GGT1 is a SNP eQTL gene involved in STAT3 activation and associated with the development of Post-ERCP pancreatitis.

Post-ERCP pancreatitis (PEP) is an acute pancreatitis caused by endoscopic-retrograde-cholangiopancreatography (ERCP). About 10% of patients develop PEP after ERCP. Here we show that gamma-glutamyltransferase 1 (GGT1)-SNP rs5751901 is an eQTL in pancreatic cells associated with PEP and a positive regulator of the IL-6 amplifier. More PEP patients had the GGT1 SNP rs5751901 risk allele (C) than that of non-PEP patients at Hokkaido University Hospital. Additionally, GGT1 expression and IL-6 amplifier activation were increased in PEP pancreas samples with the risk allele. A mechanistic analysis showed that IL-6-mediated STAT3 nuclear translocation and STAT3 phosphorylation were suppressed in GGT1-deficient cells. Furthermore, GGT1 directly associated with gp130, the signal-transducer of IL-6. Importantly, GGT1-deficiency suppressed inflammation development in a STAT3/NF-κB-dependent disease model. Thus, the risk allele of GGT1-SNP rs5751901 is involved in the pathogenesis of PEP via IL-6 amplifier activation. Therefore, the GGT1-STAT3 axis in pancreas may be a prognosis marker and therapeutic target for PEP.

Genotype-phenotype correlation for extracolonic aggressive phenotypes in patients with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) patients develop various life-threatening extracolonic comorbidities that appear individually or within a family. This diversity can be explained by the localization of the adenomatous polyposis coli (APC) variant, but few reports provide definitive findings about genotype-phenotype correlations. Therefore, we investigated FAP patients and the association between the severe phenotypes and APC variants. Of 247 FAP patients, 126 patients from 85 families identified to have APC germline variant sites were extracted. These sites were divided into six groups (Regions A to F), and the frequency of severe comorbidities was compared among the patient phenotypes. Of the 126 patients, the proportions of patients with desmoid tumor stage ≥III, number of FGPs ≥1000, multiple gastric neoplasms, gastric neoplasm with high-grade dysplasia, and Spigelman stage ≥III were 3%, 16%, 21%, 12%, and 41%, respectively, while the corresponding rates were 30%, 50%, 70%, 50%, and 80% in patients with Region E (codons 1398-1580) variants. These latter rates were significantly higher than those for patients with variants in other regions. Moreover, the proportion of patients with all three indicators (desmoid tumor stage ≥III, number of FGPs ≥1000, and Spigelman stage ≥III) was 20% for those with variants in Region E and 0% for those with variants in other regions. Variants in Region E indicate aggressive phenotypes, and more intensive management is required.

GM-CSF Promotes the Survival of Peripheral-Derived Myeloid Cells in the Central Nervous System for Pain-Induced Relapse of Neuroinflammation.

We recently discovered a (to our knowledge) new neuroimmune interaction named the gateway reflex, in which the activation of specific neural circuits establishes immune cell gateways at specific vessel sites in organs, leading to the development of tissue-specific autoimmune diseases, including a multiple sclerosis (MS) mouse model, experimental autoimmune encephalomyelitis (EAE). We have reported that peripheral-derived myeloid cells, which are CD11b+MHC class II+ and accumulate in the fifth lumbar (L5) cord during the onset of a transfer model of EAE (tEAE), play a role in the pain-mediated relapse via the pain-gateway reflex. In this study, we investigated how these cells survive during the remission phase to cause the relapse. We show that peripheral-derived myeloid cells accumulated in the L5 cord after tEAE induction and survive more than other immune cells. These myeloid cells, which highly expressed GM-CSFRα with common ß chain molecules, grew in number and expressed more Bcl-xL after GM-CSF treatment but decreased in number by blockade of the GM-CSF pathway, which suppressed pain-mediated relapse of neuroinflammation. Therefore, GM-CSF is a survival factor for these cells. Moreover, these cells were colocalized with blood endothelial cells (BECs) around the L5 cord, and BECs expressed a high level of GM-CSF. Thus, GM-CSF from BECs may have an important role in the pain-mediated tEAE relapse caused by peripheral-derived myeloid cells in the CNS. Finally, we found that blockade of the GM-CSF pathway after pain induction suppressed EAE development. Therefore, GM-CSF suppression is a possible therapeutic approach in inflammatory CNS diseases with relapse, such as MS.

