First Department Of Internal Medicine Research Articles

News from the European Journal of Therapeutics: A new issue and a new editorial board

News from the European Journal of Therapeutics: A new issue and a new editorial board

RENIN-ANGIOTENSIN-ALDOSTERONE BLOCKADE AND ITS PREDICTION OF LATE RECURENCE OF ATRIAL FIBRILLATION AFTER RADIOFREQUENCY ABLATION

Objective: Hypertension is one of the main triggers of atrial fibrillation. Patients with hypertension have 1.7 times higher risk of developing atrial fibrillation. Opinions differ on the use of RAAS blockers in atrial fibrillation. The aim is to evaluate the effect of RAAS blockers in the prevention of atrial fibrillation on the post-ablation prognosis of the patient. Design and method: A retrospective analysis of 221 patients who underwent radiofrequency ablation of atrial fibrillation at the First Department of Internal Medicine - Cardioangiology of St. Anne's University Hospital in Brno from 1 January to 31 December 2019 was performed. Recurrence within the first three months was designated as early, and in the following months as late. Results: The median age of the study population (N = 221) was 63 years, with 67.4% of men. According to pre-ablation transesophageal echocardiography, the mean left atrial dimension was 45.3mm and left ventricular ejection fraction was 59.8%. Among the comorbidities, hypertension (63.3%) and dyslipidaemia (41.6%) were the most common, followed by diabetes mellitus (14.0%), ischemic heart disease (7.2%), history of stroke (6.3%), chronic obstructive pulmonary disease (5.0%). 33.0% had a history of nicotinism. Among the baseline antihypertensive groups, beta-blockers were the most represented (69.2%) followed by angiotensin-converting enzyme inhibitors (37.5), angiotensin-receptor blockers (20.4%), calcium channel blockers (32.1%) and diuretics (32.1%). There was not a significant difference in the representation of each group of antihypertensives between the populations. n the group of patients treated with ACEis/ARBs (57.9%), the mean blood pressure resulting from pre- and post-ablation measurements was the same 149/81mm Hg. No significant differences in left atrial size or capture of early or late postablation recurrence (HR 1.26, 95% CI 0.84-1.90, p = 0.265) were detected in the RAAS inhibitor group relative to patients without ACEis/ARBs in therapy. Conclusions: Conventionally administered ACEis/ARBs before ablation procedure did not lead to a reduction in the detection of late postablation recurrence of atrial fibrillation. Despite the documented benefit of RAAS blocker therapy in atrial fibrillation patients, their routine administration before ablation procedure aimed at improving postablation prognosis was not evaluated as justified.

The second shot to walled‐off necrosis: The sooner the better versus sooner or later

To the Editor, We read with great interest the article by Pawa et al.,1 reporting a retrospective study comparing immediate and delayed direct endoscopic necrosectomy (DEN) after lumen-apposing metal stent placement for walled-off necrosis. The authors reported preferable outcomes of the delayed DEN in terms of length of stay and the number of DEN sessions as well as comparable rates of clinical success and adverse events. There has been a debate about the optimal timing of DEN during the treatment course of walled-off necrosis.2 The rationale of delaying interventions has been supported by a randomized trial by the Dutch pancreatitis group, which demonstrated the potential of delayed catheter drainage in avoiding a part of adjunctive interventions.3 However, other groups reported conflicting results that a reduction in an interval until the second intervention might be translated into that in the overall treatment duration.4 In the current study, the delayed DEN group consisted of patients presenting with systemic inflammatory response syndrome for whom DEN was postponed for at least 7 days. Since patients with systemic inflammatory response syndrome were generally associated with worse clinical outcomes, we believe that the study results in favor of delayed DEN were promising. Nonetheless, given the time to DEN of more than 7 days in the delayed DEN group, length of stay (reported to be 3 days in this group) might not be a good surrogate of treatment effectiveness. We therefore ask the authors to provide other metrics such as time to clinical success and the rate of avoiding DEN in the delayed group, which would increase the clinical relevance of their findings. In summary, along with upcoming results of randomized trials by our group (NCT05451901) and others, the current study would help us to address clinical unmet needs in endoscopic treatment of symptomatic walled-off necrosis and optimize treatment strategies. The authors would like to appreciate the following members of the WONDERFUL study group for their valuable comments on the manuscript: Tomotaka Saito, Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Mamoru Takenaka, Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan; Hideyuki Shiomi, Division of Gastroenterology and Hepatobiliary and Pancreatic Diseases, Department of Internal Medicine, Hyogo Medical University, Hyogo, Japan; Hiroyuki Isayama, Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan; Takuji Iwashita, First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan. This work was supported in part by a grant from the Japanese Foundation for Research and Promotion of Endoscopy (#1015 to T. Saito). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors declare that they have no conflicts of interest. Ichiro Yasuda serves as an Associate Editor of DEN Open, and Yousuke Nakai serves as an Associate Editor of Digestive Endoscopy. Japanese Foundation for Research and Promotion of Endoscopy (#1015).

