Non-improvement of atrophic gastritis in cases of gastric cancer after successful Helicobacter pylori eradication therapy.

BACKGROUND: Helicobacter pylori (H. pylori) infection is closely related to the development of gastric cancer (GC). However, GC can develop even after H. pylori eradication. Therefore, it would be extremely useful if GC could be predicted after eradication. The Kyoto classification score for gastritis (GA) is closely related to cancer risk. However, how the score for GC changes after eradication before onset is not well understood. AIM: To investigate the characteristics of the progression of Kyoto classification scores for GC after H. pylori eradication. METHODS: Eradication of H. pylori was confirmed in all patients using either the urea breath test or the stool antigen test. The Kyoto classification score of GC patients was evaluated by endoscopy at the time of event onset and three years earlier. In addition, the modified atrophy score was evaluated and compared between the GC group and the control GA group. RESULTS: In total, 30 cases of early GC and 30 cases of chronic GA were evaluated. The pathology of the cancer cases was differentiated adenocarcinoma, except for one case of undifferentiated adenocarcinoma. The total score of the Kyoto classification was significantly higher in the GC group both at the time of cancer onset and three years earlier (4.97 vs 3.73, P = 0.0034; 4.2 vs 3.1, P = 0.0035, respectively). The modified atrophy score was significantly higher in the GC group both at the time of cancer onset and three years earlier and was significantly improved only in the GA group (5.3 vs 5.3, P = 0.5; 3.73 vs 3.1, P = 0.0475, respectively). CONCLUSION: The course of the modified atrophy score is useful for predicting the onset of GC after eradication. Patients with severe atrophy after H. pylori eradication require careful monitoring.

Genetic variations in the ATP-binding cassette transporter ABCC10 are associated with neutropenia in Japanese patients with lung cancer treated with nanoparticle albumin-bound paclitaxel.

ABCC10/MRP7, an ATP-binding cassette (ABC) transporter, has been implicated in the extracellular transport of taxanes. Our group reported that the ABCC10 single nucleotide polymorphism (SNPs), rs2125739, influences docetaxel cytotoxicity in lung cancer cell lines as well as its side effects in clinical practice. In this study, we investigated whether the rs2125739 variant could affect paclitaxel (PTX) cytotoxicity in lung cancer cell lines. We also investigated the effect of rs2125739 on the efficacy and safety of nanoparticle albumin-bound PTX (nab-PTX) in clinical practice. The association between rs2125739 genotypes and the 50% inhibitory concentration (IC50) of PTX was investigated in 18 non-small cell lung cancer (NSCLC) cell lines, HeLa cells, and genome-edited HeLa cells. Next, blood samples from 77 patients with NSCLC treated with carboplatin plus nab-PTX were collected and analyzed for six SNPs, including rs2125739. The clinical outcomes among the different genotype groups were evaluated. In NSCLC cell lines, HeLa cells, and genome-edited HeLa cells, the IC50 was significantly higher in the ABCC10 rs2125739 T/T group than in the T/C and C/C groups. In 77 patients with NSCLC, there were no significant differences in clinical outcomes between the T/T and T/C groups. However, the rs2125739 T/T genotype was associated with a higher frequency of Grades 3/4 neutropenia. In contrast, there was no association between other SNPs and clinical efficacy or neutropenia. Our results indicate that the ABCC10 rs2125739 variant is associated with neutropenia in response to nab-PTX treatment.

Two cases of gastric penetration by fish bones with differing courses.

Most foreign bodies swallowed accidentally are naturally excreted. Gastric penetration by a fish bone is rare due to anatomical and physiological features such as the thick stomach wall, wide lumen and gastric acid. The most common penetration site is the antral region. The clinical course of fish bone penetration of the gastric antrum may differ depending on the direction of penetration. In this report, two cases of gastric perforation by fish bones that followed different courses are presented. One case was treated conservatively with antibiotics alone, and another case was considered for surgery, due to increased hematoma and penetration of the fish bone into the pancreas. However, the patient's comorbidities were so severe that surgery was not possible, resulting in meticulous follow-up. Diagnostic imaging was important in these cases.

