Carcinoid Tumor of the Middle Ear Containing Serotonin and Multiple Peptide Hormones A Case Report and Review of the Pathology Literature

A 69-year old man complaining of longstanding hearing loss and mild otorrhea was found to have a mass obliterating the external auditory canal and polypous tympanic mucosa with accompanying absence of the tympanic membrane and ossicular chain. Tumors excised from the external auditory canal and tympanum showed histologic features essentially characteristic of a carcinoid tumor: a ribbon or festoon arrangement of tumor cells, formation of anastomosing cords and glandular spaces, presence of numerous argyrophilic as well as argentaffin secretory granules within many of the tumor cells, and ultrastructur-al evidence of neurosecretory granules in the tumor cell cytoplasm. Immunohistochemically, the tumor was found to contain not only neuronal marker substances such as neuron-specific enolase, S 100 protein and chromogranin A, but also serotonin and multiple peptide hormones such as pancreatic polypeptide, glucagon, cholecystokinin and leucine-enkephalin. A review of the pathology of 17 previous cases of carcinoid of the middle ear suggested that this type of carcinoid may have a variegated hormone profile among carcinoids of foregut origin, and hormonally may resemble ileal carcinoid arising from the midgut, although their histogenetic origins may differ, because of frequent production of serotonin. Acta Pathol Jpn 42: 614–620, 1992.     

Cell-type-specific excitatory and inhibitory circuits involving primary afferents in the substantia gelatinosa of the rat spinal dorsal horn in vitro

The substantia gelatinosa (SG) of the spinal dorsal horn shows significant morphological heterogeneity and receives primary afferent input predominantly from Aδ- and C-fibres. Despite numerous anatomical and physiological studies, correlation between morphology and functional connectivity, particularly in terms of inhibitory inputs, remains elusive. To compare excitatory and inhibitory synaptic inputs on individual SG neurones with morphology, we performed whole-cell recordings with Neurobiotin-filled-pipettes in horizontal slices from adult rat spinal cord with attached dorsal roots. Based on dendritic arborization patterns, four major cell types were confirmed: islet, central, radial and vertical cells. Dorsal root stimulation revealed that each class was associated with characteristic synaptic inputs. Islet and central cells had monosynaptic excitatory inputs exclusively from C-afferents. Islet cells received primary-afferent-evoked inhibitory inputs only from Aδ-fibres, while those of central cells were mediated by both Aδ- and C-fibres. In contrast, radial and vertical cells had monosynaptic excitatory inputs from both Aδ- and C-fibres and inhibitory inputs mediated by both fibre types. We further characterized the neurochemical nature of these inhibitory synaptic inputs. The majority of islet, central and vertical cells exhibited GABAergic inhibitory inputs, while almost all radial cells also possessed glycinergic inputs. The present study demonstrates that SG neurones have distinct patterns of excitatory and inhibitory inputs that are related to their morphology. The neurotransmitters responsible for inhibitory inputs to individual SG neurones are also characteristic for different morphological classes. These results make it possible to identify primary afferent circuits associated with particular types of SG neurone.     

Delayed image of iodine-123 iomazenil as a relative map of benzodiazepine receptor binding: The optimal scan time

Delayed single-photon emission tomograpic (SPET) images after an intravenous bolus injection of iodine-123 iomazenil have been used as a relative map of benzodiazepine receptor binding. We determined the optimal scan time for obtaining such a map and assessed the errors of the map. SPET and blood data from six healthy volunteers and five patients were used. A three-compartment kinetic model was employed in simulation studies and analyses of actual data. The simulation studies suggested that, in the normal brain, the scan time at which a single SPET image best represented the relative receptor binding was 3.0–3.5 h post-injection. This finding was supported by actual data from the volunteers. The simulation studies also suggested that the optimal scan time was not greatly changed by the variability of the input functions, and that the error in the SPET image contrast in the vicinity of the optimal scan time was not increased by changes in the tracer kinetics in the entire brain. The SPET image contrast in the patients at 3.0 h post-injection agreed well with the reference receptor binding estimated by kinetic analysis, with a mean error of 3.6%. These findings support the use of a single SPET image after bolus injection of [¹²³I]iomazenil as a relative map of benzodiazepine receptor binding. For this purpose, a SPET scan time of 3.0-3.5 h post-injection is recommended.     

Developmental pattern of 3-oxo-Δ4 bile acids in neonatal bile acid metabolism

AIMS—To investigate whether a fetal pathway of bile acid synthesis persists in neonates and infants.
METHODS—3-oxo-Δ⁴ bile acids were determined qualitatively and quantitatively in the urine, meconium, and faeces of healthy neonates and infants, using gas chromatography-mass spectrometry.
RESULTS—The mean percentage of 3-oxo-Δ⁴ bile acids in total bile acids in urine at birth was significantly higher than that at 3 or 7 days, and at 1 or 3 months of age. The concentration of this component in meconium was significantly higher than that in faeces at 7 days and at 1 or 3 months of age.
CONCLUSIONS—The presence of large amounts of urinary 3-oxo-Δ⁴ bile acids may indicate immaturity in the activity of hepatic 3-oxo-Δ⁴-steroid 5β-reductase in the first week of postnatal life. Large amounts of this component in meconium may be due to the ingestion of amniotic fluid by the fetus during pregnancy.