Cancer risk and genotype-phenotype correlation in Japanese patients with Cowden syndrome.

BACKGROUND: Cowden syndrome (CS) is an autosomal-dominant hereditary disorder caused by a germline PTEN variant and characterized by multiple hamartomas and a high risk of cancers. However, no detailed data on CS in Asian patients nor genotype-phenotype correlation have been reported. METHODS: We performed the first Japanese nationwide questionnaire survey on CS and obtained questionnaire response data on 49 CS patients. RESULTS: Patients included 26 females (median age 48 years). The incidence of breast, thyroid, endometrium, and colorectal cancer was 32.7%, 12.2%, 19.2% (among females), and 6.1%, respectively. The incidence of any cancers was relatively high among all patients (46.9%, 23/49), and particularly female patients (73.1%, 19/26), compared with previous reports from Western countries. Gastrointestinal (GI) polyps were more frequently found throughout the GI tract compared with previous studies. PTEN variants were detected in 95.6% (22/23) of patients; 12 in the N-terminal region (11 in phosphatase domain) and 10 in the C-terminal (C2 domain) region. The incidence of cancer in the C2 domain group was significantly higher than in the N-terminal region (phosphatase) group. All female patients with C2 domain variant had breast cancer. CONCLUSION: Our data suggest that Japanese patients with CS, particularly female patients and patients with C2 domain variant may have a high risk of cancers.

Gastric neoplasms in patients with familial adenomatous polyposis: endoscopic and clinicopathologic features.

BACKGROUND AND AIMS: Gastric neoplasms in patients with familial adenomatous polyposis (FAP) occur at a high rate and can cause death. The endoscopic findings of gastric neoplasms in these patients are characteristic but not well recognized. To identify the relevant characteristics to enable early detection, we retrospectively investigated endoscopic findings of gastric neoplasms in patients with FAP and then compared the clinical, histopathologic, and genetic features among subgroups. METHODS: Of 234 patients with 171 pedigrees at 2 institutes, 56 cases (24%, 133 gastric neoplasms) with 44 pedigrees were examined. Immunostaining was performed for histopathologic evaluation by 1 blinded pathologist. According to the endoscopic findings, gastric neoplasms were divided into 4 types based on location (L: antrum and pylorus, UM: the rest of the stomach) and color (W: white, T: translucent, R: reddish) and their clinicopathologic features examined. RESULTS: Of the cases, 93% could be classified into a single type. Among histologic phenotypes, high-grade dysplasia was present in 26% (type L), 41% (type UM-W), 0% (type UM-T), and 22% (type UM-R). The immunologic phenotype comprised the gastric type in 69% (93% in Type UM) and the intestinal phenotype, including the mixed type, in 31% (61% in type L). Moreover, 96% of patients had concurrent duodenal neoplasms. Adenomatous polyposis coli gene status was identified in 93% of patients; the pathogenic variant was detected in 98% but did not influence any endoscopic features. CONCLUSIONS: Gastric neoplasms in patients with FAP were stratified into 4 types according to their endoscopic findings. The endoscopic phenotype was related to the histopathologic phenotype but not to germline variants.

A Case of Nasopharyngeal Tuberculosis with Cervical Lymph Node Tuberculosis Suspected of Cervical Malignant Disease at the First Examination.

