Long-term survival from adenocarcinoma of the esophagus after transthoracic and transhiatal esophagectomy

ABSTRACT: BACKGROUND: The effects of transthoracic or transhiatal esophagectomy on the long-term survival of patients who had adenocarcinoma of the esophagus were compared, as were factors applicable in preoperative stratification of patient treatment. METHODS: A cohort of 147 consecutive patients with adenocarcinoma of the esophagus was evaluated for esophagectomy between 1984 and 2000. The patients were followed prospectively and observed survival rates of patients with a transthoracic or transhiatal approach to esophagectomy were compared by standardized mortality ratio (SMR) and relative mortality ratio (RMR) using the expected survival of a matched Norwegian population. RESULTS: A R0 resection was performed by transthoracic (n = 33) or a transhiatal (n = 55) esophagectomy in 88 (60%) patients with a median age of 61 (range: 35-77) and 70 (42-88) years, respectively (P <0.001). Tumor stages and other possible risk factors were similar in the two groups. Transthoracic or transhiatal esophagectomy resulted in a median survival time of 20.5 (95% confidence interval (CI): 10.4-57.6) and 16.4 (10.6-28.7) months, respectively. The respective survival rates were 31.2% and 27.8% by 5 years, and 21.3% and 16.6% by 10 years with an overall RMR of 1.14 (P = 0.63). Median survival time in the absence or presence of lymph node metastases was 74.0 (95% CI: 17.5-166.4) and 10.7 (7.9- 14.9) months. The corresponding survival rates by 10 years with non-involved or involved nodes were 48.9% and 3.8% respectively (RMR 2.22, P = 0.007). Patients with a pT1-tumor were few and the survival rate was not very different from that of the general population (SMR = 1.7, 95% CI: 0.7-4.1). The median survival time of patients with a pT2-tumor was 30.4 (95% CI: 9.0-142) months and with a pT3-tumor 14 (9.2-16.4) months. The survival rates by 10 years among patients with a pT1 tumor were 57.0% (95% CI: 14.9-78.9), pT2 33.3% (11.8-52.2), and pT3 7.1% (1.9-15.5). The relative mortality for T3 stages compared to T1 stages was statistically significant (RMR = 3.22, P = 0.024). CONCLUSION: Transthoracic and transhiatal esophagectomy are both effective approaches for treatment of adenocarcinoma of the esophagus and survival of more than 10 years can be expected without adjuvant chemotherapy. However, increasing depth of tumor invasion and lymph node metastases reduce life expectancy.     

Identification of Risk Factors for Locoregional Recurrence in Breast Cancer Patients with Nodal Stage N0 and N1: Who Could Benefit from Post-Mastectomy Radiotherapy?

Introduction

The locoregional recurrence (LRR) rate was reported as high as approximately 20% in stage I-II breast cancer following mastectomy. To investigate the risk factors for LRR in pT1–2N0-1 breast cancer patients treated with mastectomy but not radiation, and to define a subgroup of patients at high risk of LRR who may benefit from postmastectomy radiotherapy (PMRT).

Methods and Materials

In total, 390 patients with pT1-2N0M0 (n = 307) and pT1-2N1M0 (n = 83) breast cancer who underwent total mastectomy without adjuvant radiotherapy from 2002 to 2011 were enrolled in the study.

Results

After a median follow-up period of 5.6 years (range, 0.6–11.3 years), 21 patients had 18 systemic relapses and 12 LRRs including six in the chest wall and eight in the regional nodal area. The 5-year LRR-free survival (LRRFS) rates were 97.0% in pN0, 98.8% in pN1, and 97.4% in all patients. Multivariate analysis revealed that age < 50 years (Hazard Ratio, 11.4; p = 0.01) and no adjuvant chemotherapy (Hazard Ratio, 10.2; p = 0.04) were independent risk factors for LRR in pN0 patients. Using these factors, the 5-year LRRFS rates were 100% without any risk factors, 96.4% with one risk factor, and 86.7% with two risk factors. In pN1 patients, multivariate analysis revealed that having a hormone receptor negative tumor (Hazard Ratio, 18.3; p = 0.03) was the only independent risk factor for LRR. The 5-year LRRFS rates were 100.0% for luminal type, and 92.3% for non-luminal type cancer.

Conclusion

Patients with pT1-2N0-1 breast cancer who underwent total mastectomy without PMRT could be stratified by nodal stage and risk factors for LRR. PMRT may have of value for node negative patients aged less than 50 years and who are not treated with adjuvant chemotherapy, and for non-luminal type patients with one to three positive nodes.     