Liposomal Artificial Red Blood Cell-Based Carbon Monoxide Donor Is a Potent Renoprotectant against Cisplatin-Induced Acute Kidney Injury.

Cisplatin (CDDP) is an essential anti-tumor agent for chemotherapeutic regimens against various types of cancer. However, the progression of nephrotoxicity, which is the main adverse effect of CDDP, leads to discontinuation of CDDP chemotherapy. Therefore, development of a renoprotectant against CDDP-induced nephrotoxicity is crucial. Here, the potential of a carbon monoxide (CO)-loaded hemoglobin-vesicle (CO-HbV) as a renoprotectant for CDDP-induced nephrotoxicity was evaluated for its renoprotective effects against CDDP-induced nephrotoxicity, inhibitory effects on the anti-tumor activity of CDDP, and anti-tumor activity. In healthy mice, after pretreatment with either saline, HbV, or CO-HbV prior to CDDP administration, only the CO-HbV pretreatment group ameliorated the progression of CDDP-induced nephrotoxicity by suppressing apoptosis via caspase-3. In experiments using B16-F10 melanoma cells, the half-maximal inhibitory concentration of CDDP decreased with co-incubation with CO-HbV, owing to the anti-tumor activity of CO. CO-HbV pretreatment had no impact on the anti-tumor activity of CDDP in B16-F10 melanoma cell-bearing mice, which was consistent with the results of the cell experiment. Furthermore, CO-HbV pretreatment improved body growth and survival rates. In conclusion, CO-HbV pretreatment is a potent renoprotectant for CDDP-induced nephrotoxicity, allowing treatment with CDDP to be conducted without failure of cancer treatment.

A case of Helicobacter pylori-negative gastric cancer associated with Cronkhite-Canada Syndrome.

A 43-year-old Japanese man diagnosed with Cronkhite-Canada Syndrome (CCS) underwent endoscopic submucosal dissection for Helicobacter pylori-negative gastric cancer. Histologically, the completely resected specimen showed large and small irregular glands composed of foveolar epithelial-like atypical cells, and it was immunohistochemically MUC5AC positive overall, MUC6 positive except for the surface layer and nearby parts, and MUC2 negative. The patient was diagnosed with gastric-phenotype, low-grade, well-differentiated adenocarcinoma. This is a case of gastric cancer developing in CCS definitively without H. pylori infection. We conclude that H. pylori infection is not an absolute condition in gastric cancer associated with CCS. Elucidation of the true malignant potential of CCS excluding the effects of H. pylori infection is needed.

Nab-paclitaxel Monotherapy for Relapsed Small Cell Lung Cancer: Retrospective Analysis and Review.

BACKGROUND/AIM: The utility of nanoparticle albumin-bound paclitaxel (nab-PTX) monotherapy in patients with relapsed small-cell lung cancer (SCLC) has not been fully evaluated. We aimed to investigate the efficacy and safety of nab-PTX monotherapy in relapsed SCLC patients, including heavily treated patients. PATIENTS AND METHODS: We retrospectively analysed data from 17 patients with relapsed SCLC who were treated with weekly nab-PTX monotherapy at our hospital. We also reviewed past studies on nab-PTX monotherapy for relapsed SCLC. RESULTS: The response rate, progression-free survival, and overall survival were 29.4%, 48 days (95%CI=33-89), and 134 days (95%CI=64-223), respectively. The most common adverse event of grade ≥3 was leukopenia (17.6%), followed by neutropenia, neuropathy, fatigue, and infections. Our results were consistent with previous studies. CONCLUSION: The efficacy of nab-PTX monotherapy for heavily treated relapsed SCLC patients might be moderate. Further studies to improve outcomes are warranted.

