Presence Of Paraneoplastic Syndromes Research Articles

Incidence and clinical relevance of paraneoplastic syndromes in patients with renal cell carcinoma.

Paraneoplastic syndromes (PNS) are defined as the signs and symptoms attributed to cytokines or hormones released from a tumor or a patient's immune system. PNS have been reported with many cancers for decades and data supporting their relevance in renal cell carcinoma (RCC) are largely historical. The widespread use of electronic medical record (EMR) systems provides a more robust method to capture data. The objective of this study was to establish contemporary data regarding the incidence and relevance of PNS in patients undergoing nephrectomy for suspected RCC. In this retrospective single-institution study, 851 patients undergoing nephrectomy for suspected RCC between 2011 and 2018 were assessed for the presence or absence of PNS as defined by laboratory abnormalities. Factors associated with PNS and with all-cause mortality were examined. The incidence of PNS was 33.1% among 851 patients prior to nephrectomy. The most prevalent PNS were anemia (22.4%), thrombocytosis (7.5%), and elevated C-reactive protein (CRP) (7.4%). PNS were more common in women (39.2% vs. 29.4%, p = 0.0032) and higher stage RCC (31.1% of stage I vs. 54.2% of stage IV, p = 0.0036). Factors associated with the presence of PNS in multivariable analysis included female gender, high comorbidity, and stage IV RCC. Prenephrectomy PNS were associated with poorer survival in multivariable analysis (HR: 2.12, p = 0.0002). Resolution of PNS occurred in 52.1% of patients after nephrectomy, including 55.2% with stage I to III and 38.5% with stage IV RCC (p = 0.10). Using EMR data, laboratory evidence of PNS was present in one-third of a contemporary cohort of patients undergoing nephrectomy, with >50% of PNS resolving after surgery. Consistent with prior reports, PNS are more common in higher-stage RCC and are associated with poorer survival in RCC patients.

Outcomes and Histological Variations of Neuroblastoma and Ganglioneuroblastoma with Paraneoplastic Syndromes.

Neuroblastomas are the most common extracranial solid malignancy in children with variable manifestations and complications depending on the presence of paraneoplastic syndromes. We performed a single institution retrospective cohort study of all patients less than 18years old diagnosed with neuroblastoma or ganglioneuroblastoma between January 2002 and July 2022. Patients were identified through the pathology and cancer registry and cross-referenced with pediatric records. Patient demographics, clinical presentation, treatment, and outcomes were collected. A univariate descriptive analysis of the collected data was conducted. In our study period, 130 children were diagnosed with neuroblastoma, and 15 were diagnosed with ganglioneuroblastoma. There were 12 children with a paraneoplastic syndrome identified, 8 with NBL and 4 with ganglioneuroblastoma (GNBL). The average age at diagnosis was 22months. All but 1 underwent resection prior to treatment of paraneoplastic syndrome, and 4 children required neoadjuvant therapy. Neurological complications were the most common with 10 children (83%). The average time from symptom onset to diagnosis was 0.7months. Eight children had complete resolution of their symptoms after treatment and resection, 2 children recently started treatment within a year, 1 had partial resolution, and 1 died during treatment. The presence of tumor-infiltrating lymphocytes occurred in 4 children with neurologic paraneoplastic syndromes. Six children had neuropil rich tumors. The histological profile of paraneoplastic syndromes of neuroblastoma and ganglioneuroblastoma and their treatment across a single institution can be highly variable. The presence of tumor-infiltrating lymphocytes and neuropil may have an impact on paraneoplastic pathology.

Markers for internal neoplasia in the horse

The diagnosis of internal neoplasia in horses is challenging. Increased production of hormones physiologic for adult animals (e.g., adrenocorticotropin, norepinephrine, and erythropoietin) or typical for the foetal phase (alpha-fetoprotein, anti-Müllerian hormone, and parathyroid-hormone-related protein) might aid in tumour diagnostics. Thymidine kinase-1 and alkaline phosphatase are examples of intracellular enzymes, whose activity in the blood may increase in some neoplasia cases. Furthermore, inappropriate production of abnormal monoclonal or autologous antibodies can accompany lymphoma and multiple myeloma. Many of those tumour markers lead to clinical or laboratory changes, called paraneoplastic syndromes, such as hypercalcaemia and erythrocytosis. The interpretation of the results of the tumour marker measurements in horses is complicated due to many factors affecting the markers' concentration or activity (e.g., young age, pregnancy, and inflammation) and other diseases triggering the same changes. Moreover, the presence of paraneoplastic syndromes is inconsistent, which leads to low sensitivity of those substances as tumour markers. In conclusion, screening for neoplasia in horses is not recommended. The measurement of tumour markers should be performed only in risk groups with suspicious clinical or laboratory findings, and the results should be interpreted with caution. It is advisable to add inflammatory markers to the tumour profile or repeat the measurements.

