Parapharyngeal metastasis in hepatocellular carcinoma-a rare entity.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. It most commonly metastasizes haematogenously to the lungs and bones, less commonly via lymphatics to lymph nodes. However, metastasis to the parapharyngeal space has yet to be reported. This is the first clinical report of the treatment of parapharyngeal metastasis from HCC. The case of a 46-year-old man who was found to have a parapharyngeal soft tissue mass during routine follow-up 12 years post deceased-donor liver transplantation for hepatitis B-related HCC is reported here. This was investigated and diagnosed to be metastatic HCC. He underwent excision of the parapharyngeal metastasis, followed by adjuvant radiotherapy. Parapharyngeal metastasis is a rare occurrence in HCC. It is important to be cognizant of the possibility of disease spread to this location in order to ensure early detection and treatment. Surgical excision with adjuvant radiotherapy should be considered to achieve disease control.

Subjective apnoea symptoms are associated with daytime sleepiness in patients with moderate and severe obstructive sleep apnoea: a retrospective study.

OBJECTIVES: Most previous studies have failed to show a relation between daytime sleepiness and apnoea severity in patients with obstructive sleep apnoea (OSA). We determined the relation between daytime sleepiness and subjective and objective apnoea severity in newly diagnosed patients with moderate-to-severe OSA. DESIGN: Retrospective cross-sectional study. SETTING: Tertiary referral centre. PARTICIPANTS: A total of 559 adults with newly diagnosed moderate and severe OSA. MAIN OUTCOME MEASURES: Daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS). Subjective and objective apnoea severities were assessed using the Sleep Breathing Scale (SBS) and polysomnography respectively. Sleep quality and depressive symptoms were evaluated using Medical Outcomes Study-Sleep Scale and Beck Depression Inventory (BDI) respectively. RESULTS: The mean ESS score was 9.8 (SD 5.0). ESS score was correlated with SBS score (P < 0.001), apnoea-hypopnoea index (AHI) (P = 0.027), minimal oxygen saturation (MinSaO2 ) (P = 0.021), body mass index (BMI) (P = 0.007) and BDI score (P < 0.001). Linear regression analysis showed that higher SBS (P = 0.005) and BDI scores (P < 0.001) were associated with higher ESS score after controlling for gender, BMI and AHI. Apnoea-hypopnoea index, MinSaO2 and BMI were not independently related to ESS score. CONCLUSIONS: Daytime sleepiness was related to subjective OSA symptoms but not objective apnoea severity measured by polysomnography in patients with moderate-to-severe OSA. These findings suggest the usefulness of the subjective apnoea severity as an indicator of OSA disease severity.

Survival Benefit of Early Cancer Detection Through Regular Endoscopic Screening for De Novo Gastric and Colorectal Cancers in Korean Liver Transplant Recipients.

BACKGROUND: De novo malignancy is not uncommon after liver transplantation (LT). Gastric cancer is one of the most common malignancies in both the Korean general population and LT recipients, and colorectal cancer prevalence is gradually increasing. METHODS: Among 3690 adult recipients who underwent LT from January 1999 and December 2013, the screening patterns and prognosis of 26 cases of gastric cancer and 22 cases of colorectal cancer were analyzed. RESULTS: For gastric cancer, the mean patient age was 54.6 ± 6.2 years at LT and 59.5 ± 6.7 years at cancer diagnosis, with a post-transplant interval of 60.2 ± 29.8 months. Patients were divided into regular (n = 18) and non-regular (n = 8) screening groups, with early cancer found in 14 and 0 patients; their 2-year survival rates after cancer diagnosis were 93.1% and 33.3% (P = .006), respectively. Endoscopic resection was successfully performed in 8 patients, all in the regular screening group. For colorectal cancer, the mean patient age was 53.3 ± 6.1 years at LT and 58.1 ± 6.7 years at cancer diagnosis, with a post-transplant interval of 54.3 ± 38.0 months. Patients were divided into regular (n = 19) and non-regular (n = 3) screening groups, with early cancer found in 12 and 0 patients; their 2-year survival rates after cancer diagnosis of 92.3% and 33.3% (P = .003), respectively. Endoscopic resection was successfully performed in 6 patients, all in the regular screening group. CONCLUSIONS: LT recipients are strongly advised to undergo regular screening studies for various de novo malignancies, especially cancers common in the general population. Regular endoscopic screening contributes to the timely detection of gastric and colorectal cancers, improving post-treatment survival outcomes.

