Simultaneous and sequential combination of genetic and epigenetic biomarkers for the presence of high-grade dysplasia in patients with pancreatic cyst: Discovery in cyst fluid and test in pancreatic juice.

BACKGROUND/OBJECTIVES: Screening patients with intraductal papillary mucinous neoplasms (IPMN) has the primary goal of identifying potentially curable noninvasive precursors. We aimed to evaluate the diagnostic impact of genetic and epigenetic biomarkers in the presence of noninvasive precursors. METHODS: Mutated KRAS/GNAS and methylated SOX17/TBX15/BMP3/TFPI2 DNA were assessed by droplet digital PCR in a discovery cohort of 70 surgically aspirated cyst fluids, and diagnostic performances for differentiating high-grade dysplasia (HGD) from low-grade dysplasia (LGD) was evaluated. We then tested these markers using an independent test cohort consisting of 156 serially collected pancreatic juice samples from 30 patients with IPMN. RESULTS: Mutated KRAS and GNAS are specific for IPMNs but are not helpful for the prediction of histological grades. Cyst fluids from IPMN with HGD showed higher methylation levels of SOX17 (median, 0.141 vs. 0.021; P = 0.086) and TBX15 (median, 0.030 vs. 0.003; P = 0.028) than those with LGD. The combination of all tested markers yielded a diagnostic performance with sensitivity of 69.6%, and specificity of 90.0%. Among the 30 pancreatic juice samples exhibiting the highest abundance of KRAS/GNAS mutations in each patient in the test cohort, patients with histologically proven HGD due to pancreatic resection had a significantly higher prevalence (100% vs. 31%, P = 0.018) and abundance (P = 0.037) of methylated TBX15 than those without cytohistological diagnosis undergoing surveillance. CONCLUSIONS: A simultaneous and sequential combination of mutated and methylated DNA markers in pancreatic cyst fluid and juice sample markers can help detect noninvasive pancreatic precursor neoplasms.

Facet cysts in the subaxial cervical spine: Case series focused on radiological and histopathological findings with a scoping review.

BACKGROUND: Facet cysts in the subaxial cervical spine are a relatively rare cause of neuropathy. This case series aimed to investigate the radiological and histopathological features and surgical results of these lesions, and provide possible mechanisms of cyst development. METHODS: Thirteen subaxial cervical facet cysts in 12 patients were diagnosed on the basis of magnetic resonance imaging and computed tomography with facet arthrography. Surgical outcomes were evaluated according to the Japanese Orthopaedic Association scores for cervical myelopathy, or Tanaka's scores for cervical radiculopathy. These results were presented in combination with a scoping review of the literature. RESULTS: Seven cysts were found in the posteromedial region, and six in the posterolateral portion of the spinal canal. Computed tomography revealed degeneration of all involved facet joints. All patients underwent decompression, and the mean recovery rates of Japanese Orthopaedic Association scores and Tanaka's scores were 57.1% and 87.5%, respectively. Histopathologically, all cysts were continuous with the degenerated ligamentum flavum. In the scoping review, the patients' mean age was 65.1 years. The cysts were distributed as follows: 3.6% at C2-3, 10.7% at C3-4, 14.3% at C4-5, 5.4% at C5-6, 7.1% at C6-7, and 58.9% at C7-T1. The presenting symptoms were myelopathy (49.4%) and radiculopathy (50.0%). Radiologically, 55% and 45% of the cysts were of the posteromedial and posterolateral types. Of the patients, 76.9% underwent decompression only, and 23.1% had concomitant fusion. Cyst recurrence was not observed in the mean follow-up period of 15.1 months. CONCLUSIONS: The pathogenesis of cysts is closely related to degenerative changes in the facet joint and ligamentum flavum, and rupture in degenerated ligaments can develop into a cavity, which contributes to cyst formation. The scoping review suggests that cyst resection generally results in positive outcomes without recurrence in either decompression alone or concomitant fusion.

