Decreased Serum Level of Sclerostin in Older Adults with Sarcopenia

Background@#Although muscles and bones interact with each other through various secretory factors, the role of sclerostin, an osteocyte-secreted factor, on muscle metabolism has not been well studied. We investigated the levels of serum sclerostin in Korean older adults with sarcopenia. @*Methods@#Blood samples were collected from 129 participants who underwent evaluation of muscle mass and function in an outpatient geriatric clinic of a teaching hospital. Sarcopenia and related parameters were determined using cutoff values for the Asian population. Serum sclerostin levels were measured using an enzyme-linked immunosorbent assay. @*Results@#The mean age of the participants was 69.6 years, and 20 participants (15.5%) were classified as having sarcopenia. After adjusting for age, sex, and body mass index, serum sclerostin levels were significantly lower in participants with sarcopenia, low muscle mass, or weak muscle strength (P=0.003 to 0.045). Serum sclerostin levels were positively associated with skeletal muscle index and grip strength after adjusting for confounders (P=0.001 and P=0.003), whereas sarcopenic phenotype score showed a negative association (P=0.006). These increases in muscle mass and strength were also dose dependent as serum sclerostin levels increased (P for trends=0.003 and P for trends=0.015). Higher serum sclerostin levels were associated with lower odds ratio (ORs) for sarcopenia, low muscle mass, and weak muscle strength after adjusting for confounders (OR, 0.27 to 0.50; P<0.001 to 0.025). @*Conclusion@#Higher serum sclerostin levels were associated with a lower risk of sarcopenia, low muscle mass, and weak muscle strength in Korean older adults.

Insulin Resistance Increases Serum Immunoglobulin E Sensitization in Premenopausal Women

BackgroundAlthough studies have shown that obesity is associated with aeroallergen sensitization (atopy), controversy still exists. We aimed to investigate the association between metabolic status, obesity, and atopy stratified by sex and menopausal status.MethodsA total of 1,700 adults from the 2010 Korean National Health and Nutrition Examination Survey were classified into metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) by body mass index and insulin resistance. Atopy was defined as a positive response to at least one aeroallergen. Multiple regression analysis was used to evaluate the risk of immunoglobulin E (IgE) elevation or atopy in relation to the degree of metabolic abnormality and obesity.ResultsIn premenopausal women, total IgE was positively correlated with obesity and insulin resistance. MUNO participants had a higher risk of having elevated total IgE compared to MHNO participants (odds ratio [OR], 2.271; 95% confidence interval [CI], 1.201 to 4.294), while MHO participants did not show a significant difference (OR, 1.435; 95% CI, 0.656 to 3.137) in premenopausal women. MUNO, but not MHO was also associated with atopy (OR, 2.157; 95% CI, 1.284 to 3.625). In men and postmenopausal women, there was no significant difference between metabolic status, obesity, and atopy among groups.ConclusionIncreased insulin resistance is associated with total IgE and atopy in premenopausal women but not in postmenopausal women or men.

Insulin Resistance Increases Serum Immunoglobulin E Sensitization in Premenopausal Women

BackgroundAlthough studies have shown that obesity is associated with aeroallergen sensitization (atopy), controversy still exists. We aimed to investigate the association between metabolic status, obesity, and atopy stratified by sex and menopausal status.MethodsA total of 1,700 adults from the 2010 Korean National Health and Nutrition Examination Survey were classified into metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) by body mass index and insulin resistance. Atopy was defined as a positive response to at least one aeroallergen. Multiple regression analysis was used to evaluate the risk of immunoglobulin E (IgE) elevation or atopy in relation to the degree of metabolic abnormality and obesity.ResultsIn premenopausal women, total IgE was positively correlated with obesity and insulin resistance. MUNO participants had a higher risk of having elevated total IgE compared to MHNO participants (odds ratio [OR], 2.271; 95% confidence interval [CI], 1.201 to 4.294), while MHO participants did not show a significant difference (OR, 1.435; 95% CI, 0.656 to 3.137) in premenopausal women. MUNO, but not MHO was also associated with atopy (OR, 2.157; 95% CI, 1.284 to 3.625). In men and postmenopausal women, there was no significant difference between metabolic status, obesity, and atopy among groups.ConclusionIncreased insulin resistance is associated with total IgE and atopy in premenopausal women but not in postmenopausal women or men.

