IL-10 promoter gene polymorphism associated with the occurrence of chronic GVHD and its clinical course during systemic immunosuppressive treatment for chronic GVHD after allogeneic peripheral blood stem cell transplantation

BACKGROUND: The current study attempted to evaluate the association between IL-10 promoter gene polymorphism and transplant outcomes including the occurrence of chronic graft-versus-host disease (GVHD) and its clinical course during systemic immunosuppressive treatment (IST) among 60 recipients of cytokine-mobilized peripheral blood stem cell (PBSC) from HLA-matched sibling donors. METHODS: We analyzed 3 single-nucleotide polymorphisms in proximal region of IL-10 promoter gene (-1082/-819/-592). RESULTS: In the current study, only two haplotypes (1082*A/819*T/592*A [ATA] and 1082*A/819*C/592*C [ACC]) were found. An increased occurrence of chronic GVHD was noted dependent on the IL-10 haplotypes (43% vs. 68% vs. 96% in ACC/ACC vs. ATA/ACC vs. ATA/ATA haplotype, P=0.003). In a logistic regression based on multinomial model, ATA/ATA homozygote had 7-fold increasing risk of the development of chronic GVHD compared with ACC/ACC homozygote. The incidence of chronic GVHD at 1 year was 46%+/-20%, 64%+/-10%, and 82%+/-5% in ACC/ACC, ATA/ACC and ATA/ATA group, respectively (P=0.0266). Plus, the duration of systemic IST was significantly shorter in recipients without ATA-haplotype comparing with those with ATA haplotype (339 days vs. 1,146 days, P=0.0091). CONCLUSION: IL-10 promoter gene polymorphism was found to be apparently associated with chronic GVHD after allogeneic peripheral blood stem cell transplantation from HLA-matched sibling donors.     

Clinicopathologic analysis of early ampullary cancers with a focus on the feasibility of ampullectomy

OBJECTIVE: The purpose of this study was to evaluate whether ampullectomy can substitute for pancreatoduodenectomy (PD) in early ampullary cancer by clinicopathologic study. SUMMARY BACKGROUND DATA: Although ampullectomy has been attempted in early ampullary cancer (pTis, pT1), the indication and extent of resection have not been established. METHODS: Of 201 patients who had undergone PD for ampullary cancer between 1986 and 2002, 67 patients with a histologic diagnosis of pTis (n = 5) or pT1 (n = 62) cancer were analyzed retrospectively. Pathologic PD specimens were reviewed to analyze the cancer spread pattern, and medical records were reviewed for clinical outcomes. RESULTS: The 5-year survival rate of the 66 patients with early ampullary cancer (excluding one mortality) was 83.7%. Recurrence was confirmed in 12 patients (18.2%) and all died because of the recurrence. Pathologic review showed that 22 patients (32.8%) had at least one risk factor for failure after ampullectomy: lymph node metastasis (n = 6, 9.0%), perineural invasion (n = 1), or mucosal tumor infiltration along the CBD or P-duct (n = 15, 22.4%). Mean lengths of invasion into the CBD or the P-duct beyond the sphincter of Oddi were 7.7 mm (range, 1-25 mm) or 6.3 mm (range, 2-18 mm), respectively. Moreover, these risk factors were not correlated with tumor size, histologic grade, or the gross morphology of the primary tumor, although pTis cancer or pT1 cancer sized 1.0 cm or less was found to be least associated with risk factors. CONCLUSIONS: Ampullectomy for early ampullary cancer should not be considered an alternative operation to PD because of the high possibility of recurrence. PD should be preferably performed for adequate radical resection, even in early ampullary cancer, and ampullectomy should be reserved for those who have pTis or pT1 cancer sized 1.0 cm or less with high operative risk.     

Lumbar Lordosis of Spinal Stenosis Patients during Intraoperative Prone Positioning

Background

To evaluate the effect of spondylolisthesis on lumbar lordosis on the OSI (Jackson; Orthopaedic Systems Inc.) frame. Restoration of lumbar lordosis is important for maintaining sagittal balance. Physiologic lumbar lordosis has to be gained by intraoperative prone positioning with a hip extension and posterior instrumentation technique. There are some debates about changing lumbar lordosis on the OSI frame after an intraoperative prone position. We evaluated the effect of spondylolisthesis on lumbar lordosis after an intraoperative prone position.

