Evaluation of (R)-[11C]PK11195 PET/MRI for Spinal Cord-Related Neuropathic Pain in Patients with Cervical Spinal Disorders.

Activated microglia are involved in secondary injury after acute spinal cord injury (SCI) and in development of spinal cord-related neuropathic pain (NeP). The aim of the study was to assess expression of translocator protein 18 kDa (TSPO) as an indicator of microglial activation and to investigate visualization of the dynamics of activated microglia in the injured spinal cord using PET imaging with (R)-[11C]PK11195, a specific ligand for TSPO. In SCI chimeric animal models, TSPO was expressed mainly in activated microglia. Accumulation of (R)-[3H]PK11195 was confirmed in autoradiography and its dynamics in the injured spinal cord were visualized by (R)-[11C]PK11195 PET imaging in the acute phase after SCI. In clinical application of (R)-[11C]PK11195 PET/MRI of the cervical spinal cord in patients with NeP related to cervical disorders, uptake was found in cases up to 10 months after injury or surgery. No uptake could be visualized in the injured spinal cord in patients with chronic NeP at more than 1 year after injury or surgery, regardless of the degree of NeP. However, a positive correlation was found between standardized uptake value ratio and the severity of NeP, suggesting the potential of clinical application for objective evaluation of chronic NeP.

18F-Fluoroestradiol Tumor Uptake Is Influenced by Structural Components in Breast Cancer.

PURPOSE: Estrogen receptor (ER) is expressed in the majority of invasive breast cancer and is an important prognostic indicator. The tumor stroma also plays an important role in disease progression. This study evaluated the effect of stromal components on 16α-[18F]-fluoro-17ß-estradiol (18F-FES) uptake in breast cancer and proposed a partial-volume correction method for 18F-FES PET based on histopathological analyses. PATIENTS AND METHODS: Fifteen patients with biopsy-confirmed breast cancer underwent preoperative 18F-FES PET. Estrogen receptor expression in biopsy specimens was assayed by immunohistochemistry, cellular components in surgical specimens were measured using hematoxylin-eosin staining, and nuclear components in surgical and biopsy specimens were measured using Azan-Mallory staining. The relationship between 18F-FES SUV of the primary tumor and histopathological findings including ER expression, the Allred score, ER-positive cellular component ratio, and ER-positive nuclear component ratio (NCR) was examined. The relationship between stroma-free 18F-FES SUV and ER expression was also examined. RESULTS: 18F-FES uptake was not significantly positively correlated with ER expression (r = 0.44, P = 0.10). 18F-FES uptake was significantly correlated with the Allred score, ER-positive cellular component ratio, and ER-positive NCR in surgical specimens (ρ = 0.60, P = 0.02; r = 0.55, P = 0.03; and r = 0.65, P = 0.01, respectively). 18F-FES uptake was predominantly correlated with ER-positive NCR in biopsy specimens (r = 0.84, P < 0.001). Stroma-free 18F-FES SUV was significantly correlated with ER expression (r = 0.78, P < 0.01). CONCLUSIONS: 18F-FES PET predominantly demonstrates the level of ER expression in breast cancer cell nucleus. Although tumor 18F-FES uptake is affected by the degree of stromal components, the partial volume effect on the uptake can be corrected by stroma-volume fraction in Azan-Mallory staining.

Does cellular senescence play an important role in the prognosis of sarcomatoid carcinoma of the pancreas?

AIM: Sarcomatoid carcinoma of the pancreas (SCP) is an extremely rare and aggressive disease with poor prognosis. We have already reported a rare case of SCP with long-term survival. In the present article, we investigate the underlying mechanisms of patient's long-term survival from the point of view of cellular senescence which was examined in three SCP cases, including our reported case, using immunohistochemical analysis. FINDINGS: The expressions of cellular senescence marker were observed in the sarcomatous component of the patient with long-term survival but not observed in the other patients with short- term survival. Thus, we can speculate that cellular senescence might play an important role in the reduction of the cell proliferative and metastatic activities of sarcomatous cells, leading to long-term patient survival.

Heterotopic ossification in lymph node metastasis after rectal cancer resection: a case report and literature review.

