Management of asymptomatic primary tumours in stage Ⅳ colorectal cancer: Review of outcomes

AIM: To compare outcomes for patients presenting withstage IV colorectal cancer and an asymptomatic primary tumour, undergoing primary tumour resection(PTR) plus palliative chemotherapy vs primary chemotherapy up-front.METHODS: A literature search was conducted using MEDLINE and EMBASE. The primary outcome was overall survival. Secondary outcomes included perioperative mortality, morbidity and delayed surgical intervention rates in patients undergoing PTR and subsequent complication rates in patients with an un-resected primary tumour. Tertiary outcomes included impact on systemic treatment and identification of prognostic factors relevant for survival in this cohort. RESULTS: Twenty non-randomised studies met the inclusion criteria. Eleven studies included comparative overall survival data. Three studies showed an overall survival advantage for PTR, 7 studies showed no statistically significant advantage, and 1 study showed a significant worsening in survival in the surgical group. The perioperative mortality rate ranged from 0% to 8.5%, and post-operative morbidity rate from 10% to 35%, mainly minor complications that did not preclude subsequent chemotherapy. The rate of delayed primarytumour related symptoms, most commonly obstruction, in patients with an un-resected primary tumour ranged from 3% to 46%. The strongest independent poor prognostic factor was extensive hepatic metastases, in addition to poor performance status, M1 b stage and non-use of modern chemotherapy agents.CONCLUSION: Based on the current literature, both PTR and up front chemotherapy appear appropriate initial management strategies, with a trend towards an overall survival advantage with PTR. The procedure has a low post-operative mortality, and most complications are transient and minor. The results of recruiting randomised trials are eagerly anticipated.

Evidence for Tumour Suppressor Function of DOK7 in Human Breast Cancer

Introduction: Downstream of tyrosine kinase 7 (DOK-7) is a member of the DOK family, which has been associated with the development and progression of various humancancers. Previously, identification of CpG hypermethylation in DOK-7 promoter was identified in breast cancer. Method: DOK-7 mRNA extraction and reverse transcription were performed on fresh frozen breast cancer tissue samples and normal background breast tissue. Transcript levels of expression were analyzed against TNM stage, tumour grade and clinical outcome over a 10-year follow-up period. Results: Levels of DOK-7 expression decreased significantly with increasing TNM stage. Higher DOK-7 expression was correlated with longer disease free and overall survival times. Conclusion: To our knowledge, this is the first study to investigate DOK-7 expression in human breast cancer. We identify a potential DOK-7 tumour suppressor role. DOK-7 as a prognostic biomarker in human breast cancer should be included in future validation studies.

Tumour Necrosis Factor Alpha and Oxidative Stress in the Breath Condensate of Those with Non-Small Cell Lung Cancer

Background and Aims: Lung cancer is a leading cause of cancer mortality worldwide and is associated with the release of tumour necrosis factor-α (TNF-α), subsequent cellular apoptosis and the generation of oxidative stress. Exhaled breath condensate (EBC) analysis is a non-invasive method for sampling biofluids from the lower respiratory tract. This study aimed to evaluate possible biomarkers of lung cancer by measuring the levels of TNF-α and the oxidation of ascorbic acid in EBC. Patients with lung cancer were enrolled into the study prior to treatment, during treatment and post-treatment, and results compared with an age-matched control population. Material and Methods: Patients with Stage II-IV non small cell lung cancer (NSCLC) were recruited prior to and at stages of their treatment. EBC levels of TNF-α, and rate of ascorbic acid oxidation were measured. Results: A total of 19 patients with NSCLC (mean age 71.37 ± 7.77 yrs) and 25 age-matched control subjects were enrolled. Levels of EBC TNF-α were elevated in the EBC of patients with lung cancer compared with control subjects (1.02 ± 0.07 pg/ml vs. 0.51 ± 0.06 pg/ml, p < 0.0001). Moreover, the rate of ascorbic acid oxidation was significantly greater in the EBC of patients with lung cancer compared with control subjects (2.20% [0.4 – 11.0] vs. 1.00% [0.1 – 8.5], p = 0.0244). Conclusion: TNF-α and the rate of ascorbic acid oxidation was elevated in the EBC of patients with lung cancer regardless of treatment. Longitudinal studies in a larger population are required to evaluate these markers for the effect of treatment and prognosis.

