Development and Validation of a Deep Neural Network for Accurate Evaluation of Endoscopic Images From Patients With Ulcerative Colitis.

BACKGROUND & AIMS: There are intra- and interobserver variations in endoscopic assessment of ulcerative colitis (UC) and biopsies are often collected for histologic evaluation. We sought to develop a deep neural network system for consistent, objective, and real-time analysis of endoscopic images from patients with UC. METHODS: We constructed the deep neural network for evaluation of UC (DNUC) algorithm using 40,758 images of colonoscopies and 6885 biopsy results from 2012 patients with UC who underwent colonoscopy from January 2014 through March 2018 at a single center in Japan (the training set). We validated the accuracy of the DNUC algorithm in a prospective study of 875 patients with UC who underwent colonoscopy from April 2018 through April 2019, with 4187 endoscopic images and 4104 biopsy specimens. Endoscopic remission was defined as a UC endoscopic index of severity score of 0; histologic remission was defined as a Geboes score of 3 points or less. RESULTS: In the prospective study, the DNUC identified patients with endoscopic remission with 90.1% accuracy (95% confidence interval [CI] 89.2%-90.9%) and a kappa coefficient of 0.798 (95% CI 0.780-0.814), using findings reported by endoscopists as the reference standard. The intraclass correlation coefficient between the DNUC and the endoscopists for UC endoscopic index of severity scoring was 0.917 (95% CI 0.911-0.921). The DNUC identified patients in histologic remission with 92.9% accuracy (95% CI 92.1%-93.7%); the kappa coefficient between the DNUC and the biopsy result was 0.859 (95% CI 0.841-0.875). CONCLUSIONS: We developed a deep neural network for evaluation of endoscopic images from patients with UC that identified those in endoscopic remission with 90.1% accuracy and histologic remission with 92.9% accuracy. The DNUC can therefore identify patients in remission without the need for mucosal biopsy collection and analysis. Trial number: UMIN000031430.

Cancer gland rupture as a potential risk factor for lymph node metastasis in early colorectal adenocarcinoma with deep submucosal invasion.

AIMS: Lymph node metastasis (LNM) has not been found in more than 85% of patients with early invasive colorectal adenocarcinoma (T1-CRAC) who undergo surgery after therapeutic endoscopy due to the risk for LNM. Better histological risk assessment for LNM of endoscopically resected T1-CRAC is important to avoid unnecessary additional surgery. METHODS AND RESULTS: We evaluated cancer gland rupture (CGR), i.e. cancer glands with a discontinuous epithelial lining, at the invasive front, as a potential risk factor for LNM by histological examination of differentiated T1-CRAC from 217 patients who underwent surgery with or without therapeutic endoscopy. CGR was represented by C-shaped neoplastic glands with a variable inflammatory or stromal reaction, and was occasionally accompanied by mucus lake or abscess formation. CGR was observed in 168 (77%) cases, including all 20 cases with LNM, and the odds ratio of LNM was higher for CGR than for deep invasion (depth of submucosal invasion ≥1000 µm). All cases with LNM were found among 148 cases with deep invasion and positive CGR, whereas no LNM was detected in 29 cases with deep invasion and negative CGR, regardless of vascular invasion or tumour budding. In the 148 cases, LNM was detected in 18 (19%) of 93 cases with positive vascular invasion or high-grade tumour budding, and in two (4%) of 55 cases without either. CONCLUSIONS: Our findings suggest that CGR is an easily applied and objective histological finding for predicting LNM that could be useful for assessing the risk for LNM of endoscopically resected T1-CRAC with deep invasion.

Adenocarcinoma within anorectal fistulae: different clinicopathological characteristics between Crohn's disease-associated type and the usual type.

