On the road to standardization of D2 lymph node dissection in a European population of patients with gastric cancer

The amount of lymph node dissection(LD) required during surgical treatment of gastric cancer surgery has been quite controversial.In the 1970 s and 1980 s,Japanese surgeons developed a doctrine of aggressive preventive gastric cancer surgery that was based on extended(D2) LD volumes.The West has relatively lower incidence rates of gastric cancer,and in Europe and the United States the most common LD volume was D0-1.This eventually caused a scientific conflict between the Eastern and Western schools of surgical thought.:Japanese surgeons determinedly used D2 LD in surgical practice,whereas European surgeons insisted on repetitive clinical trials in the European patient population.Today,however,one can observe the results of this complex evolution of views.The D2 LD is regarded as an unambiguous standard of gastric cancer surgical treatment in specialized European centers.Such a consensus of the Eastern and Western surgical schools became possible due to the longstanding scientific and practical search for methods that would help improve the results of gastric cancer surgeries using evidence-based medicine.Today,we can claim that D2 LD could improve the prognosis in European populations of patients with gastric cancer,but only when the surgical quality of LD execution is adequate.

Development of scanning transmission ion microscopy computed tomography at Fudan microbeam line

The computed tomography was applied to setting STIM(Scanning Transmission Ion Microscopy) projections recorded at the Fudan Ion Beam Laboratory.In this work,in order to visualize the three-dimensional mass density distribution in several specimens,example for a test structure of hollow gold cyliner was presented together with a detailed description of the developed system,including data reconstruction code(Tomorebuild 2) and image display software(AMIRA).Future development will allow the particle induced X-ray emission tomography for elemental analysis of micrometer-sized samples.

Testicular Metastasis as an Initial Manifestation of Gastrointestinal Cancer

Metastatic small bowel tumors in the testes are uncommon often indicating an advanced stage of sickness with poor prognosis. The route of spread to the scrotal level has not yet been defined. The most of these tumors are diagnosed at autopsy or orchiectomy for metastatic carcinoma. The diagnosis is mainly based on histological and immunohistochemical data. In this paper, we report the case of a 36-year-old patient with a spermatic torsion secondary to a testis metastasis from an adenocarcinoma of the small intestine confirmed histologically, occurring as first clinical manifestation that was taken care in the medical oncology department of CHU Hassan II in Fès. The aim of the subject is to highlight this rare metastatic localization of gastrointestinal cancer;how to approach the diagnosis and distinguish between primary testicular cancer and testicular metastasis;by describing the different clinical, radiological and anatomopathological aspects of metastatic gastrointestinal cancer to the testis.

Cancer Survivors’ Experience of Health-Related Quality of Life Six to Eight Years after Diagnosis—A Qualitative Study

Background: Health-related quality of life (HRQOL) is affected for many years following cancer treatment. With an increasing number of long-term cancer survivors, HRQOL will be a key concern in the future. There is a lack of qualitative studies investigating long-term cancer survivors’ needs and experience of late effects and HRQOL. Objective: The aim of this sub-study is to describe cancer survivors’ own experience of late effects affecting HRQOL six to eight years after diagnosis. Methods: We used a qualitative methodology with semi-structured focus group interviews to gain an in-depth understanding of participants’ experience of their HRQOL. Interviews were audio-recorded, transcribed and analyzed using thematic analysis. Results: All of the participants reported late effects at some point after the treatment. Some of the experienced late effects had improved over the years, while the late effects mentioned in this article were still prominent six to eight years after the diagnosis. They described, among others, late effects such as reduced physical strength, cognitive difficulties, lack of energy and increased sensitivity. The participants described the late effects as bearable, but still affecting their HRQOL by limiting their activity level, their ability to work and their social interactions. Conclusions: Six to eight years post-treatment, cancer survivors still experienced physical and cognitive late effects affecting their HRQOL. The findings indicate that some late effects affect HRQOL for a long time. To prepare cancer survivors for post-treatment life and to optimize their HRQOL, they need information concerning potential late effects before, during and after cancer treatment, as well as support services and follow-up in the municipalities.