Routine endoscopic screening for synchronous esophageal neoplasm in patients with head and neck squamous cell carcinoma: a prospective study.

Early detection of synchronous esophageal squamous cell neoplasm (ESCN) in head and neck squamous cell carcinoma (HNSCC) patients can significantly affect their prognosis. We investigated the prevalence of synchronous ESCN and the risk factors for developing ESCN in patients with HNSCC, and evaluated the effect of routine endoscopic screening in these patients. Subjects who were diagnosed as HNSCC from May 2010 to January 2014 were eligible. All patients underwent conventional white light endoscopic examinations with narrow band imaging and Lugol chromoendoscopy. Among 458 subjects screened, 28 synchronous ESCN were detected in 24 patients (5.2%). The prevalence of ESCN was greatest in patients with hypopharyngeal cancer (20.9%). In multivariate analysis, pyriform sinus involvement was independent risk factor for developing synchronous ESCN (odds ratio 171.2, P < 0.001). During the follow-up period (median, 24 months), the 3-year overall survival rates was significantly lower in patients with ESCN than in patients without ESCN (54.2% vs. 78.3%, P = 0.0013). Routine endoscopic screening for detecting synchronous ESCN should be recommended for patients with HNSCC, especially those with pyriform sinus involvement.

Efficacy and complications of enteral feeding tube insertion after liver transplantation.

BACKGROUND: Adequate nutritional support for patients undergoing major surgery significantly affects postoperative recovery. Data on enteral feeding after liver transplantation (LT) are scarce. The aim of this work was to determine the efficacy and complications of feeding tubes inserted with the use of fluoroscopic assistance, endoscopic assistance, or transperitoneal jejunostomy in patients who underwent LT. METHODS: From January 2008 to August 2013, 2,058 LTs were performed at Asan Medical Center, Seoul, Korea. Enteral feeding tubes were inserted in 155 patients (7.5%) after LT: with the use of fluoroscopic placement in 81 (52%), endoscopic placement in 49 (32%), and transperitoneal jejunostomy in 25 (16%). We retrospectively analyzed the efficacy and complications of enteral feeding tubes. RESULTS: The median age was 55 years (interquartile range [IQR] 49-60). Enteral feeding indications were a high risk of gastric aspiration (n = 90), gastric stasis (n = 27), pneumonia (n = 23), gastrointestinal bleeding (n = 12), and bowel rest (n = 3). Median enteral feeding durations were 14.5 days (IQR 8.0-30.7) for fluoroscopic placement, 20.0 days (IQR 8.0-40.0) for endoscopic placement, and 37.5 days (IQR 18.2-86.2) for transperitoneal jejunostomy. Times to establishment of oral feeding were 13.0 days (IQR 6.2-25.7) for fluoroscopic placement, 24.0 days (IQR 10.5-43.5) for endoscopic placement, and 37.0 days (IQR 17.0-64.2) for transperitoneal jejunostomy. After tube insertion, tube dislocation and blockage occurred in 34 patients (22%) and 16 patients (25%), respectively. CONCLUSIONS: Enteral feeding tube insertion in patients who can not maintain a nasogastric tube or start oral intake for a long time is important for nutritional support after LT. Proper feeding method selection according to patient condition can help patients by improving nutritional support after major operations such as LT.

Multi-modal imaging and cancer therapy using lanthanide oxide nanoparticles: current status and perspectives.

