Endoscopic ultrasound-guided versus endoscopic retrograde cholangiopancreatography-guided biliary drainage for primary treatment of distal malignant biliary obstruction: A systematic review and meta-analysis.

OBJECTIVES: Current evidence supporting the utility of endoscopic ultrasound-guided biliary drainage (EUS-BD) as primary treatment for distal malignant biliary obstruction (MBO) is limited. We conducted a meta-analysis to compare the performance of EUS-BD and endoscopic retrograde cholangiopancreatography-guided biliary drainage (ERCP-BD) as primary palliation of distal MBO. METHODS: We searched several databases for comparative studies evaluating EUS-BD vs. ERCP-BD in primary drainage of distal MBO up to 28 February 2019. Primary outcomes were technical success and clinical success. Secondary outcomes included adverse events, stent patency, stent dysfunction, tumor in/overgrowth, reinterventions, procedure duration, and overall survival. RESULTS: Four studies involving 302 patients were qualified for the final analysis. There was no difference in technical success (risk ratio [RR] 1.00; 95% confidence interval [95% CI] 0.93-1.08), clinical success (RR 1.00; 95% CI 0.94-1.06) and total adverse events (RR 0.68; 95% CI: 0.31-1.48) between the two procedures. EUS-BD was associated with lower rates of post-procedure pancreatitis (RR 0.12; 95% CI 0.02-0.62), stent dysfunction (RR 0.54; 95% CI 0.32-0.91), and tumor in/overgrowth (RR 0.22; 95% CI 0.07-0.76). No differences were noted in reinterventions (RR 0.59; 95% CI 0.21-1.69), procedure duration (weighted mean difference -2.11; 95% CI -9.51 to 5.29), stent patency (hazard ratio [HR] 0.61; 95% CI 0.34-1.11), and overall survival (HR 1.00; 95% CI 0.66-1.51). CONCLUSIONS: With adequate endoscopy expertise, EUS-BD could show similar efficacy and safety when compared with ERCP-BD for primary palliation of distal MBO and exhibits several clinical advantages.

Radiation Therapy in the Definitive Management of Oligometastatic Prostate Cancer: The Johns Hopkins Experience.

PURPOSE: The use of radiation therapy (RT) in consolidating oligometastatic prostate cancer (OPCa) is a rapidly evolving treatment paradigm. We review our institutional experience using metastasis-directed therapy in the definitive management of men with OPCa. METHODS AND MATERIALS: Patients with OPCa treated with definitive RT were included. The Kaplan-Meier method and multivariable Cox regression analysis were performed to assess biochemical progression-free survival (bPFS) and time to next intervention. Cumulative incidence functions were used to calculate rates of local failure. Toxicity was assessed using Common Terminology Criteria for Adverse Events (version 4). RESULTS: This study analyzed 156 patients with OPCa and 354 metastatic lesions with median follow-up of 24.6 months. Of 150 patients with toxicity data, 53 (35%) experienced acute grade 1 toxicity, 8 (5%) had grade 2, and none had grade 3 toxicity. Only 13 patients (9%) had late toxicities. At 24 months, the cumulative incidence of local failure was 7.4%. Median bPFS for the entire cohort was 12.9 months and 52% at 1 year. On multivariable analysis, factors associated with prolonged bPFS were peri-RT androgen deprivation therapy (ADT), lower gross tumor volume, and hormone-sensitive (HS) OPCa. Median time to next intervention, including repeat RT, was 21.6 months. Median bPFS for men with HS prostate cancer was 17.2 months compared with 7.2 months in men with castrate-resistant OPCa (P < .0001), and cumulative incidence of local failure at 24 months was lower with HS OPCa (4.8% vs 12.1%; P = .034). We analyzed 28 men with HS OPCa treated with a course of peri-RT ADT (median, 4.3 months) with recovery of testosterone. At a median follow-up of 33.5 months, 20 patients had not developed bPFS, median bPFS had not been reached, and 24-month bPFS was 77%. CONCLUSIONS: Metastasis-directed therapy can be effective across a wide range of OPCa subtypes, but with differential efficacy. Further study is warranted to investigate the use of RT across the wide range of patients with OPCa.

Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer.

BACKGROUND: Enzalutamide, an androgen-receptor inhibitor, has been associated with improved overall survival in men with castration-resistant prostate cancer. It is not known whether adding enzalutamide to testosterone suppression, with or without early docetaxel, will improve survival in men with metastatic, hormone-sensitive prostate cancer. METHODS: In this open-label, randomized, phase 3 trial, we assigned patients to receive testosterone suppression plus either open-label enzalutamide or a standard nonsteroidal antiandrogen therapy (standard-care group). The primary end point was overall survival. Secondary end points included progression-free survival as determined by the prostate-specific antigen (PSA) level, clinical progression-free survival, and adverse events. RESULTS: A total of 1125 men underwent randomization; the median follow-up was 34 months. There were 102 deaths in the enzalutamide group and 143 deaths in the standard-care group (hazard ratio, 0.67; 95% confidence interval [CI], 0.52 to 0.86; P = 0.002). Kaplan-Meier estimates of overall survival at 3 years were 80% (based on 94 events) in the enzalutamide group and 72% (based on 130 events) in the standard-care group. Better results with enzalutamide were also seen in PSA progression-free survival (174 and 333 events, respectively; hazard ratio, 0.39; P<0.001) and in clinical progression-free survival (167 and 320 events, respectively; hazard ratio, 0.40; P<0.001). Treatment discontinuation due to adverse events was more frequent in the enzalutamide group than in the standard-care group (33 events and 14 events, respectively). Fatigue was more common in the enzalutamide group; seizures occurred in 7 patients in the enzalutamide group (1%) and in no patients in the standard-care group. CONCLUSIONS: Enzalutamide was associated with significantly longer progression-free and overall survival than standard care in men with metastatic, hormone-sensitive prostate cancer receiving testosterone suppression. The enzalutamide group had a higher incidence of seizures and other toxic effects, especially among those treated with early docetaxel. (Funded by Astellas Scientific and Medical Affairs and others; ENZAMET (ANZUP 1304) ANZCTR number, ACTRN12614000110684; ClinicalTrials.gov number, NCT02446405; and EU Clinical Trials Register number, 2014-003190-42.).

Relationship Between Visceral Metastases and Survival in Patients with Metastasis-related Spinal Cord Compression.

OBJECTIVE: To investigate whether visceral metastases have a significant impact on survival in patients with metastasis-related spinal cord compression (MSCC), and to determine the difference in prognosis between patients with and without visceral metastases. METHODS: Three institutional databases were searched to identify all patients who had undergone spinal surgery for spinal metastases between March 2002 and June 2010. Data on patient characteristics including pre- and post-operative medical conditions, were collected from medical records or by telephone follow-up. Survival data were obtained either from medical records or by searching a governmental cancer registry. RESULTS: The mean age of study patients was 59.6 ± 10.5 years (range, 18-84 years), of whom 102 were male and 67 female. The median and mean postoperative survival times were 7.0 ± 0.5 (95% CI 6.0-8.0) months and 12.6 ± 1.2 (95% CI 10.1-15.0) months, respectively, in all patients, being 5.0 ± 0.5 (95% CI 4.0-6.0) months and 10.8 ± 2.4 (95% CI 6.1-15.5) months, respectively, for patients with visceral metastases and 7.0 ± 0.8 (95% CI 5.4-8.6) months and 13.0 ± 1.4 (95%CI 10.3-15.6) months, respectively, for patients without visceral metastases (P = 0.87). These survival times did not differ significantly between groups. Multivariate Cox proportional hazard regressions showed that visceral metastases had no statistically significant association with survival (P = 0.277), whereas rate of growth of primary tumor (P = 0.003), preoperative Karnofsky performance status (KPS) (P < 0.001), change in KPS (P < 0.001), and Frankel grade (P = 0.091) were independent prognostic factors in the whole cohort (P = 0.005). Changes in KPS (P = 0.001) and major complications (P = 0.003) were significantly associated with survival in patients with visceral metastases, whereas rate of growth of primary tumor (P = 0.016), change in KPS (P = 0.001), and preoperative KPS (P < 0.001) were significantly associated with survival in patients without visceral metastases. CONCLUSIONS: Visceral metastases do not appear to predict the prognosis of patients with MSCC; thus, more aggressive surgery should be considered in patients with MSCC who have visceral metastases. Additionally, prognostic factors differ according to visceral metastases status in these patients.

