Evaluation of Chemotherapy-induced Dysgeusia in Patients With Gastrointestinal Cancer: A Pilot Study.

BACKGROUND/AIM: Dysgeusia, one of the adverse effects of cancer chemotherapy, and anorexia due to taste disorder can significantly impair the quality of life of patients. However, an evaluation method for dysgeusia has not yet been established. The present prospective study aimed to utilize a combination of subjective and objective assessment methods to evaluate dysgeusia in patients with gastrointestinal cancer initiating chemotherapy, to determine chemotherapeutic drugs and regimens causing dysgeusia, and to assess whether dysgeusia was associated with zinc deficiency. PATIENTS AND METHODS: A total of 21 patients with newly diagnosed gastrointestinal cancer were registered between August 2020 to March 2021. The following regimens were also included in the evaluation if the patients did not develop dysgeusia. A total 30 regimens were administered to the patients during the study period. A salt-impregnated test paper (Salsave®) was used as a subjective assessment, and the chemotherapy-induced taste alteration scale was used as an objective assessment. RESULTS: Based on physician interviews, dysgeusia was diagnosed in 8 of 21 patients (38%) treated with 8 of 30 regimens (27%). All regimens that resulted in dysgeusia contained platinum-based drugs. The patients who developed dysgeusia had higher controlling nutritional status scores at the start of chemotherapy compared to those who did not develop dysgeusia. In both subjective and objective assessments, the patients with dysgeusia performed significantly worse than those without dysgeusia. Six of the eight patients who developed dysgeusia were administered Novelzine, which did not improve the taste disorder despite the improvement of serum zinc levels. CONCLUSION: The combined approach using subjective and objective taste assessment methods was useful in assessing chemotherapy-induced dysgeusia. Mechanisms other than hypozincemia should be considered as contributors to taste disorders caused by platinum-based drugs.

A Case of Kikuchi's Disease Without Cervical Lymphadenopathy.

Background: Kikuchi's disease with only extracervical lymphadenopathy is rare. Case Presentation. A 15-year-old male has presented with a fever lasting more than 1 week and right axillary lymphadenopathy. An axillary lymph node biopsy revealed coagulation necrosis, nuclear decay products, infiltration of histiocytes, and enlarged lymphocytes; he was diagnosed with Kikuchi's disease. The only four adult patients with Kikuchi's disease presenting without cervical lesions have been previously reported. Conclusion: This is the only pediatric case of Kikuchi's disease presenting without cervical lymphadenopathy. Kikuchi's disease should be included in the differential diagnosis even in cases of extracervical lymphadenopathy alone.

First Pediatric Case of Clinically-Diagnosed Penicillin G-Induced Hemorrhagic Cystitis.

Hemorrhagic cystitis is a diffuse inflammatory disease of the urinary bladder associated with macrohematuria. Several cases of hemorrhagic cystitis caused by penicillin G have been reported in adults but not children. Here we describe the first pediatric case of clinically-diagnosed penicillin G-induced hemorrhagic cystitis. The patient was a 9-year-old boy with a ventricular septal defect, chromosomal abnormalities, and infective endocarditis caused by Abiotrophia defectiva. After approximately four weeks of penicillin G administration, he had a culture-negative major hemorrhage with a clot. The hematuria resolved one week after penicillin G discontinuation, and a drug lymphocyte stimulation test for penicillin G was positive. In conclusion, penicillin G can also induce hemorrhagic cystitis in children. When large doses of penicillin G are used for long periods in adults or children, the patient should be monitored for hemorrhagic cystitis.

Prognostic Nutritional Index Considering Resection Range Is Useful for Predicting Postoperative Morbidity of Hepatectomy.