Surgical management of facet cysts in the thoracic spine: Radiological manifestations and results of fenestration.

BACKGROUND: Facet cysts in the thoracic spine are a rare cause of thoracic myelopathy. We aimed to investigate the clinical/radiological features and surgical results of these lesions. METHODS: Nine thoracic facet cysts in eight patients (seven men, one woman) were diagnosed based on magnetic resonance imaging (MRI) and computed tomography (CT) with facet arthrography findings and surgically treated. The mean patient age was 71 (59-83) years. The cysts were distributed as follows: one each at T8-9 and T9-10, two each at T1-2 and T11-12, and three at T10-11. The mean follow-up period was 1.8 (1-5) years. Clinical and radiological features were retrospectively investigated, and surgical outcomes were evaluated according to modified Japanese Orthopaedic Association (JOA) scores for thoracic myelopathy (full score: 11). RESULTS: Neurological examination revealed progressive thoracic transverse myelopathy in all patients with a mean disease duration of 1.2 months (2 weeks-2 months). MRI revealed a total of nine cysts across the eight patients: four in the median region and five in the paramedian portion of the spinal canal. CT revealed degeneration in all involved facet joints. All the cysts were in communication with the neighboring facet joint confirmed by CT facet arthrography. All patients underwent bilateral fenestration, and the cysts were resected with the ligamentum flavum. The mean preoperative and postoperative modified JOA scores were 4.5 and 8.8, respectively. The mean recovery rate was 67.5%. Differences in the degree of local kyphosis were 2° or less between before and after surgery. On histopathology, synovial lining cells were not noted in any case. CONCLUSIONS: Decompression surgery is recommended for treating progressive myelopathy in patients with cystic lesions. Our study suggests that thoracic facet cyst resection with satisfactory surgical outcomes would be possible through fenestration.

Case of hydrocele testis caused by vaginalitis, a rare manifestation of immunoglobulin G4-related disease.

We report an extremely rare manifestation of immunoglobulin G4-related disease, presented with hydrocele testis. A planned hydrocelectomy was converted to a high orchiectomy because of bloody fluid, suggestive of paratesticular malignancy. The histopathology showed vaginalitis, which was finally diagnosed as immunoglobulin G4-related disease. To the best of our knowledge, this is the first report of immunoglobulin G4-related disease representing hydrocele testis.

Increasing Incidence of Degenerative Spinal Diseases in Japan during 25 Years: The Registration System of Spinal Surgery in Tohoku University Spine Society.

Spinal disorders affect mainly older people and cause pain, paralysis and/or deformities of the trunk and/or extremities, which could eventually disturb locomotive functions. For ensuring safe and high-quality treatment of spinal disorders, in 1987, the Tohoku University Spine Society (TUSS) was established by orthopedic departments in Tohoku University School of Medicine and its affiliated hospitals in and around Miyagi Prefecture. All spine surgeries have been enrolled in the TUSS Spine Registry since 1988. Using the data from this registration system between 1988 and 2012, we demonstrate here the longitudinal changes in surgical trends for spinal disorders in Japan that has rushed into the most advanced "aging society" in the world. In total, data on 56,744 surgeries were retrieved. The number of spinal surgeries has annually increased approximately 4-fold. There was a particular increase among patients aged ≥ 70 years and those aged ≥ 80 years, with a 20- to 90-fold increase. Nearly 90% of the spinal operations were performed for degenerative disorders, with their number increasing approximately 5-fold from 705 to 3,448. The most common disease for surgery was lumbar spinal stenosis (LSS) (35.9%), followed by lumbar disc herniation (27.7%) and cervical myelopathy (19.8%). In 2012, approximately half of the patients with LSS and cervical myelopathy were ≥ 70 years of age. In conclusion, the number of spinal operations markedly increased during the 25-year period, particularly among older patients. As Japan has a notably aged population, the present study could provide a near-future model for countries with aging population.

Ichthyosis uteri with leiomyoma.

