Short-term outcomes of pediatric laparoscopic inguinal hernia repair in Korea based on Korean Health Insurance Big Data: 2011-2015.

PURPOSE: For pediatric inguinal hernia repairs (IHRs), open IHR (high ligation) has long been a gold standard. Recently laparoscopic IHR (LIHR) was introduced as a new treatment modality and has been performed more frequently in Korea. Unlike adults, LIHR in children is still controversial. In the present study, we investigate the short-term outcomes of pediatric LIHR in Korea using nationwide inpatient data. METHODS: We analyzed clinical practice for IHRs from 2011 to 2015 using Korean Health Insurance Review and Assessment Service-National Inpatient Sample. RESULTS: A total of 5281 patients 15 years old or younger underwent 5356 IHRs: 4507 OIHRs and 849 LIHRs. M:F ratio was 2.4:1. The proportion of LIHRs was only 1.8% at the beginning but had been continuously increased up to 29.8% at the end of the study period. LIHRs were closely related to synchronous bilateral inguinal hernia repairs (SBIHRs). Overall, SBIHRs were performed in 10.9% of open and 49.2% of LIHRs. Metachronous contralateral IHRs (MCIHRs) after initial unilateral IHRs were significantly more frequent after OIHRs (1.7%, 69/3, 951) than after LIHRs (0.2%, 1/427). Recurrence rate per side during study period was 0.1% (6/4, 993) after OIHRs and 0.2% (2/1, 259) after LIHRs, respectively (statistically insignificant). CONCLUSION: Nationwide inpatient data showed that LIHRs in pediatric patients had recently been increasingly performed in Korea. LIHRs facilitated SBIHRs, which, in turn, decreased the needs of MCIHRs. However limited numbers of patients might actually have benefited from them. Early recurrence after primary IHRs in children is quite low regardless of way of approach.

Dissolving microneedle with high molecular weight hyaluronic acid to improve skin wrinkles, dermal density and elasticity.

OBJECTIVES: Dissolving microneedle patches have been extensively studied in the field of cosmetics comparison with topical cosmetics focusing on the delivery of active ingredients. Nevertheless, the skin improvement effect of hyaluronic acid, which is mainly used as a backbone material for dissolving microneedle, was not analyzed. In this study, adenosine encapsulated high and low molecular weight hyaluronic acid dissolving microneedle patch (Ad-HMN and Ad-LMN) were evaluated with respect to skin wrinkling, dermal density, elasticity, and safety in a clinical test on the crow's feet area. METHODS: Clinical efficacy and safety tests were performed for 12 weeks on twenty three female subjects with wrinkles around their eyes. The Ad-HMN and Ad-LMN patch were applied once every 3 days, in the evening, for 8 weeks to the designated crow's feet area. Skin wrinkling, dermal density, and elasticity were measured by using PRIMOS® premium, Dermascan® C, Cutometer® MPA580, and Corneometer® CM 825, respectively. RESULTS: Both Ad-HMN and Ad-LMN groups showed statistically significant efficacy for almost all parameters. The Ad-HMN patch had better effect on the mean depth of biggest wrinkles, maximum depth of biggest wrinkles, dermal density, and skin elasticity than the Ad-LMN patch. No adverse effects were observed in either group during the test period. CONCLUSION: In the clinical efficacy test of four skin-improvement parameters, the Ad-HMN patch showed the better effect than the Ad-LMN patch with the similar adenosine dose.

