Primary central nervous system other iatrogenic immunodeficiency-associated lymphoproliferative disorders presenting as extraosseous plasmacytoma with a progressive clinical course: A case report and literature review.

Other iatrogenic immunosuppressive-associated lymphoproliferative disorders (OIIA-LPDs) rarely occur in the central nervous system (CNS). Additionally, they almost always present as lymphoma and withdrawal by cessation of immunosuppressive treatment. We report a case of primary CNS OIIA-LPD that presented as extraosseous plasmacytoma (EP) with a progressive clinical course in spite of immunosuppressive treatment cessation. A 78-year-old man with a history of rheumatoid arthritis (RA) presented with a month-long headache. Magnetic resonance imaging showed mass lesions in the left temporal lobe, left middle fossa, and intradural cervical spine. The left temporal lesion was resected and diagnosed as EP histologically, and OIIA-LPD presented as plasmacytoma integrally due to his history of immunosuppressive treatment using tacrolimus for RA. Despite immunosuppressive treatment cessation, OIIA-LPD lesions did not regress but, on the contrary, showed a progressive clinical course. Considering his advanced age and renal dysfunction, postoperative treatment with radiation and moderate chemotherapy using prednisolone were administrated. Subsequently, the disease state stabilized, and the patient had a Karnofsky performance status score of 90 for 6 months; however, the tumor recurred with meningeal dissemination, and he died 8 months after treatment. Types of OIIA-LPD onset as EP and its progressive clinical course resistant to cessation of immunosuppressive treatment are rare. Moreover, this OIIA-LPD disease state worsened despite its radiosensitivity. We believe the progressive clinical course of this OIIA-LPD case with its high cell proliferation is similar to Epstein-Barr virus negative plasmablastic lymphoma, which could lead to a poor outcome.

[Successful treatment of pure red cell aplasia complicated by multicentric Castleman disease with prednisolone].

A 76-year-old man presented with shortness of breath and the laboratory tests suggested anemia and reticulocytopenia. CBC showed only anemia, and the bone marrow aspiration smear demonstrated absence of erythroid hematopoietic cells. Consequently, pure red cell aplasia (PRCA) was diagnosed. Computed tomography (CT) showed mediastinal multiple lymph node enlargement and ground-glass opacity in both the lung fields. Biopsy specimens of the mediastinal lymph node showed mild follicular hyperplasia and polyclonal plasma cells proliferation in the interfollicular area. These findings suggest idiopathic multicentric Castleman disease plasma cell type (iMCD PC type). Ciclosporin (CyA) was administered but there was no clinical improvement after 6 weeks of therapy. Therefore, prednisolone (PSL) was started at 0.5 mg/kg/day and was very effective for the PRCA and MCD. A total of 3 cases of CD (2 cases of MCD PC type and 1 case of CD HV type) with PRCA have been previously reported. In the 2 cases of MCD PC type, anemia was improved using PSL combination therapy. However, in the single case of CD HV type, PSL was not effective and anemia was improved with CyA treatment. This case suggests the possibility of using PSL as the first-line drug for MCD PC type with PRCA.

[Two Cases of HER2-Positive Gastric Cancer with Multiple Liver Metastases Leading to Conversion Therapy with Chemotherapy].

Case 1: A 69-year-old man underwent chemotherapy with capecitabine plus cisplatin plus trastuzumab to treat advanced gastric cancer that was diagnosed as cStage IV adenocarcinoma(T3N2M1[P0, CYX, H1]). After 12 courses, liver metastases were absent on computed tomography images. The patient underwent total gastrectomy with D2 lymphadenectomy. It has been 22 months since the patient had gastrectomy without recurrence of the cancer. Case 2: A 70-year-old man underwent chemotherapy with capecitabine plus cisplatin plus trastuzumab for treatment of advanced gastric cancer that was diagnosed as cStage IV adenocarcinoma(T4aN1M1[P0, CY0, H1]). After 12 courses, regrowth of multiple liver metastases led to a treatment with weekly paclitaxel plus trastuzumab as a second-line chemotherapy. After 9 courses of second-line chemotherapy, multiple liver metastases were absent in computed tomography images. The patient underwent total gastrectomy with D2 lymphadenectomy. A small white nodule on the surface of S2 and S3 of the liver led to the patient receiving a partial liver resection. The pathological finding of the resected liver specimen was a metastasis of an adenocarcinoma. During continuous chemotherapy with weekly paclitaxel plus trastuzumab after gastrectomy, multiple liver metastases were revealed. The patient died 19 months after gastrectomy.

