Four-Tier Pathologic Tumor Regression Grading System Predicts the Clinical Outcome in Patients Who Undergo Surgical Resection for Locally Advanced Pancreatic Cancer after Neoadjuvant Chemotherapy

Background/Aims@#Neoadjuvant chemotherapy is increasingly utilized in patients with borderline or locally advanced pancreatic cancer (LAPC). However, the pathologic evaluation of tumor regression is not routinely performed or well established. We aimed to evaluate the prognostic value of three tumor regression grading systems frequently used in LAPC and to determine the correlation between pathologic and clinical response. @*Methods@#We included a total of 38 patients with LAPC who were treated with neoadjuvant chemotherapy and subsequent resection. Pathologic tumor regression was graded based on the College of American Pathologists (CAP), Evans, and MD Anderson grading systems. @*Results@#One out of 38 patients (2.6%) achieved a pathologic complete response. Unlike other grading systems (Evans, p=0.063; MD Anderson, p=0.110), the CAP grading system was a significant prognostic factor for overall survival (p=0.043). Pathologic N stage (p=0.023), margin status (p=0.044), and radiologic response (p=0.016) correlated with overall survival. In the multivariate analysis, CAP 3 was an independent predictor of shorter overall survival (p=0.026). The CAP grading system correlated with the radiologic response (p=0.007) but not the carbohydrate antigen 19-9 level (p=0.333). @*Conclusions@#The four-tier CAP pathologic tumor regression grading system predicted the clinical outcome in LAPC patients who underwent resection after neoadjuvant chemotherapy. Therefore, a more comprehensive pathologic evaluation is warranted in these patients.

Higher Tumor Cellularity in Resected Pancreatic Ductal Adenocarcinoma Is a Negative Prognostic Indicator

Background/Aims@#Desmoplasia is a prominent feature of pancreatic ductal adenocarcinoma (PDA). Stromal desmoplasia reflects the low cellularity that is characteristic of PDA, and it may play a role in PDA chemoresistance. In this retrospective study, we evaluated the relationship between tumor cellularity in resected PDA specimens and long-term patient outcomes. @*Methods@#We retrospectively reviewed the data from 175 patients who underwent PDA resection between January 2010 and December 2015 at Seoul National University Bundang Hospital, and analyzed their clinicopathological features and the relationship between tumor cellularity (high vs low based on a cutoff of 30% cellularity) and patient outcomes. @*Results@#The high-cellularity group had significantly shorter overall survival (OS) (18.7 months vs 26.6 months, p=0.006) and disease-free survival (11.0 months vs 16.9 months, p=0.031) than the low-cellularity group. Multivariate analysis revealed that high tumor cellularity was an independent risk factor for poor OS (hazard ratio, 2.008; 95% confidence interval, 1.361 to 2.962; p<0.001). Adjuvant therapy improved OS in the low-cellularity group (16.3 months vs 41.3 months, p=0.001) but not in the high-cellularity group (15.9 months vs 24.4 months, p=0.107). @*Conclusions@#Tumor cellularity in PDA specimens may be a prognostic and predictive biomarker that could aid in identifying patients who would benefit from adjuvant therapy for PDA.

Extraordinary Response of Metastatic Pancreatic Cancer to Chemotherapy / 대한소화기암학회지

A 58-year-old woman presented with right flank and back pain for one month. After undergoing an abdominal computed tomography (CT), she was referred to our hospital. The abdominal CT showed a hypodense pancreatic tail mass with multiple retroperitoneal lymph node metastases. Positron emission tomography-computed tomography (PET-CT) scan showed high 18F-FDG uptake in pancreatic tumor and enlarged lymph nodes. Endoscopic ultrasound fine needle aspiration (EUS-FNA) revealed adenocarcinoma, which stained strongly in hENT1 (human equilibrative nucleoside transporter 1) on immunohistochemistry. She received gemcitabine 1,000 mg/m² + nanoparticle albumin-bound paclitaxel 125 mg/m² as a palliative chemotherapy. Follow-up abdominal CT and PET-CT after 4 cycles of chemotherapy showed that both pancreatic mass and the metastatic retroperitoneal lymph nodes were nearly disappeared. We report a case of 58-year-old female with metastatic pancreatic cancer who had a dramatic response to palliative chemotherapy (gemcitabine plus nanoparticle albumin-bound paclitaxel).

