The prognostic role of progesterone receptor status and age in relation to axillary node status in breast cancer patients

The prognostic role of axillary lymph node status, progesterone receptor (PgR) status, age of the patient at operation, oestrogen receptor (ER) status and tumour diameter was studied in 443 breast cancer patients treated by modified radical mastectomy. Logistic and proportional hazard regression analyses were used to estimate the prognosis from the time of operation up to 60 months. We also estimated the prognosis from 36 to 60 months for those who had survived 36 months (conditional analysis).PgR and age gave significant information in each node class, old age and PgR negativity being disadvantages. PgR status relative to node status was more important for estimating early (24 months) prognosis, while age was of more importance later (60 months).Node status and age were the only variables giving significant information in the conditional analyses. It is thus of importance to consider the time dependency of the prognostic variables when predicting survival in breast cancer patients. No effect was found for ER status or tumour diameter.     

Prognostic relevance of urokinase plasminogen activator detection in micrometastatic cells in the bone marrow of patients with primary breast cancer.

Patients with an elevated level of urokinase plasminogen activator (uPA) in breast cancer tissue have an adverse prognosis. This study evaluated the prognostic relevance of uPA detection in disseminated tumour cells in bone marrow. Bone marrow was sampled intraoperatively from both iliac crests in 280 patients with primary breast cancer. Interphase cells were enhanced and stained immunocytologically with two antibodies: 2E11, which detects TAG 12--a tumour-associated glycoprotein typically expressed by almost all breast cancer cells--and the anti-uPA antibody HD-UK9. Thirty-five of the 2E11-positive women (n = 132, 47%) developed metastatic disease (median follow-up time 44 months). Of these, most were uPA positive (n = 23, 65%) and only 12 were uPA negative. Patients with uPA-positive cells in bone marrow (n = 98, 35%) had a significantly shorter metastasis-free interval (36 months) than women who were uPA negative (44.5 months). The worst prognosis was seen in patients positive for both markers (29.5 months), followed by those who were uPA negative and 2E11 positive (37 months). The detection of uPA on disseminated tumour cells characterizes a subgroup of patients with an even worse prognosis, who should undergo more aggressive adjuvant systemic therapy. For the first time, it was possible to evaluate an important qualitative parameter involved in the process of breast cancer metastases.     

Size of breast carcinomas at operation related to tumour growth rate

The mean nuclear area (MNA) of breast carcinoma cells, previously shown to be related to prognosis, is here presented as a potential overall measure of tumour growth rate prior to operation. Recording of tumour diameter and MNA in 340 infiltrating breast carcinomas demonstrated that tumours of low MNA tended to present at a lower diameter that those of high MNA. The former have thus remained small over a longer period, giving the woman more time to report them at this stage. It is suggested that mass screening from breast carcinoma may pick up these slow growing tumours, missing those of high growth rate unless the screening interval is correspondingly short.     

MYCN gene amplification is a powerful prognostic factor even in infantile neuroblastoma detected by mass screening

MYCN is the most powerful prognostic factor in cases of older children. However, how MYCN is related to the prognosis of infantile cases is not clear. A mass screening program was carried out by measuring urinary catecholamine metabolites (VMA and HVA) from 6-month-old infants. Of 2084 cases detected by the screening program, MYCN amplification (MNA) was examined by Southern blot analyses in 1533 cases from 1987 to 2000. Of the 1533 cases examined, 1500 (97.8%) showed no MNA, 20 cases (1.3%) showed MNA from three to nine copies, and 13 (0.8%) cases showed more than 10 copies. The 4-year overall survival rates of these three groups (99, 89 and 53%, respectively) were significantly different (P<0.001), indicating that MYCN copy number correlates with the prognosis. Cases with MNA more than 10 copies were more advanced than those without amplification (stage III, IV vs I, II, IVs; P<0.001). Patients with MNA more than 10 copies had significantly higher serum levels of neuron-specific-enolase (NSE) and ferritin than non-amplified patients (P=0.049, P=0.025, respectively). MYCN amplification was strongly correlated with a poor prognosis in infantile neuroblastoma cases. Therefore, for the selection of appropriate treatment, an accurate determination of MNA is indispensable.     

Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma

BACKGROUND: Recent studies have shown that the prognosis of recurrent hepatocellular carcinoma (HCC) after resection was dependent on the time of recurrence. The current study investigated whether early and late intrahepatic recurrences were associated with different risk factors and prognostic factors. METHODS: After curative resection of HCC, 246 patients were followed prospectively for recurrence. Intrahepatic recurrences were classified into early ( 1 year) recurrences. Risk factors for recurrence and prognostic factors for survival after recurrence in each group were analyzed. RESULTS: Early and late intrahepatic recurrences developed in 80 patients and 46 patients, respectively. By multivariate analysis, preoperative tumor rupture (P = 0.022) and venous invasion (P < 0.001) were independent risk factors for early recurrence, whereas cirrhosis (P = 0.018) was the only significant risk factor for late recurrence. By comparing histologic features of resected recurrent and primary tumors, 8 of 9 resected early recurrent tumors (89%) were classified as intrahepatic metastases, whereas all 6 resected late recurrent tumors (100%) were multicentric occurrences. Despite similar treatments, the prognosis for patients with early recurrence was worse than that of patients with late recurrence (median survival of 15.8 months vs. 29.6 months; P = 0.005). Independent prognostic factors for early recurrence were serum albumin level and initial tumor pTNM classification, whereas only serum bilirubin level was found to be an independent prognostic factor for late recurrence. CONCLUSIONS: Early and late intrahepatic recurrences after resection of HCC were associated with different risk factors and prognostic factors. Early recurrences appear to arise mainly from intrahepatic metastases, whereas late recurrences are more likely to be multicentric in origin. The current study suggests that different strategies may be needed for the prevention and management of early and late recurrences. Further studies based on genetic analysis of clonal origins of tumors are required to clarify fully the mechanism of early and late recurrences after resection of HCC.     

Mean nuclear area and histological grade of axillary-node tumour in breast cancer, related to prognosis

In a series of 112 cases of breast carcinoma with metastases to the axillary nodes, the mean nuclear area (MNA) in the nodal tumour showed a relationship to survival time that was similar to that given by histological grading. Combination of the 2 measurements increases the possible use of the heterogeneity of the material, leading to a more individualized prognosis.     

Radiotherapy for carcinoma of the posterior pharyngeal wall

Posterior pharyngeal carcinoma has an extremely poor prognosis regardless of the method of treatment. The purpose of this study was to assess the local control and survival in patients with carcinoma of the posterior pharyngeal wall treated with definitive radiotherapy and to determine prognostic factors which may be relevant to the current UICC staging classification. Between January 1991 and December 1995, 22 patients with a mean age of 60 years (range 44-82) received definitive radiotherapy, using a homogeneous technique, for carcinoma of the posterior pharyngeal wall. The median follow-up was 42 months (range 25-66). The overall 3-year survival and local control for the whole group was 50% and 73% respectively. Patients with early stage (T1 and T2) disease had a significantly better overall 3-year survival rate of 77% compared to 11% for patients with advanced stage (T3 and T4) disease (p=0.0010). Similarly, patients with early stage disease had a significantly improved 3-year local control rate compared to patients with more advanced stage disease (92% and 44% respectively, p=0.0080). Patients with node positive disease had an inferior survival rate of 29% compared to 60% for those with node negative disease though the difference did not reach statistical significance. In addition only one patient with initial node negative disease had isolated nodal relapse. There was no significant late morbidity. For patients with early stage disease we have obtained local control and survival rates comparable to other groups with a once daily, short fractionation radiotherapy scheme but with reduced morbidity. In late stage disease altered fractionation schemes should be considered in order to achieve better local control and survival. Isolated nodal relapse was not a significant problem in this cohort of patients. Outcome correlates with primary tumour size and this is reflected in the current UICC staging classification.     