The impact of the time factor on the outcome of a combined treatment of patients with laryngeal cancer

PurposeTo investigate the impact of the time factor on the locoregional control in combined treatment (surgery and postoperative radiotherapy) in patients with advanced laryngeal cancer.Materials and MethodsBetween January 1993 and December 1996, 254 patients with pT3 or pT4 and pN0-pN2 laryngeal cancer were treated by surgery and postoperative radiotherapy (RT). The median age of patients was 56.3 years (range: 30–70 years). The analyzed group consisted of 236 males (92%) and 18 females (8%). In all cases total laryngectomy was performed. 196 out of 254 patients underwent homolateral neck dissection and 58 out of 254 bilateral neck dissection. RT began 45 days postoperatively (range: 22 to 78 days) and continued for 47 days (range: 40–74 days). The primary tumour bed was irradiated to the median total dose of 61.2 Gy (range: 57 – 64 Gy) and all regional lymph nodes were treated in all patients to a dose of 50 Gy. Postoperative RT was indicated in case of close postoperative margins at the tumour site or pathological status of lymph nodes described as pN1 or pN2. Univariate and multivariate analyses were used to determine the predictors for locoregional failure. The following factors were studied for their prognostic importance of locoregional outcome: the overall treatment time (OTT), radiotherapy treatment time (RTT), the interval between surgery and the beginning of radiotherapy, age, sex, pT and pN categories.Results: The actuarial 5-year overall survival rate was 49%, the actuarial loco regional control rate was 70%. The univariate analysis, using a log-rank test indicated that prolongation of the overall treatment time (OTT), the time of radiotherapy (RTT), the interval time between surgery and radiotherapy, and the pN status were predicted for the loco regional control of postoperative radiotherapy. The multivariate analysis using Cox proportional hazard model indicated that only RTT, OTT, and the pathological status of lymph nodes were independent prognostic factors for the loco regional control.Conclusions: The analysis showed that the prolongation of the overall treatment time of the combined modality (OTT) and the time of radiotherapy course (RTT) were independent prognostic time factors correlated with lower loco regional control.     

A matter of the heart: myocardial metastases in neuroendocrine tumors

The aim of the present study was to evaluate frequency, clinical spectrum, and treatment of myocardial metastases in patients with histologically proven neuroendocrine tumors by analysis of our database and literature review. The literature on cardiac metastases in patients with neuroendocrine tumors published from 1973 to the present was reviewed for age, sex, primary tumor localization, metastases, symptoms, complications, treatment, diagnostic methods, and histology. Patient records from our institution were analyzed retrospectively for cardiac metastases detected by any diagnostic means and detailed patient histories are given. 4 patients with myocardial metastases could be identified in our database (n=550) while literature review identified 41 published cases. Mean age at initial diagnosis was 57.5 years (females=13, males=28), primary tumor localizations were foregut (n=7), midgut (n=28), hindgut (n=1), or unknown (n=3). Carcinoid syndrome was reported for 28 patients. Cardiac involvement was right-ventricular only (n=10), left-ventricular only (n=11), or biventricular (n=10). Diagnosis was obtained by echocardiography (n=21), CT/MRI (n=12) and other methods (n=9), or by autopsy (n=9). We describe visualization of cardiac metastases by (68)Ga-DOTATOC-PET/CT for the first time. Clinical presentation ranged from asymptomatic patients to cardiac arrest. Follow-up times ranged from <1 month up to 12 years. Clinicians treating patients with neuroendocrine tumors should be aware of the heart as a possible site of metastatic disease. Echocardiography and MRI are the methods of choice for follow-up, while PET/CT might contribute to earlier and more frequent detection. Management of cardiac metastases requires close cooperation between specialists of internal medicine, nuclear medicine, and cardiac surgery.     

Association between HSP90 and Her2 in Gastric and Gastroesophageal Carcinomas

Background

Her2 expression and amplification occurs in a significant subset of gastro-esophageal carcinomas. Her2 is a client protein of molecular chaperones, e.g. heat shock protein (HSP) 90, rendering targeted therapies against Her2/HSP90 an interesting approach. This study aimed to investigate the role and relationship of Her2 and HSP90 in gastric and gastro-esophageal adenocarcinomas.

Material and Methods

Immunohistochemical determination of HSP90 and Her2 expression was performed on 347 primary resected tumors. Her2 amplification was additionally determined by fluorescence in situ hybridization for all cases. Expression and amplification results were correlated with pathologic parameters (UICC pTNM category, tumor grading) and survival.

