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   Table of Contents - Current issue
October-December 2019
Volume 18 | Issue 4
Page Nos. 345-442

Online since Wednesday, December 18, 2019

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Advanced modalities of molecular imaging in precision medicine for musculoskeletal malignancies Highly accessed article p. 345
Narges Jokar, Erik Velez, Hossein Shooli, Habibollah Dadgar, Seyed Abbas Sadathosseini, Majid Assadi, Ali Gholamrezanezhad
Musculoskeletal malignancies consist of a heterogenous group of mesenchymal tumors, often with high inter- and intratumoral heterogeneity. The early and accurate diagnosis of these malignancies can have a substantial impact on optimal treatment and quality of life for these patients. Several new applications and techniques have emerged in molecular imaging, including advances in multimodality imaging, the development of novel radiotracers, and advances in image analysis with radiomics and artificial intelligence. This review highlights the recent advances in molecular imaging modalities and the role of non-invasive imaging in evaluating tumor biology in the era of precision medicine.
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Performance characteristic evaluation of a bismuth germanate-based high-sensitivity 5-ring discovery image quality positron emission tomography/computed tomography system as per National Electrical Manufacturers Association NU 2-2012 p. 351
Ashish Kumar Jha, Sneha Mithun, Ameya D Puranik, Nilendu C Purandare, Sneha Shah, Archi Agrawal, Venkatesh Rangarajan
National Electrical Manufacturers Association (NEMA) provides guidelines to assess the performance of Positron Emission Tomography (PET). A PET/CT scanner, Discovery IQ, GE Medical systems, Milwaukee, USA was installed in our department which has high a sensitivity PET component. We have performed the NEMA NU-2 2012 quality control tests to evaluate this system on site before clinical use. Performance measurements of the PET scanner were made using the NEMA NU2-2012 procedures for spatial resolution, scatter fraction, sensitivity, count rate loss and random coincidence estimation, Noise Equivalent Count Rate (NECR) and image quality. As per NU2 2012, spatial resolution was measured at 1 cm, 10 cm and 20 cm vertically from the centre and at each of these points resolution was measured at tangential, radial and axial directions. Sensitivity was measured at centre and 10 cm off center vertically from the center. The system sensitivity is reported as an average of the two measured values. Scatter fraction and NECR measurements, Image quality test was also performed. The tangential, radial and axial FWHM were 4.99 mm, 4.20 mm and 4.79 mm at 1 cm off centre, 5.49 mm, 4.69 mm and 4.81 mm at 10 cm off centre and 7.99 mm, 5.07 mm and 4.95 mm at 20 cm off centre respectively. The absolute sensitivity of this scanner was found to be 20.1 cps/kBq. The scatter fraction calculated from the decay method was 37.94% and NECR was 125 kcps. The peak NECR was achieved at activity concentration of 8.7 KBq/ml and the count loss below the peak NECR was found to be 0.68%. Image quality test for, contrast recovery, background variability and lung error residual mean met all specifications. Overall PET performance of Discovery IQ whole-body scanner was satisfactory and the scanner met all the performance specifications required by NEMA 2012.
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Using positron-emission tomography–computed tomography for predicting radiotherapy-induced tumor regression in carcinoma esophagus in an Indian population p. 361
Sankalp Singh, Niharika Bisht, Arti Sarin, A. V. S. Anil Kumar, Samir Gupta, Amul Kapoor, Prabha Shankar Mishra
Carcinoma esophagus is a common malignancy of the Indian subcontinent. The role of positron-emission tomography–computed tomography (PET-CT) in the assessment of response to radiotherapy has been widely studied and accepted. However, its precise use as a predictive tool for actual histopathological response to radiotherapy needs further evaluation, especially in an Indian population. The aim of this study was to identify a quantum of metabolic response on PET-CT that can also predict for a good pathological response. Forty-four patients of carcinoma esophagus treated with neoadjuvant chemoradiotherapy followed by surgery were included in the study. All patients underwent a PET-CT before starting treatment as well as at 4–6 weeks after completion of radiotherapy. The percentage change in pre and posttreatment maximum standardized uptake value (SUVmax) value (ΔSUV%) of the primary tumor was correlated against histopathological tumor regression grade (TRG) as per the Mandard's system. Seventy-five percent of the patients with a significant metabolic response, i.e., a ΔSUV% of 60% or more, also had a good pathological response to treatment. Thus, by considering a ΔSUV% of 60%, we could predict for a good pathological response (TRG of 1 or 2) to chemoradiotherapy in our patient set with a sensitivity of 95.45% and a specificity of 72.72%.
