Unsuspected Disease Research Articles

Shared and unique antibody and B cell profiles in HIV-positive and HIV-negative individuals with cryptococcal meningoencephalitis.

Host non-T cell markers to aid in the diagnosis of cryptococcal meningoencephalitis (CM) have not been identified. In this case-control study, we characterized antibody and B cell profiles in HIV-negative and HIV-positive Vietnamese individuals of the Kinh ethnicity recently diagnosed with CM and controls. The study included 60 HIV-negative with no known immunocompromising condition and 60 HIV-positive individuals, with 30 CM cases and 30 controls in each group. Participants were matched by age, sex, HIV serostatus, and CD4 count in the HIV-positive group. Plasma immunoglobulin (Ig) levels, including IgG1, IgG2, IgM, and IgA, Cryptococcus spp. glucuronoxylomannan (GXM)- and laminarin (branched ${\rm{\beta }}$-[1-3]-glucan)-binding IgG, IgM, IgA levels, and peripheral blood B cell subsets were measured. Logistic regression, principal component, and mediation analyses were conducted to assess associations between antibody, B cell levels, and CM. The results showed that GXM-IgG levels were higher and IgG1 and IgG2 were lower in CM cases than controls, regardless of HIV status. In HIV-negative individuals, IgG2 mediated an inverse association between CD19+CD27+CD43+CD5- (B-1b-like) cells and CM. In HIV-positive individuals, lower levels of IgA, laminarin-IgA, and CD19+CD27+IgM+IgD- (IgM+ memory B) cells were each associated with CM. The shared and distinct antibody and B cell profiles identified in HIV-negative and HIV-positive CM cases may inform the identification of non-T-cell markers of CM risk or unsuspected disease, particularly in HIV-negative individuals.

Impact of 18FDG Positron Emission Tomography - Computed Tomography (PET-CT) on Management of Gallbladder Carcinoma

Background: Reports concerning the clinical usefulness 18F-FDG PET-CT for patients with gallbladder cancer are relatively scarce. The purpose of this study was to assess the diagnostic value of 18FGD- PET-CT in relation to a conventional imaging modality, multidetector row CT (MDCT), for patients with gallbladder cancer. Materials and Methods: Seventy patients with suspected gallbladder cancer who underwent both PET-CT and MDCT for initial staging were included in our study. The results of these two imaging modalities for evaluating primary tumors, regional lymph nodes and distant metastases were compared with the final diagnoses based on histopathological examination. Change in management of patients with gallbladder cancer based on PET-CT was also evaluated. Results: A maximum standardized uptake value (SUVmax) of 5.37 was taken as cutoff value for detecting a malignant tumor. PET-CT demonstrated no significant advantage over MDCT for the diagnosis of a primary tumor. PETCT showed a significantly higher accuracy (90.8 vs. 80.0%, P = 0.04) than that found for MDCT in the diagnosis of regional lymph node metastasis. PET-CT showed higher sensitivity (92.3 vs. 61.5%, P = 0.04) than that found for MDCT in the diagnosis of distant metastasis. Addition of PET-CT in preoperative staging of the disease changed management in 10 patients (14.3%). Conclusions: In patients with gallbladder carcinoma, the addition of 18FDG-PET-CT to standard staging CT may be helpful in detecting distant nodal metastasis and unsuspected metastatic disease that may preclude patients from surgical resection and result in a change of management in a significant number of patients.

Radiologic Imaging of Metabolic and Endocrine Disorders as They Affect the Hand and Wrist.

Metabolic and endocrine disorders have systemic effects on the musculoskeletal system, frequently producing characteristic changes in the hand and wrist. Radiographs historically played an instrumental role in the diagnostic pathway of many of these disorders, but the myriad of endocrinologic tests readily available to current clinicians may suggest their importance has lessened. We disagree. Recognition of these often subtle features can avoid the expense and psychological impact of an inappropriate diagnostic work-up, as well as expediting the diagnosis of potentially unsuspected disease. The metabolic and endocrine disorders discussed here are based on the distinctive changes produced around the hand and wrist.