Biomedical imaging is an essential tool for diagnosis and therapy of diseases such as cancers. It is likely true that medicine has developed with biomedical imaging methods. Sensitivity and resolution of biomedical imaging methods can be improved with imaging agents. Furthermore, it will be ideal if imaging agents could be also used as therapeutic agents. Therefore, one dose can be used for both diagnosis and therapy of diseases (i.e., theragnosis). This will simplify medical treatment of diseases, and will be also a benefit to patients. Mixed (Ln(1x)Ln(2y)O3, x + y = 2) or unmixed (Ln2O3) lanthanide (Ln) oxide nanoparticles (Ln = Eu, Gd, Dy, Tb, Ho, Er) are potential multi-modal imaging and cancer therapeutic agents. The lanthanides have a variety of magnetic and optical properties, useful for magnetic resonance imaging (MRI) and fluorescent imaging (FI), respectively. They also highly attenuate X-ray beam, useful for X-ray computed tomography (CT). In addition gadolinium-157 ((157)Gd) has the highest thermal neutron capture cross section among stable radionuclides, useful for gadolinium neutron capture therapy (GdNCT). Therefore, mixed or unmixed lanthanide oxide nanoparticles can be used for multi-modal imaging methods (i.e., MRI-FI, MRI-CT, CT-FI, and MRICT- FI) and cancer therapy (i.e., GdNCT). Since mixed or unmixed lanthanide oxide nanoparticles are single-phase and solid-state, they can be easily synthesized, and are compact and robust, which will be beneficial to biomedical applications. In this review physical properties of the lanthanides, synthesis, characterizations, multi-modal imagings, and cancer therapy of mixed and unmixed lanthanide oxide nanoparticles are discussed.

Is right-sided colon cancer different to left-sided colorectal cancer? - a systematic review.

Colorectal cancer (CRC) exhibits differences in incidence, pathogenesis, molecular pathways and outcome depending on the location of the tumor. This review focuses on the latest developments in epidemiological and scientific studies, which have enhanced our understanding on the underlying genetic and immunological differences between the proximal (right-sided) colon and the distal (left-sided) colorectum. The different ways in which environmental risk factors influence the pathogenesis of CRC depending on its location and the variations in surgical and oncological outcomes are also discussed in this review. In the current era of personalized medicine, we aim to reiterate the importance of tumor location in management of CRC and the implication on future clinical and scientific research.

Genetic testing in inherited polyposis syndromes - how and why?

There have been recent advances in genetic testing enabling accurate diagnosis of polyposis syndromes by identifying causative gene mutations, which is essential in the management of individuals with polyposis syndrome and predictive genetic testing of their extended families. There are some similarities in clinical presentation of various polyposis syndromes, which may pose a challenge to diagnosis. In this review, we discuss the clinical presentation of the main polyposis syndromes and the process of genetic testing, including the latest advancement and future of genetic testing. We aim to reiterate the importance of genetic testing in the management of polyposis syndromes, potential pitfalls associated with genetic testing and recommendations for healthcare professionals involved with the care of polyposis patients.

Novel signaling axis for ROS generation during K-Ras-induced cellular transformation.

Reactive oxygen species (ROS) are well known to be involved in oncogene-mediated cellular transformation. However, the regulatory mechanisms underlying ROS generation in oncogene-transformed cells are unclear. In the present study, we found that oncogenic K-Ras induces ROS generation through activation of NADPH oxidase 1 (NOX1), which is a critical regulator for the K-Ras-induced cellular transformation. NOX1 was activated by K-Ras-dependent translocation of p47(phox), a subunit of NOX1 to plasma membrane. Of note, PKCδ, when it was activated by PDPK1, directly bound to the SH3-N domain of p47(phox) and catalyzed the phosphorylation on Ser348 and Ser473 residues of p47(phox) C-terminal in a K-Ras-dependent manner, finally leading to its membrane translocation. Notably, oncogenic K-Ras activated all MAPKs (JNK, ERK and p38); however, only p38 was involved in p47(phox)-NOX1-dependent ROS generation and consequent transformation. Importantly, K-Ras-induced activation of p38 led to an activation of PDPK1, which then signals through PKCδ, p47(phox) and NOX1. In agreement with the mechanism, inhibition of p38, PDPK1, PKCδ, p47(phox) or NOX1 effectively blocked K-Ras-induced ROS generation, anchorage-independent colony formation and tumor formation. Taken together, our findings demonstrated that oncogenic K-Ras activates the signaling cascade p38/PDPK1/PKCδ/p47(phox)/NOX1 for ROS generation and consequent malignant cellular transformation.

