Is chemotaxis a factor in the migration of precardiac mesoderm in the chick?

Summary The chick heart is formed from bilateral patches of presumptive cardiac mesoderm cells which migrate over the endoderm and fuse in the midline. We have tested the possibility that this migration is controlled, at least in part, by a chemotactic substance exuded by the anterior end of the endoderm. We have used chick/quail combinations to follow naturally marked cells during the course of their migration. Chimaeric embryos were formed by fusing together parts of chick and quail embryos of stage 5–6. Each embryo possessed two pairs of precardiac regions, the quail pair lying immediately anterior to that of the chick. These chimaeras were then explanted in embryo culture. In the event of chemotaxis, cells from the posterior end of the quail precardiac mesoderm might be expected to invade the chick area. Samples of explants and chimaeras were examined at intervals from 2 to 24 h, but in no case were cells found to have changed their direction of migration as a result of the proximity of anterior endoderm. It is concluded that this work does not provide evidence for a chemotactic attraction by the anterior end of the endoderm. Supported by the following grants: NIH HD 21048, HD 06819, and AHA 880696 (JWL); the British Heart Foundation, and Action Research (R.B.); and an SERC postgraduate studentship (HSE).     

Lateral Lymph Nodes in Rectal Cancer: Do we all Think the Same? A Review of Multidisciplinary Obstacles and Treatment Recommendations

Lateral lymph nodes in low, locally advanced, rectal cancer have proven implications for local recurrence rates, which increase drastically in the presence of persistently enlarged lateral lymph nodes. These clinical implications warrant a thorough understanding of lateral nodal disease with awareness and knowledge from all three specialties involved – radiology, radiation oncology, and surgery – to ensure proper treatment. Relevant literature for each specialty, including all current guidelines and perspectives, were examined. Variations in definitions and treatment paradigms were evaluated. There is still no consensus for the standardized treatment of lateral nodal disease. Each discipline works according to their own available evidence, but relevant data are scarce. Current international guidelines and standard recommendations for the diagnostics and treatment of lateral lymph nodes are lacking. This results in differing perspectives and interpretations between the disciplines which can lead to challenging communication in an area where multidisciplinary collaboration is essential. This review addresses this by presenting the current evidence, perspectives and practices of each specialty and makes suggestions for each phase of the diagnostic and treatment process for patients with lateral nodal disease. By doing this, steps are taken toward achieving international consensus, and multidisciplinary collaboration.     

宫颈癌动脉灌注化疗栓塞的临床应用

目的:应用超选择子宫动脉灌注化疗栓塞治疗宫颈癌并观察其疗效,并对介入治疗的药物选择、化疗的疗程及间隔及介入加手术的远期效果等方面进行探讨。方法:对24例经病理证实的宫颈癌患者,经双侧子宫动脉做局部灌注化疗,部分病例辅以明胶海绵栓塞双侧子宫动脉,治疗后定期复查。结果:介入治疗后临床症状缓解,15例肿块体积明显缩小,16例行根治手术。7例病情稳定,1例病情进展。结论:子宫动脉化疗栓塞是一种有效的治疗子宫颈癌辅助治疗方法。     

Influence of human papillomavirus and p16INK4a on treatment outcome of patients with anal cancer

BackgroundThe purpose of this study was to evaluate HPV-DNA and p16^INK4a (p16) expression as prognostic markers for outcome in patients with anal cancer.MethodsFrom January 2000 to December 2011 a cohort of 105 anal cancer patients was treated with definitive chemoradiation at our institution. Tumor biopsies from 90 patients were analyzed for HPV-DNA by polymerase chain reaction and for p16 expression by immunohistochemistry.ResultsMedian follow-up was 48.6 months (range 2.8–169.1 months). HPV-DNA or p16-expression was found in 75 anal cancers each (83.3%), concordance was detectable in 70 tumors (77.8%). Significantly improved overall survival (OS) [77.1% vs. 51.4%, p = 0.005], progression-free survival (PFS) [64.0% vs. 35.0%, p < 0.001] and improved local control [81.0% vs. 55.9%, p = 0.023] was found for concomitant HPV- and p16-positive anal carcinomas (cHPPAC) in univariate analysis. Multivariate analysis showed better OS [p = 0.015] and PFS [p = 0.002] for cHPPAC.ConclusionThe combination of HPV-DNA and p16 can be used as an independent prognostic parameter in anal cancer patients.     