A 58-year-old, postmenopausal, multiparous woman presented with a chief complaint of abnormal vaginal bleeding. Endometrial cytology was evaluated twice, revealing only squamous epithelial cells both times. Degenerated leiomyoma or uterine sarcoma was suspected from imaging findings, and total abdominal hysterectomy and bilateral salpingo-oophorectomy were therefore performed. However, histopathological examination revealed no signs of malignancy, and the patient was diagnosed as having ichthyosis uteri with uterine leiomyoma. No koilocytosis was evident, and immunostaining for p16 was also negative. Ichthyosis uteri is an extremely rare disease of unknown origin in which squamous metaplasia of the endometrium occurs across a wide area. Although regarded as a benign condition, cases have been reported in which the underlying condition was squamous cell carcinoma or endometrial adenocarcinoma. If ichthyosis uteri is present, a comprehensive approach is required, and the possibility of uterine malignancy should be considered. However, there may be no direct association between the malignant lesions and ichthyosis uteri.

[Primary Malignant Melanoma of the Gallbladder].

Primary malignant melanoma of the gallbladder is a rare disease, and 37 cases have been reported in the literature.The current patient was a 78-year-old man who was admitted with a pelvic tumor and left leg edema due to compression of the external iliac vein by the pelvic tumor.The edema improved following resection of the tumor, which was diagnosed at pathology as a malignant melanoma.After surgery, the patient became anorexic and complained of discomfort in the upper right abdomen.A whole body FDG-PET scan demonstrated significant uptake in the gallbladder and in the lymph nodes of the lower abdomen.The patient underwent open cholecystectomy, and the pathological diagnosis was malignant melanoma. Junctional activity was seen in the gallbladder, suggesting that this was the primary site.No melanocytic lesions of the skin or eyes were detected, further supporting the diagnosis of primary malignant melanoma of the gallbladder.Chemotherapy was initiated, but the patient died on February 28, 2016.

Reoperation rates after fenestration for lumbar spinal canal stenosis: a 20-year period survival function method analysis.

PURPOSE: Fenestration is the gold standard surgery for lumbar spinal canal stenosis in Japan. Several previous studies have analyzed the reoperation rates in large numbers of patients undergoing several surgical procedures such as laminectomy with or without instrumented spinal fusion; however, there have been few studies focusing solely on fenestration. The purpose of this study was to calculate the reoperation rates after fenestration using the survival function method. METHODS: Form 1988-2007, 6,998 surgeries for lumbar spinal canal stenosis occurred in Miyagi prefecture, Japan, and these patients were enrolled by the spinal surgery registration system of the Department of Orthopaedic Surgery, Tohoku University. Among these, 5,835 surgeries involved fenestration as a primary surgery and for those who underwent ≥2 lumbar surgeries we analyzed the reoperation rates using the Kaplan-Meier method. RESULTS: Among the 5,835 patients undergoing primary fenestration, 215 patients underwent 221 revisions; 112 included the same spinal levels and 103 were revised only at other levels as primary fenestration. The overall reoperation rates were 0.8% at 1 year, 2.9% at 5 years, 5.2% at 10 years, 7.5% at 15 years and 8.6% at >17.7 years. Reoperation rates for those at the same spinal levels were 0.6% at 1 year, 1.7% at 5 years, 2.7% at 10 years, 3.8% at 15 years, and 4.1% at >17.0 years. CONCLUSIONS: Fenestration can be performed at low cost using standard spinal surgery equipments. The reoperation rates of this procedure were lower than previously reported for several other surgical procedures.