BACKGROUND: Poor preoperative nutritional and immunological status are major risk factors for postoperative complications in patients with various malignancies. Lower preoperative prognostic nutrition index (PNI) is associated with higher rates of postoperative complications and poorer prognosis in those patients. The aim of this study was to analyze the predictive value of the PNI for post-hepatectomy complications in patients with hepatocellular carcinoma (HCC), and evaluate its utility in the surgical procedure. METHODS: This retrospective study included 510 patients who underwent open hepatectomies for HCC. The predictive value of the preoperative nutritional and immunological status for postoperative complications was assessed using the PNI. Postoperative complications were defined as grade II or higher per the Clavien-Dindo classification. Postoperative complication rates were compared according to surgical procedure (major hepatectomy vs minor hepatectomy). RESULTS: Patients with postoperative complications had significantly lower PNIs than those without (43.1 ± 5.5 vs 47.0 ± 5.7, P < 0.001). In the multivariate analysis, low preoperative PNI (< 45) was an independent risk factor for postoperative complications after hepatectomy (hazard ratio, 3.85). When patients were classified per their PNI (high vs low) and extent of surgical procedures (major vs minor), there were more complications among patients with low PNI than those with high PNI, regardless of the extent of surgical procedures. Specifically, the group of patients with low PNI who underwent major hepatectomy had significantly higher rates of postoperative complications than the other groups. CONCLUSIONS: Adding the resection range to the PNI is useful for predicting the postoperative morbidities of hepatectomy patients.

Three-Quarters Adrenalectomy for Infantile-Onset Cushing Syndrome due to Bilateral Adrenal Hyperplasia in McCune-Albright Syndrome.

BACKGROUND: Bilateral adrenalectomy is performed in cases with infantile-onset Cushing syndrome due to bilateral adrenal hyperplasia in McCune-Albright syndrome (MAS) because severe Cushing syndrome with heart failure and liver dysfunction can have a lethal outcome. This procedure can completely ameliorate hypercortisolism, although lifetime steroid replacement therapy and steps to prevent adrenal crisis are necessary. Recently, the efficacy of unilateral adrenalectomy has been reported in adult cases of bilateral macronodular adrenal hyperplasia, but there is no consensus regarding the appropriate surgical treatment for bilateral adrenal hyperplasia in MAS. OBJECTIVE: A 6-month-old girl presented with café-au-lait spots, short stature, central obesity, a moon face, and hypertension. Endocrinological tests and imaging studies led to the diagnosis of ACTH-independent Cushing syndrome due to bilateral adrenal hyperplasia induced by MAS. "Three-quarters adrenalectomy", namely right-sided total adrenalectomy and left-sided half adrenalectomy, was carried out. An activating mutation of the GNAS1 gene (p.Arg201Cys) was identified in the adrenal tissues. Since the operation, our patient has been in a state of clinical remission for more than 2 years. CONCLUSION: Our original surgical intervention, three-quarters adrenalectomy, may be a new treatment option for Cushing syndrome associated with MAS.

Progressive dysautonomia in two patients with xeroderma pigmentosum group A.

BACKGROUND: Xeroderma pigmentosum group A (XPA) is a rare autosomal-recessive disorder caused by a defect in nucleotide excision repair. Progressive dysautonomia in patients with XPA is rarely described. PATIENTS: Two juvenile male patients with XPA suffered from dysphagia, sleep interruption, and dysuria from the age of 10 to 19 years, successively. These autonomic symptoms might have been caused by progressive descending degeneration of cranial nerves IX and X and the sacral parasympathetic nerve, including Onuf's nucleus. One patient died from sudden cardiopulmonary arrest during postural change and tracheal suction. RESULTS: Heart rate variability analyses of these patients revealed parasympathetic dysautonomia, based on decreased high-frequency values. CONCLUSIONS: The insidiously progressive dysautonomia in these two patients with XPA suggested progressive descending degeneration extending from the medulla oblongata to the sacral spinal cord, which is an ominous sign of end-stage disease and a risk factor of sudden death attributable to XPA.

A transient myelodysplastic/myeloproliferative neoplasm in a patient with cardio-facio-cutaneous syndrome and a germline BRAF mutation.

A male infant, born at 32 weeks gestation by cesarean because of hydrops fetalis, presented with multiple anomalies, such as sparse and curly scalp hair, absent eyebrows, frontal bossing, an atrial septal defect, pulmonary artery stenosis, and whole myocardial thickening. He was clinically diagnosed with cardio-facio-cutaneous (CFC) syndrome, and was confirmed to have a germline V-raf murine sarcoma viral oncogene homologue B1 (BRAF) c.721 A>C mutation. At 1 month of age, he presented with a transient myelodysplastic/myeloproliferative neoplasm (MDS/MPN), which improved within a month without the administration of antineoplastic agents. This is the first report of CFC syndrome with MDS/MPN. The coexistence of MDS/MPN may be related to this BRAF c.721 A>C mutation.