OBJECTIFS: Les patches à micro-aiguilles dissolvantes ont fait l'objet d'études approfondies dans le domaine de la cosmétique en comparaison avec la cosmétique topique axée sur la diffusion de principes actifs. Cependant, l'effet améliorant de l'acide hyaluronique sur la peau, principalement utilisée comme matière de base pour la dissolution des micro-aiguilles, n'a pas été analysé. Dans la présente étude, les patchs à micro-éguilles dissolvant l'acide hyaluronique à poids moléculaire élevé et faible, encapsulé dans l'adénosine (Ad-HMN et Ad-LMN) ont été analysés par rapport à la formation des rides, la densité cutanée, l'élasticité et la sécurité d'emploi lors d'un test clinique sur la zone de pattes d'oie. MÉTHODES: Des tests d'efficacité et de sécurité cliniques ont été réalisés pendant 12 semaines sur 23 sujets féminins ayant des rides autour des yeux. Les patchs Ad-HMN et Ad-LMN ont été appliqués une fois tous les trois jours, le soir, pendant huit semaines, dans la zone à pattes d'oie désignée. La formation de rides, la densité cutanée et l'élasticité ont été mesurées à l'aide de PRIMOS® premium, Dermascan® C, Cutometer® MPA580 et Corneometer® CM825, respectivement. RÉSULTATS: Les deux groupes Ad-HMN et Ad-LMN ont présenté une efficacité statistiquement significative pour la quasi-totalité des paramètres. Le patch Ad-HMN a eu un meilleur effet sur la profondeur moyenne des rides les plus importantes, la profondeur maximale des rides les plus importantes, la densité cutanée et l'élasticité de la peau par rapport au patch Ad-LMN. Aucun effet indésirable n'a été observé dans aucun des groupes pendant la période d'essai. CONCLUSION: Lors du test d'efficacité clinique des quatre paramètres d'amélioration de la peau, le patch Ad-HMN a eu un meilleur effet que le patch Ad-LMN avec la dose d'adénosine similaire.

Utility of Pre-Hematopoietic Cell Transplantation Sinus CT Screening in Children and Adolescents.

BACKGROUND AND PURPOSE: The clinical benefit of pre-hematopoietic cell transplantation sinus CT screening remains uncertain, while the risks of CT radiation and anesthesia are increasingly evident. We sought to re-assess the impact of screening sinus CT on pretransplantation patient management and prediction of posttransplantation invasive fungal rhinosinusitis. MATERIALS AND METHODS: Pretransplantation noncontrast screening sinus CTs for 100 consecutive patients (mean age, 11.9 ± 5.5 years) were graded for mucosal thickening (Lund-Mackay score) and for signs of noninvasive or invasive fungal rhinosinusitis (sinus calcification, hyperattenuation, bone destruction, extrasinus inflammation, and nasal mucosal ulceration). Posttransplantation sinus CTs performed for sinus-related symptoms were similarly graded. Associations of Lund-Mackay scores, clinical assessments, changes in pretransplantation clinical management (additional antibiotic or fungal therapy, sinonasal surgery, delayed transplantation), and subsequent development of sinus-related symptoms or invasive fungal rhinosinusitis were tested (exact Wilcoxon rank sums, Fisher exact test, significance P < .05). RESULTS: Mean pretransplantation screening Lund-Mackay scores (n = 100) were greater in patients with clinical symptoms (8.07 ± 6.00 versus 2.48 ± 3.51, P < .001) but were not associated with pretransplantation management changes and did not predict posttransplantation sinus symptoms (n = 21, P = .47) or invasive fungal rhinosinusitis symptoms (n = 2, P = .59). CONCLUSIONS: Pre-hematopoietic cell transplantation sinus CT does not meaningfully contribute to pretransplantation patient management or prediction of posttransplantation sinus disease, including invasive fungal rhinosinusitis, in children. The risks associated with CT radiation and possible anesthesia are not warranted in this setting.

Author Correction: Anti-angiogenic drug scheduling optimisation with application to colorectal cancer.

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Anti-angiogenic drug scheduling optimisation with application to colorectal cancer.

Bevacizumab (bvz) is a first choice anti-angiogenic drug in oncology and is primarily administered in combination with chemotherapy. It has been hypothesized that anti-angiogenic drugs enhance efficacy of cytotoxic drugs by "normalizing" abnormal tumor vessels and improving drug penetration. Nevertheless, the clinical relevance of this phenomenon is still unclear with several studies over recent years suggesting an opposing relationship. Herein, we sought to develop a new computational tool to interrogate anti-angiogenic drug scheduling with particular application in the setting of colorectal cancer (CRC). Specifically, we have employed a mathematical model of vascular tumour growth which interrogates the impact of anti-angiogenic treatment and chemotherapeutic treatment on tumour volume. Model predictions were validated using CRC xenografts which underwent treatment with a clinically relevant combinatorial anti-angiogenic regimen. Bayesian model selection revealed the most appropriate term for capturing the effect of treatments on the tumour size, and provided insights into a switch-like dependence of FOLFOX delivery on the tumour vasculature. Our experimental data and mathematical model suggest that delivering chemotherapy prior to bvz may be optimal in the colorectal cancer setting.