Contributions from Japan to gastrointestinal endoscopy training and development: Special report.

Contributions from Japan to gastrointestinal endoscopy training and development: Special report.

First Department of Internal Medicine, Kansai Medical University

First Department of Internal Medicine, Kansai Medical University

Outcomes of Patients with Newly Diagnosed Cardiac Myxoma: A Retrospective Multicentric Study.

The patient database at the First Department of Internal Medicine in Martin, the Central Slovak Institute for Cardiac and Vascular Diseases in Banska Bystrica, and the National Slovak Institute of Cardiovascular Diseases in Bratislava was searched to identify patients with benign tumors of the heart seen during the 5-year period between 2011 and 2016. Forty-one patients with primary cardiac myxomas were identified and their medical records were reviewed for details pertaining to presenting symptoms, staging modalities, treatment approaches, and outcomes. Most of the studied patients were diagnosed with echocardiography (n = 35, 85%). The occurrence of the tumor was higher in the female population (n = 25, 61%). The most common presenting symptoms were dyspnoea (n = 17, 42%), chest pain (n = 3, 7%), or pain and paraesthesia of the limbs (n = 2, 5%). Acute embolic event due to embolization of tumor fragments resulted in cerebral stroke (n = 5, 12%). All patients were treated by resection. Only one comorbid patient died due to multiple-organ dysfunction syndrome two weeks after the resection. The most common postoperative complication was bleeding (n = 2, 5%) and infection (n = 2, 5%). The early diagnosis and appropriate treatment are often curative, with very low risk of recurrence. Postoperative survival is high.

New prognostic biomarkers and therapeutic effect of bevacizumab for patients with non-small-cell lung cancer.

BackgroundSeveral biomarkers have emerged as potential prognostic and predictive markers for non-small-cell lung cancer (NSCLC). Successful inhibition of angiogenesis with the antivascular endothelial growth factor antibody, bevacizumab, has improved the efficacy seen with standard cytotoxic therapy of NSCLC. However, despite such enhanced treatment strategies, the prognosis for patients with advanced NSCLC remains poor.Patients and methodsWe assessed potential biomarkers in 161 NSCLC patients and 42 control patients. Enzyme-linked immunosorbent assay methods were used to evaluate three biomarkers: platelet-derived microparticle (PDMP), high-mobility group box-1 (HMGB1), and plasminogen activator inhibitor-1 (PAI-1). We studied the effects of bevacizumab on the expression of these markers. We also analyzed the relationship of the newly designed risk factor (NDRF) to overall survival and disease-free survival. The NDRF classification of patients was determined from the levels of PDMP, HMGB1, and PAI-1. To determine the individual prognostic power of PDMP, HMGB1, and PAI-1, we evaluated associations between their levels and patient outcomes by Kaplan–Meier survival analysis in a derivation cohort.ResultsPDMP, HMGB1, and PAI-1 levels were higher in NSCLC patients compared with control patients. Notably, the difference in PDMP levels exhibited the strongest statistical significance (p<0.001). Multivariate analysis showed that HMGB1 and PAI-1 levels were significantly correlated with PDMP levels. Patients who received standard chemotherapy with bevacizumab exhibited significantly reduced levels of all three markers compared with patients who received standard chemotherapy. NDRF3 status (high levels of all three markers) was significantly correlated with a poor prognosis (p<0.05 for overall survival and disease-free survival).ConclusionOur results demonstrate that abnormal levels of PDMP, HMGB1, and PAI-1 are related to each other in NSCLC. Moreover, our findings suggest that the vascular complications associated with these markers may contribute to a poor prognosis for NSCLC patients.