BACKGROUND: Heterotopic ossification (HO) is the formation of osseous tissue outside the skeleton. HO in malignant tumors of the digestive tract is extremely rare, as is ossification in metastatic lesions from HO-negative digestive tract tumors. Regarding the pathogenesis of HO, two theories have been proposed. The first is that the osteoblastic metaplasia of tumor cells (driven by the epithelial-mesenchymal transition, EMT) results in HO, and the second is that factors secreted by cancer cells lead to the metaplasia of stromal pluripotent cells into osteoblasts. However, the osteogenic mechanisms remain unclear. CASE PRESENTATION: An 83-year-old Japanese woman underwent low anterior rectal resection for rectal cancer before presentation at our institution, in June 2018. The final diagnosis was stage IIB rectal adenocarcinoma (T4aN0M0). Histological examination did not reveal HO in the primary tumor. Thirteen months after the operation, a solitary metastatic lesion in the brain 20 mm in size and a solitary metastatic lesion in a right axillary lymph node 20 mm in size were diagnosed. The patient was treated with gamma-knife therapy for the brain metastasis. One month later, she was referred to our institution. She underwent lymph node resection. Histological examination revealed that most portions of the affected lymph node were occupied by metastatic tumor cells and that central necrosis and four small ossified lesions without an osteoblast-like cell rim were present in the peripheral region. Immunohistochemical analysis showed tumor cells positive for BMP-2, osteonectin, osteocalcin, AE1/AE3, TGF-ß1, Gli2, Smad2/3, and CDX2 and negative for nestin, CD56, and CK7. CONCLUSION: This is the first English case report of HO in a metachronous metastatic lymph node after the curative resection of HO-negative rectal cancer. Unlike HO lesions in past reports, the HO lesion did not show peripheral osteoblast-like cells, and the immunohistochemical findings indicated that the present case resulted from the EMT.

An autopsy case of tuberculous meningitis undiagnosed by nested-PCR of CSF samples and brain biopsy.

Nested polymerase chain reaction (PCR) testing of cerebrospinal fluid (CSF) has higher diagnostic sensitivity with regard to tuberculous meningitis (TBM) than conventional methods. Herein we describe the autopsy case of a 70-year-old woman with TBM that could not be diagnosed via nested PCR in CSF, even though it was performed three times. The clinical course, magnetic resonance imaging results, and elevated adenosine deaminase levels in CSF were consistent with TBM. We also performed a brain biopsy from the thickened leptomeninges of the patient, which showed granulomatous leptomeningitis consistent with TBM. However, we were not able to identify tuberculous bacilli by the acid-fast bacterial staining, single PCR test, and culture of the biopsy preparations. We finally diagnosed TBM in this case by the positive results of both the fourth PCR test and culture of her CSF, which were taken 7 days before her death. This case suggests that even the combination of repetitive nested PCR in CSF and brain biopsy lacks adequate sensitivity to exclude TBM in some patients.

Capillary hemangioma arising from the lesser omentum in an adult: A case report.

RATIONALE: Although capillary hemangiomas, common lesions involving the proliferation of small capillary vessels and a single layer of endothelial cells, can arise in any organ, they are rarely reported in the greater or lesser omentum. Here in, we report a case of capillary hemangioma arising from the lesser omentum in an adult with interesting diagnostic imaging findings, including changes in tumor size over time on computed tomography (CT), that was resected using laparoscopic surgery. To our knowledge, this is the first English report to describe a capillary hemangioma arising from the lesser omentum. PATIENT CONCERNS: A 63-year-old Japanese man received hemodialysis for chronic renal failure due to diabetic nephropathy, and a small, gradually enlarging tissue mass was found near the lesser curvature of the stomach on plain CT performed annually, without any associated complaints. Diagnostic imaging revealed an 18 × 15-mm tumor with a homogenous, highly enhanced effect in the early phase that was attenuated but prolonged in the delayed phase. Magnetic resonance imaging showed a mass with low signal intensity on T1-weighted imaging and relatively high signal intensity on T2-weighted imaging. DIAGNOSIS: The patient was diagnosed with capillary hemangioma arising from the lesser omentum according to the pathological and immunohistological findings. INTERVENTIONS: The patient underwent laparoscopy for excision of the tumor from the lesser omentum. OUTCOMES: At the 1 year follow-up, the patient had no recurrence of the tumor. LESSONS: We describe the first case worldwide of capillary hemangioma that was a true vascular tumor arising from the lesser omentum. Although capillary hemangioma arising from the lesser omentum is extremely rare, it should be considered in the differential diagnosis of patients presenting with a highly enhanced lesser omental tumor, and laparoscopy can be safely applied for the excision of this tumor.