Candidate selection for quadrant-based focal ablation through a combination of diffusion-weighted magnetic resonance imaging and prostate biopsy.

OBJECTIVES: To identify prostatic quadrants that could be preserved without intervention, using diffusion-weighted magnetic resonance imaging (DWI) and extended core biopsy, as a step toward implementation of quadrant-based focal ablation with potential preservation of erectile and ejaculatory functions, based on comparisons with unilateral hemi-gland ablation. PATIENTS AND METHODS: We conducted a prebiopsy DWI study including 648 quadrants in 162 men who underwent 14-core biopsy including anterior sampling and radical prostatectomy (RP) for localised cancer. Imaging and pathology were analysed on a quadrant basis. Each quadrant was assessed through four-core sampling. Predictive performance of DWI and biopsy for quadrant status was analysed. RESULTS: On RP specimens, 170 anterior (52.5%) and 172 posterior quadrants (53.1%) harboured significant cancer. Negative predictive values of DWI, biopsy, and their combination for significant cancer were 79.7%, 70.6%, and 91.1%, respectively, in anterior quadrants, and 78.5%, 81.3%, and 91.7%, respectively, in posterior quadrants. DWI incrementally improved the negative predictive values of biopsy in anterior (P < 0.001) and posterior quadrants (P = 0.025), without untoward impacts on positive predictive values. Negative findings on both DWI and biopsy were identified in posterior quadrants of 109 sides (33.6%), but in entire hemi-glands of 54 sides (16.7%). CONCLUSIONS: The combination of DWI and 14-core biopsy including anterior sampling efficiently identifies quadrants without significant cancer in men with localised prostate cancer; the remaining quadrants, therefore, could be potential candidate areas for focal ablation. Focal therapy designed based on quadrant-based assessment could be superior to unilateral hemi-gland ablation for preservation of posterior quadrants and retaining of sexual function in more sides.

A Simple Index to Predict Liver Functional Reserve after Hepatectomy.

BACKGROUND/AIMS: It is difficult to estimate the functional reserve of the liver required for safe hepatectomy in patients with severe chronic liver disease The aim of this study was to retrospectively construct simple model based on routine laboratory data to predict both early liver failure (ELF) and mortality from recurrence-free liver failure (MLF) as an index for late liver failure after hepatectomy. METHODOLOGY: Between 2000 and 2004, 196 consecutive patients underwent curative hepatectomy, and data from 127 minor hepatectomies were included in this study. RESULTS: Mean survival time was [mean (SD)] 1252 (670) days after hepatectomy. ELF and MLF were observed in 29 and 13 patients, respectively. PT%, TB, and direct bilirubin (DB) were the best predictors in patients with both ELF and MLF. PT% alone was the best predictor of ELF and MLF with area under ROC curves of 0.70 and 0.81, respectively. By using a preoperative PT% of ≤ 70, we could accurately predict ELF and MLF in 77% and 87% of patients, respectively. ICG-R15 could not accurately predict both ELF and MLF for any cut-off values. CONCLUSIONS: Unlike ICG-R15, PT% is a simple noninvasive index for estimating liver functional reserve to predict both ELF and MLF.

Non-human primate model of amyotrophic lateral sclerosis with cytoplasmic mislocalization of TDP-43.