Research Progress of Breast Cancer Stem Cell Stemness and Breast Cancer Recurrence

Currently, breast cancer is the most common malignant tumour in Chinese women with a high incidence rate, and recurrence and metastasis are the main reasons affecting survival. Breast Cancer Stem Cells (BCSCs) are stem cells capable of continuous regeneration in vivo with strong self-renewal ability and multidirectional differentiation potential, which are highly tumourigenic and insensitive to radiotherapy and chemotherapy, and are highly susceptible to breast cancer recurrence. Therefore, exploring the stemness of BCSCs and their mechanism associated with recurrence is important for developing new therapeutic strategies, improving therapeutic efficacy, and improving patient prognosis.

Diagnostic strategies and the incidence of prostate cancer： reasons for the low reported incidence of prostate cancer in China

We have analysed the reasons for the low reported incidence of prostate cancer in China and argue for early diagnosis and treatment of this disease. According to the 2002 database of the International Agency for Research on Cancer （IARC）, the age-standardized incidence of prostate cancer in China is 1.6/105 person years （PY）, with a mortality rate of 1.0/105 PY and mortality-to-incidence rate ratio （MR/IR） = 0.63. The MR/IR ratio of prostate cancer in China was found to be higher than the average in Asia （MR/IR = 0.57） and much higher than that in North America （MR/IR = 0.13）. These data indicate that in China most prostate cancers were in the advanced stages at the time of diagnosis, and that patients had a short survival time thereafter. In 2004, Stamey et al. reported a retrospective American study of prostate cancer for the years 1983-2003. It was shown that most cases of prostate cancer detected by prostate-specific antigen （PSA） screening were in the advanced stage at the start of this 20-year period. These early follow-up data are quite similar to the results obtained from mass PSA screening of elderly men in Changchun, China. However, after the American programmes for early diagnosis and treatment of prostate cancer were accepted, tumours were diagnosed at earlier stages. On the basis of these findings, mass screening should be performed in the whole of China using serum PSA to facilitate early diagnosis and treatment of prostate cancer.

Pancreatic cancer and its stroma: A conspiracy theory

Pancreatic cancer is characterised by a prominent desmoplastic/stromal reaction that has received little attention until recent times. Given that treatments focusing on pancreatic cancer cells alone have failed to significantly improve patient outcome over many decades, research efforts have now moved to understanding the pathophysiology of the stromal reaction and its role in cancer progression. In this regard, our Group was the first to identify the cells(pancreatic stellate cells, PSCs) that produced the collagenous stroma of pancreatic cancer and to demonstrate that these cells interacted closely with cancer cells to facilitate local tumour growth and distant metastasis. Evidence is accumulating to indicate that stromal PSCs may also mediate angiogenesis, immune evasion and the well known resistance of pancreatic cancer to chemotherapy and radiotherapy. This review will summarise current knowledge regarding the critical role of pancreatic stellate cells and the stroma in pancreatic cancer biologyand the therapeutic approaches being developed to target the stroma in a bid to improve the outcome of this devastating disease.