Metastatic pheochromocytoma in MEN 2A: A rare association.

A 45-year-old woman was diagnosed as having multiple endocrine neoplasia type 2A in 2014. She had bilateral pheochromocytoma, medullary thyroid carcinoma and biopsy-proven cutaneous lichen amyloidosis in the interscapular area. She underwent bilateral adrenalectomy; following which, she achieved clinical and biochemical remission. She was planned for total thyroidectomy at a later date; however, she was lost to follow-up. She presented to us again in December 2016 with abdominal pain. Examination revealed hypertension with postural drop. Positron emission tomography scan showed Ga68 and fluorodeoxyglucose (FDG)-avid suprarenal, hepatic, peritoneal and mesenteric masses with abdominal lymph nodes. Twenty-four-hour urinary metanephrines/normetanephrines were elevated. Serum calcitonin was as high as it was 2-1/2 years ago. Ultrasonography-guided fine-needle aspiration cytology (FNAC) from the liver mass revealed neuroendocrine cells that did not stain for calcitonin. Hence, a diagnosis of metastatic pheochromocytoma was made. She underwent total thyroidectomy and was started on cyclophosphamide, vincristine, dacarbazine-based chemotherapy regimen.

Association of Surgical Treatment, Systemic Therapy, and Survival in Patients With Abdominal Visceral Melanoma Metastases, 1965-2014: Relevance of Surgical Cure in the Era of Modern Systemic Therapy.

Importance: Systemic therapy for metastatic melanoma has evolved rapidly during the last decade, and patient treatment has become more complex. Objective: To evaluate the survival benefit achieved through surgical resection of melanoma metastatic to the abdominal viscera in patients treated in the modern treatment environment. Design, Setting, and Participants: This retrospective review of the institutional melanoma database from the John Wayne Cancer Institute at Providence St Johns Health Center, a tertiary-level melanoma referral center, included 1623 patients with melanoma diagnosed as having potentially resectable abdominal metastases before (1969-2003) and after (2004-2014) advances in systemic therapy. Main Outcomes and Measures: Overall survival (OS). Results: Of the 1623 patients identified in the database with abdominal melanoma metastases, 1097 were men (67.6%), and the mean (SD) age was 54.6 (14.6) years. Of the patients with metastatic melanoma, 1623 (320 [19.7%] in the 2004-2014 period) had abdominal metastases, including 336 (20.7%) with metastases in the gastrointestinal tract, 697 (42.9%) in the liver, 138 (8.5%) in the adrenal glands, 38 (2.3%) in the pancreas, 109 (6.7%) in the spleen, and 305 (18.8%) with multiple sites. Median OS was superior in surgical (n = 392; 18.0 months) vs nonsurgical (n = 1231; 7.0 months) patients (P < .001). The most favorable 1-year and 2-year OS was seen after surgery for gastrointestinal tract (52% and 41%) and liver (51% and 38%) metastases, respectively. Multivariable analysis found increasing age (hazard ratio [HR], 1.01; 95% CI, 1.00-1.01; P = .02) and the presence of ulceration (HR, 1.21; 95% CI, 1.01-1.45; P = .04) were associated with a worse OS. Alternatively, treatment with metastasectomy (HR, 0.59; 95% CI, 0.46-0.74; P < .001) and metastases involving the gastrointestinal tract (HR, 0.65; 95% CI, 0.48-0.87; P = .004) were associated with a better OS. The systemic treatment era did not significantly affect outcomes (HR, 0.82; 95% CI, 0.67-1.02; P = .15). Overall, patients with gastrointestinal tract metastases undergoing complete, curative resection derived the greatest benefit, with a median OS of 64 months. Conclusions and Relevance: To our knowledge, this series is the largest single-institution experience with abdominal melanoma metastases, demonstrating that surgical resection remains an important treatment consideration even in the systemic treatment era.