Feasibility of preoperative and postoperative chemoradiotherapy in gastric adenocarcinoma. Two phase II studies done in parallel. Fédération Francophone de Cancérologie Digestive 0308

BackgroundFor resectable gastric cancer, both postoperative chemoradiotherapy and perioperative chemotherapy demonstrate high-level evidence for improved survival in Western populations. To evaluate the feasibility of pre- or postoperative chemoradiotherapy, we proposed two multicentre phase II studies.Patients and methodsPatients with localised, histologically confirmed gastric cancer and Eastern Cooperative Oncology Group (ECOG) performance status <2 judged suitable for curative resection were eligible. Eligible patients were assigned to either preoperative chemoradiotherapy followed by surgical resection or surgical resection followed by chemoradiotherapy depending on each centre. Chemoradiotherapy regimen included four courses of FOLFIRI (5 Fluorouracil, Leucovorin, Irinotecan) regimen then Concurrent fluorouracil at 200 mg/m²/d by continuous infusion 5 days each week. A dose of 50 Gy in 25 fractions in the preoperative study, or 45 Gy in 25 fractions in the postoperative study, was delivered. The primary end-point for both studies was the proportion of patients, who completed the therapeutic sequence.ResultsBetween September 2007 and January 2010, 63 patients were included in both studies. The postoperative study was stopped for futility at the first step. In the preoperative study, 31 patients (73.8%, confidence interval (CI) 95%: 65.8–90.1%) received complete therapeutic sequence. Serum albumin and dietary restriction evaluated by QLQ-STO22 (Quality of Life-Stomach module) score were significantly linked with chemoradiotherapy feasibility in univariate analysis with respectively Odds-ratio (OR) 1.16 [CI 95%: 1.01–1.33] and 0.17 [0.03–0.89], p = 0.04. Median overall survival time was 26.4 months in the preoperative study.ConclusionFeasibility of chemoradiotherapy was not achieved for these studies: 73.8% (CI 95%: 65.8–90.1) and 42.9% (CI 95%: 21.8–66%) in preoperative and postoperative settings respectively.     

Mandard Tumour Regression Grade,Perineural Invasion,Circumferential Resection Margin and Post-chemoradiation Nodal Status Strongly Predict Outcome in Locally Advanced Rectal Cancer Treated with Preoperative Chemoradiotherapy

AimsThe pathology of tumours after chemo/radiotherapy for locally advanced rectal cancer can be difficult to interpret. The ypTNM staging does not accurately predict outcomes. Therefore, we developed a new prognostic index for this purpose.Materials and methodsThe Nottingham Rectal Cancer Prognostic Index (NRPI) is based on a study of 158 patients with locally advanced rectal cancer treated with preoperative chemo/radiotherapy at Nottingham University Hospital between April 2001 and December 2008. Patients were treated with radiotherapy to a dose of 50 Gy in 25 fractions over 5 weeks with/without concurrent capecitabine chemotherapy. Surgery was carried out after an interval of 6–10 weeks. Factors found to be significant on univariate analysis to predict for disease-free (DFS) and overall survival were further explored in multivariate analysis. The significant factors (Mandard tumour regression grade, perineural invasion, circumferential resection margin status and nodal status) were weighted to establish a score for the index. The median follow-up was 40 months (range 3–90 months).ResultsOn survival analysis, four distinct prognostic groups were found: Score 0 = excellent prognosis, 1–3 = good prognosis, 4–8 = moderate prognosis, 9–14 = poor prognosis. The NRPI significantly predicted both DFS and overall survival (P < 0.0001). DFS at 5 years was 95, 63, 25 and 0% for the four groups. On multivariate analysis the NRPI was found to be the strongest predictor of DFS including nodal and circumferential resection margin status (P < 0.0001). It was a stronger predictor of overall survival than the American Joint Committee on Cancer/Dukes staging (P < 0.0001).ConclusionsThe NRPI allocates patients into distinct prognostic categories. This seems to be a much stronger predictive factor than the American Joint Committee on Cancer/Dukes staging. This requires further validation, but seems to be a useful clinical index for future studies.     

