Equivocal test results and prognostic staging uncertainties in the evaluation of patients with cancer of the prostate

In the staging of cancer, equivocal test results may occur in subjectively evaluated imaging procedures whose interpretations raise the possibility of metastases but are too uncertain to rule in or rule out metastatic spread, and in tests whose repetitions in the same patient yield conflicting results about dissemination. We assessed the frequency and prognostic correlates of test results giving equivocal evidence of disseminated (Stage IV) disease in an inception cohort of 280 patients receiving initial treatment for prostatic cancer between 1973-76. Among tests used for clinical staging, lymphangiograms (equivocal in 28 percent of tested patients), bone scans (equivocal in 25 percent of tested patients), and bone radiographs (equivocal in 20 percent of tested patients) most frequently yielded interpretations that equivocally suggested metastatic spread. Eighty-three (45 percent) of the 185 patients without clear-cut dissemination (Stages I-III) had at least one equivocal test result that suggested dissemination and that remained unresolved at the time of selection of therapy. Five-year survival (30 percent) for the 20 patients with local extracapsular spread (Stage III) and multiple equivocal results suggesting dissemination was identical to that for patients with clear-cut dissemination. In contrast, other patients with equivocal dissemination in Stages I-III had survival rates similar to those patients in the same stage and lacking equivocal dissemination. Unresolved equivocal staging results frequently complicate management decisions for patients with prostatic cancer. Survival analyses aid these decisions by demonstrating that equivocal findings of dissemination are prognostically unimportant unless they are multiple and occur in the context of unequivocal extracapsular spread.     

Five-year survival of women with breast cancer in northern Alberta.

Five-year survival rates for all 519 women with breast carcinoma in northern Alberta in 1971 and 1972 were analysed with the use of data from the computerized northern Alberta breast registry and the Alberta cancer registry. The relative 5-year survival was 73%, which is higher than most rates reported from other centres. Lymph node involvement was significant as a prognostic factor, with the relative 5-year survival falling from 92% in the group without lymph node involvement to 58% in the group with three or more involved nodes. The prognosis was also significantly affected by the stage of the disease according to the 1973 TNM classification: the 5-year survival rates ranged from 88% for patients with stage 1 disease to 17% for those with stage IV disease. Women 40 to 59 years of age had a higher survival rate (79%) than those under 40 years (65%) or over 60 years (66%) of age. Analyses by 5-year age groups showed that women 35 to 39 years old had a particularly poor survival rate (59%). Postmenopausal women less than 55 years old had a higher survival rate than did perimenopausal or premenopausal women in the same age group. Further follow-up is indicated to correlate possible high-risk factors with survival.     

Breast cancer in northern Alberta: pilot study in computerized registration.

Analysis of data from 643 breast cancer patients seen between 1971 and 1973 in northern Alberta was undertaken as a preliminary study leading towards a comprehensive breast registry. Age at first treatment and menopausal status were found to be related significantly to the clinical stage of the disease. Other data reported included age at menarche, lymph node involvement and methods of primary treatment. A decline in use of the radical mastectomy was noted. The comprehensive breast registry, which will be used to identify high-risk groups, assess treatment modalities, test hypotheses and generate ideas, has a high probability of success because of compulsory registration of new cases of breast cancer in Alberta and collection of data by the same four individuals.     

A Lymph Node Staging System for Gastric Cancer: A Hybrid Type Based on Topographic and Numeric Systems

Although changing a lymph node staging system from an anatomically based system to a numerically based system in gastric cancer offers better prognostic performance, several problems can arise: it does not offer information on the anatomical extent of disease and cannot represent the extent of lymph node dissection. The purpose of this study was to discover an alternative lymph node staging system for gastric cancer. Data from 6025 patients who underwent gastrectomy for primary gastric cancer between January 2000 and December 2010 were reviewed. The lymph node groups were reclassified into lesser-curvature, greater-curvature, and extra-perigastric groups. Presence of any metastatic lymph node in one group was considered positive. Lymph node groups were further stratified into four (new N0–new N3) according to the number of positive lymph node groups. Survival outcomes with this new N staging were compared with those of the current TNM system. For validation, two centers in Japan (large center, n = 3443; medium center, n = 560) were invited. Even among the same pN stages, the more advanced new N stage showed worse prognosis, indicating that the anatomical extent of metastatic lymph nodes is important. The prognostic performance of the new staging system was as good as that of the current TNM system for overall advanced gastric cancer as well as lymph node—positive gastric cancer (Harrell C-index was 0.799, 0.726, and 0.703 in current TNM and 0.799, 0.727, and 0.703 in new TNM stage). Validation sets supported these outcomes. The new N staging system demonstrated prognostic performance equal to that of the current TNM system and could thus be used as an alternative.     

