Clinicopathological study of surgically treated non-neoplastic diseases of the pancreas with special reference to autoimmune pancreatitis.

PURPOSE: After the popularization of serum immunoglobulin G4 (IgG4) measurement and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in our institute, surgical resection for non-neoplastic diseases of the pancreas became less common. Although the incidence of such false-positive cases was clarified in the 10-year period after the introduction of these measures (2009-2018), these data were not compared with the 30 years before 2009 (1979-2008). This study was performed to determine the percentage of autoimmune pancreatitis (AIP) that was included during the latter period and how the numbers of false-positive cases differed between the two periods. METHODS: From 1979 to 2008, 51 patients had clinical suspicion of pancreatic carcinoma (false-positive disease). Among these 51 patients, 32 non-alcoholic patients who had tumor-forming chronic pancreatitis (TFCP) were clinically, histologically, and immunohistochemically compared with 11 patients who had TFCP during the latter 10-year period. RESULTS: Retrospective IgG4 immunostaining of false-positive TFCP revealed 14 (35.0%) cases of AIP in the former 30 years versus 5 (45.5%) in the latter 10 years. There were 40 (5.9%) cases of TFCP among 675 patients in the former 30 years and 11 (0.9%) among 1289 patients in the latter 10 years. CONCLUSIONS: When the TFCP ratio of pancreatic resections and the AIP ratio of false-positive TFCPs were compared between the two periods, the TFCP ratio was 5.9% versus 0.9% and the AIP ratio was 35.0% versus 45.5%, respectively. It can thus be speculated that IgG4 measurement and EUS-FNA are absolutely imperative for the diagnosis of TFCP.

Marked reduction in the number of white globe appearance lesions in the noncancerous stomach after exchanging vonoprazan for esomeprazole treatment: a follow-up case report.

Recently, an association has been suggested between development of white globe appearance lesions in the noncancerous stomach and treatment with a potassium-competitive acid blocker or a proton pump inhibitor. We previously reported two cases with development of white globe appearance lesions after vonoprazan treatment, suggesting a similar association. Here, we present the follow-up report of one of those two cases, concerning a 68-year-old woman who developed multiple white globe appearance lesions 1 year after starting vonoprazan treatment for severe gastroesophageal reflux disease leading to esophageal stricture. The patient refused to continue vonoprazan treatment after the lesions developed, and esomeprazole was initiated instead. Three months later, most of the white globe appearance lesions had disappeared, without worsening of her gastroesophageal reflux disease. Histologically, mucosal structural changes induced by vonoprazan, such as parietal cell protrusion with oxyntic gland dilatation, remained unchanged, whereas the gastric glands became less packed and a small calcification in the concentrated eosinophilic material was observed in a remaining white globe appearance cyst after esomeprazole treatment. Here, we discuss possible pathogenic mechanisms of these dramatic gastric mucosal changes observed in the present case, based on our endoscopic and histological findings.

Development of white globe appearance lesions in the noncancerous stomach after vonoprazan administration: a report of two cases with a literature review.

White globe appearance has recently been identified as a novel endoscopic marker useful in the diagnosis of early gastric cancer. Recently, this lesion has also been reported in the noncancerous stomach, including cases with autoimmune atrophic gastritis, although the clinical significance remains unclear. We present the details of a 68-year-old woman who began vonoprazan therapy for severe gastroesophageal reflux disease causing esophageal stricture. On follow-up endoscopy 1 year after beginning vonoprazan, multiple white globe appearance lesions developed in all sections of her stomach, except for the antrum. We also detected lesions during a yearly follow-up in the noncancerous stomach of a 70-year-old man who had received vonoprazan for 3 years. Lesions in both cases constituted cystic gland dilatations containing eosinophilic material. There was no evidence of accompanying autoimmune atrophic gastritis in either patient. This report is the first to our knowledge describing newly developed white globe appearance lesions in the noncancerous stomach during follow-up in two cases who received vonoprazan. Our findings suggest that these lesions in the noncancerous stomach might be associated with vonoprazan treatment. We investigated the two cases endoscopically and histologically, and we report our findings with a literature review.

