A novel variant of PHEX in a Korean family with X-linked hypophosphatemic rickets

X-linked dominant hypophosphatemic rickets are the most common form of familial hypophosphatemic rickets resulting from hypophosphatemia caused by renal phosphate wasting, which in turn is a result of loss-of-function mutations in PHEX.Herein, we report a 39-year-old female with short stature and skeletal deformities and 12-month-old asymptomatic daughter.The female has a history of multiple surgical treatments because of lower limb deformities. Her biochemical findings revealed low serum phosphorus levels with elevated serum alkaline phosphatase activity and normal serum calcium levels, suggesting presence of hypophosphatemic rickets. To identify the molecular causes, we used a multigene testing panel and found a mutation, c.667dup (p.Asp223GlyfsTer15), in PHEX gene. To the best of our knowledge, this is a novel mutation. A heterozygous form of the same variant was detected in daughter, who showed no typical symptoms such as bow legs, frontal bossing, or waddling gate, but presented early signs of impaired mineralization in both X-ray and biochemical findings. The daughter was initiated onto early medical treatment with oral phosphate supplementation and an active vitamin D analog. Because the daughter was genetically diagnosed based on a family history before the onset of symptoms, appropriate medical management was possible from early infancy.

Machine learning based potentiating impacts of 12‑lead ECG for classifying paroxysmal versus non‑paroxysmal atrial fibrillation

Background@#Conventional modality requires several days observation by Holter monitor to differentiate atrial fibril‑ lation (AF) between Paroxysmal atrial fibrillation (PAF) and Non-paroxysmal atrial fibrillation (Non-PAF). Rapid and practical differentiating approach is needed. @*Objective@#To develop a machine learning model that observes 10-s of standard 12-lead electrocardiograph (ECG) for real-time classification of AF between PAF versus Non-PAF. @*Methods@#In this multicenter, retrospective cohort study, the model training and cross-validation was performed on a dataset consisting of 741 patients enrolled from Severance Hospital, South Korea. For cross-institutional validation, the trained model was applied to an independent data set of 600 patients enrolled from Ewha University Hospital, South Korea. Lasso regression was applied to develop the model. @*Results@#In the primary analysis, the Area Under the Receiver Operating Characteristic Curve (AUC) on the test set for the model that predicted AF subtype only using ECG was 0.72 (95% CI 0.65–0.80). In the secondary analysis, AUC only using baseline characteristics was 0.53 (95% CI 0.45–0.61), while the model that employed both baseline characteris‑ tics and ECG parameters was 0.72 (95% CI 0.65–0.80). Moreover, the model that incorporated baseline characteristics, ECG, and Echocardiographic parameters achieved an AUC of 0.76 (95% CI 0.678–0.855) on the test set. @*Conclusions@#Our machine learning model using ECG has potential for automatic differentiation of AF between PAF versus Non-PAF achieving high accuracy. The inclusion of  Echocardiographic parameters further increases model per‑ formance. Further studies are needed to clarify the next steps towards clinical translation of the proposed algorithm.

Long-term Efficacy of S-1 Monotherapy or Capecitabine Plus Oxaliplatin as Adjuvant Chemotherapy for Patients with Stage II or III Gastric Cancer after Curative Gastrectomy: a Propensity Score-Matched Multicenter Cohort Study