BAX inhibitor-1-associated V-ATPase glycosylation enhances collagen degradation in pulmonary fibrosis.

Endoplasmic reticulum (ER) stress is considered one of the pathological mechanisms of idiopathic pulmonary fibrosis (IPF). Therefore, we examined whether an ER stress regulator, Bax inhibitor-1 (BI-1), regulates collagen accumulation, which is both a marker of fibrosis and a pathological mechanism of fibrosis. The presence of BI-1 inhibited the transforming growth factor-ß1-induced epithelial-mesenchymal transition of epithelial pulmonary cells and bleomycin-induced pulmonary fibrosis in a mouse model by enhancing collagen degradation, most likely by enhanced activation of the lysosomal V-ATPase through glycosylation. We also found a correlation between post-translational glycosylation of the V-ATPase and its associated chaperone, calnexin, in BI-1-overexpressing cells. BI-1-induced degradation of collagen through lysosomal V-ATPase glycosylation and the involvement of calnexin were confirmed in a bleomycin-induced fibrosis mouse model. These results highlight the regulatory role of BI-1 in IPF and reveal for the first time the role of lysosomal V-ATPase glycosylation in IPF.

The error-prone DNA polymerase ι provides quantitative resistance to lung tumorigenesis and mutagenesis in mice.

Opposite undamaged nucleotide T, DNA polymerase ι (Polι) preferentially incorporates G rather than A, violating the Watson-Crick rule. Although the actual biological role of Polι remains enigmatic, we have identified its coding gene as a candidate for pulmonary adenoma resistance 2 (Par2), a mouse quantitative trait locus modulating chemically induced lung tumor susceptibility. Notably, the most tumor-sensitive Par2 allele possessed by the 129X1/SvJ mouse is associated with a loss-of-function mutation in Polι. To determine whether the nonfunctional Polι is responsible for the 129X1/SvJ-specific Par2 phenotype, we knocked out Polι in a C57BL/6J mouse carrying a less tumor-sensitive Par2 allele. Disruption of the C57BL/6J Polι conferred 129X1/SvJ-like sensitivity on the C57BL/6J Par2 locus and increased the in vivo mutation frequency in the lung, providing definitive proof that Polι causes the Par2 effect and inhibits tumorigenesis and mutagenesis, despite its extreme replication infidelity.

Association study of anti-Mullerian hormone and anti-Mullerian hormone type II receptor polymorphisms with idiopathic primary ovarian insufficiency.

STUDY QUESTION: Are the genetic polymorphisms of the anti-Müllerian hormone (AMH) and anti-Müllerian hormone type II receptor (AMHR2) genes associated with idiopathic primary ovarian insufficiency (POI) in a Korean population? SUMMARY ANSWER: The distribution of the AMH and the AMHR2 polymorphisms in a Korean POI population was not significantly different from controls. WHAT IS KNOWN ALREADY: AMH plays an important role in regulating both the primordial follicle recruitment and the cyclic selection of the antral follicles. The AMHR2 -482A>G polymorphism was associated with an earlier menopause and nulliparous women with the GG genotype had a 2.6 years earlier onset of menopause compared with the AA genotype women. Therefore, genetic variants in the AMH signal transduction pathway might affect the ovarian function of women. STUDY DESIGN, SIZE, DURATION: Case-control study. The subjects consisted of 211 idiopathic POI patients and 233 post-menopausal controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: The frequency of the AMH Ile(49)Ser and AMHR2 -482A>G polymorphisms was analyzed in 211 patients with idiopathic POI and in 233 post-menopausal controls, and we also analyzed clinical characteristics, such as age at the time of POI and LH, FSH as well as estradiol levels according to the specific genotype. Genotyping for the AMH Ile(49)Ser and the AMHR2 -482A>G polymorphisms was performed by a minor groove binder primer/probe Taqman assay. MAIN RESULTS AND THE ROLE OF CHANCE: The genotype distributions and allele frequencies for the AMH Ile(49)Ser and the AMHR2 -482A>G polymorphisms were similar between the POI patients and the controls. Within POI population, the AMH Ile(49)Ser and the AMHR2 -482A>G polymorphisms were not associated with age at the time of POI and LH, FSH as well as estradiol levels. Haplotype analysis also showed no significant difference between groups. LIMITATIONS, REASONS FOR CAUTION: Study is limited to a Korean population. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that genetic variants in the AMH signal transduction pathway may not influence the susceptibility of idiopathic POI. This is the first report on the association between the AMH and AMHR2 polymorphisms and idiopathic POI. STUDY FUNDING/COMPETING INTEREST(S): No conflict of interest exists. This study was supported by a grant of Seoul National University Hospital Research Fund (04-2011-0870). TRIAL REGISTRATION NUMBER: N/A.

