Potential value of biliary CEA assay in early detection of colorectal adenocarcinoma liver metastases.

Elevation of the biliary CEA level in patients with liver metastases from colorectal carcinoma has been reported. The aim of this study is to determine the potential value of biliary CEA assay in the early detection of liver metastases. Biliary and serum CEA levels were determined in patients operated on for a colorectal cancer and in control groups. Among 13 patients with liver metastases from colorectal carcinomas, biliary CEA levels were markedly elevated (> 40 ng/ml) in nine, moderately elevated (5-40 ng/ml) in two and normal (arbitrarily defined as < 5 ng/ml) in two. Of 28 patients with primary colorectal carcinoma without detectable hepatic secondaries, three had marked CEA elevation in the bile, 10 had moderate CEA elevation and 15 had normal levels. Among nine patients with non-malignant hepatobiliary pathology, there was one marked biliary CEA elevation, one moderate elevation and seven normal levels. None of the 13 individuals with no identified hepatobiliary pathology had elevated biliary CEA levels. The follow-up of patients with a primary colorectal tumour, no evidence of hepatic secondaries and a biliary CEA elevation is of particular interest. If subsequent appearance of liver metastases is found in such cases, intra-operative biliary CEA assay could be considered a valuable diagnostic test. Further studies will then have to prove the possible benefit of a specific treatment for this group of patients.

Diarrea crónica refractaria y malabsorción secundaria a hipogammaglobulinemia común variable, infestación crónica por giardia lambila y gastrectomía total por adenocarcinoma gástrico: un manejo nutricional complejo

Gastric cancer is a frequent cause of cancer-related mortality in the world. Surgery is the only potentially curative therapy, although the adverse effects of surgery are common and considerable. Common variable immunodeficiency is in many cases cause of gastrointestinal system problems such as chronic diarrhea caused by infestation with giardia lamblia, nodular lymphoid hiperplasia ad loss of villi leading frequently to malapsortion and malnutrition. Nutritional deficiencies due to malapsorption (postgastrectomy and secondary to loss of villi, giardiasis and common variable inmunodeficiency) are common. We present the case of a patient with gastric cancer who underwent a gastrectomy with common variable hipogammaglobulinemia and chronic infestation by giardia lamblia, with serious diarrhea resistant to treatment and malabsorption.

Sphenoid sinus metastasis as the presenting manifestation of a prostatic adenocarcinoma: case report and overview of the literature.

Although a metastatic presentation of an occult prostatic adenocarcinoma is not uncommon, the majority of these patients present with bone metastasis affecting the axial skeleton. Cranial metastases to the paranasal sinuses are extremely rare. A 56-year-old man presented with loss of vision and numbness of the right side of the face. Computed tomography (CT) scan and cranial magnetic resonance imaging (MRI) revealed a mass invading the sphenoid sinus. The patient underwent surgery to remove the lesion, and the histopathological examination suggested metastasis of an adenocarcinoma, with positive staining to prostatic specific antigen (PSA). However, serum PSA was 4 ng/mL, and the patient did not report any lower urinary tract symptoms or bone pain. Transrectal ultrasound-guided biopsy revealed prostatic adenocarcinomas with a Gleason score of 8 [4 + 4]. The subsequent treatment consisted of radiotherapy and androgen deprivation, followed by first- and second-line chemotherapy (docetaxel and cabazitaxel) when the disease progressed. The patient achieved a good response with the last cycle of cabazitaxel and after a 5-year followup is currently alive. Cranial metastases of prostate adenocarcinoma are rare, and there is currently no standard treatment for these patients. Whenever possible, surgery combined with radiotherapy and hormonotherapy is the recommended option.

Nephron-sparing surgery for adenocarcinoma in a renal allograft.

The incidence of malignant tumors in recipients of renal allografts is higher than in the general population. Renal cell carcinoma (RCC) accounts for 4.6% of the tumors in transplanted patients; of them, only 10% are found in transplanted kidneys. Transplantectomy has always been the usual treatment. However, during the last years, nephron-sparing surgery of the allograft is more frequently done in well-selected cases, and therefore dialysis can be avoided. We report the case of a 37-year-old female patient with renal transplant, diagnosed with a 4.5 cm tumor in the lower pole of the renal allograft. The patient underwent partial nephrectomy successfully. Six years after surgery, there is no evidence of recurrence of the disease and the patient maintains an adequate renal function.