Favorable response of colonic mixed adenoneuroendocrine carcinoma to streptozocin monotherapy.

Mixed adenoneuroendocrine carcinoma (MANEC) of the colon is rare and has a poor prognosis. Here, we report a case of MANEC in the ascending colon, in which streptozocin monotherapy achieved a partial response. A 36-year-old woman underwent right hemicolectomy for colonic polyposis, which included ascending colon cancer. Pathological examination revealed that some mucosal polyps were adenocarcinoma while one submucosal polyp was neuroendocrine carcinoma. Adjuvant chemotherapy was not administered, and 5 months after the operation, multiple liver metastases were identified. She was started on modified (5-FU, leucovorin, oxaliplatin) followed by XELOX (capecitabine, oxaliplatin) plus bevacizumab. Although these regimens helped achieve stable disease, computed tomography showed that the hepatic metastatic lesions had enlarged 4 months later. Subsequently, the regimen was changed to streptozocin monotherapy (1000 mg/m2, weekly). After 5 cycles, the regimen achieved partial response and was continued for a total of 17 courses without significant adverse events until progressive disease. As a third-line chemotherapy regimen, cisplatin plus etoposide (EP) was administered. The EP regimen reduced the size of the hepatic and ovarian metastatic lesions but severe neutropenia and anemia was observed. Amrubicin monotherapy was also administered as fourth-line chemotherapy but a good clinical response was not detected, and the patient died 20 months after the operation. Streptozocin monotherapy has the potential to be a therapeutic option for mixed adenoneuroendocrine carcinoma of the colon.

Utility of postmortem imaging system for anatomical education in skull base surgery.

Although cadaver dissections are important for skull base surgeons to acquire anatomical knowledge and techniques, their opportunities are limited in Japan. The Autopsy Imaging Center of the University of Fukui Hospital has both a CT scanner and an MR unit solely for deceased patients. The authors applied the postmortem imaging to cadaver dissections and evaluated its usefulness in surgical education. Ten sides of five formalin-fixed cadaver heads were dissected by ten neurosurgeons. Five neurosurgeons were young, three were moderately experienced, and two were experts in skull base surgery. They performed orbitozygomatic, anterior transpetrosal, posterior transpetrosal, and transcondylar approaches. CT bone images were taken before and after dissections, and MR images were taken before dissection to merge with the CT bone images. The usefulness of the images for each neurosurgeon and for each skull base approach was evaluated. The postmortem imaging system was useful for all neurosurgeons, especially in anterior transpetrosal, posterior transpetrosal, and transcondylar approaches. They could find the insufficiency or excessiveness of their drilling of specific bony structures with the images. Even the experts in skull base surgery could identify regions in which they could add drilling safely to widen the surgical field more. The postmortem imaging system was useful for skull base cadaver dissections. This system is expected to be utilized for education and research on surgical anatomy.

Risk factor analysis for bone marrow histiocytic hyperplasia with hemophagocytosis: an autopsy study.

The excessive release of inflammatory cytokines occasionally induces life-threatening hemophagocytosis referred to as hemophagocytic syndrome (HPS). A similar condition, histiocytic hyperplasia with hemophagocytosis (HHH), is often seen in bone marrow collected during autopsy. Unlike HPS, the pathogenesis of HHH remains unclear. Therefore, we performed a clinicopathological analysis of HHH from 70 autopsy cases at the University of Fukui Hospital. HHH was detected in 29 of 70 autopsies (41.4 %) and was significantly complicated with hematological diseases (p < 0.05) and sepsis (p < 0.05). The percentage of macrophages in bone marrow (BM) nucleated cells was significantly increased in HHH (p < 0.001). Data from medical records indicated no significant changes, except for the minimum values of white blood cell counts (p < 0.05) and platelet counts (p < 0.05) in HHH patients as compared with non-HHH patients. Concentrations of inflammatory mediators including IL-1ß, IL-6, and IL-8 were significantly increased in HHH patients. Multivariate risk factor analysis identified hematological diseases (odds ratio (OR), 11.71), ≥ 15 % BM macrophages (OR, 9.42), sepsis (OR, 7.77), and high serum IL-6 levels (OR, 1.00) as independent risk factors for HHH. HHH with hypocellular BM, the most aggressive form of HHH, was recognized in 8 of 29 HHH patients and was associated with ≥ 25 % BM macrophages (p < 0.001), leukocytopenia (p < 0.05), and high IL-8 levels (p < 0.05). None of the HHH patients fulfilled the diagnostic criteria of HPS. These findings suggest that HHH is a different entity from HPS and that it preferentially develops under conditions of excessive inflammation and its associated risks, such as hematological diseases and sepsis.