Restaging [18F] fludeoxyglucose positron emission tomography/computed tomography scan in recurrent cutaneous squamous cell carcinoma: Diagnostic performance and prognostic significance

There are no specific recommendations for [18F] fludeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in assessing recurrent cutaneous squamous cell carcinoma (cSCC). To evaluate FDG-PET/CT in recurrent cSCC. FDG-PET/CT scans were retrospectively reviewed. Sites of abnormal uptake were noted and correlated with biopsy/histopathology studies, where available, and with follow-up imaging or clinical data in others. Comparison with available CT/magnetic resonance imaging was performed. The prognostic significance of PET/CT parameters was evaluated, and PET/CT-based change in management was recorded. A total of 115 FDG-PET/CT scans were analyzed in 100 consecutive patients with cSCC. Of these, 96 (84%) scans were positive for recurrence, and 25 showed distant metastases. PET/CT detected unsuspected disease sites in 39 of 115 scans (34%), locoregional disease in 14, distant metastases in 11, both locoregional disease and distant metastases in 8, additional local cutaneous disease in 5, and second malignancy in 1. Comparison of 78 PET/CT scans with available CT/magnetic resonance imaging showed 37 additional abnormalities on 23 PET/CT scans, predominantly including skin/subcutaneous lesions and nodes. PET/CT led to change in management in 28% of patients. On univariate/multivariate analysis, increased number of FDG-positive lesions and lung metastases on PET/CT was associated with increased risk of death/disease progression. Retrospective study. FDG-PET/CT was sensitive in detecting recurrent disease in cSCC, led to change inmanagement for 28% of patients, and proved to be of prognostic value.

Incidental Gallbladder Cancer: A Clinicopathological Study

Abstract Objectives Incidental gallbladder cancer (iGBC) is defined as gallbladder cancer (GBC) diagnosed at the time of or after cholecystectomy, performed for unsuspected benign gallbladder disease. Being rare, it is found in 0.2% to 2.9% cases of cholecystectomies performed for cholecystitis and represents approximately 40% of all GBCs. Here, we present the clinical and pathological features of iGBC diagnosed at our institute over a 10-year period. Methods The pathology reports of GBC in patients who underwent simple cholecystectomies due to sole complain of cholecystitis between 2008 and 2018 were retrieved from electronic medical records. Cases with dysplasia (without invasive component), clinically suspected gallbladder malignancy, polyp (nonincidental), or cholecystectomies performed as a part of any other procedure were excluded. Results Twenty-two cases of iGBC were diagnosed during the study period. Average patient age was 69.59 (range; 48-91) years, with a slight female (n = 12, 54.5%) predominance. Most common site was body (n = 7), followed by fundus (n = 4), neck (n = 2), and unknown (n = 9). Mean tumor size was 1.6 cm, where measurement of tumor size was possible (n = 16). Histopathological diagnoses were adenocarcinoma (n = 21) and carcinosarcoma (n = 1). The AJCC tumor staging was pT1a (n = 3), pT1b (n = 3), pT2 (n = 12), pT3 (n = 3), and unidentifiable (n = 1). Four cases were identified with N1 lymph node status. Cystic duct margin was positive in two cases. Perineural invasion was identified in three cases. Conclusion iGBC after a cholecystectomy for clinically benign condition is a rare finding. Although cholecystitis is much more frequent in female, iGBC had only a slight predominance for female population in our study. It is more common in people over 60 years of the age, which is comparable to the literature. This entity still remains a diagnostic and therapeutic challenge, and management is often more complicated in cases with advanced stage.

Point-of-Care Ultrasound Identifies Decompensated Heart Failure in a Young Male with Methamphetamine-Associated Cardiomyopathy Presenting in Severe Sepsis to the Emergency Department

We describe a case of a young male who presents to the emergency department with severe sepsis and decompensated heart failure with underlying Methamphetamine-Associated Cardiomyopathy that was previously undiagnosed. This presentation is unique because Methamphetamine-Associated Cardiomyopathy is an uncommonly reported condition that presented in a complex clinical scenario of severe sepsis and decompensated congestive heart failure. We discuss how we used point-of-care ultrasound (POCUS) in this case to identify an unsuspected disease process and how it changed our initial resuscitation strategy and management. Emergency physicians can utilize point-of-care ultrasound (POCUS) to help identify these high-risk patients in the emergency department and guide appropriate resuscitation. Methamphetamine-Associated Cardiomyopathy (MAC) is an infrequently described complication of methamphetamine abuse, most commonly presented as a nonischemic dilated cardiomyopathy. With the rise in methamphetamine abuse in the United States, complications from methamphetamine use are more commonly presenting to the emergency department. Proper education and rehabilitation, with a goal of abstinence from amphetamine use, may allow patients to potentially regain normal cardiac function. Since the majority of patients present late with severe cardiac dysfunction, early detection is essential amongst critically ill patients since recognition may significantly influence ED management.