Dynamic Changes in Helicobacter pylori Status Following Gastric Cancer Surgery

BACKGROUND/AIMS: Helicobacter pylori eradication is recommended in patients with early gastric cancer. However, the possibility of spontaneous regression raises a question for clinicians about the need for “retesting” postoperative H. pylori status. METHODS: Patients who underwent curative gastrectomy at Seoul National University Bundang Hospital and had a positive H. pylori status without eradication therapy at the time of gastric cancer diagnosis were prospectively enrolled in this study. H. pylori status and atrophic gastritis (AG) and intestinal metaplasia (IM) histologic status were assessed pre- and postoperatively. RESULTS: One hundred forty patients (mean age, 59.0 years; 60.7% male) underwent subtotal gastrectomy with B-I (65.0%), B-II (27.1%), Roux-en-Y (4.3%), jejunal interposition (0.7%), or proximal gastrectomy (4.3%). Preoperative presence of AG (62.9%) and IM (72.9%) was confirmed. The mean period between surgery and the last endoscopic follow-up was 38.0±25.6 months. Of the 140 patients, 80 (57.1%) were found to be persistently positive for H. pylori, and 60 (42.9%) showed spontaneous negative conversion at least once during follow-up. Of these 60 patients, eight (13.3%) showed more complex postoperative dynamic changes between negative and positive results. The spontaneous negative conversion group showed a trend of having more postoperative IM compared to the persistent H. pylori group. CONCLUSIONS: A high percentage of spontaneous regression and complex dynamic changes in H. pylori status were observed after partial gastrectomy, especially in individuals with postoperative histological IM. It is better to consider postoperative eradication therapy after retesting for H. pylori.

Effects of Age on Esophageal Motility: Use of High-resolution Esophageal Impedance Manometry

BACKGROUND/AIMS: Disturbances of esophageal motility have been reported to be more frequent the aged population. However, the physiology of disturbances in esophageal motility during aging is unclear. The aim of this study was to evaluate the effects of age on esophageal motility using high-resolution esophageal impedance manometry (HRIM). METHODS: Esophageal motor function of 268 subjects were measured using HRIM in 3 age groups, 65 years (Group C, n = 62). Lower esophageal sphincter (LES) and upper esophageal sphincter (UES) pressures, integrated relaxation pressure, distal contractile integral, contractile front velocity, distal latency, and pressures and duration of contraction on 4 positions along the esophagus, and complete bolus transit were measured. RESULTS: Basal UES pressure was lower in Group C (P < 0.001) but there was no significant difference in the LES pressure among groups. Contractile duration on position 3 (10 cm from proximal LES high pressure zone) was longer in Group C (P = 0.001), and the contractile amplitude on position 4 (5 cm from proximal LES high pressure zone) was lower in Group C (P = 0.005). Distal contractile integral was lower in Group C (P = 0.037). Contractile front velocity (P = 0.015) and the onset velocity (P = 0.040) was lower in Group C. There was no significant difference in impedance values. CONCLUSIONS: The decrease of UES pressure, distal esophageal motility, and peristaltic velocity might be related with esophageal symptoms in the aged population.

A successful rendezvous endoscopic ultrasonography-guided gallbladder drainage in malignant cystic duct obstruction

Endoscopic ultrasonography-guided gallbladder drainage (EUS-GBD) has been developed as an alternative drainage method in patients with malignant cystic duct obstruction. However, the procedure of track dilation is difficult in case of severe gallbladder wall thickening with tumor involvement or inflammation. The rendezvous technique via external fistulous track is considered in failed attempts to dilate an internal track between the gallbladder and the stomach/duodenum using conventional approach of EUS-GBD. This report presents a 56-year-old man with pancreatic cancer with malignant cystic duct obstruction who underwent percutaneous transhepatic gallbladder drainage. The patient was successfully treated using rendezvous EUS-GBD technique after he failed the conventional EUS-GBD procedure of internal track dilation.