Adenosine-loaded dissolving microneedle patches to improve skin wrinkles, dermal density, elasticity and hydration.

OBJECTIVE: Although dissolving microneedle patches have been widely studied in the cosmetics field, no comparisons have been drawn with the topical applications available for routine use. In this study, two wrinkle-improving products, adenosine-loaded dissolving microneedle patches and an adenosine cream, were evaluated for efficacy, with respect to skin wrinkling, dermal density, elasticity, and hydration, and safety in a clinical test on the crow's feet area. METHODS: Clinical efficacy and safety tests were performed for 10 weeks on 22 female subjects with wrinkles around their eyes. The adenosine-loaded dissolving microneedle patch was applied once every 3 days, in the evening, for 8 weeks to the designated crow's feet area. The adenosine cream was applied two times per day, in the morning and evening, for 8 weeks to the other crow's feet area. Skin wrinkling, dermal density, elasticity, and hydration were measured by using PRIMOS® premium, Dermascan® C, Cutometer® MPA580, and Corneometer® CM 825, respectively. In addition, subjective skin irritation was evaluated by self-observation, and objective skin irritation was assessed through expert interviews. RESULTS: The adenosine-loaded dissolving microneedle patches had a similar or better efficacy than the adenosine cream. Both groups showed statistically significant efficacy for almost all parameters (P < 0.05). The dissolving microneedle patches had a long-lasting effect on the average wrinkle depth (P < 0.05), only showed efficacy in dermal density (P < 0.05), had an early improving effect on elasticity (P < 0.05), and demonstrated better hydration efficacy (P < 0.001). No adverse effects were observed in either group during the test period. CONCLUSIONS: In the clinical efficacy test of four skin-improvement parameters, adenosine-loaded dissolving microneedle patches showed the same or better effect than the adenosine cream, although the weekly adenosine dose was 140 times lower. The dissolving microneedle patches caused no adverse reactions. These adenosine-loaded dissolving microneedle patches are expected to be safe, effective, and novel cosmetics for skin improvement.

Aberrant GATA2 epigenetic dysregulation induces a GATA2/GATA6 switch in human gastric cancer.

Six GATA transcription factors play important roles in eukaryotic development. Among these, GATA2, an essential factor for the hematopoietic cell lineage, exhibits low expression in human gastric tissues, whereas GATA6, which is crucial for gastrointestinal development and differentiation, is frequently amplified and/or overexpressed in human gastric cancer. Interestingly, we found that GATA6 was overexpressed in human gastric cancer cells only when GATA2 expression was completely absent, thereby showing an inverse correlation between GATA2 and GATA6. In gastric cancer cells that express high GATA6 levels, a GATA2 CpG island is hypermethylated, repressing expression in these cells. In contrast, GATA6 expression is undetectable in GATA2-overexpressing gastric cancer cells, which lack GATA2 DNA methylation. Furthermore, PRC2 complex-mediated transcriptional silencing of GATA6 was observed in the GATA2-overexpressing cells. We also show that the GATA2 and PRC2 complexes are enriched within the GATA6 locus, and that the recruitment of the PRC2 complex is impaired by disrupting GATA2 expression, resulting in GATA6 upregulation. In addition, ectopic GATA2 expression significantly downregulates GATA6 expression, suggesting GATA2 directly represses GATA6. Furthermore, GATA6 downregulation showed antitumor activity by inducing growth arrest. Finally, we show that aberrant GATA2 methylation occurs early during the multistep process of gastric carcinogenesis regardless of Helicobacter pylori infection. Taken together, GATA2 dysregulation by epigenetic modification is associated with unfavorable phenotypes in human gastric cancer cells by allowing GATA6 expression.

Relationships among Cortical Glutathione Levels, Brain Amyloidosis, and Memory in Healthy Older Adults Investigated In Vivo with 1H-MRS and Pittsburgh Compound-B PET.