Results

Elevated Her2 copy numbers were observed in 87 tumors, 21 of them showing amplification. 174 tumors showed Her2 immunoreactivity/expression. HSP 90 immunoreactivity was found in 125 tumors. There was no difference between gastric carcinomas and carcinomas of the gastroesophageal junction regarding Her2 or HSP90. Both high HSP90 and Her2 expression/amplification were associated with earlier tumor stages (p<0.01), absence of lymph node metastases (p<0.02) and Laurens intestinal type (p<0.001). HSP90 correlated with Her2 expression and amplification (p<0.001 each). Expressions of HSP90 and Her2, but not Her2 amplification were associated with better prognosis (p=0.02; p=0.004; p=0.802). Moreover, Her2 expression was an independent prognostic factor for overall survival in the subgroup of gastric carcinoma patients (p=0.014) besides pT category, pN category and distant metastases.

Conclusion

Her2 expression and gene amplification occurred in a significant subset of cases. Our results suggest a favorable prognostic impact of Her2 expression. This warrants further investigations regarding the significance of Her2 non-amplified tumors showing Her2 immunoreactivity and the definition of Her2 status in gastric cancers. Moreover, the correlation of Her2 expression with the expression of Her2 chaperoning HSP90 may indicate a synergistic regulation. Targeting HSP90 with or without Her2 may offer additional therapeutic options for gastric carcinoma treatment.     

Radiofrequency ablation as locoregional therapy for unresectable hepatic malignancies: initial results in 24 patients with 5-years follow-up

Radiofrequency ablation (RFA) is one treatment modality for unresectable liver metastases. Patients with hepatic malignancies (n = 24) underwent elective RFA. All tumors were ablated with a curative intent, with a margin of 1 cm, in a single session of RFA. The median diameter of tumor was 3.1 cm (range 1.7-6.9 cm). Studied patients were not candidates for resection due to multifocal hepatic disease, extrahepatic disease, proximity to major vascular structures or presence of cirrhosis with functional hepatic reserve inadequate to tolerate major hepatic resection. Complete tumor necrosis was achieved in 87.5% and tumor recurred in 3 patients (12.5%) with lesions larger than 5 cm. Distant intrahepatic recurrence was diagnosed in another 4 (16.7%). Distant metastases were found in 7 (29.2%) patients. Four of these 7 patients had also distant intrahepatic recurrence of disease. Two and 5-years survival rates were 41.7% (10 patients) and 8.3% (2 patients) respectively. RFA is safe and effective option for patients with unresectable hepatic malignancies smaller than 5 cm without distant metastatic disease. RF ablation resulted in complete tumor necrosis in 87.5% with 2 and 5-years survival rates much higher than with chemotherapy alone or only supportive therapy, when survival is measured in weeks or months. If RFA is unavailable, percutaneous ethanol injection therapy can be done but with inferior survival rates.     

非小细胞肺癌脑部转移瘤适形与调强放疗的剂量研究

为探讨NSCLC脑部转移瘤调强放疗与适形放疗的剂量特点,本研究选取57例非小细胞肺癌脑转移瘤患者,其中单个脑转移灶患者5例,多个脑转移灶患者52例,分别设计全脑放疗+适形放疗与调强放疗计划,用均匀指数(HI)和适形指数(CI)评价靶区剂量,危及器官(OAR)剂量用近似最大剂量D_2%(串联)和中位剂量D_50%(并联)进行评价。研究发现,单个脑转移灶IMRT与WBRT+CRT比较中,CI为(PTV,(0.80±0.15) cGy,(0.34±0.19) cGy, p=0.00),HI为(PTV,(0.52±0.03) c Gy,(0.71±0.12) cGy, p=0.24),两者OARs剂量比较:脑干为((4 348±236) cGy,(4 593±149) cGy, p=0.01),脑垂体为((4 258±166) cGy,(4 581±123) cGy, p=0.02);在多个脑转移灶中,IMRT与WBRT+CRT比,较CI为(PTV,(0.59±0.33) cGy,(0.49±0.27) cGy, p=0.03),HI为(PTV,(0.93±0.01) cGy,(0.58±0.03) cGy, p=0.19),两者OARs剂量比较:脑干为((4 946±132) cGy,(4 843±196) cGy, p=0.51),脑垂体为((4 597±180) cGy,(4 705±149) cGy, p=0.70)。本研究的结果说明,单个脑转移灶患者,IMRT较WBRT+CRT有更好的靶区适形性、稍差的靶区异质性,脑干和垂体的IMRT剂量低于WBRT+CRT,而眼球、晶体的剂量两者差别不明显。多个脑转移灶患者,IMRT较WBRT+CRT有更好的靶区适形性、稍差的靶区异质性,而OARs剂量,IMRT较WBRT+CRT差异不明显。在临床实践过程中,应当根据患者不同的病灶情况选择合适的放疗方案,以获取更优的临床治疗效果。     