A component of lobular carcinoma in clinically lymph node–negative patients predicts for an increased likelihood of upstaging to pathologic stage III breast cancer

PurposePhysical examination and diagnostic imaging are often less precise in determining the extent of disease in invasive lobular carcinoma (ILC) relative to nonlobular histologies. Anecdotally, surgical axillary evaluation frequently reveals positive lymph nodes in clinically N0 patients with ILC; however, few studies quantify the likelihood of finding unsuspected disease at the time of surgery. In this study, we evaluate whether the presence of lobular histology increases the incidence of surgical upstaging to pathologic stage IIIA or greater in patients with a clinically node-negative axilla and positive sentinel lymph node (SLN) biopsy. Methods and materialsWe examined patients from our institution between 1997 and 2009 treated specifically with mastectomy, SLN biopsy, and completion axillary lymph node dissection due to a positive SLN. For analysis, patients were grouped according to the presence of any lobular component on surgical pathology. The number of total positive lymph nodes, cancer stage, age, final tumor size, and ER/PR/HER2 status were assessed based on tumor histology. ResultsWe evaluated 345 previously untreated women with clinical T0-T2 and N0 disease at the time of surgery. A total of 110 patients (32%) had a component of ILC on surgical pathology. In addition, 295 patients (85.5%) had ER + breast carcinoma, 243 (70.4%) had PR + disease, 56 (16.2%) were HER2 + , and 28 (8.1%) were triple negative. At the time of surgery, women with lobular disease were observed to have a greater number of positive lymph nodes (2.79 vs 2.26; P = .009) and were more frequently upstaged to at least pathologic stage IIIA compared with nonlobular patients (30.9% vs 17.4%; P = .007). ConclusionsIn this cohort, patients with a component of lobular carcinoma were more often surgically upstaged to pathologic stage IIIA or higher, which is a classical indication for postmastectomy radiation therapy. Our findings suggest that ILC is often more extensive than it appears clinically and has significant implications for management of patients with lobular carcinoma after the discovery of a positive SLN.

Unsuspected N2-positive non-small cell lung cancer after complete resection: is there a place for multimodal adjuvant therapy?

Unsuspected N2 disease after surgical resection is found in a substantial proportion of patients with locally advanced non-small cell lung cancer (NSCLC) despite adequate preoperative mediastinal staging. This situation is challenging for clinicians, as optimal adjuvant strategies remain controversial and such patients are at risk of local recurrence and distant metastasis (1,2).

The Impact of 68Ga-PSMA PET/CT on Management Intent in Prostate Cancer: Results of an Australian Prospective Multicenter Study.

68Ga-PSMA PET/CT scanning has been shown to be more sensitive than conventional imaging techniques in patients with prostate cancer. This prospective Australian multicenter study assessed whether 68Ga-PSMA PET/CT imaging affects management intent in patients with primary or recurrent prostate cancer. Methods: Before undertaking 68Ga-PSMA PET imaging, referring medical specialists completed a questionnaire detailing relevant demographic and clinical data as well as their proposed management plan. A separate follow-up questionnaire was completed after the 68Ga-PSMA PET/CT scan results were available to determine whether the management plan would change. Results: A total of 431 patients with prostate cancer from 4 Australian centers had pre- and post-68Ga-PSMA management plans completed. Scans were obtained for primary staging of intermediate- and high-risk disease in 25% of patients and for restaging/biochemical recurrence in 75% of patients. Overall, 68Ga-PSMA PET/CT scanning led to a change in planned management in 51% of patients. The impact was greater in the group of patients with biochemical failure after definitive surgery or radiation treatment (62% change in management intent) than in patients undergoing primary staging (21% change). Imaging with 68Ga-PSMA PET/CT revealed unsuspected disease in the prostate bed in 27% of patients, locoregional lymph nodes in 39%, and distant metastatic disease in 16%. Conclusion:68Ga-PSMA PET/CT scans detect previously unsuspected disease and may influence planned clinical management in a high proportion of patients with prostate cancer. The impact was greater in patients with biochemical recurrence. These results demonstrate the potential clinical value of 68Ga-PSMA PET/CT in management of prostate cancer.

Parathyroid cysts: the Latin-American experience.