Clinical Features of Varicose Vein in Pediatric Population / 소아외과

PURPOSE: Varicose veins requiring operative treatment have been more common recently, but there are not enough studies among children dermographics because most patients belong to the adult population. We concentrated on varicose vein of under 18 years old, and here intend to report cases of our clinical experiences. METHODS: From January 2003 until December 2014, there were 6 children under 18 years old who required varicose vein management. Data was collected by the investigation of medical records retrospectively, including preoperative symptoms, diagnostic tools, treatment methods, results of treatment, and complications. RESULTS: The mean age was 11 years (range, 3-17 years), and gender ratio was 1:2 (2 male, 4 female). The involved legs were on the right in 3 cases, on the left in 2 cases, and on both in 1 case. The most common symptoms were venous bulging and tortuosity in 6 cases, and other symptoms were Klippel-Trenaunay-Weber syndrome in 2 cases, pain and fatigue in 1 case, port-wine stain in 1 case, and telangiectasia in 1 case. Duplex sonography was performed to confirm venous reflux in all cases. The additional venography was performed to check for anatomical variation in 1 case, and three-dimensional CT in 2 cases. Treatments were high ligation and stripping in 3 cases, and endovenous laser therapy in 3 cases. Additionally, remnant varicosities after first operations were treated by endovenous laser therapy in all cases. During the mean postoperative follow-up period of 60 months, complications included edema of the foot and petechia in 2 cases each, and were not severe. CONCLUSION: Operative treatments including high ligation and stripping, and endovenous laser therapy are very effective for the management of varicose vein in the pediatric population, with improvements in quality of life including relief of symptoms and management of the cosmetic aspect.

PMK-S005 Alleviates Age-Related Gastric Acid Secretion, Inflammation, and Oxidative Status in the Rat Stomach

BACKGROUND/AIMS: The aim of this study was to evaluate the effect of the synthetic S-allyl-l-cysteine (SAC) PMK-S005 on gastric acid secretion, inflammation, and antioxidant enzymes in aging rats. METHODS: The rats were divided into four groups at 31 weeks of age and were continuously fed a diet containing a vehicle control, PMK-S005 (5 or 10 mg/kg), or lansoprazole (5 mg/kg). Gastric acid secretion and connective tissue thickness of the lamina propria were evaluated at 74 weeks and 2 years of age. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and COX-2 levels were measured by using enzyme-linked immunosorbent assays (ELISAs) or Western blot assays. Levels of antioxidant enzymes, including heme oxyganase 1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1), were also measured. RESULTS: As the rats aged, gastric acid secretion significantly decreased, and the connective tissue of the lamina propria increased. However, 74-week-old rats in the PMK-S005 group exhibited greater levels of gastric acid secretion than those of the control and lansoprazole groups. The increase of TNF-α, IL-1β, and COX-2 expression in 74-week and 2-year-old control rats were inhibited by PMK-S005. In addition, the decrease in HO-1 and NQO-1 protein expression that occurred with aging was inhibited by PMK-S005 in the 74-week-old rats. CONCLUSIONS: These results suggest that PMK-S005 has therapeutic potential as an antiaging agent to ameliorate age-related gastric acid secretion, inflammation, and oxidative stress in the stomach.

Case Series of Different Onset of Skin Metastasis According to the Breast Cancer Subtypes / Journal of the Korean Cancer Association, 대한암학회지

We report on five cases of skin metastasis according to the breast cancer (BC) subtype. Two cases of HER2 positive BC showed only skin metastasis after immediate postoperative period and rapid clinical response to targeted therapy. Another two cases of triple negative BC showed thyroid and lung metastasis in addition to skin metastasis, and their response of cytotoxic chemotherapy was not definite. The other hormone positive BC showed skin metastasis only, with a longer, slower, less progressive pattern than other subtypes. Most cases of skin metastasis were detected at terminal stage of malignancy and were considered to have a limited survival period. However, some BC patients can survive longer if the targeted agents are effective. Therefore, physicians should provide detailed follow up of BC after curative treatment and understand the metastatic pattern of BC according to the subtype.