Adenocarcinoma within anorectal fistulae is rare and is sometimes associated with Crohn's disease. Crohn's disease-associated adenocarcinoma within anorectal fistulae has a poor prognosis; however, little is known about the clinicopathological differences between Crohn's disease-associated adenocarcinoma within anorectal fistulae and usual adenocarcinoma within anorectal fistulae. We retrospectively searched patients' charts and pathology archives at Tokyo Yamate Medical Center and Tokyo Medical and Dental University Hospital for adenocarcinoma within anorectal fistulae. Clinical and pathological data were collected and immunohistochemical examinations were conducted. Overall survival rate was estimated using the Kaplan-Meier method. Prognostic factors of overall survival were assessed using univariate and multivariate Cox regression analyses. We examined 82 cases of adenocarcinoma within anorectal fistulae. Fifty-nine of 82 cases (72%) had usual adenocarcinoma within anorectal fistulae, while the remaining 23 cases (28%) had Crohn's disease-associated adenocarcinoma within anorectal fistulae. Patients with Crohn's disease-associated adenocarcinoma within anorectal fistulae were diagnosed at a younger age and at a more advanced stage than those with usual adenocarcinoma within anorectal fistulae. Macroscopic and histological types were also different between usual adenocarcinoma within anorectal fistulae and Crohn's disease-associated adenocarcinoma within anorectal fistulae. Crohn's disease-associated adenocarcinoma within anorectal fistulae included more ulcerative types and high-grade adenocarcinomas. The rate of lymphovascular invasion was higher in Crohn's disease-associated adenocarcinoma within anorectal fistulae. Immunohistochemically, the expression of E-cadherin, p53, and MUC5AC differed between usual adenocarcinoma within anorectal fistulae and Crohn's disease-associated adenocarcinoma within anorectal fistulae. Patients with Crohn's disease-associated adenocarcinoma within anorectal fistulae exhibited worse overall survival than those with usual adenocarcinoma within anorectal fistulae, and vascular invasion was the strongest significant independent predictor of overall survival in patients with adenocarcinoma within anorectal fistulae. In conclusion, usual adenocarcinoma within anorectal fistulae and Crohn's disease-associated adenocarcinoma within anorectal fistulae have different clinicopathological characteristics and should be considered separate clinical entities.

Predictors of mucosal healing during induction therapy in patients with acute moderate-to-severe ulcerative colitis.

BACKGROUND AND AIM: The treat-to-target strategy has emerged in ulcerative colitis management. Mucosal healing is the best target, albeit not in induction therapy of acute diseases as clinical conditions vary over a short duration. To determine the targets during induction therapy for acute ulcerative colitis, we identified markers to predict mucosal healing at 3 and 12 months of initiating the induction therapy. METHODS: This single-center prospective observational study enrolling 61 adult patients hospitalized for disease exacerbation collected the partial Mayo scores, ulcerative colitis endoscopic index of severity, fecal markers, and laboratory data (0 day, 2 weeks, and 3 and 12 months) of initiating induction therapy. RESULTS: At 2 weeks, patients with mucosal healing at 3 months had had lower partial Mayo and ulcerative colitis endoscopic index of severity scores and higher white blood cell count and total cholesterol than those without mucosal healing. At 3 months, patients with mucosal healing at 12 months had had lower partial Mayo and ulcerative colitis endoscopic index of severity scores than those without mucosal healing. A kinetic analysis demonstrated a difference in the partial Mayo scores and total cholesterol and albumin levels at 2 weeks and in the ulcerative colitis endoscopic index of severity, fecal calprotectin, and fecal immunochemical tests at 3 months between patients who achieved mucosal healing at 12 months and those who did not. CONCLUSIONS: Partial Mayo scores and total cholesterol levels act as short-term therapeutic targets during induction therapy in patients with acute ulcerative colitis. Mucosal healing at 3 months correlates to longer time mucosal healing.

Endoscopic features and genetic background of inflammatory bowel disease complicated with Takayasu arteritis.