Resolution of adefovir-related nephrotoxicity by adefovir dose-reduction in patients with chronic hepatitis B.

BACKGROUND: Chronic hepatitis B patients (CHB) treated with adefovir were followed up to evaluate nephrotoxicity and its outcome. AIM: To assess the incidence of renal dysfunction during adefovir therapy in Asian patients and factors associated with it, and evaluate strategies to improve adefovir-related renal dysfunction and their impact on viral suppression. METHODS: Chronic hepatitis B clinic patients from a tertiary hospital on adefovir treatment, with their clinical and laboratory parameters were extracted from the hospital electronic clinical database in an observational study design. Patients were excluded if they had liver/renal transplant, baseline renal impairment or were on dialysis. Adefovir-related renal dysfunction was defined as adefovir-related abnormal serum creatinine (ARASC) > 125 µmol/L (males), >90 µmol/L (females); adefovir-related abnormal GFR <60 mL/min; and adefovir-related increased serum creatinine >0.5 mg/dL, without other known causes of nephrotoxicity. RESULTS: A total of 271/383 adefovir-treated patients were suitable for analysis and 33(12%) patients developed abnormal serum creatinine. Cumulative increase in proportion of patients with ARASC was 33.8% and GFR ≤60 mL/min was 38.3% by 6 years, while serum creatinine increase ≥0.5 mg/dL was 21.48% by 5 years. Using multivariate analysis, the only independent baseline predictor of ARASC was GFR ≤76.1 mL/min. Patients who had ARASC had similar levels of viral suppression to those who did not have ARASC. Those who had ARASC either continued adefovir (24%), switched therapy (24%) or had adefovir dose reduction (52%). ARASC resolved and GFR normalised in almost all patients after either switching therapy or reducing adefovir dose, with no difference between the two strategies (P = 0.737). Those with adefovir dose reduction had no significant increase in HBV DNA (P = 0.170). CONCLUSIONS: Adefovir-related renal dysfunction occurred in a significant number of adefovir-treated patients, but reduction of the dose led to renal improvement without compromising treatment efficacy.

Endoscopic submucosal dissection for sessile, nonampullary duodenal adenomas.

Although endoscopic submucosal dissection (ESD) is increasingly utilized to treat early neoplasms of the gastrointestinal tract, its use for duodenal neoplasms is limited by the thin wall and narrow lumen of the duodenum. We have reviewed cases where ESD was used to treat sessile, nonampullary duodenal neoplasms. To do this, we retrospectively reviewed the medical records of patients treated with ESD for adenomas of the duodenum from January 2001 to December 2010, assessing the curative outcomes and complication rates. A total of 14 cases were reviewed. Mean patient age was 56.4 years. The mean size of tumors and mean size of the specimens were 17.1 mm and 26.4 mm, respectively. The en bloc resection rate with ESD was 78.6%, and the complete (R0) resection rate was 85.7%. No patient in the study experienced major bleeding. However, second-look endoscopy revealed minor bleeding requiring endoscopic homeostasis in one case (7.1%). Perforations were observed in five cases (35.7%). Two of the five patients with perforation underwent surgery. The ESD methods yielded acceptable curative resection rates for duodenal adenomas, although ESD was associated with a higher rate of perforation. Therefore, duodenal ESD should be performed with care and only in selected patients to avoid serious complications.