Identification and survival outcomes of a cohort of patients with cancer of unknown primary in Ontario, Canada.

BACKGROUND: Cancer of unknown primary origin (CUP) is defined by the presence of pathologically identified metastatic disease without clinical or radiological evidence of a primary tumour. Our objective was to identify incident cases of CUP in Ontario, Canada, and determine the influence of histology and sites of metastases on overall survival (OS). MATERIAL AND METHODS: We used the Ontario Cancer Registry (OCR) and the Same-Day Surgery and Discharge Abstract Database (SDS/DAD) to identify patients diagnosed with CUP in Ontario between 1 January 2000, and 31 December 2005. Patient diagnostic information, including histology and survival data, was obtained from the OCR. We cross-validated CUP diagnosis and obtained additional information about metastasis through data linkage with the SDS/DAD database. OS was assessed using Cox regression models adjusting for histology and sites of metastases. RESULTS: We identified 3564 patients diagnosed with CUP. Patients without histologically confirmed disease (n = 1821) had a one-year OS of 10.9%, whereas patients with confirmed histology (n = 1743) had a one-year OS of 15.6%. The most common metastatic sites were in the respiratory or digestive systems (n = 1603), and the most common histology was adenocarcinoma (n = 939). Three-year survival rates were 3.5%, 5.3%, 41.6% and 3.6% among adenocarcinoma, unspecified carcinoma, squamous cell carcinoma and undifferentiated histology, respectively. Three-year survival rates were 40%, 2.4%, 8.0% and 4.6% among patients with metastases localised to lymph nodes, the respiratory or digestive systems, other specified sites, and unspecified sites, respectively. CONCLUSION: CUP patients in Ontario have a poor prognosis. Some subgroups may have better survival rates, such as patients with metastases localised to lymph nodes and patients with squamous cell histology.

The impact of PET/CT on the management of hepatic and extra hepatic metastases from gastrointestinal cancers.

PURPOSE: To investigate the efficacy of positron emission tomography/computed tomography (PET/CT) in detection and management of hepatic and extrahepatic metastases from gastrointestinal cancers. MATERIALS AND METHODS: Between February 2008 and July 2010, patients histopathologically diagnosed with gastrointestinal cancer and showing suspected metastasis on CT screening were subsequently evaluated with PET/CT. All patients were subgrouped according to histopathological origin and localization of the primary tumor. Localization of gastrointestinal cancers was further specified as lower gastrointestinal system (GIS), upper GIS, or hepato-pancreato-biliary (HPB). Both accuracy and impact of CT and PET/CT on patient management were retrospectively evaluated. RESULTS: One hundred and thirteen patients diagnosed histopathologically with gastrointestinal cancers were retrospectively evaluated. Seventy-nine patients had adenocarcinoma and 34 patients other gastrointestinal tumors. Forty-one patients were in the upper GIS group, 30 patients in the HPB group, and 42 patients in the lower GIS group. Evaluation the diagnostic performance of PET/CT for suspected metastasis according to histopathological origin of the tumor, revealed that the sensitivity of PET/CT - although statistically not different - was higher in adenocarcinomas than in non-adenocarcinomas (90% (95% CI, 0.78-0.96) vs. 71.4% (95% CI, 0.45-0.88), P=0.86). The specificity was not significantly different (85.7% (95% CI, 0.70-0.93) vs. 85% (95% CI, 0.63-0.94), P=1.00). In the overall patient group; CT was significantly more sensitive than PET/CT for detection of hepatic metastases (94.7% vs. 78.9%, P=0.042), whereas PET/CT was significantly more specific than CT (48% vs. 98.7%, P<0.001). In subgroup analysis, sensitivity was not significantly different (P>0.05) but specificity was significantly higher in PET/CT than CT (P<0.05). The specificity of PET/CT was highest in upper GIS (100%) and HPB (100%) subgroups. In the overall patient group; for detection of extrahepatic metastasis, the sensitivity of CT (75%) and PET/CT (87.5%) showed no significant difference (P=0.437). However, PET/CT was significantly more specific than CT (88.7% vs. 70.4%, P=0.007). In subgroup analysis, no significant difference was found between CT and PET/CT either in sensitivity or in specificity (P>0.05). The specificity of PET/CT was highest in the lower GIS subgroup (93%). The management of 45 patients (39.8%) was revised after PET/CT evaluation. CONCLUSIONS: PET/CT has a higher specificity than CT in detecting suspected hepatic and extrahepatic metastases of gastrointestinal cancers, and has an impact of nearly 40% on changing patient management strategies.