Purpose@#To compare long-term disease-free survival (DFS) between patients receiving tegafur/gimeracil/oteracil (S-1) or capecitabine plus oxaliplatin (CAPOX) adjuvant chemotherapy (AC) for gastric cancer (GC). @*Materials and Methods@#This retrospective multicenter observational study enrolled 983 patients who underwent curative gastrectomy with consecutive AC with S-1 or CAPOX for stage II or III GC at 27 hospitals in Korea between February 2012 and December 2013. We conducted propensity score matching to reduce selection bias. Long-term oncologic outcomes, including DFS rate over 5 years (over-5yr DFS), were analyzed postoperatively. @*Results@#The median and longest follow-up period were 59.0 and 87.6 months, respectively. DFS rate did not differ between patients who received S-1 and CAPOX for pathologic stage II (P=0.677) and stage III (P=0.899) GC. Moreover, hazard ratio (HR) for recurrence did not differ significantly between S-1 and CAPOX (reference) in stage II (HR, 1.846; 95% confidence interval [CI], 0.693–4.919; P=0.220) and stage III (HR, 0.942; 95% CI, 0.664–1.337; P=0.738) GC. After adjustment for significance in multivariate analysis, pT (4 vs. 1) (HR, 11.667; 95% CI, 1.595–85.351; P=0.016), pN stage (0 vs. 3) (HR, 2.788; 95% CI, 1.502–5.174; P=0.001), and completion of planned chemotherapy (HR, 2.213; 95% CI, 1.618–3.028; P<0.001) were determined as independent prognostic factors for DFS. @*Conclusions@#S-1 and CAPOX AC regimens did not show significant difference in over-5yr DFS after curative gastrectomy in patients with stage II or III GC. The pT, pN stage, and completion of planned chemotherapy were prognostic factors for GC recurrence.

Erratum: A Validation Study of a Multiple Reaction Monitoring-Based Proteomic Assay to Diagnose Breast Cancer / 한국유방암학회지

In the article, “A Validation Study of a Multiple Reaction Monitoring-Based Proteomic Assay to Diagnose Breast Cancer” in Volume 22(4), page 579-586 was error in the table. In Table 1, the value of pN0 was incorrectly listed as 29 (56.9) in ‘diagnosed as normal by biomarker’ and corrected to 39 (76.5). The authors apologize for any inconvenience that this may have caused.

A Validation Study of a Multiple Reaction Monitoring-Based Proteomic Assay to Diagnose Breast Cancer / 한국유방암학회지

Nationwide survey of partial fundoplication in Korea: comparison with total fundoplication

PURPOSE: Laparoscopic total fundoplication is the standard surgery for gastroesophageal reflux disease. However, partial fundoplication may be a viable alternative. Here, we conducted a nationwide survey of partial fundoplication in Korea. METHODS: The Korean Anti-Reflux Surgery study group recorded 32 cases of partial fundoplication at eight hospitals between September 2009 and January 2016. The surgical outcomes and postoperative adverse symptoms in these cases were evaluated and compared with 86 cases of total fundoplication. RESULTS: Anterior partial fundoplication was performed in 20 cases (62.5%) and posterior in 12 (37.5%). In most cases, partial fundoplication was a secondary procedure after operations for other conditions. Half of patients who underwent partial fundoplication had typical symptoms at the time of initial diagnosis, and most of them showed excellent (68.8%), good (25.0%), or fair (6.3%) symptom resolution at discharge. Compared to total fundoplication, partial fundoplication showed no difference in the resolution rate of typical and atypical symptoms. However, adverse symptoms such as dysphagia, difficult belching, gas bloating and flatulence were less common after partial fundoplication. CONCLUSION: Although antireflux surgery is not popular in Korea and total fundoplication is the primary surgical choice for gastroesophageal reflux disease, partial fundoplication may be useful in certain conditions because it has less postoperative adverse symptoms but similar efficacy to total fundoplication.

Who Can Perform Adjuvant Chemotherapy Treatment for Gastric Cancer? A Multicenter Retrospective Overview of the Current Status in Korea

PURPOSE: To investigate the current status of adjuvant chemotherapy (AC) regimens in Korea and the difference in efficacy of AC administered by surgical and medical oncologists in patients with stage II or III gastric cancers. MATERIALS AND METHODS: We performed a retrospective observational study among 1,049 patients who underwent curative resection and received AC for stage II and III gastric cancers between February 2012 and December 2013 at 29 tertiary referral university hospitals in Korea. To minimize the influence of potential confounders on selection bias, propensity score matching (PSM) was used based on binary logistic regression analysis. The 3-year disease-free survival (DFS) rates were compared between patients who received AC administered by medical oncologists or surgical oncologists. RESULTS: Between February 2012 and December 2013 in Korea, the most commonly prescribed AC by medical oncologists was tegafur/gimeracil/oteracil (S-1, 47.72%), followed by capecitabine with oxaliplatin (XELOX, 16.33%). After performing PSM, surgical oncologists (82.74%) completed AC as planned more often than medical oncologists (75.9%), with statistical significance (P=0.036). No difference in the 3-year DFS rates of stage II (P=0.567) or stage III (P=0.545) gastric cancer was found between the medical and surgical oncologist groups. CONCLUSIONS: S-1 monotherapy and XELOX are a main stay of AC, regardless of whether the prescribing physician is a medical or surgical oncologist. The better compliance with AC by surgical oncologists is a valid reason to advocate that surgical oncologists perform the treatment of AC for stage II or III gastric cancers.