Inhibition of Ceramide Accumulation in Podocytes by Myriocin Prevents Diabetic Nephropathy

Background@#Ceramides are associated with metabolic complications including diabetic nephropathy in patients with diabetes.Recent studies have reported that podocytes play a pivotal role in the progression of diabetic nephropathy. Also, mitochondrial dysfunction is known to be an early event in podocyte injury. Thus, we tested the hypothesis that ceramide accumulation in podocytes induces mitochondrial damage through reactive oxygen species (ROS) production in patients with diabetic nephropathy. @*Methods@#We used Otsuka Long Evans Tokushima Fatty (OLETF) rats and high-fat diet (HFD)-fed mice. We fed the animals either a control- or a myriocin-containing diet to evaluate the effects of the ceramide. Also, we assessed the effects of ceramide on intracellular ROS generation and on podocyte autophagy in cultured podocytes. @*Results@#OLETF rats and HFD-fed mice showed albuminuria, histologic features of diabetic nephropathy, and podocyte injury, whereas myriocin treatment effectively treated these abnormalities. Cultured podocytes exposed to agents predicted to be risk factors (high glucose, high free fatty acid, and angiotensin II in combination [GFA]) showed an increase in ceramide accumulation and ROS generation in podocyte mitochondria. Pretreatment with myriocin reversed GFA-induced mitochondrial ROS generation and prevented cell death. Myriocin-pretreated cells were protected from GFA-induced disruption of mitochondrial integrity. @*Conclusion@#We showed that mitochondrial ceramide accumulation may result in podocyte damage through ROS production.Therefore, this signaling pathway could become a pharmacological target to abate the development of diabetic kidney disease.

Association between urinary sodium levels and iodine status in Korea

Background/Aims@#To evaluate the association between the urinary sodium concentration and iodine status in different age groups in Korea. @*Methods@#This nationwide, population-based, cross-sectional study used data from the Korean National Health and Nutrition Examination Survey (VI 2-3, 2014 to 2015). We included 3,645 subjects aged 10 to 75 years with normal kidney function and without a history of thyroid disease. Adequate iodine intake was defined as a urinary iodine/creatinine (I/Cr) ratio of 85 to 220 µg/g. The urinary sodium/ creatinine (Na/Cr) ratios were classified as low ( 114 mmol/g). @*Results@#The median urinary iodine concentration (UIC) was 292 µg/L (interquartile range [IQR], 157 to 672), and the median urinary I/Cr ratio was 195 µg/g (IQR, 104 to 478). Iodine deficiency ( 300 µg/L) were observed in 11.3% and 49.0% of subjects, respectively. The UIC was significantly associated with the urinary sodium concentration, and the urinary I/Cr ratio was significantly correlated with the urinary Na/Cr ratio (both p < 0.001). The distributions of UIC, urinary I/Cr ratio, and Na/Cr ratio varied among age groups. Low urinary I/Cr and Na/Cr ratios were most common in young adults (age, 19 to 29 years), while high urinary I/Cr and Na/Cr ratios were most common in elderly people (age, 60 to 75 years). @*Conclusions@#Iodine intake was significantly associated with sodium intake in the Korean population. Our study suggested that an adequately low salt intake might be helpful for preventing iodine excess in Korea.