A case of nasopharyngeal tuberculosis with cervical lymph node tuberculosis is reported. The patient was a 20-year-old female immigrant from Vietnam and cook apprentice. Her chief complaint was left neck swelling with pain for three months. She was diagnosed with left neck lymphadenitis at a previous hospital, which suspected malignant lymphoma and referred her to our hospital. At the time of the first visit, she had left lymph swelling with tenderness and granuloma-like masses in the nasopharynx. PET-CT showed accumulations in both the swollen left neck lymph and nasopharynx. The diagnosis of this case would appear to be nasopharyngeal cancer with left and neck lymph node metastasis or nasopharyngeal tuberculosis with cervical lymph node tuberculosis in addition to malignant lymphoma. Based on some examinations (biopsy, bacteria culture, and imaging), it was diagnosed as nasopharyngeal tuberculosis with cervical lymph node tuberculosis. Therefore, she was treated with anti-tuberculosis agent in respiratory medicine.

Tracheal stenosis and recurrent nerve paralysis due to thyroid malignant lymphoma with huge chronic thyroiditis.

We experienced a case of huge chronic thyroiditis with malignant lymphoma that caused dyspnea with tracheal stenosis, dysphagia with esophagus stenosis and recurrent nerve paralysis. In this case, thyroidectomy was performed and, after the surgery, there was no sign of breathing or swallowing difficulties, and it was confirmed by the postoperative computed tomography that the tracheal stenosis had improved. We considered two possible explanations for the preoperative right recurrent nerve paralysis. In the first, the right recurrent nerve could have suffered from mechanical stimulation such as compression and traction to the recurrent nerve due to enlargement of the malignant lymphoma together with chronic thyroiditis. The second possible explanation was that malignant cells had invaded neurons. We could not distinguish between the two possibilities, since this right recurrent nerve was spared and could not be examined histopathologically.

Minimally invasive and inexpensive percutaneous abscess drainage using an indwelling needle cannula.

PURPOSE: Abscess is still a formidable disease and requires adequate drainage. Moreover, drainage in the head and neck area needs cosmetic care, especially in the pediatric population. In this report, we introduce our method of percutaneous abscess drainage using an indwelling needle cannula. PATIENTS AND METHODS: Ten pediatric and five adult patients with cervical and/or facial abscess treated with this drainage method were retrospectively reviewed. Using an indwelling needle cannula (18-14 G Surflow®, Terumo, Tokyo, Japan), abscesses were penetrated under ultrasonic examination. Once purulent retention was identified, the inner metal needle was removed and the outer elastic needle was left and fixed. The outer needle was connected to the tube for continuous suction drainage for large abscess. RESULTS: The primary diseases of these abscesses were cervical abscess of dental origin (5), purulent lymphadenitis (3), pyriform sinus fistula (2) and subperiosteal abscess due to mastoiditis (2), circumorbital cellulitis (1), infection of Warthin's tumor (1), and unknown origin (1). The median (range) duration of drainage was 4 days (3-9 days). Abscesses were successfully treated, and no patients required additional incision for abscess drainage. No apparent scars after drainage were observed. CONCLUSION: This technique resembles the usual venous placement of an indwelling needle cannula and is thought to be familiar to physicians. Although simple and inexpensive, this drainage is safe, effective, and minimally invasive for the treatment of abscess.

Development of a novel automatic ascites filtration and concentration equipment with multi-ring-type roller pump units for cell-free and concentrated ascites reinfusion therapy.

