Prognostic Parameters and Spinal Metastases: A Research Study

Object

To identify pre-operative prognostic parameters for survival in patients with spinal epidural neoplastic metastasis when the primary tumour is unknown.

Methods

This study was a retrospective chart review of patients who underwent surgery for spinal epidural neoplastic metastases between February 1997 and January 2011. The inclusion criteria were as follows: known post-operative survival period, a Karnofsky Performance Score equal to or greater than 30 points and a post-operative neoplastic metastasis histological type. The Kaplan-Meier method was used to estimate post-operative survival, and the Log-Rank test was used for statistical inference.

Results

A total of 52 patients who underwent 52 surgical procedures were identified. The mean age at the time of spinal surgery was 53.92 years (std. deviation, 19.09). The median survival after surgery was 70 days (95% CI 49.97–90.02), and post-operative mortality occurred within 6 months in 38 (73.07%) patients. Lung cancer, prostate cancer, myeloma and lymphoma, the 4 most common primary tumour types, affected 32 (61.53%) patients. The three identified prognostic parameters were the following: pre-operative walking incapacity (American Spinal Injury Association, A and B), present in 86.53% of the patients (p-value = 0.107); special care dependency (Karnofsky Performance Score, 10–40 points), present in 90.38% of the patients (p-value = 0.322); and vertebral epidural neoplastic metastases that were in contact with the thecal sac (Weinstein-Boriani-Biagini, sector D), present in 94.23% of the patients (p-value = 0.643). When the three secondary prognostic parameters were combined, the mean post-operative survival was 45 days; when at least one was present, the survival was 82 days (p-value = 0.175).

Conclusions

Walking incapacity, special care dependency and contact between the neoplastic metastases and the thecal sac can help determine the ultimate survival of this patient population and, potentially, which patients would benefit from surgery versus palliation alone. A 2- to 3-month post-operative survival period justified surgical treatment.     

The reliability and accuracy of intraoperative imprint cytology of sentinel lymph nodes in breast cancer

OBJECTIVE: Sentinel lymph node (SLN) biopsy is a new component of the surgical treatment of breast cancer that accurately predicts axillary status. In this study the authors evaluated the accuracy of intraoperative imprint cytology (IC) in comparison with definitive histologic evaluation of SLN in breast cancer patients. METHODS: A total 413 women with breast carcinoma and clinically negative axillary nodes underwent breast surgery and SLN biopsy. Mapping of SLN involved injection of (99m)Technecium labelled human albumin nanocolloid particles and Patent Blue dye. At the Department of Pathology, SLNs were bisected along its major axis. Both halves were imprinted 2-4 times on the slides and immediate staining with Hemacolor (Merck Germany) was performed for intraoperative examination. Imprint node negative women underwent no further surgery, while node positive women proceeded to full axillary clearance. Histological analysis of the SLN involved serial sectioning of the whole node with H&E and immunostaining for cytokeratin. RESULTS: Definitive histology revealed metastases (pN+) in 159/413 patients (38.5%): 69 (16.7%) macro metastases, 57 (13.8%) micro metastases, and 33 (8%) women with only isolated IHC positive cells or positive cell groups smaller than 0.2 mm (pNO sn+). The other 254 women had negative SLN biopsy. Imprint cytology detected 54/69 macro metastases, and 4/57 micro metastases. In the group with negative SLN (254), 2 cases were 'false positives'. CONCLUSIONS: Imprint of SLN biopsy can identify a negative axilla with high accuracy (specificity 99.2%). Overall sensitivity is only 36.5%, but macrometastases are detected in 77% which is important for performing ALDN in one session with operation of primary tumour.     

The Significance of Regional Lymph Node Metastases in Breast Carcinoma

The significance traditionally attached to regional lymph node metastases has been questioned following a retrospective review of 922 patients with early breast cancer.Conservative surgical removal of axillary lymph node metastases and conservative irradiation of internal mammary lymph node metastases did not prejudice the five- and 10-year survival rates of patients so treated.Axillary lymph node recurrences had an ominous prognosis and occurred more commonly in the conservatively treated patients, yet survival rates were the same as those following radical mastectomy. Many axillary lymph node recurrences occurred more than five years after primary therapy, or with or after other evidence of reactivation of the breast cancer.It is suggested that breast cancer patients do not do poorly because they have regional lymph node metastases, but rather they have these metastases when they do poorly.     