BACKGROUND AND AIM: Takayasu arteritis (TA) is occasionally complicated with inflammatory bowel disease (IBD). This study assessed the endoscopic and genetic features of IBD complicated with TA (IBD-TA). METHODS: This study retrospectively reviewed the clinical charts of 142 TA patients (14 men and 128 women; median age 48.5 years [range, 18-97 years]). Human lymphocyte antigen (HLA) types and a single-nucleotide polymorphism rs6871626 in the IL12B gene were assessed in 101 and 81 patients with TA, respectively. RESULTS: Inflammatory bowel disease was diagnosed in 13 (9.2%) of the 142 patients. The endoscopic features of IBD-TA at initial diagnosis (n = 8) showed discontinuous and focal mucosal inflammations (n = 7, 87.5%), and only one case was diagnosed as ulcerative colitis (UC) at the first colonoscopy. In the genetic comparison of HLA class I between TA patients with IBD and those without IBD, HLA-B*52:01 and C*12:02 were more frequent in the IBD-TA group (P = 0.001 and P = 0.009, respectively). Meanwhile, HLA-DRB-1*15:02, DQA-1*01:03, DQB-1*06:01, and DPB-1*09:01 as HLA class II were positively associated with IBD-TA (P = 0.004, P = 0.019, P = 0.019, and P = 0.002, respectively). IL12B rs6871626 did not show an association with IBD-TA compared with that with TA without IBD. CONCLUSIONS: The endoscopic findings of IBD-TA at initial diagnosis were atypical for UC or Crohn's disease. IBD-TA possessed the HLA haplotype, which had a susceptible effect on UC.

Caudal type homeobox 2 expression induced by leukocytapheresis might be associated with mucosal healing in ulcerative colitis.

BACKGROUND AND AIM: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with an intractable, recurrent course. Although the goal of UC therapy has recently been to target mucosal healing, the molecular mechanism of mucosal healing remains unknown. In this study, we aimed to elucidate the molecular dynamics related to the proliferation and differentiation of intestinal epithelial cells during cytapheresis therapy in a short duration. METHODS: Endoscopy was performed in 26 patients with UC in multicentre hospitals, and biopsy specimens were collected from the rectum before and within two weeks after leukocytapheresis (LCAP). The expression of representative proteins in intestinal epithelial cells and pathological findings was compared before and after LCAP. RESULTS: The expression of caudal type homeobox 2 (CDX2) and a hes family bHLH transcription factor 1(HES1) markedly increased after LCAP. Patients with endoscopic improvement after LCAP showed the expression of CDX2 before LCAP. Moreover, the number of goblet cells significantly increased after LCAP. Patients without endoscopic improvement after LCAP did not show the expression of CDX2 before LCAP. However, the expression of CDX2 markedly increased after LCAP. CONCLUSION: This study suggests that cytapheresis might induce CDX2 expression without affecting the cell proliferation, thus resulting in mucosal healing with goblet cell restoration.

Atonal homolog 1 protein stabilized by tumor necrosis factor α induces high malignant potential in colon cancer cell line.

Patients with inflammatory bowel disease (IBD) have an increased risk of developing colitis-associated colorectal cancer (CAC). CAC cells often develop chemoresistance, resulting in a poorer prognosis than that of sporadic colorectal cancer (CRC). The mechanism by which CAC enhances malignant potential remains unknown. We have previously reported that the proteasomal degradation of the transcription factor Atonal homolog 1 (Atoh1) protein results in the non-mucinous form of CRC. It also remains unknown whether Atoh1 protein is expressed in CAC. Therefore, in the present study, we investigated whether Atoh1 protein stabilizes in CAC. Consequently, the treatment with TNF-α stabilized Atoh1 protein through the inactivation of GSK-3ß via Akt, resulting in the mucinous form of CRC cell lines. Atoh1 protein also enriched cancer stem cells with upregulated Lgr5 expression and cells in G0/G1 cell cycle phase, resulting in both the chemoresistance to 5-fluorouracil and oxaliplatin and the promotion of cell migration. Immunofluorescence of the human mucinous CAC specimens showed the accumulation of NF-κB p65 at nuclei with the expression of Atoh1 in mucinous cancer. In conclusion, the inflammation associated with carcinogenesis may preserve the differentiation system of intestinal epithelial cell (IEC), resulting in the acquisition of both the mucinous phenotype and high malignant potential associated with the enrichment of cancer stem cell.