Hepatic steatosis in leptin-deficient mice is promoted by the PPARgamma target gene Fsp27.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is induced in leptin-deficient (ob/ob) mouse liver and is critical for the development of hepatic steatosis. The present study shows that fat-specific protein 27 (Fsp27) in ob/ob liver is a direct target gene of PPARgamma and can elevate hepatic triglyceride levels. FSP27 belongs to the CIDE family, composed of CIDE A, CIDE B, and FSP27/CIDE C, all of which contain a conserved CIDE-N domain. FSP27 was recently reported to be a lipid droplet-binding protein and to promote lipid accumulation in adipocytes. The Fsp27 gene was expressed at high levels in ob/ob liver and at markedly lower levels in ob/ob livers lacking PPARgamma. Forced expression of FSP27 by adenovirus in hepatocytes in vitro or in vivo led to increased triglyceride levels. Knockdown by adenovirus expressing FSP27 shRNA resulted in lower accumulation of hepatic triglycerides compared to control adenovirus-infected liver. Taken together, these results indicate that FSP27 is a direct mediator of PPARgamma-dependent hepatic steatosis.

Quantitative diagnosis of diffuse alveolar damage using extravascular lung water.

OBJECTIVES: Acute respiratory distress syndrome is characterized by diffuse alveolar damage and increased extravascular lung water levels. However, there is no threshold extravascular lung water level that can indicate diffuse alveolar damage in lungs. We aimed to determine the threshold extravascular lung water level that discriminates between normal lungs and lungs affected with diffuse alveolar damage. DESIGN: A retrospective analysis of normal lungs and lungs affected with diffuse alveolar damage was performed. SETTING: Normal lung cases were taken from published data. Lung cases with diffuse alveolar damage were taken from a nationwide autopsy database. All cases of autopsy followed hospital deaths in Japan from more than 800 hospitals between 2004 and 2009; complete autopsies with histopathologic examinations were performed by board-certified pathologists authorized by the Japanese Society of Pathology. PATIENTS: Normal lungs: 534; lungs with diffuse alveolar damage: 1,688. INTERVENTIONS: We compared the postmortem weights of both lungs between the two groups. These lung weights were converted to extravascular lung water values using a validated equation. Finally, the extravascular lung water value that indicated diffuse alveolar damage was estimated using receiver operating characteristic analysis. MEASUREMENTS AND MAIN RESULTS: The extravascular lung water values of the lungs showing diffuse alveolar damage were approximately two-fold higher than those of normal lungs (normal group, 7.3±2.8 mL/kg vs diffuse alveolar damage group 13.7±4.5 mL/kg; p<0.001). An extravascular lung water level of 9.8 mL/kg allowed the diagnosis of diffuse alveolar damage to be established with a sensitivity of 81.3% and a specificity of 81.2% (area under the curve, 0.90; 95% CI, 0.88-0.91). An extravascular lung water level of 14.6 mL/kg represented a 99% positive predictive value. CONCLUSIONS: This study may provide the first validated quantitative bedside diagnostic tool for diffuse alveolar damage. Extravascular lung water may allow the detection of diffuse alveolar damage and may support the clinical diagnosis of acute respiratory distress syndrome. The best extravascular lung water cut-off value to discriminate between normal lungs and lungs with diffuse alveolar damage is around 10 mL/kg.

SNPD-CRISPR: Single Nucleotide Polymorphism-Distinguishable Repression or Enhancement of a Target Gene Expression by CRISPR System.

A wide range of diseases, including cancer, autoimmune diseases, or neurodegenerative diseases, have been associated with single nucleotide mutations in their causative genes. Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system is a flexible and efficient genome engineering technology widely used for researches and therapeutic applications which offers immense opportunity to treat genetic diseases. The complex of Cas9 and the guide RNA acts as an RNA-guided endonuclease. Cas9 recognizes a sequence motif known as a protospacer adjacent motif (PAM), and then the guide RNA base pairs with its proximal target region of 20 nucleotides with sequence complementarity. Here we describe the procedure named single nucleotide polymorphism-distinguishable (SNPD)-CRISPR system which can suppress or enhance the expression of disease-causative gene with single nucleotide mutation distinguished from its wild-type. In this study, we used HRAS, one of most famous cancer-causative genes, as an example of a target gene.

Are T1-Weighted Three-Dimensional Magnetic Resonance Images Inferior to T2-Weighted Images for Diagnosing Lumbar Foraminal Stenosis in the Fifth Lumbar Nerve Root? A Prospective, Comparative Study in Identical Patients.