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Software development for hepatopulmonary shunt estimation by gamma camera method in transarterial radioembolization p. 366
Ashish Kumar Jha, Sneha Mithun, Ameya Puranik, Nilendu C Purandare, Sneha Shah, Archi Agrawal, Suyash S Kulkarni, Nitin Shetty, Venkatesh Rangarajan
Trans-arterial radioembolization (TARE) is an established treatment for inoperable hepatocellular carcinoma and liver metastases from Carcinoma of gastrointestinal tract. Radiation-induced toxicity to the lung parenchyma is the dose-limiting factor in TARE. Pretreatment hepatopulmonary shunt (HPS) is estimated by gamma camera method by transarterial administration of 370MBq99mTc macro aggregated albumin. We have developed HPS software on XELERIS-1.123 workstation, GE medical systems, Milwaukee, USA, for accurate calculation of HPS. This software has also been tested on a higher version of XELERIS workstation, and it has been found to work well in all versions.
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The correlation between myocardial perfusion scintigraphy and three-dimensional echocardiography in ejection fraction and cardiac volumes for determination of the nearest filtering parameters p. 373
Ali Reza Mardanshahi, Abas Alavi, Jamshid Yazdani, Seyed Jalal Hosseinimehr, Mohammad Khoshakhlagh, Mozhdeh Dabirian, Seyed Mohammad Abedi
End-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) are cardiac volumes that have crucial roles in diagnosis of cardiovascular diseases (CVD) in patients. There are differences between these mentioned parameters in echocardiography (Echo) and myocardial perfusion scintigraphy (MPS) in clinical practice. In this study, we determined the nearest filtering parameters in the analysis of MPS data in comparison with three-dimensional echocardiography (3DE). All of patients were in this study, and 3DE and MPS were performed for all patients at rest phase in the same day. MPS images were analyzed through quantitative gated single photon emission computer tomography (SPECT) software with Butterworth filter which was a fixed order (order = 5) and variable cutoffs (COs) of 0.3, 0.35, 0.4, 0.45, and 0.5. The EDV, ESV, and EF values were measured by 3DE and MPS and compared. Based on the above different COs, the ESVs of MPS were 15.5 ± 18 mL, 18 ± 20 mL, 21 ± 22.5 mL, 22 ± 23 mL, and 22.5 ± 23.5 mL, respectively, while ESV of 3DE was 44.4 ± 23.5 mL. It was observed as a significant difference between MPS and 3DE for ESV. The EDVs of MPS were 61.3 ± 24.5 ml, 64 ± 26.5 ml, 68 ± 29.5 ml, 72 ± 31 ml, and 76 ± 32.2 ml, respectively, while EDV of 3DE was 105 ± 30 ml, which was significantly different between two methods. The EFs of MPS were 79% ± 14%, 76% ± 13%, 73.5% ± 12%, 73.5% ± 11%, and 74% ± 11%, respectively. The EF of 3DE was 58.4% ± 10% ml. It was statistically significant difference in values of EF between SPECT analysis parameters and 3DE. It was interesting when the COs increased from 0.3 to 0.5; the cardiac volumes increased while the EF decreased. The measured ESV and EDV values were lower in females than males while the EFs of females were higher than males. Finally, we demonstrate that the nearest Cos for measuring of EF and cardiac volumes for analysis of MPS data in comparison with 3DE are 0.45 and 0.5, respectively.