Metastatic primary adenocarcinoma of the bladder in a twenty-five years old woman.

Primary adenocarcinoma of the bladder is a rare tumor. The classification between primary vesical and urachal is debated. We present the case of a young female who presented clinicopathological features of a metastatic urachal adenocarcinoma, but the histological result revealed primary adenocarcinoma of the bladder contrary to expectancy. To the best of our knowledge this is the first reported case of a metastatic adenocarcinoma of the bladder in a 25 years old female. This case emphasizes the challenge for urologists to recognize and manage this aggressive tumor in the setting described.

Prevalence and Clinical Outcomes for Patients With ALK-Positive Resected Stage I to III Adenocarcinoma: Results From the European Thoracic Oncology Platform Lungscape Project.

PURPOSE: The prevalence of anaplastic lymphoma kinase (ALK) gene fusion (ALK positivity) in early-stage non-small-cell lung cancer (NSCLC) varies by population examined and detection method used. The Lungscape ALK project was designed to address the prevalence and prognostic impact of ALK positivity in resected lung adenocarcinoma in a primarily European population. METHODS: Analysis of ALK status was performed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) in tissue sections of 1,281 patients with adenocarcinoma in the European Thoracic Oncology Platform Lungscape iBiobank. Positive patients were matched with negative patients in a 1:2 ratio, both for IHC and for FISH testing. Testing was performed in 16 participating centers, using the same protocol after passing external quality assessment. RESULTS: Positive ALK IHC staining was present in 80 patients (prevalence of 6.2%; 95% CI, 4.9% to 7.6%). Of these, 28 patients were ALK FISH positive, corresponding to a lower bound for the prevalence of FISH positivity of 2.2%. FISH specificity was 100%, and FISH sensitivity was 35.0% (95% CI, 24.7% to 46.5%), with a sensitivity value of 81.3% (95% CI, 63.6% to 92.8%) for IHC 2+/3+ patients. The hazard of death for FISH-positive patients was lower than for IHC-negative patients (P = .022). Multivariable models, adjusted for patient, tumor, and treatment characteristics, and matched cohort analysis confirmed that ALK FISH positivity is a predictor for better overall survival (OS). CONCLUSION: In this large cohort of surgically resected lung adenocarcinomas, the prevalence of ALK positivity was 6.2% using IHC and at least 2.2% using FISH. A screening strategy based on IHC or H-score could be envisaged. ALK positivity (by either IHC or FISH) was related to better OS.

Prognostic impact of MGMT promoter methylation and MGMT and CD133 expression in colorectal adenocarcinoma.

BACKGROUND New biomarkers are needed for the prognosis of advanced colorectal cancer, which remains incurable by conventional treatments. O6-methylguanine DNA methyltransferase (MGMT) methylation and protein expression have been related to colorectal cancer treatment failure and tumor progression. Moreover, the presence in these tumors of cancer stem cells, which are characterized by CD133 expression, has been associated with chemoresistance, radioresistance, metastasis, and local recurrence. The objective of this study was to determine the prognostic value of CD133 and MGMT and their possible interaction in colorectal cancer patients. METHODS MGMT and CD133 expression was analyzed by immunohistochemistry in 123 paraffin-embedded colorectal adenocarcinoma samples, obtaining the percentage staining and intensity. MGMT promoter methylation status was obtained by using bisulfite modification and methylation-specific PCR (MSP). These values were correlated with clinical data, including overall survival (OS), disease-free survival (DFS), tumor stage, and differentiation grade. RESULTS Low MGMT expression intensity was significantly correlated with shorter OS and was a prognostic factor independently of treatment and histopathological variables. High percentage of CD133 expression was significantly correlated with shorter DFS but was not an independent factor. Patients with low-intensity MGMT expression and ≥50% CD133 expression had the poorest DFS and OS outcomes. CONCLUSIONS Our results support the hypothesis that MGMT expression may be an OS biomarker as useful as tumor stage or differentiation grade and that CD133 expression may be a predictive biomarker of DFS. Thus, MGMT and CD133 may both be useful for determining the prognosis of colorectal cancer patients and to identify those requiring more aggressive adjuvant therapies. Future studies will be necessary to determine its clinical utility.

Prognosis Relevance of Serum Cytokines in Pancreatic Cancer.

The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients' outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox's proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease.

Micropapillary pattern in lung adenocarcinoma: aspect on 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging.