Parathyroid cyst is an infrequent and unsuspected disease. There are more than 300 hundred cases reported in the world literature, a few of them are from Latin America. The experience of our centers and a review of the cases are presented. Case report of a series of patients with parathyroid cyst from our institutions according to the CARE guidelines (Case Reports). A search of Medline, Embase, BIREME (Biblioteca Regional de Medicina) LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud), Google Scholar and Scielo (Scientific Electronic Library on Line) databases and telephonic or email communications with other experts from Latin-America was performed . Six patients with parathyroid cyst were found in our centers in Colombia. Most of them were managed with aspiration of the cyst. Two of them required surgery. Only one case was functional. Twelve reports from Latin America were found for a total of 18 cases in our region adding ours. Parathyroid cysts are uncommonly reported in Latin America. Most of them are diagnosed postoperatively. Suspicion for parathyroid cyst should be raised when a crystal clear fluid is aspirated from a cyst. The confirmation of the diagnosis may be easily done if parathyroid hormone (PTH) level is measured in the cyst fluid.

Comparison of MRI and 18F-FDG PET/CT in the preoperative evaluation of uterine carcinosarcoma

ObjectiveTo compare the validities of magnetic resonance imaging (MRI) and 18F-fluoro-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in preoperative evaluation of uterine carcinosarcoma. MethodsPathologic results of primary tumor lesions and paraaortic and pelvic lymph node (LN) areas were compared with the preoperative image findings. Differences in the validity parameters of both images were compared using McNemar test. ResultsFor detecting primary tumor lesions (n=56), the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for 18F-FDG PET/CT versus MRI were 98.1% versus 98.1% (P=1.000), 33.3% versus 100% (P=0.157), 94.6% versus 98.2% (P=0.500), 96.3% versus 100%, and 50% versus 75%, respectively. For paraaortic LN areas, the values were 77.8% versus 51.9% (P=0.016), 90.2% versus 100% (P=0.025), 85.9% versus 83.3% (P=0.774), 80.8% versus 100%, and 88.5% versus 79.7%, respectively. For pelvic LN areas, the values were 61.1% versus 50% (P=0.125), 86.8% versus 89.5% (P=0.727), 78.6% versus 76.8% (P=0.774), 68.8% versus 69.2%, and 82.5% versus 79.1%, respectively. For extrauterine disease, the patient-based values for 18F-FDG PET/CT were 100%, 78.9%, 85.7%, 69.2%, and 100%, respectively. ConclusionIn patients with uterine carcinosarcoma, 18F-FDG PET/CT is comparable to MRI in detecting primary uterine lesions. For predicting LN metastases, though 18F-FDG PET/CT might be insufficient for replacing lymphadenectomy or MRI, it might allow lymphadenectomy to be omitted in poor surgical candidates. For detecting extrauterine metastases, it could also be useful to identify unsuspected disease.

Extra-cardiac findings in cardiovascular magnetic resonance: what the imaging cardiologist needs to know.

Cardiovascular magnetic resonance (CMR) is an established non-invasive technique to comprehensively assess cardiovascular structure and function in a variety of acquired and inherited cardiac conditions. A significant amount of the neck, thorax and upper abdomen are imaged at the time of routine clinical CMR, particularly in the initial multi-slice axial and coronal images. The discovery of unsuspected disease at the time of imaging has ethical, financial and medico-legal implications. Extra-cardiac findings at the time of CMR are common, can be important and can change clinical management. Certain patient groups undergoing CMR are at particular risk of important extra-cardiac findings as several of the cardiovascular risk factors for atherosclerosis are also risk factors for malignancy. Furthermore, the presence of certain extra-cardiac findings may contribute to the interpretation of the primary cardiac pathology as some cardiac conditions have multi-systemic extra-cardiac involvement. The aim of this review is to give an overview of the type of extra-cardiac findings that may become apparent on CMR, subdivided by anatomical location. We focus on normal variant anatomy that may mimic disease, common incidental extra-cardiac findings and important imaging signs that help distinguish sinister pathology from benign disease. We also aim to provide a framework to the approach and potential further diagnostic work-up of incidental extra-cardiac findings discovered at the time of CMR. However, it is beyond the scope of this review to discuss and determine the clinical significance of extracardiac findings at CMR.