Cell-free and concentrated ascites reinfusion therapy (CART) is an effective therapy for refractory ascites. However, CART is difficult to perform as ascites filtration and concentration is a complicated procedure. Moreover, the procedure requires the constant assistance of a clinical engineer or/and the use of an expensive equipment for the multi-purpose blood processing. Therefore, we developed a CART specialized equipment (mobility CART [M-CART]) that could be used safely with various safety measures and automatic functions such as automatic washing of clogged filtration filter and self-regulation of the concentration ratio. Downsizing, lightning of the weight, and automatic processing in M-CART required the use of newly developed multi-ring-type roller pump units. This equipment was approved under Japanese regulations in 2018. In performing 41 sessions of CART (for malignant ascites, 22 sessions; and hepatic ascites, 19 sessions) using this equipment in 17 patients, no serious adverse event occurred. An average of 4494 g of ascites was collected and the total amount of ascites was processed in all the sessions without any trouble. The mean weight of the processed ascites was 560 g and the mean concentration ratio was 8.0. The ascites were processed at a flow rate of 50 mL/min. The mean ascites processing time was 112.5 minutes and a 106.5-minutes (95.2%) ascites processing was performed automatically. The operator responded to alarms or support information 3.2 times on average (3.1 minutes, 2.1% of ascites processing time). Human errors related to ascites processing were detected by M-CART at 0.4 times per session on average and were appropriately addressed by the operator. The frequencies of automatic washing of clogged filtration filter and self-regulation of the concentration ratio were 31.7% and 53.7%, respectively. The mean recovery rates (recovery dose) of protein, albumin, and immunoglobulin G were 72.9%, 72.9%, and 71.2% (65.9 g, 34.9 g, and 13.2 g), respectively. Steroids were administered in 92.7% of the sessions to prevent fever and the mean increase in body temperature was 0.53°C. M-CART is a compact and lightweight automatic CART specialized equipment that can safely and easily process a large quantity of ascites without the constant assistance of an operator.

Characteristics of ultrasonographic images of ductal carcinoma in situ with abnormalities of the ducts.

PURPOSE: Although the number of ductal carcinoma in situ (DCIS) cases has increased with the spread of breast cancer screening in Japan, there are very few reports that summarize ultrasound image features of DCIS. The Japan Association of Breast and Thyroid Sonology (JABTS) investigated the incidence of DCIS with masses and non-mass abnormalities and the characteristics of US images in a retrospective, multicenter, observational study (JABTS BC-02 study). The purpose of this report is to clarify the proportion of DCIS with abnormalities of the ducts with each ultrasound finding and the characteristics of US images. METHODS: The JABTS BC-02 study population was comprised of patients who were examined by ultrasonography, underwent surgery, and were histopathologically diagnosed with DCIS at each study site between January 2008 and December 2012. The US images of DCIS and pathology and clinical information were retrospectively collected from 16 institutions in Japan. The US images were evaluated by 22 experts on the Central Image Interpretation Committee of JABTS. RESULTS: Abnormalities of the ducts were noted in 78 (10.5%) of 705 US images of DCIS. Of the 78 cases, the distribution of abnormalities of the ducts was focal or segmental. The second characteristic was the presence of internal echoes in dilated ducts. All cases were accompanied by intraductal solid echoes, and 40 cases (51.3%) were accompanied by echogenic foci. In addition, intraductal solid echoes were continuous or multiple in 72 cases (92.4%), and the shape of the solid echoes was broad-based and/or irregular in 62 cases (79.5%). CONCLUSION: DCIS cases with duct abnormalities on ultrasound were investigated in this study. The important characteristics were as follows: (1) the distribution of ductal dilatation was focal or segmental, (2) solid parts were present in the dilated ducts, (3) the distribution of internal echoes was continuous or multiple, (4) the shape of solid echoes was broad-based and/or irregular, and (5) internal echoes were sometimes accompanied by echogenic foci. Accurate evaluation of these findings may be useful for diagnosing DCIS. Although the duct abnormalities are included in "ASSOCIATED FEATURES" in ACR BI-RADS ATLAS (USA), we emphasize that this concept is very important for understanding US characteristics of DCIS.

Different phenotypes of gastric fundic gland polyposis and cancer in patients with familial adenomatous polyposis depending on Helicobacter pylori infection.