We diagnosed a non-small cell lung carcinoma in a 49-year-old female patient with the histopathological diagnosis of stage IIIB mixed bronchioloalveolar and papillary adenocarcinoma with extensive micropapillary feature, which was not visualized on the preoperative multimodality imaging with positron emission tomography (PET) and computed tomography (CT). The micropapillary component characterized by a unique growth pattern with particular morphological features can be observed in all subtypes of lung adenocarcinoma. Micropapillary component is increasingly recognized as a distinct entity associated with higher aggressiveness. Even the most modern multimodality PET/CT imaging technology may fail to adequately visualize this important component with highly relevant prognostic implications. Thus, the pathologist needs to consciously look for a micropapillary component in the surgical specimen or in preoperative biopsies or cytology. This may have potential future treatment implications, as adjuvant or neoadjuvant chemotherapy may be of relevance, even in the early stages of the disease.

Lung adenocarcinoma with BRAF G469L mutation refractory to vemurafenib.

BRAF V600E is an emerging drug target in lung cancer, but the clinical significance of non-V600 BRAF mutations in lung cancer and other malignancies is less clear. Here, we report the case of a patient with metastatic lung adenocarcinoma with BRAF G469L mutation refractory to vemurafenib. We calculated a structure model of this very rare type of mutated BRAF kinase to explain the molecular mechanism of drug resistance. This information may help to develop effective targeted therapies for cancers with non-V600 BRAF mutations.

Severe postoperative complications adversely affect long-term survival after r1 resection for pancreatic head adenocarcinoma.

BACKGROUND: Survival after pancreatic head adenocarcinoma surgery is determined by tumor characteristics, resection margins, and adjuvant chemotherapy. Few studies have analyzed the long-term impact of postoperative morbidity. The aim of the present study was to assess the impact of postoperative complications on long-term survival after pancreaticoduodenectomy for cancer. METHODS: Of 294 consecutive pancreatectomies performed between January 2000 and July 2011, a total of 101 pancreatic head resections for pancreatic ductal adenocarcinoma were retrospectively analyzed. Postoperative complications were classified on a five-grade validated scale and were correlated with long-term survival. Grade IIIb to IVb complications were defined as severe. RESULTS: Postoperative mortality and morbidity were 5 and 57 %, respectively. Severe postoperative complications occurred in 16 patients (16 %). Median overall survival was 1.4 years. Significant prognostic factors of survival were the N-stage of the tumor (median survival 3.4 years for N0 vs. 1.3 years for N1, p = 0.018) and R status of the resection (median survival 1.6 years for R0 vs. 1.2 years for R1, p = 0.038). Median survival after severe postoperative complications was decreased from 1.9 to 1.2 years (p = 0.06). Median survival for N0 or N1 tumor or after R0 resection was not influenced by the occurrence and severity of complications, but patients with a R1 resection and severe complications showed a worsened median survival of 0.6 vs. 2.0 years without severe complications (p = 0.0005). CONCLUSIONS: Postoperative severe morbidity per se had no impact on long-term survival except in patients with R1 tumor resection. These results suggest that severe complications after R1 resection predict poor outcome.

Adenocarcinoma of the pancreas: Comparative single centre analysis between ductal and mucinous type.

