Changes and Influential Factors of Chemotherapy Usage for Non-Small Cell Lung Cancer Patients in China: A Multicenter 10-Year (2005-2014) Retrospective Study.

BACKGROUND: Chemotherapy has improved the survival of non-small cell lung cancer (NSCLC) patients over the past few decades. However, there have not been any epidemiological studies on chemotherapy for Chinese NSCLC patients. PATIENTS AND METHODS: The patients diagnosed as primary lung cancer between January 1, 2005, and December 31, 2014, in eight hospitals from eight provinces in China were retrospectively reviewed. Demographic and clinical data were extracted from medical history systems. Chi-square test and logistic regression were used to analyze the changes of chemotherapy usage and influential factors. RESULTS: A total of 7184 lung cancer cases were eligible, among which 6481 NSCLC cases were included in this analysis. Among stage I/II patients, the percentages of receiving adjuvant chemotherapy did not change significantly between the earlier (28.5%) and the latter five years (25.7%) (p = 0.1288). Among stage IIIA patients, the percentages of chemotherapy usage did not change significantly between the earlier and the latter five years in neo-adjuvant (7.5% vs 5.6%, p = 0.1478) and adjuvant (23.1% vs 26.8%, p = 0.1129) treatment. The proportions of first-line platinum-based doublets for stage IIIB/IV patients changed significantly over the 10 years (p < 0.0001). Patients from provinces with inferior gross domestic product, with lower medical reimbursement rates and without smoking history were more likely to use the docetaxel/paclitaxel doublets, comparing with the gemcitabine doublets. CONCLUSION: From 2005 to 2014, there was no significant change in the chemotherapy pattern of early NSCLC. Economic factors mainly contributed to the significant changes in the first-line chemotherapy regimen selection for advanced patients.

What are the clinical symptoms and physical signs for non-small cell lung cancer before diagnosis is made? A nation-wide multicenter 10-year retrospective study in China.

BACKGROUND: Most lung cancer patients are diagnosed after the onset of symptoms. However, whether the symptoms of lung cancer were independently associated with the diagnosis of lung cancer is unknown, especially in the Chinese population. METHODS: We conducted a 10 years (2005-2014) nationwide multicenter retrospective clinical epidemiology study of lung cancer patients diagnosed in China. As such, this study focused on nonsmall cell lung cancer (NSCLC). We calculated the odds ratios (ORs) for variables associated with the symptoms and physical signs using multivariate unconditional logistic regressions. RESULTS: A total of 7184 lung cancer patients were surveyed; finally, 6398 NSCLC patients with available information about their symptoms and physical signs were included in this analysis. The most common initial symptom and physical sign was chronic cough (4156, 65.0%), followed by sputum with blood (2110, 33.0%), chest pain (1146, 17.9%), shortness of breath (1090, 17.0%), neck and supraclavicular lymphadenectasis (629, 9.8%), weight loss (529, 8.3%), metastases pain (378, 5.9%), fatigue (307, 4.8%), fever (272, 4.3%), and dyspnea (270, 4.2%). Patients with squamous carcinoma and stage III disease were more likely to present with chronic cough (P < 0.0001) and sputum with blood (P < 0.0001) than patients with other pathological types and clinical stages, respectively. Metastases pain (P < 0.0001) and neck and supraclavicular lymphadenectasis (P = 0.0006) were more likely to occur in patients with nonsquamous carcinoma than in patients with other carcinomas. Additionally, patients with stage IV disease had a higher percentage of chest pain, shortness of breath, dyspnea, weight loss, and fatigue than patients with other stages of disease. In multivariable logistic analyses, compared with patients with adenocarcinoma, patients with squamous carcinoma were more likely to experience symptoms (OR = 2.885, 95% confidence interval [CI] 2.477-3.359) but were less likely to present physical signs (OR = 0.844, 95% CI 0.721-0.989). The odds of having both symptoms and physical signs were higher in patients with late-stage disease than in those with early-stage disease (P < 0.0001). CONCLUSIONS: The symptoms and physical signs of lung cancer were associated with the stage and pathological diagnosis of NSCLC. Patients with squamous carcinoma were more likely to develop symptoms, but not signs, than patients with adenocarcinoma. The more advanced the stage at diagnosis, the more likely that symptoms or physical signs are to develop. Further prospective cohort studies are needed to explore these results.

Clinical characteristics and medical service utilization of lung cancer in China, 2005-2014: Overall design and results from a multicenter retrospective epidemiologic survey.