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by progressive motoneuron loss. Redistribution of transactive response deoxyribonucleic acid-binding protein 43 from the nucleus to the cytoplasm and the presence of cystatin C-positive Bunina bodies are considered pathological hallmarks of amyotrophic lateral sclerosis, but their significance has not been fully elucidated. Since all reported rodent transgenic models using wild-type transactive response deoxyribonucleic acid-binding protein 43 failed to recapitulate these features, we expected a species difference and aimed to make a non-human primate model of amyotrophic lateral sclerosis. We overexpressed wild-type human transactive response deoxyribonucleic acid-binding protein 43 in spinal cords of cynomolgus monkeys and rats by injecting adeno-associated virus vector into the cervical cord, and examined the phenotype using behavioural, electrophysiological, neuropathological and biochemical analyses. These monkeys developed progressive motor weakness and muscle atrophy with fasciculation in distal hand muscles first. They also showed regional cytoplasmic transactive response deoxyribonucleic acid-binding protein 43 mislocalization with loss of nuclear transactive response deoxyribonucleic acid-binding protein 43 staining in the lateral nuclear group of spinal cord innervating distal hand muscles and cystatin C-positive cytoplasmic aggregates, reminiscent of the spinal cord pathology of patients with amyotrophic lateral sclerosis. Transactive response deoxyribonucleic acid-binding protein 43 mislocalization was an early or presymptomatic event and was later associated with neuron loss. These findings suggest that the transactive response deoxyribonucleic acid-binding protein 43 mislocalization leads to α-motoneuron degeneration. Furthermore, truncation of transactive response deoxyribonucleic acid-binding protein 43 was not a prerequisite for motoneuronal degeneration, and phosphorylation of transactive response deoxyribonucleic acid-binding protein 43 occurred after degeneration had begun. In contrast, similarly prepared rat models expressed transactive response deoxyribonucleic acid-binding protein 43 only in the nucleus of motoneurons. There is thus a species difference in transactive response deoxyribonucleic acid-binding protein 43 pathology, and our monkey model recapitulates amyotrophic lateral sclerosis pathology to a greater extent than rodent models, providing a valuable tool for studying the pathogenesis of sporadic amyotrophic lateral sclerosis.

New-onset minimal change disease following the Moderna COVID-19 vaccine.

We report the case of nephrotic syndrome after COVID-19 vaccination. The patient was a man in his 30s with no comorbidities other than atopic dermatitis. Over the course of 2 weeks after the first COVID-19 vaccination, systemic oedema gradually appeared. He was referred to the nephrology department for investigation of the systemic oedema. On admission, he presented with pitting oedema in his lower extremities. Initial examinations revealed massive urinary protein and decreased serum albumin, at 13.9 g/g Cr and 1.5 g/dL, respectively. Renal biopsy was performed, and minimal change disease was diagnosed. Prednisolone 60 mg/day was promptly started on the 5th day of hospitalisation, and complete remission was achieved on the 12th day. Prednisolone was once tapered off in 1.5 years successfully though minimal change disease was relapsed in 1 month after the steroid withdrawal.

Clinicoradiological course of abemaciclib-induced pneumonitis with histology findings.

A woman in her late 40s presented with multiple abnormal shadows on high-resolution CT (HRCT), was treated with abemaciclib for recurrent right breast cancer post-surgery and chemoradiation therapy. During the 10-month chemotherapy, HRCT revealed a recurrent pattern of a partly appearing and disappearing organising pneumonia pattern without clinical symptoms. Bronchoalveolar lavage analysis revealed lymphocytosis, while transbronchial lung biopsy revealed alveolitis with epithelial cell injury. Based on the diagnosis of drug-induced pneumonitis due to abemaciclib, the discontinuation of abemaciclib and administration of prednisolone were effective. Abnormal shadow on HRCT disappeared gradually, while elevated Krebs von den Lungen (KL)-6 and surfactant protein (SP)-D levels were restored to normal range. This is the first case report of abemaciclib-induced pneumonitis with histology findings. Since the severity of abemaciclib-induced pneumonitis ranges from mild to fatal, regular monitoring of pneumonitis with radiography, HRCT, and measurement of KL-6 and SP-D levels should be considered.