Surgical outcome prediction in patients with advanced ovarian cancer using computed tomography scans and intraoperative findings.

OBJECTIVE: This study aimed to identify features on preoperative computed tomography (CT) scans that are predictive of suboptimal primary cytoreduction and to evaluate the correlation between CT findings and intraoperative findings in advanced ovarian cancer. MATERIALS AND METHODS: We retrospectively reviewed preoperative CT scans and operative findings from patients with stage III/IV epithelial ovarian cancer who underwent primary cytoreduction between 2003 and 2006. Fourteen criteria were assessed. Clinical data were extracted from medical records. Residual tumors measuring ≥1 cm were considered suboptimal. RESULTS: We retrospectively identified 118 patients who met the study inclusion criteria. The rate of optimal cytoreduction (≤1 cm residual disease) was 40%. On preoperative CT scans, omental extension to the stomach or spleen and inguinal or pelvic lymph nodes >2 cm were predictors of suboptimal cytoreduction on univariate (p = 0.016 and p = 0.028, respectively) and multivariate analysis (p = 0.042 and p = 0.029, respectively). Involvement of both omental extension and inguinal or pelvic lymph nodes had a positive predictive value (PPV) of 100%, a specificity of 100%, and an accuracy of 45.8% in predicting suboptimal cytoreduction. We correlated the preoperative CT findings with the intraoperative findings. There were significant correlations between CT and intraoperative findings of omental extension (p = 0.007), inguinal or pelvic lymph nodes >2 cm (p < 0.001), and large bowel mesentery implants >2 cm (p = 0.001). CONCLUSION: The combination of omental extension to the stomach or spleen and involvement of inguinal or pelvic lymph nodes in preoperative CT scans is considered predictive of suboptimal cytoreduction. These patients may be more appropriately treated with neoadjuvant chemotherapy followed by surgical cytoreduction.

Co-overexpression of HER2/HER3 is a predictor of impaired survival in breast cancer patients.

BACKGROUND: Recently, HER3-expression was postulated as independent risk factor for metastatic spread. Therefore, we investigated the role of HER3 expression as prognostic marker in metastatic breast cancer patients. METHODS: Patients of different breast cancer subtypes diagnosed with metastatic disease (visceral and/or brain metastases) were identified from a breast cancer database. Tissue samples of the respective primary tumors were retrieved, and immunohistochemical staining for estrogen-receptor, progesterone-receptor, HER2, and HER3 was performed. In HER2 equivocal and selected HER3 positive cases, subsequent fluorescent in situ hybridization (FISH) analysis was performed. RESULTS: Tissue specimens of 110 patients were available for this analysis. 21% had strong, complete, membranous HER3 staining of at least 10% of all tumor cells; HER3 protein expression was not associated with HER3 gene amplification. HER2/HER3 co-overexpression was observed in 12/110 (11%) specimens and HER3-overexpression showed a statistically significant association with HER2-overexpression (p = 0.02). No correlation was observed for HER3-overexpression and overall survival (OS), time to diagnosis of brain metastases, and incidence of brain metastases. Still, in patients with HER3 overexpression, a higher rate of 'brain only' metastatic behavior was observed (p = 0.042). In the HER2-positive subgroup, HER3-overexpression was significantly associated with shorter OS from diagnosis of metastatic disease (median 17 vs. 35 months; p = 0.04; log rank test). CONCLUSIONS: HER2/HER3 co-overexpression is significantly associated with impaired OS from diagnosis of metastatic disease in patients with HER2-positive metastatic breast cancer. Co-inhibition of HER2 and HER3 or the inhibition of HER2/HER3 hetero-dimerization may improve clinical outcome in this subgroup.