CD47 expression patterns in thymic epithelial tumors.

8586 Background: Blockade of CD47, an immunoglobulin overexpressed on solid tumor cells that inhibits macrophage phagocytosis, is a promising anti-cancer immunotherapy which has not yet been explored in thymic epithelial tumors (TETs). TETs, including thymomas and thymic carcinomas, are rare tumors with limited immunotherapy treatment options due to the high rates of immune-related adverse effects observed with PD-1/PD-L1 checkpoint inhibitors. This study aimed to examine CD47 protein expression in TETs. Methods: A clinically annotated tissue microarray of 67 TETs consisting of 64 thymomas and 3 thymic carcinomas, as well as 14 thymic controls were included. Each sample with an average of 3 cores was stained for CD47 epithelial expression (rabbit monoclonal antibody SP279, Abcam, USA). Samples were scored for intensity as follows: 0 = none, 1 = weak, 2 = moderate, and 3 = strong. An H-score, defined as intensity x percentage of tumor involved, was also assigned and ranged from 0 to 300. Samples with an intensity score of < 2 or an H-score of < 150 were categorized as CD47low, while the rest as CD47high. Multivariate linear regression analysis accounted for WHO subtype, stage, resection status and presence of paraneoplastic syndrome (Prism 9, Graphpad). Results: Compared to normal thymic tissue, TETs were more frequently CD47 positive and had significantly higher levels of CD47 expression. CD47 was present in 91% of TETs, compared to 64.3% of normal thymus. Importantly, the level of expression was significantly higher in TETs by 16-fold (mean H-score 75.0 vs 4.6, p = 0.003). Among tumors, univariate analyses showed that higher CD47 expression was correlated with a lower stage (p = 0.032) and more complete resection (p = 0.058). A multivariate analysis accounting for these factors showed that CD47 expression by both H-score and intensity were each highly correlated with WHO histology subtype (p = 0.0005; p = 0.0017 respectively) with lower grade subtypes more frequently found in CD47high tumors. The most frequent subtype in CD47high, when compared to CD47low tumors, was AB (61.5% vs 13.7%) and the least frequent was B2 (0% vs 37.3%). Tumors with the highest grade (subtype C, thymic carcinomas) were exclusively CD47low. CD47high tumors were associated with an increased incidence of paraneoplastic syndromes (52.4% vs 12.0%, p = 0.0014). Conclusions: CD47 expression was found in the vast majority of TETs, and in significantly higher levels than normal thymic tissue. Among tumors, those with higher CD47 expression tended to have lower grade and stage, as well as higher frequency of paraneoplastic syndromes. This study is the first to examine CD47 expression in TETs. Given the prevalent expression of CD47 found in TETs and current available CD47 targeted agents, this study lends support for further investigation of this novel therapeutic approach.

Hypercalcemia in bitches with malignant mammary neoplasms

Malignant hypercalcemia is a paraneoplastic syndrome. It has been detected in several types of malignant tumours in dogs, such as lymphomas, and also in mammary neoplasms, without the exact determination of the mechanisms involved in its occurrence as well as its incidence. In this study, 100 bitches with mammary malignant neoplasia, diagnosed by histopathological analysis, were submitted to clinical evaluation for disease staging, haematological evaluation, serum biochemistry, including renal function tests, hepatic and total calcium serum levels and ionized fraction. These parameters were analyzed at the time of the initial attendance and 30 days after the treatment. The most frequent histological pattern was carcinoma in mixed tumors (26%). In 52% of the diseased dogs, hypercalcemia was observed by means of ionized calcium dosing, which was not verified by means of total calcium dosing, where only 4% presented hypercalcemia. No correlation was found between hypercalcemia and the histological pattern of the neoplasms. However, the correlation was verified between hypercalcemia and more advanced stages of the disease, mainly from stage III, suggesting that the detection of hypercalcemia may be correlated with worse prognosis, showing the importance of the research concerning the presence of paraneoplastic syndromes in bitches with mammary neoplasms.