Outcome of Gastric Cancer Surgery in Elderly Patients

PURPOSE: Owing to increased life expectancy, the number of elderly patients with gastric cancer has increased. This study aimed to identify the outcomes of gastric cancer patients aged 80 years or older through comparison of their clinicopathological characteristics, surgical outcomes, and oncologic outcomes. MATERIALS AND METHODS: Between January 2006 and December 2013, the records of 478 patients who underwent surgery for gastric cancer were retrospectively evaluated. Patients were divided into two groups: patients <80 years old (n=446) and patients ≥80 years old (n=32). RESULTS: There were no significant differences in sex, body mass index, length of hospital stay, duration of surgery, depth of invasion, nodal metastasis, histologic type, or tumor size between the two groups. However, significant differences were found for the American Society of Anesthesiologist score and the serum albumin level between the two groups. Postoperative morbidity, mortality, disease-free survival, and recurrence rate did not differ between curatively resected patients in the two groups. CONCLUSIONS: In elderly patients with gastric cancer, active treatment including radical gastrectomy is necessary.

Clinical outcomes of subtotal cholecystectomy performed for difficult cholecystectomy

PURPOSE: Laparoscopic subtotal cholecystectomy (LSC) can be an alternative surgical technique for difficult cholecystectomies. Surgeons performing LSC sometimes leave the posterior wall of the gallbladder (GB) to shorten the operation time and avoid liver injury. However, leaving the inflamed posterior GB wall is a major concern. In this study, we evaluated the clinical outcomes of standard laparoscopic cholecystectomy (SLC), LSC, and LSC removing only anterior wall of the GB (LSCA). METHODS: We retrospectively reviewed the medical records of laparoscopic cholecystectomies performed between January 2006 to December 2015 and analyzed the outcomes of SLC, LSC, and LSCA. RESULTS: A total of 1,037 patients underwent SLC. 22 patients underwent LSC; and 27 patients underwent LSCA. The mean operating times of SLC, LSC, and LSCA were 41, 74, and 68 minutes, respectively (P < 0.01). Blood loss was 5, 45, and 33 mL (P < 0.05). The mean lengths of postoperative hospitalization were 3.4, 5.4, and 5.8 days. Complications occurred in 24 SLC patients (2.3%), 2 LSC patients (9%), and 1 LSCA patient (3.7%). There was no mortality among the LSC and LSCA patients. CONCLUSION: LSC and LSCA are safe and feasible alternatives for difficult cholecystectomies. These procedures help surgeons avoid bile duct injury and conversion to laparotomy. LSCA has the benefits of shorter operation time and less bleeding compared to LSC.

Analysis of patient-dropouts from the critical pathways for gastric cancer

PURPOSE: This study was designed to determine the factors affecting completion of critical pathway for elective gastrectomy. METHODS: Since 2008, a critical pathway has been applied for elective gastrectomy at Chosun University Hospital. We retrospectively analyzed 252 patients who underwent elective gastrectomies from January 2009 to April 2013. The completion rate was determined, and risk factors for patient dropout were examined. RESULTS: The completion rate of the critical pathway was 45.6% (115/252). Mean length of stay was 11.7 +/- 8.6 days (8-59 days). Readmission rates were 4.4% (11/252). Causes of failure for clinical pathway were systemic complications (21/137, 15.3%), intra-abdominal complications (44/137, 32.8%), patient factors (41/137, 29.9%), and wound complications (30/137, 21.9%). There were no significant differences between the two groups in age, sex, American Society of Anesthesiologists (ASA) score, operation time, readmission, and underlying disease (P > 0.05). Body mass index (P = 0.008) and pathologic stage (P = 0.001) were significantly different between the two groups. In multivariate analysis, the conventional approach (odds ratio, 2.0), and total gastrectomy (odds ratio, 5.3) were determined to be independent risk factors to drop the critical pathway. But there were no significant differences between total and distal gastrectomy groups in age, gender, underlying diseases, ASA score, readmission, operation time, and cause of dropout (P > 0.05). CONCLUSION: We concluded that total gastrectomy may not be suitable for the critical pathway. We suggest that the critical pathway for elective distal gastrectomy is divided 2 subgroups, according to the surgical approach.