Diffusion-weighted magnetic resonance neurography for parapharyngeal schwannomas: preoperative determination of the originating nerves.

OBJECTIVE: The aim of this study was to assess the feasibility of diffusion-weighted (DW) magnetic resonance neurography (MRN) for determining the originating nerve of parapharyngeal schwannomas preoperatively. METHODS: Six patients who underwent DW-MRN preoperatively for a parapharyngeal schwannoma were studied. Prediction of the originating nerve was performed. With the conventional method, a tumor showing "separation" between the internal jugular vein and carotid artery was determined to originate from the vagus nerve, with "no separation" from the sympathetic chain. With DW-MRN, the relationships between the vagus nerve and sympathetic chain to the tumor were characterized as "connected" or "dislocated." A nerve connected to the tumor was determined as the origin. RESULTS: Surgeries revealed that the origins included 1 vagus nerve and 5 sympathetic chains. Using a conventional method, all 6 cases were diagnosed correctly, whereas DW-MRN successfully predicted only 4 cases with a sympathetic chain origin. CONCLUSIONS: The DW-MRN is a feasible approach for determining an originating nerve.

Aggressive diffuse large B-cell lymphoma manifested by splenic rupture progressed 2 months after transverse myelitis: an autopsy case report.

Background: Splenic rupture by diffuse large B-cell lymphoma (DLBCL), which usually progresses insidiously, is extremely rare. Case Presentation: A 60-year-old man presented with paralysis in his lower left extremity. A magnetic resonance imaging suggested transverse myelitis. No lymphadenopathy or organomegaly was noted. Two months after remission, he was referred to the emergency department complaining of presyncope. He was in preshock due to splenic rupture, and underwent laparotomy after attempts of transcatheter arterial embolization. Splenomegaly, hepatomegaly, and disseminated enlarged lymph nodes were observed. Histological examinations of the resected spleen showed DLBCL. He died of multiple organ failure associated with intractable bleeding. His autopsy revealed diffuse systemic invasions of lymphoma cells except for the brain and spinal cord. Microscopically, the spinal cord showed macular incomplete necrosis and histiocytic infiltration, suggestive of hemophagocytic syndrome. Conclusion: The progression of DLBCL in our case is drastically rapid. Undiagnosed transverse myelitis preceded the onset.

The efficacy of dupilumab in induction and maintenance of remission in an adult patient with steroid-dependent eosinophilic enteritis (EoN).

Eosinophilic enteritis (EoN) is associated with an eosinophilic infiltrate confined to the small intestine, but treatment options other than diet and corticosteroid therapy are scarce. There is only one report of the use of dupilumab for eosinophilic gastrointestinal disease, involving three pediatric patients. We report a case of successful induction of remission with dupilumab in a 53 year-old female patient with steroid-dependent EoN. The patient presented to the emergency room with uncontrollable abdominal pain and CT revealed a thickened ileal wall and small amount of ascites. Despite no abnormalities on endoscopy, histological examination revealed numerous eosinophilic infiltrates (> 100/HPF) and degranulation in the ileal lamina propria, diagnosing the patient with EoN. The patient achieved clinical remission with prednisolone, but EoN relapsed during tapering. Long-term steroid therapy was inappropriate due to mandibular osteomyelitis and osteoporosis, and she was switched to 9 mg budesonide, an intestine-soluble topical steroid without effect. Dupilumab administration resulted in resolution of abdominal pain, and remission was maintained after discontinuation of budesonide. Histological remission was confirmed 2 months after dupilumab administration. This is the first report of remission induced and maintained with dupilumab in an adult patient with EoN.