     

Two-staged hepato-pancreatoduodenectomy and interventional pancreaticojejunostomy

Two-staged pancreatoduodenectomy, including exteriorization of the pancreatic juice and second-look pancreaticojejunostomy, has been recommended for high-risk patients to avoid pancreatic leakage, which often causes intra-abdominal hemorrhage. We present a new technique of interventional pancreaticojejunostomy under both fluoroscopy and endoscopy without second-look laparotomy. A 77-year-old woman with local recurrence and liver metastasis from colon cancer underwent hepato-pancreatoduodenectomy with the external drainage of pancreatic juice via the pancreatic duct tube without pancreaticojejunostomy. Two months later, the jejunum was punctured with the insertion of a 5-F needle-knife into the pancreatic fistula during endoscopic observation of jejunal lumen, followed by the insertion of two 0.35-inch guidewires into the jejunum and the pancreatic fistula. Finally, a 10-Fr stenting tube was placed between the jejunum and the pancreatic fistula. No complications developed.     

Suture Granuloma With False-Positive Findings on FDG-PET/CT Resected via Laparoscopic Surgery

A 61-year-old woman who had undergone total hysterectomy 16 years previously exhibited a pelvic tumor on computed tomography (CT). F-18 fluorodeoxyglucose (FDG) combined positron emission tomography (PET)/CT imaging revealed a solitary small focus of increased FDG activity in the pelvis. A gastrointestinal stromal tumor originating in the small intestine or another type of tumor originating in the mesentery (desmoid, schwannoma, or foreign body granuloma) was suspected; therefore, laparoscopic resection was conducted. A white, hard tumor was found to originate from the mesentery of the sigmoid colon and adhered slightly to the small intestine. The tumor was resected with a negative margin, and the pathologic diagnosis was suture granuloma. The possibility of suture granuloma should be kept in mind in cases of tumors with positive PET findings and a history of surgery close to the lesion. However, it is difficult to preoperatively diagnose pelvic tumors using a biopsy. Therefore, considering the possibility of malignancy, it is necessary to achieve complete resection without exposing the tumor.Key words: Suture granuloma, Laparoscopy, Positron emission tomography (PET)It is very difficult to diagnose suture granulomas preoperatively. F-18 fluorodeoxyglucose (FDG) combined positron emission tomography (PET)/computed tomography (CT) imaging is often used to differentiate benign from malignant tumors that are difficult to diagnose on other modalities, such as ultrasound (US), CT, and magnetic resonance imaging. However, it is not easy to differentiate tumors associated with inflammation or malignancy using FDG-PET/CT. Suture granulomas are known to be benign; however, false-positive findings were observed on PET/CT in our case. In the literature, there are few reports of suture granulomas showing false-positive findings on PET/CT.^1–5 We report here a case in which it was not possible to rule out the potential for malignancy using CT or FDG-PET/CT and the lesion was confirmed to be a suture granuloma based on a pathologic examination following laparoscopic resection.     

Protein thiol oxidation does not change in skeletal muscles of aging female mice

Oxidative stress caused by reactive oxygen species is proposed to cause age related muscle wasting (sarcopenia). Reversible oxidation of protein thiols by reactive oxygen species can affect protein function, so we evaluated whether muscle wasting in normal aging was associated with a pervasive increase in reversible oxidation of protein thiols or with an increase in irreversible oxidative damage to macromolecules. In gastrocnemius muscles of C57BL/6J female mice aged 3, 15, 24, 27, and 29 months there was no age related increase in protein thiol oxidation. In contrast, there was a significant correlation (R ² = 0.698) between increasing protein carbonylation, a measure of irreversible oxidative damage to proteins, and loss of mass of gastrocnemius muscles in aging female mice. In addition, there was an age-related increase in lipofuscin content, an aggregate of oxidised proteins and lipids, in quadriceps limb muscles in aging female mice. However, there was no evidence of an age-related increase in malondialdehyde or F₂-isoprostanes levels, which are measures of oxidative damage to lipids, in gastrocnemius muscles. In summary, this study does not support the hypothesis that a pervasive increase in protein thiol oxidation is a contributing factor to sarcopenia. Instead, the data are consistent with an aging theory which proposes that molecular damage to macromolecules leads to the structural and functional disorders associated with aging.     

A Low Serum CCL4/MIP-1β Level May Predict a Severe Asthmatic Responsiveness to Mepolizumab

Objective Mepolizumab, a humanized anti-interleukin-5 monoclonal antibody, is effective for treating eosinophilic severe asthma. However, there is a need for more biomarkers that can predict the patient response to mepolizumab before starting therapy. This study aimed to identify a new biomarker in the serum that is able to accurately predict the responsiveness to mepolizumab. Methods This study enrolled 11 patients who had all been diagnosed with severe eosinophilic asthma and were then administered mepolizumab every 4 weeks for at least 4 months. Blood samples were collected, and pulmonary function tests and questionnaires were administered at baseline and after 4, 8 and 16 weeks of treatment. The response to mepolizumab was then assessed based on the difference in the Asthma Quality of Life Questionnaire (AQLQ) score after 16 weeks of mepolizumab therapy compared with that at baseline. Patients with an increase in the AQLQ score of more than 0.5 were defined as responders. The cytokine levels in the blood were measured by LUMINEX 200 and ELISA. Results There were 6 responders and 5 non-responders. The responders showed a significantly lower serum level of chemokine (C-C motif) ligand 4/macrophage inflammatory protein-1β (CCL4/MIP-1β) at baseline compared to the non-responders. Receiver operating characteristic curves to distinguish responders from non-responders using the baseline serum CCL4/MIP-1β level showed a good area under the curve of 0.9. The non-responders showed a significant increase in the level of CCL4/MIP-1β after 4 weeks compared to the baseline. Conclusion A low baseline serum CCL4/MIP-1β level may be useful for predicting a good mepolizumab response in severe eosinophilic asthma.