Early Gastric Cancer with Neurofibroma Mimicking a Metastatic Node: A Case Report

Neurofibromas are benign tumors that originate from the peripheral nerves, including neurites and fibroblasts. Generally, a solitary neurofibroma is located in the skin and rarely in other places. A 72-year-old female suffered from epigastric discomfort for 2 months. Endoscopic findings showed an early gastric cancer type IIc at the antrum. Abdominal computed tomography revealed early gastric cancer with a 1.6 cm-sized metastatic node posterior to the duodenum. Laparoscopic assisted distal gastrectomy and retro-pancreatic dissection were performed uneventfully. Histological examination revealed gastric adenocarcinoma, invading the mucosa without nodal metastasis, and a neurofibroma. Herein, we present a case of a gastric cancer patient with a solitary retroperitoneal neurofibroma which mimicked a distant metastatic node.

Early Gastric Cancer with Neurofibroma Mimicking a Metastatic Node: A Case Report

Neurofibromas are benign tumors that originate from the peripheral nerves, including neurites and fibroblasts. Generally, a solitary neurofibroma is located in the skin and rarely in other places. A 72-year-old female suffered from epigastric discomfort for 2 months. Endoscopic findings showed an early gastric cancer type IIc at the antrum. Abdominal computed tomography revealed early gastric cancer with a 1.6 cm-sized metastatic node posterior to the duodenum. Laparoscopic assisted distal gastrectomy and retro-pancreatic dissection were performed uneventfully. Histological examination revealed gastric adenocarcinoma, invading the mucosa without nodal metastasis, and a neurofibroma. Herein, we present a case of a gastric cancer patient with a solitary retroperitoneal neurofibroma which mimicked a distant metastatic node.

Diagnostic imaging of malignant insulinoma in a dog / 대한수의학회지

Endocrine test data from a 13-year old intact female Maltese was indicative of the presence of an insulinoma, however ultrasonography identified a pancreatic mass only after 10 months after the first admission. Following identification of both pancreatic tumor and hepatic metastasis on computed tomography (CT), surgical excision of the mass was attempted. However, total excision failed because of tumor adhesion to adjacent large vessels. The pancreatic mass was monitored over the next 25 months via ultrasonography, CT, and positron emission tomography-computed tomography (PET-CT). Histopathological and immunohistochemical data confirmed the diagnosis of insulinoma with hepatic metastasis.

Ewing's Sarcoma of the Stomach; Rare Case of Ewing's Sarcoma and Suggestion of New Treatment Strategy

Ewing's sarcoma is a neoplasm of the undifferenciated small round cells, which generally affects the bone and deep soft tissues of children and adolescents. We present a case of gastric Ewing's sarcoma; a 35-year-old female who had no symptoms. While she was at a routine medical checkup, a protruding mass in her gastric antrum was incidentally found on esophagogastroduodenoscopy. Endoscopic ultrasonogram showed a submucosal mass on the same lesion and a laparosopic wedge resection was done. Pathologic gross findings showed a granular grape appearance tissue and histoloigc examination revealed a small round cell tumor with CD 99 immunoexpression positive. In general, a combined modality therapy for Ewing's sarcoma such as surgical resection with chemotherapy, is accepted as an effective method. However, this patient had no adjuvant chemotherapy after surgery and she has no recurrence for eleven months.