Localization of propionibacterium acnes in granulomas supports a possible etiologic link between sarcoidosis and the bacterium.

Sarcoidosis likely results from the exposure of a genetically susceptible subject to an environmental agent, possibly an infectious one. Mycobacterial and propionibacterial organisms are the most commonly implicated potential etiologic agents. Propionibacterium acnes is the only microorganism, however, found in sarcoid lesions by bacterial culture. To evaluate the pathogenic role of this indigenous bacterium, we screened for the bacterium in sarcoid and non-sarcoid tissues using immunohistochemical methods with novel P. acnes-specific monoclonal antibodies that react with cell-membrane-bound lipoteichoic acid (PAB antibody) and ribosome-bound trigger-factor protein (TIG antibody). We examined formalin-fixed and paraffin-embedded samples of lungs and lymph nodes from 196 patients with sarcoidosis, and corresponding control samples from 275 patients with non-sarcoidosis diseases. The samples were mostly from Japanese patients, with 64 lymph node samples from German patients. Immunohistochemistry with PAB antibody revealed small round bodies within sarcoid granulomas in 20/27 (74%) video-assisted thoracic surgery lung samples, 24/50 (48%) transbronchial lung biopsy samples, 71/81 (88%) Japanese lymph node samples, and 34/38 (89%) German lymph node samples. PAB antibody did not react with non-sarcoid granulomas in any of the 45 tuberculosis samples or the 34 samples with sarcoid reaction. In nongranulomatous areas, small round bodies detected by PAB antibody were found in alveolar macrophages of lungs and paracortical macrophages of lymph nodes from many sarcoid and some non-sarcoid patients. Large-spheroidal acid-fast bodies, Hamazaki-Wesenberg bodies, which were found in 50% of sarcoid and 15% of non-sarcoid lymph node samples, reacted with both PAB and TIG antibodies. Electron microscopy revealed that these Hamazaki-Wesenberg bodies had a single bacterial structure and lacked a cell wall with occasional protrusions from the body. The high frequency and specificity of P. acnes, detected by PAB antibody within sarcoid granulomas, indicates that this indigenous bacterium might be the cause of granuloma formation in many sarcoid patients.

Case report of recurrent spontaneous tumor lysis syndrome in a patient with esophageal cancer recovered via chemotherapy.

Tumor lysis syndrome (TLS) is a life-threatening oncological emergency. Only one TLS case has been reported in patients with esophageal cancer. We report the case of a 61-year-old man with recurrent spontaneous TLS caused by esophageal cancer. He was admitted to our hospital to investigate low back pain and dysphagia. Endoscopy and computed tomography revealed esophageal cancer with multiple liver and bone metastases. He was diagnosed with laboratory TLS based on high serum uric acid and phosphorus. After intravenous fluids and allopurinol were administrated, chemotherapy with 5-fluorouracil and cisplatin was started the next day. Although he transiently developed clinical TLS, it was resolved with conservative treatment. However, mild renal dysfunction was prolonged and cisplatin was reduced in the second course. As a consequence, recurrence of spontaous TLS (sTLS) was induced at the end of the course. In the third course, docetaxel was added to the regimen, and since then the patient have not develop sTLS. To the best of our knowledge, this is the first report regarding recurrent sTLS developed on the basis of solid tumors and was successfully controlled by chemotherapy. Although TLS complications are rare in esophageal cancer, early diagnosis and the adjustment of regimen resulted in stable chemotherapy.

A case of localized colorectal wild-type ATTR amyloidosis complicated by early stage colorectal cancer and a CMV-associated ulcer during the long-term follow-up.