A Phase II Study of Avelumab Monotherapy in Patients with Mismatch Repair–Deficient/Microsatellite Instability–High or POLE-Mutated Metastatic or Unresectable Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We evaluated the efficacy and safety of avelumab, an anti-PD-L1 antibody, in patients with metastatic or unresectable colorectal cancer (mCRC) with mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) or POLE mutations. @*Materials and Methods@#In this prospective, open-label, multicenter phase II study, 33 patients with mCRC harboring dMMR/MSI-H or POLE mutations after failure of ≥1st-line chemotherapy received avelumab 10 mg/kg every 2 weeks. dMMR/MSI-H was confirmed with immunohistochemical staining (IHC) by loss of expression of MMR proteins or polymerase chain reaction (PCR) for microsatellite sequences. POLE mutation was confirmed by next-generation sequencing (NGS). The primary endpoint was the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors ver. 1.1. @*Results@#The median age was 60 years, and 78.8% were male. Thirty patients were dMMR/MSI-H and three had POLE mutations. The ORR was 24.2%, and all of the responders were dMMR/MSI-H. For 21 patients with MSI-H by PCR or NGS, the ORR was 28.6%. At a median follow-up duration of 16.3 months, median progression-free survival and overall survival were 3.9 and 13.2 months in all patients, and 8.1 months and not reached, respectively, in patients with MSI-H by PCR or NGS. Dose interruption and discontinuation due to treatment-related adverse events occurred in 4 and 2 patients, respectively, with no treatment-related deaths. @*Conclusion@#Avelumab displayed antitumor activity with manageable toxicity in patients with previously treated mCRC harboring dMMR/MSI-H. Diagnosis of dMMR/MSI-H with PCR or NGS could be complementary to IHC to select patients who would benefit from immunotherapy.

Magnetic Resonance-Based Texture Analysis Differentiating KRAS Mutation Status in Rectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Mutation of the Kirsten Ras (KRAS) oncogene is present in 30%-40% of colorectal cancers and has prognostic significance in rectal cancer. In this study, we examined the ability of radiomics features extracted from T2-weighted magnetic resonance (MR) images to differentiate between tumors with mutant KRAS and wild-type KRAS. @*Materials and Methods@#Sixty patients with primary rectal cancer (25 with mutant KRAS, 35 with wild-type KRAS) were retrospectively enrolled. Texture analysis was performed in all regions of interest on MR images, which were manually segmented by two independent radiologists. We identified potentially useful imaging features using the two-tailed t test and used them to build a discriminant model with a decision tree to estimate whether KRAS mutation had occurred. @*Results@#Three radiomic features were significantly associated with KRASmutational status (p < 0.05). The mean (and standard deviation) skewness with gradient filter value was significantly higher in the mutant KRAS group than in the wild-type group (2.04±0.94 vs. 1.59±0.69). Higher standard deviations for medium texture (SSF3 and SSF4) were able to differentiate mutant KRAS (139.81±44.19 and 267.12±89.75, respectively) and wild-type KRAS (114.55±29.30 and 224.78±62.20). The final decision tree comprised three decision nodes and four terminal nodes, two of which designated KRAS mutation. The sensitivity, specificity, and accuracy of the decision tree was 84%, 80%, and 81.7%, respectively. @*Conclusion@#Using MR-based texture analysis, we identified three imaging features that could differentiate mutant from wild-type KRAS. T2-weighted images could be used to predict KRAS mutation status preoperatively in patients with rectal cancer.

Validity and Reliability of Korean Version of Simplified Nutritional Appetite Questionnaire in Patients with Advanced Cancer: A Multicenter, Longitudinal Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Malnutrition and a loss of muscle mass are frequent in cancer patients and have a negative effect on clinical outcome. Nutrition risk screening aims to increase awareness and allow early recognition and treatment of cancer cachexia. Therefore, screenings should be brief, inexpensive, highly sensitive, and have good specificity. Simplified Nutritional Appetite Questionnaire (SNAQ) is a simple screening tool including four questions, and validated to predict weight loss within 6 months in community-dwelling adults and nursing home residents. Our study aimed to translate the SNAQ into Korean, and to assess the validity and reliability of the translated screening tool in advanced cancer patients. MATERIALS AND METHODS: The SNAQ was translated into Korean according to linguistic validation. The internal consistency of the SNAQ was evaluated by Cronbach's alpha coefficient. Test-retest reliability was evaluated using the intraclass correlation coefficient. Concurrent validity was evaluated by measuring the Pearson's correlation coefficient between the SNAQ and Mini-Nutritional Assessment (MNA) and Patient-Generated Subjective Global Assessment (PG-SGA). RESULTS: In the 194 patients included in full analysis set, cancer stage was predominantly metastatic (98.5%), the mean age was 60 years (range, 23 to 81 years), and the mean body mass index was 24 kg/m² (range, 15.6 to 39.6 kg/m²). According to MNA score ≤ 11, 57 patients (29.4%) were malnourished. The mean score (±standard deviation) of the Korean version of the SNAQ was 13.8±2.5 with a range of 6-19. Cronbach's alpha coefficient was 0.737, and intraclass correlation coefficient was 0.869. The SNAQ was moderately correlated with MNA (r=0.404, p 5% of the original bodyweightwithin 6 months occurred in 46 of the 186 patients (24.7%). SNAQ score ≤ 14 predicted > 5% weight loss with a sensitivity of 56.5% and a specificity of 44.3%. CONCLUSION: The Korean version of the SNAQ had high validity and reliability. SNAQ is useful for the screening tool for advanced cancer patients. The SNAQ had a limitation to predict impending weight loss in advanced cancer patients.