Canine Thymoma Associated to Myasthenia Gravis

Background: Thymomas are epithelial neoplasms of the thymus, although lymphocyte infiltration is common. Histological features are not sufficient to define its biological behaviour, which is dependent of clinical criteria of invasiveness and resectability. Myasthenia gravis may happen as a paraneoplastic syndrome in up to 47% of canine thymomas. Thisarticle aims at reporting a case of thymoma associated with myasthenia gravis in a dog, emphasizing the morphological, phenotypical and therapeutical aspects.Case: A 7-year-old, male Labrador, was presented with a history of acute dyspnea and exercise intolerance. The physical examination revealed a “red-brick” mucousa, tachycardia and cardiac and pulmonar hypofonese. Chest radiographs revealed an area of increased radiopacity in the cranial mediastinum without a plane of separation to the heart. The eccodopplercardiogram exam identified a poorly delimited mass adjacent to the base of the heart, measuring 9.5x6.8cm. Computed tomographydemonstrated it as an expansive neoformation (9.5x6.5x7.8cm). Mass was removed through intercostal thoracotomy and the removed tissue was submitted to histopathology with a diagnosis compatible with type AB thymoma (mixed). Immunohistochemistry was positive for AE1/AE3 citokeratin in 90% of epithelial cells, confirming tumour origin. Tumour infiltrating lymphocytes were positive for CD79a (70%) and CD3 (20%). The proliferation index (Ki-67 imunolabeling) was 60%. About 45 days after surgery the patient was presented with generalized muscle weakness and regurgitation, with confirmed megaesophagus on chest X-ray. Treatment with pyridostigmine was initiated because of suspected myasthenia gravis, and complete remission of the neurological signs occurred within a month. A chemotherapeutic protocol with carboplatin wasthen instituted. After four sessions, a new thoracic radiograph revealed tumour recurrence in the cranial mediastinum. Therefore, metronomic chemotherapy was started sequentially with oral chlorambucil and firocoxib. Patient remained well for nine months when regurgitation and muscle weakness re-initiated, even with pyridostigmine treatment. New chestX-ray demonstrated increased tumour mass and the owner decided for euthanasia, resulting in a survival time of 368 days.Discussion: The prognosis of the thymoma depends on the histological type, clinical staging and presence of paraneoplastic syndromes. Due to the heterogeneity of the cases, there are not enough studies available to compare the animals submitted to different therapeutic modalities. In humans, when possible, and in the absence of metastases, complete surgical resection is the standard treatment followed by chemotherapy and/or adjuvant radiotherapy. In dogs, surgical resection of thymomasshould be considered, despite the invasiveness detected in imaging studies. The presence of paraneoplastic syndromes, such as myasthenia gravis, are commonly associated with worse prognosis, however, as evidenced in this case, pyridostigmine was useful in maintaining the neuromuscular function and patient´s quality of life, along with surgery and adjuvant chemotherapy, which probably contributed to the increase of the expectation of life. Further studies are necessary to evaluate the efficacy of adjuvant chemotherapy in maximum tolerated and metronomic dosage, for thymic neoplasms in dogs.Keywords: thymus, neoplasia, paraneoplastic syndrome, carboplatin, cyclophosphamide.