Serum HER-2 extracellular domain: relationship with clinicobiological presentation and prognostic value before and after primary treatment in 701 breast cancer patients

PURPOSE: To determine the clinical correlations and prognostic value of serum HER-2 (sHER-2) before and after primary breast cancer treatment. METHODS: sHER-2 from 701 consecutive patients with stage I-III tumors (median follow-up 7.7 years) was assayed by an enzyme-linked immunosorbent assay (Immuno 1, Bayer Diagnostics). RESULTS: The median pretreatment sHER-2 concentration was 8.30 ng/mL (range 3.15-82.00 ng/mL). Forty-seven patients (6.7%) had sHER-2 concentrations >12 ng/mL (cutoff level). Pretreatment sHER-2 correlated positively with CA 15.3 (p=0.0169), pathological tumor size (p=0.0082), number of invaded lymph nodes (pN, p=0.0160) and histological grading (p=0.0086). Kaplan-Meier analyses indicated that pretreatment sHER-2 was of prognostic value for contralateral breast cancer (p=0.0018), metastasis-free survival (MFS) (p=0.0008) - particularly lung (p=0.0082) and liver metastases (p=0.0035) - and overall disease-specific survival (DSS) (p=0.0020). According to pN status, pretreatment sHER-2 was of prognostic value only for pN-positive patients (p=0.0017). When combined with estradiol or progesterone receptor status, patients with elevated sHER-2 and receptor-negative tumors had a significantly shorter DSS (p<0.0001 for both receptors). Post-treatment sHER-2 also had individual prognostic value for MFS (p=0.0144) and DSS (p=0.0212). In multivariate analysis, only sHER-2 after primary treatment was an independent prognostic variable for MFS and DSS (p=0.0078 and p=0.0058, respectively). CONCLUSION: sHER-2 elevation in early breast cancer correlates with the principal criteria of tumor aggressiveness, thus permitting selection of patients with a high risk of visceral metastases and contralateral breast tumors. Post-treatment sHER-2 is an independent prognostic factor enabling to identify patients likely to benefit from aggressive adjuvant treatments.     

Can the Tumor Deposits Be Counted as Metastatic Lymph Nodes in the UICC TNM Staging System for Colorectal Cancer?

Objective

The 7th edition of AJCC staging manual implicitly states that only T1 and T2 lesions that lack regional lymph node metastasis but have tumor deposit(s) will be classified in addition as N1c, though it is not consistent in that pN1c is also an option for pT3/T4a tumors in the staging table. Nevertheless, in this TNM classification, how to classify tumor deposits (TDs) in colorectal cancer patients with lymph node metastasis (LNM) and TDs simultaneously is still not clear. The aim of this study is to investigate the possibility of counting TDs as metastatic lymph nodes in TNM classification and to indentify its prognostic value for colorectal cancer patients.

Methods and Results

In this retrospective study, 513 cases of colorectal cancer with LNM were reviewed. We proposed a novel pN (npN) category in which TDs were counted as metastatic lymph nodes in the TNM classification. Cancer-specific survival according to the npN or pN category was analyzed using Kaplan-Meier survival curves. Univariate and multivariate analyses were performed to indentify significant prognostic factors. Harrell''s C statistic was used to test the predictive capacity of the prognostic models. The results revealed that the TD was a significant prognostic factor in colorectal cancer. Univariate and multivariate analyses uniformly indicated that the npN category was significantly correlated with prognosis. The results of Harrell''s C statistical analysis demonstrated that the npN category exhibited a superior predictive capacity compared to the pN category of the 7th edition TNM classification. Moreover, we also found no significant prognostic differences in patients with or without TD in the same npN categories.

Conclusions

The counting of TDs as metastatic lymph nodes in the TNM classification system is potentially superior to the classification in the 7th edition of the TNM staging system to assess prognosis and survival for colorectal cancer patients.     