Prospective Validation of The Korean Cancer Study Group Geriatric Score (KG)-7, a Novel Geriatric Screening Tool, in Older Patients with Advanced Cancer Undergoing First-line Palliative Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to prospectively validate the Korean Cancer Study Group Geriatric Score (KG)-7, a novel geriatric screening tool, in older patients with advanced cancer planned to undergo first-line palliative chemotherapy. MATERIALS AND METHODS: Participants answered the KG-7 questionnaire before undergoing geriatric assessment (GA) and first-line palliative chemotherapy. The performance of KG-7 was evaluated by calculating the sensitivity (SE), specificity (SP), positive and negative predictive value (PPV and NPV), balanced accuracy (BA), and area under the curve (AUC). RESULTS: The baseline GA and KG-7 results were collected from 301 patients. The median age was 75 years (range, 70 to 93 years). Abnormal GA was documented in 222 patients (73.8%). Based on the ≤ 5 cut-off value of KG-7 for abnormal GA, abnormal KG-7 score was shown in 200 patients (66.4%). KG-7 showed SE, SP, PPV, NPV, and BA of 75.7%, 59.7%, 84.4%, 46.0%, and 67.7%, respectively; AUC was 0.745 (95% confidence interval, 0.687 to 0.803). Furthermore, patients with higher KG-7 scores showed significantly longer survival (p=0.006). CONCLUSION: KG-7 appears to be adequate in identifying patients with abnormal GA prospectively. Hence, KG-7 can be a useful screening tool for Asian countries with limited resources and high patient volume.

The Impact of Surgical Timing on Pathologic Tumor Response after Short Course and Long Course Preoperative Chemoradiation for Locally Advanced Rectal Adenocarcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: A pooled analysis of multi-institutional trials was performed to analyze the effect of surgical timing on tumor response by comparing short course concurrent chemoradiotherapy (CCRT) with long course CCRT followed by delayed surgery in locally advanced rectal cancer. MATERIALS AND METHODS: Three hundred patients with cT3-4N0-2 rectal adenocarcinoma were included. Long course patients from KROG 14-12 (n=150) were matched 1:1 to 150 short course patients from KROG 10-01 (NCT01129700) and KROG 11-02 (NCT01431599) according to stage, age, and other risk factors. The primary endpoint was to determine the interval between surgery and the last day of neoadjuvant CCRT which yields the best tumor response after the short course and long course CCRT. Downstaging was defined as ypT0-2N0M0 and pathologic complete response (ypCR) was defined as ypT0N0M0, respectively. RESULTS: Both the long and short course groups achieved lowest downstaging rates at < 6 weeks (long 20% vs. short 8%) and highest downstaging rates at 6-7 weeks (long 44% vs. short 40%). The ypCR rates were lowest at < 6 weeks (both long and short 0%) and highest at 6-7 weeks (long 21% vs. short 11%) in both the short and long course arms. The downstaging and ypCR rates of long course group gradually declined after the peak at 6-7 weeks and those of the short course group trend to constantly increase afterwards. CONCLUSION: It is optimal to perform surgery at least 6 weeks after both the short course and long course CCRT to obtain maximal tumor regression in locally advanced rectal adenocarcinoma.