Natural course of noncurative endoscopic resection of differentiated early gastric cancer.

BACKGROUND AND STUDY AIMS: Following noncurative endoscopic resection of early gastric cancer (EGC), the patient should be observed when the underlying disease is severe, the patient is elderly, or the patient refuses further treatment. The aim of this study was to analyze the clinical outcomes of patients with differentiated EGC who underwent noncurative endoscopic resection without additional treatment. PATIENTS AND METHODS: Included patients underwent noncurative endoscopic resection for differentiated EGC without additional treatment at the Asan Medical Center between July 1994 and January 2009. Clinical and oncological outcomes were analyzed. RESULTS: A total of 159 patients were included in the analysis. The median follow-up period was 33 months (interquartile range [IQR] 22 - 52 months). In total, 40 patients died (25.2 %) - 3 due to stomach cancer, 34 due to other causes, and 3 from unknown causes; the median survival time after endoscopic treatment for these patients was 27.5 months (IQR 13.8 - 48.3 months). Multivariate analysis showed that the rates of underlying disease (P < 0.001) and lymphovascular invasion (P = 0.005) were higher among the 40 patients who died than among the 119 survivors. The overall 3-  and 5-year survival rates were 82.9 % and 77.1 %, respectively; the rates of the patients with lymphovascular invasion were 61.9 % and 42.4 %, respectively, and the rates of patients without lymphovascular invasion were 86.1 % and 81.8 %, respectively (P < 0.001). CONCLUSIONS: Additional treatment provides fewer benefits to patients who do not have long life expectancies. Additional surgery can be considered for patients with lymphovascular invasion because of its high mortality rate; however, the benefits and risks of surgery should be considered carefully.

Spontaneous bilateral compartment syndrome of the legs: A case report and review of the literature.

INTRODUCTION: Bilateral acute compartment syndrome of the legs is a rare presentation requiring emergent surgical intervention. PRESENTATION OF CASE: We report the case of 41-year-old woman who presented with acute bilateral compartment syndrome of the legs, complicated by rhabdomyolysis and acute renal failure. DISCUSSION: There are very few previously reported cases of bilateral compartment syndrome of the legs. In the present case, despite any clear causative factor, we suggest that the aetiology is related to inadvertent posture during sleep. CONCLUSION: The diagnosis of acute bilateral compartment syndrome of the legs requires a high index of suspicion, particularly in the absence of obvious aetiology. A successful outcome can be achieved with early diagnosis, prompt surgical intervention and a multidisciplinary approach.

Transnasal endoscope-assisted endoscopic submucosal dissection for gastric adenoma and early gastric cancer in the pyloric area: a case series.

Endoscopic submucosal dissection (ESD) is an important therapeutic option for gastric adenoma and early gastric cancer (EGC). However, ESD is technically difficult when lesions are located in the pyloric area. Our aim was to introduce the transnasal endoscope-assisted ESD method, which provides for excellent cutting-line visualization through control of submucosal traction. A total of eight patients with gastric adenoma or EGC located in the pyloric area were consecutively enrolled. A primary operating endoscope was used to perform marking, incision, submucosal dissection, and hemostasis, while a thinner, transnasal endoscope operated by a second endoscopist was used to retract connective submucosal tissue to provide cutting-line visualization using V-shaped grasping forceps. En bloc resection was achieved in all eight cases, as was complete resection. The median longest lesion diameter was 19 mm (range: 12-25 mm), and the median procedure time was 37.5 minutes (range: 29-59 minutes). There were no incidents of significant bleeding or perforation. Transnasal endoscope-assisted ESD was useful for treating gastric neoplasms in the pyloric area. The procedure was relatively easy and safe, provided excellent visualization through tissue retraction, and allowed for complete en bloc resection.