BACKGROUND AND PURPOSE: Oxidative stress has been implicated as an important pathologic mechanism in the development of Alzheimer disease. The purpose of this study was to assess whether glutathione levels, detected noninvasively with proton MR spectroscopy, are associated with brain amyloidosis and memory in a community-dwelling cohort of healthy older adults. MATERIALS AND METHODS: Fifteen cognitively healthy subjects were prospectively enrolled in this study. All subjects underwent 1H-MR spectroscopy of glutathione, a positron-emission tomography scan with an amyloid tracer, and neuropsychological testing by using the Repeatable Battery for the Assessment of Neuropsychological Status. Associations among glutathione levels, brain amyloidosis, and memory were assessed by using multivariate regression models. RESULTS: Lower glutathione levels were associated with greater brain amyloidosis in the temporal (P = .03) and parietal (P = .05) regions, adjusted for apolipoprotein E ε4 carrier status. There were no significant associations between glutathione levels and cognitive scores. CONCLUSIONS: This study found an association between cortical glutathione levels and brain amyloidosis in healthy older adults, suggesting a potential role for 1H-MR spectroscopy measures of glutathione as a noninvasive biomarker of early Alzheimer disease pathogenesis.

Diagnostic assessment of intraoperative cytology for papillary thyroid carcinoma: using a decision tree analysis.

PURPOSE: The aim of this study was to elucidate the cytological characteristics and the diagnostic usefulness of intraoperative cytology (IOC) for papillary thyroid carcinoma (PTC). In addition, using decision tree analysis, effective features for accurate cytological diagnosis were sought. METHODS: We investigated cellularity, cytological features and diagnosis based on the Bethesda System for Reporting Thyroid Cytopathology in IOC of 240 conventional PTCs. The cytological features were evaluated in terms of nuclear score with nuclear features, and additional figures such as presence of swirling sheets, psammoma bodies, and multinucleated giant cells. The nuclear score (range 0-7) was made via seven nuclear features, including (1) enlarged, (2) oval or irregularly shaped nuclei, (3) longitudinal nuclear grooves, (4) intranuclear cytoplasmic pseudoinclusion, (5) pale nuclei with powdery chromatin, (6) nuclear membrane thickening, and (7) marginally placed micronucleoli. RESULTS: Nuclear scores in PTC, suspicious for malignancy, and atypia of undetermined significance cases were 6.18 ± 0.80, 4.48 ± 0.82, and 3.15 ± 0.67, respectively. Additional figures more frequent in PTC than in other diagnostic categories were identified. Cellularity of IOC significantly correlated with tumor size, nuclear score, and presence of additional figures. Also, IOCs with higher nuclear scores (4-7) significantly correlated with larger tumor size and presence of additional figures. In decision tree analysis, IOCs with nuclear score >5 and swirling sheets could be considered diagnostic for PTCs. CONCLUSIONS: Our study suggests that IOCs using nuclear features and additional figures could be useful with decreasing the likelihood of inconclusive results.

One-Year Follow-up of the Changes in Renal Function After Liver Transplantation in Patients Without Chronic Kidney Disease.

BACKGROUND: Impaired renal function is a strong risk factor for morbidity and mortality after liver transplantation (LT). There is clearly a progressive deterioration in renal function after LT. The greatest loss of renal function occurs within the 1st year after LT. Several factors, including calcineurin inhibitors, are associated with decreased renal function. The aims of the present study were to identify changes in renal function before and after LT and to determine the risk factors related to decreased renal function after LT. METHODS: We reviewed medical records of 106 LT recipients without moderate to severe chronic kidney disease (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m(2)). We investigated eGFR changes from before to 1 year after LT with the use of propensity score matching. Statistical significance of differences between clinical parameters and 1-year eGFR changes was assessed with the use of univariate and multivariate analyses. RESULTS: Mean age was 49.5 ± 10.9 years, and 66% of the patients were male. Mean differences in 1-year eGFR and serum creatinine were -32.0 ± 29.2 mL/min/1.73 m(2) and 0.3 ± 0.3 mg/dL, respectively. Variables significantly associated with renal dysfunction 1 year after LT were old age, low pre-LT eGFR, low post-LT hemoglobin, and perioperative acute kidney injury. Multivariate analysis showed that pre-LT renal function was an independent risk factor for decreased renal function after LT. However, there was no significant correlation between 1-year eGFR change and serum tacrolimus level. CONCLUSIONS: Renal function significantly decreased the 1st year after LT, and baseline renal function was an independent risk factor for worsening renal function in LT recipients.