Late relapse of testicular cancer presenting as differentiated teratoma - report of a case and discussion of the clinical implications

This report describes the unusual case of a patient with late relapse of testicular cancer, histologically defined as differentiated teratoma occurring 76 months after primary therapy for metastatic non-seminomatous germ cell cancer. During initial treatment the patient received 4 cycles of cisplatin-based chemotherapy followed by secondary resection of residual retroperitoneal and pulmonary metastases which had histologically revealed necrotic tissue. The patient had been without evidence of disease during the follow-up until May 1994 when a cystic mass was noted in the left fossa obturatoria. There was no concomitant elevation of serum tumour markers, while alpha-fetoprotein (AFP) could be detected in fluid gained by fine-needle aspiration from inside the cystic structure. Histological resection showed a differentiated teratoma. Late relapses defined as tumour recurrences later than 24 months after primary chemotherapy for metastatic testicular cancer are rather rare and affect only 2-5% of patients. However, the prognosis of patients with late relapse is poor with only 20-30% of patients achieving a second remission after chemotherapy +/- surgery. Patients presenting with only differentiated teratoma at late relapse and in whom the tumour can be completely surgically resected have the best prognosis among the subgroup of patients with late relapses with a long-term survival in approximately 50% of patients. The incidence and clinical implications of late relapses after chemotherapy for testicular cancer are discussed in the current report.     

Nutritional assessment in overweight and obese patients with metastatic cancer: does it make sense?

BackgroundObesity is causally related with tumor development, and thus, many cancer patients are overweight or obese at diagnosis. Whether these patients need regular nutritional assessment is not known. In the present study, we evaluated the utility of Mini Nutritional Assessment (MNA), a nutritional screening/assessment questionnaire, in overweight or obese patients with metastatic tumors.Patients and methodsOverweight or obese patients referred for initiation of systemic therapy in three cancer centers were eligible. Basic demographics and clinical data were recorded. MNA was completed at baseline and patients were divided into three groups: A (well nourished), B (at risk), and C (malnourished). Survival data were subsequently collected. The prevalence of malnutrition and prognostic significance were evaluated.ResultsIn total, 1469 patients with metastatic primaries were identified. Of them, 594 (41.9%) were overweight or obese and included in the analysis. According to MNA, almost 50% were at risk and around 12% were already malnourished at presentation. A significant difference in overall survival was found between groups [group A 17.8 (15.5–20.1) months, group B 8.2 (7.3–9.3) months, and group C 6.4 (3.2–9.6) months, P < 0.001]. Moreover, MNA was the only independent predictor of survival.ConclusionsOur findings support that a significant percentage of overweight or obese cancer patients may be at nutritional risk and this is moreover related with adverse prognosis. An MNA score could be used for the identification of this risk.     

Flow cytofluorometric evidence for the differential radioresponsiveness of aneuploid and diploid cervix tumours

We are presently involved in a prospective study of the relationship between DNA content profiles, and their changes during treatment, determined by flow cytofluorometry, and patient prognosis and response to therapy for cancer of the uterine cervix. To date, 348 patients have been included in the study over a 54-month period. Data on these patients have shown that DNA aneuploid tumours are significantly more radioresponsive than diploid cervix tumours. Analysis of the data on 213 patients with a minimum follow-up time of 15 months has, however, failed to show an overall more favourable prognosis conferred by tumour DNA aneuploidy. Analysis of the relationship between clinical stage and disease state and tumour DNA ploidy, however, suggests that aneuploid tumours metastasize to distant sites at an earlier stage of the disease than diploid tumours and local recurrence rates for diploid tumours, in late stage disease, are double those for aneuploid tumours. Improved staining procedures, and instrument modification, has also shown that cervix tumour heterogeneity is of considerably greater frequency than at first appeared to be the case (approximately 75% of DNA aneuploid tumours show heterogeneity.     

The detection of oesophageal adenocarcinoma by serum microsatellite analysis.