CT及MRI在直肠癌诊断和分期的应用价值研究

目的:探究在直肠癌的诊断以及分期方面,CT与MRI技术的应用价值。方法:选取我院近年来经过病理检测,确诊为直肠癌的患者160例,随机分为两个实验组,其中一组采取CT成像方法,另一组患者采取MRI成像。并记录在不同的分期中CT及MRI的应用价值。CT诊断包含了常规CT平扫以及CT增强扫描,MRI诊断包括轴位DWI、T2W1冠状位以及矢状位、轴位T1WI、轴位T2WI的图像。结果:在直肠癌的诊断中,CT诊断的T分期与病理性T分期差异不大,其准确率为70.0%。MRI诊断的T分期和病理性T分期差异极小,其准确率为85.0%。CT诊断的N分期与病理性N分期差异不大,准确率为72.5%;MRI诊断的N分期与病理性N分期差异较小,其准确率为87.5%。CT诊断的T分期以及N分期的准确率与MRI诊断的T分期以及N分期的准确率之间差异均存在统计学意义(P0.05)。结论:在直肠癌的术前诊断以及局部分期中,MRI诊断与CT诊断相比,有更高的诊断价值。     

Preoperative plasma soluble urokinase plasminogen activator receptor as a prognostic marker in rectal cancer patients. An EORTC-Receptor and Biomarker Group collaboration

BACKGROUND AND AIMS: Since approximately 30% of patients with Dukes' stage B colorectal cancer will experience disease recurrence within five years of primary treatment, current staging of patients with early colorectal cancer apparently fails to adequately predict patient outcome. It has previously been shown that the preoperative plasma concentration of soluble urokinase plasminogen activator receptor (suPAR) is associated with the survival of patients with early colorectal cancer. In this study we sought to confirm the independent prognostic value of suPAR in rectal cancer. METHODS: suPAR was retrospectively determined by two different versions of a suPAR ELISA in preoperatively collected plasma samples from a Swedish (n = 354) and a Danish (n = 255) cohort of rectal cancer patients. RESULTS: In both cohorts the suPAR concentration was significantly higher in Dukes' stage D patients than in Dukes' stage A-C patients (p < 0.0001). Among Dukes' stage A-C patients, no differences in median suPAR values were seen. In univariate analysis, continuous suPAR was found to be associated with survival (p < 0.0001 in both cohorts). Of particular interest was that similar results were obtained for Dukes' stage A and B patients when analyzed separately. In multivariate analysis, continuous suPAR was found in both cohorts to be independent of Dukes' stage. CONCLUSIONS: This study confirms that the preoperative concentration of plasma suPAR contains independent prognostic information on patients with rectal cancer. This result was independent of the two different versions of an in-house suPAR ELISA used to perform the analyses. The next step in the evaluation of suPAR as a prognostic parameter in rectal cancer will be to launch an appropriately dimensioned prospective study where the benefit of applying preoperative plasma suPAR measurement to clinical decision-making regarding adjuvant therapy is assessed.     

Sialic acid and carcinoembryonic antigen (CEA) as markers of colon cancer: Preliminary report]

Tumor markers known to date are not sensitive and specific enough to detect malignant tumors. Therefore, attempts to find new markers have led to sialic acid assays in cancer patients. Serum sialic acid, CEA and ESR have been determined in 33 patients with the cancer of the colon. All patients have been divided into four groups, according to TNM cancer staging. Serum sialic acid levels have been increased by 100% of patients in groups I and IV. The most significant correlation was noted between sialic acid levels and ESR. No significant relationship between serum sialic acid and CEA have been noted. No correlation of the colon cancer stage, according to TNM staging, and sialic acid and CEA levels in the peripheral blood has been observed. It seems, however, that serum sialic acid assay may be useful auxiliary technique in the detection and monitoring of patients with colon cancer.     

Field focusing n.m.r. (FONAR) and the formation of chemical images in man

The first proposals for n.m.r. scanning in medical diagnosis was made by Damadian (1971a; 1972) and were followed by Lauterbur (1973). Damadian's method of scanning used the principle that the forced precessions of a nuclear magnetization under radio frequency (r.f.) driving field specify the conditions for obtaining spatial resolution of the signal producing domains of a nuclear resonance sample. Sufficient coupling of the nuclear spins to the radiation field to produce a signal detectable by r.f. spectroscopy requires that the stringent Bohr frequency condition, hv = microH0/I, be met. It became possible to construct, with the aid of direct current auxiliary coils, a small volume, called the resonance aperture, inside the applied static field of the magnetic resonance experiment. The correct value of H0 for the applied frequency is restricted to this aperture. The technique (Damadian 1972) was developed to provide a method for non-surgically detecting chemical abnormalities in the diseased organs of patients (Damadian 1971a). The first n.m.r. scans of normal patients and of those with malignant disease are discussed.     