Ewing's Sarcoma of the Stomach; Rare Case of Ewing's Sarcoma and Suggestion of New Treatment Strategy

Ewing's sarcoma is a neoplasm of the undifferenciated small round cells, which generally affects the bone and deep soft tissues of children and adolescents. We present a case of gastric Ewing's sarcoma; a 35-year-old female who had no symptoms. While she was at a routine medical checkup, a protruding mass in her gastric antrum was incidentally found on esophagogastroduodenoscopy. Endoscopic ultrasonogram showed a submucosal mass on the same lesion and a laparosopic wedge resection was done. Pathologic gross findings showed a granular grape appearance tissue and histoloigc examination revealed a small round cell tumor with CD 99 immunoexpression positive. In general, a combined modality therapy for Ewing's sarcoma such as surgical resection with chemotherapy, is accepted as an effective method. However, this patient had no adjuvant chemotherapy after surgery and she has no recurrence for eleven months.

Consideration of Cardia Preserving Proximal Gastrectomy in Early Gastric Cancer of Upper Body for Prevention of Gastroesophageal Reflux Disease and Stenosis of Anastomosis Site

PURPOSE: The aim of this study is to evaluate the feasibility and safety of cardia preserving proximal gastrectomy, in early gastric cancer of the upper third. MATERIALS AND METHODS: A total of 10 patients were diagnosed with early gastric cancer of the upper third through endoscopic biopsy. The operation time, length of resection free margin, number of resected lymph nodes and postoperative complications, gastrointestinal symptoms, nutritional status, anastomotic stricture, and recurrence were examined. RESULTS: There were 5 males and 5 females. The mean age was 56.5+/-0.5 years. The mean operation time was 188.5+/-0.5 minutes (laparoscopic operation was 270 minutes). Nine patients were T1 stage (T2 : 1), and N stage was all N0. The mean number of resected lymph nodes was 25.2+/-0.5. The length of proximal resection free margin was 3.1+/-0.1 cm and distal was 3.7+/-0.1 cm. Early complications were surgical site infection (1), bleeding (1), and gastro-esophageal reflux disease (1) (this symptom was improved with medication). Late complications were dyspepsia (3) (this symptom was improved without any treatment), and others were nonspecific results of endoscopy or symptom. CONCLUSIONS: Cardia preserving proximal gastrectomy was feasible for early gastric cancer of the upper third. Further evaluation and prospective research will be required.

Clinical Effectiveness of Regular Use of Unripe Apple Mask Pack on Skin Status of Middle-aged Women

The effects of unripe apple mask pack made from unripe apple extracts on the skin status of middle-aged women for 4 weeks were investigated. The subjects were divided into three groups: placebo mask pack as the control (PM, n = 8), apple mask pack (AM, n = 16), and apple mask pack + apple intake (AAM, n = 12). The study included a survey questionnaire, and evaluations of nutrients intakes and of skin status. Skin status was measured by Aramo-TS. After 4 weeks, facial moisture, elasticity, evenness, and wrinkle level were improved in AM and AAM. The facial moisture level (AM: +3.13 +/- 2.73, AAM: +2.25 +/- 2.93) and elasticity level (AM: +5.81 +/- 8.27, AAM: +5.50 +/- 6.13) of AM (p < 0.001) and AAM (p < 0.05) were increased. The facial evenness level (AM: -5.25 +/- 8.13, AAM: -9.17 +/- 4.26) and wrinkle level (AM: -10.88 +/- 11.74, AAM: -17.83 +/- 12.22) were significantly decreased. AAM was more effective in improving skin elasticity, evenness, and wrinkle. The skin status of PM was not changed. While the macronutrient intakes of all the subjects were not different before and after the study, the daily intakes of some vitamins (vitamins B6, C, and E and folic acid) during the study were significantly increased in AAM. These findings suggested that regular use of apple mask pack was effective in improving overall skin status. Furthermore, the consumption of apples with mask pack application was much better in improving skin status.