Extended biopsy based criteria incorporating cumulative cancer length for predicting clinically insignificant prostate cancer.

UNLABELLED: What's known on the subject? and What does the study add? The criteria used for selecting patients with prostate cancer for active surveillance (AS) are still not satisfactory due to the difficulty in predicting the significance of the prostate cancer. Urologists could predict insignificant prostate cancer by incorporating cumulative cancer length and biopsy Gleason score, derived from extended biopsy. The present study has added new criteria for predicting insignificant prostate cancer, which would lead to a better selection of candidates for AS. OBJECTIVE: • To develop extended biopsy based criteria for predicting insignificant cancer (IC) using extended biopsy findings. PATIENTS AND METHODS: • From 2000 to 2009, 1575 patients with prostate cancer were primarily treated by radical prostatectomy in two referral hospitals. • Of these, the study cohort comprised 499 patients with extended biopsy confirmed, clinically organ-confined (cT1-2N0M0) prostate cancer with PSA levels of <20 ng/mL. • Cancer information obtained through extended biopsy included cumulative cancer length (CCL) divided by the number of biopsy cores (CCL/core). RESULTS: • Pathological examination revealed 39 ICs (7.8%). All these ICs fell in a category of prostate cancer with clinical stage ≤ T2a and 2005 International Society of Urological Pathology Consensus Conference (ISUP) modified biopsy Gleason score ≤ 7. • Accordingly, we analysed predictors of IC in a subset cohort of 370 patients in this category. A multivariate logistic regression analysis revealed that 2005 ISUP modified biopsy Gleason score and CCL/core were independently significant predictors of IC. • We determined a threshold value of CCL/core of 0.20 mm for predicting IC using receiver operating characteristic analysis. • Based on these findings, we developed simple extended biopsy based criteria for predicting IC as follows: (i) PSA level of <20 ng/mL; (ii) Clinical stage ≤ T2a; (iii) 2005 ISUP modified biopsy Gleason score ≤ 6; (iv) CCL/core of <0.20 mm. • The specificity of the criteria was 91%, which was significantly higher than the value from a subset of criteria without item iv (P < 0.001). CONCLUSION: • We have developed extended biopsy based criteria for predicting IC incorporating the 2005 ISUP modified biopsy Gleason score and CCL/core.

Prognoses of GEP-NETS with undetermined malignant potentials of their primary sites.

BACKGROUND/AIMS: In gastroenteropancreatic neuroendocrine tumors (GEP-NETs), primary lesions cannot be resected when the patients have highly advanced disease or when the primary sites are undefined. Such GEP-NETs cannot be evaluated with Ki-67 or the mitotic index. The aim of this study was to examine the prognosis of GEP-NETs that were ungraded by WHO G1-3 grading (U-NET group). METHODOLOGY: Between 2000 and 2011, 75 patients with sporadic GEP-NETs were treated at our institution. The prognosis of patients graded as new WHO grading (G-NET group) was compared with that of the U-NET group. Cox proportional hazard regression analyses were performed to estimate the risk factors for overall survival (OS). RESULTS: Overall 1-, 3- and 5-year survival rates were 90.7%, 79.9% and 74.9%, respectively. The odds ratio (OR) of patients with synchronous liver metastasis and U-NET was 1.73 (p=0.01) and 5.84 (p=0.002), respectively. Multivariate analyses of OS according to baseline characteristics revealed the only independent risk factor to be U-NET (OR, 3.95; p=0.02). CONCLUSIONS: The malignant potential of U-NET may be no less than that of G-NET, while WHO-G3 patients have the worst prognoses in the G-NET group.

The importance of clinical information in patients with gastroenteropancreatic neuroendocrine tumor.