BACKGROUND AND AIMS: Organ-confined oesophageal cancer in an early stage can be cured in many patients, whereas more extensive lesions have a poor prognosis. We sought to develop a non-invasive test for cancer detection and evaluation of the prognosis of the patients by using a novel molecular approach. MATERIAL AND METHODS: Matched normal-, tumour- and serum-samples were obtained from 32 patients with adenocarcinoma of the oesophagus. DNA was extracted and the samples were subjected to microsatellite analysis using 12 markers. Serum and normal samples from 10 healthy individuals served as controls. RESULTS: Twenty-seven of the 32 patients (84.4%) with malignant tumours were found to have one or more microsatellite DNA alterations in their primary tumour. Twenty-six of the 32 patients (81.3%) had alterations in the serum by microsatellite analysis. Interestingly, all patients without lymphatic metastasis and three early carcinomas (pT1pN0) already displayed LOH alteration in the serum, while all serum DNA of samples from normal control subjects were negative. Survival was not significantly correlated with either LOH in the tumour or LOH in the serum. CONCLUSION: These data suggest that microsatellite DNA analysis in serum specimens might provide a potentially valuable tool for early detection of oesophageal cancer. The evidence of circulating tumour DNA reflects the propensity of these tumours to spread to distant sites. Up to now the follow-up is still too short to draw further conclusions on the prognostic impact of this finding.     

Estrogen receptor in breast cancer; its relation to mean nuclear area, age and lymph node status

A study of 378 patients with infiltrating breast carcinoma using linear logistic regression and ANOVA analysis demonstrated a different relation between age at operation and estrogen-receptor (ER) concentration in the lymph-node negative and the lymph-node positive groups. Tumours from patients between 51 and 70 years old had lower median ER concentration in the lymph-node negative group than in the lymph-node positive group. In the group older than 70 years, however, tumours from lymph-node negative patients had higher median ER concentrations than those from the lymph-node positive patients. Patients 50 years and younger had similar median ER concentrations in both lymph-node groups. Low mean nuclear area (MNA) of the tumour cells was associated with high frequency of tumours able to produce ER. No such association was found for age. Independent of age and lymph-node status tumours with low MNA also had high ER concentration. These findings suggest that tumours from different lymph-node/age groups may have different biological properties. The relationship between ER and nuclear size point to a key function of the nucleus, both as regards the ability to produce ER and its level of production.     

Operable breast cancer patients with diagnostic delay--oncological and emotional characteristics.

AIMS: Delayed diagnosis in cancer patients often implies presentation with advanced disease with poorer prognosis as a consequence. The aim of the present study was to gain more insight into mechanisms which determine patient delay in the diagnosis of operable breast cancer, stages I and II. METHODS: Patient delay was related to socio-demographic, psychological and clinical-oncological variables in 96 consecutive patients investigated one day before surgery. RESULTS: Patients with a diagnostic delay for one month or more (N=29) reported increased emotional control compared to patients without delay (N=67) (Mean score on Courtauld Emotional Control scale (CEC) 54.5 vs 46.4; p=0.003) and more often grade I tumour (17 out of 29 vs 16 out of 67 patients; p=0.002). Diagnostic delay was predicted independently by tumour differentiation (hazard ratio=5.0; p<0.01 (95% CI: 1.7-14.8)) and emotional control (hazard ratio=5.1; p<0.01 (95% CI: 1.6-16.1)). Multivariate survival analysis with tumour grading and patient delay as covariates showed significant survival effect for tumour differentiation only (hazard ratio=4.4; p<0.05 (95% CI: 1.3-15.4)). CONCLUSION: There seems to be an association between aggressiveness of tumour growth, diagnostic delay and emotional control in patients with early stage breast cancer. Clinical implications of these findings are discussed.     

Effectiveness between early and late temporary ileostomy closure in patients with rectal cancer: A prospective study