PC 02.01 Thoracic Radiation - YES

Small cell lung cancer (SCLC) accounts for 15%–20% of all lung cancers, and the overwhelming majority (>95%) are associated with tobacco exposure. The incidence of all types of lung cancer, including SCLC, has been declining in the United States with the onset of tobacco smoking cessation programs, although this trend took nearly 20 years to become evident among men. Overall survival (OS) rates for patients with lung cancer have also increased by about 5% since the advent of low-dose spiral computed tomography (CT) scanning to detect early lung cancer. The prognosis for patients with SCLC continues to be poor but has improved with the advent of smoking cessation campaigns, more effective chemotherapy agents and radiation planning and delivery techniques, and the use of prophylactic cranial irradiation (PCI) for those who experience a complete response to therapy. Consolidation with chest radiotherapy has improved OS among patients with extensive-stage SCLC who achieved a complete response to chemotherapy. SCLC often presents as bulky symptomatic masses, and mediastinal involvement is common with or without pleural effusion and extrathoracic disease. Extrathoracic spread (i.e., extensive-stage disease) is also quite common, being present in 80%-85% of cases at diagnosis. Brain metastases are present in approximately 20% of patients at diagnosis; roughly half of these metastases are symptomatic and the other half are detected by imaging. Predictors of poor prognosis include poor performance status, older age, and being male. The pathologic subtypes of the disease (small cell carcinoma and combined small cell carcinoma) all carry a similarly poor prognosis. Current guidelines of the U.S. National Comprehensive Cancer Network recommend the use of positron emission tomography (PET), CT scanning, or fused PET/CT scanning of the chest, liver, adrenals, bone, and other areas of concern in the diagnosis and staging of SCLC (NCCN guideline-SCLC 2017). Thoracic radiotherapy has also become important for improving OS among patients with SCLC who achieved a complete response to chemotherapy. In one prospectively randomized study of 498 patients with extensive-stage SCLC (WHO performance status score 0-2) who achieved complete response to chemotherapy, patients who received consolidation thoracic radiotherapy (30 Gy in 10 fractions) had significantly better 2-year OS rates than did those who did not receive thoracic radiotherapy (13% vs. 3%, P=0.004). Thoracic radiotherapy further improved thoracic-only failure rates (19.8% vs. 46% without, P=0.001) (Slotman B et al, Lancet Oncol 2015;385:36-42). However, many patients with extensive-stage SCLC do not respond to the standard etoposide/cisplatin chemotherapy (Fig 1). Those patients may need to receive molecular-targeted therapies or immunotherapy with the consolidating thoracic radiotherapy. Several histologic and immunohistochemical markers have been evaluated for diagnosing or monitoring treatment response in SCLC, including transcription thyroid factor-1 (positive in >85% of SCLC cases); cytokeratin 7; deletions in chromosome 3; Leu-7; chromogranin A; synaptophysin; myc amplification; and p53 mutations (present in ∼75% of cases). Deletions in tumor-suppressor genes are also relatively common and include fragile histidine triad (FHIT) (80%); RAS effector homologue (RASSF1) (>90%); TP53 (>75%); retinoblastoma-1 (RB1) (>90%); and retinoic acid receptor-beta (72%). However, to date no biomarkers have been validated for use in diagnosing SCLC. Moreover, mutations that are often present in non-small cell lung cancer (such as epidermal growth factor receptor [EGFR] mutations and anaplastic lymphoma kinase [ALK]) are rare in SCLC. Several clinicopathologic features have been linked with worse prognosis, including poor performance status, significant weight loss, high lactate dehydrogenase levels, large numbers of metastatic sites, and the presence of paraneoplastic syndromes. Because SCLC has the among the highest rates of somatic driver mutations, and because more than 95% of patients with SCLC are former or current smokers, immunotherapy seems a reasonable approach, as high mutation burdens correlate with good response to chemoradiotherapy and sensitivity to immunomodulators (Peifer M et al., Nat Genet 2012;44(10):1104-10). At MD Anderson Cancer Center, an ongoing phase I/II study of patients with extensive-stage SCLC has been proposed to the NRG as a prospective randomized study (PI J Welsh) (Fig 2). Use of thoracic radiotherapy to consolidate a site at which SCLC is quite likely to recur is reasonable, given that recurrence considerably reduces quality of their life as well as OS. In summary, in most cases SCLC presents as extensive-stage disease, for which outcomes are very poor. Consolidation with thoracic radiotherapy for patients who achieve a complete response to chemotherapy can improve 2-year OS rates. However, less toxic and more effective systemic treatment is also required to derive the greatest benefit from consolidation thoracic radiotherapy. thoracic radiotherapy extensive small-cell lung cancer, immunotherapyFig 2View Large Image Figure ViewerDownload Hi-res image Download (PPT)

P2.04-013 Prognosis Factors and Survival Analysis in Thymic Epithelial Tumors: Topic: Thymic Malignancies Clinical and Translational