Neonatal onset diffuse cutaneous mastocytosis: a case report and review of the literature.

Diffuse cutaneous mastocytosis is a rare variant of mast cell disease with widespread erythroderma, which is normally clinically apparent in early infancy. We report the case of a neonate who presented with diffuse erythrodermic rash and bullous lesions. Biopsy specimens showed a dense dermal infiltrate of mast cells. Serum histamine and tryptase levels were elevated. No somatic mutation of the c-kit gene was found. Blistering ceased at 5 months of age, but atopic dermatitis appeared at 6 months and allergic workup revealed a high level of food-specific IgE. Herein, we describe the case and provide the first review of the literature on neonatal onset diffuse cutaneous mastocytosis to clarify the prognosis of this condition.

The indication and effectiveness of low-dose erythromycin therapy in pediatric patients with bronchial asthma.

To elucidate the mechanisms of intractable pediatric bronchial asthma and the indication of low-dose erythromycin (EM) therapy, the serum chemokine levels of and the angiogenic factor were evaluated in 55 pediatric patients with bronchial asthma; 7.4 +/- 3.5 yr old, who had been treated with inhaled steroid, leukotriene receptor antagonist, theophylline and others for more than a year. Both the levels of interleukin (IL) 8 (p = 0.036) and vascular endothelial growth factor (VEGF) (p = 0.005) were higher in patients with severe type than those of patients with the milder type, while other chemokine levels such as serum eotaxin and MCP1 did not show the correlation with the severity of bronchial asthma. Induction of therapy with low-dose EM induced improvement of the clinical symptoms in patients with severe type and decrease of their serum chemokine levels: IL8; from 736 +/- 88 to 75 +/- 85 pg/ml (p < 0.0005), and VEGF; from 352.0 +/- 160.5 to 132.2 +/- 59.9 pg/ml (p = 0.021) within the next 6 months. Moreover, low-dose EM resulted in a decreased daily peak-trough fluctuation rate of the serum theophylline concentration; (C(max )- C(min))/C(min), from 1.3 +/- 0.5 to 0.5 +/- 0.3, which led to the maintenance of effective serum levels. These results indicated that IL8 and VEGF affect the severity of standard therapies resistance intractable bronchial asthma. Through the suppression of these chemokines and maintenance of effective theophylline levels, low-dose EM therapy improves the symptoms of bronchial asthma.

[Alterations in immunological responses: conformational changes of allergens and application to hyposensitivity therapy].

To establish a novel strategy for allergen immunotherapy, human immunoresponses against conformational variants of a mite allergen were examined. Heat treatment of major house dust mite allergen, Der f2 caused molecular aggregation, while its ability to bind IgE remained unchanged. C8/119S, a mutant protein of Der f2 with the cysteine residues at positions 8 and 119 being replaced by serines, leads to degenerate secondary structure, molecular polymerization and Th1 cell differentiation. C8/119S also lost the ability to bind IgE. On the other hand, misfolded recombinant Der f2 also exhibits degenerate secondary structure, molecular polymerization and Th1 cell differentiation, however, its ability to bind IgE is retained. Loss of IgE binding ability and Th1 skewed immunogenicity of C8/119S are attributed to alterations in antigen-presenting cells and its cytokine profiles. These findings may lead to a novel allergen immunotherapy.

The subclassification of schizencephaly and its clinical characterization.

We subclassified schizencephaly based on the association with optic nerve hypoplasia (ONH) and the absence of the septum pellucidum (ASP), and then characterized their clinical presentation and prognosis. The subjects of our study consisted of 10 cases with a mean age at the final evaluation of 10 years 3 months (range, 7 months to 25 years). The subclassification of schizencephaly consisted of the septo-optic dysplasia (SOD) group (n=3), with ONH and ASP; the optic hypoplasia (OHP) group (n=2), with ONH and without ASP, and; the classical group (n=5), without ONH. The subjects with an open-lip cleft in the SOD and the classical group showed hydrocephalus, but those in the OHP group did not. The SOD and the OHP group displayed severe psychomotor retardation regardless of the cleft morphology, but in the classical group, the subjects with an open-lip cleft or with diffuse cortical dysplasia were severely retarded. The SOD and the OHP group displayed intractable epilepsy. In contrast, all subjects in the classical group showed good control of epilepsy. The results of our investigation show that the subclassification of schizencephaly based on the association with ONH and ASP is useful. The SOD group means early fetal brain injury which results in extended cortical dysplasia while the OHP group means severe destructive brain injury which results in cerebro-cerebellar disruption.