Assessment of vascular invasion in gastric cancer: A comparative study

AIM: To evaluate and compare detection of lymphatic and blood vessel invasion (LVI and BVI) by hematox-ylin-eosin (HE) and immunohistochemistry (IHC) in gastric cancer specimens, and to correlate with lymph node status. METHODS: IHC using D2-40 (a lymphatic endothelial marker) and CD34 (a pan-endothelial marker) was performed to study LVI and BVI in surgical specimens froma consecutive series of 95 primary gastric cancer cases. The results of the IHC study were compared with the detection by HE using McNemar test and kappa index. The morphologic features of the tumors and the presence of LVI and BVI were related to the presence of lymph node metastasis. A χ2 test was performed to obtain associations between LVI and BVI and other prognostic factors for gastric cancer. RESULTS: The detection rate of LVI was considerably higher than that of BVI. The IHC study identified eight false-positive cases and 13 false-negative cases for LVI, and 24 false-positive cases and 10 false-negative cases for BVI. The average Kappa value determined was moderate for LVI (k=0.50) and low for BVI (k=0.20). Both LVI and BVI were statistically associated with the presence of lymph node metastasis (HE: P=0.001, P=0.013, and IHC: P=0.001, P=0.019). The mor-phologic features associated with LVI were location of the tumor in the distal third of the stomach (P=0.039), Borrmann's macroscopic type (P=0.001), organ inva-sion (P=0.03) and the depth of tumor invasion (P=0.001). The presence of BVI was related only to the depth of tumor invasion (P=0.003). CONCLUSION: The immunohistochemical identification of lymphatic and blood vessels is useful for increasing the accuracy of the diagnosis of vessel invasion and for predicting lymph node metastasis.

Immunological battlefield in gastric cancer and role of immunotherapies

Like the wars predating the First World War where human foot soldiers were deemed tools in the battlefield against an enemy, so too are the host immune cells of a patient battling a malignant gastric cancer. Indeed, the tumour microenvironment resembles a battlefield, where the patient's immune cells are the defence against invading tumour cells. However, the relationship between different immune components of the host response to cancer is more complex than an "us against them" model. Components of the immune system inadvertently work against the interests of the host and become pro-tumourigenic while other components soldier on against the common enemy – the tumour cell.

Pancreatic cancer: Are 'liquid biopsies' ready for prime-time?

Pancreatic cancer is a disease that carries a poor prognosis. Accurate tissue diagnosis is required. Tumours contain a high content of stromal tissue and therefore biopsies may be inconclusive. Circulating tumour cells(CTCs) have been investigated as a potential "liquid biopsy" in several malignancies and have proven to be of prognostic value in breast, prostate and colorectal cancers. They have been detected in patients with localised and metastatic pancreatic cancer with sensitivities ranging from 38%-100% using a variety of platforms. Circulating tumour DNA(ct DNA) has also been detected in pancreas cancer with a sensitivity ranging from 26%-100% in studies across different platforms and using different genetic markers. However, there is no clear consensus on which platform is the most effective for detection, nor which genetic markers are the most useful to use. Potential roles of liquid biopsies include diagnosis, screening, guiding therapies and prognosis. The presence of CTCs or ct DNA has been shown to be of prognostic value both at diagnosis and after treatment in patients with pancreatic cancer. However, more prospective studies are required before this promising technology is ready for adoption into routine clinical practice.

Blood classical monocytes phenotype is not altered in primary non-small cell lung cancer

AIM: To evaluate the M1 and M2 monocyte phenotype in patients with non-small cell lung cancer(NSCLC) compared to controls. Also, to examine the expression of Th1 and Th2 cytokines in plasma of NSCLC vs controls. METHODS: Freshly prepared peripheral blood mononuclear cells samples were obtained from patients with NSCLC(lung adenocarcinoma and squamous cell lung carcinoma) and from non-cancer controls. Flow cytometry was performed to investigate M1 and M2 phenotypes in peripheral monocytes(classical monocytes CD14+, CD45+ and CD16-) using conventional surface markers. Th1 and Th2 cytokine production was alsoanalysed in the plasma using cytometric bead array technique. RESULTS: There were no significant difference in expression of M1(HLA-DR) and/or M2 markers(CD163 and CD36) markers on classical monocytes in patients with NSCLC compared to non-cancer controls. Expression of CD11 b, CD11 c, CD71 and CD44 was also shown to be similar in patients with NSCLC compared to noncancer controls. Th1 and Th2 cytokines [interleukin(IL)-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12(p70), tumor necrosis factor(TNF)-α, TNF-β, and interferon-γ] analysis revealed no significant difference between patients with NSCLC and non-cancer controls. CONCLUSION: This study shows no alteration in peripheral monocyte phenotype in circulating classical monocytes in patients with NSCLC compared to noncancer controls. No difference in Th1 and Th2 cytokine levels were noted in the plasma of these patients.