Molecular Aberrations Associated with Seizure Control in Diffuse Astrocytic and Oligodendroglial Tumors.

Diffuse astrocytic and oligodendroglial tumors are frequently associated with symptomatic epilepsy, and predictive seizure control is important for the improvement of patient quality of life. To elucidate the factors related to drug resistance of brain tumor-associated epilepsy from a pathological perspective. From January 2012 to October 2017, 36 patients diagnosed with diffuse astrocytic or oligodendroglial tumors were included. Assessment for seizure control was performed according to the Engel classification of seizures. Patient clinical, radiological, and pathological data were stratified based on the following 16 variables: age, sex, location of tumor, existence of the preoperative seizure, extent of resection, administration of temozolomide, radiation therapy, recurrence, Karnofsky performance scale, isocitrate dehydrogenase 1, 1p/19q co-deletion, Olig2, platelet-derived growth factor receptor alpha, p53, ATRX, and Ki67. These factors were compared between the well-controlled group and drug-resistant seizure group. Twenty-seven patients experienced seizures; of these, 14 cases were well-controlled, and 13 cases were drug-resistant. Neither clinical nor radiological characteristics were significantly different between these two groups, though p53 immunodetection levels were significantly higher, and the frequency of 1p/19q co-deletion was significantly lower in the group with drug-resistant seizures than in the well-controlled group. In the multivariate analysis, only one item was selected according to stepwise methods, and a significant difference was observed for p53 (OR, 21.600; 95% CI, 2.135-218.579; P = 0.009). Upregulation of p53 may be a molecular mechanism underlying drug resistant epilepsy associated with diffuse astrocytic and oligodendroglial tumors.

Choreo-ballistic movement after thalamotomy in a patient with Lewy body dementia.

Thalamotomy is an established treatment for medically refractory tremor. Major complications of thalamotomy include cognitive disturbance, paralysis, dysphagia, sensory loss, and speech disturbance. Hemiballism is a rare complication after thalamotomy. We herein present a 74-year-old female patient who developed choreo-ballistic movement after thalamotomy. She was diagnosed with Lewy body dementia at the age of 70 years and exhibited worsening bilateral hand tremor. Her tremor was severe and pharmacoresistant. Left thalamotomy was planned with the trajectory passing through the ventralis intermedius (VIM) nucleus to the posterior subthalamic area (PSA). The right VIM nucleus and PSA were both coagulated with one trajectory, resulting in the immediate amelioration of right hand tremor. However, four days after surgery, choreo-ballistic movement appeared in the right leg and persisted for six months. Furthermore, tremor recurred after one month. Postoperative MRI showed a small coagulated lesion in the subthalamic nucleus. Although choreo-ballistic movement is a rare complication, it needs to be considered, particularly in patients in which the inferior border of the VIM nucleus is targeted.

A key metabolic gene for recurrent freshwater colonization and radiation in fishes.

Colonization of new ecological niches has triggered large adaptive radiations. Although some lineages have made use of such opportunities, not all do so. The factors causing this variation among lineages are largely unknown. Here, we show that deficiency in docosahexaenoic acid (DHA), an essential ω-3 fatty acid, can constrain freshwater colonization by marine fishes. Our genomic analyses revealed multiple independent duplications of the fatty acid desaturase gene Fads2 in stickleback lineages that subsequently colonized and radiated in freshwater habitats, but not in close relatives that failed to colonize. Transgenic manipulation of Fads2 in marine stickleback increased their ability to synthesize DHA and survive on DHA-deficient diets. Multiple freshwater ray-finned fishes also show a convergent increase in Fads2 copies, indicating its key role in freshwater colonization.

The Influence of Anesthesia on Corticocortical Evoked Potential Monitoring Network Between Frontal and Temporoparietal Cortices.