Pneumatosis cystoides intestinalis lesions changing into yellowish plaque-like elastosis lesions during healing.

Pneumatosis cystoides intestinalis (PCI) is a rare disease characterized by multiple gas-filled cysts in the intestinal wall. The majority of patients with PCI are asymptomatic and have a benign clinical course without treatment. Regular colonoscopic follow-up is not always clinically necessary for PCI; therefore, whether all patients with PCI eventually achieve complete endoscopic resolution remains unclear. We herein present the details of an asymptomatic 58-year-old man diagnosed with PCI in the right colon in 2011 by colonoscopy. We followed him using colonoscopy for 8 years without treatment. The PCI lesions gradually changed into multiple flat yellowish plaque-like lesions, and biopsies revealed that these were elastosis, which is a very rare pathological finding in the colon. To our knowledge, only two reports discuss morphological or histological changes similar to those of PCI. Because the development of yellowish plaque-like lesions histologically representing elastosis associated with PCI is an unrecognized entity, we herein discuss its clinical features, endoscopic findings, and histological findings with a literature review.

Manuka honey incorporated cellulose acetate nanofibrous mats: Fabrication and in vitro evaluation as a potential wound dressing.

Wound dressings are the primary barrier between the wound surface and the outer environment. Here we report the fabrication of cellulose acetate (CA)-Manuka honey (MH) composite nanofibrous mats as a biocompatible and antimicrobial wound dressing. CA mats with different quantities of MH were developed by electrospinning. The ATR-FTIR spectra confirm the inclusion of MH in the composite CA-MH nanofibrous mats. The fibers were continuous and bead-free with acceptable mechanical properties. The fiber diameter increased with an increase in MH content. Inclusion of MH in the electrospun composite CA-MH nanofibrous mats shows high efficacy to prevent bacterial growth on the wound surface. The MH loaded CA nanofiber mats showed good antioxidant abilities, while the ability to free radicalize the DPPH was dependent upon the factors of MH content in the fiber and the time of immersion in the DPPH solution. Besides, the nanofibrous mat's high porosity (85-90%) and WVTR values of 2600 to 1950 g/m2/day, suitable for wound breathability and the mats show high cytocompatibility to NIH 3T3 cell line in in vitro testing, proving to be effective for promoting wound healing.

Pneumatosis cystoides intestinalis accompanied by intestinal spirochetosis.

Pneumatosis cystoides intestinalis (PCI) is a rare but well-recognized entity characterized by multiple gas-filled cysts in the intestinal wall. Although the pathogenesis of PCI remains unclear, several theories, including a bacterial theory, have been postulated. Intestinal spirochetosis (IS) is an uncommon condition defined by the presence of spirochetes attached to the surface of the colonic epithelium. The nature of IS as a commensal or pathogenic process remains debatable. However, recent evidence supports the idea that IS can be invasive and highly pathogenic in both immunocompromised and immunocompetent individuals. We present the case of a 35-year-old asymptomatic and immunocompetent man who underwent colonoscopy because of a positive fecal blood test. Multiple submucosal cystic lesions were detected accompanied by erythematous areas along the ascending colon. Computed tomography-colonography and biopsy specimens from the erythematous areas confirmed coexisting PCI and IS. Both PCI and IS recovered completely 3 months after administration of metronidazole. To the best of our knowledge, this case represents only the second report of the extremely rare concurrence of PCI with IS. Taking into account the published literature, we also discuss the possibility that the development of PCI may be related to IS.

Polypoid gallbladder tumors with a deep hypoechoic area and a conically thickened outermost hyperechoic layer suggest shallow T2 carcinoma.