九州大学第一内科「臨床心理研究室」の発祥と変遷をみぐって(特別寄稿)

九州大学第一内科「臨床心理研究室」の発祥と変遷をみぐって(特別寄稿)

Long Term Anagrelid Treatment Significantly Reduces Trombotic Risk in ET Patients As Compared to Hydroxyurea + Aspirin Treatment

The HUMYPRON GROUPBackground: The heterogeneity of MPN care in Hungary prompted us to establish the Hungarian MPN Working Group (HUMYPRON GROUP) in year 2012.Aims: The HUMYPRON GROUP created our MPN Registry in 2013, the aims were: (1) to gain epidemiological, diagnostic, therapeutic data, to follow up complications and disease transformations. (2) to investigate the adherence to the WHO/2008 diagnostic criteria and to the Landolfi therapeutic guidelines, to gain insight into vascular and haematological complications. (3) to try to identify crucial issues and possible gaps, and promote internationally accepted, standard care in MPN.Methods: The questionnaire had been thoroughly updated regarding the 2008 WHO diagnostic criteria (morphology, mutations, etc.) with focus on complications, risk stratification and treatment. The electronic platform can be continuously updated as needed by our steering committee (new molecular results e.g. calreticulin mutations can be included). All haematologists using the system are entitled to initiate search and association analysis. Our MPN Registry is legally permitted by our authorities (ETT-TUKEB) .The data entry was started in 2014. The centers entered the data of all the essential thrombocythaemia (ET), polycythaemia vera (PV)PV and idiopathic myelofibrosis (IMF) patients they had diagnosed and treated.In the present work we have compared the outcome of ET patients treated with either with anagrelid (ANA) or with Hydroxyurea (HU) + aspirin (ASA) based on registry data.Results: During the first active year of the Hungarian MPN Registry 15 of our major or smaller haematological centers provided patient data, all together reaching the evaluable ET patient number of 350. Because of the method we used entering the data, (all patients of a center) a long follow up period was gained, allowing us analyzing effectiveness of different treatment modalities. We have found the data of 141 ET patients, treated with HU + ASA, and 139 ET patients, treated with anaghrelid +/- ASA. There were 65 thrombotic events among the HU+ASA treated group ,while only 25 among the anagrelid group. The major vascular events were the same, but the minor events were different. There were 2 hemorrhagic complications in HU group and 3 in anagrelid group. The male/female ratio, the median age, the follow up period, the Landolfi risk results, the JAK2V617F positivity ratio were comparable between the two groups. We found a significant difference in the frequency of thrombotic events in favour of the anagrelid treatment arm. (Table 1)Table 1Comparison of Anagrelid versus Hydroxyurrea + aspirin treated ET patientsET/ANA (n=139)ET/HU+ASA (n=141)GenderMale4748Female9293Age et the time of diagnosis (years)Median6063Minimum2527Maximum9289Follow-up time (months)8378JAK V617F mut + (%)57.059.0Risk stratification according Landolfi (median)4.564.59Thrombotic events p: 0,0004732563Arterial minor628Arterial major22Venous minor527Venous major126Major bleeding events32Progression54Myelofibrosis43MDS/AML01Solid tumor10Anagrelid was found to be significantly superior when total thrombotic risk and the frequency of minor thrombotic events was evaluated.The Chi-square statistic is 12.2199. The p value is 0.000473. This result is significant at p< 0.05Summary/Conclusion:1. We have created a national MPN Registry covering a large part of Hungary. The database is operational, online, user friend, easily adjustable to the new professional needs. It is convenient for complex search, correlation and other multiparametric analysis. The data collected so far are in concert with the international epidemiological data.2. Our first evaluation of two treatment modalities of ET reached a very interesting result. The earlier publications showed superiority of HU based treatments over anagrelid. Here we report an opposite result, based on the data of a large number of ET patients and a very long follow up period. When comparing the frequency of the major thrombotic events both treatments proved equally effective, but anagrelid was found to be significantly superior when total thrombotic risk and the frequency of minor thrombotic events was evaluated. DisclosuresJudit:Semmelweis University First Department of Internal Medicine, Division of Haematology: Employment, Other: advisory board BMS, Roche, Novartis, Amgen.

Iron Deficiency Significantly Contributes to Thrombotic Risk and to the Risk of Myelofibrotic Transformation in PV and ET Patients