OBJECTIVES: This study aimed to explore the clinical profile and its trajectory of lung cancer on clinicopathological characteristics and medical service utilization in China. METHODS: Patients diagnosed with primary lung cancer in tertiary hospitals during 2005-14 were selected from seven geographic regions of China. Data on clinical characteristics and medical service utilization was extracted from medical record, and the ten-year trends were explored. RESULTS: A total of 7184 patients were included, the mean age was 58.3 years and the male-to-female-ratio was 2.7. From 2005 to 2014, the proportion of ≥60 year-old patients increased from 41.2% to 56.2% (p < 0.001). The smoking rate decreased from 62.9% to 51.1% (p < 0.001) and the proportion of females increased from 23.5% to 31.9% (p < 0.001). The proportion of advanced stage increased from 41.9% to 47.4% (p < 0.001). Adenocarcinoma's proportion increased from 36.4% to 53.5% (p < 0.001) while that of squamous carcinoma decreased from 45.4% to 34.4% (p < 0.001). The application of chest X-ray dropped from 50.2% to 31.0% (p < 0.001) but that of chest CT increased from 65.8% to 81.4% (p < 0.001). As two main treatment options, chemotherapy (p = 0.290) and surgery (p = 0.497) remained stable. The medical expenditure per patient increased from 40,508 to 66,020 Chinese Yuan (p < 0.001). CONCLUSIONS: The sustaining high smoking exposure, increasing proportion of female patients, advancing clinical stage, shifting of predominant pathology and increasing medical expenditure demonstrate potential challenges and directions on lung cancer prevention and control in China. Despite substantial changes of clinical characteristics, main treatment options remained unchanged, which needs further investigation.

[Analysis of clinicopathological features of intestinal neuroendocrine neoplasms].

OBJECTIVE: To analyze the clinicopathological features of intestinal neuroendocrine neoplasms. METHODS: The clinicopathological features of 114 patients with intestinal neuroendocrine neoplasms treated in our hospital from April 1999 to March 2011 were retrospectively reviewed, including tumor location, histological classification, muscle invasion, metastasis and clinical data. Immunohistochemical SP staining was applied to examine the expression of 15 markers in the tumor specimens. RESULTS: The male:female ratio of the patients was 1.33, and most of the tumors were located in the rectum of polypoid type. The positive rate of immunohistochemical staining of Syn expression was 97.4%, NSE 95.6%, PGP9.5 84.2%, CD56 75.4%, CD57 72.8%, CgA 43.0%, S100 36.0%, Syn combined with CgA 99.1%, and the two marker Syn and CgA combined with any one of CD56, CD57 or PGP9.5 reached to 100%. The 5-years survival rates of G1, G2 were 98.9% and 76.9%, respectively, and the overall 5-year survival rate of intestinal neuroendocrine neoplasms was 92.9%. Two of the 7 cases of poor differentiated neuroendocrine carcinoma died after operation, another 2 of them lost to follow up. Others were still alive during the follow-up. Among the 3 patients with small cell carcinoma, two survived for 8 to 24 months after operation, and one lost to follow up. Two cases of mixed adenoneuroendocrine carcinoma (MANEC) were still surviving during the follow-up. Different histological types of intestinal neuroendocrine neoplasms were significantly different in sex, primary tumor site, pathological type, tumor size, types of combined tumors, pT stage, aggressive nervous and vascular invasion, and metastasis (all P < 0.05). Single factor analysis of the intestinal neuroendocrine neoplasms indicated that tumor size (Z = -6.334, P < 0.001), histological classification (χ(2) = 31.175, P < 0.001) and muscle invasion (χ(2) = 63.567, P < 0.001) were associated with metastasis of intestinal neuroendocrine neoplasms. Logistic analysis showed that muscle invasion was the main behavior risk factor of this tumor (OR = 1.827, P < 0.05). CONCLUSIONS: Intestinal neuroendocrine neoplasms usually occur in males, and the most common involved organ is the rectum. Their histological types are related to the prognosis, and the depth of invasion is an important metastasis factor of intestinal neuroendocrine neoplasms. Of the neuroendocrine makers, the combination of CgA and Syn shows a higher diagnostic sensitivity.

Improvement in T-staging of rectal carcinoma: using a novel endorectal ultrasonography technique with sterile coupling gel filling the rectum.

Our purpose was to study the accuracy of using endorectal ultrasonography (ERUS) with sterile coupling gels filling the rectum in the preoperative T-staging of rectal carcinoma. A total of 189 patients with confirmed rectal carcinoma were recruited. All underwent ERUS and surgery within the week following sonography. EURS was performed by introducing sterile coupling gel into the rectum. Two radiologists looked at the images at the same time and agreed upon staging. Rectal carcinoma was staged from Tis to T4. The accuracy of T-staging by ERUS was 89.95%. The sensitivity, specificity, PPV and NPV for ERUS at different stages were calculated. For early stage (Tis and T1), these values were 93.62%, 97.89%, 93.62% and 97.89%, respectively. ERUS filling with sterile coupling gel in the rectum overcomes the pressure effect from a water bath and the restriction caused by tumor stenosis, thus, greatly improving the accuracy of T-staging. The examination is real-time, safe and inexpensive.