ErbB-receptors expression and survival in breast carcinoma: a 15-year follow-up study

Aberrant expression of the epidermal growth factor receptor family has been implicated in the pathogenesis and progression of breast cancer and associated with poor prognosis. To evaluate the prognostic impact of the ErbB receptors expression profile, we analyzed a well-characterized series of 145 primary breast carcinomas for the simultaneous expression of epidermal growth factor receptor (EGFR/HER-1), ErbB-2 (HER-2), ErbB-3 (HER-3), and ErbB-4 (HER-4), using immunohistochemistry. Tumors were considered negative or positive for each marker when less than or more than 25% of the cancer cells were immunopositive. Expression of EGFR, ErbB-2, ErbB-3, and ErbB-4 was observed in 31 (21.4%), 65 (44.8%), 72 (49.7%), and 81 (55.9%) of the cases, respectively. There were significant associations between EGFR expression and pT status (P = 0.01), and between ErbB-3 expression and pN (P = 0.003), menopausal (P = 0.01) and PR (P < 0.001) status. The majority of the cases co-expressed two or more receptors. ErbB-3 resulted positive in 51/81 (63.0%) of the ErbB-4 positive cases and ErbB-3/ErbB-4 co-expression was statistically significant (P = 0.0003). As expected, ErbB-2 expression was associated with reduced overall survival at 15 years of follow-up (P = 0.04), even after adjusting for a series of other prognostic factors (P = 0.05). Moreover, cumulative analysis of ErbB-2/3/4 expression showed a strong positive association between higher total ErbB-2/3/4 expression score and worse prognosis (P = 0.002). The simultaneous expression in cancer cells of more than one ErbB receptor identifies a subset of breast cancer patients at high risk for poor survival.     

Immunohistochemical determination of HER-2/neu overexpression in malignant melanoma reveals no prognostic value, while c-Kit (CD117) overexpression exhibits potential therapeutic implications

BACKGROUND: HER-2/neu and c-kit (CD117) onco-protein are increasingly being recognized as targets for therapy in solid tumors, but data on their role in malignant melanoma is currently limited. We studied the prevalence of overexpression of HER-2/neu and c-Kit in 202 patients with malignant melanoma to evaluate a possible prognostic value of these molecular targets in malignant melanoma. METHODS: Overexpression of HER-2/neu and c-Kit was evaluated using immunohistochemical assays in 202 archival tissue specimens. RESULTS: Between 1991 and 2001, 202 subjects (109 males; 54% and 93 females; 46%) with malignant melanoma were studied with a mean age of 57 years (age range: 15-101 years). The most common histologic type was amelanotic melanoma (n = 62; 30.7%) followed by superficial spreading melanoma (n = 54; 26.7%). The depth of penetration of melanoma (Breslow thickness, pT Stage) ranged from 0.4 mm (stage pT1) to 8.0 mm (stage pT4A). Mean thickness was 2.6 mm (stage pT3A). The ECOG performance scores ranged from 0 to 3. Only 2 patients (0.9%) revealed HER-2/neu overexpression, whereas 46 (22.8%) revealed c-Kit overexpression. Multivariate analysis performed did not show a significant difference in survival between c-Kit positive and negative groups (p = 0.36). Interestingly, not only was c-Kit more likely to be overexpressed in the superficial spreading type, a preliminary association between the presence or absence of c-Kit overexpression and the existence of another second primary tumor was also observed. CONCLUSIONS: The results of our large study indicate that the HER-2/neu onco-protein neither has a role in melanogenesis nor is a potential target for clinical trials with monoclonal antibody therapy. This indicates there is no role for its testing in patients with malignant melanoma. Although c-Kit, expressed preferentially in the superficial spreading type, may not have prognostic value, it does have significant therapeutic implications as a molecular target warranting further investigation.     

Is the urokinase-type plasminogen activator system a reliable prognostic factor in gastric cancer?

AIM: The aim of this prospective study was to evaluate the clinical and prognostic impact of immunohistochemically assessed uPA and PAI-1 in patients with gastric cancer. METHODS: This prospective study analyzed specimens obtained from 105 gastric cancer patients who underwent gastrectomy with extended lymphadenectomy. The immunohistochemical expression of uPA and PAI-1 was studied semiquantitatively in the tumor epithelium and was correlated with the clinicopathological features of each patient. RESULTS: Univariate analysis revealed no statistically significant association of uPA levels with pT and pN category (p=0.655 and 0.053, respectively), grading (p=0.374), depth of tumor invasion (p=0.665), UICC classification (p=0.21) and the Laurén classification (p=0.578). PAI-1 expression showed no statistically significant correlation with pT, pN and M category (p=0.589, 0.414, and 0.167, respectively), grading (p=0.273), and the Laurén classification (p=0.368). Only the UICC classification was significantly correlated with PAI-1 (p=0.016). Kaplan-Meier analysis revealed no significant association of uPA and PAI-1 with overall survival (p=0.0929 and 0.0870, respectively). CONCLUSIONS: Our results could not verify any prognostic value of uPA and PAI-1 levels in patients with gastric carcinoma. Therefore, the uPA-system as a biologically defined prognostic marker to identify high-risk gastric cancers should be applied with caution. However, considering the number of patients involved and the borderline level of significance observed in this study, a larger number of events may have resulted in significant differences.     