Prognostic value of non-MHC-restricted killer cell activity in lung cancer

The prognostic value of peripheral blood non-MHC-restricted cytotoxicity against the myeloid leukaemic line K562 in lung cancer patients was studied. At the time of diagnosis and before operation, 57 patients with lung cancer were tested for cytotoxicity and subsequently followed for up to 4 years. In addition, 145 lung cancer patients, 30 patients with non-neoplastic lung diseases and 76 healthy donors were tested for cytotoxicity without the follow-up, in order to correlate the stage of lung cancer and the growth rate of tumours to the level of non-MHC-restricted cytotoxicity. On average, lung cancer patients had similar non-MHC-restricted cytotoxicity to the controls. However, patients with stage II–IV diseases showed an impaired activity, stages III and IV differing significantly from the controls. This result shows that the decline in natural killer (NK) activity is associated with tumour burden. Patients with slowly growing neoplasms had stronger cytotoxic activity than patients with fast or moderately progressing disease. In the follow-up study, the whole material of 57 patients showed only a slight correlation between cytotoxicity and survival: 42% of the patients with strong activity survived for more than 2.5 years, whereas 6% of the patients with weak activity did so. In stage I patients there was no correlation between cytotoxicity and survival, nor was there a correlation in patients with stages II–IV of the disease. Hence, in our group of patients the determination of cytotoxicity preoperatively yielded no prognostic information beyound that already available from staging. However, those stage II–IV patients that survived for 1 year or more after the diagnosis and cytotoxicity tests, showed a significant correlation between cytotoxicity and survival.     

The role of endoscopic ultrasound in the evaluation of rectal cancer

Accurate staging of rectal cancer is essential for selecting patients who can undergo sphincter-preserving surgery. It may also identify patients who could benefit from neoadjuvant therapy. Clinical staging is usually accomplished using a combination of physical examination, CT scanning, MRI and endoscopic ultrasound (EUS). Transrectal EUS is increasingly being used for locoregional staging of rectal cancer. The accuracy of EUS for the T staging of rectal carcinoma ranges from 80-95% compared with CT (65-75%) and MR imaging (75-85%). In comparison to CT, EUS can potentially upstage patients, making them eligible for neoadjuvant treatment. The accuracy to determine metastatic nodal involvement by EUS is approximately 70-75% compared with CT (55-65%) and MR imaging (60-70%). EUS guided FNA may be beneficial in patients who appear to have early T stage disease and suspicious peri-iliac lymphadenopathy to exclude metastatic disease.     

Genetic regulation of antibody heterogeneity: Its possible significance in human allergy

Conclusion Finally, in a broader context, part of the fascination of this subject is its relevance to the questions of how responses in the different Ig classes and subclasses are orchestrated, and why such a diversity of Ig classes exists at all. These questions are of great theoretical interest in themselves, and are also highly relevant to those immunological diseases that are characterized by production of auto-or isoantibodies of very restricted subclass (e.g., Karpatkinet al. 1973, Morellet al. 1973) or clonality (e.g., Goldberg and Fudenberg 1971, Harboe 1971, Kunkelet al. 1973). They are also questions that the IgE system—since it is so sophisticated and well-Defined—highlights in a particularly telling way.     

Failure to detect intra-abdominal metastases from breast cancer: a case for staging laparotomy

Two studies were performed to assess the accuracy of non-invasive methods in detecting intra-abdominal metastases from breast cancer. Firstly, the sites of spread detected at the time of first presentation with metastases were compared with the sites of spread shown at necropsy in the same patients. Although about two-thirds of the patients with bone and lung metastases at necropsy had had metastases detected at these sites when they first presented with metastases, only a third of the patients with liver metastases and none of those with other intra-abdominal metastases had had evidence of disease at first presentation with metastases. The second study confirmed a poor detection rate of liver and other intra-abdominal metastases in patients with breast cancer undergoing laparotomy and oophorectomy who were staged immediately before operation.Pre-mastectomy staging laparotomy should be considered in those patients with primary breast cancer who are most likely to have disseminated disease beyond the regional nodes. In the presence of occult gross metastases detected by staging laparotomy, mastectomy will not provide additional protection against loca recurrence of disease. Patients with occult gross metastases should also be excluded from studies on adjuvant chemotherapy (designed to treat micrometastases). Aggressive methods of staging are justified to protect the patient as far as possible against unnecessary mastectomy and to identify those patients who should be treated by therapeutic chemotherapy rather than adjuvant chemotherapy.     