Patterns of visceral metastasis in cutaneous melanoma: a descriptive study.

BACKGROUND AND OBJECTIVES: Some types of cancer tend to spread to certain organs. In the case of melanoma, uveal melanoma spreads almost exclusively to the liver, while cutaneous melanoma spreads to the liver and other organs. Although important advances have been made in our understanding of the molecular mechanisms underlying melanoma, few recent studies have focused on the patterns of visceral metastasis in cutaneous melanoma. The aim of this study was to retrospectively investigate whether clinicopathologic variants of cutaneous melanoma and primary tumor site might be associated with pattern and time of onset of metastasis to visceral sites, including the central nervous system (CNS). MATERIALS AND METHODS: We included patients diagnosed with cutaneous melanoma between 1988 and 2009 with at least 2 years' follow-up. RESULTS: Of the 1083 patients studied, 92 developed visceral metastasis. The CNS was affected in 21 cases, the lungs in 24, the liver in 17, the digestive tract in 7, and multiple organs simultaneously in 23. Metastasis to the lungs, the liver, and the digestive tract occurred within 5 years in most cases, while metastasis to the CNS and multiple organs occurred later (>5 years in 38% and 43% of cases, respectively). CONCLUSIONS: Unlike uveal melanoma, cutaneous melanoma spreads to different organs without any particular predilection. We observed no significant associations between the site of visceral metastasis and either clinicopathologic variant or location of the primary tumor. Metastasis occurred within 5 years of diagnosis in most cases, but it can occur after 10 years.

Comparison of EORTC criteria and PERCIST for PET/CT response evaluation of patients with metastatic colorectal cancer treated with irinotecan and cetuximab.

UNLABELLED: The study aim was to compare European Organization for Research and Treatment of Cancer (EORTC) criteria with PET Response Criteria in Solid Tumors (PERCIST) for response evaluation of patients with metastatic colorectal cancer treated with a combination of the chemotherapeutic drug irinotecan and the monoclonal antibody cetuximab. METHODS: From 2006 to 2009, patients with metastatic colorectal cancer were prospectively included in a phase II trial evaluating the combination of irinotecan and cetuximab every second week, as third-line treatment. (18)F-FDG PET/CT was performed between 1 and 14 d before the first treatment and after every fourth treatment cycle until progression was identified by CT with Response Evaluation Criteria in Solid Tumors (RECIST). Response evaluation with (18)F-FDG PET/CT was retrospectively performed according to both EORTC criteria and PERCIST, classifying the patients into 4 response categories: complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD). Individual best overall metabolic response (BOmR) was registered with both sets of criteria, as well as survival within response categories, and compared. RESULTS: A total of 61 patients and 203 PET/CT scans were eligible for response evaluation. With EORTC criteria, 38 had PMR, 16 had SMD, and 7 had PMD as their BOmR. With PERCIST, 34 had PMR, 20 had SMD, and 7 had PMD as their BOmR. None of the patients had CMR. There was agreement between EORTC criteria and PERCIST in 87% of the patients, and the corresponding κ-coefficient was 0.76. Disagreements were confined to PMR and SMD. Median overall survival (OS) in months with EORTC criteria was 14.2 in the PMR group and 7.2 in the combined SMD + PMD group. With PERCIST, it was 14.5 in the PMR group and 7.9 in the SMD + PMD group. CONCLUSION: Response evaluation with EORTC criteria and PERCIST gave similar responses and OS outcomes with good agreement on BOmR (κ-coefficient, 0.76) and similar significant differences in median OS between response groups. Compared with EORTC criteria, we find PERCIST unambiguous because of clear definitions and therefore more straightforward to use.

Comparison of survival of patients with metastases from known versus unknown primaries: survival in metastatic cancer.