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Role of18F-fluorodeoxyglucose positron emission tomography/computed tomography and magnetic resonance imaging in prediction of response to neoadjuvant chemotherapy in pediatric osteosarcoma p. 378
Jehan Ahmed Younis, Ismael Mohammed Al Antably, Manal Zamzam, Hala Taha Salem, Eman Mohammed Zaki, Omneya Ahmed Hassanian
The aim of our study was to evaluate the role of18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) in prediction of response to neoadjuvant chemotherapy (NAC) in pediatric osteosarcoma (OS) patients compared to percentage of tumor necrosis after surgical excision of the tumor. Forty-six pediatric OS patients treated with neoadjuvant chemotherapy and surgery were underwent PET/CT and MRI before, after 3 cycles, and after the completion of neoadjuvant chemotherapy. Imaging parameters include maximum standardized uptake value (SUVmax1, 2, and 3), tumor liver ratio (TLR 1, 2, and 3), and MRI tumor volume (MRTV 1, 2, and 3) at initial assessment before starting NAC, after finishing three cycles and after finishing 6 cycles before tumor excision, respectively. Cutoff values of the PET/CT and MRI parameters were determined using receiver operating characteristic (ROC) curve analysis and percentage of tumor necrosis of postsurgical specimen. Fourteen patients were good responders (30.4%), with more than 90% tumor necrosis, while 31 patients were poor responders (67.4%). The results of one patient were missed. We noticed that higher sensitivity for detecting poor responders was detected by SUVmax3/1, TLR3/1, and MRTV2/1 ratio cutoff values, while higher specificity was detected by TRL2 and SUVmax3 cutoff values. ROC curve analysis of MRTV2/1 and MRTV3/1 ratio was fair in predicting poor responders. PET/CT parameters are capable of predicting histological response to NAC in OS patients with overall sensitivity and specificity higher than MRI parameters.
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Implications of fluorodeoxyglucose uptake in low-intermediate grade metastatic neuroendocrine tumors from peptide receptor radionuclide therapy outcome viewpoint: A semi-quantitative standardized uptake value-based analysis p. 389
Aadil Adnan, Nikita Sampathirao, Sandip Basu
Dual tracer positron emission tomography (PET) imaging approach (with68Ga-DOTATATE PET-computed tomography (CT) for somatostatin receptor and 18-fluorodeoxyglucose (18FDG) PET-CT for glucose transporter receptor) plays a vital role in baseline differentiation, treatment decision-making, and prognostic assessment of neuroendocrine tumors (NETs). The aims of this study were to observe and compare the clinical behavior of low-/intermediate-grade NETs depending on their baseline FDG metabolism (calculated through pre-peptide receptor radionuclide therapy [PRRT] FDG standardized uptake value [SUV]) and to determine its prognostic importance in predicting extent of therapeutic response (post-PRRT) in terms of symptomatic, biochemical, and scan parameters along with the long-term impact on progression-free survival (PFS) and overall survival (OS). Fifty-nine patients with low (≤2%) and intermediate (3–20% Mib-1/Ki-67 index) grade metastatic NET were selected for this retrospective analysis and divided into three groups: Group 1 consisted of patients having low-grade FDG uptake at baseline, predefined as SUVmax<5 (n = 13); Group 2 consisted of those having intermediate-grade FDG uptake at baseline, SUVmax5–10 (n = 34), and Group 3 consisted of patients having high-grade FDG uptake at baseline, defined as SUVmax>10 (n = 12). The trend of FDG avidity was studied from the baseline till the time of analysis and the overall outcomes were compared in terms of symptomatic response (Karnofsky and ECOG performance score), biochemical response, scan response (anatomical and metabolic, RECIST 1.1 and PERCIST 1.0), PFS and OS. Patients in Groups 1 and 2 showed highest proportion of symptomatic complete response, biochemical partial response, and stable disease on scan. These patients also demonstrated better PFS and OS and lowest hazard ratio compared to patients in the Group 3. An important finding was a substantial fraction of the complete metabolic responders (CMRs) across the groups, achieved CMR within first 2 cycles of PRRT (85% of Group 1, 51% of Group 2, and 47% of Group 3). In conclusion, most of the patients of low-/intermediate-grade NET having low-to-moderate baseline tumor FDG metabolism (SUVmax≤10) showed favorable symptomatic response with good biochemical and anatomical disease control and were associated with prolonged PFS and OS, compared to that of those having high-grade baseline tumor FDG metabolism (SUVmax> 10).