Redefining the Positive Circumferential Resection Margin by Incorporating Preoperative Chemoradiotherapy Treatment Response in Locally Advanced Rectal Cancer: A Multicenter Validation Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was conducted to validate the prognostic influence of treatment response among patients with positive circumferential resection margin for locally advanced rectal cancer. MATERIALS AND METHODS: Clinical data of 197 patientswith positive circumferential resection margin defined as ≤ 2 mm after preoperative chemoradiotherapy followed by total mesorectal excision between 2004 and 2009 were collected for this multicenter validation study. All patients underwent median 50.4 Gy radiation with concurrent fluoropyrimidine based chemotherapy. Treatment response was dichotomized to good response, including treatment response of grade 2 or 3, and poor response, including grade 0 or 1. RESULTS: After 52 months median follow-up, 5-year overall survival (OS) for good responders and poor responders was 79.1% and 48.4%, respectively (p < 0.001). In multivariate analysis, circumferential resection margin involvement and treatment response were a prognosticator for OS and locoregional recurrence-free survival. In subgroup analysis, good responders with close margin showed significantly better survival outcomes for survival. Good responders with involved margin and poor responders with close margin shared similar results, whereas poor responders with involved margin had worst survival (5-year OS, 81.2%, 57.0%, 50.0%, and 32.4%, respectively; p < 0.001). CONCLUSION: Among patients with positive circumferential resection margin after preoperative chemoradiotherapy, survival of the good responders was significantly better than poor responders. Subgroup analysis revealed that definition of positive circumferential resection margin may be individualized as involvement for good responders, whereas ≤ 2 mm for poor responders.

Healthcare Costs of Osteoporotic Fracture in Korea: Information from the National Health Insurance Claims Database, 2008-2011

BACKGROUND: The present study estimated healthcare costs of osteoporotic fractures including spine, hip, distal radius and humerus in Koreans over 50 years of age using national claims data. METHODS: Korea National Health Insurance data between 2008 and 2011 was searched for all claims records of outpatient visits or hospital admissions of patients ≥50-year-of-age. Osteoporosis-related fractures were identified using certain the International Classification of Diseases, Tenth Revision codes and site-specific physician claims for procedures in a patient age cut-off value of 50 years. The healthcare costs included acute phase costs accounting for emergency medical care given immediately after fracture, costs due to further hospitalization and surgical procedures, physiotherapy sessions according to the site of the fracture, and outpatient visits in the year after discharge. RESULTS: The total estimated healthcare costs of osteoporotic fractures in 2011 was $722 million. From 2008 to 2011, the total number and healthcare costs of osteoporotic fractures increased 28.9% (from 127,070 to 163,823) and 31.6% (from $549 million to $722 million), respectively. The portion of national health care expenditure was ranged from 2.3% in 2008 to 2.2% in 2011. The mean healthcare cost of osteoporotic fractures per person increased 2.1% from $4,321 in 2008 to $4,410 in 2011.The mean healthcare costs were highest for hip fractures followed by spine, humerus, and distal radius fractures. CONCLUSIONS: Total Healthcare costs of osteoporotic fractures in South Koreans ≥50-year-of-age increased between 2008 and 2011. This trend will likely continue, which is an important health problem in the elderly population and economically.

Endoscopic Criteria for Evaluating Tumor Stage after Preoperative Chemoradiation Therapy in Locally Advanced Rectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Local excision may be an another option for selected patients with markedly down-staged rectal cancer after preoperative chemoradiation therapy (CRT), and proper evaluation of post-CRT tumor stage (ypT) is essential prior to local excision of these tumors. This study was designed to determine the correlations between endoscopic findings and ypT of rectal cancer. MATERIALS AND METHODS: In this study, 481 patients with locally advanced rectal cancer who underwent preoperative CRT followed by surgical resection between 2004 and 2013 at a single institution were evaluated retrospectively. Pathological good response (p-GR) was defined as ypT ≤ 1, and pathological minimal or no response (p-MR) as ypT ≥ 2. The patients were randomly classified according to two groups, a testing (n=193) and a validation (n=288) group. Endoscopic criteria were determined from endoscopic findings and ypT in the testing group and used in classifying patients in the validation group as achieving or not achieving p-GR. RESULTS: Based on findings in the testing group, the endoscopic criteria for p-GR included scarring, telangiectasia, and erythema, whereas criteria for p-MR included nodules, ulcers, strictures, and remnant tumors. In the validation group, the kappa statistic was 0.965 (p < 0.001), and the sensitivity, specificity, positive predictive value, and negative predictive value were 0.362, 0.963, 0.654, and 0.885, respectively. CONCLUSION: The endoscopic criteria presented are easily applicable for evaluation of ypT after preoperative CRT for rectal cancer. These criteria may be used for selection of patients for local excision of down-staged rectal tumors, because patients with p-MR could be easily ruled out.