A Patient-Centered Methodology That Improves the Accuracy of Prognostic Predictions in Cancer

Individualized approaches to prognosis are crucial to effective management of cancer patients. We developed a methodology to assign individualized 5-year disease-specific death probabilities to 1,222 patients with melanoma and to 1,225 patients with breast cancer. For each cancer, three risk subgroups were identified by stratifying patients according to initial stage, and prediction probabilities were generated based on the factors most closely related to 5-year disease-specific death. Separate subgroup probabilities were merged to form a single composite index, and its predictive efficacy was assessed by several measures, including the area (AUC) under its receiver operating characteristic (ROC) curve. The patient-centered methodology achieved an AUC of 0.867 in the prediction of 5-year disease-specific death, compared with 0.787 using the AJCC staging classification alone. When applied to breast cancer patients, it achieved an AUC of 0.907, compared with 0.802 using the AJCC staging classification alone. A prognostic algorithm produced from a randomly selected training subsample of 800 melanoma patients preserved 92.5% of its prognostic efficacy (as measured by AUC) when the same algorithm was applied to a validation subsample containing the remaining patients. Finally, the tailored prognostic approach enhanced the identification of high-risk candidates for adjuvant therapy in melanoma. These results describe a novel patient-centered prognostic methodology with improved predictive efficacy when compared with AJCC stage alone in two distinct malignancies drawn from two separate populations.     

Quality of life and disease-specific functional status following microvascular reconstruction for advanced (T3 and T4) oropharyngeal cancers

In an effort to evaluate quality-of-life benefits of ablative head and neck cancer surgery and microvascular reconstruction, a longitudinal study was undertaken in which patients with T3 or T4 oropharyngeal cancers without systemic metastases at presentation were administered both general and disease-specific quality-of-life instruments preoperatively and postoperatively. In an initial prospective pilot study, 17 cancer patients were evaluated both preoperatively and postoperatively using the Medical Outcomes Short-Form Health Survey questionnaire (SF-36) and the Performance Status Scale for Head and Neck Cancer Patients. In the second part of the study, the need was recognized for a different disease-specific measure, for more frequent intervals of longitudinal follow-up (rather than be limited by a single data collection point), and for a noncancer control group. Since then, 17 more cancer patients were evaluated in the second part of the study and were compared with patients who had similar reconstructions after suffering head and neck trauma and also with age-matched controls. Instead of the performance status scale, the University of Washington Head and Neck Quality of Life questionnaire was substituted. Interval assessments were done at 1, 3, 6, and 12 months and preoperatively. Whereas many of the general and disease-specific quality of life subclasses initially worsened following extensive surgery and radiation therapy, most returned to the preoperative baseline by 6 months following conclusion of treatment and surpassed pretreatment values at 1 year. It can be concluded, based on this study, that large resections and reconstructions for head and neck cancer patients are justified in terms of outcome; the resection controls the local disease, and the microvascular reconstruction restores quality of life and functional status.     

To Shigella sonnei phage typing.

The epidemiological significance of phage types changes in the course of years. In Czechoslovakia, in the years 1967-1971, the most frequent phage types were 2,6, 3, 30 and 65, and, in the Middle-Bohemian Region, 2,30, 6, 3 and 65. In the epidemiological years 1972-1973 the sequence of the most frequent S. sonnet phage types changed in the Middle-Bohemian region to: 65, 23, 6, 2 and 12. Some problems concerning the instability of phage types and the part of further auxiliary tests (biochemical differentiation according to Bojlen and drug sensitivity pattern) are discussed.     

