Possible Role of High-Dose Barbiturates and Early Administration of Parenteral Ketogenic Diet for Reducing Development of Chronic Epilepsy in Febrile Infection-Related Epilepsy Syndrome: A Case Report.

We describe the efficacy of high-dose barbiturates and early administration of a parenteral ketogenic diet (KD) as initial treatments for acute status epilepticus (SE) in an 8-year-old girl with febrile infection-related epilepsy syndrome (FIRES). The patient was admitted to our hospital with refractory focal SE. Abundant epileptic discharges over the left frontal region were observed on electroencephalogram (EEG). Treatment with continuous infusion of thiamylal for 4 hours, increased incrementally to 40 mg/kg/h, successfully ended the clinical SE, and induced a burst-suppression coma. The infusion rate was then gradually decreased to 4 mg/kg/h over the next 12 hours. Parenteral KD was administered from days 6 to 21 of illness. Continuous infusion of thiamylal was switched to midazolam on day 10 without causing seizures or EEG exacerbations. The patient has remained seizure free in the 15 months since hospital discharge. The effectiveness of KD for the treatment of FIRES has attracted attention amongst clinicians, but KD treatment may need to last for 2 to 4 days before it can stop SE, a time period that could cause irreversible brain damage. Considering the severity of SE in our patient and the dose of barbiturates needed to treat it, we consider this case to have had a good clinical outcome. The results suggest that rapid termination of seizure using high-dose barbiturates in conjunction with early administration of parenteral KD could reduce the development of chronic epilepsy in patients with FIRES.

Seizure focus in the frontal interhemispheric fissure leads to ipsilateral isolated eye deviation.

OBJECTIVE: Few studies have examined the localization of seizures presenting with ictal eye deviation (ED) in the absence of other motor symptoms. We aimed to investigate differences in the localization of the ictal onset zone (IOZ) between patients with isolated ED and those with ED plus head turning (HT) during focal seizures. METHODS: We reviewed intracranial video-EEG data for 931 seizures in 80 patients with focal onset epilepsy in whom the IOZ could be confirmed. The 233 seizures in 49 patients with ED were classified into two semiological groups based on initial ED and the presence/absence of HT: (1) isolated ED (i.e., ED without HT), and (2) ED + HT (i.e., ED with HT). We analyzed the localization and lateralization of IOZs in each semiological group. We performed multivariate logistic regression analysis using a mixed-effects to determine the associations between IOZs and isolated ED/ED + HT. RESULTS: A total of 183 IOZs in 24 patients were included in the isolated ED group, while a total of 143 IOZs in 31 patients were included in the ED + HT group. Sixty-eight IOZs of eight patients in the isolated ED group were located in the ipsilateral frontal interhemispheric fissure (F-IHF). Only ipsilateral F-IHF was significantly associated with isolated ED (odds ratio [OR], 2.43; 95% confidence interval [CI], 0.37-4.49; P = 0.021). The contralateral lateral frontal cortex (latF) (P = 0.007) and ipsilateral mesial temporal region (mT) (P = 0.029) were significantly associated with ED + HT. CONCLUSION: The present study is the first to demonstrate that seizures with an F-IHF focus tend to present with initial ipsilateral isolated ED. This finding may aid in identifying the seizure focus in patients with isolated ED prior to resection.

Epilepsy surgery reduced seizure frequency for patients with severe motor and intellectual disorders.