Introduction: Imaging analysis of foraminal stenosis in the fifth lumbar (L5) nerve root remains to be a challenge because of the anatomical complexity of the lumbosacral transition. T2-weighted three-dimensional (3D) magnetic resonance images (MRI) have been dominantly used for diagnosis of lumbar foraminal stenosis, while the reliability of T1-weighted images (WI) has also been proven. In this study, we aim to compare the reliability and reproducibility of T1- and T2-weighted 3D MRI in diagnosing lumbar foraminal stenosis (LFS) of the L5 nerve root. Methods: In this study, 39 patients with unilateral L5 radiculopathy (20 had L4-L5 intracanal stenosis; 19 had L5-S foraminal stenosis) were enrolled, prospectively. T1- and T2-weighted 3D lumbar MRI were obtained from each patient. T1WI and T2WI were blinded and then separately reviewed twice by four examiners randomly. The examiners were instructed to answer the side of LFS or absence of LFS. The correct answer rate, sensitivity, specificity, and area under the curve were analyzed and compared between T1WI and T2WI. Also, intra- and interobserver agreements were calculated using kappa (κ)-statistics and compared in the same manner. Results: The average correct answer rate, sensitivity, specificity, and area under the curve of the T1WI/T2WI were 84.6%/80.1%, 82.9%/80.3%, 86.3%/81.3%, and 0.846/0.801, respectively. The intraobserver κ-values of the four examiners ranged from 0.692 to 0.916 (average: 0.762) and from 0.669 to 0.801 (average: 0.720) for T1WI and T2WI, respectively. The interobserver κ-values calculated in a round-robin manner (24 combinations in total) ranged from 0.544 to 0.790 (average: 0.657) and from 0.524 to 0.828 (average: 0.652), respectively. Conclusions: As per our findings, T1- and T2-weighted 3D MRI were determined to have nearly equivalent reliability and reproducibility in terms of diagnosing LFS of the L5 nerve root.

Disseminated aspergillosis associated with tsunami lung.

Many survivors of the tsunami that occurred following the Great East Japan Earthquake on March 11, 2011, contracted a systemic disorder called "tsunami lung," a series of severe systemic infections following aspiration pneumonia caused by near drowning in the tsunami. Generally, the cause of aspiration pneumonia is polymicrobial, including fungi and aerobic and anaerobic bacteria, but Aspergillus infection is rarely reported. Here we report a case of tsunami lung complicated by disseminated aspergillosis, as diagnosed during autopsy.

Reoperation for recurrent lumbar disc herniation: a study over a 20-year period in a Japanese population.

BACKGROUND: Many studies have been reported on recurrent lumbar disc herniations covering several pathological conditions. In those studies, reoperation rate of revised disc excisions was calculated by simple division between the number of reoperations and that of the total primary disc excisions. To determine the real reoperation rate, strict definition of pathologies, a large number of patients, a long observation period, and survival function method are necessary. METHODS: Between 1988 and 2007, 5,626 patients with disc excision were enrolled by the spine registration system of the Department of Orthopaedic Surgery, Tohoku University, Japan. Among them, 192 had revised disc surgery, and we obtained data of 186 patients whose clinical features were assessed and reoperation rates analyzed using the Kaplan-Meier method. RESULTS: In total, 205 disc herniations were excised in the revision surgery (including contralateral herniation at the same level and new herniation at a different level), and 101 were real recurrent herniations (recurrence at the same level and side as the primary herniation). The kappa coefficient of the spinal level and side between the primary and revision surgeries was 0.41, indicting moderate correlations. Real recurrent herniations showed shorter intervals between primary and revision surgeries. Male patients with surgery at a younger age carried a higher risk of reoperation. In the revision surgery, transligamentous extrusion was significantly more common than other types of herniation. On Kaplan-Meier analysis, the reoperation rate of overall revised excisions was 0.62% at 1 year, 2.4% at 5 years, 4.4% at 10 years, and 5.9% after 17 years. That of real recurrent herniations was 0.5%, 1.4%, and 2.1%, respectively, and 2.8% after 15.7 years. CONCLUSION: Reoperation rate of real recurrent herniations calculated using survival function method gradually increased year by year, from 0.5% at 1 year after primary surgery to 2.8% at 15.7 years.