Rapid memory T-cell reconstitution recapitulating CD45RA-depleted haploidentical transplant graft content in patients with hematologic malignancies.

T-cell depletion of an HLA-haploidentical graft is often used to prevent GVHD, but the procedure may lead to increased graft failure, relapse and infections due to delayed immune recovery. We hypothesized that selective depletion of the CD45RA+ subset can effectively reduce GVHD through removal of naive T cells, while providing improved donor immune reconstitution through adoptive transfer of CD45RA- memory T cells. Herein, we present results from the first 17 patients with poor-prognosis hematologic malignancy, who received haploidentical donor transplantation with CD45RA-depleted progenitor cell grafts following a novel reduced intensity conditioning regimen without TBI or serotherapy. Extensive depletion of CD45RA+ T cells and B cells, with preservation of abundant memory T cells, was consistently achieved in all 17 products. Neutrophil engraftment (median day +10) and full donor chimerism (median day +11) was rapidly achieved post transplantation. Early T-cell reconstitution directly correlated with the CD45RA-depleted graft content. T-cell function recovered rapidly with broad TCR Vß spectra. There was no infection-related mortality in this heavily pretreated population, and no patient developed acute GVHD despite infusion of a median of >100 million per kilogram haploidentical T cells.

Survey on awareness and perceptions of bisphosphonate-related osteonecrosis of the jaw in dental hygienists in Seoul.

We investigated awareness in dental hygienists of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in patients with osteoporosis and cancer and assessed the situation in systemic history investigations to broaden the scope of the dental hygienists' BRONJ awareness as a basis for contributing to preventing this disease. The study was carried out through a survey; 217 dental hygienists responded to the survey. They worked at 12 university and general hospitals, 10 dental hospitals and 35 dental clinics, for a total of 57 institutions in Seoul. The survey consisted of 37 questions: general characteristics (J Oral Maxillofac Surg 65: 2007; 369), systemic history investigations (Ruggiero et al. J Oral Maxillofac Surg 62: 2004; 527) and awareness of BRONJ (Park et al. J Korean Dent Assoc 49: 2011; 389). Among them, 79.7% were aware of BRONJ. Recognition was highest among those from 25 to 35 years old (P < 0.05). In terms of work experience, those with 5-10 years experience showed the highest awareness (P < 0.05). In terms of institutions type, dental clinics showed lower awareness than general and dental hospitals (P < 0.05). It was found that 55.3% of the dental hygienists had been educated about BRONJ. Those aged 25-35 years were the most educated. In terms of institutions, dental clinic staff were the least educated. The degree of understanding about BRONJ was analysed with the average score of 6.14 points. According to these results, dental hygienists working in university hospitals and general hospitals had more opportunity to receive training than those working in dental clinics. Thus, it is considered that the development of professional training programs about BRONJ for all dental hygienists is necessary.

SIRT2 regulates tumour hypoxia response by promoting HIF-1α hydroxylation.

Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that has a central role in the regulation of tumour metabolism under hypoxic conditions. HIF-1α stimulates glycolytic energy production and promotes tumour growth. Sirtuins are NAD(+)-dependent protein deacetylases that regulate cellular metabolism in response to stress; however, their involvement in the hypoxic response remains unclear. In this study, it is shown that SIRT2-mediated deacetylation of HIF-1α regulates its stability in tumour cells. SIRT2 overexpression destabilized HIF-1α under hypoxic conditions, whereas HIF-1α protein levels were high in SIRT2-deficient cells. SIRT2 directly interacted with HIF-1α and deacetylated Lys709 of HIF-1α. Deacetylation of HIF-1α by SIRT2 resulted in increased binding affinity for prolyl hydroxylase 2, a key regulator of HIF-1α stability, and increased HIF-1α hydroxylation and ubiquitination. Moreover, a pharmacological agent that increased the intracellular NAD(+)/NADH ratio led to the degradation of HIF-1α by increasing SIRT2-mediated deacetylation and subsequent hydroxylation. These findings suggest that SIRT2-mediated HIF-1α deacetylation is critical for the destablization of HIF-1α and the hypoxic response of tumour cells.