A Case of Bilateral Knee Septic Arthritis Caused by Pneumococcal Bacteremia / 대한구급학회지

Pneumococcus can cause pneumonia, sinusitis, infective endocarditis, meningitis and primary bacteremia. However, few reports in the literature show bilateral septic arthritis with pneumococcal bacteremia. We report on a case of a 78-year old woman who presented with fever, pain and swelling in both knees. Both knee fluid aspirates were purulent with thick viscosity, and the gram stain revealed gram positive cocci in chains. The patient underwent emergent washing and arthroscopic debridement, followed with empirical antibiotics treatment. Two out of two blood cultures were positive for penicillin-susceptible Streptococcus pneumonia. Synovial fluid cultures were also positive for S. pneumoniae. The patient was treated with intravenous ceftriaxone for 4 weeks. Bilateral knee septic arthritis with pneumococcal bacteremia is rarely reported. Here we report on the case with a review of the literature.

Clinical utility of tumor marker cutoff ratio and a combination scoring system of preoperative carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 72-4 levels in gastric cancer / 대한외과학회지

PURPOSE: The present study is to investigate the clinical utility of tumor marker cutoff ratio (TMR) and develop a TMR combination scoring system based on preoperative tumor marker (TM) levels to prognosis prediction in gastric cancer. METHODS: We include 1,142 patients for whom two or more TMs were measured and who underwent radical gastrectomy between 1990 and 2003. RESULTS: Five-year risk of recurrence (5 YRR) for carcinoembryonic antigen (CEA) TMRs were 18.3%, 29.8%, 61.4% for TMR or = 2.0 respectively. 5 YRR for carbohydrate antigen 19-9 (CA 19-9) TMR were 19.7%, 35.6%, 58.4% for TMR or = 3.0, respectively. 5 YRR for carbohydrate antigen 72-4 (CA 72-4) TMR were 15.2% and 33.6% for TMR or = 1.0, respectively. We defined high TMR (TMR > or = 2.0 for CEA, TMR > or = 3.0 for CA19-9), low TMR (1.0 < or = TMR < 2 for CEA, 1.0 < or = TMR < 3.0 for CA 19-9 and 1.0 < or = TMR for CA72-4) and negative TMR (TMR < 1.0 for all TMs). A TMR combination scoring system was devised with negative scored as zero points, low as 1 and high as 2 for each TMR. TMR scores were divided into four categories (score 0, 1, 2, 3 and above) based on the calculated TMR score and 5 YRR were found to be 12.8%, 23.9%, 45.5%, and 68.3%, respectively (P < 0.05). Multivariate analysis showed that our scoring system was a significant independent prognostic factor. CONCLUSION: Preoperative TMRs such as CEA, CA 19-9, and CA 72-4 show a correlation with prognosis and the TMR combination scoring system could be a useful tool for the prediction of prognosis in gastric cancer.

Two Cases of Humoral Hypercalcemia of Malignancy in Metastatic Cholangiocarcinoma / Journal of the Korean Cancer Association, 대한암학회지

Humoral hypercalcemia of malignancy (HHM) is rarely associated with cholangiocarcinoma (CC), and represents dismal prognosis. A 63-year-old male was admitted for evaluation of an intrahepatic mass. He was diagnosed with HHM associated with locally advanced CC. As the tumor responded to the concurrent chemoradiotherapy with capecitabine and cisplatin, serum calcium level was normalized. However, according to the disease progression, he suffered recurrence of HHM and he expired approximately one year after initial diagnosis. A 68-year-old male who presented with abdominal pain was diagnosed with metastatic CC. After the eighth cycle of gemcitabine and cisplatin, progression of the disease was found with HHM. He was treated with the best supportive care, until his demise approximately one month after the diagnosis of HHM. We report on two cases of HHM associated with CC that demonstrate strong correlation between hypercalcemia and disease burden.