Multimodality palliative treatment of (111)In-pentetreotide negative/(123)I-MIBG positive metastatic carcinoid - a case report

Patients with carcinoid tumours frequently present with metastatic disease. There are only a few therapeutic options for these patients, and the main goal of palliative treatment is to reduce symptoms and thus to improve quality of life. Current therapy includes surgical resection, hepatic artery embolisation, chemotherapy and somatostatin analogue treatment; however, all these options have limitations. It seems probable that therapeutic modalities based on radiopharmaceuticals may provide better therapy, not only in relation to symptom reduction but may also improve patient survival. In this case report we present a 46-year-old woman with a symptomatic carcinoid, who at the time of diagnosis had liver and abdominal lymph node metastases, the primary tumour being located in the terminal ileum. (111)In-pentetreotide scanning was negative, whereas (123)I-MIBG scanning showed high avidity in the tumour tissue. After right hemicolectomy, two courses of (131)I-MIBG treatment were given (12.95 GBq and 12 GBq, respectively). After the second dose of (131)I-MIBG temporary pancytopenia was present. Octreotide therapy was given empirically only for a short time and was stopped because of drug intolerance. The patient underwent tricuspid and pulmonary valve replacement because of her carcinoid heart disease, followed by two courses of embolisation of liver metastases. While (131)I-MIBG therapy reduced the patient's symptoms of flushing and diarrhoea, there has not yet been any effect on tumour response or 5-HIAA production. This case illustrates the multimodality and multidisciplinary approach to such patients.     

非小细胞肺癌脑转移瘤综合治疗的预后影响因素分析

目的:研究综合治疗的非小细胞肺癌(non-small cell lung cancer,NSCLC)脑转移瘤患者生存预后影响因素,为NSCLC脑转移瘤的治疗提供更多的参考依据。方法:收集83例诊断为NSCLC脑转移瘤的患者进行回顾性研究,随访后建立临床资料数据库,采用单因素分析及Cox回归模型分析不同因素对非小细胞肺癌脑转移瘤患者生存期的影响。结果:患者中位生存期为11个月,6月、12月、18月的生存率分别为79.0%、32.7%、19.4%。经单因素和多因素分析结果显示脑转移瘤的病理类型、原发灶控制情况、治疗方式、靶向治疗是NSCLC脑转移生存的独立影响预后因素。单发转移瘤中,手术联合全脑放疗(Whole brain radiotherapy,WBRT)与手术相比风险率(hazard rate,HR)为0.645(P>0.05),说明联合方式并没有在生存中获益。多发转移瘤中,手术与WBRT相结合与单纯手术对比HR=0.297(P<0.05),有统计学意义。结论:病理类型为非腺癌,原发灶未得到控制,治疗方式不当以及未应用靶向治疗是NSCLC脑转移瘤的独立危险因素。对于单发脑转移瘤患者的局部治疗,单独手术治疗可能具有更高的优势;对于多发脑转移瘤患者的局部治疗,手术与WBRT联合可能具有更多的生存获益。     

Neuron specific enolase-positive breast carcinomas

Ninety-eight patients treated for breast carcinomas were followed from 54 to 75 months after primary diagnosis. All had undergone a modified radical mastectomy with removal of axillary lymph nodes. 36 breast carcinomas were NSE-positive and 62 were negative. NSE-positive tumours were significantly more frequently estrogen receptor-positive than the NSE-negative tumours, and the estrogen receptor values were higher in the NSE-positive groups. Patients with NSE-positive tumours and patients with NSE-negative tumours did not differ with regard to presence of lymph node metastases at the time of primary surgery. However, the study showed that patients with NSE-positive tumours had a tendency towards more lymph node metastases after primary surgical intervention, but a better outcome than patients with NSE-negative tumours and metastases. This study, with a 5-year follow up, failed to demonstrate any major prognostic significance of immunostaining for NSE.     