The Efficacy of a Formula Food for Preventing Postoperative Recurrence in a Tumor Dormancy Model

Objective To establish a lung cancer dormancy mouse model and verify the effects of Wushen(WS),a formula food,on postoperative recurrence.Methods We established a Lewis cell tumor dormancy model system that definitively links surgery and the subsequent wound-healing response to the outgrowth of lung cancer cells.We used this model to observe the effects of WS on the postoperative recurrence and the nutritional status of the mice.Finally,the immunocyte subtypes and cytokine levels in the serum and spleens of mice were detected by flow cytometry and ELISA.Results The recurrence rate in the WS group was obviously lower than that in the control group.Wushen increased the body weights and serum albumin levels of the mice.The levels of NK,Gr1+CD11b+CD3+CD8+and CD3+CD4+T cells in the spleens of mice in the WS group were also increased.Compared with the control group,the levels of CD4+IFN-γ+,CD4+IL-2 and CD4+/IL-10+in the spleens of mice in the WS group were decreased.Wushen also seemed to decrease the levels of IL-6 and TNF-α,but the decrease was not significant.Conclusion The postoperative lung cancer recurrence model was successfully established.Wushen inhibited postoperative recurrence,apparently by regulating the level of immune cell subtypes and cytokines in the serum and spleen.

Targeted therapy in advanced metastatic colorectal cancer: Current concepts and perspectives

The introduction of new cytotoxic substances as well as agents that target vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) signaling has improved clinical outcome of patients with metastatic colorectal cancer (mCRC). In this review we summarize the most relevant clinical data on VEGF and EGFR targeting regimens in mCRC. The effects of available treatment strategies for mCRC are often temporary, with resistance and disease progression developing in most patients. Thus, new treatment strategies are urgently needed. Some GI peptides including gastrin and gastrin releasing peptide, certain growth factors such as insulin-like growth factor-I and II and neuropeptides such as growth hormone releasing hormone (GHRH) are implicated in the growth of CRC. Experimental investigations in CRC with antagonistic analogs of bombesin/gastrin-releasing peptide, GHRH, and with cytotoxic peptides that can be targeted to peptide receptors on tumors, are summarized in the second part of the review.

Histological differentiation impacts the tumor immune microenvironment in gastric carcinoma:Relation to the immune cycle

BACKGROUND Various histological types of gastric carcinomas(GCs)differ in terms of their pathogenesis and their preexisting background,both of which could impact the tumor immune microenvironment(TIME).However,the current understanding of the immune contexture of GC is far from complete.AIM To clarify the tumor-host immune interplay through histopathological features and the tumor immune cycle concept.METHODS In total,50 GC cases were examined(15 cases of diffuse GC,31 patients with intestinal-type GC and 4 cases of mucinous GC).The immunophenotype of GC was assessed and classified as immune desert(ID),immune excluded(IE)or inflamed(Inf)according to CD8+cell count and spatial pattern.In addition,CD68+and CD163+macrophages and programmed death-ligand 1(PD-L1)expression were estimated.RESULTS We found that GCs with different histological differentiation demonstrated distinct immune contexture.Most intestinal-type GCs had inflamed TIMEs rich in both CD8+cells and macrophages.In contrast,more aggressive diffuse-type GC more often possessed ID characteristics with few CD8+lymphocytes but abundant CD68+macrophages,while mucinous GC had an IE-TIME with a prevalence of CD68+macrophages and CD8+lymphocytes in the peritumor stroma.PD-L1 expression prevailed mostly in intestinal-type Inf-GC,with numerous CD163+cells observed.Therefore,GCs of different histological patterns have specific mechanisms of immune escape.While intestinal-type GC was more often related to PD-L1 expression,diffuse and mucinous GCs possessing more aggressive behavior demonstrated low immunogenicity and a lack of tumor antigen recognition or immune cell recruitment into the tumor clusters.CONCLUSION These data help to clarify the links between tumor histogenesis and immunogenicity for a better understanding of GC biology and more tailored patient management.

Changes of activated circulating endothelial cells and survivin in patients with non-small cell lung cancer after antiangiogenesis therapy