A 37-year-old male with tarry stool presented to our hospital. Esophagogastroduodenoscopy revealed advanced gastric cancer, fundic gland polyposis (FGPsis), and negativity for Helicobacter pylori (HP) infection. Computed tomography exhibited multiple liver tumors. Total colonoscopy (TCS) demonstrated 139 tubular adenomas. He was diagnosed as having unresectable gastric cancer and received systemic chemotherapy. His sister and mother had colorectal adenomatous polyposis as revealed by TCS. His sister had FGPsis and was negative for HP infection, whereas his mother had early gastric cancer with HP infection but not FGPsis. Genetic analysis revealed a novel mutation in exon 15 of the APC gene (NM_000038.5: c.7647_7648_delTG) for the patient, his mother, and his sister, whereas no mutation was found for his father who had no gastrointestinal polyps. Therefore, the pedigree was diagnosed as an FAP family with a novel APC germline mutation which had different gastric phenotypes depending on the status of HP infection.

Intensity-modulated radiation therapy using TomoDirect for postoperative radiation of left-sided breast cancer including lymph node area: comparison with TomoHelical and three-dimensional conformal radiation therapy.

Intensity-modulated radiation therapy (IMRT) delivers an excellent dose distribution compared with conventional three-dimensional conformal radiation therapy (3D-CRT) for postoperative radiation including the lymph nodes in breast cancer patients. The TomoTherapy system, developed exclusively for IMRT, has two treatment modes: TomoDirect (TD) with a fixed gantry angle for beam delivery, and TomoHelical (TH) with rotational beam delivery. We compared the characteristics of TD with TH and 3D-CRT plans in the breast cancer patients. Ten consecutive women with left breast cancer received postoperative radiation therapy using TD including the chest wall/residual breast tissue and level II-III axial and supraclavicular lymph node area. Fifty percent of the planning target volume (PTV) was covered with at least 50 Gy in 25 fractions. TD, TH and 3D-CRT plans were created for each patient, with the same dosimetric constraints. TD and TH showed better dose distribution to the PTV than 3D-CRT. TD and 3D-CRT markedly suppressed low-dose spread to the lung compared with TH. Total lung V5 and V10 were significantly lower, while V20 was significantly higher in the TD and 3D-CRT plans. The mean total lung, heart and contralateral breast doses were significantly lower using TD compared with the other plans. Compared with 3D-CRT and TH, TD can provide better target dose distribution with optimal normal-organ sparing for postoperative radiation therapy including the chest wall/residual breast tissue and lymph node area in breast cancer patients. TD is thus a useful treatment modality in these patients.

Epidermal growth factor receptor-targeted molecular imaging of colorectal tumors: Detection and treatment evaluation of tumors in animal models.

To overcome the problem of overlooking colorectal tumors, a new and highly sensitive modality of colonoscopy is needed. Moreover, it is also important to establish a new modality to evaluate viable tumor volume in primary lesions of colorectal cancer (CRC) during chemotherapy. Therefore, we carried out molecular imaging of colorectal tumors targeting epidermal growth factor receptor (EGFR), which is highly expressed on tumor cells, for evaluating chemotherapeutic efficacy and for endoscopic detection of colorectal adenomas. We first attempted to image five CRC cell lines with various levels of EGFR expression using an Alexa Fluor-labeled anti-EGFR monoclonal antibody (AF-EGFR-Ab). A strong fluorescence signal was observed in the cells depending on the level of EGFR expression. When nude mice xenografted with LIM1215 CRC cells, which highly express EGFR, were i.v. injected with AF-EGFR-Ab, a strong fluorescence signal appeared in the tumor with a high signal to noise ratio, peaking at 48 hours after injection and then gradually decreasing, as shown using an IVIS Spectrum system. When the xenografted mice were treated with 5-fluorouracil, fluorescence intensity in the tumor decreased in proportion to the viable tumor cell volume. Moreover, when the colorectum of azoxymethane-treated rats was observed using a thin fluorescent endoscope with AF-EGFR-Ab, all 10 small colorectal adenomas (≤3 mm) were detected with a clear fluorescence signal. These preliminary results of animal experiments suggest that EGFR-targeted fluorescent molecular imaging may be useful for quantitatively evaluating cell viability in CRC during chemotherapy, and also for detecting small adenomas using a fluorescent endoscope.

Massive hemobilia following plastic stent removal in common bile duct cancer associated with primary sclerosing cholangitis (with video).