PWE-122 Autoimmune hepatitis (aih): assessment of usefulness of diagnosic liver biopsy and of “simplified” diagnostic scoring system

Introduction Although recommended in published guidelines, only 62% of UK Gastroenterologists routinely recommend diagnostic liver biopsy in patients with suspected AIH (Dhaliwal Gut 2012:62). Also, the relative usefulness of the International AIH Group diagnostic criteria (full 1999 or simplified 2008) is not established. Our aim was to assess the relationships between histological and immunological diagnostic features and response to treatment in patients meeting the 1999 IAIHG criteria, which we also assessed against the 2008 simplified criteria. Method 90 patients were identified; 79% women, with median age 61 yrs (14–85) presenting since 2006 with suspected AIH and underwent diagnostic liver biopsy. Histology was assessed using the Ishak system by one liver Histopathologist (AKD) without reference to other results. Results Interface hepatitis was found in 87(97%) of biopsies, mainly plasma cell infiltrate in 74(83%), rosettes in 68(76%) and emperipolesis in 100% (of 48 patients assessed). Biliary changes were seen in 14% and mild steatosis in 24%. Prior to biopsy, patients had 13(7–19) diagnostic points by IAIHG criteria, with 11 of the 90 patients not having the required 10 points. Biopsy contributed an additional 5(0–6) points and all patients then met the 1999 IAIHG criteria (61 definite, 29 probable) with 17(12–22) points. In 49 patients, with a pre biopsy score of >13, biopsy contributed 4(0–5) points and was not needed for diagnosis of AIH but detected biliary changes in 10 patients (3 AMA -ve,1 weak +ve subsequently diagnosed as PBC and started on treatment, 2 PSC overlap and 4 not overlap) and also detected cirrhosis in 9. Histological features did not differ between: patients with (n = 68) and without (n = 22) serum autoantibodies (nuclear, smooth muscle or LKM-1); between those with (n = 72) and without (n = 10) raised serum IgG; or between treated patients who did (n = 75) and did not (n = 8) achieve normal serum ALT within 6 months. Eighteen patients (20%) did not meet the 2008 simplified diagnostic criteria for AIH (6 points). In these, necro-inflammatory score was 9(2–15), fibrosis score was 3(0–5) and 13 of 14 treated patients achieved normal serum ALT by 6 months. Conclusion Liver biopsy is important for diagnosis of AIH in those with lower, but less so in those with higher pre-biopsy IAIHG (1999) diagnostic scores. It may also detect cirrhosis or indicate additional unsuspected biliary disease. Histological features are not associated with immunological features or response to treatment. The 2008 simplified diagnostic criteria will “miss” 20% of patients with AIH by 1999 criteria. Most of these patients have significant disease and respond to treatment. Disclosure of interest None Declared.

Ethics of preparticipation cardiovascular screening for athletes.

Preparticipation screening for unsuspected cardiovascular disease is a controversial topic in the medical and lay communities. Much attention has been directed towards young competitive athletes, particularly the proposed strategy of incorporating 12-lead electrocardiograms into the screening process, even on a national or worldwide basis. However, sudden deaths of young athletes owing to genetic or congenital heart diseases have a low incidence in the general population. Furthermore, young people not engaged in competitive sports can harbour the same conditions that cause sudden death in athletes, which has gone largely unrecognized. Notably, sudden deaths from these diseases are numerically far more common in the much larger population of nonathletes. In this Perspectives article, we propose that an ethical dilemma has emerged, raising the important public-health issue of whether young individuals should be arbitrarily excluded from potentially life-saving clinical screening evaluations because they do not engage in competitive sports programmes.

Evaluating the cause of death in obese individuals: a ten-year medical autopsy study.

Background. Obesity is a growing public health problem associated with increased morbidity and rate of death. Postmortem examination is imperative to determine the cause of death, to detect clinically unsuspected disease entities, and consequently to determine the actual impact of obesity on patient mortality. Methods. A total of 849 adult autopsies were retrospectively reviewed. Obese (BMI ≥ 30 kg/m2) and nonobese patients were separately studied. The primary cause of death in each group was categorized into malignancy, infection, stroke, ischemic and nonischemic heart disease, pulmonary embolism, hemorrhage, and primary nonneoplastic diseases of different organ systems. Results. Of 849 autopsies, 32.3% were obese. The leading causes of death in the obese population were malignancy (31.4%), infection (25.9%), ischemic heart disease (12.8%), and pulmonary embolism (6.2%). Obese individuals were statistically more likely to die from pulmonary embolism and liver disease and less likely to die from neurologic diseases and nonischemic heart disease. Conclusion. Autopsies on obese individuals constitute a third of all adult medical autopsies in our center. Increased death rates in the obese due to pulmonary embolism and liver disease should receive special clinical attention. Autopsy findings in the obese population should contribute to overall premortem disease detection, prevention, and management.