Motor cortex glutathione deficit in ALS measured in vivo with the J-editing technique.

This study compared in vivo levels of the antioxidant glutathione (GSH) in the motor cortex of 11 ALS patients with those in 11 age-matched healthy volunteers (HV). Using the standard J-edited spin-echo difference MRS technique, GSH spectra were recorded on a 3.0 T GE MR system from a single precentral gyrus voxel. GSH levels expressed as ratios to the unsuppressed voxel tissue water (W) were 31% lower in ALS patients than in HV (p=.005), and 36% lower in ALS than in HV (p=.02) when expressed as ratios to the total creatine peak (tCr), supporting a role for oxidative stress in ALS. Levels of the putative neuronal marker N-acetylaspartate (NAA) relative to W did not differ between ALS and HV (p=.26), but were lower by 9% in ALS than in HV (p=.013) when expressed as ratios relative to tCr. This discrepancy is attributed to small but opposite changes in NAA and tCr in ALS that, as a ratio, resulted in a statistically significant group difference, further suggesting caution in using tCr as an internal reference under pathological conditions.

Quercetagetin inhibits macrophage-derived chemokine in HaCaT human keratinocytes via the regulation of signal transducer and activator of transcription 1, suppressor of cytokine signalling 1 and transforming growth factor-ß1.

BACKGROUND: Inflammatory chemokines, such as macrophage-derived chemokine (MDC/CCL22), are elevated in the serum and lesioned skin of patients with atopic dermatitis (AD), and are ligands for C-C chemokine receptor 4, which is predominantly expressed on T helper 2 lymphocytes, basophils and natural killer cells. We have previously reported that quercetagetin has an inhibitory activity on inflammatory chemokines, which is induced by interferon (IFN)-γ and tumour necrosis factor (TNF)-α, occurring via inhibition of the signal transducer and activator of transcription 1 (STAT1) signal. OBJECTIVES: To investigate the specific mechanisms of quercetagetin on the STAT1 signal. METHODS: We confirmed the inhibitory activity of quercetagetin on MDC and STAT1 in HaCaT keratinocytes. The interaction between STAT1 and IFN-γR1 was investigated using immunoprecipitation. The small interfering RNA approach was used to investigate the role of suppressor of cytokine signalling 1 (SOCS1) and transforming growth factor (TGF)-ß1 induced by quercetagetin. RESULTS: Quercetagetin inhibited the expression of MDC at both the protein and mRNA levels in IFN-γ- and TNF-α-stimulated HaCaT human keratinocytes. Moreover, quercetagetin inhibited the phosphorylation of STAT1 through upregulation of SOCS1. Increased expression of SOCS1 disrupted the binding of STAT1 to IFN-γR1. Furthermore, quercetagetin augmented the expression of TGF-ß1, which is known to modulate the immune response and inflammation. CONCLUSIONS: These results suggest that quercetagetin may be a potent inhibitor of the STAT1 signal, which could be a new molecular target for anti-inflammatory treatment, and may thus have therapeutic applications as an immune modulator in inflammatory diseases such as AD.

Risk-adapted donor lymphocyte infusion based on chimerism and donor source in pediatric leukemia.

Donor lymphocyte infusion (DLI) is commonly used to treat leukemia relapse following stem cell transplantation. In florid relapse, however, the efficacy of DLI is limited with substantial risk of severe graft-versus-host disease (GvHD). Here, we develop a novel risk-adapted strategy characterized by pre-emptive DLI initiated at the time of mixed chimerism, a small starting dose based on donor source, dose-escalation guided by real-time chimerism monitoring and withholding of DLI immediately in patients achieving full donor chimerism. A total of 178 DLIs were given to 38 patients with mixed chimerism; thereafter, 33 patients (86.8%) had donor chimerism successfully increased, including 30 (78.9%) who had chimerism fully converted back to 100% donor. Cumulative incidence of relapse was significantly lower (P=0.00004) and overall survival higher (P=0.0003) in patients with chimerism fully corrected as compared with those of patients whose chimerism remained mixed. Only 13.2% of the patients developed acute grade III-IV GvHD with no associated mortality. In conclusion, the risk-adapted DLI strategy is useful in minimizing the risk of childhood leukemia relapse, GvHD and death.