Hemobilia is defined as bleeding into the biliary tract. Herein, we report a very rare case of massive hemobilia following plastic stent (PS) removal in common bile duct (CBD) cancer. A 72-year-old man with primary sclerosing cholangitis had undergone repeated insertion of a PS into the CBD. Biliary tract biopsy was performed based on suspicion of combined CBD cancer. Biopsy revealed poorly differentiated adenocarcinoma of the CBD. One month after the biliary tract biopsy, he was admitted for acute cholangitis, and endoscopic retrograde cholangiography was performed for the exchange of the PS. When one of the two biliary PSs was removed, spurting bleeding from the major papilla began abruptly. The massive bleeding caused the patient to be in a pre-shock state. A retrieval balloon catheter was compressed against the papilla for hemostasis. Although he was treated conservatively, the patient developed a bloody discharge. Upper gastrointestinal endoscopy revealed that the pulsatile bleeding beside the PSs started immediately after the removal of the coagula. Emergent contrast-enhanced computed tomography showed right hepatic artery aneurysm across the CBD. Therefore, transarterial embolization was performed. The patient's post-therapeutic course was uneventful. He received chemotherapy, but died about a half year after hemobilia occurred.

Thermal Stress Relaxation and High-Temperature Corrosion of Cr-Mo Steel Processed Using Multifunction Cavitation.

This research investigated high-temperature corrosion (500 °C) of Cr-Mo steel processed using water jet peening or multifunction cavitation (MFC), and the suitability of such steel for high-temperature boilers and reaction vessels. High-temperature corrosion was induced using an embedment test and a coating test using sulfide-type K2SO4-Na2SO4 powder. To measure the relaxation of the residual stress due to the decrease in work hardening caused by an increase in specimen temperature and the difference in thermal shrinkage between the surface and interior of the specimen, a thermal cycling test was conducted. For the MFC-processed specimen, the oxide film that formed on the surface suppressed mass loss, prevented crack formation, and reduced the compressive residual stress caused by high-temperature corrosion. MFC-processed Cr-Mo steel is thus suitable for a high-temperature corrosion environment.

Clinicopathological Assessment of Gastric Xanthoma as Potential Predictive Marker of Gastric Cancer.

BACKGROUND/AIMS: Gastric xanthomas are frequently observed in the stomach as small yellowish plaques or nodules. A close relationship among Helicobacter pylori infection, atrophic gastritis, and xanthomas has been reported. We assessed the clinicopathological features of gastric cancer with or without xanthomas. METHODS: A total of 91 patients who were diagnosed as having early gastric cancer were enrolled. We evaluated the gastritis status using scores for gastritis and atrophy, positivity of H. pylori infection, the prevalence rate of xanthomas, and the clinicopathological features of gastric cancer. RESULTS: Gastric xanthomas were observed in 72.5% of early gastric cancer cases. Scores for gastritis and atrophy were significantly higher in the xanthoma-positive group than those in the xanthoma-negative group. A higher prevalence of differentiated-type adenocarcinoma was found in the xanthoma-positive group. Among the cases with multiple gastric xanthomas, the prevalence of males was significantly higher than that of females. CONCLUSION: A high prevalence rate of gastric xanthomas in gastric cancer cases was shown. Xanthomas were highly associated with age, the severities of gastritis and atrophy, and differentiated-type adenocarcinoma. Regardless of the eradication of H. pylori, xanthomas may be useful predictive markers for the development of differentiated-type adenocarcinoma.

Ultrasound Image Classification of Ductal Carcinoma In Situ (DCIS) of the Breast: Analysis of 705 DCIS Lesions.