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B – Flow assessment of femoral artery as predictor of coronary artery disease in patients evaluated for chest pain by radionuclide myocardial perfusion scintigraphy p. 396
Petar Avramovski, Maja Avramovska, Zaklina Servini, Zorica Nikleski, Keti Veljanovska, Snezana Mihajlova, Kosta Sotiroski, Aleksandar Sikole
In the evaluation of patients with suspected coronary artery disease (CAD), the presence of the superficial femoral artery (SFA) plaque is more informative than a carotid plaque and at least as informative as coronary plaque in the identification of coronary death individuals. In 60 patients with chest pain with a normal electrocardiogram, B-flow ultrasound estimation of SFA plaque and radionuclide myocardial perfusion scintigraphy (MPS) estimation for CAD was performed. We found significant positive correlations between age and SFA plaque score (PS) (P = 0.0084), myocardial ischemia in rest and SFA PS (P < 0.0001), and between transient ischemic dilation (TID) and SFA PS (P = 0.0069), too. The TID correlates only with myocardial ischemia in rest (P = 0.0022) and SFA PS (P = 0.0069). The results we got by the receiver operating characteristics (ROC) curve analysis with TID/without TID were the area under curve (0.704, P = 0.0038). The multiple regression analysis showed standardized coefficient β coefficients for SFA PS and TID (3.4577 and 1.9903, P < 0.001 and P = 0.0021), respectively. By proven correlative relationship of SFA atherosclerotic plaques and CAD, we can use B-flow as a screening method for triage of patients with chest pain before being sent to the assessment of coronary circulation with radionuclide MPS.
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177Lu-DOTATATE and177Lu-prostate-specific membrane antigen therapy in a patient with advanced metastatic radioiodine-refractory differentiated thyroid cancer after failure of tyrosine kinase inhibitors treatment p. 406
Majid Assadi, Hojjat Ahmadzadehfar
Patients with radioiodine-refractory differentiated thyroid cancer (RrDTC) have only a limited or no benefit from radioiodine therapy. For these patients, tyrosine kinase inhibitors have demonstrated encouraging results in advanced RrDTC. Nevertheless, these therapies are related with substantial side effects and a high cost. Somatostatin receptor-based therapies have shown promising findings in advanced RrDTC. Recently, prostate-specific membrane antigen (PSMA) expression was seen in advanced RrDTC in imaging studies. This study presents a case of RrDTC who was treated with177Lu-DOTATATE and177Lu-PSMA, presumably as a first report in this regard.
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Fibrous dysplasia as a possible false-positive finding in68Ga-labeled prostate-specific membrane antigen positron emission tomography/computed tomography study in the follow-up of prostate cancer p. 409
André Marcondes Braga Ribeiro, Eduardo Nóbrega Pereira Lima, Maurìcio Murce Rocha
Positron emission tomography/computed tomography (PET/CT) using68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) has become an important tool in restaging patients with prostate cancer (PCa). Despite its high sensitivity and specificity, this method may produce false-positive findings, as indicated by previous studies. This case report aims to warn nuclear medicine physicians, oncologists, and urologists about the possibility of false-positive findings using this imaging modality, especially when the detected site is unusual for bone metastasis. A 68-year-old man with PCa underwent restaging tests after presenting with increased prostate-specific antigen.68Ga-PSMA PET/CT imaging revealed abnormal uptake in the left humeral head, which anatomically corresponded to the intramedullary and cortical sclerotic area. A biopsy was performed, and the pathology showed a lesion consisting of hard bone tissue with a small focal spot of fibrous dysplasia. Diagnostic issues related to68Ga-PSMA PET/CT imaging should be disseminated to help physicians make appropriate treatment choices for each patient.