卵巢上皮癌淋巴结转移化疗的临床疗效分析

背景与目的：卵巢上皮癌属化疗中度敏感肿瘤,随着肿瘤细胞减灭术及铂类联合化疗的应用,其疗效有明显改善,但其淋巴结转移病灶对化疗的敏感性尚存异议。本研究通过回顾性分析临床资料,以评价卵巢上皮癌患者淋巴结转移对化疗的敏感性及其预后,方法：对1986年6月－2001年2月收治的50例卵巢上皮癌淋巴结转移患者进行回顾性分析,其中Ⅲ-Ⅳ期32例,治疗后复发18例,50例均有可评价疗交的淋巴结转移灶,其中38例有可评价的盆腔,腹腔肿瘤。46例接受术前化疗1－3疗程,肿瘤细胞减灭术、术后化疗。化疗疗效评价按实体瘤疗效评价标准。化疗包括术前、术后或复发患者的化疗,其中45例接受含铂类联合化疗,包括CP（环磷酰胺＋顺铂）,CAP（环磷酰胺＋顺铂＋阿霉素或表阿霉素）,TC（紫杉醇＋卡铂）,TP（紫杉醇＋顺铂）,吉西他滨＋卡铂及IEP（顺铂＋异环磷酰胺＋足叶乙甙）方案,1例用美法仑,1例用CF（环磷酰胺和5－氟尿嘧啶）方案,3例用IFO＋VP－16（异环磷酰胺＋足叶乙甙）,结果：全组淋巴结转移灶和肿瘤的有效率分别为68．0％、71．1％,Ⅲ-Ⅳ期初治患者淋巴结转移和盆腹腔肿瘤有效率分别为78．1％,76．6％,而复发组两者有效率均为50．0％,结论：卵巢上皮癌的淋巴结转移,无论Ⅲ-Ⅳ期还是复发患者,其对化疗敏感性与盆腹腔肿瘤相近,Ⅲ-Ⅳ期患者预后与减瘤术是否彻底,以及化疗的疗程数多少有明显的相关性。     

Clinical radiation nephropathy

An analysis of the normal tissue effects of irradiation of the kidney is presented. Various clinical syndromes resulting from treatment are described as well as the potential cellular basis for these findings. Effects of concurrent and/or sequential treatment with irradiation and various chemotherapeutic agents are discussed and the impact of these agents on toxicity presented. Adverse consequences of renal treatment in the child is described and possible radiation effects on so-called compensatory hypertrophy following nephrectomy presented. Renal consequences described to date of bone marrow transplantation programs utilizing irradiation are also presented. The necessity of a dose-volume histogram analysis approach to analyzing renal toxic effects in patients followed for long (> 10 year) periods is essential in developing accurate guidelines of renal tolerance.     

宫颈癌动脉灌注化疗栓塞的临床应用

目的：应用超选择子宫动脉灌注化疗栓塞治疗宫颈癌并观察其疗效，并对介入治疗的药物选择、化疗的疗程及间隔及介入加手术的远期效果等方面进行探讨。方法：对24例经病理证实的宫颈癌患者，经双侧子宫动脉做局部灌注化疗，部分病例辅以明胶海绵栓塞双侧子宫动脉，治疗后定期复查。结果：介入治疗后临床症状缓解，15例肿块体积明显缩小，16例行根治手术。7例病情稳定，1例病情进展。结论：子宫动脉化疗栓塞是一种有效的治疗子宫颈癌辅助治疗方法。