Gastrointestinal involvement is a rare manifestation of systemic amyloidosis, and few reports have been published on localized amyloidosis of the colon. Only one case report has been published on the long-term prognosis of localized colorectal amyloidosis, and there are no previous reports on localized colorectal ATTR amyloidosis. Here, we report an 80-year-old male with localized colorectal wild-type ATTR amyloidosis who presented with edematous mucosa with vascular changes throughout the colon. He did not exhibit any symptoms or endoscopic exacerbation for 8 years after diagnosis. However, after 8 years, he developed early stage colorectal cancer and cytomegalovirus-associated ulcer. He was treated with endoscopic submucosal dissection, which was relatively challenging due to his hemorrhagic condition and poor elevation of the submucosa caused by amyloid deposits. Since the tumor was completely resected, he will undergo regular follow-up. Our review of 20 previous cases of localized colorectal amyloidosis revealed its clinical features and long-term prognosis. Specifically, ours is the second case of a diffuse pan-colon type of colorectal localized amyloidosis, which may lead to various complications, such as colorectal cancer, over a long period of time, and thus, regular follow-up is necessary.

A rare case of ulcerative colitis in a patient who developed acute ischemic colitis associated with Takayasu arteritis.

Intestinal ischemia is a rare complication of Takayasu arteritis (TAK), which often requires colectomy. We report the case of a 27 year-old man with ulcerative colitis (UC), who was admitted to our hospital due to abdominal pain. Computed tomography revealed an edematous wall of the ascending colon with ascites and a thickened aortic wall with mild stenosis of the superior mesenteric artery (SMA), suggesting large vessel vasculitis, especially TAK. Colonoscopy revealed acute ischemic colitis associated with mild stenosis of the SMA caused by TAK, but there was no worsening of UC. The patient was successfully treated with conservative therapy.

Substantial Epstein-Barr virus reactivation in a case of severe refractory ulcerative colitis: a possible role in exacerbation.

Ulcerative colitis (UC) is an inflammatory bowel disease that causes chronic inflammation in the colon. 5-aminosalicylic acid and immunosuppressive medications such as corticosteroids, immunomodulators, and biologic agents are used to treat these patients. However, patients with UC who receive immunosuppressive medications may be at risk for certain opportunistic infections. Epstein-Barr virus (EBV) is one of those opportunistic infections, and its pathogenic role has been implicated in refractory UC, but its pathogenicity should be further investigated. Here, we report a surgical case of refractory UC that demonstrated a serologically post-infected pattern of EBV at admission but that later had a high load of EBV in both the peripheral blood and colonic mucosa. These findings suggest that EBV may have been reactivated in the colon, after which it damaged the colonic mucosa and aggravated inflammation in this patient with UC. Thus, EBV might lead to severity and a refractory response against corticosteroids and anti-TNFα agents, necessitating emergency surgery. Viral surveillance for EBV in patients with refractory UC may facilitate understanding of the patient's pathophysiology and predicting response to medications, and the development of antiviral intervention for those patients may improve their prognosis.

Schlafen 11 Is a Novel Target for Mucosal Regeneration in Ulcerative Colitis.

BACKGROUND AND AIMS: Ulcerative colitis [UC] is a chronic inflammatory disease of the colon with an intractable course. Although the goal of UC therapy is to achieve mucosal healing, the pathogenesis of mucosal injury caused by chronic inflammation remains unknown. We therefore aim to elucidate molecular mechanisms of mucosal injury by establishing in vitro and in vivo humanised UC-mimicking models. METHODS: An in vitro model using human colon organoids was established by 60 weeks of inflammatory stimulation. The key gene for mucosal injury caused by long-term inflammation was identified by microarray analysis. An in vivo model was established by xenotransplantation of organoids into mouse colonic mucosa. RESULTS: An in vitro model demonstrated that long-term inflammation induced irrecoverable changes in organoids: inflammatory response and apoptosis with oxidative stress and suppression of cell viability. This model also mimicked organoids derived from patients with UC at the gene expression and phenotype levels. Microarray analysis revealed Schlafen11 [SLFN11] was irreversibly induced by long-term inflammation. Consistently, SLFN11 was highly expressed in UC mucosa but absent in normal mucosa. The knockdown of SLFN11 [SLFN11-KD] suppressed apoptosis of intestinal epithelial cells [IECs] induced by inflammation. Moreover, SLFN11-KD improved the take rates of xenotransplantation and induced the regenerative changes of crypts observed in patients with UC in remission. CONCLUSIONS: In vitro and in vivo UC-mimicking models were uniquely established using human colonic organoids. They revealed that SLFN11 is significant for mucosal injury in UC, and demonstrated its potential as a novel target for mucosal regeneration.