[Clinical and pathological analysis of 114 cases with non-ductal pancreatic adenocarcinoma occupying lesions].

OBJECTIVE: To improve the diagnosis and treatment of non-ductal pancreatic adenocarcinoma-occupying lesions. METHODS: A retrospective analysis was made for 114 cases of pancreatic non-ductal adenocarcinoma-occupying pathologically confirmed lesions. RESULTS: (1) There were 36 males (31.6%) and 78 females (68.42%); (2) presenting symptoms and signs were abdominal pain (n = 56, 49.1%), back pain (n = 24, 21.1%), weight loss (n = 18, 15.8%) and obstructive jaundice (n = 8, 0.07%); (3) the positive rates of CA19-9, CA242 and CEA were 21.1%, 19.7% and 5.6% respectively; (4) pancreaticoduodenectomy was performed in 26 patients, distal pancreatectomy in 53, tumor enucleation in 15, segmental pancreatectomy in 9, partial resection in 3, duodenum-preserving pancreatic head resection in 1 and palliative surgery (either cholecystojejunostomy anastomosis or gastrojejunostomy) in 7; (5) pathologic analysis revealed 35 solid pseudopapillary neoplasm of pancreas, 28 pancreatic endocrine tumors, 18 focal chronic pancreatitis, 11 serous cystic neoplasms, 9 mucinous cystic neoplasms, 4 pancreatic cysts, 3 acinar cell carcinomas, 2 pancreatic cavernous hemangiomas, 1 sarcoma of pancreas, 1 sarcomatoid carcinoma of pancreas, 1 pancreatic schwannoma and 1 pancreatic neuroblastoma. CONCLUSION: The non-ductal pancreatic adenocarcinoma-occupying lesions have no specific clinical presentation or serum tumor marker. An understanding of the natural history of these lesions is important for optimal management.

[Correlation between aneuploidy of chromosome 17, over-expression of TP53 and TOPIIalpha, and the clinicopathological features and diagnosis of gastric adenocarcinoma].

OBJECTIVE: The purpose of this study was to investigate the markers which can be used in auxiliary diagnosis of gastric adenocarcinoma (GAC), and their correlation with their clinicopathological features. METHODS: 122 surgical specimens including 99 gastric adenocarcinoma (GAC), 18 adjacent mucosa and 5 distal normal mucosa were collected, and analyzed by in situ hybridization (FISH). The centromere probe cen17, specific for chromosome 17, which was reported to be frequently amplified in GAC, was selected for the FISH analysis. The clinicopathological features of the 99 GAC cases were reviewed, and the level of TP53 and TOPIIalpha gene expression, located in chromosome 17, was detected using tissue micro-array (TMA), compared with that of corresponding adjacent normal mucosa. Data were analyzed with SPSS 11.5 for Windows. RESULTS: The statistical results of FISH and TMA showed that 58.6% of cen17 in tumor tissues were aneuploid, and 45.5% of TP53 and 84.7% of TOPIIalpha were over-expressed in GAC samples, significantly higher than those in non-tumor gastric mucosa (0, 12.1% and 14.1%, respectively) (P = 0.000). 58 GAC tissues were aneuploid of cen17, including 26 cases TP53-positive and 49 cases TOPIIalpha-positive. The expression of TP53 in non-tumor gastric mucosa with dysplasia was significantly higher than that in the mucosa without dysplasia (P = 0.009). Aneuploidy of cen17 was more frequent in grade 1 or 2 than in grade 3 GAC (P < 0.05). Higher frequency of aneuploidy of cen17 was also observed in the gastric cardia than in pylorus (P < 0.05), while no correlation was found between aneuploidy of cen17 and age, sex of patients, lymph node metastasis, and clinical stage of tumors. Over-expression of TP53 protein was associated with the size of tumors (P < 0.05). In addition, a negative correlation was observed between over-expression of TOPIIalpha and lymph node metastasis (LNM) as well as TNM classification (P < 0.05). CONCLUSION: Detection of aneuploidy of cen17 as well as over-expression of TP53 and TOPIIalpha may be helpful in the diagnosis and prognostic prediction of gastric adenocarcinoma.

[Clinicopathological features of uterine neoplasms with perivascular epithelioid cell differentiation].