BACKGROUND/AIMS: The WHO 2010 grading system for gastroenteropancreatic neuroendocrine tumors(GEP-NETs) is used to evaluate the malignant potential without clinicopathological information. This study was conducted to examine whether the new index is superior to the previous WHO 2004 classification, e.g.for well-differentiated endocrine carcinoma (WEC),involving clinical information. METHODOLOGY: Between 2000 and 2011, 77 patients with sporadic GEP-NETs were treated at our institution and statistically estimated risk factors for overall survival (OS) were evaluated. Cox proportional hazards regression analyses were performed to estimate risk factors for OS. RESULTS: Overall 1-, 3- and 5-year survival rates were 92.8%, 78.4% and 76.0%, respectively. Median OS was 551 days in WEC-patients (odds ratio (OR)for OS=13.1, 95% confidence interval (CI)=2.90-59.5;p=0.001). The median OS was 813 days in G3-patients as compared with 1885 days in G1/G2-patients(OR for OS= 2.64, p=0.002). Multivariate analyses according to baseline characteristics revealed WEC as independent risk factor (OR=9.06, p=0.01). WEC was the only predictor of prognosis with an area under the receiver operating characteristic curves of 0.78(p=0.001). CONCLUSIONS: Clinical information was the best predictor for the prognosis of NETs.

Progression of ulcerative colitis following diversion colitis.

Diversion colitis and ulcerative colitis (UC) can be caused by different mechanisms; however, several case reports have described the development of typical UC following diversion colitis. A 63-year-old man underwent Hartmann's operation following a diagnosis of perforation of a sigmoid colon diverticulum and peritonitis. Stoma closure was performed 4 months later, and the portion of the sigmoid colon with the diverticulum was unintentionally left as a blind end. Following stoma closure, hematochezia worsened, and he was diagnosed as having developed diversion colitis only in the blind sigmoid colon. Intermittent use of topical mesalazine enemas controlled the bowel symptoms; however, 4 years after the stoma closure, bloody stools were observed again. Colonoscopy revealed coarse and friable granular mucosa with adherent mucopurulent exudate in the rectum, and mucosal erythematous edema with adherent mucopurulent exudate in the blind sigmoid colon. The histological findings indicated basal plasmacytosis, and goblet cell depletion and cryptitis in the lamina propria, which is characteristic of UC. To the best of our knowledge, this is the fourth description of a patient who developed UC following diversion colitis. Local inflammation may have triggered the development of UC through hematogenous or lymphogenous circulation of lymphocytes or autoantibodies.

Prostate Cancer Associated with Minimal Change Disease: A Case Report.

Introduction: Minimal change disease (MCD), a common cause of primary nephrotic syndrome that accounts for 10%-15% of all primary nephrotic syndrome cases in adults, is frequently associated with malignant lymphoma. However, studies on MCD associated with prostate cancer are scarce. Case Presentation: A 73-year-old male with prostate cancer was referred to our department with hypoalbuminemia and severe proteinuria while waiting for prostatectomy. We diagnosed the patient with nephrotic syndrome and performed a renal biopsy. Renal pathological findings were consistent with those of MCD. The clinical course suggested an association between prostate cancer and MCD as our patient achieved complete remission of MCD after receiving androgen deprivation and radiation therapy for prostate cancer without the use of glucocorticoids or other immunosuppressants. Discussion: Although MCD can be associated with solid tumors, MCD associated with prostate cancer is very rare. The current case is the first to directly raise the possibility that secondary MCD may develop due to prostate cancer in some patients.

An integrated approach of differential mass spectrometry and gene ontology analysis identified novel proteins regulating neuronal differentiation and survival.