Early Postoperative Retrograde Jejunojejunal Intussusception after Total Gastrectomy with Roux-en-Y Esophagojejunostomy: A Case Report

Intussusception is a rare cause of postoperative intestinal obstruction in adults. Many retrograde intussusceptions occur during the period following gastrectomy. A 77-year-old woman visited our hospital because of detected gastric adenocarcinoma. She received radical total gastrectomy with Roux-en-Y esophagojejunostomy. On the fifth postoperative day, she complained of abdominal pain, and we found leakage at the esophagojejunostomy site and dilatation of the Roux limb and the afferent limb of the jejunojejunostomy. Emergency surgery was performed. Retrograde jejunojejunal intussusception accompanied with a nasojejunal feeding tube was found at the efferent loop of the jejunojejunostomy. No ischemic change was found; therefore, manual reduction and primary repair of esophagojejunostomy was performed. She was discharged without complications on the 23rd re-postoperativeday. We suggest that the nasojejunal feeding tube acted as a trigger of intussusception because there was no definitive small bowel mass or postoperative adhesion. We present our findings here along with a brief review of the literature.

A Case of Enteropathy-Type T-Cell Lymphoma Diagnosed by Small Bowel Enteroscopy: A Perspective on Imaging-Enhanced Endoscopy

Enteropathy-type T-cell lymphoma (ETL) or enteropathy-associated T-cell lymphoma is a very rare malignant intestinal tumor. ETL is usually diagnosed by surgery. Endoscopic findings of ETL are not well known, and there are few reports of findings from endoscopy that has been performed only using white light. Additionally, there are no definite treatment guidelines for ETL. Therefore, we report a case of ETL diagnosed by enteroscopy with imaging-enhanced endoscopy and also review recently developed treatment options.

Comparison among Endoscopic Variceal Obliteration, Endoscopic Band Ligation, and Balloon-occluded Retrograde Transvenous Obliteration for Treatment of Gastric Variceal Bleeding / 대한소화기학회지

BACKGROUND/AIMS: Endoscopic variceal obliteration (EVO), endoscopic variceal ligation (EVL), and balloon-occluded retrograde transvenous obliteration (BRTO) are used to manage gastric variceal bleeding. We compared the re-bleeding rates and survival times of these modalities. METHODS: The study enrolled 103 patients with suspected gastric variceal bleeding between July 2001 and May 2009. For the management of gastric variceal bleeding, 52 patients underwent EVO; 36, EVL; and 15, BRTO. We evaluated their laboratory results and vital signs, and calculated the Child score, Child classification, and Model for End-stage Liver Disease score. Rebleeding was defined as new-onset hematemesis, hematochezia, melena, or endoscopically proven bleeding. Time-to-rebleeding and survival time were examined by Kaplan-Meyer analysis. A value of p<0.05 indicated statistical significance. RESULTS: There were no significant differences in baseline characteristics among the three groups. The overall follow-up period averaged 65.13 months. During follow-up, rebleeding occurred in 17 patients (11 EVO, 5 EVL, and 1 BRTO). The times-to-rebleeding were 63.59, 75.79, and 51.41 months for EVO, EVL, and BRTO, respectively, and did not differ significantly (p=0.515). The median survival times were 77.42, 70.14, and 42.79 months, respectively, and also were not different significantly (p=0.978). CONCLUSIONS: There were no significant differences in the time-to-rebleeding or survival time among EVO, EVL, and BRTO. Further prospective, large-scale studies are needed.

Correlation of Narrow Band Imaging with Magnifying Colonoscopy and Histology in Colorectal Tumors

BACKGROUND/AIMS: Narrow band imaging (NBI) is a new technique that uses optical filters for imaging of mucosal morphology. The aim of this study was to correlate findings of NBI with magnifying colonoscopy and histology for prediction of neoplastic colorectal lesion. METHODS: Between September 2005 and December 2007, 107 colon polyps from 68 patients were detected by conventional colonoscopy and subsequently evaluated by NBI with magnifying colonoscopy and analyzed for a pit pattern and a capillary pattern. More analysis was done regarding thickness and irregularity of capillary features. RESULTS: Pit pattern with NBI magnification to discriminate between neoplastic and non-neoplastic lesions had a sensitivity of 88.9% and a specificity of 87.5%; capillary pattern yielded test performance characteristics of 91.9% and 87.5%. In respect of capillary thickness, invisible capillaries were found significantly more often in hyperplastic lesions. All thick capillaries were found in neoplastic polyps, and found significantly more often in carcinomas with submucosal massive invasion (sm-m) (p<0.01). In respect of capillary irregularity, invisible capillaries were found significantly more often in hyperplasic lesions, and severely irregular capillaries were found significantly more often in sm-m lesions (p<0.01). CONCLUSIONS: Observation of capillary thickness and irregularity by NBI magnification is useful for correlating histological grade with carcinoma, especially with depth of submucosal invasion.