INTRODUCTION: Little is known about epilepsy surgery for patients with severe motor and intellectual disorders (SMIDs). We hypothesized that epilepsy surgery could reduce epileptic seizure frequency in these patients. The purpose of this study was to compare pre- and postoperative seizure frequency in patients with SMIDs. METHODS: A total of 288 surgeries were performed for pediatric patients, including those with SMIDs, from 2009 to 2018. Inclusion criteria were as follows: Oshima classification 1 (intelligence quotient <20 and bedridden), ≥2 years old, proven ictal events evaluated by long-term video electroencephalography, and ≥1-year follow-up. Seizure frequency and the number of antiseizure medications (ASMs) were compared between pre- and postepilepsy surgery. Patients' respiratory and feeding conditions were also examined to determine comorbidities. RESULTS: Nineteen patients (5 girls, 14 boys; age: 2 to 12 years) fulfilled the inclusion criteria. One patient underwent focus resection, 2 patients underwent total corpus callosotomy, and 16 patients underwent vagus nerve stimulation therapies. Of 19 patients, 16 (84.2%) had daily seizures, and 3 (15.8%) had weekly seizures before surgery. Epilepsy surgery significantly reduced seizure frequency (p = 0.029). Five patients (26.3%) had status epilepticus (SE) before surgery, which disappeared in all but one after surgery (p = 0.046). The number of ASMs did not change between before and after surgery (p = 0.728). CONCLUSION: Epilepsy surgery reduced the frequency of epileptic seizures and improved SE even among patients with compromised respiratory function and compromised food intake.

Association between diffuse cerebral MRI lesions and the occurrence and intractableness of West syndrome in tuberous sclerosis complex.

OBJECTIVE: We aimed to clarify the association between magnetic resonance imaging (MRI)-lesion patterns, including cortices and white matters, and the development, occurrence, and intractableness of West syndrome in patients with tuberous sclerosis complex (TSC), using visual analysis. METHODS: We collected data for 44 patients with TSC who had undergone brain MRI and developmental evaluation after the ages of 2 and 3 years, respectively. Fluid-attenuated inversion recovery (FLAIR) and T1-weighted images were used to analyze the number of cyst-like tubers, the number of cyst-like subcortical lesions, and the presence of diffuse lesions involving the cortices and white matter. RESULTS: Developmental delays were observed in 28 patients. Nineteen patients had a history of West syndrome. Cyst-like tubers (range: 1-10), cyst-like subcortical lesions (range: 1-4), and diffuse lesions (range: 1-6 areas) were observed in 15, 9, and 14 patients, respectively. In the univariate analyses, all MRI findings were associated with development and/or history of West syndrome. However, in the multivariate analyses, only the diffuse lesion was associated with severe development (p = 0.003) and history of West syndrome (p = 0.012). In the subanalysis of patients with West syndrome, the diffuse lesions were also associated with pharmacological intractableness. Patients with diffuse lesions had a history of West syndrome with sensitivity of 68% and specificity of 96%. Patients with two or more areas of diffuse lesions had history of pharmacologically intractable West syndrome with sensitivity of 89% and specificity of 91%. CONCLUSIONS: Diffuse lesions may help to predict the poor neurological outcomes in patients with TSC.

Activities of daily living are associated with outcomes of epilepsy treatment in elderly patients.

AIM: Controlling epileptic seizures in elderly populations is widely considered to be relatively easy, but we hypothesized that the lifestyles of elderly individuals may affect the outcomes of epilepsy treatment. The purpose of this study was to review the activities of daily living (ADL) of elderly individuals with epilepsy and compare them with the outcomes of epilepsy treatment. METHODS: Of the 177 patients ≥65 years old who were referred to our epilepsy centre, epilepsy was diagnosed in 84. ADL and treatment outcomes were then reviewed, with ADL classified into three levels: ADL I, without disability; ADL II, disabled only in some instrumental ADL; and ADL III, disabled in some basic ADL. Epilepsy syndromes and use of anti-seizure drugs were also evaluated. RESULTS: Forty-five patients (53.6%) achieved freedom from seizures, 23 (27.4%) achieved ≥80% but <100% reduction in seizures, 5 (6%) achieved ≥50% but <80% reduction in seizures, and 11 (13.1%) achieved <50% reduction in seizures. Thirty-five patients (81.4%) with ADL I achieved freedom from seizures, compared with seven patients with ADL II (28.0%) and three patients with ADL III (19.0%). A significant difference was evident among the three groups (F = 6.145, P = 0.003). CONCLUSIONS: ADL should be taken into account when an epilepsy treatment is being selected.