TNM staging update for lung cancer:Why is this important?

Cancer staging characterises the extent of disease facilitating selection of the most appropriate management and therapy and providing prediction of prognosis.As understanding of lung cancer evolves the opportunities arises to adjust disease staging.The adoption of the 7th edition tumour,node,metastasis staging system should result in improved treatment selection and more accurate prognostic information for the individual patient.

晚期恶性肿瘤患者癌因性疲乏现状及其影响因素

目的 了解晚期恶性肿瘤患者抗肿瘤治疗期间癌因性疲乏现状,并分析其影响因素,为临床护理干预提供依据。方法 采用便利抽样法,选取2022年1月至8月在北京市某三级甲等综合医院肿瘤内科住院并接受抗肿瘤治疗的279例晚期恶性肿瘤患者作为研究对象,采用癌症疲乏量表(cancer fatigue scale,CFS)、化疗消化道症状量表(chemotherapy-related gastrointestinal symptoms inventory,CGISI)、营养风险筛查2002量表(nutritional risk screening 2002,NRS2002)进行调查,采用Logistic回归分析患者癌症疲乏得分的影响因素。结果 279例患者均完成研究。204例(73.1%)患者存在癌因性疲乏。Logistic回归分析显示,体质量指数(body mass index,BMI)、文化程度、家庭人均月收入和糖尿病均是癌因性疲乏的影响因素(均P<0.05)。结论 晚期恶性肿瘤患者在抗肿瘤治疗期间癌因性疲乏发生率较高,BMI过低、文化程度低、家庭人均月收入较低及糖尿病为晚期恶性肿瘤患者癌因性疲乏的危险因素,可据此实施针对性干预,降低疲乏发生率。

Preliminaries for a New Mathematical Framework for Modelling Tumour Growth Using Stress State Decomposition Technique

The main goal of the present paper is to present a mathematical framework for modelling tumour growth based on stress state decomposition technique (SSDT). This is a straightforward extension of the model for multi-phase nonsaturated soil consolidation with pollutant transport presented by the authors and may be regarded as an alternative to classical frameworks based on TCAT theory. In this preliminary work, the Representative Volume Element (RVE) for tumour is proposed along with its comparison with the corresponding one for soils modelling developed formerly by the authors. Equations standing for tumour phase are flawlessly brought into correspondence with those of gaseous phase in the soil problem showing that a similar task may be carried out for the remainders phases taking part in both RVEs. Furthermore, stresses induced by nonlinear saturation and permeability dependence on suction for soil interstitial fluids transport finds its counterpart on the contact between the cancer cell membrane and interstitial fluids rendering a higher primary variables coupling degree than what was attained in TCAT theory. From these preliminaries assessments, it may be put forward that likewise the stress state decomposition procedure stands for an alternative for modelling multi-phase nonsaturated soil consolidation with pollutant transport;it does for modelling cancer as well.

Defining response to radiotherapy in rectal cancer using magnetic resonance imaging and histopathological scales