Clinical presentation of patients with neurofibromatosis type 1 in infancy and childhood: genetic traits and gender effects.

The clinical presentations of 32 patients with neurofibromatosis type 1 were examined based on genetic traits, clinical findings, electroencephalogram, and neuroimaging findings. Twenty-eight sequential magnetic resonance images showed multifocal hyperintense T2-weighted images in 14 patients. Seven (5 boys and 2 girls) of the 8 patients (88%) who inherited neurofibromatosis type 1 from affected mothers, and 7 (2 boys and 5 girls) of the 16 de novo patients (44%) had multifocal hyperintense T2-weighted images. In contrast, the patients who inherited this disease from affected fathers did not have any multifocal hyperintense T2-weighted images. Multiple plexiform neurofibromas were observed in 4 patients, of whom 3 boys inherited through at least 3 generations of women. They all presented severe psychomotor delay and epilepsy. These findings suggest that genetic traits, especially through the passage of several generations of women, may affect the clinical presentation in patients with neurofibromatosis type 1.

Theophylline-associated seizures and their clinical characterizations.

BACKGROUND: To elucidate the basic mechanism of theophylline-associated seizures (TAS), the clinical symptoms, electroencephalogram (EEG) and neuroradiological imaging of eight pediatric patients were all retrospectively evaluated. METHODS: Patients whose seizures represented their first episode were selected, while patients with cerebrospinal fluid abnormalities including pleocytosis and protein elevation, present illness of head trauma, epilepsy, febrile convulsion or any psychomotor retardation were excluded although they were given theophylline. RESULTS: Eight patients, 3.5 +/- 1.7 years of age, thus fulfilled the definition of TAS in the past 5 years. Based on their seizure patterns, EEG findings, brain single-photon emission computed tomography and head magnetic resonance imaging, a total of seven of eight patients had either localized or unilateral dominant lesions. They all had fever, > or =38 degrees C, and six of eight patients had a family history of febrile convulsions and/or idiopathic epilepsy. Thereafter none of them had convulsions after the cessation of theophylline administration. Through the TAS event, a 6-year-old female patient was found to have a right deep lateral cerebral venous angioma. CONCLUSION: In infants with idiopathic low seizure threshold and fever, theophylline administration might possibly trigger a seizure. Moreover, based on these patients' clinical findings, some kind of cerebral vascular involvements is speculated to be related with TAS.

Hemophagocytic lymphohistiocytosis in a human immunodeficiency virus-positive homosexual high school student.

The spread of human immunodeficiency virus (HIV) infection has exploded over the past two decades and such infections in young people are no longer uncommon. However, the major infection route of pediatric patients remains vertical transmission, and sexual, especially homosexual transmission, is highly unusual. We herein describe the case of a 17-year-old boy who developed hemophagocytic lymphohistiocytosis (HLH). Although HLH was remitted soon with dexamethasone therapy, an HIV infection caused by homosexual transmission was detected.

Congenital neuromuscular disease with uniform type-1 fibers, presenting early stage dystrophic muscle pathology.

We report two male siblings presenting with severe hypotonia, generalized muscle atrophy, multiple joint contractures and respiratory failure. The serum creatine kinase levels were within normal limits, 75 IU/l in the younger boy and 123 IU/l in the older one. Muscle biopsies at the age of 28 days in the younger boy and 48 days in the older one revealed dystrophic pathology with increased interstitial fibrous tissue, scattered basophilic fibers and an increased number of undeveloped type-2C fibers. Although the elder brother died from respiratory failure at 4 months of age, the younger child has been sustained with mechanical ventilation, and has been exhibiting non-progressive muscle symptoms. Upon re-biopsy of the younger sibling at the age of 3 years, neither basophilic regenerating fibers nor degenerating fibers were found. All muscle fibers were found to be extremely atrophic and behaved mostly like type-1 fibers, displaying the features of congenital neuromuscular disease with uniform type-1 fibers. Since early biopsies in congenital myopathies reveal numerous undifferentiated immature muscle fibers, it is difficult to make a definite diagnosis, unless we recognize disease-specific cytoplastic abnormalities of nemaline body formation and abnormalities of core structure.