Background: The heterogeneity of MPN care in Hungary prompted us to establish the Hungarian MPN Working Group (HUMYPRON GROUP) in year 2012.Aims: The HUMYPRON GROUP created our MPN Registry in 2013, the aims were: (1) to gain epidemiological, diagnostic, therapeutic data, to follow up complications and disease transformations. (2) to investigate the adherence to the WHO/2008 diagnostic criteria and to the Landolfi therapeutic guidelines, to gain insight into vascular and hematological complications (3) to try to identify crucial issues and possible gaps, and promote internationally accepted, standard care in MPN.Methods: There was close cooperation between hematologists and information technicians (IT) experts to create an easily evaluable questionnaire. Data of classical MPN patients were collected from Hungarian centers. The thrombotic risk and the risk adapted treatment characteristics were stratified according to the Landolfi criteria. The data entry was started in 2014. The centers entered the data of all the essential thrombocythemia (ET), polycythemia vera (PV) and idiopathic myelofibrosis (IMF) patients they had diagnosed and treated.In the present work we have analysed the tromboembolic (TE) events that have been observed between the diagnosis and data entry, with special emphasis on iron deficiency.Results: During the first active year of the Hungarian MPN Registry 15 of our major or smaller hematological centers provided patient data, all together reaching the evaluable PV(426)+ET(350) patient number of 776. Because of the method we used entering the data, (all patients of a center) a long follow up period (68 months) was gained, allowing us registering and analyzing 294 TE events. (Table 1)Table 1. Occurence of TE events between diagnosis and data entry period (68 months, 776 PV+ET patients)Amin: 113 TE eventsAmaj: 18 TE eventsVmin: 103 TE eventsVmaj: 60 TE eventsAmong the 776 PV/ET patients, the data of iron metabolism were registered in 570 records. 142 of them were iron deficient (47 ET/95 PV). There were 73 TE events registered in 142 iron deficient MPN patients and 140 in the iron non deficient (428 patients) group. The male/female ratio, the median age, the median follow up, the Landolfi risk result were similar in the two groups. Comparing the TE events of iron deficient patients to non iron deficients, significantly more events could have been observed in the former group. (Table 2)Table 2Comparison of the TE events in iron deficient /non deficient groupsTE eventsNo of ptsMale / FemaleMedian age (years)Follow up (months)Landolfi risk result (median)Arterial minorArterial majorVenous minorVenous majorTotal TE events% of pts having TEIron defficient14263/7961,2604,5931326137351%Non defficient428193/23560,1624,53576512614032%The Chi-square statistic is 6.82. The p value is 0.009014. This result is significant at p < 0.05.Phlebotomy in PV patients and aspirin in both (PV and ET) groups seemed to be worsening the high thrombotic risk caused by iron deficiency, observed at the time of diagnosis, but the result was not significant.There were 7 major bleeding episodes in the iron deficient group and 12 in the non deficient. Transformation to myelofibrosis occurred in 9 out of 142 patients with iron deficiency and 12 patients in the 428 non iron deficient patients.The p value is 0.06. This result is significant at p < 0.1.Conclusions:1. We have created a national MPN Registry covering a large part of Hungary. The database is operational, online, user friend, easily adjustable to the new professional needs. It is convenient for complex search, correlation and other multiparametric analysis. The data collected so far are in concert with the international epidemiological data.2. The earlier publications (PVSG) showed iron deficiency as a protective factor in PV patients. Here we report an opposite result, based on the data of a large number of PV+ ET patients and a very long follow up period. When comparing the frequency of the major thrombotic events both group showed the same very low TE frequency, but iron deficiency was found to be significantly inferior when total thrombotic risk and the frequency of minor thrombotic events was evaluated.3. There were slightly more major bleeding episodes in the iron deficient group.4. There were significantly more transformation to myelofibrosis in the iron deficient group. [Display omitted] DisclosuresJudit:Semmelweis University First Department of Internal Medicine, Division of Haematology: Employment, Other: advisory board BMS, Roche, Novartis, Amgen.

Trusting internal medicine in hard times

The health system must adapt to the changing burden of disease. Changes in environmental and social conditions, new individual behaviors, emerging causative factors, and even innovative diagnostic technologies and therapeutic capacity contribute to determining these continuous transformations [1]. Internal medicine has been traditionally considered as the epitome of medical education, and whether it is still able to deal with the changing task of medicine is under debate. Actually, its true meaning is not always understood, even among medical educators, students, health-care practitioners, and policy makers. Its original definition pointed to diseases of the internal organs, but after William Osler, internal was no longer considered to refer to the body, but to the ‘inside’ of the clinical problem [2, 3]. Thus, the definitive connotations of this specialty were clarified: generally oriented, covering a wider field than other specialties characterized by narrow-minded routine or devotion to a particular technique; scientifically driven, applying laboratory sciences to clinical work; hospital based, applying to a clinical domain different from family practice, and humanistically focused, stressing the importance of the doctor–patient relationship [3]. This model of consultant physician, albeit affected by recurrent crises, lasted right through the twentieth century, and has been handed down to our generation of physicians. The most important and longest of these crises, which challenged the existence of internal medicine as a specialty, began around the 1950s, and reached a peak in the early 1990s [4]. The huge progress made by biomedical science meant, on the one hand, that it became impossible for anyone to master internal medicine in its entirety, and, on the other, the need to translate this progress into advanced clinical services provided by highly specialized physicians. This growing fragmentation of medical knowledge and practice led to the fact that the optimal use of economic and technological resources does not correspond to the maximal use of them being overlooked. How did internal medicine react to this widespread and costly reductionism in clinical reasoning? It apparently did not react, but a number of trends became selected and accentuated almost automatically: the holistic approach, which focuses on the patient as an individual rather than on organs or diseases, and the methodological approach, which consists in rearranging the clinical picture in a more easily and interpretable way. In internal medicine, the very extent of the doctrine made it necessary to develop strategies aimed at improving clinical reasoning [5]. The question arises as to whether internal medicine, with these characteristics that at a first glance are not so innovative, can in fact adapt to the challenge of these changes. In the past few years, this difficult task has been further complicated by a global financial crisis whose duration and consequences are difficult to foresee [6]. This crisis is the most serious economic downturn witnessed since the 1930s, which unlike previous ones, started in the most developed countries, severely affecting health spending, health services, health-seeking behavior and health outcomes [7]. Nevertheless, while it is true that the G. R. Corazza M. V. Lenti A. Di Sabatino First Department of Internal Medicine, St. Matteo Hospital, University of Pavia, Pavia, Italy