The Japan Association of Breast and Thyroid Sonology (JABTS) proposed, in 2003, a conceptual classification system for non-mass abnormalities to be applied in addition to the conventional concept of masses, to facilitate detecting ductal carcinoma in situ (DCIS) lesions. The aim of this study was to confirm the utility of this system and to clarify the distribution of these findings in DCIS lesions. Data on 705 surgically treated DCIS lesions from 16 institutions in Japan were retrospectively reviewed. All 705 DCIS lesions could be classified according to the JABTS classification system. The most frequent findings were hypo-echoic areas in the mammary gland (48.6%), followed by solid masses (28.0%) and duct abnormalities (10.2%) or mixed masses (8.1%). Distortion (1.3%), clustered microcysts (1.4%) and echogenic foci without a hypo-echoic area (2.5%) were uncommon. These results suggest that the concept of non-mass abnormalities is useful in detecting DCIS lesions.

Duodenal cancer in a young patient with Peuts-Jeghers syndrome harboring an entire deletion of the STK11 gene.

A 21-year-old woman with Peuts-Jeghers syndrome (PJS) was referred to our hospital for gastrointestinal surveillance. She had been diagnosed as having PJS from a young age based on her family history and the presence of mucocutaneous pigmentation on her lips and oral mucosa. Her mother and brother had PJS harboring an entire deletion of the STK11 gene. She had tetralogy of Fallot, atrial tachycardia, sick sinus syndrome, and mental retardation in her past history. Esophagogastroduodenoscopy identified a protruded lesion with a depressed area that occupied the lumen half-circumferentially in the duodenal second portion and also showed a 10-mm protruded lesion on the anterior wall of the lower gastric body. Colonoscopy revealed a 3-mm protruded lesion on the rectum. No polyp was found in a barium small bowel series. Biopsies were taken from the duodenal tumor and gastric and colon polyps. Histopathologically, the duodenal tumor revealed a well-differentiated tubular adenocarcinoma, whereas gastric and colon polyps showed hamartomatous polyp. Therefore, subtotal stomach-preserving pancreatoduodenectomy was performed, and subsequent histopathological examination revealed that the duodenal tumor consisted of hamartomatous polyp and a well-differentiated tubular adenocarcinoma with invasion to the muscularis propria. Immunohistochemistry revealed accumulation of nuclear p53 protein, but no accumulation of nuclear ß-catenin protein. No RAS mutation was detected. Furthermore, direct sequencing of the STK11 gene in genomic DNA from peripheral blood mononuclear cells did not detect any mutation initially. However, multiplex ligation-dependent probe amplification (MLPA) analysis revealed entire deletion of STK11. These findings suggest that entire deletion of the STK11 gene caused hamartomatous polyps in the entire gastrointestinal tract and, subsequently, duodenal polyps likely gave rise to cancer through p53 mutation.

Colon capsule endoscopy: toward the future.

Colon capsule endoscopy is a wireless and minimally invasive technique for visualization of the whole colon. With recent improvements of technical features in second-generation systems, a more important role for colon capsule endoscopy is rapidly emerging. Although several limitations and drawbacks are yet to be resolved, its usefulness as a tool for colorectal cancer screening and monitoring disease activity in inflammatory bowel diseases has become more apparent with increased use. Further investigations, including multicenter trials, are required to evaluate the substantial role of the colon capsule in managing colorectal diseases.

Hepatosplenic Hodgkin lymphoma without lymphadenopathy following reversible methotrexate-associated lymphoproliferative disorder.

Lymphoproliferative disorders (LPDs) occur more frequently in rheumatoid arthritis (RA) patients treated with immunosuppressive agents than in the non-RA population. However, the various forms of disease progression have not yet been elucidated in detail. We encountered a case of Epstein-Barr virus (EBV)-positive atypical polymorphous LPD in the cervical and intraabdominal lymph nodes with hepatosplenomegaly in an 88-year-old female with RA who had taken infliximab and methotrexate (MTX) for six years. Although spontaneous remission occurred following the withdrawal of infliximab and MTX, reversible LPD evolved into hepatosplenic Hodgkin lymphoma without lymphadenopathy presenting as a cholestatic febrile illness. Our findings suggest that the recurrent lesions of MTX-associated LPDs may not always coincide with the primary lesion and may present unexplained findings based on various extranodal diseases.