A temporary stoma is often used in rectal cancer surgery to protect a distal anastomosis, which remains a major concern after rectal cancer surgery, particularly after low anterior resection. The temporary stoma is scheduled for closure. However, the optimal time of closure of the protecting stoma remains unclear because of sparse studies and data. We aimed to detect the efficacy between early and late temporary ileostomy closure in patients with rectal cancer during or after neoadjuvant chemoradiotherapy. We conducted a prospective, 2-group design between early and late ileostomy closure group in patients after rectal cancer surgery with temporary stoma. Participants were recruited in a teaching hospital in Guangzhou, China. A total of 161 patients confirmed diagnosis of rectal cancer underwent curative surgery and temporary ileostomy. Participants with temporary ileostomy received closure surgery after 1 (early) or 6 (late) months were assessed by clinical parameters and quality of life. Patients in late closure group received more adjuvant chemotherapy cycles but with comparable incidence of stoma closure–related complications and length of hospital stay compared to early closure group. Participants in late closure group with standardized postoperative chemotherapy might have a better prognosis compared with those in early closure group. An increased emphasis should be given to choose the optimal closure time of patients with rectal cancer having temporary ileostomy. Colorectal nurses could provide support to physician for observation of prognosis of different closure time.     

Prognosis of cancer in persons with infrequent consultations in general practice: A population‐based cohort study

Cancer survival rates are lower in Denmark than in comparable European countries. This may partly be attributable to subgroups of cancer patients who seek medical attention at late disease stages. It is unknown if differences in usual (i.e. customary) consultation frequency in general practice are associated with cancer prognosis. We aimed to estimate the cancer prognosis of cancer patients stratified by their usual consultation frequency in general practice. We performed a population‐based cohort study including 123,943 incident cancer patients aged 50 to 89 years diagnosed in Denmark in 2009 to 2013. We estimated associations between the patient's usual general practitioner (GP) consultation frequency 19 to 36 months before the cancer diagnosis and all‐cause mortality by using hazard ratios (HR), estimated by Cox proportional hazards regression. We also estimated the associations between the patient's usual GP consultation frequency and tumour stage, by using logistic regression estimates of odds ratios (ORs). Patients who usually did not see their GP (non‐consulters) had higher all‐cause mortality [HR = 1.39 (95% CI: 1.33–1.44)] compared to patients who usually saw their GP three to five times during an 18 months period (average consulters). Non‐consulters had higher odds of having distant tumour stage [OR = 1.46 (95% CI: 1.38–1.57)] than average consulters. Similar, yet less strong, patterns were seen among patients with low usual GP consultation frequency, yet not statistically significant for all cancer types. In conclusion, the association between usual GP non‐consultation and cancer prognosis is a combination of at least two things: a mechanism through more advanced tumour stage and other independent factors.     

Bcl-2 as prognostic factor in head and neck squamous cell carcinoma

A series of 66 cases of oral squamous cell carcinoma (OSCC) was retrospectively analyzed by immunohisto-chemistry for bcl-2 expression to verify its predictive value for clinical outcome in patients with OSCC. After grouping for bcl-2 expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G), TNM, staging, recurrence, and overall survival rate. Univariate and multivariate (Cox regression) analyses were performed. Thirty-six OSCC (54.5%) showed expression for bcl-2, whereas 30 (44.5%) were negative. No statistical association was found between bcl-2 expression and any variables considered at baseline. Overall disease-specific survival rate at 72 months was 51%, independently from the extent of the tumor. In terms of prognostic significance, the bcl-2-positive group showed more than 60% survival at 72 months whereas the bcl-2-negative group showed none. An independent association of bcl-2 expression was found with an improved overall survival rate (p = 0.048), although grading and staging were established to be the best baseline markers of prognosis. On the basis of these results, it is possible to suggest bcl-2 as an early marker of prognosis: lack of bcl-2 expression could constitute a hallmark of aggressive biological behavior in OSCC.     

A model to predict the outcome of the bilharzial bladder cancer patient after radical cystectomy

The aim of the present study was to evaluate the prognostic factors of bilharzial bladder cancer treated by radical cystectomy: good prognosis is defined as a survival of more than one year, free of local recurrence or metastasis. Two groups of 155 patients, one with a good prognosis (GPG) and the other with a bad prognosis (BPG), through the period 1977-1983 at the National Cancer Institute of Cairo were systematically analyzed for 13 variables evaluated at the commencement of the one year follow-up. Nine factors proved to be of high prognostic value: age, tumour stage, size, grade and location in the bladder, lymph node involvement, metastasis, renal insufficiency and type of urinary diversion. Four variables appeared not to have prognostic value viz: sex, type of tumour (multiplicity), histopathology, and presence of ova of schistosoma haematobium in the specimen. Using a discriminant analysis technique to take into account the inter-relationships between the factors, it was found that tumour grade was the most important prognostic factor followed, in order of importance, by tumour stage, renal insufficiency, size of the tumour and lymph node involvement. Moreover, a simplified score for prognosis was determined: X = 10 grade (1 to 3) +5 stage (1 to 4) +6 renal insufficiency (Y/N) +1 diameter of the tumour (cm) +4 lymph node involvement (Y/N). The larger the score, the poorer the prognosis.     