Development of thyroid gland and ultimobranchial body cyst is independent of p63.

The ultimobranchial body (UBB) and thyroid primordium are the origins of the thyroid gland that fuse around embryonic day 14.5 of mouse gestation, ultimately giving rise to calcitonin-producing C cells and thyroglobulin-producing follicular cells, respectively. A homeodomain transcription factor NKX2-1 is expressed both in the UBB and the thyroid primordium, and is critical for development of the thyroid gland. In this study, the role of p63 in development of UBB and the thyroid gland was analyzed by histological, immunohistochemical, and electron microscopic analyses using mice with various combinations of Nkx2-1 and p63 wild-type, heterozygous, and null alleles. In the absence of p63, a normal thyroid gland develops, as revealed by expression of thyroglobulin and calcitonin, thus showing that p63 is not required for thyroid development. However, in mice carrying the Nkx2-1-null allele, the UBB remains as a cystic vesicular structure and/or in nested patterns consisting of p63-positive cells surrounding the vesicle and undifferentiated immature cells with occasional cilia lying inside. The cystic UBB was present even in the Nkx2-1;p63 double-null mice. The structure and p63 expression pattern of the UBB cyst strikingly resemble the solid cell nest. These results show that in the absence of NKX2-1, UBB becomes cystic independent of p63, which is likely the origin of SCN.

Detailed DARPP-32 expression profiles in postmortem brains from patients with schizophrenia: an immunohistochemical study.

The prevalence of dopamine and cAMP-regulated phosphoprotein 32kD (DARPP-32) is associated with the pathogenesis of schizophrenia. To date, the findings on DARPP-32 cellular expression and distribution in postmortem brains from patients with schizophrenia have been inconsistent. To clarify the detailed cellular expression of DARPP-32 in patients with schizophrenia, we immunohistochemically stained sections from postmortem brains using specific antibodies. We measured the density of immunopositive cells in various brain regions including the prefrontal cortex and compared the data from nine schizophrenia subjects with those of nine age- and sex-matched control subjects. The density of DARPP-32-immunoreactive (IR) neurons was significantly lower in layers II-V of the dorsolateral prefrontal cortex (DLPFC) from subjects with schizophrenia. In contrast, there were no marked differences in DARPP-32 expression in other brain regions. In addition, the density of threonine (Thr34)-phosphorylated DARPP-32-IR neurons was significantly higher in layer V of DLPFC from subjects with schizophrenia. These results suggest that the decrease in DARPP-32 in schizophrenia was more marked in neurons of DLPFC than in other cells or other brain regions, and that this decrease might be partly compensated for by an increase in expression of Thr34-phosphorylated DARPP-32 in DLPFC.

A case of a hematocele of the spermatic cord mimicking epididymal tumor.

A 68-year-old man visited our hospital complaining of painless left scrotal swelling. Stony hard mass was palpable at cephalad side of the testis. MRI showed a solid component mass mimicking epididymal tumor. Thus, exploratory surgery was performed. Since the tumor was firmly adhesive to the spermatic cord, an orchiectomy was unavoidable. The pathological result was hematocele of the spermatic cord.

Rate of spinal surgery in a rapidly aging society: the 27-year changes in Miyagi prefecture, Japan.