Background Although antiangiogenesis therapy plays an important role in anti-neoplastic treatment with its recognized efficacy and slight adverse effect, there is no prospective clinical trial to define ideal markers for predicting efficacy of antiangiogenic therapy. This study was undertaken to investigate the changes of activated circulating endothelial cells （aCECs） and survivin after anti-angiogenesis therapy and their significance in predicting the efficacy of the therapy. Methods Patients of non-small cell lung cancer （NSCLC） treated with chemotherapy with or without Endostar were observed. The amount of activated CECs was detected by flow cytometry, and the expression of survivin mRNA was determined by real-time polymerase chain reaction （PCR）. Results After treatment, the amount of activated CECs decreased significantly in clinical benefit cases （P=0.021 in chemotherapy alone, P=0.001 in chemotherapy plus Endostar）, increased in disease progressive cases （P=0.015 in chemotherapy alone, but P=0.293 in chemotherapy with Endotatar）. After therapy, the expression of survivin mRNA decreased in clinical benefit cases （P=0.001） and increased in disease progressive cases （P=0.018）. A positive correlation was found between activated CECs and survivin in the chemotherapy group pre- and post-therapy （P=0.001 and 0.021, respectively）, but only in the chemotherapy with Endostar group pre-therapy （P=0.030） rather than post-therapy. A positive correlation was found between the decreased activated CECs after therapy and time to progression （TTP） （r=0.322, P=0.012）; a negative correlation was found between the amount of survivin mRNA in serum post-therapy and -l-I-P（r= -0.291, P=0.048）. Conclusions Activated CECs and survivin may be ideal markers forecasting efficacy and prognosis of NSCLC. The former can reflect more sensitively antiangiogenic efficacy and the latter is more sensitive to shrinkage or swelling of tumors. Their combination can evaluate more accurately the efficacy of antiangiogenic therapy of NSCLC.

Blood Serum Levels of IL-2, IL-6, IL-8, TNF-α and IL-1β in Patients on Maintenance Hemodialysis

Cytokines are essential mediators of immune response and inflammatory reactions. Patients with chronic renal failure （CRF） commonly present with abnormalities of immune function related with impaired kidney function and the accumulation of uremic toxins in addition to bioincompatibility of dialyzer membranes. During a hemodialysis （HD） session, cytokines are released mainly by monocytes activated by endotoxin-type compounds in dialyzer fluid, complement factors and direct contact with dialyzer membrane. The study included 15 CRF patients, aged 36.4 ± 2.9 years, on regular HD maintenance therapy for mean 68 ± 10 months and 15 healthy controls. It was designed to assess serum levels of a panel of inflammatory cytokines： IL-1β, IL-2, IL-6, IL-8 and TNF-α in CRF patients on regular maintenance HD before, 20, 60 and 240 minutes of a single HD session in parallel with C-reactive protein （CRP） as an additional parameter. CRP concentration was increased in HD patients when compared with healthy controls. The concentrations of IL-1, IL-6, IL-8 and TNF-α were increased, whereas the serum level of IL-2 was not altered during a single HD session.

Polymorphisms of dihydropyrimidine dehydrogenase gene and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population

Background Dihydropyrimidine dehydrogenase （DPD）, a key enzyme involved in the catabolism of 5-fluorouracil （5-FU）, is the attractive candidate for pharmacogenetic research on efficacies and toxicities of 5-FU. The aim of this study is to explore the association between polymorphisms of dihydropyrimidine dehydrogenase gene （DPYD） and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in the Chinese population.

Polymorphism of methylenetetrahydrofolate reductase gene is associated with response to fluorouracil-based chemotherapy in Chinese patients with gastric cancer

Background The importance of polymorphisms in the methylenetetrahydrofolate reductase （MTHFR） gene for the prediction of the response to fluorouracil-based adjuvant chemotherapy in gastric cancer patients remains unclear. The aim of this study is to assess the predictive value of several polymorphisms of the MTHFR gene for clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population. Methods Three hundred and sixty-two Chinese patients with gastric cancer were treated with fluorouracil-based adjuvant chemotherapy. DNA samples were isolated from peripheral blood collected before treatment. The three single nucleotide polymorphisms （SNPs） （rs1801131, rs1801133, rs2274976） genotypes of the MTHFR gene were determined by matrix- assisted laser desorption/ionization time-of-flight mass spectrometry （MALDI-TOF MS）. Results The average response rate for chemotherapy was 46.7%. Homozygous genotypes rs2274976G/G （X2=22.7, P 〈0.01） and rs1801131A/A （X2=14.3, P=0.008） were over-represented in responsive patients. Carriers of the rs2274976A allele genotypes （G/A and A/A） and of the rs1801131C allele genotypes （A/C and C/C）were prevalent in nonresponsive patients. In the haplotype association analysis, there was a significant difference in global haplotype distribution between the groups （X2=20.69, P=0.000 124）. Conclusions These results suggest that polymorphisms of the MTHFR gene may be used as predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in Chinese population. Well-designed, comprehensive, and prospective studies on determining these polymorphisms of MTHFR gene as clinical markers for predicting the response to fluorouracil-based therapy in gastric cancer patients is warranted.