Catalase expression of Propionibacterium acnes may contribute to intracellular persistence of the bacterium in sinus macrophages of lymph nodes affected by sarcoidosis.

Bacterial catalase is important for intracellular survival of the bacteria. This protein of Propionibacterium acnes, one of possible causes of sarcoidosis, induces hypersensitive Th1 immune responses in sarcoidosis patients. We examined catalase expression in cultured P. acnes isolated from 19 sarcoid and 18 control lymph nodes and immunohistochemical localization of the protein in lymph nodes from 43 sarcoidosis and 102 control patients using a novel P. acnes-specific antibody (PAC) that reacts with the catalase protein, together with the previously reported P. acnes-specific PAB and TIG antibodies. High catalase expression of P. acnes cells was found during stationary phase in more isolates from sarcoid than from non-sarcoid lymph nodes and was associated with bacterial survival under H2O2-induced oxidative stress. In many sarcoid and some control lymph nodes, catalase expression was detected at the outer margins of PAB-reactive Hamazaki-Wesenberg (HW) bodies in sinus macrophages, the same location as catalase expression on the surface of cultured P. acnes and the same distribution as bacterial cell membrane-bound lipoteichoic acid in HW bodies. Some or no catalase expression was detected in sarcoid granulomas with PAB reactivity or in clustered paracortical macrophages packed with many PAB-reactive small-round bodies. HW bodies expressing catalase may be persistent P. acnes in sinus macrophages whereas PAB-reactive small-round bodies with undetectable catalase may be activated P. acnes proliferating in paracortical macrophages. Intracellular proliferation of P. acnes in paracortical macrophages may lead to granuloma formation by this commensal bacterium in sarcoidosis patients with Th1 hypersensitivity to certain P. acnes antigens, including catalase.

Small intestinal obstruction due to the metastasis of intrahepatic cholangiocarcinoma: A case report.

RATIONALE: The small intestine (SI) does not commonly harbor cancer but is occasionally involved by metastatic cancer from other organs. To manage SI cancer appropriately, surveillance for primary origin outside the SI is essential. PATIENT CONCERNS: This study presents a 54-year-old Thai man diagnosed with SI obstruction which required laparoscopy- assisted partial ileal resection. DIAGNOSES: On the basis of the expression pattern of cytokeratins (CKs) and mucins (MUCs) in the resected SI adenocarcinoma, we suspected this was metastasized from the pancreatobiliary tract. Imaging studies revealed a hepatic segmental atrophy with an occlusion of the posterior segmental blanch of the portal vein without any contrast-enhanced lesions in the liver. Pathology of the liver biopsy revealed intrahepatic cholangiocarcinoma (ICC) with the same expression pattern of CKs and MUCs as the SI adenocarcinoma. INTERVENTIONS: Systemic chemotherapy (gemcitabine and cisplatin) was initiated. OUTCOMES: Despite of the chemotherapy for 20 months, he died of ICC. LESSONS: This is the first case of SI obstruction caused by the metastasis of ICC. We demonstrate that immunohistochemical staining of CKs and MUCs discriminate between primary and metastatic SI cancer and predict its primary origin outside the SI. This case also suggests that a hepatic segmental atrophy with portal vein occlusion would be an atypical but important finding to diagnose ICC.