MS-based quantitative proteomics is widely used for large scale identification of proteins. However, an integrated approach that offers comprehensive proteome coverage, a tool for the quick categorization of the identified proteins, and a standardized biological study method is needed for helping the researcher focus on investigating the proteins with biologically important functions. In this study, we utilized isobaric tagging for relative and absolute quantification (iTRAQ)-based quantitative differential LC/MS/MS, functional annotation with a proprietary gene ontology tool (Molecular Annotation by Gene Ontology (MANGO)), and standard biochemical methods to identify proteins related to neuronal differentiation in nerve growth factor-treated rat pheochromocytoma (PC12) cells, which serve as a representative model system for studying neuronal biological processes. We performed MS analysis by using both nano-LC-MALDI-MS/MS and nano-LC-ESI-MS/MS for maximal proteome coverage. Of 1,482 non-redundant proteins semiquantitatively identified, 72 were differentially expressed with 39 up- and 33 down-regulated, including 64 novel nerve growth factor-responsive PC12 proteins. Gene ontology analysis of the differentially expressed proteins by MANGO indicated with statistical significance that the up-regulated proteins were mostly related to the biological processes of cell morphogenesis, apoptosis/survival, and cell differentiation. Some of the up-regulated proteins of unknown function, such as PAIRBP1, translationally controlled tumor protein, prothymosin alpha, and MAGED1, were further analyzed to validate their significant functions in neuronal differentiation by immunoblotting and immunocytochemistry using each antibody combined with a specific short interfering RNA technique. Knockdown of these proteins caused abnormal cell morphological changes, inhibition of neurite formation, and cell death during each course of the differentiation, confirming their important roles in neurite formation and survival of PC12 cells. These results show that our iTRAQ-MANGO-biological analysis framework, which integrates a number of standard proteomics strategies, is effective for targeting and elucidating the functions of proteins involved in the cellular biological process being studied.

Diagnostic significance of fat globules in blood in fulminant-type fat embolism syndrome.

Fat globule detection in the blood in fat embolism syndrome (FES) diagnosis remains controversial. This case illustrates two life-threatening, possibly FES-related, episodes with dramatic increases in blood fat globule level. Future studies should aim at evaluating the significance of the quantitative changes in blood fat levels in diagnosing FES.

A case of ramucirumab-induced renal failure with nephrotic-range proteinuria and its pathological findings.

Ramucirumab-induced renal dysfunction is rarely reported. The pathology of ramucirumab-associated nephropathy in past reports primarily shows thrombotic microangiopathy (TMA) lesions but podocytopathy is not yet known. We report a case of kidney injury induced by ramucirumab in a 71-year-old man with cecal cancer. He was referred to our department for increasing serum creatinine (Cr) levels from 1.08 mg/dL to 2.56 mg/dL after changing anticancer drugs from bevacizumab to ramucirumab. He showed nephrotic-range proteinuria (12.1 g/gCr). A renal biopsy revealed endothelial cell injuries, such as TMA and podocytopathy with epithelial cell hyperplasia, which looked like a crescent. After discontinuing ramucirumab, his renal function and proteinuria improved, as seen by his Cr levels and proteinuria which decreased to 1.74 mg/dL and 1.21 g/gCr, respectively, in 3 months. Unlike previous reports, we found that ramucirumab caused podocyte injuries.

Cervical cancer of the uterus complicated by renal AA amyloidosis.

Cervical cancer of the uterus rarely develops systemic secondary amyloidosis. We present the case of a 66-year-old female patient who manifested systemic amyloid A (AA) amyloidosis in the kidney, digestive tract, and cervix of the uterus, secondary to cervical cancer. She exhibited nephrotic syndrome, intractable diarrhea, and mild fever 3 months after she underwent an extended hysterectomy with postoperative cisplatin-based chemotherapy and whole pelvic irradiation. Further examinations revealed AA amyloidosis of the kidney and colon and cytomegalovirus infection in the colon. AA amyloid deposition was positive in the resected tissues of uterine cancer. The patient was diagnosed with systemic AA amyloidosis consecutive to cervical cancer. Despite a decrease in urinary protein after antiviral therapy, it increased 14 months later with neither apparent symptoms nor an increase in tumor marker. A second renal biopsy revealed AA amyloidosis of the kidney. Subsequent investigations revealed the recurrence of cervical cancer in the lung, liver, and lymph nodes. This case report indicated that AA amyloidosis would complicate cervical cancer and recur even after resection of neoplasm owing to other stimulation. Moreover, urine protein could be a marker for cancer relapse in known cases of cancer-derived AA amyloidosis.