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Serendipitous actinomycosis infection mimicking malignant lesion in carcinoma of unknown primary p. 413
Sayak Choudhury, Archi Agrawal, Swapnil Rane, V Rangarajan
Actinomycosis is a bacterial infection caused by Actinomyces species that are commensal in the human oral cavity, digestive tract, and genital tract. The present case highlights actinomycosis of the hypopharynx, mimicking malignancy in18F-fluorodeoxyglucose positron emission tomography-computed tomography.
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Uptake of prostate-specific membrane antigen-targeted18F-DCFPyL in avascular necrosis of the femoral head p. 416
Gonzalo Torga, Yafu Yin, Martin G Pomper, Kenneth J Pienta, Michael A Gorin, Steven P Rowe
In recent years, the emergence of prostate-specific membrane antigen (PSMA)-targeted positron-emission tomography (PET) imaging has brought about a paradigm shift in the way that prostate cancer (PCa) is imaged in many parts of the world. Although PSMA-targeted PET imaging has been demonstrated to be a highly sensitive and specific imaging modality for the identification of sites of PCa, its clinical utility hinges on the ability of imaging specialists and their clinical colleagues to recognize potential false-positive sources of uptake and to tailor therapy based on that recognition. In this manuscript, we report the case of a 74-year-old male with a history of recurrent PCa who was referred for a restaging PSMA-targeted18F-DCFPyL PET/computed tomography (PET/CT). PET images demonstrated low level but focal and definitive uptake in the left femoral head. This uptake corresponded to sclerotic changes on CT whose morphology was most compatible with avascular necrosis without femoral head collapse. In the presented case, the integrated assessment of the CT imaging together with the PET findings was fundamental to avoid misinterpretation of the left femur finding as metastatic disease, which would have ultimately altered the clinical management of the patient.
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Reverse redistribution on Rb-82: Does the mechanism of stress play a role? p. 420
Patrick Martineau, Francois Harel, Matthieu Pelletier-Galarneau
We present a case of reverse redistribution in a patient imaged with Rb-82 positron-emitting tomography. The patient was imaged twice in rapid succession using pharmacological stress – once with dipyridamole and once with dobutamine. The patient demonstrated reverse redistribution after dipyridamole but not after dobutamine administration. We speculate on the relationship between the pharmacological stressing agent and the presence of reverse redistribution.
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Vas deferens infiltration by prostate cancer on prostate-specific membrane antigen-targeted18F-DCFPyL positron emission tomography/computed tomography: A unique visual pattern p. 424
Yafu Yin, Channing J Paller, Martin G Pomper, Kenneth J Pienta, Michael A Gorin, Steven P Rowe
New radiotracers for positron emission tomography imaging that target prostate-specific membrane antigen (PSMA) have emerged as important clinical tools for imaging prostate cancer (PCa). PSMA-targeted radiotracers have demonstrated high sensitivity and high specificity for detecting sites of PCa and are demonstrably superior to conventional imaging modalities such as computed tomography and bone scan. Vas deferens invasion is a rarely encountered poor prognostic feature of PCa. In this case report, we describe a novel pattern of radiotracer uptake in a patient with PCa imaged with PSMA-targeted18F-DCFPyL positron emission tomography/computed tomography that is consistent with diffuse vas deferens involvement.