BACKGROUND: Previous studies have reported the usefulness of intraoperative corticocortical evoked potentials (CCEPs) for preserving language function during brain surgery. OBJECTIVE: This study aimed to assess the influence of depth of anesthesia on CCEP to establish its clinical utility. METHODS: Twenty patients with brain tumors or epilepsy who underwent awake craniotomy were included in this study. Before resection, the electrode plates were placed on the frontal and temporoparietal cortices, and 1-Hz alternating electrical stimuli were delivered to the pars opercularis/pars triangularis in a bipolar fashion. Electrocorticograms from the temporoparietal cortices time-locked to stimuli were averaged to obtain CCEP responses from a state of deep anesthesia until the awake state. The correlation between CCEP waveforms and bispectral index (BIS) was evaluated. RESULTS: CCEP amplitude increased with the increase in the BIS level. CCEP latency decreased in 5 patients and increased in 15 patients under anesthesia compared with the awake state. CCEP amplitudes decreased by 11.3% to 75.2% (median 31.3%) under anesthesia with <65 BIS level. These differences were statistically significant (P < 0.01, Wilcoxon signed-rank test). With respect to CCEP latencies, there was no significant difference between the awake and anesthetic states. CONCLUSIONS: CCEP amplitudes were correlated with depth of anesthesia, whereas CCEP latencies were not affected by anesthesia. The influence of anesthesia should be considered when applying this technique to intraoperative monitoring.

Immunonutritional status and pulmonary cavitation in patients with tuberculosis: A revisit with an assessment of neutrophil/lymphocyte ratio.

BACKGROUND: Several reports have described the importance of immunological and nutritional factors in the morbidity and/or mortality of patients with tuberculosis. The aim of this study was to evaluate the association between pulmonary cavitation and immunonutritional status, assessed by parameters such as neutrophil/lymphocyte ratio (NLR) and prognostic nutritional index (PNI), in patients with pulmonary tuberculosis. METHODS: We retrospectively analyzed the data of 137 patients with culture-positive active pulmonary tuberculosis without bacterial pneumonia diagnosed at Kainan Hospital between April 2008 and March 2016. The associations between the levels of serum albumin, lymphocytes, NLR, PNI, platelet to lymphocyte ratio (PLR), and body mass index (BMI) and pulmonary cavitation were evaluated in the patients. RESULTS: A total of 83 men and 63 women (median age, 75 years; range, 16-94 years) were included in the study. Sixty-six patients had smoking history; 55 patients had respiratory symptoms, while 44 patients did not have any symptoms. Patient׳s delay, defined as medical examination performed over 60 days after the onset of symptoms was observed in 25 patients. Univariate analysis showed that high NLR (≥ 5), high PLR (≥200), low serum albumin (<3 g/dL), high neutrophil count (≥6000/mm3), and low lymphocyte count (<1000/mm3) were associated with pulmonary cavitation. Multivariate analysis showed that high NLR and low serum albumin were associated with pulmonary cavitation. CONCLUSION: Malnutrition and increased severity of inflammation may be associated with pulmonary cavitation in patients with tuberculosis. Further studies are warranted to confirm the findings of the present study.

Peri-electrode edema after deep brain stimulation.

Peri-electrode edema can occur after deep brain stimulation (DBS). The diagnosis and management of peri-electrode edema may be challenging. We herein report non-infectious peri-electrode edema after the placement of DBS electrodes in patients with Parkinson's disease (PD). Fifteen patients who underwent DBS surgery between 2010 and 2018 at Sapporo Medical University were included to identify post-operative peri-electrode edema. Pre- and post-operative CT and MRI were retrospectively analyzed. Six patients showed hyperintensity around the electrodes on FLAIR/T2 MRI without neurological deficits. Two patients showed limited FLAIR and DWI hyperintensities in deep white matter, and microvessels may have been occluded in these patients. In five patients, MRI revealed extensive FLAIR or T2 hyperintensity in surface white matter around the electrodes without vessel injury, whereas DWI showed no abnormal signals. The eosinophil count was increased in one of these five patients. Peri-electrode edema after DBS surgery is not an uncommon phenomenon, and includes two types: (1) limited edema in deep white matter and (2) extensive edema in surface white matter. Different mechanisms may be associated with these types of edemas.