BACKGROUND: Ultrasound findings of shallow T2 gallbladder carcinoma (GBC) with a favorable prognosis are not known. PURPOSE: To confirm the criteria for ultrasound diagnosis of shallow T2 GBC. MATERIAL AND METHODS: A detailed analysis of ultrasound and pathological correlation was conducted in two patients with pT1 GBC and seven with shallow pT2 GBC (subserosal-invasion depth ≤ 2 mm) at our institution from January 1988 to December 2017. RESULTS: A polypoid gallbladder tumor with a deep hypoechoic area represented a papillary adenocarcinoma invading the subserosa accompanied by abundant fibrosis and lymphocytic infiltration. Two cases of pT1 GBC did not present a deep hypoechoic area, whereas all seven cases of shallow pT2 GBC did. One case of pT1b GBC and four cases of pT2 GBC showed conical thickening of the outermost hyperechoic layer, whereas one case of pT1a GBC and three cases of pT2 GBC presented no change of the layer thickness. All shallow T2 GBCs showing a conically thickened outermost hyperechoic layer provided good postoperative prognoses. CONCLUSION: Ultrasound images of shallow T2 GBC show a deep hypoechoic area with conical thickening or unchanging of an outermost hyperechoic layer. The former demonstrates pulling up the top of the layer at first and then thinning later as carcinoma invades with enlargement of the hypoechoic area, whereas the latter thinning of the layer from the beginning. Polypoid gallbladder tumors with a deep hypoechoic area and a conically thickened outermost hyperechoic layer suggest shallow T2 GBC and may provide good postoperative prognoses.

Acute appendicitis with a neuroendocrine tumor G1 (carcinoid): pitfalls of conservative treatment.

A man in his early thirties presented to our clinic with right lower abdominal pain. Computed tomography (CT) and ultrasonography (US) revealed a swollen appendix and an appendicolith. Abscess formation was not observed but ongoing appendiceal rupture was not ruled out. Three months after successful conservative therapy, the lumen of the apical portion was kept dilated and laparoscopic interval appendectomy was performed. No tumorous findings were observed macroscopically. However, histology revealed many tiny nests infiltrating the submucosa, muscular layer, and subserosa at the root of the appendix. An appendiceal neuroendocrine tumor G1 (NET G1; carcinoid) was diagnosed immunohistologically. Neither CT nor US visualized the tumor because of its non-tumor-forming but infiltrative growth. In conclusion, after successful conservative treatment, interval appendectomy should be considered to uncover a possible appendiceal NET G1 (carcinoid), particularly when dilatation of the distal lumen is kept under observation.

Analysis of Image Gently Abdominal CT Protocol With the Use of Body Phantom Adapted to the Japanese Size.

OBJECTIVE: The purpose of this study was to analyze in detail the quality of abdominal CT images obtained using three protocols reported by Image Gently in 2014 (hereafter referred to as Image Gently 2014), with the use of a handmade body phantom adapted to typical body sizes of the Japanese population. Moreover, we converted the findings of Image Gently 2014 to match Japanese body sizes and referred to our converted findings as Image Gently Japan. MATERIALS AND METHODS: We scanned each phantom in a mechanical isocenter in accordance with the Image Gently 2014 abdominal imaging protocol. We changed the tube current-exposure time product per rotation from 25 to 250 mAs. The bowtie filter was set with a minimum FOV for the phantom size. We then analyzed the volume CT dose index (CTDIvol)-measured CT number curve. We then used this CT number curve to calculate the CT number recommended by Image Gently Japan for each of the designated patient ages. RESULTS: The CTDIvol-measured CT number curve showed that, as the CTDIvol increased with each age, image noise decreased. When we assumed that the CTDIvol value for adults was 20 mGy, the measured CT number was 12.5 HU. We then multiplied each reduction coefficient by age (neonate and 1, 5, 10, and 15 years). The measured CT numbers for Image Gently Japan performed to attain limited dose reduction were 3.0, 3.9, 4.9, 6.0, and 9.0 HU, respectively, whereas those for Image Gently Japan performed to achieve moderate dose reduction were 3.3, 4.3, 5.3, 6.3, and 9.3 HU, respectively, and those for Image Gently Japan performed to attain aggressive dose reduction were 4.1, 5.1, 5.8, 6.8, and 9.5 HU, respectively. CONCLUSION: We analyzed the abdominal image quality demanded by Image Gently 2014, and we were able to adapt the results to the Japanese population and present them as our own Image Gently Japan recommendations. If the results of the present study become a foundation for scanning parameters for Japanese patients, we believe that they will eventually lead to a reduction in medical radiation exposure for this patient population.