1. Background¦Adenocarcinomas of the pancreas are exocrine tumors, originate from ductal system, including two morphologically distinct entities: the ductal adenocarcinoma and mucinous adenocarcinoma. Ductal adenocarcinoma is by far the most frequent malignant tumor in the pancreas, representing at least about 90% of all pancreas cancers. It is associated with very poor prognosis, due to the fact that actually there are no any biological markers or diagnostic tools for identification of the disease at an early stage. Most of the time the disease is extensive with vascular and nerves involvement or with metastatic spread at the time of diagnosis (1). The median survival is less than 5% at 5 years, placing it, at the fifth leading cause of death by cancer in the world (2). The mucinous form of pancreatic adenocarcinoma is less frequent, and seems to have a better prognosis with about 57% survival at 5 years (1)(3)(4).¦Each morphologic type of pancreatic adenocarcinoma is associated with particular preneoplastic lesions. Two types of preneoplastic lesions are described: firstly, pancreatic intra-epithelial neoplasia (PanIN) which affects the small and peripheral pancreatic ducts, and the intraductal papillary-mucinous neoplasm (IPMN) interested the main pancreatic ducts and its principal branches. Both of preneoplastic lesions lead by different mechanisms to the pancreatic adenocarcinoma (1)(2)(3)(4)(5)(6)(7)(8)(9)(10).¦The purpose of our study consists in a retrospective analysis of various clinical and histo-morphological parameters in order to assess a difference in survival between these two morphological types of pancreatic adenocarcinomas.¦1.2 Material and methods¦We conducted a retrospective analysis including 35 patients, (20 men and 15 women), beneficed the surgical treatment for pancreas adenocarcinoma at the Surgical Department of University Hospital in Lausanne. The patients involved in our study have been treated between 2003 and 2008, permitting at least 5-years mean follow up. For each patient the following parameters were analysed: age, gender, type of operation, type of preneoplastic lesions, TNM stage, histological grade of the tumor, vascular invasion, lymphatic and perineural invasion, resection margins, and adjuvant treatment.¦The results from these observations were included in a univariate and multivariate statistical analysis and compared with overall survival, as well as specific survival for each morphologic subtype of adenocarcinoma.¦As a low number of mucinous adenocarcinomas (n=5) was insufficient to conduct a pertinent statistical analysis, we compared the data obtained from adenocarcinomas developed on PanIN with adenocarcinomas developed on IPMN including both, ductal or mucinous types.¦1.3 Result¦Our results show that adenocarcinomas developed on pre-existing IPMN including both morphologic types (ductal and mucinous form) are associated with a better survival and prognosis than adenocarciomas developed on PanIN.¦1.4 Conclusion¦This study reflects that the most relevant parameter in survival in pancreatic adenocarcinoma seems to be the type of preneoplastic lesion. The significant difference in survival was noted between adenocarcinomas developing on PanIN as compared to adenocarcinomas developed on IPMN precursor lesions. Ductal adenocarcinomas developped on IPMN present significantly longer survival than those developed on PanIN lesions (P value= 0,01). Therefore we can suggest that the histological type of preneoplastic lesion rather than the histological type of adenocarcinoma should be the determinant prognosis factor in survival of pancreatic adenocarcinoma.

Effect of grade on disease-free survival and overall survival in FIGO stage I adenocarcinoma of the endometrium.

OBJECTIVE: To analyse the effect of differentiation on disease-free survival (DFS) and overall survival (OS) in patients with stage I adenocarcinoma of the endometrium. PATIENTS AND METHODS: From 1979 to 1995, 350 patients with FIGO stage IA-IC with well (G1), moderately (G2) or poorly (G3) differentiated tumors were treated with surgery and high dose-rate brachytherapy with or without external radiation. Median age was 65 years (39-86 years). RESULTS: The 5-year DFS was 88+/-3% for the G1 tumors, 77+/-4% for the G2 tumors, and 67+/-7% for the G3 tumors (P=0.0049). With regard to the events contributing to DFS, the 5-year cumulative percentage of local relapse was 4.6% for the G1 tumors, 9.0% for the G2 tumors, and 4.6% (P=0.027) for the G3 tumors. Cumulative percentage of metastasis was 1.4, 6.3 and 7.2% (P<0.001), respectively, whereas percentages of death were 6.0, 7.9 and 20.7% (P<0.001). The 5-year OS was 91+/-3, 83+/-4 and 76+/-7%, respectively (P=0.0018). In terms of multivariate hazard ratios (HR), the relative differences between the three differentiation groups correspond to an increase of 77% of the risk of occurrence of either of the three events considered for the DFS (HR=1.77, 95% CI [0.94-3.33]), (P=0.078) for the G2 tumors and of 163% (HR=2.63, 95% CI [1.27-5.43]), (P=0.009) for the G3 tumors with respect to the G1 tumors. The estimated relative hazards for OS are, respectively, in line with those for DFS: HR=1.51 (P=0.282) for the G2 tumors; and HR=3.37 (P=0.003) for the G3 tumors. CONCLUSION: Patients with grade 1 tumors are those least exposed to either local relapse, metastasis, or death. In contrast patients with grade 2 tumors seem to be at higher risk of metastasis, whereas patients with grade 3 tumors appear at higher risk of death. Since we have looked at the first of three competing events (local relapse, metastasis and death), this suggests that patients with grade 3 tumors probably progress to death so fast that local relapse, if any, cannot be observed.

Comprehensive molecular profiling of lung adenocarcinoma.

Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.