Airway Responsiveness to Inhaled Aspirin is Influenced by Airway Hyperresponsiveness in Asthmatic Patients

BACKGROUND/AIMS: Many patients with aspirin-induced asthma have severe methacholine airway hyperresponsiveness (AHR), suggesting a relationship between aspirin and methacholine in airway response. This study was performed to determine whether methacholine AHR affects the response of asthmatics to inhaled aspirin. METHODS: The clinical records of 207 asthmatic patients who underwent inhalation challenges with both aspirin and methacholine were reviewed retrospectively. An oral aspirin challenge was performed in patients with a negative inhalation response. The bronchial reactivity index (BRindex) was calculated from the percent decrease in lung function divided by the last dose of the stimulus. RESULTS: Forty-one (20.9%) and 14 (7.1%) patients showed a positive response to aspirin following an inhalation and oral challenge, respectively. Only 24.3 and 14.3% of the responders had a history of aspirin intolerance, respectively. The methacholine BRindex was significantly higher in the inhalation responders (1.46 +/- 0.02) than in the oral responders (1.36 +/- 0.03, p < 0.01) and in non-responders (n = 141, 1.37 +/- 0.01, p < 0.001). The aspirin BRindex was significantly correlated with the methacholine BRindex (r = 0.270, p < 0.001). Three of four patients who received the oral challenge, despite a positive inhalation test, showed negative responses to the oral challenge. Two of these patients had severe AHR. CONCLUSIONS: A considerable number of asthmatic patients with no history of aspirin intolerance responded to the inhalation aspirin challenge. The airway response to aspirin was significantly correlated with methacholine-AHR, and a false-positive response to aspirin inhalation test seemed to occur primarily in patients with severe AHR.

Long-Surviving Patients with Recurrent GIST after Receiving Cytoreductive Surgery with Imatinib Therapy

In the treatment of recurrent or metastatic gastrointestinal stromal tumors (GIST), good prognoses may not be expected by surgery alone. Recently, imatinib has been applied for the treatment of GISTs, resulting in improved patient survival. However, long-term success is limited due to the development of resistance. Herein, we report two cases of long-surviving patients with recurrent GIST after receiving cytoreductive surgery with imatinib therapy. A 49 year-old man was diagnosed to a duodenal GIST with single hepatic metastasis, and an antrectomy including the duodenal lesion with intraoperative radiofrequency ablation were performed in April, 2002. After four months, a new metastatic hepatic lesion was identified. Percutaneous radiofrequency ablation was done, and imatinib therapy was started. A 56 year-old man underwent laparoscopic segmental resection of the distal ileum and partial excision of parietal peritoneum in March, 2001 to treat a malignant GIST of the distal ileum that was attached to parietal peritoneum. After six months, recurrence of GIST with peritoneal seeding and hepatic metastasis was found, and he underwent cytoreductive surgery including right hemicolectomy and wedge resection of liver. After surgery, there was no residual tumor grossly and imatinib therapy was started. In both cases, they were doing well with no evidence of recurrence for 5 years with imatinib therapy. Therefore, in patients with a recurrent GIST, improved survival can be expected with imatinib therapy after cytoreductive surgery.

The Clinicopathologic Features of Synchronous and Metachronous Cancer in Patients with Gastric Cancer

PURPOSE: With the development of diagnostic techniques, second primary neoplasms such as synchronous or metachronous cancers in gastric cancer patients are being increasingly found. In this study, we investigated the clinicopathological features and clinical significance of gastric neoplasms combined with synchronous and metachronous cancers. MATERIALS AND METHODS: 1,048 patients who were diagnosed with gastric cancer in Chosun University Hospital from January 1998 to March 2008 were retrospectively reviewed. RESULTS: 38 of the 1,048 patients with gastric cancer (3.6%) had synchronous and metachronous cancers. Of the 38 patients, 16 patients (42.1%) had synchronous cancer and 22 patients (57.9%) had metachronous cancer. The average time interval between gastric cancer and the secondary primary cancer was 27.08+/-31.25 months. The most common second primary neoplasm was lung cancer (8/38, 21.1%), followed by colorectal cancer (8/38, 21.1%). Among the 27 patients who underwent surgical resection for gastric cancer, 5 patients (18.5%) were in the synchronous group and 22 patients (81.5%) were in the metachronous group. The mean survival time of the 38 patients was 49.8 months. The mean survival time was 24.6 months for the synchronous cancer patients and 68.1 month for the metachronous cancer patients. The 3 year survival rate of the synchronous group and the metachronous group was 33.3% and 81.1%, respectively. CONCLUSION: We must pay attention on the preoperative workup for synchronous cancer and on the postoperative follow-up for metachronous cancer in gastric cancer patients.