BACKGROUND: Cancer of unknown primary site (CUP) is considered an aggressive metastatic disease but whether the prognosis differs from metastatic cancers of known primary site is not known. Such data may give insight into the biology of CUP and the metastatic process in general. METHODS: 6,745 cancer patients, with primary metastatic cancer at diagnosis, were identified from the Swedish Cancer Registry, and were compared with 2,881 patients with CUP. Patients were diagnosed and died between 2002 and 2008. The influence of the primary site, known or unknown, on survival in patients with metastases at specific locations was investigated. Hazard ratios (HRs) of death were estimated for several sites of metastasis, where patients with known primary sites were compared with CUP patients. RESULTS: Overall, patients with metastatic cancers with known primary sites had decreased hazards of death compared to CUP patients (HR = 0.69 [95% CI = 0.66-0.72]). The exceptions were cancer of the pancreas (1.71 [1.54-1.90]), liver (1.58 [1.36-1.85]), and stomach (1.16 [1.02-1.31]). For individual metastatic sites, patients with liver or bone metastases of known origin had better survival than those with CUP of the liver and bone. Patients with liver metastases of pancreatic origin had an increased risk of death compared with patients with CUP of the liver (1.25 [1.06-1.46]). The median survival time of CUP patients was three months. CONCLUSIONS: Patients with CUP have poorer survival than patients with known primaries, except those with brain and respiratory system metastases. Of CUP sites, liver metastases had the worst prognosis. Survival in CUP was comparable to that in metastatic lung cancer. The aggressive behavior of CUP may be due to initial immunosuppression and immunoediting which may allow accumulation of mutations. Upon escape from the suppressed state an unstoppable tumor spread ensues. These novel data on the epidemiology of the metastatic process at the population level demonstrated large survival differences in organ defined metastases depending on the original cancer.

Endoscopic ultrasound, endoscopic sonoelastography, and strain ratio evaluation of lymph nodes with histology as gold standard.

BACKGROUND AND STUDY AIMS: Accurate lymph node staging is essential for the selection of an optimal treatment in patients with upper gastrointestinal cancer. Endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) are considered to be the most accurate method for locoregional staging. Endoscopic sonoelastography (ESE) assesses the elasticity of lymph nodes and has been used to differentiate lymph nodes with promising results. The aim of this study was to evaluate the use of EUS, EUS - FNA, ESE, and ESE-strain ratio using histology as the gold standard. PATIENTS AND METHODS: Patients with upper gastrointestinal cancer who were referred for EUS examination were enrolled if surgical treatment was planned and the patient had a lymph node that was accessible for EUS - FNA and EUS-guided fine-needle marking (FNM). The lymph node was classified using EUS, ESE, and ESE-strain ratio. Finally, EUS - FNA and EUS - FNM were performed. The marked lymph node was isolated during surgery for histological examination. RESULTS: The marked lymph node was isolated for separate histological examination in 56 patients, of whom 22 (39 %) had malignant lymph nodes and 34 (61 %) had benign lymph nodes. There were no complications of EUS - FNM. The sensitivity of EUS for differentiation between malignant and benign lymph nodes was 86 % compared with 55 % - 59 % for the different ESE modalities. The specificity of EUS was 71 % compared with 82 % - 85 % using ESE modalities. CONCLUSION: The use of the EUS - FNM technique enabled the identification of a specific lymph node and thereby the use of histology as gold standard. ESE and ESE-strain ratio were no better than standard EUS in differentiating between malignant and benign lymph nodes in patients with resectable upper gastrointestinal cancer.

Kidney transplant recipients with cutaneous squamous cell carcinoma have an increased risk of internal malignancy.

This study aimed to investigate whether the occurrence of cutaneous squamous cell carcinomas (SCCs) is associated with an increased risk of internal malignancies (IMs) in kidney transplant recipients (KTRs). In a cohort study, all patients receiving kidney transplantation in Leiden, the Netherlands, between 1966 and 2006 were followed up. All malignancies that had developed between 1966 and 2007 were recorded. Time-dependent Cox regression analyses were used to calculate the association between the development of cutaneous SCCs and IMs. The incidence of IMs in the KTRs after transplantation was also compared with the general Dutch population by calculating standardized morbidity ratios (SMRs) and was matched for age, sex, and time period in which the malignancy had occurred. Among 1,800 KTRs, 176 (9.8%) developed cutaneous SCCs and 142 (7.9%) developed IMs after transplantation. In patients with prior cutaneous SCCs, the adjusted risk to develop IMs was 3.0 (1.9; 4.7). In KTRs without cutaneous SCCs, the risk of IM compared with the general population was hardly increased. KTRs with cutaneous SCCs have an increased risk to develop IMs, and this information can be used to identify KTRs who are at an increased risk for IMs.