BACKGROUND: Japan has had a rapidly aging population during the past 30 years. This study aimed to investigate longitudinal changes in the surgical rate for spinal disorders in Miyagi Prefecture (2.35 million inhabitants) with a similar population composition to Japan. METHODS: Data of spinal surgeries were collected using the spine registry by Tohoku University Spine Society. Data on the annual number of spinal surgeries between 1988 and 2014 of all populations, in those aged ≥65 years old, in those aged ≥75 years old, and for each pathology were collected. The annual surgical rate per 100,000 inhabitants was calculated. RESULTS: The surgical rate in 2010-2014 in total, at ≥65 years old, and at ≥75 years old showed 3.2-, 3.8- and 7.1-fold increases, respectively, compared with that in 1988-1989. Degenerative spinal disorders, spinal trauma and pyogenic spondylitis markedly increased, while metastatic spinal tumor and tuberculous spondylitis decreased over time. The surgical rate at ≥75 years with lumbar spinal stenosis showed a 12.6-time increase. CONCLUSIONS: During a rapid period of aging, the rate of spinal surgeries has markedly increased, particularly, that for degenerative disorders. This is the first report on the long-term longitudinal changes in the rate of spinal surgery.

Role of NKX2-1 in N-bis(2-hydroxypropyl)-nitrosamine-induced thyroid adenoma in mice.

NKX2-1 is a homeodomain transcription factor that is critical for genesis of the thyroid and transcription of the thyroid-specific genes. Nkx2-1-thyroid-conditional hypomorphic mice were previously developed in which Nkx2-1 gene expression is lost in 50% of the thyroid cells. Using this mouse line as compared with wild-type and Nkx2-1 heterozygous mice, a thyroid carcinogenesis study was carried out using the genotoxic carcinogen N-bis(2-hydroxypropyl)-nitrosamine (DHPN), followed by sulfadimethoxine (SDM) or the non-genotoxic carcinogen amitrole (3-amino-1,2,4-triazole). A significantly higher incidence of adenomas was obtained in Nkx2-1-thyroid-conditional hypomorphic mice as compared with the other two groups of mice only when they were treated with DHPN + SDM, but not amitrole. A bromodeoxyuridine incorporation study revealed that thyroids of the Nkx2-1-thyroid-conditional hypomorphic mice had >2-fold higher constitutive cell proliferation rate than the other two groups of mice, suggesting that this may be at least partially responsible for the increased incidence of adenoma in this mouse line after genotoxic carcinogen exposure. Thus, NKX2-1 may function to control the proliferation of thyroid follicular cells following damage by a genotoxic carcinogen.

Reoperation Rates after Laminoplasty for Cervical Disorders: A 26-Year Period Survival Function Method Analysis.

INTRODUCTION: Laminoplasty is a common surgery for cervical myelopathy. Previous studies have analyzed the reoperation rates in posterior decompression surgeries of the cervical spine. However, few studies have solely focused on midline-splitting laminoplasty (MSL) using a large number of patients. This aims to analyze the reoperation rates after MSL using the survival function method. METHODS: Between 1988 and 2013, 4,208 MSLs were performed as a primary operation for cervical myelopathy and enrolled in our spinal surgery registration system. The Kaplan-Meier survival function method was used to analyze the rates of reoperation. RESULTS: Of 4,208 patients with primary MSL, 40 underwent reoperation for neurological complications. The overall reoperation rate was 0.26%, 0.64%, 0.83%, 0.93%, and 0.95% at 1, 5, 10, 20, and >20 years, respectively. The causes of reoperation were postoperative cervical radiculopathy in 10 patients, stenosis at an adjacent level in 8, stenosis due to failed "open-door" lamina in 6, instability of the cervical spine in 4, cervical disc herniation in 3, elongation of ossification of the posterior longitudinal ligament in 3, spinal cord injury in 1, fracture of the cervical spine in 1, postoperative scar formation in 1, ossification of anterior longitudinal ligament in 1, and unknown in 2. The number of patients with surgical site infection (SSI) who needed surgical debridement was 34 (0.81%). CONCLUSIONS: Excluding reoperations for SSI, the reoperation rate of MSL was approximately 1.0% at the maximum of 26 years after surgery. MSL was determined to be a reliable surgical procedure regarding postoperative complications requiring additional surgeries.