Increased intratumoral neutrophil in colorectal carcinomas correlates closely with malignant phenotype and predicts patients' adverse prognosis

Background

Substantial evidence suggests that the presence of inflammatory cells plays a critical role in the development and/or progression of human tumors. Neutrophils are the common inflammatory cells in tumors; however, the infiltration of intratumoral neutrophils in colorectal carcinoma (CRC) and its effect on CRC patients'' prognosis are poorly understood.

Methodology/Principal Findings

In this study, the methods of tissue microarray and immunohistochemistry (IHC) were used to investigate the prognostic significance of intratumoral CD66b+ neutrophil in CRC. According to receiver operating characteristic curve analysis, the cutoff score for high intratumoral CD66b+ neutrophil in CRC was defined when the mean counts were more than 60 per TMA spot. In our study, high intratumoral CD66b+ neutrophil was observed in 104/229 (45.4%) of CRCs and in 29/229 (12.7%) of adjacent mucosal tissues. Further correlation analysis showed that high intratumoral neutrophil was positively correlated with pT status, pM status and clinical stage (P<0.05). In univariate survival analysis, a significant association between high intratumoral neutrophil and shortened patients'' survival was found (P<0.0001). In different subsets of CRC patients, intratumoral neutrophil was also a prognostic indicator in patients with stage II, stage III, grade 2, grade 3, pT1, pT2, pN0 and pN1 (P<0.05). Importantly, high intratumoral neutrophil was evaluated as an independent prognostic factor in multivariate analysis (P<0.05).

Conclusions/Significance

Our results provide evidence that increased intratumoral neutrophil in CRC may be important in the acquisition of a malignant phenotype, indicating that the presence of intratumoral neutrophil is an independent factor for poor prognosis of patients with CRC.     

Breast metastasis from squamous cell carcinoma of the oropharynx: a case report

Background

Breast metastases from extramammary tumors are extremely rare, the most common primary tumors being contralateral breast carcinoma, followed by lung, gynecological, gastrointestinal, melanoma, and hematological cancers. Only a few cases deriving from head and neck squamous cell carcinoma have been reported in the literature to date.

Case presentation

We report a case of a 47-year-old Caucasian woman who presented to our hospital with a solitary breast lesion in the right upper external quadrant associated with multiple bone and visceral metastases. Two years before, she had undergone radical resection of a squamous cell carcinoma of the oropharynx (stage pT2, pN1), which was followed by adjuvant radiotherapy. Breast ultrasound showed a hypoechogenic tumor lesion of 4 cm in the right upper external quadrant that was associated with multiple axillary and infra-/supraclavicular adenopathies. A positron emission tomographic scan documented multiple visceral and bone metastases with a single hypermetabolic lesion of the right breast. The results of histology and immunohistochemistry were consistent with a metastasis from a squamous cell carcinoma. The patient died of acute respiratory insufficiency 1 month after her breast metastasis diagnosis and before starting any systemic antitumoral treatment.

Conclusions

Although breast metastases are extremely rare, they should be considered in any patient with a history of cancer and confirmed by histology and immunohistochemistry because they are very difficult to distinguish from other primary breast tumors based only on clinical and radiological features. There are no standardized treatment guidelines for breast metastasis management. Surgery and radiotherapy can play a role in symptom palliation, but they do not have any relevant impact on survival, the prognosis being poor, with an estimated overall survival less than 1 year from diagnosis.