A Revised Classification System and Recommendations From the Baltimore Consensus Meeting for Neoplastic Precursor Lesions in the Pancreas.

International experts met to discuss recent advances and to revise the 2004 recommendations for assessing and reporting precursor lesions to invasive carcinomas of the pancreas, including pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm, and other lesions. Consensus recommendations include the following: (1) To improve concordance and to align with practical consequences, a 2-tiered system (low vs. high grade) is proposed for all precursor lesions, with the provision that the current PanIN-2 and neoplasms with intermediate-grade dysplasia now be categorized as low grade. Thus, "high-grade dysplasia" is to be reserved for only the uppermost end of the spectrum ("carcinoma in situ"-type lesions). (2) Current data indicate that PanIN of any grade at a margin of a resected pancreas with invasive carcinoma does not have prognostic implications; the clinical significance of dysplasia at a margin in a resected pancreas with IPMN lacking invasive carcinoma remains to be determined. (3) Intraductal lesions 0.5 to 1 cm can be either large PanINs or small IPMNs. The term "incipient IPMN" should be reserved for lesions in this size with intestinal or oncocytic papillae or GNAS mutations. (4) Measurement of the distance between an IPMN and invasive carcinoma and sampling of intervening tissue are recommended to assess concomitant versus associated status. Conceptually, concomitant invasive carcinoma (in contrast with the "associated" group) ought to be genetically distinct from an IPMN elsewhere in the gland. (5) "Intraductal spread of invasive carcinoma" (aka, "colonization") is recommended to describe lesions of invasive carcinoma invading back into and extending along the ductal system, which may morphologically mimic high-grade PanIN or even IPMN. (6) "Simple mucinous cyst" is recommended to describe cysts >1 cm having gastric-type flat mucinous lining at most minimal atypia without ovarian-type stroma to distinguish them from IPMN. (7) Human lesions resembling the acinar to ductal metaplasia and atypical flat lesions of genetically engineered mouse models exist and may reflect an alternate pathway of carcinogenesis; however, their biological significance requires further study. These revised recommendations are expected to improve our management and understanding of precursor lesions in the pancreas.

A novel deletion in the splice donor site of MLH1 exon 6 in a Japanese colon cancer patient with Lynch syndrome.

Lynch syndrome is an autosomal dominantly inherited disease that is characterized by a predisposition to cancers, mainly colorectal cancer. Germline mutations of DNA mismatch repair genes such as MLH1, MSH2, MSH6 and PMS2 have been described in patients with Lynch syndrome. Here, we report deletion of 2 bp in the splice donor site of the MLH1 exon 6 (c.545+4_545+5delCA) in a 48-year-old Japanese woman with Lynch syndrome. RT-PCR direct sequencing analysis revealed that this mutation led to an increase in the level of an MLH1 transcript in which exon 6 was skipped, and may cause a frameshift (p.E153FfsX8). Therefore, this mutation appears to be pathogenic and is responsible for Lynch syndrome. Additionally, analysis of the patient's tumor cells indicated microsatellite instability high phenotype and loss of the MLH1 and PMS2 proteins. To our knowledge, this is a germline splice site mutation of MLH1 that has not been reported previously.

A three-tier classification system based on the depth of submucosal invasion and budding/sprouting can improve the treatment strategy for T1 colorectal cancer: a retrospective multicenter study.