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Positron emission tomography-computed tomography in subcutaneous panniculitis-like T-cell lymphoma p. 428
Prathyusha Bikkina, Kamala Reddy, Zakir Ali, Naveen Kumar
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare and poorly differentiated type of cutaneous T-cell lymphoma. In this variant, the lymphoma cells infiltrate preferentially into the subcutaneous adipose tissue. It is an indolent type of non-Hodgkin's lymphoma and can be mistaken for panniculitis. Here, we describe the case of a 59-year-old female patient who presented with altered skin pigmentation with diffuse plaque-like patches in the skin around the thighs and legs. A skin biopsy revealed subcutaneous lobular panniculitis composed of lymphocytes, epithelioid histiocytes, and occasional giant cells admixed with atypical lymphoid cells, which were suggestive of cutaneous lymphoma. Immunohistochemistry showed CD3 positive, CD20 negative, CD8 positive, CD4 occasional cells positive, CD56 negative, and CD5 few cells positive, confirming the diagnosis of SPTCL. Therefore, cases with atypical and nonresolving dermatological lesions should raise a suspicion of SPTCL as diagnosis against other benign conditions.
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Metastatic large cell neuroendocrine carcinoma of larynx: Individualizing tumor biology by dual tracer positron emission tomography/computed tomography (68Ga-DOTATATE and18F-fluorodeoxyglucose) molecular imaging and disease stabilization following177Lu-DOTATATE peptide receptor radionuclide therapy after initial progression on chemoradiotherapy p. 431
Sonali Jadhav, Sandip Basu
Debate exists on the disease biology and course of primary large cell neuroendocrine carcinoma (LCNEC) of larynx, being classified as a variant of atypical carcinoid by the World Health Organisation-2005 classification, while literature of its aggressive behavior indicating poorly differentiated neuroendocrine carcinoma (akin to pulmonary LCNEC) exists. The utility of dual tracer positron emission tomography/computed tomography (68Ga-DOTATATE and18F-fluorodeoxyglucose) in deciphering the dynamic tumor biology and feasibility of peptide receptor radionuclide therapy (PRRT) is illustrated in metastatic LCNEC of epiglottis after disease progression following conventional chemoradiotherapy. Relatively, atypical sites of soft-tissue metastases (subcutaneous tissue of arm, scrotal sac, peritoneum, and lamina of thyroid cartilage) and xiphisternum and disease stabilization following177 Lu-DOTATATE PRRT were other noteworthy unique aspects of this report.
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A unicorn in Alice in Wonderland syndrome p. 434
Anne Landais, Thibault Michelin
We report the case of a 56-year-old man presenting several episodes of body image distortions with a sensation of having a horn growing on his forehead, as a unicorn, corresponding to the Alice in Wonderland syndrome. Brain single-photon emission computed tomography with technetium-99m hexamethylpropyleneamine oxime showed hypoperfusion of the visual primary cortex, expanding to the temporo-occipital junction bilaterally but predominantly on the right side.
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Infliximab-induced hot kidneys on bone scintigraphy p. 437
Derya Cayir, Mehmet Bozkurt, Mustafa Filik, Salih Sinan Gultekin
99mTechnetium-methylene diphosphonate bone scintigraphy is widely used in various clinical settings to detect bone abnormalities. Many reasons may cause abnormal tracer uptake in soft tissues on bone scintigraphy. Here, we present a 70-year-old man diagnosed with rheumatoid arthritis receiving chimeric anti-tumor necrosis factor alpha (TNF-α) therapy (infliximab). In order to evaluate the bone involvement of rheumatic disease, the patient underwent a whole-body bone scan that revealed left side dominant diffuse uptake in both kidneys defined as the “hot kidneys.” Since the patient had no other identifiable reason, anti-TNF-α therapy might be responsible for the “hot kidneys” on bone scan. Thus, therapy regiment of the patient changed from the chimeric anti-TNF-α to a human monoclonal TNF inhibitor (golimumab). After 6 months of the change of the therapy, the bone scintigraphy was repeated and revealed that the previous “hot kidneys” finding had disappeared.
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The dolichosigma partially located on the right: How justified is the concept of the right slow transit constipation? p. 440
Michael David Levin
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