Su1393 A Prospective Multicenter Study of a Fully-Covered Metal Stent in Patients With Distal Malignant Biliary Obstruction: WATCH-2 Study

A Prospective Multicenter Study of a Fully-Covered Metal Stent in Patients With Distal Malignant Biliary Obstruction: WATCH-2 Study Shomei Ryozawa*, Hiroyuki Isayama, Iruru Maetani, Yousuke Nakai, Hiroshi Kawakami, Ichiro Yasuda, Hitoshi Mochizuki, Hirotoshi Iwano, Hiroyuki Maguchi, Mitsuhiro Kida, Kensuke Kubota, Tsuyoshi Mukai, Osamu Hasebe, Yoshinori Igarashi, Keiji Hanada, Atsushi Irisawa, Takao Itoi, Kei Ito, Hirofumi Kogure Digestive Disease Center, Showa Univ. Northern Yokohama Hospital, Yokohama, Japan; Gastroenterology, Graduate School of Medicine, The Univ. of Tokyo, Tokyo, Japan; Internal Medicine, Toho Univ. Ohashi Medical Center, Tokyo, Japan; Gastroenterology, Hokkaido Univ. Graduate School of Medicine, Sapporo, Japan; First department of Internal Medicine, Gifu University Hospital, Gifu, Japan; Gastroenterology, Yamanashi Prefectural Central Hospital, Kofu, Japan; Center of Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Japan; Gastroenterology, Kitasato Univ. East Hospital, Sagamihara, Japan; Gastroenterology, Yokohama City Univ. Graduate School of Medicine, Yokohama, Japan; Gastroenterology, Gifu Municipal Hospital, Gifu, Japan; Gastroenterology, Nagano Municipal Hospital, Nagano, Japan; Gastroenterology and Hepatology, Toho Univ. Omori Medical Center, Tokyo, Japan; Center of Gastroenterology, Onomichi General Hospital, Onomichi, Japan; Gastroenterology, Preparatory Office for Aizu Medical Center, Fukushima Medical University School of Medicine, Fukushima, Japan; Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan; Gastroenterology, Sendai City Medical Center, Sendai, Japan Background: We previously reported a longer time to recurrent biliary obstruction with less stent migration (8%) using a new partially-covered nitinol self-expandable metallic stent with flared ends (WallflexTM Biliary RX Partially Covered Stent; Boston Scientific Corp, Natick, Mass) in a multicenter prospective study: WATCH study (Gastrointest Endosc. 2012;76:84-92). A fully-covered type of this SEMS (WallflexTM Biliary RX Fully Covered Stent) is commercially available but there is a concern about the increased risk of stent migration in fully-covered self-expandable metal stents (FCSEMS). Here we conducted a multicenter prospective study of this FCSEMS to evaluate safety and efficacy as well as its removability in patients with distal malignant biliary obstruction. Aim: To evaluate the safety and efficacy of a new, commercially available FCSEMS with flared ends (WallflexTM Biliary RX Fully Covered Stent). Patients and Methods: Between September 2011 and July 2012, 156 patients (112 pancreatic cancer, 64 males, a median age of 75 years old, and median survival time of 196 days) with unresectable distal malignant biliary obstruction underwent FCSEMS placement in sixteen Japanese referral centers. Data on baseline characteristics, survival, stent patency, stent-related complications and removability were prospectively collected. Final analysis at 6 months from the last patient accrual is planned in Feb 2013. Primary endpoint was recurrent biliary obstruction (RBO) and secondary endpoints were technical success rate, stent-related complications and stent removal. Results: Stent placement was technically successful in all patients. The rate of RBO was 28% (stent occlusion, 15% and stent migration, 13%). The cause of stent occlusion was biliary sludge (7%), food impaction (2%), tumor overgrowth (2%) and others (4%). Tumor ingrowth was not observed. Median cumulative time to RBO was 269 (interquartile range: 156-464) days. Other stent-related complications included pancreatitis (6%; mild in 5% and moderate in 1%), cholecystitis (4% of 149 patients with gallbladder in situ) and cholangitis without stent occlusion (3%). Stent removal was successful without complications in all 24 attempted cases (100%) after a median of 120 (range, 3471) days from stent placement. Conclusion: In this interim analysis, WallflexTM FCSEMS appeared comparable to PCSEMS in terms of RBO, but stent migration rate was relatively high. Endoscopic removal is easily and safely accomplished in all 24 attempted cases. (Clinical trial registration number: UMI07131).