IDH-Mutant Astrocytoma With Chromosome 19q13 Deletion Manifesting as an Oligodendroglioma-Like Morphology.

Partial deletions in chromosomes 1p and 19q are found in a subset of astrocytic tumors; however, it remains unclear how these alterations affect their histological features and prognosis. Herein, we present 3 cases of isocitrate dehydrogenase (IDH)-mutant astrocytoma with chromosome 19q13 deletion. In the first case, the primary tumor harbored an IDH1 mutation with chromosome 1p/19q partial deletions, which covered 19q13 and exhibited a durable initial response to radiotherapy and temozolomide (TMZ) treatment. However, the tumor lost the chromosome 1p/19q partial deletions at recurrence and became resistant to TMZ. Histologically, an oligodendroglioma-like feature was found in the primary tumor but not in the recurrent tumor. Capicua transcriptional repressor (CIC), located on 19q13, was less expressed in the primary tumor but was highly expressed in the recurrent tumor. Similar histological findings were observed in 2 other astrocytic tumors with IDH1 or IDH2 mutations. These tumors also had chromosome 19q13 deletion, including the CIC gene, weakly expressed CIC, and oligodendroglioma-like morphology. These tumors recurred at 6 and 32 months, respectively. These findings suggest that IDH-mutant astrocytoma with chromosome 19q13 partial deletion, including the CIC gene, may induce an oligodendroglioma-like phenotype, but the clinical prognosis may not be similar to that of genetically defined oligodendroglioma.

Engrailed Homeobox 1 and Cytokeratin 19 Are Independent Diagnostic Markers of Eccrine Porocarcinoma and Distinguish It From Squamous Cell Carcinoma.

OBJECTIVES: The diagnostic utility of En1 in the histopathologic differentiation of eccrine porocarcinoma (EPC) from invasive squamous cell carcinoma (SCC) was investigated. METHODS: Expression of En1 and CK19 in 16 cases of EPC was immunohistochemically examined and compared with that in 32 cases of SCC. RESULTS: In all 16 EPCs, En1 was expressed in 3% to 100% of tumor cells. In 20 of the 32 SCCs, En1 was expressed in 3% to 90% of tumor cells. A total of 13 of the 16 EPCs and five of the 32 SCCs were judged as En1 positive, with a cutoff value of 25%. In addition, 11 of the 16 EPCs and four of the 32 SCCs were CK19 positive. The frequencies of En1- and CK19-positive cases were significantly higher in EPCs than in SCCs. In a logistic regression analysis for predicting EPC, En1 and CK19 were independent markers. When expression patterns of En1 and CK19 were combined, none of the 32 SCCs was both positive. In contrast, 15 of the 16 EPCs were positive for either En1 or CK19. CONCLUSIONS: A combination of En1 and CK19 expression can improve the accuracy of histologic diagnosis of EPC.

Pancreas-specific aquaporin 12 null mice showed increased susceptibility to caerulein-induced acute pancreatitis.

Aquaporin 12 (AQP12) is the most recently identified member of the mammalian AQP family and is specifically expressed in pancreatic acinar cells. In vitro expression studies have revealed that AQP12 is localized at intracellular sites. To determine the physiological roles of AQP12 in the pancreas, we generated knockout mice for this gene (AQP12-KO). No obvious differences were observed under normal conditions between wild-type (WT) and AQP12-KO mice in terms of growth, blood chemistry, pancreatic fluid content, or histology. However, when we induced pancreatitis through the administration of a cholecystokinin-8 (CCK-8) analog, the AQP12-KO mice showed more severe pathological damage to this organ than WT mice. Furthermore, when we analyzed exocytosis in the pancreatic acini using a two-photon excitation imaging method, the results revealed larger exocytotic vesicles (vacuoles) in the acini of AQP12-KO mice at a high CCK-8 dose (100 nM). From these results, we conclude that AQP12 may function in the mechanisms that control the proper secretion of pancreatic fluid following rapid and intense stimulation.