Thymic epithelial tumors (TET) include thymomas (T) and thymic carcinomas (TC). TET are rare malignant tumors usually associated with paraneoplastic syndromes (PNPS). The objective of the study is to describe our experience and to analyze the prognostic factors. Retrospective analysis of the clinical and pathological characteristics of 42 patients (pts) diagnosed with TET in our institution from 1990 to 2016. We analyzed the outcomes in terms of progression-free survival (PFS) and overall survival (OS) and their association with clinical factors: age, perfomance status, presence of PNPS, TNM staging, WHO classification, complete resection and treatment. Kaplan Meier method and Cox regression were used. Mean age: 55 years (27-86). 19 (45.2%): women. First treatment: surgery in 34 pts (81%) and platinum based chemotherapy in 6 pts (14%). 2 pts (5%) were untreated. 14 pts (41%) received postoperative radiotherapy. WHO classification: 6 pts (14.3%) type A, 12 (28.6%) AB, 3 (7.1%) B1, 7 (16.7%) B2, 7 (16.7%) B3 and 7 (16.7%) C. TNM staging: 20 pts (48.8%) stage I,4 (9.8%) stage II, 6 (14.6%) stage III and 9 (22%) stage IV. 25 ptss (59.5%) had PNPS at diagnosis: 21 (50%) myasthenia gravis, 2 (4.75%) aplastic anemia and 2 (4.75%) others. Table 1 shows OS and PFS according to WHO classification:Tabled 1WHO CWHO: A, AB, B1, B2, B3p valueHR (univariate)p valuePFS (months)(95%CI)21.2 (5.8-36.7)89.3(69.1-109.6)0.033.120.04OS (months)(95%CI)66.5 (0-157.5)296 (98.6-493.3)<0.00120.20.007 Open table in a new tab The presence of PNPS were associated with better OS than those without PNPS (236m, 95%CI 147-448m vs 66.5m, 95% CI 1.3-131.7m, p=0.006, HR 0.76, p=0.026 ) and also with early diagnosis (stage I for pts with PNPS 56% vs 42% without PNPS). In the multivariate analysis, only C type remained statistically significant (HR:13.5, p=0.024). No differences were found when using TNM classification or complete resection. Patients with C type TET had worst prognosis. The presence of a PNPS is associated with better OS possibly due to and early diagnosis.

Differentiation of epithelial ovarian cancer subtypes by use of imaging and clinical data: a detailed analysis.

BackgroundPrimary epithelial ovarian carcinoma is sub-classified into serous, mucinous, endometrioid and clear cell subtypes. Neoadjuvant chemotherapy has become an alternative treatment option past several years, as serous carcinoma, the most common subtype, is known as chemotherapy-sensitive tumor. On the other hand, mucinous and clear cell carcinoma are known as chemotherapy-resistive. Therefore, it may be meaningful to estimate subtype of ovarian carcinoma using imaging modality. The purpose of this study is to study whether CT or MRI can determine the subtypes of epithelial ovarian cancers.MethodsThe imaging and clinical findings obtained from 125 consecutive patients with primary ovarian carcinoma were retrospectively analyzed. Forty-four of the patients had serous carcinoma; 13, mucinous carcinoma; 53, clear cell carcinoma; and 15, endometrioid carcinoma. We studied the bilateralism, morphological type, tumor diameter, solid portion ratio, relative signal intensity on T2WI and DWI, contrast ratio, and endometriosis on MRI and the calcification, peritoneal dissemination and lymph node metastasis, clinical staging, and thromboembolism on CT. We also studied the tumor markers and serum calcium concentrations. Each parameter was statistically analyzed by univariate and multivariate analyses.ResultsSerous carcinoma showed a significantly higher incidence of bilateral disease, smaller tumor size, higher signal intensity on DWI, and less frequent hypercalcemia. The CA19-9 level was significantly higher in mucinous carcinoma, in which most of the tumors appeared as multilocular cystic masses. Clear cell carcinoma appeared as unilateral disease with a larger solid portion and hypercalcemia in younger patients. Endometrioid carcinoma only showed a lower incidence of intraperitoneal dissemination.ConclusionsCT and MRI combined with clinical data especially tumor markers and presence of paraneoplastic syndrome could partly predict epithelial ovarian cancer subtypes.

Perioperative Mortality and Long‐Term Survival in 80 Dogs and 32 Cats Undergoing Excision of Thymic Epithelial Tumors

To examine perioperative mortality, long-term survival, causes of death, and prognostic factors for dogs and cats undergoing surgical excision of thymic epithelial tumors (TETs). Multi-institutional case series. Eighty dogs and 32 cats. Follow-up information was obtained for dogs and cats that underwent surgical excision of a TET between 2001 and 2012. Perioperative mortality was 20% in dogs and 22% in cats. No independent risk factors for perioperative mortality were identified. The estimated median survival time for all dogs was 1.69 years (95% CI 0.56-4.32) and the 1- and 4-year survival rates were 55% (95% CI 44-67) and 44% (95% CI 32-56). The estimated median survival time for all cats was 3.71 years (95% CI 0.56-unestimatable) and the 1- and 4-year survival rates were 70% (95% CI 53-87) and 47% (95% CI 0-100). Of animals that survived to discharge, 42% of dogs and 20% of cats eventually died of TET-related causes. The presence of paraneoplastic syndromes (hazard ratio [HR] 5.78, 95% CI 1.64-20.45, P = .007) or incomplete histologic margins (HR 6.09, 95% CI 1.50-24.72, P = .01) were independently associated with decreased survival in dogs. No significant predictors of survival were identified in cats. Conclusions regarding the effect of chemotherapy or radiation therapy could not be made. While there is substantial risk of perioperative death in dogs and cats undergoing surgery for TETs, many animals that survive to discharge have prolonged survival. Survival is significantly decreased in dogs with paraneoplastic syndromes or incomplete histologic margins.