The Role of PET/TC in the Full Range of Monoclonal Gammopathies

Positron emission tomography (PET) with 18fluorine-fluoro-deoxyglucose (FDG) integrated with computed tomography (PET/CT) is a functional imaging technique helping us to assess bone marrow infiltration as well as unsuspected disease sites involving the bones and/or extramedullary sites. PET/TC has proved to be an independent prognostic factor for overall survival (OS) in symptomatic multiple myeloma (MM)(Zamagni,2011). However, its role in other monoclonal gammopathies (MG) is still a matter of debate.We have prospectively analyzed the contribution of baseline PET/TC in a unselected consecutive series of 158 patients with MG, including 88 MM, 7 MM smoldering (MMS), 11 Waldenstrm’s macroglobulinemia (WM), 3 WM smoldering (WMS), 3 solitary bone plasmacytoma (SBP) and 46 monoclonal gammopathy of uncertain significance (MGUS). Patients with only palliative care were excluded. The pattern of bone marrow uptake on PET/TC was described as negative (NEG), diffuse involvement (DI) or focal lesions (FLs). Patients with more than 3 FLs as well as the presence of extramedullary disease (EMD) were analyzed separately. Overall survival (OS) was estimated by the Kaplan-Meier method.The main characteristics of PET/TC findings according to the type of MG are shown in Table 1. PET/TC was positive in 70 (79,5 %) of MM and 8 (72,7%) of WM. PET/TC was NEG in 100 % of MMS, WMS and SBP (except for the primary lesion). In MGUS, the findings reflect the clinical heterogeneity of this group: 19,6 % had bone disease (all but one case of probable inflammatory etiology), 17,4 % positive lymphadenopathy, 15,2 % lung disease (infection, fibrosis, pulmonary nodules), 6,5 % splenomegaly, 6,5 % liver disease, 6,5 % positive uptake in adrenal gland and other organs such as thyroid, stomach, colon or skin were affected less frequently.Median age of MM patients was 62 years (12-91), 51 men and 37 women (42%), the distribution according ISS was I (36,5 %), II (28,2 %) and III (35,3%). Among PET-positive MM, 39 (55,7 %) had >3 FLs, 17 (24,3 %) 3 or less FLs and 14 (24,3 %) DI. Median OS was 40 months, not reached (NR) and 85,7 months, respectively (p=ns). Mean bone marrow plasma cells in the >3 FLs group vs 3 or less FLs was 25 vs 12 (p=0,028). EMD was present in 13 (18,6 %) of PET-positive MM. Response with PET/CT was available in 32 patients: 18 achieved CR, 8 PR and 8 progressed. OS was NR for CR and PR vs 40 months (p <0,0001). In WM, patients with NEG or FL had NR OS vs 26 months in those with DI (p=0,16).PET/CT is positive in the majority of MM and WM patients, helping to separate patients with true indolent disease. At baseline, PET/TC is a useful tool to improve prognostic assessment in patients with MG. MM with >3 FLs or EMD at baseline had a trend towards lower OS. Negative serial PET/CT in MM is associated with favorable prognosis.TableSEQ Tabla \\* ARABIC 1. Characteristics of main PET/TC findings according to the type of MGTypeMMMMSWMWMSSBPMGUSn887113346Positive n /%70/79,508/72,7009/19,6->3 FLs39/55,700000-3 or < FLs17/24,301/12,5001/2,2-DI14/2005/62,5001/2,2-EMD13/18,600000-Adenopathy2/2,92/28,62/25008/17,4-Spleen3/4,301/12,5003/6,5 MGMonoclonal gammopathy; MM: Multiple myeloma symptomatic; MMS: Smoldering myeloma; WM: Waldenstrm’s macroglobulinemia; WMS: Smoldering Waldenstrm’s macroglobulinemia; SBP: Solitary bone plasmocytoma; MGUS: Monoclonal gammopathy of uncertain significance; FL: Focal lesion; DI: Diffuse involvement; EMD: Extramedullary disease. DisclosuresNo relevant conflicts of interest to declare.