Management of osteoporosis patients for prosthetic restoration

The average life expectancy has been increased, so the proportion of elderly patients that visit to the dental clinic for prosthetic restoration has increased. Elderly patients have various chronic diseases. Recent trends show an increase of osteoporosis in elderly patients, and thus, the number of osteoporosis patients is expected to escalate. Currently, the most widely used drug for osteoporosis is bisphosphonate. However, osteonecrosis of the jaw has been reported as a side effect derived from long-term oral administration or injection treatment of the drug. Surgical dental treatment was the main cause of medication related osteonecrosis of the jaw (MRONJ). As MRONJ is very difficult to cure, it is important to take preventive measures. Surgical operation may be needed for the mouth preparation before prosthetic restoration. For successful treatment, the dentist should have a full understanding of osteoporosis and show a continued interest toward this disease for careful management.

What Is the Ideal Tumor Regression Grading System in Rectal Cancer Patients after Preoperative Chemoradiotherapy? / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Tumor regression grade (TRG) is predictive of therapeutic response in rectal cancer patients after chemoradiotherapy (CRT) followed by curative resection. However, various TRG systems have been suggested, with subjective categorization, resulting in interobserver variability. This study compared the prognostic validity of four different TRG systems in order to identify the most ideal TRG system. MATERIALS AND METHODS: This study included 933 patients who underwent preoperative CRT and curative resection. Primary tumors alone were graded according to the American Joint Committee on Cancer (AJCC), Dworak, and Ryan TRG systems, and both primary tumors and regional lymph nodes were graded according to a modified Dworak TRG system. The ability of each TRG system to predict recurrence-free survival (RFS) and overall survival (OS) was analyzed using chi-square and C statistics. RESULTS: All four TRG systems were significantly predictive of both RFS and OS (p < 0.001 each), however none was a better predictor of prognosis than ypStage. Among the four TRGs, the mDworak TRG system was a better predictor of RFS and OS than the AJCC, Dworak, and Ryan TRG systems, and both the chi-square and C statistics were higher for the former, although the differences were not statistically significant. The combination of ypStage and the modified Dworak TRG better predicted RFS and OS than ypStage alone. CONCLUSION: The modified Dworak TRG system for evaluation of entire tumors including regional lymph nodes is a better predictor of survival than current TRG systems for evaluation of the primary tumor alone.

Dipeptidyl Peptidase 10, a Novel Prognostic Marker in Colorectal Cancer

PURPOSE: The dipeptidyl peptidase IV (DPPIV) gene family exhibits multiple functions and is involved in the pathogenesis of various diseases. It has attracted pharmaceutical interest in the areas of metabolic disorders as well as cancer. However, clinicopathologic significance of DPPIV family in colorectal cancer is not fully understood. MATERIALS AND METHODS: The clinical relevance of DPPIV and DPP10 expression was determined by immunohistochemical staining, and by assessing its clinicopathologic correlation in 383 colorectal cancer patients with known clinical outcomes. RESULTS: DPPIV was not expressed in normal colon mucosa, but it showed luminal expression in 52 of the 383 colorectal cancers (13.5%). DPPIV expression in tumors was associated with right-sided location of the colon (p=0.010) and more advanced tumor stage (p=0.045). DPP10 was expressed in normal colonic mucosa, but its expression varied in primary colorectal cancer tissues. Loss of DPP10 expression was found in 11 colorectal cancers (CRCs) (2.9%), and multivariate analysis showed that loss of DPP10 expression was an independent factor for poor patient prognosis (p=0.008). CONCLUSION: DPP10 may play a role in disease progression of colorectal cancer and loss of DPP10 expression in primary CRC is significantly associated with poor survival outcomes.