More than 85% of patients with T1 colorectal cancer have no lymph node metastasis and can be cured by endoscopic resection. To avoid unnecessary surgery after complete endoscopic resection, accurate histologic methods for evaluating resected specimens are needed to discriminate those at high risk for lymph node metastasis. A retrospective multi-institutional, cross-sectional study of 806 T1 colorectal cancer patients was conducted. A budding/sprouting score was incorporated for predicting lymph node metastasis in addition to other parameters, including the depth of submucosal invasion, histologic grade, and lymphovascular invasion. Lymph node metastasis was detected in 97 patients. Independent predictors of lymph node metastasis by multivariate analysis were depth of submucosal invasion ≥1000 µm (odds ratio (95% confidence interval)=5.56 (2.14-19.10)) and high-grade budding/sprouting (3.14 (1.91-5.21)). Among lesions with a depth of submucosal invasion ≥1000 µm, lymph node metastasis was detected in 59 (29%) of 207 patients with high-grade budding/sprouting, and in 34 (9%) of 396 with low-grade budding/sprouting. Lymph node metastasis was detected in only 4 (2%) of 203 lesions with a depth of submucosal invasion <1000 µm. Of these four tumors, three invaded lymphatic and/or venous vessels. Thus, the risk for lymph node metastasis can be classified into three groups: high risk with a depth of submucosal invasion ≥1000 µm and high-grade budding/sprouting, intermediate-risk with a depth of submucosal invasion ≥1000 µm and low-grade budding/sprouting, and low-risk with a depth of submucosal invasion <1000 µm. These findings revealed that a depth of submucosal invasion ≥1000 µm and high-grade budding/sprouting are powerful predictive parameters for lymph node metastasis in T1 colorectal cancer. This three-tier risk classification system will facilitate the decision for additional major surgery for T1 colorectal cancer patients after successful endoscopic treatment.

Determination of locations on a tactile sensor suitable for respiration and heartbeat measurement of a person on a bed.

Sleep monitoring systems that can be used in daily life for the assessment of personal health and early detection of diseases are needed. To this end, we are developing a system for unconstrained measurement of the lying posture, respiration and heartbeat of a person on a soft rubber-based tactile sensor sheet. The respiration and heartbeat signals can be detected from only particular locations on the tactile sensor, and the locations depend on the lying location and posture of the measured person. In this paper, we describe how to determine the measurement locations on the sensor. We also report a realtime program that detects the respiration rate and the heart rate by using this method.

Simple pathological examination technique for detection of cancer located at the surgical margin of the stomach.

BACKGROUND: The technique for examining surgical resection margins described in the Japanese Classification of Gastric Carcinoma is based on the examination of continuous infiltration by the primary tumor, and discontinuous lesions such as multiple cancers are not examined. However, examining lesions-particularly cancers-at the resection margins is important for the prevention of cancers in the remaining stomach that result from cancer remnants (remnant gastric cancer). METHODS: The clinical usefulness of a simple pathological examination technique for detecting cancer located at the surgical margin of the stomach was studied. A specimen 5-8 mm wide was resected from the surgical cut margin along the entire circumference of the stomach. When the pathological margin was positive for cancer, the surgical margin was also examined, and cases that were positive for cancer were regarded as marginally positive. RESULTS: Of the 1,498 patients with early gastric cancer who were examined using this method, 17 (1.1 %) were marginally positive for multiple cancers, and 8 of these 17 patients (57 %) had microcancers <5 mm in diameter. CONCLUSION: This method is simple and useful for detecting cancer involving the surgical margin, which occurs at a rate of 1.1 %, making it possible to prevent remnant gastric cancer by reoperation.

Multicenter study evaluating the clinical performance of the OSNA assay for the molecular detection of lymph node metastases in gastric cancer patients.