Specificity and sensitivity of 99mTc-EDDA/HYNIC-Tyr³-octreotide (99mTc-TOC) for imaging neuroendocrine tumors.

OBJECTIVES: Gastroenteropancreatic neuroendocrine tumors (NETs) are cancers originating from neuroendocrine organs such as the pancreas, pituitary, thyroid, and adrenal glands and tumors arising from the diffuse neuroendocrine cells that are widely distributed throughout the body. NETs express somatostatin (SS) and contain a high density of SS receptors; therefore, they can be specifically targeted with SS-based radiopharmaceuticals. The aim of this research was to determine the validity in terms of specificity, sensitivity, and the agreement beyond chance with the biopsy (gold standard) of the 99mTc-EDDA-HYNIC-Tyr³octreotide (99mTc-TOC) to image and localize NETs and their metastases. MATERIALS AND METHODS: Freeze-dried kits containing 0.0125 mg HYNIC-octreotide and co-ligands were easily labeled and quality controlled within the hospital radiopharmacy. Fifty-six consecutive Mexican patients with a previous presumptive diagnosis of NETs underwent several clinical and laboratory studies and were referred to the Nuclear Medicine Department for a routine scan with 99mTc-TOC. The patients were injected with 500-600 MBq 99mTc-TOC, and whole-body images were obtained 2 h later with a SPECT or a SPECT/CT camera. Two nuclear medicine physicians observed the images and classified them as 17 negative and 39 positive. After correlating the image of each patient with our 'gold standard' (biopsy, clinical history, morphological images, and tumor marker assays), the 99mTc-TOC images were classified by the same two physicians as 12 true negatives, five false negatives, 38 true positives and one false positive. RESULTS: The validity of 99mTc-TOC in terms of relative frequencies with corresponding 95% confidence intervals were as follows: 92.3% (64-100%) specificity; 88.4% (78-97%) sensitivity; and the agreement beyond chance was 73% (60-84%). The positive predictive value was 97.4% (87-100%); the negative predicted value was 70.6% (48-93%); the accuracy was 89.3% (89-97%); and the prevalence was 76.8% (64-87%). CONCLUSION: Because of these high values, we strongly recommend scintigraphy with the Mexican-produced 99mTc-TOC for the localization of NETs and their metastases, and we conclude that it is a good tool for detecting neuroendocrine disease in a Mexican population.

Acoustic radiation force impulse elastography in distinguishing hepatic haemangiomata from metastases: preliminary observations.

OBJECTIVE: The increasing quality of diagnostic ultrasound has resulted in the detection of greater numbers of potentially benign hepatic lesions. Current radiological practice requires contrast enhanced ultrasound, CT or MRI to confirm the diagnosis. Acoustic radiation force impulse (ARFI) elastography is an imaging technique measuring the elasticity of biological tissues. Recent technical advances in ultrasound have made it possible to generate shear waves, whose velocity in the liver is proportional to the degree of hepatic elasticity. METHODS: This shear wave velocity (SWV) may be used as a marker for both focal and diffuse liver pathology.We used this technique to examine patients with normal livers and those with haemangiomata and metastases. RESULTS: Patients with normal ultrasound examinations and normal liver enzymes, n = 99, had SWVs of 1.24 ± 0.23 m s(-1) (mean ± standard deviation) independent of site of measurement, age or gender. Results of SWV measurements in haemangiomata, n = 35, produced values of the same order, 1.35 ± 0.48 m s(-1). In contrast, patients with metastases, n = 10, had SWVs of 4.23 ± 0.59 m s(-1). With a cut-off value of 2.5 m s(-1), the sensitivity and specificity for haemangiomata were 97.1% and 100%, respectively, with an area under the curve of 0.999. CONCLUSION: ARFI elastography with SWV measurements is a promising new technique which could replace invasive investigations for benign hepatic lesions.