Should prophylactic thrombolysis be routine in clinical practice? Evidence from an autopsy case of septicemia.

BACKGROUND: Central venous catheters provide easy access for intravenous infusion and nutrition, but they can bring about complications such as catheter-related infections. Infected central venous catheters often cause nosocomial bloodstream infections with high morbidity and mortality. However, most of the morphological data that have been published are derived from in vitro and in vivo studies and few reports of direct evidence obtained from patient-derived samples have been described. Here we present visual evidence of catheter-related candidemia. To our knowledge, this is the first reported conventional histopathological evidence of a Candida-infected intraluminal thrombus in a patient's central venous catheter. CASE PRESENTATION: A 62-year-old Japanese female with obstructive jaundice, gastrointestinal bleeding, and liver metastasis from pancreatic head cancer was given an implantable subcutaneous central venous port for nutrition and chemotherapy administration. High fever ensued on day 16 after the central venous port insertion and blood cultures revealed Candida albicans. Although the patient was given 300 mg/day of fosfluconazole according to the suggestion of the infection control team, she died from respiratory failure. Postmortem computed tomography revealed findings consistent with acute respiratory distress syndrome, suggesting that the patient's course was complicated by catheter-related sepsis. Autopsy revealed a subcutaneous abscess around the port, from which C. albicans was cultured. However, no catheter-adherent thrombus, thrombosis of the great central veins, or endocardial vegetations were detected in the patient. Histological analysis revealed scattered abscesses in several organs including lungs and kidneys. Hyaline membrane formation and Candida colonies were found in the lungs. The central venous port tube, together with the part of the subclavian vein into which it had been inserted, was involved in an intraluminal fibrin thrombus containing neutrophils and macrophages, indicating that the thrombus existed while the patient was alive. Histopathological examination following use of the periodic acid-Schiff reagent and the Grocott stain revealed scattered Candida in the thrombus. CONCLUSIONS: Prophylactic thrombolysis should be encouraged to prevent central venous catheter-related candidiasis in clinical practice.

Ruptured mucinous cystic neoplasm with an associated invasive carcinoma of pancreatic head in a pregnant woman: report of a case and review of literature.

Mucinous cystic neoplasm (MCN) of the pancreas is characterized by mucin-producing columnar epithelium and an ovarian-type stroma. It occurs almost exclusively in women and is almost always located in the pancreatic body or tail. Here, we report a case of large MCN located in the pancreatic head but not in the body nor tail in a 32-year-old pregnant woman, which was thought to have grown rapidly during pregnancy. It was ruptured at 34 weeks of gestation and the patient was admitted to the emergency department of the University of Fukui Hospital with an acute abdomen. Emergency cesarean section followed by pancreaticoduodenectomy was performed. The tumor consisted of many small cysts lined by a single-layer of mucinous epithelium with papillary growth and partial solid parts showing invasive growth and sarcomatoid changes, indicating mucinous cystic neoplasm with an associated invasive carcinoma (previously referred as mucinous cystadenocarcinoma). Thickened septa revealed ovarian-type stroma strongly positive for α-inhibin and partly positive for progesterone receptor immunohistochemically. We also review and discuss previous reports of MCNs including those with an associated invasive carcinoma in pregnant patients.

Norovirus gastroenteritis accompanied by ischemic colitis: a case report.

A 57-year-old woman was admitted to our hospital because of frequent bloody diarrhea, vomiting, and abdominal cramps. While the patient was diagnosed with norovirus gastroenteritis based on the presence by chance of positive norovirus antigen in the stool samples, endoscopic as well as pathological examinations demonstrated left-sided ischemic colitis. The patient soon recovered solely by supportive treatment. Although it is believed that patients with viral gastroenteritis do not develop bloody diarrhea, the present case suggested that conditions of viral gastroenteritis, such as intensified peristalsis, elevation of the intraluminal gut pressure, hypovolemia, and hemoconcentration might trigger ischemic colitis resulting in bloody diarrhea. Physicians should not exclude the diagnosis of viral gastroenteritis simply by depending on the presence of bloody diarrhea. Further studies to clarify the incidence of ischemic colitis in patients with viral gastroenteritis are indispensable.