Ovarian cancer: imaging in treatment selection and planning with FIGO update

The International Federation of Gynecologists and Obstetricians (FIGO) has recently revised the staging of ovarian cancer [1]. It includes a revision of the stage III patients and allotment to stage IIIA1 is based on spread to the retroperitoneal lymph nodes without intraperitoneal dissemination, because an analysis of these patients indicates that their survival is significantly better than those who have intraperitoneal dissemination [1]. The FIGO staging system for ovarian cancer is surgically based. It does not formally include imaging but the FIGO committee encourages the use of imaging techniques if available to assess the important prognostic factors such as disease resectability and lymph node status. The standard of care for patients with newly diagnosed advanced ovarian cancer has been comprehensive staging laparotomy and primary optimal surgical cytoreduction followed by adjuvant chemotherapy. However, the use of neoadjuvant chemotherapy followed by interval debulking surgery (IDS) as a suitable alternative is supported by multicenter randomized controlled trials [2]. Imaging is therefore of paramount importance in helping triage patients for appropriate management by accurately evaluating the extent and anatomical location of peritoneal spread, which in turn dictates the feasibility of cytoreductive surgery and predicts the likelihood of optimal primary cytoreduction. Optimal cytoreductive surgery (residual disease <1 cm) is a very strong predictor of survival, and even after the threshold for optimal cytoreduction has been reached, it is important to remove as much of the residual tumor as possible. CT is the primary imaging modality used to stage ovarian cancer. It is complimentary to surgical staging identifying possible sites of unsuspected disease such as pelvic peritoneum, paraaortic nodes, diaphragm and chest [3,4]. The thorax frequently harbors undiagnosed pleural disease at the time of the initial diagnosis which is likely to affect survival even in cases of optimal debulking [5,6]. Accurate imaging helps guide the surgeon to areas of disease that may be difficult to identify surgically. Relative criteria for non-optimally resectable disease have been developed [7]. They include lymph node enlargement above the renal hilum, presence of abdominal wall invasion, parenchymal liver and subcapsular liver metastases, peritoneal implants of >2 cm along the diaphragm, lesser sac, porta hepatis, intersegmental fissure, gall bladder fossa, gastrosplenic, gastrohepatic ligament and small bowel mesentery. However, it is important to realize that these criteria may vary and will depend on the aggressiveness of the surgical procedure and on the performance status of the patient. Therefore, they should only be used as a basis for a multidisciplinary consensus. It is important to note that upper abdominal disease and pleural metastases can be surgically resected, but this requires careful planning as it involves a team of surgeons (e.g. liver surgeons for hepatic resection). There has been a growing awareness of the potential of diffusion weighted magnetic resonance imaging (DW-MRI) in improving the mapping of the extent of ovarian cancer [8,9]. There is also growing evidence that FDG-PET/CT may play a role in pre-operative staging of patients with advance ovarian cancer [10].

Neoadjuvant capecitabine and oxaliplatin (CAPOX) followed by chemoradiation (CRT) in high-risk rectal cancer: A single-institution experience.

e14100 Background: Total Mesorectal Excision (TME) is standard of care in early rectal cancer. Pre-operative CRT facilitates microscopic complete resection (R0), improving outcome in high risk disease. Recent Phase 2 studies investigated the role of neoadjuvant CAPOX chemotherapy pre-CRT with promising results. We have adopted this strategy in high risk cancers with threatened circumferential resection margin (CRM) on MRI, and report our institution’s early outcome data. Methods: Retrospective data was collected on 37 patients with high risk disease treated March 2007 to December 2011. Patients received 12 weeks oxaliplatin (130mg/m2) and capecitabine (1000mg/m2 BD for 14 days) every 3 weeks, followed by CRT (45 Gy/ 25 #) with concurrent capecitabine (800mg/m2 BD). 11/37 patients had a 5.4 Gy/ 3 # boost with CRT. 4 patients were in a clinical trial, 2 of whom had cetuximab in addition to CAPOX. Patients deemed operable on repeat MRI had TME and 4 cycles of adjuvant CAPOX. Results: Median age was 64 (33-78) and male: female ratio 2.1:1. Median follow-up was 22 months (1.9-53.7). 2 patients did not complete 4 cycles neoadjuvant CAPOX due to toxicity. Median time to surgery post CRT was 6.6 weeks (4.7-10 weeks). 1 patient had an embolic event and femoral embolectomy. 7/31 (23%) patients had no post-operative chemotherapy (4 wound; 2 previous toxicity; 1 comorbidity). Radiological response rates post CRT were 26/34 (76%). 2 patients progressed and were unable to have radical surgery. 1 further patient was found to have unsuspected metastatic disease (liver) at time of surgery. 28/35 (80%) patients had R0 resection and pathological complete response (pCR) was 6/37 (16%). 2 year DFS and OS was 89% and 91.3%. Conclusions: Our outcomes, within an unselected cohort, reflect outcomes consistent with published trial data and support routine use of pre-operative CAPOX and CRT in high risk rectal cancers. This strategy is feasible in a non-trial population, and offers the benefit of early sterilisation of micrometastases, better prediction of chemotherapy response and facilitates the incorporation of novel agents within neoadjuvant window studies.