Effects of erythropoietin administration on iron status in patients with ST-elevation myocardial infarction who underwent successful percutaneous coronary intervention

myocardial infarctionwho underwent successful percutaneous coronary intervention Tomoyasu Suzuki , Ken Toba ⁎, Kiminori Kato , Takuya Ozawa , Hiroshi Suzuki , Naohisa Tomosugi , Hideki Saitoh , Yoshifusa Aizawa a a First Department of Internal Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan b Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan c Proteomics Research Unit, Kanazawa Medical University, Kanazawa, Japan d Chugai Pharmaceutical Co., Ltd, Tokyo, Japan

Balb/3T3細胞のcontact-sensitivemonolayer(cell mat)を利用したヒト癌細胞の抗癌剤感受性試験

Balb/3T3細胞のcontact-sensitivemonolayer(cell mat)を利用したヒト癌細胞の抗癌剤感受性試験

Endobronchial Ultrasound-guided Transbronchial Needle Aspiration for the Diagnosis of Intrathoracic Lesions : Experience of a Single Academic Medical Center

Masanori YASUO ,Takashi KOBAYASHI ,Yayoi TOKORO ,Toshimichi HORIUCHI Michiko IT O ,Kazushi KOJIMA ,Kayoko IK E G A W A ,Atsuhito USHIKI Hiroshi YAMAMOTO ,Masayuki HANAOKA ,Tomonobu KOIZUMI Akihiko YOSHIZAWA ,Takayuki HONDA and Keishi KUBO 1) Endoscopic Examination Center, Shinshu University School of Medicine, Shinshu University Hospital 2) First Department of Internal Medicine, Shinshu University School of Medicine 3) Comprehensive Cancer Center, Division of Clinical Oncology, Shinshu University School of Medicine, Shinshu University Hospital 4) Undergraduate, School of Medicine, Shinshu University School of Medicine 5) Department of Laboratory Medicine, Shinshu University School of Medicine

FROM LANG TO REAVEN History of the First Department of Internal Medicine at Pavlov St Petersburg State Medical University

The review provides evidence that in the early twentieth century the research on the mechanisms of «metabolic cardiovascular syndrome» was started at the Department of Faculty Therapy in Pavlov St Petersburg State Medical University (that was called St Petersburg Women’s Medical University at that time). The investigations were initiated by G.F. Lang, and extended by A.L. Myasnikov, D.M. Grotel, B.V. Ilyinskiy, V.M. Dilman, V.A. Almazov and others, and based on the results they proposed the concept of a cascade of metabolic syndrome and its main components — obesity, insulin resistance and hyperinsulinemia. Nowadays, as the continuation of those studies, the first epidemiological Russian study NICA (National Investigation of Cardiovascular Complications in mеtАbolic syndrome) is conducted by the employees of the Department of Faculty Therapy and Almazov Federal Heart, Blood and Endocrinology Centre.

Coeliac disease and type 1 diabetes mellitus: epidemiology, clinical implications and effects of gluten-free diet