Paraneoplastic syndromes in patients with laryngeal neuroendocrine carcinomas: clinical manifestations and prognostic significance.

Paraneoplastic syndromes are associated with a variety of malignant neoplasms and are systemic and non-metastatic manifestations that develop in a minority of cancer patients. This review examines all published cases of paraneoplastic syndromes associated with neuroendocrine carcinomas of the larynx. There are a total of ten patients reported with paraneoplastic syndromes associated with laryngeal neuroendocrine carcinomas in the literature. Of these, nine died and the tenth is alive with liver metastases. There were five cases of small-cell neuroendocrine carcinoma, four cases of moderately differentiated neuroendocrine carcinoma, and one case of well-differentiated neuroendocrine carcinoma associated with paraneoplastic syndromes. As these syndromes have significant clinical relevance, physicians should be aware of the possible presence of paraneoplastic syndromes in the diagnostic process of patients with neuroendocrine carcinoma of the larynx.

Epidemiology and Prognosis of Paraneoplastic Syndromes in Hepatocellular Carcinoma

Background. Paraneoplastic syndromes (PNS) such as hypercalcaemia, hypercholesterolaemia, and erythrocytosis have been described in hepatocellular carcinoma (HCC). Aims. (1) To examine the prevalence, clinical characteristics, and survival of PNS in HCC patients and (2) to evaluate the extent to which each individual PNS impacts on patient survival. Methods. We prospectively evaluated the prevalence, clinical characteristics, and survival of PNS among 457 consecutive HCC patients seen in our department over a 10-year period and compared them with HCC patients without PNS. Results. PNS were present in 127 patients (27.8%). The prevalence of paraneoplastic hypercholesterolemia, hypercalcemia, and erythrocytosis 24.5%, 5.3%, and 3.9%, respectively. Patients with PNS had significantly higher alpha-fetoprotein levels, more advanced TNM stage, and shorter survival. Among the individual PNS, hypercalcemia and hypercholesterolemia were associated with more advanced disease and reduced survival but not erythrocytosis. On multivariate analysis, the presence of PNS was not found to be an independent prognostic factor for reduced HCC survival. Conclusion. PNS are not uncommon in HCC and are associated with poor prognosis and reduced survival due to their association with increased tumor burden. However, they do not independently predict poor survival. Individual PNS impact differently on HCC outcome; paraneoplastic hypercalcemia in particular is associated with poor outcome.

Primary Neuroendocrine Tumors of the Thymus: A Multicenter Experience of 35 Patients

Primary neuroendocrine tumors of the thymus (NETT) are rare tumors and represent a distinct category of tumors collectively displaying morphologic and biological neuroendocrine features. We sought to evaluate factors influencing long-term survival in patients with primary NETT. From January 1990 to April 2011, 35 patients (27 male patients and 8 female patients) were surgically treated for primary NETT at 5 institutions. No operative (30-day) mortality occurred. Morbidity was 37.14% (13/35 patients). All patients were followed for a total of 2,703 months. Fourteen patients had associated paraneoplastic syndrome. Twenty-four patients are alive, 19 of whom are free of disease and 5 of whom continue to have disease. The median overall survival was 153 months. The overall 5-year and 10-year actuarial survival rates were 84.34% and 60.82%, respectively. The 10-year survival was evaluated according to histologic type (typical carcinoid, 77.92%; atypical carcinoid, 54.55%; large-cell neuroendocrine carcinomas, 0%; Masaoka staging (stage I, 100%; stage II, 66.67%; stage III, 61.9%; stage Iva, 25%; stage IVb, 0%), presence of paraneoplastic syndrome (no = 70.67%; yes = 32.14%), postoperative radiotherapy (yes = 39.71%; no = 85.71.%), Surveillance, Epidemiology, and End Results (SEER) staging system (localized disease, 83.3%; regional disease, 53.3%; distant disease, 0%), tumor size (<7 cm = 90.9%; ≥7cm = 28.7%; p = 0.0007), and Ki67 expression, which was available in 23 patients (<10% = 85.71%; ≥10% = 0%; p = 0.0037). The prognosis of primary NETT is statistically significantly related to tumor size >7 cm and to the proliferation index (evaluated by Ki67 expression >10%). The histologic type of the neoplasm, the presence of a paraneoplastic syndrome, the Masaoka staging, the evidence of distant disease, and postoperative radiotherapy also impact prognosis.