Corpus callosotomy for drug-resistant spasms associated with tuberous sclerosis complex.

BACKGROUND: Corpus callosotomy (CC) has recently been adopted for the treatment of drug-resistant epileptic spasms and tonic spasms. In the present study, we investigated CC outcomes among patients with drug-resistant epileptic spasms or tonic spasms associated with tuberous sclerosis complex (TSC). METHODS: We retrospectively collected data from seven patients (3 women, 4 men) with diagnosed TSC and who were treated using CC at Seirei Hamamatsu General Hospital in Japan. All patients had experienced drug-resistant epileptic spasms (<3 s of muscular contraction) or tonic spasms (>3 s) prior to CC, which were confirmed via video-electroencephalogram monitoring. RESULTS: All patients exhibited multiple bilateral cortical tubers on brain magnetic resonance imaging. The main seizure types were epileptic spasms in four, tonic spasms in one, and both seizure types in two patients. Patients underwent total CC between the ages of 25 months and 21.5 years. Additional resection or disconnection was performed in two patients. The follow-up period after CC ranged between 9 months and 3.5 years. Three patients achieved remission from spasms following CC alone. Two other patients became free from spasms several months after CC but required an additional focus disconnection or medical treatment. The remaining two patients continued to show spasms or asymmetrical tonic seizures. CONCLUSION: Total CC resulted in freedom from drug-resistant epileptic or tonic spasms in several patients with TSC. Stepwise progression from CC to additional resection or disconnection surgery may aid in the treatment of spasms secondary to TSC.

Inclusion of general physicians in the multidisciplinary treatment team for epilepsy may lead to an economic benefit.

INTRODUCTION: The purpose of this study was to compare epileptic seizure control and economic impact in patients with epilepsy between when they were seen by general physicians (GPs) versus epilepsy specialists. METHOD: We began distributing a booklet we named the "Epi Passport" to patients with epilepsy in December 2014 to share information within the regional epilepsy network of GPs, epilepsy specialists, and patients (Gep). We compared seizure control and household income levels before and after the introduction of this booklet. RESULTS: There was no significant difference in seizure control between patients who saw specialists or GPs (P = 0.215). Significant increases in household income were seen among 134 patients (36.6%) in the post-Epi Passport period who were primarily seen by GPs (P < 0.001). However, 35 patients (9.6%) showed a decrease in income between periods, and 197 patients (53.8%) showed no change. Age of 20-39 years old was significantly associated with increases in household income (P = 0.0287). CONCLUSION: After the introduction of the Epi Passport, about one-third of the patients with epilepsy who were mainly seen by GPs in their community showed an increase in household income. There was no difference in seizure control among those who saw a GP or a specialist. Inclusion of GPs in the multidisciplinary treatment team for epilepsy may lead to increased patient income because of the fact that patients can manage their epilepsy in their community using their GP.

Double match of 18F-fluorodeoxyglucose-PET and iomazenil-SPECT improves outcomes of focus resection surgery.

BACKGROUND: When the results of electroencephalography (EEG), magnetic resonance imaging (MRI), and seizure semiology are discordant or no structural lesion is evident on MRI, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are important examinations for lateralization or localization of epileptic regions. We hypothesized that the concordance between interictal 2-[18F]fluoro-2-deoxy-D-glucose (18FDG)-PET and iomazenil (IMZ)-SPECT could suggest the epileptogenic lobe in patients with non-lesional findings on MRI. METHOD: Fifty-nine patients (31 females, 28 males; mean age, 29 years; median age, 27 years; range, 7-56 years) underwent subdural electrode implantation followed by focus resection. All patients underwent 18FDG-PET, IMZ-SPECT, and focus resection surgery. Follow-up was continued for ≥ 2 years. We evaluated surgical outcomes as seizure-free or not and analyzed correlations between outcomes and concordances of low-uptake lobes on PET, SPECT, or both PET and SPECT to the resection lobes. We used uni- and multivariate logistic regression analyses. RESULTS: In univariate analyses, all three concordances correlated significantly with seizure-free outcomes (PET, p = 0.017; SPECT, p = 0.030; both PET and SPECT, p = 0.006). In multivariate analysis, concordance between resection and low-uptake lobes in both PET and SPECT correlated significantly with seizure-free outcomes (p = 0.004). The odds ratio was 6.0. CONCLUSION: Concordance between interictal 18FDG-PET and IMZ-SPECT suggested that the epileptogenic lobe is six times better than each examination alone among patients with non-lesional findings on MRI. IMZ-SPECT and 18FDG-PET are complementary examinations in the assessment of localization-related epilepsy.