Coeliac disease (CD) is a gluten sensitive chronic enteropathy that affects between 1:100 and 1:300 individuals in the general population of the western world [1]. It is characterised by an increased mortality [2]. Autoimmune disorders such as autoimmune thyroiditis, type 1 diabetes (T1DM), Addison’s disease, autoimmune liver disease, and Sjogren’s syndrome occur much more frequently in patients with CD than in the general population. The clinical relevance of autoimmunity in coeliac disease is threefold: first, it further deteriorates the clinical course of coeliac disease; second, patients might present only with symptoms of secondary autoimmunity and this could favour the diagnosis of minor coeliac disease; and third, gluten withdrawal could improve the control of some associated autoimmune disorders [3]. The associations between CD and T1DM was recognized over 30 years ago, particularly by paediatricians. The prevalence of CD among adults and children with T1DM varies in different geographical populations and is observed to range between 1 and 11 % [4–7]. This close association has been ascribed to the same HLA pattern, namely HLA-DQ2 and/or DQ8, which predisposes individuals to both disorders. Recently, Greco et al. performed a study in the western part of Sicily where they saw that the prevalence of CD among patients with T1DM is 4.5 %. They studied 492 subjects (children and adult patients) with T1DM who had been followed-up regularly at their diabetes unit over a fiveyear period. They found CD in 22 patients [8]. In addition, in accordance with previous studies, they confirmed that CD is more prevalent in female subjects with T1DM than in males [5] and that the age of onset of T1DM is younger in patients with double the disease than in those with diabetes only [6]. None of Greco’s patients presented gastrointestinal symptoms, only two patients presented extraintestinal symptoms (short stature, anaemia and hyposideraemia) and one female patient developed concurrent herpetiformis dermatitis. In fact, one quarter of CD patients with T1DM are totally asymptomatic but the remainder show gastrointestinal symptoms (such as diarrhoea, anorexia, constipation, vomiting, abdominal distension, pain and malnutrition) or extraintestinal symptoms. The most frequent clues in extraintestinal signs are short stature and iron-deficiency anaemia which are present in approximately 50 % of cases; however, fatigue, pubertal delay and vitamin deficiencies are also common, especially in children. Other systemic signs suggesting CD in T1DM patients are a reduced BMI, diminished mass bone, bleeding due to vitamin K deficiency and raised levels of transaminases [9]. CD symptoms (both gastrointestinal and extraintestinal) seem to be much more frequent in children than in adolescents and adults [10]. In the majority of cases (more than 90 %), the diagnosis of T1DM precedes that of CD and Greco et al. confirmed this finding. However, some studies reported that T1DM onset can frequently occur in patients already diagnosed with CD [5]. These data suggest the importance of screening for CD for patients with T1DM at the time of diabetes diagnosis and then annually for several years after diagnosis. In particular, antibody positivity for CD may appear within 6 years from the initial diagnosis of T1DM [4]. Serologial screening for CD consists of endomysial antibodies, antibodies against tissue transglutaminase and deamidated gliadin peptide antibodies. When these antibodies are positive, small intestinal biopsy is mandatory. CD histology is characterized by different degrees of villous A. Marchese E. Lovati F. Biagi (&) G. R. Corazza First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Piazzale Golgi, 19, 27010 Pavia, PV, Italy e-mail: f.biagi@smatteo.pv.it

Desmoplastic malignant mesothelioma originating from the peritoneum

To the Editor, Malignant mesothelioma is an uncommon tumor arising in body cavities lined by mesothelium. Primary malignant peritoneal mesotheliomas make up 20–30 % of all mesotheliomas as represented by the total of pleural origin and are categorized into an epitheloid type. Desmoplastic mesothelioma categorized as a specific subtype of sarcomatoid mesothelioma is very rare and has a poor prognosis. Consequently, a peritoneal origin combined with desmoplastic histology is an extremely rare disease entity. A 74-year-old man presented to our hospital in February 2008 complaining of progressive abdominal distension due to an enlarging abdominal mass. Soluble interleukin-2 receptor was slightly elevated (452 U/mL) while the tumor markers examined were within the normal range. The tumor was rich in lipid content with an ill-defined border by contrast-enhanced abdominal CT scan (Fig. 1a) and magnetic resonance imaging (MRI) (Fig. 1b) the tumor was not enhanced but appeared to be originating from small bowel mesentery. It was difficult to make a definitive diagnosis of malignant lymphoma or mesenteric panniculitis without histological examination. Exploratory laparotomy revealed disseminated small white nodules in the mesentery (Fig. 1c) and the histology led to a pathologic diagnosis of desmoplastic mesothelioma, with a spindlelike shape based on collagenous fibers forming a storiform pattern (Fig. 1d). On immunohistochemistry, the tumor cells expressed vimentin, a smooth muscle actin, and D2-40 but tests for the following epithelial markers, calretinin, WT-1, desmin, CD34, and S-100 were negative (Fig. 1e–g). FISH analysis excluded a p16 deletion. Combination therapy based on either irinotecan (CPT-11) or gemcitabine (GEM) with cisplatin (CDDP) [1] was ineffective. We then gave CDDP intraperitoneally for 15 courses until we judged him to have unresponsive progressive disease. He was placed on optimal supportive care and survived for 49 months after the initial diagnosis. This is the first report on desmoplastic malignant mesothelioma of the peritoneum, since the disease entity was defined by the WHO in 2004. In an extensive review of the literature, we have identified only one previous report of this rare disease, published in 1982 [2]. The present patient is categorized as a diffuse mesothelioma based on the type of tumor spread. Generally, malignant peritoneal mesothelioma is considered to have a poor prognosis. Risk factors for malignant mesothelioma tumorigenesis are known to be an exposure to SV40 virus or to asbestos. The association of peritoneal mesothelioma with asbestos exposure is limited to a few cases and the associations authenticity is controversial. Regarding molecular mechanisms, somatic mutations of CDKN2A or NF2 or epigenetic alterations of RASSF1 gene promoter have been reported to be involved in tumorigenesis [3]. Currently, there are no established standard treatments for malignant peritoneal mesothelioma. Multidisciplinary strategies involving cyto-reductive surgery, systemic chemotherapy, and/or intraperitoneal chemotherapy as the present patient received have improved patient survival. Early diagnosis by exploratory laparotomy followed by combination chemotherapy may have contributed to longer survival for our patient than those of previous reports (median overall survival time for 20.1–26.8 months [1]). In conclusion, our patient highlights two important lessons; first, earlier intervention may contribute to longer H. Takamaru (&) Y. Arimura Y. Shinomura First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan e-mail: h.takamaru@gmail.com