Neuroblastoma Presented with Polyhydramniosis

Neuroblastoma is the most common extracranial solid tumor in pediatric age group. Clinical presentation of neuroblastoma is mostly related to origin of the tumor, extent of disease, and the presence of paraneoplastic syndromes. Here the authors report a neonate with neuroblastoma with an atypical presentation, diagnosed with postnatal abdominal ultrasonography performed due to polyhydramniosis in her mother during pregnancy.

Primary neuroendocrine tumours of the thymus: a clinicopathologic and prognostic study in 19 patients☆

We sought to evaluate factors influencing long-term survival in 19 patients with primary neuroendocrine tumours of the thymus. From January 1990 to December 2004, 19 patients (14 males, 5 females; mean age 48.6 years) were surgically treated for a primary neuroendocrine tumour of the thymus. All patients underwent radical R0 thymomectomy and were followed up for a total of 1,459 months (median: 69 months; range: 8-180). Nine patients had associated paraneoplastic syndrome. No operative mortality occurred. Two patients underwent re-do surgery because of local recurrence, respectively, 25 and 35 months after surgery. Five patients died of disease, respectively, 51, 70, 95, 131 and 153 months after surgery. One patient died of myocardial infarction with no evidence of disease. Thirteen patients are alive, of which 10 are free from disease and three with disease. The overall 5-year and 10-year actuarial survival rates were 91.6% and 69.8%, respectively (median survival: 153 months). The 10-year survival was evaluated according to histology (typical carcinoid 100%; atypical carcinoid: 66.6%; large cell neuroendocrine tumours: 0%), Masaoka staging (stage I: 100%; stage II: 50%; stage III: 66.6%; stage IV: 0%), presence of paraneoplastic syndrome (no: 87.5%; yes: 0%) and postoperative radiotherapy (yes: 40%; no: 83.3%). The prognosis of primary neuroendocrine tumours of the thymus is related to the grading of the neoplasm, the presence of a paraneoplastic syndrome and to the Masaoka staging but not to the postoperative radiotherapy.

The IASLC Lung Cancer Staging Project: Data Elements for the Prospective Project

The International Association for the Study of Lung Cancer Retrospective Staging Project culminated in a series of recommendations to the International Union Against Cancer and to the American Joint Committee on Cancer regarding the seventh edition of the tumor, node, metastasis (TNM) classification for lung cancer. The International Staging Committee of the International Association for the Study of Lung Cancer now issues this call for participation in the Prospective Project designed to assess the validity of each component of T, N, and M, and other factors relevant to lung cancer staging and prognosis. In the Retrospective Project, the original data acquisition was typically motivated by interests other than staging. In contrast, the Prospective Project offers online data entry. Alternatively, participants may transfer existing data, provided core objectives are addressed. Cancer Research and Biostatistics will coordinate data management and analysis. The study population is newly diagnosed lung cancer patients. Data elements include patient characteristics, baseline laboratory values, first-line treatment, TNM plus supporting evidence, and survival. Pretreatment TNM will be collected for all cases; postsurgical TNM, if resection is attempted. T descriptors include size and degree of tumor extension, with further description of extent of visceral pleural invasion, venous invasion, carcinomatous lymphangitis, and pleural lavage cytology. M descriptors characterize the newly proposed M1a category and sites of distant metastases. Nodal station involvement is described by means of a newly proposed nodal map, facilitating international participation, and allowing further investigation of nodal zones. Successful collection and analysis of these data can be expected to yield unprecedented improvements in the utility and validity of lung cancer staging.