Enzymes that hydrolyze adenine nucleotides in platelets from breast cancer patients

The activities of NTPDase (EC 3.6.1.5, apyrase, CD39) and 5'-nucleotidase (EC 3.1.3.5, CD73) enzymes were analyzed in platelets from breast cancer patients. Initially, patients were compared in terms of length (years) of tamoxifen use. The following groups were studied: breast cancer patients who did not use tamoxifen, patients using tamoxifen for 1-48 months, patients using tamoxifen for 49-84 months, and controls (healthy subjects). Results demonstrated that adenosine triphosphate (ATP) hydrolysis was enhanced (F(3,114)=8.53; P<0.001) and adenosine diphosphate (ADP) hydrolysis was reduced (F(3,106)=5.09, P=0.002) as a function of tamoxifen use, while adenosine monophosphate (AMP) hydrolysis was unchanged. Next, patients were compared statistically according to disease stage, determined by the tumor-node-metastasis (TNM) staging system for classifying breast tumor. ATP hydrolysis was significantly elevated in patients with stage I and II breast cancer (F(4,113)=4.35; P=0.003), but was normal in patients with stage III and IV cancer. ADP hydrolysis was reduced in stages II to IV (F(4,105)=3.88, P=0.006) and AMP hydrolysis was elevated in stage II (F(4,105)=3.45 P=0.01), but was normal in stages III and IV. Platelet aggregation time was similar in all patients regardless of tamoxifen use or disease stage. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were also within the normal range and similar among all groups. Similarly, fibrinogen and fibrin degradation product (FDP) were unchanged in all groups. In conclusion, our study demonstrated for the first time that hydrolysis of adenine nucleotides is modified in platelets from breast cancer patients taking tamoxifen.     

基于医疗数据信息集成系统的3D打印技术在肺癌手术中的应用

目的:探讨基于医疗数据信息集成系统的3D打印技术在治疗肺癌中的应用。方法:2014年10月~2015年10月收治的符合肺癌临床路径,进入医疗数据信息集成系统,并接受320排螺旋CT扫描三维重建,3D打印出实体1:1大小的患侧肺血管及肺病灶模型,术前制定手术方案且模拟手术过程的42例非小细胞肺癌(NSCLC)患者,经电视胸腔镜应用内镜缝合切割器切除病灶,术中快速冰冻切片明确诊断,行肺段切除术,肺叶切除术。观察术中肺血管与3D打印符合程度。记录手术时间、术中出血量、切除淋巴结数量、有无术中死亡、病理结果、并发症、引流时间和引流量及术后生存情况。结果:术中证实95%以上的肺血管可被3D打印出来。手术时间(51.4±18.1)min,术中出血量(40.2±20.3)mL。切除淋巴结(7.1±2.8)枚。无术中死亡。术后病理回报示肺鳞癌13例,肺腺癌29例。病理分期:T1aN0M0 12例,T1aN1M0 10例,T1bN0M0 3例,T1bN1M0 3例,T2aN0M0 2例,T2aN1M0 12例。术后患者无严重并发症,其中肺感染6例、肺膨胀不全6例、房颤5例,所有患者经积极后痊愈;术后引流时间(3.0±1.2)d,引流量(200.7±66.1)mL/d。42例随访2~12个月,中位随访时间8.0月,40例无瘤生存,术后6个月发生转移脑转移2例,分别于术后7和10个月死亡。结论:基于医疗数据信息集成系统的3D打印技术可以应用于肺癌手术。     

Estudio de cohorte retrospectivo de pacientes diagnosticados de cáncer de tiroides del área suroeste de Madrid. Factores pronósticos en el cáncer diferenciado de tiroides

ObjectivesTo analyze the clinical and histopathological features of patients with thyroid cancer in the southwest Madrid area and to identify poor prognostic factors in the subgroup with differentiated thyroid carcinoma (DTC) of the follicular epitelium.Patients and methodsA retrospective cohort study of patients diagnosed with thyroid cancer at our hospital from 1998 to 2009. Significant clinical, surgical, and histopathological variables were included in Cox proportional hazard and logistic regression models to identify baseline factors predicting for death, recurrence, and persistent disease in DTC.ResultsA total of 150 patients with a median age of 49 years and a median follow-up of 5.4 years were enrolled. Histological subtypes were: papillary carcinoma (86%), follicular carcinoma (6.6%), medullary carcinoma (4%), poorly differentiated carcinoma (2.7%), and anaplastic carcinoma (0.7%). At the end of the study, 68% of patients were cured, 3.3% had died (disease-specific mortality, 1.3%), 1.3% were lost to follow-up, 6.7% had persistent biochemical disease, and 2.7% persistent clinical disease, while 18% of patients were pending assessment. The best prognostic model for DTC recurrence was TNM staging (stage II-IV vs. I: HR 5.9, 95% CI 1.3-26.6), while the best model for persistent disease or death was ETA clinical staging (high risk vs. low or very low risk: OR 9.2, 95% CI 2.6-33.2).ConclusionsIn our study, disease-specific mortality and persistent clinical disease were low. Classification of DTC patients based on ETA staging after initial treatment was a good predictor of persistent disease or death.