Methods

Sixty-seven patients, who underwent spinal fusion at the Department of Orthopaedic Surgery of Gwangmyeong Sungae Hospital between May 2007 and February 2012, were included in this study. The study compared lumbar lordosis on preoperative upright, intraoperative prone and postoperative upright lateral X-rays between the simple stenosis (SS) group and spondylolisthesis group. The average age of patients was 67.86 years old. The average preoperative lordosis was 43.5° (± 14.9°), average intraoperative lordosis was 48.8° (± 13.2°), average postoperative lordosis was 46.5° (± 16.1°) and the average change on the frame was 5.3° (± 10.6°).

Results

Among all patients, 24 patients were diagnosed with simple spinal stenosis, 43 patients with spondylolisthesis (29 degenerative spondylolisthesis and 14 isthmic spondylolisthesis). Between the SS group and spondylolisthesis group, preoperative lordosis, intraoperative lordosis and postoperative lordosis were significantly larger in the spondylolisthesis group. The ratio of patients with increased lordosis on the OSI frame compared to preoperative lordosis was significantly higher in the spondylolisthesis group. The risk of increased lordosis on frame was significantly higher in the spondylolisthesis group (odds ratio, 3.325; 95% confidence interval, 1.101 to 10.039; p = 0.033).

Conclusions

Intraoperative lumbar lordosis on the OSI frame with a prone position was larger in the SS patients than the spondylolisthesis patients, which also produced a larger postoperative lordosis angle after posterior spinal fusion surgery. An increase in lumbar lordosis on the OSI frame should be considered during posterior spinal fusion surgery, especially in spondylolisthesis patients.     

100 multivisceral transplants at a single center

OBJECTIVE: The objective of this study was to summarize the evolution of multivisceral transplantation over a decade of experience and evaluate its current status. SUMMARY BACKGROUND DATA: Multivisceral transplantation can be valuable for the treatment of patients with massive abdominal catastrophes. Its major limitations have been technical and rejection of the intestinal graft. METHODS: This study consisted of an outcome analysis of 98 consecutive patients who received multivisceral transplantation at our institution. This represents the largest single center experience to date. RESULTS: The most common diseases in our population before transplant were intestinal gastroschisis and intestinal dysmotility syndromes in children, and mesenteric thrombosis and trauma in adults. Kaplan Meier estimated patient and graft survivals for all cases were 65% and 63% at 1 year, 49% and 47% at 3 years, and 49% and 47% at 5 years. Factors that adversely influenced patient survival included transplant before 1998 (P = 0.01), being hospitalized at the time of transplant (P = 0.05), and being a child who received Campath-1H induction (P = 0.03). Among 37 patients who had none of these 3 factors (15 adults and 22 children), estimated 1- and 3-year survivals were 89% and 71%, respectively. Patients transplanted since 2001 had significantly less moderate and severe rejections (31.6% vs 67.6%, P = 0.0005) with almost half of these patients never developing rejection. CONCLUSIONS: Multivisceral transplantation is now an effective treatment of patients with complex abdominal pathology. The incidences of serious acute rejection and patient survival have improved in the most recent experience. Our results show that the multivisceral graft seems to facilitate engraftment of transplanted organs and raises the possibility that there is a degree of immunologic protection afforded by this procedure.     

Effects of obesity on lower urinary tract symptoms in Korean BPH patients

We analyzed the effects of obesity on lower urinary tract symptoms （LUTSs） in Korean benign prostatic hyperplasia （BPH） patients. This is a multicenter, cross-sectional, prospective study conducted in four centers in Korea. A total of 602 men with LUTSs secondary to BPH were included. BPH/LUTSs cases were men aged ≥ 40 years with intemational prostate symptom scores （IPSS） ≥ 8 points. Height, weight and waist circumference were measured. Among the 602 patients, 156 patients had a waist circumference above 90 cm, representing central obesity, and 215 patients had a body mass index above 25 kg m2. Waist circumference was positively correlated with prostate volume （P = 0.034）. Men with waist circumference 〉 90 cm experienced a 1.36-fold increased risk of severe LUTSs （95% CI 0.82-2.41） compared with men with waist circumference ≤ 90 cm. Prostate volume was positively correlated with urgency and nocturia in men with central obesity. In this population of Korean men diagnosed with BPH, central obesity rather than overall obesity seems to be the more important predictor of LUTSs correlated with BPH.     