Renal cell carcinoma with bilateral synchronous adrenal gland metastases: a case report

IntroductionRenal cell carcinoma is characterized by its potential of metastasizing widely and to unusual sites, with the metastases occasionally preceding clinical recognition of the primary tumor. Synchronous bilateral adrenal metastases from renal cell carcinoma, without other metastases, are rare and, to our knowledge, only 17 cases have been published in the literature to date. In general, patients with synchronous bilateral adrenal metastases from renal cell carcinoma have a poor prognosis.Case presentationWe report a case of right-sided renal cell carcinoma with simultaneous bilateral adrenal metastases in a 58-year-old woman. The primary tumor was localized in the upper and mid pole of the kidney. The diagnosis was established preoperatively by abdominal ultrasound and computed tomography. Surgical treatment consisted of a right radical nephrectomy and bilateral adrenalectomy. Postoperative cortisone acetate replacement was instituted. The pathological findings of the right renal tumor showed clear cell carcinoma and both adrenal tumors showed the same pathology as the right renal tumor. There was no evidence of recurrence after 6 months of follow-up.ConclusionPatients with bilateral synchronous adrenal metastases should be considered to have disseminated metastatic disease. However, good performance status, the presence of paraneoplastic syndrome and the alleviation of refractory pain are important reasons make an urologist to consider radical nephrectomy in renal cell carcinoma patient with metastases.

Paraneoplastic syndromes in patients with hepatocellular carcinoma in Taiwan

Hepatocellular carcinoma (HCC) is the most common malignancy in Taiwan. Some patients may manifest paraneoplastic syndromes during the clinical course of the disease. In this study, the authors evaluated the clinical significance of these paraneoplastic syndromes, compared the prevalence of these syndromes between cases of hepatitis B virus (HBV)-related and hepatitis C virus (HCV)-related HCC, and estimated significant predictors associated with the syndromes.Clinical data on 1197 HCC patients, including age, gender, Child-Pugh score, survival time, laboratory data (including liver biochemistry, hepatitis markers, and serum alpha-fetoprotein [AFP]), and tumor features (including tumor size, portal vein thrombosis, and histologic pictures), were retrospectively reviewed.A total of 232 of 1197 patients (19.4%) had paraneoplastic syndromes. HCC patients with paraneoplastic syndromes had significantly higher serum AFP; higher rates of initial main portal vein thrombosis, metastasis, and bilobal tumor involvement; larger tumor volume; and shorter survival than those without these syndromes. Patients with HBV-related HCC had a significantly higher prevalence of paraneoplastic syndromes than patients with HCV-related HCC (20.1% vs. 11.2%, P = 0.005). In a stepwise multivariate logistic regression analysis, AFP >50,000 ng/mL and tumor volume >30% were significant predictive variables associated with the presence of paraneoplastic syndromes in HCC patients.HCC patients with paraneoplastic syndromes usually had higher levels of serum AFP and larger tumor volumes than those without. Patients with HBV-related HCC had a significantly higher prevalence of paraneoplastic syndromes than those with HCV-related HCC.

Paraneoplastic syndromes in patients with hepatocellular carcinoma in Taiwan.

Hepatocellular carcinoma (HCC) is the most common malignancy in Taiwan. Some patients may manifest paraneoplastic syndromes during the clinical course of the disease. In this study, the authors evaluated the clinical significance of these paraneoplastic syndromes, compared the prevalence of these syndromes between cases of hepatitis B virus (HBV)-related and hepatitis C virus (HCV)-related HCC, and estimated significant predictors associated with the syndromes. Clinical data on 1197 HCC patients, including age, gender, Child-Pugh score, survival time, laboratory data (including liver biochemistry, hepatitis markers, and serum alpha-fetoprotein [AFP]), and tumor features (including tumor size, portal vein thrombosis, and histologic pictures), were retrospectively reviewed. A total of 232 of 1197 patients (19.4%) had paraneoplastic syndromes. HCC patients with paraneoplastic syndromes had significantly higher serum AFP; higher rates of initial main portal vein thrombosis, metastasis, and bilobal tumor involvement; larger tumor volume; and shorter survival than those without these syndromes. Patients with HBV-related HCC had a significantly higher prevalence of paraneoplastic syndromes than patients with HCV-related HCC (20.1% vs. 11.2%, P = 0.005). In a stepwise multivariate logistic regression analysis, AFP >50,000 ng/mL and tumor volume >30% were significant predictive variables associated with the presence of paraneoplastic syndromes in HCC patients. HCC patients with paraneoplastic syndromes usually had higher levels of serum AFP and larger tumor volumes than those without. Patients with HBV-related HCC had a significantly higher prevalence of paraneoplastic syndromes than those with HCV-related HCC.