BACKGROUND: The accurate diagnosis of lymph node (LN) metastasis is important for making treatment decisions for gastric cancer patients. This multicenter study evaluated the clinical performance of the one-step nucleic acid amplification (OSNA) assay (Sysmex Corp.), an automated system that detects cytokeratin 19 (CK19) mRNA, in detecting LN metastases in gastric cancer patients. METHODS: LNs retrieved from patients who had undergone gastric cancer surgery at one of the four Japanese hospitals involved in this study were divided into blocks at 2-mm intervals. Alternate blocks were examined with the OSNA assay and the remaining blocks were assessed histologically. RESULTS: A total of 394 LNs from 61 patients were examined. The concordance rate between the OSNA assay and the histological examination was 0.942 (95 % CI, 0.914-0.963). Sensitivity and specificity of the OSNA assay compared to the histological examination were 0.833 (95 % CI, 0.707-0.921) and 0.959 (95 % CI, 0.932-0.977), respectively. Discordant results were observed in 23 LNs (5.8 %), and these were mainly the result of tissue allocation bias and/or low CK19 protein expression. CONCLUSION: The OSNA assay can detect lymph node metastases in gastric cancer patients as accurately as the histological examination of blocks sectioned at 2-mm intervals. The OSNA assay is a useful tool for the intraoperative diagnosis of LN metastasis in gastric cancer patients.

Acute life-threatening portal venous dilatation induced by a huge solitary fibrous tumor of the omentum.

An 85-year-old woman was referred to the medical oncology department because of a hypogastric mass. Contrast-enhanced CT showed a large hypervascular mass in the lower abdomen. CT angiography with volume rendering imaging revealed a vascular pedicle with an arborizing pattern of vessels. Many thick, early draining veins shunting into the portal vein were detected. Before surgery, the maximum size of the portal vein was 22 mm in diameter. Laparotomy revealed a huge, encapsulated, well-defined, hard tumor with hypervascularization, which was appended to the omentum. The mass with the omentum was curatively resected; it was 19 cm x 17 cm x 13 cm in size and 1915 g in weight. Histological features were consistent with a benign solitary fibrous tumor of the omentum, despite the tumor size and necrotic area found in the specimen. q Ultrasonography and CT performed at a 28-month follow-up revealed no evidence of tumor recurrence. Venous dilatation including that of the portal veins had diminished.

An optimal mRNA marker for OSNA (One-step nucleic acid amplification) based lymph node metastasis detection in colorectal cancer patients.

BACKGROUND: We previously reported that the one-step nucleic acid amplification assay is effective for lymph node metastasis detection in breast cancer patients. This paper describes the identification of CK19 mRNA as an optimal marker and its cut-off value for use in the detection of one-step nucleic acid amplification-based lymph node metastasis in colorectal cancer patients. METHODS: Candidate mRNA markers selected from the genome-wide expressed sequence tag database were evaluated by quantitative RT-PCR using a mixture of metastasis-positive and another mixture of metastasis-negative lymph nodes (n = 5 each), followed by quantitative RT-PCR using metastasis-positive and -negative lymph nodes (n = 10 each) from 20 patients. The one-step nucleic acid amplification assay for mRNA markers selected above was examined using 28 positive lymph nodes from 19 patients and 38 negative lymph nodes from the 11 pN0 patients. RESULTS: Quantitative RT-PCR analyses of the 98 mRNAs selected from the genome-wide expressed sequence tag database and the subsequent quantitative RT-PCR analyses of the nine mRNAs selected above indicated that CK19 and CEA mRNAs have the highest capability for distinguishing between positive and negative lymph nodes. CK19, CEA and CK20 mRNAs were evaluated by the one-step nucleic acid amplification assay. An area under a receiver-operating-characteristic curve for CK19 mRNA (0.999) was slightly larger than that for CEA mRNA (0.946; P = 0.062) and significantly larger that than for CK20 mRNA (0.875; P = 0.006). CONCLUSION: We found that CK19 mRNA has the best diagnostic performance and its cut-off value for discriminating positive from negative lymph nodes can be set in the range of 75-500 copies/µl with 96.4% sensitivity and 100% specificity.