Prognostic implication of the CpG island methylator phenotype in colorectal cancers depends on tumour location.

BACKGROUND: Colorectal cancer (CRC) is usually categorised as proximal or distal CRC. Recently, many researchers have tried to determine the molecular heterogeneity of CRCs along bowel subsites. However, the differential effects of the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) on the clinical outcome according to tumour location are not well-known. METHODS: We analysed clinicopathologic and molecular characteristics, including CIMP, MSI, KRAS and BRAF mutations, in 734 CRCs according to bowel subsites. And the prognostic value of CIMP and MSI was analysed according to tumour location. RESULTS: We found a linear increase of female predominance, T, N category, stage, differentiation, absence of luminal necrosis, tumour -infiltrating lymphocytes, Crohn's-like lymphoid reaction, serration and mucin production from the rectum to caecum. CpG island methylator phenotype -high and MSI-high gradually increased from the rectum to caecum. CpG island methylator phenotype is a poor prognostic factor of overall survival (hazard ratio (HR): 4.13, 95% confidence interval (CI): 1.27-13.46) and disease-free survival (HR: 2.90, 95% CI: 1.04-8.08) in rectal cancers. CONCLUSION: Clinicopathologic and molecular profiles of CRCs gradually change along bowel subsites, and the prognostic implication of CIMP is different according to tumour location.

Prognostic implication of mucinous histology in colorectal cancer patients treated with adjuvant FOLFOX chemotherapy.

BACKGROUND: There have been controversies in prognostic impact of mucinous histology on colorectal cancer, and its implication in patients treated with adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is unclear. METHODS: Stage II and III colorectal cancer patients who underwent curative resection followed by adjuvant FOLFOX were included. Patients were grouped according to the mucinous content: >50%, mucinous adenocarcinoma (MAC); <50%, adenocarcinoma with intermediated mucinous component (AIM); and without any mucinous component, non-MAC (NMA). Clinicopathological features and disease-free survival (DFS) were compared. RESULTS: Among a total of 521 patients, 27 patients (5.2%) had MAC, 41 patients (7.9%) had AIM, and 453 patients (86.9%) had NMA. Mucinous adenocarcinoma and AIM had higher frequency of proximal location and microsatellite instability, but lower frequency of angiolymphatic invasion. Disease-free survival was significantly worse in the MAC compared with NMA (3-year DFS 57% and 86%, respectively; P<0.001) and AIM (3-year DFS 87%, P=0.01 vs MAC). Multivariate analysis revealed MAC as an independent negative prognostic factor of DFS (adjusted hazard ratio 7.96, 95% confidence interval 3.76-16.8). CONCLUSION: Adenocarcinoma with intermediated mucinous component and MAC have distinct clinicopathological features compared with NMA. Mucinous adenocarcinoma has an adverse prognostic impact on stage II or III colorectal cancer treated with adjuvant FOLFOX.

The beneficial effect of palliative resection in metastatic colorectal cancer.

BACKGROUND: We aimed to determine the role of palliative resection in metastatic colorectal cancer (mCRC) and ascertain which patient populations would benefit most from this treatment. METHODS: A total of 1015 patients diagnosed with mCRC at Seoul National University Hospital between 2000 and 2009 were retrospectively studied. RESULTS: Of the 1015 patients, 168 patients with only liver and/or lung metastasis received curative resection. The remaining 847 patients were treated with palliative chemotherapy and/or palliative resection combined with best supportive care. Palliative resection was performed in 527 (62.2%) cases (complete resection with negative margin (R0) in 93, R1/2 in 434). Resected patients had a more prolonged median overall survival (OS) than unresected patients (21.3 vs 14.1 months; P<0.001). In multivariate analysis, R0 resection was found to be associated with a superior OS compared with R1/2 resection (51.3 vs 19.1 months; P<0.001) and no resection (51.3 vs 14.1 months; P<0.001). When we performed propensity score matching, palliative resection was found to be related to prolonged OS (hazard ratio=0.72, 95% confidence interval=0.59-0.89; P=0.003). CONCLUSION: Palliative resection without residual disease and chemotherapy confers a longer-term survival outcome than palliative chemotherapy alone in mCRC patient subset.