AIM To define good and poor regression using pathology and magnetic resonance imaging(MRI) regression scales after neo-adjuvant chemotherapy for rectal cancer.METHODS A systematic review was performed on all studies up to December 2015, without language restriction, t h a t w e r e i d e n t i f i e d f r o m M E D L I N E, C o c h r a n e Controlled Trials Register(1960-2015), and EMBASE(1991-2015). Searches were performed of article bibliographies and conference abstracts. MeS H and text words used included "tumour regression", "mr TRG", "poor response" and "colorectal cancers". Clinical studies using either MRI or histopathological tumour regression grade(TRG) scales to define good and poor responders were included in relation to outcomes [local recurrence(LR), distant recurrence(DR), disease-free survival(DFS), and overall survival(OS)]. There was no age restriction or stage of cancer restriction for patient inclusion. Data were extracted by two authors working independently and using pre-defined outcome measures.RESULTS Quantitative data(prevalence) were extracted and analysed according to meta-analytical techniques using comprehensive meta-analysis. Qualitative data(LR, DR, DFS and OS) were presented as ranges. The overall proportion of poor responders after neo-adjuvant chemoradiotherapy(CRT) was 37.7%(95%CI: 30.1-45.8). There were 19 different reported histopathological scales and one MRI regression scale(mrT RG). Clinical studies used nine and six histopathological scales for poor and good responders, respectively. All studies using MRI to define good and poor response used one scale. The most common histopathological definition for good response was the Mandard grades 1 and 2 or Dworak grades 3 and 4; Mandard 3, 4 and 5 and Dworak 0, 1 and 2 were used for poor response. For histopathological grades, the 5-year outcomes for poor responders were LR 3.4%-4.3%, DR 14.3%-20.3%, DFS 61.7%-68.1% and OS 60.7-69.1. Good pathological response 5-year outcomes were LR 0%-1.8%, DR 0%-11.6%, DFS 78.4%-86.7%, and OS 77.4%-88.2%. A poor response on MRI(mr TRG 4,5) resulted in 5-year LR 4%-29%, DR 9%, DFS 31%-59% and OS 27%-68%. The 5-year outcomes with a good response on MRI(mrT RG 1,2 and 3) were LR 1%-14%, DR 3%, DFS 64%-83% and OS 72%-90%.CONCLUSION For histopathology regression assessment, Mandard 1, 2/Dworak 3, 4 should be used for good response and Mandard 3, 4, 5/Dworak 0, 1, 2 for poor response. MRI indicates good and poor response by mr TRG1-3 and mrT RG4-5, respectively.

TNF-a-308 polymorphism and risk of digestive system cancers:A meta-analysis

AIM:To evaluate the association between the tumour necrosis factor alpha-308(TNF-a-308)gene polymorphism and the risk of digestive system cancers.METHODS:All eligible case-control studies published up to December 2012 were identified by searching PubMed,Web of Science,Embase and China National Knowledge Internet without language restrictions.The risk of digestive system cancers associated with the TNF-a-308 polymorphism was estimated for each study using odds ratio(OR)together with its 95%CI,respectively.Cochrane Collaboration RevMan 5.1 was used to perform the analysis.Aχ2-test-based Q statistic test and an I2test were performed to assess the betweenstudy heterogeneity.When the Q test was significant(P<0.05)or I2>50%,the random effects model was used,otherwise the fixed effects model was used.RESULTS:Fifty-eight studies from fifty-five publications with a total of 9986 cancer patients and 15511 healthy controls were included.Overall,a significant association was found between the TNF-a-308 polymorphism and the risk of digestive system cancers[dominant model:OR=1.23,95%CI:1.09-1.39,(G/A)vs(G/G):OR=1.15,95%CI:1.02-1.28,(A/A)vs(G/G):OR=1.44,95%CI:1.19-1.73,recessive model:OR=1.38,95%CI:1.15-1.66].Furthermore,when the analysis was stratified by ethnicity,similar results were observed in both the Asian and Caucasian populations,except for the dominant model and heterozygote comparisons in the Asian population[dominant model:OR=1.24,95%CI:0.99-1.56,(G/A)vs(G/G):OR=1.09,95%CI:0.96-1.24].When the cancer type subgroups were examined,similar results were detected in gastric and hepatocellular carcinomas;however,no significant association was observed among other digestive system cancers.CONCLUSION:The TNF-a-308 gene polymorphism may be significantly associated with the risk of gastric and hepatocellular carcinomas,but not colorectal,pancreatic,or oesophageal cancer,in the Asian population.

Epidemiological and Clinical Aspects of Bladder Tumours at the Nianankoro Fomba Hospital in Segou in the Urology Department

Objectives: To study the epidemiological, diagnostic and prognostic aspects of bladder tumours in Segou Hospital. Patients and Methods: We conducted a descriptive cross-sectional study of bladder tumours over the period from 1 April 2012 to 1 April 2017, in the urology department of the Nianankoro Fomba Hospital in Segou. The first three years were used for patient recruitment, and the last two years for follow-up of the patients in the series. Results: Over a period of three years, we collected 165 cases of bladder tumours hospitalised out of 1308 hospitalisations from 7007 consultations, i.e. 12.6% of hospitalisations and 2.3% of consultations. The sex ratio was 1.2 in favour of men. A history of treated bilharzia was reported in 78.8% of cases and untreated bilharzia in 9.1% of cases. Haematuria was the most common reason for consultation. The majority of our patients were at stage T4 and T3 at the time of diagnosis, i.e. 53.3% and 44.3% respectively. Most patients consulted within 13 to 24 months after the first sign, i.e. 44.8%. Conclusion: The prognosis is still clouded by the delay in management. All the patients diagnosed had a bladder tumour infiltrating the muscle.