Adjuvant therapy after radical surgery of cervical cancer: Zagreb experience

The results of the analysis of the treatment of 72 patients with carcinoma of the uterine cervix are presented. Seventy-two patients with Stage IB1 carcinoma of the cervix underwent a radical hysterectomy and pelvic lymphadenectomy. The low-risk group includes the patients without unfavourable prognostic factors that were treated by surgery alone. The high-risk group included women with pelvic node metastases, clinical tumour size greater than 3.0 cm, depth of stromal invasion greater than 1/3 of the cervical wall, Grade 3 tumours and the presence of lympho-vascular space involvement. High-risk patients received whole pelvic radiotherapy between two and four weeks following surgery. Thirty-four patients (47.2%) were in the low-risk group and thirty-eight patients (52.8%) were in the high-risk group. Locoregional recurrences were diagnosed in three cases (8.8%) in the surgery group and in four patients (10.5 %) assigned to postoperative radiotherapy. The incidence of distant metastases was 2.9% in the group treated by surgery alone and 5.3% in the group treated by surgery and radiotherapy. Overall survival at five years was 91.2% in the low-risk group and 89.5% in the high-risk group of patients. Five-year overall survival, locoregional and distant metastases were similar in the low-risk and high-risk groups of patients, which emphasizes the value of whole pelvic radiation in patients with one or more unfavourable prognostic factors after radical surgery in Stage IB1 cervical cancer     

The role of big endothelin-1 in colorectal cancer

INTRODUCTION: Changes in liver blood flow caused by an unknown splanchnic vasoconstrictor have been noted in colorectal cancer patients with liver metastases. This prospective study was performed to assess whether plasma levels of big endothelin-1 (big ET-1) were raised in patients with colorectal cancer. METHODS: Plasma samples from peripheral vein of patients who underwent surgery for primary colorectal cancer (n=60) and those with known colorectal liver metastases (n=45) for a period of 15 months were taken prior to treatment and compared to age- and sex-matched controls (n=20). Plasma samples were analysed by using a single-step sandwich enzyme immunoassay. Immunohistochemistry and in situ hybridisation were also performed on tumour sections to investigate the expression of ET-1 by cancer cells. RESULTS: The median (range) plasma concentration of big ET-1 in controls was 2.1 pg/mL (1.2-13.4 pg/mL). The median (range) plasma concentration of big ET-1 in colorectal cancer patients with no overt hepatic metastases was 3.8 pg/mL (1.2-15.8 pg/mL), p=0.002, and the median (range) plasma concentration of big ET-1 in colorectal cancer patients with hepatic metastases was 5.2 pg/mL (1.7-30 pg/mL), p=0.0001; both were significantly elevated compared to the control group. A significant difference in immunostaining for big ET-1 was noted between paired normal colonic mucosa (median score-1) and tumour sections (median score-3), p=0.01. CONCLUSION: This study has demonstrated elevated concentrations of big ET-1 in colorectal cancer patients, especially in those with hepatic metastases. Upregulation of ET activity in colorectal cancer could be inferred by the increased immunostaining of big ET-1 in cancer cells. Therefore, plasma big ET-1 levels should be evaluated as a potential tumour marker for the identification of hepatic metastases at an earlier stage.     

Women with large breasts are at an increased risk of advanced breast cancer

Background

The risk of nodal metastasis is higher in women with bigger breast. It is not clear if this increase is due to the size of the breast (largely related to obesity) or is the result of larger tumour size at presentation (due to delayed diagnosis). It is hypothesised that women with large breasts are more likely to have node positive disease mainly attributable to their breast size.

Patients and methods

One hundred and twenty consecutive patients who underwent mastectomy during the year 2004 and 2005 for primary breast cancers in a large Teaching Hospital were included in the study. Patient's variable and tumour variable were collected and analysed by SPSS^® computer programme.

Results

It was found that big breasted women (those patients with mastectomy weight greater than 800 g) had a significantly greater tumour size than those with smaller breasts (p = 0.019, Mann-Whitney test) but there was no significant difference in grade (Kendall's tau-b = 0.055, p = 0.57) or lymph node positivity (Kendall's tau-b = 0.011, p = 0.93) between the two groups. Although, the tumour size was significantly greater in those with lymph node metastases (p < 0.001) but mastectomy weight was not found to be significantly greater in those with lymph node metastases (p = 0.11). For patients with similar tumour sizes mastectomy weight was not significantly greater in those patients with lymph node metastases (p = 0.28).