OBJECTIVE: To study the neoplasm with perivascular epithelioid cell differentiation (PEComa) with respect to their morphologic, immunohistochemical and clinical phenotypes. METHODS: Three PEComas were included in this study, one located at the left uterine horn, and two presented as a mass in the uterine corpus. The tumors were examined by histopathology and immunohistochemistry. RESULTS: The lesions were composed of spindle, blunt epithelioid cells, with foci of, or scattered, cells showing adipose differentiation in two cases. The myomelanocytic differentiation was demonstrated, proving the diagnosis as PEComa. Mild nuclear atypia and focal necrosis was observed in one lesion, and the rest two showed malignant morphologic phenotypes including moderate nuclear atypia and coagulative necrosis. The mitotic and Ki67-labelling indices ranged from 0.5/10 HPF to 14/10 HPF and 0.6% to 7.0%, respectively. All of the three patients remain alive. Malignant nature of the two lesions with worrisome morphology was confirmed by occurrence of metastases after hysterectomy. CONCLUSION: PEComa is a rare tumor, occurring preferentially in the uterus. It is regarded as a tumor with uncertain malignant potential, but a minority of them shows malignant clinical behaviors. Some pathologic parameters including large tumor size, sheet-like necrosis, marked nuclear atypia, elevated mitotic index (> or = 10/10 HPF), aberrant mitotic figure and vascular invasion may help to establish a diagnosis of malignant PEComa.

The ubiquitin-proteasome pathway mediates gelsolin protein downregulation in pancreatic cancer.

A well-known observation with respect to cancer biology is that transformed cells display a disturbed cytoskeleton. The underlying mechanisms, however, remain only partly understood. In an effort to identify possible mechanisms, we compared the proteome of pancreatic cancer with matched normal pancreas and observed diminished protein levels of gelsolin--an actin filament severing and capping protein of crucial importance for maintaining cytoskeletal integrity--in pancreatic cancer. Additionally, pancreatic ductal adenocarcinomas displayed substantially decreased levels of gelsolin as judged by Western blot and immunohistochemical analyses of tissue micoarrays, when compared with cancerous and untransformed tissue from the same patients (P < 0.05). Importantly, no marked downregulation of gelsolin mRNA was observed (P > 0.05), suggesting that post-transcriptional mechanisms mediate low gelsolin protein levels. In apparent agreement, high activity ubiquitin-proteasome pathway in both patient samples and the BxPC-3 pancreatic cancer cell line was detected, and inhibition of the 26s proteasome system quickly restored gelsolin protein levels in the latter cell line. The status of ubiquitinated gelsolin is related to lymph node metastasis of pancreatic cancer. In conclusion, gelsolin levels are actively downregulated in pancreatic cancer and enhanced targeting of gelsolin to the ubiquitin-proteasome pathway is an important contributing factor for this effect.

Overexpression of annexin 1 in pancreatic cancer and its clinical significance.

AIM: To investigate the expression of annexin I in pancreatic cancer and its relationship with the clinicopathologic factors, and to evaluate its potential clinical significance. METHODS: Annexin I expression was analyzed by Western blot and immunohistochemical staining in pancreatic adenocarcinoma and multi-tissue microarrays (MTAs). RESULTS: Western blot analysis showed that annexin I was overexpressed in 84.6% (11/13) pancreatic ductal adenocarcinomas. Immunohistochemistry analysis of pancreatic cancer in MTAs showed that annexin I protein was 71.4%(30/42) positive which was markedly increased compared with that in the tumor matched normal pancreas tissues 18.4%(7/38) (P<0.01). In the meantime, the high expression of annexin 1 was correlated with the poor differentiation of pancreatic adenocarcinoma. CONCLUSION: Annexin 1 overexpression is a frequent biological marker and correlates with the differentiation of pancreatic cancer during tumorigenesis.

[Primary gastric endocrine tumors].

OBJECTIVE: To study the clinicopathological features of gastric neuroendocrine tumors. METHODS: Twenty cases were reviewed. The specimens were formalin-fixed, paraffin-embedded and immunostained by S-P method. RESULTS: Among the twenty cases, one case was carcinoid, three were malignant carcinoids, six had small cell carcinomas and ten had mixed extocrine--endocrine carcinomas. Immunohistological examination of tumor cells found 80% positive for S-100, NSE (85%), CgA (50%), SY (50%), gastrin (30%), serotonin (65%), AE1/AE3 (50%), and CEA (80%). CONCLUSIONS: In the WHO classification, there are five histological types in endocrine tumors of gastrointestinal tract. They are carcinoid, malignant carcinoid, small cell carcinoma, mixed exocrine--endocrine carcinoma and tumor-like lesions. But some cases in our paper were so different that they could not be classified. The gastric endocrine tumors are different from intestinal endocrine tumors and in classification, treatment and prognosis.