     

Thyroid carcinoma: A follow-up study of 11 years

Summary During a follow-up of 11 years of thyroid carcinoma 136 patients were repeatedly examined. 43% papillary, 43% follicular, 11% anaplastic and 2% medullary carcinomas was found. The incidence of these types of carcinoma differed considerably; the frequency peak of papillary carcinomas was reached in 45-year-old humans, that of the follicular carcinomas in people aged 60, that of the anaplastic carcinomas in 70-year-old humans.84% of the patients was female. Classification in pTNM-system: 8% in pT1, 27% in pT2, 12% in pT3 and 49% in pT4. Local and distant metastases were found at a low rate equally in pT1, pT2 and pT3; 26% of patients in pT4 had local metastases and 18% had distant ones in addition. There were 6 patients with metastases of a differentiated adenocarcinoma accumulating no 131-iodine and with no thyroglobulin in serum. 29% of patients had after thyroidectomy an unilateral paresis of the nervus recurrens and 4% a bilateral one. 26% of patients had a permanent hypoparathyroidism after thyroidectomy.Dedicated to Prof. L.E. Feinendegen on the occasion of his 60th birthday     

Pancreastatin-like immunoreactivity in human carcinoid disease

Pancreastatin-like immunoreactivity has been demonstrated in human carcinoid tumors by immunohistochemistry and radioimmunoassay, employing antisera raised to a synthetic C-terminal fragment of porcine pancreastatin. Immunohistochemistry revealed intense immunoreactivity in all tumors. By radioimmunoassay, high concentrations of pancreastatin-like immunoreactivity were measured in carcinoid tumors arising from the fore-gut (mean +/- S.D. and range: 369 +/- 955 and 9.4-3670 pmol g-1, respectively, n = 14), mid-gut (mean +/- S.D. and range: 1354 +/- 1538 and 337-3978 pmol g-1, respectively, n = 5) and in metastases associated with mid-gut tumors (mean +/- S.D. and range: 684 +/- 739 and 31-2255 pmol g-1, respectively, n = 7), compared to corresponding normal tissues (less than 1.4 pmol g-1). Individuals with hepatic metastases and carcinoid syndrome had elevated circulating levels of pancreastatin-like immunoreactivity (mean +/- S.D. and range: 770 +/- 1249 and 42-4120 pmol l-1; n = 12), significantly above the normal, fasting range (mean +/- S.D. and range: 14.9 +/- 7.5 and 4-37.5 pmol l-1, respectively, n = 42). However, patients with non-metastatic carcinoid tumors (n = 4), who had been clinically cured after primary tumor resection, had plasma levels within the normal range. Chromatographic analysis of extracts of primary lung and ileal tumors, hepatic metastases from ileal tumors and plasma from individuals with carcinoid syndrome revealed molecular heterogeneity of pancreastatin-like immunoreactivity.     

The Promher Study: An Observational Italian Study on Adjuvant Therapy for HER2-Positive,pT1a-b pN0 Breast Cancer

BackgroundThe management of pT1a-b pN0 HER2-positive breast cancer is controversial and no data about the efficacy of trastuzumab in this setting are available from randomized clinical trials. The aims of this retrospective study were to assess how patients are managed in clinical practice in Italy, which clinical or biological characteristics influenced the choice of adjuvant systemic therapy and the outcome of patients.MethodsData of consecutive patients who underwent surgery from January 2007 to December 2012 for HER2-positive, pT1a-b pN0 M0 breast cancer were retrospectively collected from 28 Italian centres. Analysis of contingency tables and multivariate generalized logit models were used to investigate the association between the baseline clinical and biological features and the treatment strategy adopted.ResultsAmong 303 enrolled patients, 204 received adjuvant systemic therapy with trastuzumab, 65 adjuvant systemic therapy without trastuzumab and 34 did not receive adjuvant systemic therapy. At the multivariate analysis age, tumor size, proliferation index and hormone receptor status were significantly associated with the treatment choice. Five-year disease-free survival (DFS) probability was 95%, 94.3% and 69.6% for patients treated with adjuvant systemic therapy and trastuzumab, with adjuvant systemic therapy without trastuzumab and for patients who did not receive adjuvant systemic therapy, respectively (p<0.001).ConclusionsThe majority of patients (66%) with pT1a-b pN0 HER2-positive breast cancer enrolled in this retrospective study received adjuvant systemic therapy with trastuzumab, whereas only 11% patients did not receive any adjuvant systemic therapy. The choice of treatment type seems to be mainly influenced by tumor size, proliferation index, hormone receptor status and age. The 5-year DFS probability was significantly higher for patients receiving adjuvant systemic therapy with trastuzumab compared with patients not receiving adjuvant systemic therapy or receiving adjuvant systemic therapy without trastuzumab.     

Relationship between steroid receptors (as continuous variables) and response to adjuvant treatments in postmenopausal women with node-positive breast cancer.