Acute Exacerbation of Pulmonary Fibrosis in Syndrome of Combined Pulmonary Fibrosis and Emphysema Following Lung Surgery : A Report of Two Cases

Yoshiaki KITAGUCHI ,Keisaku FUJIMOTO ,Shiro HORIE ,Keiko ISH II Jiro HIRAYAMA ,Ryosuke MACHIDA ,Masayuki HANAOKA and Keishi KUBO 1) Department of Internal Medicine, Okaya Municipal Hospital 2) Departments of Biomedical Laboratory Sciences, Shinshu University School of Health Sciences 3) Department of Pathology, Okaya Municipal Hospital 4) First Department of Internal Medicine, Shinshu University School of Medicine

Surgery is a real alternative to rescue therapy in patients with steroid-refractory ulcerative colitis

Dear Editor: The life-time risk of a fulminant flare of ulcerative colitis, which is a potentially life-threatening condition, is approximately 15–20 %. The mainstay of conventional therapy is intravenous corticosteroids of 1 mg/bwkg, however approximately one third of the patients fail to respond to a 3to 5-day intensive intravenous regimen, which sets up an interdisciplinary challenge for the surgeon and internist alike. The three options to be considered are intravenous cyclosporin (CsA) therapy, infliximab (IFX) treatment or total proctocolectomy. With the introduction of CsA in the early 1990, the rate of urgent colectomies decreased, since 76 % to 86 % of the patients will initially respond to CsA rescue medication, thus avoiding colectomy in the short run. However, 88 % of patients initially responding to CsA rescue therapy will require colectomy upon 7 years of follow-up and CsA use is still restricted by potential serious adverse events. Colectomy and receiving even a temporary stoma are of the most fearful complications for patients with inflammatory bowel disease. The recommended surgical procedure is restorative proctocolectomy with ileal pouch anal anastomosis (IPAA), which is considered to be a cure for ulcerative colitis; however, reports on functional outcome and postoperative quality of life are contradictory and a variety of complications can occur after surgery. In steroid-refractory ulcerative colitis our therapeutic decision between medical rescue and colectomy remains theoretical in the lack of comparative data. The aim of our study was to evaluate and compare long-term disease outcome in patients with steroid-refractory colitis who either responded to CsA rescue therapy or had to be operated on due to failure of rescue medication. Data of 90 patients with steroid-refractory severe ulcerative colitis were analyzed, of whom 44 patients responded to CsA rescue therapy (CsA responders) and 46 patients underwent colectomy due to early or late failure of rescue therapy (colectomy group). Clinical disease severity was assessed by the Lichtiger score. CsA was introduced intravenously, 4 mg/bwkg initially, which was changed to oral administration after 1 week and maintained for 6–12 months (earlier discontinuation of the therapy was either due to side effects or loss of therapeutic effect); the dosing was continuously monitored by drug serum level. Twenty-six patients received corticosteroids and 17 patients were on immunomodulator therapy at the time of the initiation of CsA rescue. The indication of colectomy was severe disease activity with early failure of the rescue medication or relapse after rescue medication. The mean disease duration was 10 years at the time of surgery. Twenty-five patients K. Gecse :K. Farkas : Z. Szepes : F. Nagy : T. Wittmann : T. Molnar (*) First Department of Internal Medicine, University of Szeged, H-6720, Koranyi fasor 8, Szeged, Hungary e-mail: molnar.tamas@med.u-szeged.hu