Is the determination of ctDNA a scientific “spy” that foresees cancer?

Since 1948, circulating tumour DNA(ctDNA) was first identified in human blood. ctDNA is in fact DNA shed by tumour cells from all metastatic tumour locations throughout the whole body, and is thrown into the bloodstream and can then be isolated by a standard blood draw. Using this technique scientists can obtain a wide view of tumour heterogeneity, identify different mechanisms of drug resistance, what is its predominance and the clinical rational of precision cancer medicine become a part of our daily practice. Secondly, early detection of cancer may also contribute to global decrease in cancer mortality.

The prognostic significance of percentage of tumour involvement according to disease risk group in men treated with radical prostatectomy

We investigated the prognostic significance of percentage of tumour involvement （PTI） according to the clinicopathological features of prostate cancer among patients who underwent radical prostatectomy （RP）. A retrospective study of 534 patients who underwent RP between September 2003 and March 2008 without any neoadjuvant or adjuvant therapy was performed. The associations of PTI with various clinicopathological features and biochemical recurrence-free survival were examined via uni- and multivariate analyses. The predictive accuracy of the multivariate model was assessed with a receiver operating characteristics-derived area under the curve. PTI was demonstrated to be significantly associated with preoperative prostate-specific antigen （PSA） level （P=0.001）, pathological Gleason score （P〈0.001）, extraprostatic tumour extension （P〈0.001）, seminal vesicle invasion （P〈0.001） and positive surgical margin （P〈0.001） in univariate analyses. When patients were stratified into disease risk groups, PTI was an independent predictor of biochemical recurrence-free survival in multivariate analysis only among the low-risk group （P=0.033） but not the intermediate- （P=0.287） or the high-risk groups （P=0.828）. The addition of the PTI did not significantly increase the accuracy of the multivariate model devised for the prediction of biochemical recurrence-free survival among both total patients （P=-0.459） and the low-risk group （P=0.268）, respectively. In conclusion, although PTI appeared to be a more significant prognostic factor among patients with low-risk disease than among those with higher risk diseases, overall, the PTI may not provide additional prognostic information beyond what can already be obtained via established prognostic factors.

Towards a Field Theoretical Stochastic Model for Description of Tumour Growth

We develop a field theory-inspired stochastic model for description of tumour growth based on an analogy with an SI epidemic model, where the susceptible individuals (S) would represent the healthy cells and the infected ones (I), the cancer cells. From this model, we obtain a curve describing the tumour volume as a function of time, which can be compared to available experimental data.

A Case of Bilateral Secondary Pneumothorax Shortly after the Completion of Concurrent Chemoradiotherapy for Tongue Cancer

Metastatic lung tumours rarely lead to development of pneumothorax, and no case of bilateral secondary pneumothorax due to lung metastases arising from tongue cancer has been reported. Here, we report a case of a patient with tongue cancer with lung metastases complicated by bilateral secondary pneumothorax soon after the completion of concurrent chemoradiotherapy. A 39-year-old man with cervical lymph node metastases originating from pT2N0M0 tongue cancer underwent neck dissection and postoperative concurrent chemoradiotherapy. Shortly after the completion of chemoradiotherapy, he developed bilateral secondary pneumothorax. Subsequently, he underwent partial lung resection for the pulmonary fistulae for diagnostic and therapeutic purposes;nodular lesions found in both the lungs. The diagnosis of secondary pneumothorax was based on histopathological findings. Although all pulmonary fistulae disappeared after partial lung resection, he died of the primary disease despite our best efforts to control the metastatic pulmonary lesions.