A Case of Capecitabine-Induced Sarcoidosis / 결핵및호흡기질환

Sarcoidosis is an inflammatory disease involving multiple-organs with an unknown cause. The new onset of sarcoidosis associated with therapeutic agents has been observed in 3 clinical settings; tumor necrosis factor antagonists in autoimmune rheumatologic diseases, interferon alpha with or without ribavirin in patients with chronic hepatitis C or melanoma, and antineoplastic agent-associated sarcoidosis in patients with hematologic malignancies. Here, we report a female patient who developed sarcoidosis after capecitabine treatment as an adjuvant chemotherapy for sigmoid colon cancer. To our knowledge, this is the first report of a capecitabine-induced sarcoidosis.

Tumor Budding and Recurrence in Submucosal Invasive Colorectal Cancers of Favorable Histology: Case Reports of Two Early Colorectal Cancers with Advanced Recurrences

Complete resection of submucosal invasive colorectal cancer (SICC) showing favorable histology is regarded as curative. We report on two cases of SICC showing recurrence within 5 years despite complete resection. The first patient was a 68-year-old woman with well differentiated rectal adenocarcinoma invading the superficial submucosa, which recurred after 4.7 years. The second patient was a 53-year-old man with pT1N0 moderately differentiated colonic adenocarcinoma. He developed widespread tumor recurrence after 3.9 years. Retrospective pathologic review of the original tumors showed multiple foci of tumor budding at the invasive front. Immunohistochemical staining for D2-40 of deeper levels of the paraffin blocks showed rare foci of small lymphatic invasion. Tumor budding at the invasive front may be an important indicator for SICC aggressiveness or may reflect early lymphatic invasion. More aggressive pathologic examination and follow-up is required for patients with SICC showing tumor budding, even in the absence of unfavorable histologic findings.

Tumor Budding and Recurrence in Submucosal Invasive Colorectal Cancers of Favorable Histology: Case Reports of Two Early Colorectal Cancers with Advanced Recurrences

Complete resection of submucosal invasive colorectal cancer (SICC) showing favorable histology is regarded as curative. We report on two cases of SICC showing recurrence within 5 years despite complete resection. The first patient was a 68-year-old woman with well differentiated rectal adenocarcinoma invading the superficial submucosa, which recurred after 4.7 years. The second patient was a 53-year-old man with pT1N0 moderately differentiated colonic adenocarcinoma. He developed widespread tumor recurrence after 3.9 years. Retrospective pathologic review of the original tumors showed multiple foci of tumor budding at the invasive front. Immunohistochemical staining for D2-40 of deeper levels of the paraffin blocks showed rare foci of small lymphatic invasion. Tumor budding at the invasive front may be an important indicator for SICC aggressiveness or may reflect early lymphatic invasion. More aggressive pathologic examination and follow-up is required for patients with SICC showing tumor budding, even in the absence of unfavorable histologic findings.

Pretreatment Serum CEA as a Prognostic Factor for Rectal Cancer Treated with Preoperative Chemoradiotherapy

PURPOSE: Preoperative serum carcinoembryonic antigen (s-CEA) is well known to be a prognostic factor in patients with colorectal cancer. However, the prognostic effect of s-CEA in patients with rectal cancer treated with preoperative chemoradiotherapy (CRT) has not been well studied. The aim of this study is to evaluate the prognostic value of pretreatment s-CEA for rectal cancer treated with preoperative CRT. METHODS: This study analyzed the data of 436 patients who received preoperative CRT and underwent curative surgery for locally advanced rectal cancer from January 2002 to July 2007. Patients were categorized into two groups according to pretreatment CEA levels: 10 ng/mL. The disease-free survivals between the two groups were compared. RESULTS: The three-year disease-free survival rates of the CEA 10 ng/mL group were 80.4% and 67.3%, respectively (P=0.002). Multivariate analysis revealed the following independent risk factor for recurrence: pretreatment CEA >10 ng/mL (hazard ratio [HR] 1.616; 95% confidence interval [CI], 1.007 to 2.594; P=0.047), positive lymph node status (HR, 2.580; 95% CI, 1.625 to 4.094; P<0.001), and positive circumferential resection margin (HR, 1.889; 95% CI, 1.035 to 3.446; P=0.038). CONCLUSION: Pretreatment s-CEA (cutoff value 10 ng/mL) may be a prognostic factor for disease-free survival in rectal cancer patients treated with preoperative CRT and surgery.