An evaluation of the prognostic significance of alpha-1-antitrypsin expression in adenocarcinomas of the lung: an immunohistochemical analysis.

Expression of alpha-1-antitrypsin (AAT) in tumour cells of 102 surgically resected lung adenocarcinomas was examined by immunohistochemical method using anti-AAT antiserum. While only 13 cases (13%) were negative for AAT expression, 89 cases (87%) contained AAT at varying degrees. The degree of AAT-positive tumour cells was significantly higher in advanced cases than in early cases. Clinical follow-up study of the patients, particularly in stage I, showed that strongly AAT-positive cases have poor prognosis than weak-to-moderately AAT-positive or AAT-negative cases. Thus, AAT expression status in tumour cells of lung adenocarcinoma may be a biological marker of prognostic significance in regard to tumour growth.     

乳腺癌复发时间的临床病理因素及DCE-MRI预测价值研究

目的:分析乳腺癌患者的临床病理特征、DCE-MRI形态学表现及动态参数指标在预测患者复发时间中的价值。方法:回顾性分析2012年11月至2014年12月在我院就诊,经术后病理确诊并有术前乳腺MRI检查资料的乳腺癌患者,经过3年以上时间随访,依据病理证实或定期影像检查随访确诊为复发的患者58例,对比分析早期复发（术后≤2年）和晚期复发（术后＞2年）患者的临床病理和DCE-MRI特征。结果:在临床病理特征分析中,58例患者2年内乳腺癌术后复发率最高,平均复发时间为23个月（5~49个月）,首发复发转移部位为骨转移多见。淋巴结转移数＜4枚时多见于晚期复发组,≥4枚时多见于早期复发组,二者之间有统计学差异（P<0.05）;HER-2阳性多见于早期复发组,阴性多见于晚期复发组,二者之间有统计学差异（P<0.05）。早期复发患者死亡率（39.39%）高于晚期复发者（4.00%）,且二者具有统计学差异（P<0.05）。在DCE-MRI特征中,早期复发组与晚期复发组间Vpmax值、MaxConcmean值、AUCmean值及MaxSlopemean值存在差异,且差异具有统计学意义（P<0.05）。结论:乳腺癌患者的淋巴结转移情况、免疫组化表型及DCE-MRI动态参数预测乳腺癌患者的复发时间有一定的价值。     

Patterns of breast relapse after local excision +/- radiotherapy for early stage breast cancer

One hundred patients with breast recurrence have been identified from patients at the Royal Marsden Hospital, treated by local excision +/- radiotherapy for early stage primary invasive breast cancer between 1961 and 1985. The mean follow-up was 58 months (range 1 month - 19 years). In 74/100 patients, breast recurrence occurred within the breast parenchyma, was not associated with systemic relapse and carried a relatively good prognosis with a median survival of 77 months from the time of breast relapse. In 67 patients with parenchymal relapse in whom the site of relapse could be reliably compared with that of the original tumour, 60 (90%) patients developed recurrent tumours at or close to the primary site. In 24/100 patients, breast recurrence occurred in the overlying skin and in only two of these patients (2% of total) did recurrence actually occur within the scar tissue. Skin relapse was associated with systemic relapse and carried a relatively poor prognosis with a median survival of 36 months from the time of recurrence. The pattern of breast relapse was similar in irradiated and unirradiated patients. Skin relapse appears to be a manifestation of metastatic disease while parenchymal relapse may represent regrowth of primary tumour. This pattern of breast relapse questions the requirement for radiotherapy to the whole breast after local excision for early stage breast cancer.