Multiple inflammatory cytokine-productive ThyL-6 cell line established from a patient with thymic carcinoma.

Thymic epithelial cells can produce many kinds of cytokines, and interleukin (IL)-6-producing thymic carcinoma cases have been reported. However, a cytokine-producing human thymic tumor cell line has not previously been established. In this paper, we report a novel, multiple inflammatory cytokine-productive cell line that was established from a patient with thymic carcinoma. This cell line, designated ThyL-6, positively expressed epithelial membrane antigen, cytokeratins, vimentin intermediate filament and CD5, although hematological markers were not present in the cells. Cytokine antibody array analysis showed that the cells secreted several cytokines including IL-1alpha, IL-6, IL-8, RANTES, soluble TNFalpha-receptor 1, VEGF and CTLA into the culture medium. The addition of ThyL-6-cultured supernatant supported the growth of human myeloma ILKM-3 cells, which require the presence of IL-6 in the culture medium for the maintenance of cell growth, suggesting that the secreted IL-6 from ThyL-6 cells was biologically active. Chromosome analysis demonstrated that ThyL-6 cells had complex karyotype anomalies, including der(16)t(1;16); the latter has been recognized in thymic squamous cell carcinoma and thymic sarcomatoid carcinoma cases, as well as in several other kinds of malignancies. Heterotransplantation of the cells into nude mice showed tumorigenesis with neutrophil infiltration and liquefactive necrosis. These findings suggest that ThyL-6 cells will provide us with a new experimental tool for investigating not only the pathogenesis, biological behavior, chromo-somal analysis and therapeutic reagents of human thymic carcinoma, but also for studying cytokine-chemokine network systems.

Frequent detection of multidrug-resistant pneumonia-causing bacteria in the pneumonia lung tissues of patients with hematological malignancies.

Pneumonia is a critical issue during the agonal phase, and often becomes lethal in the absence of pathogen detection. Autopsy is a powerful tool for analyzing the cause of a patient's death, progression of the disease, and the therapeutic response. However, it is frequently limited to the identification of bacterial strains. To elucidate the pathogenesis during the agonal phase of pneumonia, intrapulmonary sputum was harvested by directly inserting a swab into a resected lung, and the bacterial composition was analyzed using both pathological and microbiological techniques from 15 patients with hematological malignancies, and the results were compared with those from 25 patients with other medical and surgical diseases. Among the 54 bacteria strains isolated from the 40 patients, multidrug-resistant strains were significantly more prevalent in hematological group than in other diseases (16/21 versus 11/33, P = .002). Enterococcus faecium was preferentially isolated from the hematological patients, whereas the methicillin-resistant Staphylococcus aureus was predominantly found in the nonhematological group. Two coagulase-negative Staphylococcus epidermidis strains in hematological diseases may be diagnosed as causative bacteria of pneumonia by both bacterial and pathological techniques. Although the results of this study may not be directly applicable for clinical diagnosis, this approach has a potential to become not only a diagnostic method for bacterial pneumonia, but may be also useful for the analysis of multidrug-resistant pathogens.

Histopathological abnormalities in painful bipartite patellae in adolescents.

The purpose of this study was to clarify the etiology of painful bipartite patella in adolescents by histopathological examination of excised specimens. We performed excision of a fragment of painful bipartite or tripartite patella from six patients (six knees). The articular cartilage, interposed tissue, bone, and bone marrow of the excised specimens were histologically examined. The articular cartilage was intact in all but two patellae. The predominant composition of the interposed tissue was fibrous tissue in one patient; fibrous tissue and fibrocartilage in four patients; and fibrous tissue, fibrocartilage, and hyaline cartilage in one patient. In the interposed tissue, diffuse degenerative and necrotic fibrocartilage was observed in four patients and focal necrotic fibrocartilage was seen in two patients. In all patients, the central region of the interposed tissue almost completely lacked blood vessels. Other histological features of the interposed tissue included necrosis of the trabecular bone in three patients, irregularly shaped spicules of immature bone in three patients, and fragments of hyaline cartilage in two patients. In all patients the bone marrow adjacent to the interposed tissue showed numerous small blood vessels, and trabecular bone surfaces and the fibrocartilage surface adjacent to this bone marrow was scalloped and lined with numerous osteoclasts. The striking histopathological features of the interposed tissue were fibrous tissue and necrosis of the fibrocartilage. These abnormalities may ultimately lead to the failure of an accessory ossification center to unite with the main portion of the patella.