Effect of radiofrequency radiation exposure on mouse skin tumorigenesis initiated by 7,12-dimethybenz[α]anthracene

Purpose: Although radiofrequency (RF) radiation is not considered mutagenic, it has been suggested as a promoter of tumorigenesis. To study if RF radiation has a tumor promoting effect, we exposed mice with skin tumorigenesis initiated by 7,12-dimethybenz[α]anthracene (DMBA) to RF radiation.

Materials and methods: Eighty male ICR mice were subjected to a single DMBA application (100 μg/100 μl acetone/mouse) on shaved dorsal skin at the age of 7 weeks. After one week, the mice were randomized into four equal groups of 20 mice each: i.e., sham-, 849 MHz-, 1,763 MHz-exposed, and 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated groups. The RF exposure was conducted at a whole body average specific absorption rate (SAR) of 0.4 W/Kg, for 2 cycles of 45 min exposure with a 15 min interval each day, 5 days a week for 19 weeks. The TPA-treated group served as a positive control for skin tumorigenesis and were administered TPA (4 μg/100 μl acetone/mouse) twice weekly without RF exposure.

Results: All mice were examined weekly at a macroscopic level. No skin tumors were observed in any groups except in the TPA-treated positive control group. TPA is known tumor promoter in DMBA-induced skin carcinogenesis and tumor incidence in the TPA treated group was 95%. At week 20 after DMBA initiation, skin tissues were analyzed immunohistochemically using anti-proliferating cell nuclear antigen (PCNA) antibody. No differences were observed by pathological examination or by PCNA staining between the sham- and the RF-exposed groups. The expression of cyclin D1 and c-fos were detected only in the tumorous skin tissues of the TPA-treated group.

Conclusion: No evidence was found that RF radiation serves as a tumor promoter for skin tumors. Our data suggests that 849 MHz and 1,763 MHz RF radiations, similar to those emitted from mobile phones, do not have any promoting effect on skin tumor development in DMBA-initiated mice.     

Primary Endobronchial Marginal Zone B-Cell Lymphoma of Bronchus-Associated Lymphoid Tissue: CT Findings in 7 Patients

Objective

To investigate CT and ¹⁸F-flurodeoxyglucose (¹⁸F-FDG) positron-emission tomography/CT findings of primary endobronchial marginal zone B-cell lymphoma of the bronchus-associated lymphoid tissue (BALT).

Materials and Methods

From June 2006 through April 2012, seven patients (six female, one male; age range, 21-61 years; mean age, 49 years) were examined who were pathologically diagnosed with the primary endobronchial marginal zone B-cell lymphoma of BALT. We evaluated the locations and characteristics of the lesions on CT and ¹⁸F-FDG-PET/CT scans. The lesions were classified into the following three patterns: 1) solitary intraluminal nodule; 2) several tiny nodular protrusions; and 3) diffuse wall thickening.

Results

A solitary intraluminal nodule was observed in four patients (57.1%), several tiny nodular protrusion in two patients (28.6%), and diffuse wall thickening in one patient (14.3%). The lesions were categorized into 3 major locations: confined to the trachea (n = 3), confined to the lobar bronchus (n = 2), and diffuse involvement of the trachea and both main bronchi (n = 2). All lesions demonstrated homogeneous iso-attenuation as compared with muscle on pre- and post-enhancement scans. Secondary findings in the lungs (n = 3; 42.9%) included postobstructive lobar atelectasis (n = 1), air trapping (n = 1), and pneumonia (n = 1). On ¹⁸F-FDG-PET/CT (n = 5), 4 lesions showed homogeneous uptake with maximum standardized uptake values (mSUV), ranging 2.3-5.7 (mean mSUV: 3.3). One lesion showed little FDG uptake.

Conclusion

Primary endobronchial marginal zone B-cell lymphoma of the BALT manifests as three distinct patterns on CT, with the solitary intraluminal nodule presenting as the main pattern. Most lesions demonstrate homogeneous but weak FDG uptake on ¹⁸F-FDG-PET/CT.     