Conclusion

It is concluded that increased incidence of lymph node positivity at presentation big-breasted women is because of larger size of the primary tumour and not due to the size of the breast alone.

     

Micrometastases in bone marrow in patients with primary breast cancer: evaluation as an early predictor of bone metastases.

The bone marrow of 307 patients with primary breast cancer was examined for tumour cells by immunocytochemistry using an antiserum to epithelial membrane antigen. Micrometastases were found in 81 cases (26.4%) and their presence was related to various poor prognostic factors: spread to lymph nodes, vascular invasion, T stage, and pathological size. The median duration of follow up was 28 months. Seventy five patients relapsed, 60 at distant sites. Of these 60 patients, 26 had micrometastases detected at presentation and 34 were free of micrometastases initially. The relapse free interval was significantly shorter for patients with micrometastases, and these patients had a shorter survival. Analysis of the sites of relapse showed that the test predicted bone metastases only. Thus 10 out of 19 patients (53%) who developed bone metastases at first relapse had micrometastases at presentation compared with only 41 out of 288 patients (14%) who remained free of bone metastases or relapsed in non-skeletal sites. The presence of micrometastases detected at the time of initial surgery in a patient with primary breast cancer is a useful predictor of early relapse in bone and may help in selecting patients for subsequent systemic treatment.     

Management of selected patients with hyperprolactinaemia by partial hypophysectomy.

Results are reported in 35 patients with prolactinomas who underwent pituitary surgery within the past five years. After surgery prolactin concentrations became normal in 26 patients and symptoms were alleviated, and nine normal pregnancies were achieved in seven women, including all those who had complained of infertility. Normal prolactin concentrations were restored in 16 of 17 patients with tumours 5-19 mm in diameter but in only six of 11 with tumours less than or equal to 4 mm and four of seven with tumours greater than or equal to 20 mm. Normal prolactin concentrations were restored in all those with preoperative concentrations below 1000 mU/l but in none of those with concentrations above 10 000 mU/l. Although not all of the patients were followed up for five years, hyperprolactinaemia did not recur in any patient whose prolactin concentration had returned to normal six weeks after surgery. This included 16 patients with macroprolactinomas (greater than 10 mm in diameter), who were followed up for from two to five years. These data contrast strikingly with those reported by others at similar stages of follow up and show clearly that partial hypophysectomy offers an acceptable alternative treatment for selected patients with prolactinomas.     

Gallbladder carcinoma: a retrospective analysis of twenty-two years experience of a single teaching hospital

BACKGROUND: The purpose of this study was to retrospectively evaluate our experience with gallbladder cancer since the establishment of a tumour registry in our institute. METHODS: Between 1975 and 1998, 23 consecutive patients with gallbladder cancer were identified using the tumour registry database. There were 18 females (78%) and 5 (22%) males. The mean age at diagnosis was 70.6 (range 42-85) years. The diagnosis was achieved either intra-operatively or following the histological analysis of the gallbladder (n = 17), following gallbladder or liver biopsy (n = 4) or at autopsy (n = 2). Presenting symptoms included upper abdominal pain, weight loss, nausea, vomiting, fever, painless jaundice, hepatomegaly, upper abdominal mass, upper abdominal tenderness, and gastrointestinal haemorrhage. RESULTS: Histological examination revealed 20 adenocarcinomas (87%), 2 squamous cell carcinomas (9%) and one spindle cell sarcoma (4%). At presentation, 14 (61%) gallbladder cancers were stage IV, 5 (22%) were stage III and 4 (17%) were stage II. Kaplan Meier analysis revealed a mean survival of 3.2, 7.8 and 8.2 months for stage IV, III, and II disease respectively. Out of 14 patients with stage IV disease, 8 patients received adjuvant chemotherapy and survived for 4.6 months whereas six patients who did not receive adjuvant chemotherapy survived for 1.3 months. This difference was statistically significant (p = 0.04). CONCLUSION: The majority of patients with gallbladder cancer presented with advanced stage disease (stage IV) which carries a dismal prognosis. Patients who received chemotherapy with stage IV disease, however, did better than those who did not, but this is probably a reflection of patient selection.     