[Osimertinib for an Elderly Patient with Adenocarcinoma of the Lung Harboring EGFR T790M Mutation Diagnosed Using a Pleural Fluid Cell Block].

A 90-year-old woman was referred to our hospital because of dyspnea with pleural effusion that was detected using a chest X-ray. Pleural fluid cell block specimens from the left pleural effusion were shown to be an adenocarcinoma harboring an epidermal growth factor receptor(EGFR)gene mutation(L858R). Erlotinib was administered and the patient responded to treatment for 15 months. Subsequent re-accumulation of the left pleural effusion was detected, and re-evaluation using cell block specimens revealed EGFR T790M mutation positivity. Osimertinib was initiated and the patient responded to treatment for 11 months. Re-evaluation of the left pleural effusion upon failure of osimertinib treatment revealed EGFR T790M mutation negativity. Hence this report summarizes the case of osimertinib therapy being administered to a 90-year-old patient who had EGFR T790M mutation positivity based on a pleural fluid cell block.

A case of wild-type transthyretin amyloidosis associated with organizing pneumonia.

An 81-year-old man was referred to our hospital with bilateral multiple patchy opacities on chest radiography. His chief complaints were a few months' history of intermittent mild cough and slightly yellow sputum. Chest computed tomography (CT) showed non-segmental air-space consolidations with ground-glass opacities. Amyloid deposition with organizing pneumonia (OP) was seen in transbronchial lung biopsy (TBLB) specimens from the left S8. Three months later, the infiltration originally seen in the left lower lobe was remarkably diminished, and new infiltrations in the lingual and right lower lobes were detected on chest CT. Amyloid deposition with OP was seen in TBLB specimens from the left S4. Transthyretin was detected following immunohistochemical examination. The presence of wild-type transthyretin (ATTRwt) was proven using genetic analysis. The present report describes a rare case of ATTRwt amyloidosis associated with OP.

Electrophysiological influence of temporal occlusion of the parent artery during aneurysm surgery.

Intraoperative monitoring of the motor evoked potential (MEP) during cerebral aneurysm surgery has been widely used to confirm surgical safety. In this study, we retrospectively analyzed the influence of the MEP amplitude resulting from temporal occlusion of the parent artery, and appropriate judgement in the surgery was discussed. Ten patients underwent temporal occlusion of the parent artery during aneurysm surgery, and five of these patients showed a decrease in the MEP amplitude following temporal arterial occlusion. Clinical factors in patients with and without MEP decrease were compared. The time gap between the surgical procedure and the MEP change and recovery was then investigated. A decrease in the MEP amplitude caused by temporal occlusion had a significantly higher occurrence compared with permanent clip failure. The time from the release procedure to MEP amplitude recovery was relatively longer than the time from the occlusion procedure to the decrease in MEP amplitude. The time from release procedure to MEP amplitude recovery showed a weak correlation with the parent artery occlusion time. There is a time gap between releasing the temporal arterial occlusion and MEP recovery that is similar to temporal parent arterial occlusion and the MEP decrease. The cause of MEP amplitude should be judged carefully, and influence of parent artery temporal occlusion should be taken into consideration during aneurysm clipping.

Immunological Status May Predict Response to Nivolumab in Non-small Cell Lung Cancer without Driver Mutations.