I-MIBG myocardial scintigraphy as a noninvasive screen for the diagnosis of coronary artery spasm

Background. It has been suggested that the sympathetic nervous system might play an important role in the development of coronary artery spasm. However, no cardiac imaging modality has been able to demonstrate abnormal sympathetic innervation in patients with coronary artery spasm. The purpose of this study was to assess the presence and location of abnormal sympathetic innervation using iodine 123-metaiodobenzylguanidine (¹²³I-MIBG) single photon emission computed tomography (SPECT) and to evaluate the clinical efficacy of ¹²³I-MIBG SPECT as a noninvasive screening test in patients with coronary artery spasm.Methods and Results. Coronary arteriography and a provocative test with intravenous administration of ergonovine maleate were performed in 26 patients (20 men, 6 women, mean age 48.2 ± 12.0 years, range 20 to 67 years) who were suspected of having a coronary artery spasm. The subjects were divided into 2 groups: group 1 (n = 18) comprised subjects with a positive provocative test result, and group 2 (n = 8) comprised subjects with negative provocative test results. Ten healthy subjects served as controls. No abnormal MIBG uptake was observed in the control subjects. Abnormal sympathetic nervous innervation using ¹²³I-MIBG SPECT was observed either as a reduced uptake or a defective pattern in the perfused areas in 13 of the 18 regions supplied by vessels of ergonovine-induced vasospasm. Normal sympathetic innervation, as evidenced by normal ¹²³I-MIBG uptake, was noted in all of the 60 segments of normal vessel territories. Reduced uptake of ¹²³I-MIBG was not detected in the perfused areas of 5 vasospasm-induced vessels (perfusion territory of left anterior descending coronary artery [LAD] and the right coronary artery [RCA] in 2 and 3 patients, respectively). The sensitivity and specificity of ¹²³I-MIBG for detection of coronary artery spasm were 72.2% (95% confidence interval [CI] 55 % to 89 %) and 100 %, respectively. The positive predictive and negative predictive values were 100% and 92.3% (95% CI 91% to 93%), respectively.Conclusion. ¹²³I-MIBG SPECT is a feasible method to evaluate noninvasively and localize the territories of coronary arteries with spasm. Invasive diagnostic coronary arteriography with ergonovine provocation test may be unnecessary for diagnosis of coronary artery spasm in patients with typical resting pain, negative exercise test or normal thallium perfusion scan results, but showing abnormalities in ¹²³I-MIBG SPECT.     

123I-MIBG myocardial scintigraphy as a noninvasive screen for the diagnosis of coronary artery spasm

Background  It has been suggested that the sympathetic nervous system might play an important role in the development of coronary artery spasm. However, no cardiac imaging modality has been able to demonstrate abnormal sympathetic innervation in patients with coronary artery spasm. The purpose of this study was to assess the presence and location of abnormal sympathetic innervation using iodine 123-metaiodobenzylguanidine (¹²³I-MIBG) single photon emission computed tomography (SPECT) and to evaluate the clinical efficacy of ¹²³I-MIBG SPECT as a noninvasive screening test in patients with coronary artery spasm. Methods and Results  Coronary arteriography and a provocative test with intravenous administration of ergonovine maleate were performed in 26 patients (20 men, 6 women, mean age 48.2±12.0 years, range 20 to 67 years) who were suspected of having a coronary artery spasm. The subjects were divided into 2 groups: group 1 (n=18) comprised subjects with negative provocative provocative test result, and group 2 (n=8) comprised subjects with negative provocative test results. Ten healthy subjects served as controls. No abnormal MIBG uptake was observed in the control subjects. Abnormal sympathetic nervous innervation using ¹²³I-MIBG SPECT was observed either as a reduced uptake or a defective pattern in the perfused areas in 13 of the 18 regions supplied by vessels of ergonovine-induced vasospasm. Normal sympathetic innervation, as evidenced by normal ¹²³I-MIBG uptake, was noted in all of the 60 segments of normal vessel territories. Reduced uptake of ¹²³I-MIBG was not detected in the perfused areas of 5 vasospasm-induced vessels (perfusion territory of left anterior descending coronary artery [LAD] and the right coronary artery [RCA] in 2 and 3 patients, respectively). The sensitivity and specificity of ¹²³I-MIBG for detection of coronary artery spasm were 72.2% (95% confidence interval, [CI] 55% to 89%) and 100%, respectively. The positive predictive and negative predictive values were 100% and 92.3% (95% CI 91% to 93%), respectively. Conclusion   ¹²³I-MIBG SPECT is a feasible method to evaluate noninvasively and localize the territories of coronary arteries with spasm. Invasive diagnostic coronary arteriography with ergonovine provocation test may be unnecessary for diagnosis of coronary artery spasm in patients with typical resting pain, negative exercise test or normal thallium perfusion scan results, but showing abnormalities in ¹²³I-MIBG SPECT. Presented in part at the European Association of Nuclear Medicine Congress, September 1996, Copenhagen, Denmark.