Subarachnoid haemorrhage above the age of 59: are intracranial investigations justified?

Out of 186 patients aged over 59 referred to a neurosurgical department after spontaneous subarachnoid haemorrhage, 143 underwent cerebral angiography; only 28 (15%) of the patients had surgery, of whom 16 were independent one year later. The doubtful benefit of surgery and the small proportion of patients who underwent surgery have economic and ethical implications; in particular, neurosurgical beds and neuroradiological facilities should not be occupied by such patients if this delays the admission of younger patients and those requiring investigation of intracranial space-occupying and spinal lesions.     

Fine needle aspiration cytology of eyelid tumors

Fine needle aspiration (FNA) biopsy was performed on 19 patients with eyelid masses. Six of the patients also had preauricular/submandibular nodal enlargements aspirated. Histopathologic study was performed in ten of the cases. FNA cytology made the diagnosis of an epithelial malignancy in 17 cases (10 sebaceous carcinomas, 4 poorly differentiated carcinomas, 2 squamous cell carcinomas and 1 malignant melanoma). The diagnostic accuracy of FNA cytology in evaluating eyelid masses was thus 89.4%; there were two false-negative cases. All nodal FNA smears revealed metastases of the respective primary tumors. This study indicated that FNA cytology is a simple and efficient method for making the diagnosis of malignancy in eyelid masses, especially in those patients who are not suitable candidates for surgery. Subsequent nodal metastases and tumor recurrence were detected without difficulty using FNA smears.     

Surgical Treatment of Pulmonary Metastases from Testicular Tumours

Isolated pulmonary metastases from testicular tumours were treated by surgery in nine patients. Six are alive and well with no clinical evidence of recurrence. Three of the survivors were operated on more than 10 years ago. Surgical treatment should be considered in such patients, particularly as the metastases are often solitary and may be better differentiated histologically than the primary tumour. Mortality and morbidity rates after thoracotomy are minimal.     

微创颅内血肿清除术治疗高血压脑出血的效果分析

目的:探讨微创颅内血肿清除术在高血压脑出血治疗中的应用效果。方法:选择我院收治的80例高血压脑出血患者(2014年12月至2015年12月),通过随机数字表将其分为实验组和对照组。在患者知情同意基础上,实验组患者(42例)采用微创颅内血肿清除术进行治疗,而对照组患者(38例)使用开颅血肿清除术进行治疗。观察并比较两组患者治疗前后颅内压、GCS评分(格拉斯哥昏迷评分)、神经功能,同时对两组患者治疗有效性以及安全性进行评价。结果:治疗前,两组患者颅内压、神经功能以及GCS评分无明显差异性(P0.05),而治疗后,实验组患者上述指标值明显优于对照组,且差异性明显(P0.05)。实验组患者总有效率明显高于对照组(P0.05),而不良反应发生率却低于对照组(P0.05)。结论:颅内血肿清除术治疗高血压脑出血不仅能有效降低颅内压,改善患者神经功能及其昏迷症状,并且安全性较高。     

Radiation therapy for seminoma of the testis: results in British Columbia.

Between 1942 and 1978 radiation therapy was given to 362 patients with seminoma of the testis, 40 (11%) of whom had a history of maldescent of either testis. The disease was classified retrospectively according to the extent of the primary tumor, the involvement of the regional lymph nodes and the presence of distant metastases (the TNM system), and the results of treatment were analysed according to the classifications. Among the 275 patients referred for treatment at least 5 years before this analysis the 5-year survival rates were 87% overall, 96% for those with a T1 or T2 (relatively localized) tumour but no evidence of nodal involvement or distant metastases and 62% for the 24 with palpable or distant metastases at the time of clinical presentation. Of the 28 patients in whom the disease recurred 15 were successfully treated. A second primary testicular tumour developed in the contralateral testis of eight patients. The incidence of other cancers was not increased over the expected rate in the general male population of the same age.     

Características y manejo del cáncer de mama primario en pacientes octogenarias: estudio retrospectivo

Background

The number of elderly patients with breast cancer is increasing, and a large proportion of these older patients do not receive conventional treatment. Clinical and biological characteristics of tumours at this age and survival according to local or systemic therapy were analysed.