Correlation of Narrow Band Imaging with Magnifying Colonoscopy and Histology in Colorectal Tumors

BACKGROUND/AIMS: Narrow band imaging (NBI) is a new technique that uses optical filters for imaging of mucosal morphology. The aim of this study was to correlate findings of NBI with magnifying colonoscopy and histology for prediction of neoplastic colorectal lesion. METHODS: Between September 2005 and December 2007, 107 colon polyps from 68 patients were detected by conventional colonoscopy and subsequently evaluated by NBI with magnifying colonoscopy and analyzed for a pit pattern and a capillary pattern. More analysis was done regarding thickness and irregularity of capillary features. RESULTS: Pit pattern with NBI magnification to discriminate between neoplastic and non-neoplastic lesions had a sensitivity of 88.9% and a specificity of 87.5%; capillary pattern yielded test performance characteristics of 91.9% and 87.5%. In respect of capillary thickness, invisible capillaries were found significantly more often in hyperplastic lesions. All thick capillaries were found in neoplastic polyps, and found significantly more often in carcinomas with submucosal massive invasion (sm-m) (p<0.01). In respect of capillary irregularity, invisible capillaries were found significantly more often in hyperplasic lesions, and severely irregular capillaries were found significantly more often in sm-m lesions (p<0.01). CONCLUSIONS: Observation of capillary thickness and irregularity by NBI magnification is useful for correlating histological grade with carcinoma, especially with depth of submucosal invasion.

A Validated Tool for Psychiatric Comorbidity in the Patients With Functional Dyspepsia

No abstract available.

Clinical Evaluation of Sleep Disorders in Childhood and Adolescence

PURPOSE: Sleep disorders cause serious complications to growth and development in children given that sleep plays an important role in maintaining physical and psychological health. In this study, we investigated the clinical characteristics of sleep disorders in childhood and adolescence, their polysomnographs (PSG), as well as other related diseases. METHODS: Forty-two patients who took PSG in Severance Children's Hospital from September 2006 to April 2010 were involved in this study. Their medical records were retrospectively reviewed. RESULTS: Among 42 patients, there were 29 boys and 13 girls; their mean age was 9 years 10 months. Twenty-three (55%) patients reported headache as their chief complaint. Symptoms associated with headache were insomnia, snoring and mouth breathing, daytime sleepiness, abnormal behavior during sleep, and hyperactivity. Among the 23 patients with headaches, nine (39%) had abnormal PSG. Among 21 patients with snoring and mouth breathing, only five (24%) were diagnosed as obstructive sleep apnea and others had primary snoring. In the analysis of sleep disorders according to age, obstructive sleep apnea was evenly distributed across all ages. CONCLUSION: In this study, various clinical symptoms related to childhood and adolescence sleep disorder with headache being the most common symptom. Although sleep disorders are harmful to children and adolescence, they are frequently overlooked. Therefore, careful attention related to the diagnosis and treatment of sleep disorders is required.

Resistance to Thyroid Hormone with Missense Mutation (V349M) in the Thyroid Hormone Receptor Beta Gene

Resistance to thyroid hormone (RTH) is a syndrome characterized by reduced sensitivity to the thyroid hormone. It is generally caused by mutations in the thyroid hormone receptor beta (TRbeta) gene. On the basis of its clinical features, two different forms of this syndrome have been described: generalized resistance and pituitary resistance. A total of 122 TRbeta gene mutations have been identified thus far. A 38-year-old woman presented with intermittent palpitation. Thyroid function tests revealed elevated levels of free T4 and TSH. TSH alpha-subunit levels were 0.41 mIU/mL, and magnetic resonance images of the sellar region evidenced no abnormal findings. The TSH response to TRH stimulation was found to be normal. The sequence analysis of the TRbeta gene verified a missense mutation in exon 11, and the observed amino acid alteration was a substitution of a valine for a methionine at codon 349. We report the first case of a woman with RTH, which was found to be caused by a missense mutation (V349M) in the TRbeta gene.