In current clinical practice for breast cancer patients, estrogen (ER) and progesterone receptor (PgR) concentrations, quantified by the dextran-coated charcoal assay, are categorized by an arbitrary cutoff into a negative or positive status. However, although the results obtained with this approach are easy to interpret, such a representation could oversimplify the relationship between ER and PgR content and patient outcome and imply an assumption of monotonicity, which is generally expected but rarely proven. We evaluated the relationship between ER and PgR content (considered on a continuous scale) and clinical outcome, using a flexible statistical model, in a group of postmenopausal patients with N-positive operable tumors who were submitted to surgery and different adjuvant treatments (tamoxifen or CMF). Univariate analysis indicated that in the tamoxifen-treated group, ER level, number of metastatic nodes (pN) and age, but not PgR, were significant indicators of clinical outcome (p = 0.032, p = 0.021 and p = 0.029, respectively). Multivariate analysis indicated that in this group of patients there was no interaction between variables, and in the final model for disease-free survival (DFS) only ER and pN were retained with an overall predictive ability of the regression model of 0.723, as evaluated by Harrell's c. However, pN markedly contributed to the predictive ability of the model with respect to ER, since a marked decrease in Harrell's c statistic (c = 0.582) was observed when pN was removed from the model. In the CMF-treated group, only pN affected clinical outcome. When the estimated DFS curves obtained from the final Cox regression models were plotted according to four values of ER (in the tamoxifen-treated group) or three values of pN (in the CMF-treated group) we observed that in the tamoxifen-treated group patients with an ER concentration equal to 0 fmol/mg cytosol protein had the worst prognosis, whereas a marked improvement of the expected DFS was observed for patients with a low but detectable ER level (generally classified as ER-negative because falling below the conventional cutoff value of 10 fmol/mg cytosol protein). Our results seem to suggest that the use of steroid receptor concentrations on a continuous scale, instead of dichotomous "status", is to be preferred in the choice of adequate therapeutic strategies.     

Prognostic Value of Metastatic Axillary Lymph Node Ratio for Chinese Breast Cancer Patients

Objective

The prevalence of breast cancer varies among countries and regions. This retrospective study investigated the prognostic value of the lymph node ratio (LNR) compared with the number of positive lymph nodes (pN) in Chinese breast cancer patients.

Methods

The medical records of female breast cancer patients (N = 2591) were retrospectively evaluated. The association of LNR and TMN staging system were compared with respect to overall, disease-free, and distant metastasis-free survival.

Results

Out of 2591 patients, 2495 underwent modified radical surgery and 96 received breast conserving surgery. All patients had adjuvant chemotherapy following surgery. The median follow up period 66.9 months (range 5–168 months). The 5-year and 10-year overall survival rates were 89.3% and 78.8%, respectively, and 5-year disease-free survival and distant metastasis-free survival rates were 81.6% and 83.5%, respectively. Univariate analysis indicated that in general T, pN, LNR, as well as tumor expression of the estrogen receptor, progesterone receptor, and HER2 were associated with overall, disease-free, and distant metastasis-free survival (all P-values <0.05). Mutlivariate analysis found pN stage and LNR were independent predictors of overall, disease-free, and distant metastasis-free survival (all P-values <0.001). If pN stage and LNR were both included in a multivariate analysis, LNR was still an independent prognostic factor for overall, disease-free, and distant metastasis-free survival (all P-values <0.001).

Conclusion

Our findings support the use of LNR as a predictor of survival in Chinese patients with breast cancer, and that LNR is superior to pN stage in determining disease prognosis.     

Prognostic value of DNA flow cytometry in sympathoadrenal paragangliomas.

OBJECTIVE: To determine whether ploidy patterns are related to prognosis in sympathoadrenal paragangliomas (SAP) using flow cytometry. STUDY DESIGN: DNA flow cytometric analysis of formalin-fixed, paraffin-embedded tumor samples from 36 patients with SAP was performed. Eight cases fulfilled at least one of the following malignancy criteria: (1) extensive invasion of adjacent structures (5 cases), (2) local recurrence (3 cases), or (3) metastases (4 cases). RESULTS: Of the 36 tumors, 22 (61%) showed nondiploid patterns (12 aneuploid, 10 tetraploid). All diploid tumors were benign, while all malignant cases showed nondiploid patterns (P = .0131). The differences between diploid and aneuploid tumors and between diploid and tetraploid tumors, with regard to the malignancy of the disease, were statistically significant (P = .03311 and .01976, respectively). Only one malignant tumor had a DNA index < 1.75 (P = .00259). CONCLUSION: Anomalous DNA ploidy patterns are frequent in SAP, without necessarily implying malignancy. However, diploid DNA content may be a marker of a good prognosis. The likelihood of malignancy is greater in the tetraploid and peritetraploid range.