Material and method

A total of 96 consecutive early breast cancer patients over 80 years of age diagnosed in our Unit between January 2002 and September 2008 were retrospectively investigated. Of them, 54 underwent surgery with or without adjuvant hormonal treatment, and 42 received primary hormonal therapy.

Results

Tumours of patients 80 years old or older had more favourable biological characteristics, including expression of steroid receptors, and absence of c-erb B2 expression. Overall survival was 50 months for the group subjected to surgery, and 44 months for the group who did not undergo surgery. The survival free of local recurrence in the surgery group was 44 months, whereas it was 18 months in the non-surgery group.

Conclusion

In a cohort of patients aged 80 years and older, survival was similar in those who received hormonal or surgical therapy, although the former had a shorter period of progression-free survival or local recurrence.     

Eicosanoids and metastasis: experimental aspects in Lewis lung carcinoma

Lewis lung primary carcinomas have been extracted for eicosanoids, and the findings examined in relation to lung metastases. The order of the 5 compounds measured was PGE2 greater than PGE1 greater than PGF2 alpha greater than 6-keto-PGF1 alpha greater than TXB2. On the basis of the observation that the balance of PGI2 and TXA2 is altered in metastasis (Honn et al., 1983), the effects of Nafazatrom, a PGI2 enhancing agent, and imidazole, a thromboxane synthetase inhibitor, were tested. The experimental approach taken was to study spontaneous lung metastases after removal of the primary tumour at 13 days after tumour cell inoculation. Both Nafazatrom and imidazole decreased the lung weight when given during the period either before or after the excision of the primary tumour. There was a general trend toward an increase in the number of small lung nodules (greater than 2 mm) and a decrease in large lung nodules (greater than 2 mm) as a result of the chemotherapy. Mean survival time of the mice was significantly different among the five groups, with the mice surviving the longest in the group treated with Nafazatrom after the excision of the primary tumour.     

The role of PET-CT in detecting unknown primary tumour in patients with cervical lymph node metastases

PET-CT examination was conducted with 440 patients treated at the Department of Head and Neck Surgery, National Institute of Oncology, Budapest, between January 1, 2006 and December 31, 2010. Out of them 77 patients were selected with whom no examination of any sort (physical, pan-endoscopy, or any of the conventional imaging techniques) succeeded in identifying the primary tumour. In each case the primary examination (aspiration cytology and histology) verified cervical metastases, most of them being squamous cell carcinoma. The significance of PET-CT was retrospectively evaluated in cases of unknown primary tumour with verified cervical metastases. We tested the sensitivity of PET-CT in detection of the primary malignant tumour, and possible distant metastases or a second primary in order to plan an optimal treatment schedule for the patient. Patients with whom the examinations specified in the treatment protocol (physical examination, pan-endoscopy, conventional imaging, biopsy) had failed to diagnose the primary tumour were referred to PET-CT. In each case 18F-FDG tracer was used. In 21/77 patients (27%), the PET-CT yielded unequivocal evidence for the primary tumour confirmed by histology, as well. With 10 others (13%), the precarious diagnoses by various imaging techniques were confirmed by the PET-CT. False positive findings with PET-CT that were not verified either by histology or control examination tests occurred but in 10 patients (13%). Concerning the primary tumour, false negative result was obtained only with 3 patients (4%). It should be noted that their retrospective evaluation proved diagnostic errors, the primary tumours were visible in all the scans. With 33 patients (43%) PET-CT furnished no additional information compared to the previous examinations. In 10 patients, asymptomatic distant metastases and in 3 patients synchronous tumours were diagnosed. We also acknowledge that the significance of PET-CT using 18F-FDG is unquestionable in the detection of unknown primary tumours. It is strongly recommended to re-include the detection of unknown primaries in the approved national indication list of PET-CT. (Note, until January 1, 2008 it had been included!) PET-CT is capable of detecting a primary tumour, after all unsuccessful diagnostic examinations till then, in 25-40% of the cases. One cannot disregard the role and significance of PET-CT in the detection of asymptomatic synchronous tumours, or distant metastases. These benefits make PET-CT a suitable tool for the refinement of individually tailored treatment strategies leading to better therapeutic results and more favourable cost-benefit ratio.