TREATMENT OF CONDYLOMATA ACUMINATA AND BOWENOID PAPULOSIS WITH CO2 LASER AND IMIQUIMOD

INTRODUCTION: In patients with colorectal cancer (CRC), preoperative evaluation and staging should focus on techniques that might alter the preoperative or intraoperative surgical plan. Conventional imaging methods (CT, MRI) have low accuracy for identifying the depth of tumour infiltration and have limited ability to detect regional lymph node involvement. The aim of this study was to evaluate the utility of FDG-PET in the initial staging of patients with CC in comparison with conventional staging methods and to determine its impact on therapeutic management. METHODS: In First Clinic of Surgery at University Hospital “St. Marina” one hundred and four patients with a diagnosis of CRC (53 males and 51 females; mean age 66.76± 12.36 years), selected prospectively. All patients were studied for staging using a standard procedure (CT) and FDG-PET. The reference method was histology. The effect of FDG-PET on the diagnose and the operative treatment was studied. RESULTS: In 14 patients, surgery was contraindicated by FDG-PET owing to the extent of disease (only 6/14 suspected by CT). FDG-PET revealed four synchronous tumours. For N staging, both procedures showed a relatively high specificity but a low diagnostic accuracy (PET 56%, CT 60%) and sensitivity (PET 21%, CT 25%). For M assessment, diagnostic accuracy was 92% for FDGPET and 87% for CT. FDG-PET results led to modification of the therapy approach in 17.85% of the patients with rectal cancer and in 14.8% of the patients with colon cancer. CONCLUSION: Compared with conventional techniques, FDGPET appears to be useful in pre-surgical staging of CC, revealing unsuspected disease and impacting on the treatment approach.

Cluster Analysis of Obesity and Asthma Phenotypes

BackgroundAsthma is a heterogeneous disease with variability among patients in characteristics such as lung function, symptoms and control, body weight, markers of inflammation, and responsiveness to glucocorticoids (GC). Cluster analysis of well-characterized cohorts can advance understanding of disease subgroups in asthma and point to unsuspected disease mechanisms. We utilized an hypothesis-free cluster analytical approach to define the contribution of obesity and related variables to asthma phenotype.Methodology and Principal FindingsIn a cohort of clinical trial participants (n = 250), minimum-variance hierarchical clustering was used to identify clinical and inflammatory biomarkers important in determining disease cluster membership in mild and moderate persistent asthmatics. In a subset of participants, GC sensitivity was assessed via expression of GC receptor alpha (GCRα) and induction of MAP kinase phosphatase-1 (MKP-1) expression by dexamethasone. Four asthma clusters were identified, with body mass index (BMI, kg/m2) and severity of asthma symptoms (AEQ score) the most significant determinants of cluster membership (F = 57.1, p<0.0001 and F = 44.8, p<0.0001, respectively). Two clusters were composed of predominantly obese individuals; these two obese asthma clusters differed from one another with regard to age of asthma onset, measures of asthma symptoms (AEQ) and control (ACQ), exhaled nitric oxide concentration (FENO) and airway hyperresponsiveness (methacholine PC20) but were similar with regard to measures of lung function (FEV1 (%) and FEV1/FVC), airway eosinophilia, IgE, leptin, adiponectin and C-reactive protein (hsCRP). Members of obese clusters demonstrated evidence of reduced expression of GCRα, a finding which was correlated with a reduced induction of MKP-1 expression by dexamethasoneConclusions and SignificanceObesity is an important determinant of asthma phenotype in adults. There is heterogeneity in expression of clinical and inflammatory biomarkers of asthma across obese individuals. Reduced expression of the dominant functional isoform of the GCR may mediate GC insensitivity in obese asthmatics.