Localization and density of Porphyromonas gingivalis and Tannerella forsythia in gingival and subgingival granulation tissues affected by chronic or aggressive periodontitis.

Porphyromonas gingivalis and Tannerella forsythia have been thought to be associated with periodontitis; however comprehensive histopathological localization of bacteria in affected human periodontal tissues is not well documented. In the present study, we examined formalin-fixed paraffin-embedded gingival and subgingival granulation tissues from 71 patients with chronic periodontitis and 11 patients with aggressive periodontitis, using immunohistochemistry with novel monoclonal antibodies specific to P. gingivalis or T. forsythia, together with quantitative real-time polymerase chain reaction for each bacterial DNA. Immunohistochemisty revealed both bacterial species extracellularly, as aggregates or within bacterial plaque, and intracellularly in stromal inflammatory cells, squamous epithelium, and capillary endothelium of granulation tissue. Combined analysis with the results from polymerase chain reaction suggested that localization and density of T. forsythia is closely associated with those of P. gingivalis, and that bacterial density is a factor responsible for the cell-invasiveness and tissue-invasiveness of these periodontal bacteria. Detection of these bacteria in the capillary endothelium in some samples suggested possible bacterial translocation into the systemic circulation from inflamed gingival and subgingival granulation tissues. Immunohistochemistry with the novel antibodies showed high specificity and sensitivity, and can be used to locate these periodontal bacteria in routinely-used formalin-fixed paraffin-embedded human tissue sections from systemic locations.

Propionibacterium acnes-derived insoluble immune complexes in sinus macrophages of lymph nodes affected by sarcoidosis.

BACKGROUND: Propionibacterium acnes is thought to be a causative agent of sarcoidosis. Patients with sarcoidosis have circulating immune complexes. We attempted to detect P. acnes-derived immune complexes in sarcoid lesions. METHODS: We evaluated formalin-fixed and paraffin-embedded lymph node samples from 38 sarcoidosis patients and 90 non-sarcoidosis patients (27 patients with necrotizing lymphadenitis, 28 patients with reactive lymphadenitis, 16 patients with colon cancer, 19 patients with gastric cancer) by immunohistochemistry using anti-human immunoglobulins (IgG, IgA, and IgM) and complement (C1q and C3c) antibodies, and a P. acnes-specific monoclonal antibody (PAB antibody) that reacts with the membrane-bound lipoteichoic acid of P. acnes. RESULTS: Small round bodies (SRBs) bound to IgA, IgM, or IgG were detected in sinus macrophages, in 32 (84%), 32 (84%), or 11 (29%) sarcoid samples, respectively, and in 19 (21%), 26 (29%), or no (0%) control samples, respectively. Some of these insoluble immune complexes (IICs) also bound to C1q and C3c. We developed a microwave treatment followed by brief trypsin digestion (MT treatment) to detect PAB-reactive SRBs bound to immunoglobulins (IIC-forming P. acnes). MT treatment revealed abundant IIC-forming P. acnes in most (89%) of the sarcoid samples and sparse distribution in some (20%) of the control samples with lymphadenitis, but no IIC-forming P. acnes was detected in control samples without inflammation. IIC-forming P. acnes were mostly bound to both IgA and IgM. The PAB-reactive antigen and immunoglobulins were both located at the peripheral rim of the IIC-forming P. acnes. Conventional electron microscopy identified many SRBs (0.5-2.0 µm diameter) in sinus macrophages of sarcoid lymph nodes with many IIC-forming P. acnes, some of which were in phagolysosomes with a degraded and lamellar appearance. CONCLUSIONS: P. acnes-derived IICs in sinus macrophages were frequent and abundant in sarcoid lymph nodes, suggesting a potential etiologic link between sarcoidosis and this commensal bacterium.