumors was from 2.5 to 15.0 cm, the average was 6.5 cm. The 38 cases (92.7%) chosed surgery as the first treatment, among which 25 cases (61.0%) were performed radical tumor resection, 13 cases (31.7%) went through palliative resection, and 3 cases (7.3%) just employed chemotherapy. The initial II, III, IV stage were 2, 31 and 8 cases, respectively. The overall median survival time was 19 months, median disease free survival time was 11 months, 1-, 2-, 5-years survival rates were 70.7%, 46.3% and 36.6%, respectively. In univariate survival analysis, the tumor size (χ² = 5.565), change of the body weight (χ² = 3.688), type of operation (χ² = 11.747) and relapse or not (χ² = 17.966) were obviously correlaed with the prognosis (P < 0.05). CONCLUSIONS: Gastric SCC is a rare disease of the gastrointestinal tract, the misdiagnosis rate is high, and the prognosis is dismal. Muti-modality management, with radical surgical resection of the primary lesion followed by standard adjuvant-chemotherapy, affords better local disease control and a better survival outcome.

Clinicopathologic characteristics and prognostic factors of 63 gastric cancer patients with metachronous ovarian metastasis.

OBJECTIVE: This study aims to explore the clinicopathologic characteristics and prognostic factors of gastric cancer patients with metachronous ovarian metastasis. METHODS: Clinicopathologic data were collected from 63 post-operative gastric cancer patients with metachronous ovarian metastasis. The patients were admitted to the Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College between January 1999 and December 2011. A log-rank test was conducted for survival analysis. Possible prognostic factors that affect survival were examined by univariate analysis. A Cox regression model was used for multivariate analysis. RESULTS: The incidence of ovarian metastasis was 3.4% with a mean age of 45 years. Up to 65.1% of the patients were pre-menopausal. The mean interval between ovarian metastasis and primary cancer was 16 months. Lowly differentiated carcinoma ranked first in the primary gastric cancers. The majority of lesions occurred in the serous membrane (87.3%). The metastatic sites included N2-3 lymph nodes (68.3%), bilateral ovaries (85.7%), and peritoneal membrane (73%). Total resection of metastatic sites was performed (31.7%). The overall median survival was 13.6 months, whereas the overall 1-, 2-, and 3-year survival rates were 52.5%, 22.0%, and 9.8%, respectively. The 5-year survival rate was zero. Univariate analysis showed that the patient prognosis was correlated with metastatic peritoneal seeding, vascular tumor embolus, range of lesion excision, and mode of comprehensive treatment with adjuvant chemotherapy (P<0.05). Multivariate analysis indicated that metastatic peritoneal seeding was an independent prognostic factor for gastric cancer patients with ovarian metastasis (P<0.01). CONCLUSION: Effective control of peritoneal seeding-induced metastasis is important for improving the prognosis of gastric cancer patients with ovarian metastasis.

Identification and expression of a tumor-associated antigen in esophageal squamous cell carcinoma.

OBJECTIVE: To search for novel tumor associated antigens (TAA) in esophageal squamous cell carcinoma (ESCC). METHODS: The proteins extracted from tissues of ESCC were separated by two dimensional polyacrylamide gel electrophoresis and transferred to PVDF membrane. Sera from ESCC patients and healthy individuals were used for primary antibodies for Western blot analysis. The differential spots were excised for trypsin hydrolysis and the tryptic peptides were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The identified TAA of ESCC was validated by immunohistochemical staining (IHC). RESULTS: Sera from ESCC patients yielded multiple positive spots, and one 28 800 Da protein that exhibited positive reactivity with 60% (12/20) sera of ESCC patients and only 5% (1/20) sera of healthy controls (P<0.01). The 28 800 Da protein was identified as phosphoglycerate mutase 1 (PGAM1) by MALDI-TOF-MS. Immunohistochemical analysis showed that PGAM1 was located in both cytoplasm and nucleus, and had a higher expression in cancer tissues. CONCLUSION: PGAM1 maybe a candidate of ESCC.

[Effects of hyperthermic chemotherapy on gastrointestinal cancer cells in vitro].

BACKGROUND & OBJECTIVE: Little evidence is known from experimental research for intraoperative hyperthermic intraperitoneal chemotherapy. This study was to investigate the effect of hyperthermic chemotherapy on gastrointestinal cancer cells in vitro and explore the possible factors which may affect this method. METHODS: Gastric cancer cell line MGC-803 and intestinal cancer cell line HCT-116 were chosen. Cells were treated with different drugs, temperatures and duration. Cell viability and growth were measured by MTS-PMS assay. The morphology of the cells was observed under a microscope. RESULTS: Significant synergistic effect was observed when the two cancer cell lines were treated with 5-FU, MMC, DDP and THP in combination with elevated hyperthermia from 41 degrees C to 45 degrees C compared with control group (P<0.01). The strongest effect was achieved at 45 degrees C, which the inhibitory effects of these four drugs were 61.7%, 79.2%, 88.7%, 94.7% on MGC-803 and 76.4%, 78.7%, 77.8%, 91.7 on HCT-1116, respectively. The inhibitory effect demonstrated a time and dose-dependent manner in HCT-116 cells within a certain period of time. The effect revealed a flat curve after 90 min when HCT-116 was treated with 43 centigrade. THP had the strongest effect at any conditions among all tested drugs (P<0.01). Either simple thermotherapy or chemohyperthermia displayed considerable killing effects on cancer cells which were confirmed by microscope observation. And a great deal of dead cells were observed when treated with chemohyperthermia. CONCLUSIONS: DDP or MMC reveals relatively satisfactory antitumor effects with the optimal temperature of 43-45 degrees C. Taken practical application into consideration, 60 min may be selected in clinical use. Synergistic antitumor effects of THP in combination with hyperthermia were prior to 5-FU, DDP or MMC, which deserve further clinical research.

[Peritoneal lavage cytology in 66 patients with gastric carcinoma].

OBJECTIVE: To evaluate the clinical and prognostic value of peritoneal lavage cytology (PLC) in detecting free cancer cells (FCC). METHODS: PLC of 66 gastric cancer patients being operated was prospectively analyzed to assess the prognostic significance of positive cytological finding and its relation with serosal invasion, lymph node metastasis and stage classification. RESULTS: The overall positive rate of cytology was 36.4% (24/66). These was a closely relation between positive cytology results and serosal invasion (P = 0.025), abdominal lymph node involvement (P < 0.005) and stage classification. Peritoneal recurrence in patients with positive cytological findings was significantly higher than that with negative results (P = 0.006 7). CONCLUSION: Micrometastasis to the abdominal cavity, formed by free cancer cells exfoliated from the tumor, are significantly responsible for peritoneal dissemination. Serosal invasion and metastatic nodes have greater risk for positive cytology and implies poor prognosis. Peritoneal lavage cytology, if practiced in all gastric cancer patients being operated, can predict the operative effect and prognosis, increase the accuracy of clinical stage and provide information for further adjuvant therapy.