BACKGROUND/AIM: It remains challenging to select patients with non-small cell carcinoma (NSCLC) for nivolumab monotherapy. We evaluated whether early termination of nivolumab monotherapy correlated with pretreatment neutrophil/lymphocyte ratio (NLR) and prognostic nutritional index (PNI). PATIENTS AND METHODS: Twenty patients received nivolumab monotherapy for NSCLC with wild-type epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) during 2016. Early termination and continued therapy were defined as ≤5 and ≥6 cycles of monotherapy, respectively. RESULTS: Early termination and continued therapy groups included 9 and 11 patients, respectively. High pretreatment NLR and low pretreatment PNI were significantly associated with early termination of nivolumab, both in an overall analysis (p<0.001 and p=0.016) and in subgroup analyses of patients with performance scores of 0-1 and ≥30 days of pretreatment drug holidays. CONCLUSION: High NLR and low PNI were associated with early termination of nivolumab monotherapy, suggesting they might be useful biomarkers for treatment selection.

Complementary Relation Between Direct and Indirect Bypass in Progress of Collateral Circulation in Moyamoya Disease.

BACKGROUND: One of the important aims of surgery for moyamoya disease is to establish indirect revascularization. The purpose of this study was to assess the progress of the middle meningeal artery (MMA) after our novel preservation method and to evaluate the relation between direct and indirect bypass in the chronic stage. METHODS: A total of 24 hemispheric sides of 19 patients with moyamoya disease were included in this study. Craniotomy was performed with preservation of the MMA during the procedure, then direct bypass was carried out. The relationship between anatomic variations of the MMA and success rate of preserving the MMA during craniotomy was noted. The alteration of the MMA and superficial temporal artery (STA) diameters was then evaluated using magnetic resonance imaging, and the correlation between the MMA and the STA in the chronic stage was examined. RESULTS: In total, the MMA was preserved during craniotomy in 20 hemispheric sides (83.3%). During the 3-year follow-up period, the MMA and STA diameters were significantly increased. At 3 years after surgery, the alteration of the MMA diameter was significantly more marked in pediatric cases than in adult cases, and MMA diameter was moderately but significantly negatively correlated with STA diameter. CONCLUSIONS: In moyamoya disease, the MMA could be developed as a pathway for indirect revascularization even after simple preservation, especially in pediatric patients. The progress of the MMA and the STA occurs through their synergistic interaction, and the balance might be decided based on their complementary relations in the chronic stage.

[CLINICAL INVESTIGATION OF TUBERCULOSIS PATIENTS IN A GENERAL HOSPITAL LACKING A TUBERCULOSIS WARD IN WESTERN AICHI PREFECTURE.]

With the recent decrease in the number of tuberculosis wards and increase in elderly tuber- culosis patients with comorbidities, the role of regional refer- ral hospitals has become more important in tuberculosis management. [Objective]. This study aimed to assess the current state of tuberculosis management and related issues in a general hospital lacking a tuberculosis ward. [Methods] We retrospectively evaluated the clinical char- acteristics and course of patients diagnosed with tuberculosis by culture testing from April 2008 to March 2015 at Kainan Hospital. [Results] A total of 146 patients (83 males and 63 females; mean age 76, range 18-94 years) were diagnosed with active tuberculosis. Of these, 129 were diagnosed with pulmonary tuberculosis (23 had pulmonary tuberculosis with pleurisy), and 17 patients were diagnosed with extrapulmonary tuber- culosis. The chief complains were cough/sputum in 40 cases, fever in 24, and no symptoms in 36. Associated major comorbidities included diabetes mellitus, chronic kidney disease, and malignancy. In 33 patients, over 30 days were required to diagnose tuberculosis after initial evaluation. Drug-resistant strains were detected in 14 patients. 57 were diagnosed with smear-positive pulmonary tuberculosis, and 66 were transferred to a tuberculosis hospital. Modify in anti- tuberculosis therapy due to adverse reactions were reported in 27 patients. [Conclusion] This study evaluated the current state of tuberculosis management in our hospital. Further educational guidance regarding tuberculosis is needed for the hospital staff, and is important for improvement of tuberculosis management in our hospital.