Morphophenotypic characteristics of intralymphatic cancer and stromal cells susceptible to lymphogenic metastasis.

The intravessel microenvironment has significant effects on cancer metastasis. The aim of the present study was to determine how the morphologic and immunophenotypic features of cancer cells and infiltrating stromal cells within the permeated lymphatic vessels are associated with lymphogenic metastasis. A total of 137 primary lung adenocarcinoma patients with extratumoral lymphatic permeations were examined. Morphologically, the floating cancer nests within the permeated lymphatic vessels were divided into two types: Type A, consisting of a single large cancer nest; and Type B, consisting of multiple small cancer nests. We compared the clinicopathologic characteristics and the immunophenotypes of the cancer cells and infiltrating stromal cells between the Type A and Type B nests. Eleven of 54 Type A patients (20%) had intrapulmonary metastases, compared with 36 of 83 Type B patients (43%; P = 0.006). Immunohistochemically, Type B cancer cells expressed significantly higher levels of CD44 than Type A cancer cells (mean scoresAUTHOR: Scores - what is this score? Is it the number of cells expressing CD44 or the concentration of CD44 or some other type of scoring system? 43.0 vs 20.5, respectively) and E-cadherin (60.5 vs 31.5, respectively), but lower levels of Geminin (11.9% vs 20.3%, respectively) and cleaved caspase 3 (2.4% vs 7.8%AUTHOR: 11.9% vs 20.3%, respectively) and cleaved caspase 3 (2.4% vs 7.8%, - what do the percentages here refer to? The number of cells expressing geminin and caspase 3? The levels of these factors? Please clarify., respectively). Moreover, a significantly larger number of CD204-positive macrophages were present within the cancer-permeated lymphatic vessels in Type B patients than in Type A patients (mean number 9.5 vs 4.6, respectively). The present study reveals that intralymphatic cancer cell and stromal cell phenotypes are susceptible to lymphogenic metastasis, suggesting that lymphogenic metastasis may be affected by the intralymphatic microenvironment they create.

Recruitment of podoplanin positive cancer-associated fibroblasts in metastatic lymph nodes predicts poor prognosis in pathological N2 stage III lung adenocarcinoma.

BACKGROUND: Cancer-associated fibroblasts (CAFs) directly communicate with cancer cells and play important roles in cancer progression. Recent studies have reported that primary cancer tissue with podoplanin-expressing CAFs predicted a poorer outcome among stage I lung adenocarcinoma patients. However, whether podoplanin(+)-CAFs also can be recruited into metastatic lymph nodes and influence the prognosis remains unclear. METHODS: We selected 112 patients with pathological N2 stage III lung adenocarcinoma and examined the podoplanin expression of CAFs and their prognostic impact in primary and metastatic N2 lesions. RESULTS: Podoplanin(+)-CAFs were observed in 61 (54.5 %) primary sites and 44 (39.3 %) metastatic lymph nodes. Podoplanin(+)-CAFs were found at metastatic lymph nodes in 33 (54.1 %) primary podoplanin-positive and 11 (21.6 %) primary podoplanin-negative sites. These findings suggest a significant positive correlation in podoplanin expression in CAFs between pairs of primary and metastatic lesions (P < 0.001). The difference in the overall survival of patients with podoplanin-positive/negative CAFs in their primary lesion was not correlated (P = 0.927). In contrast, patients with podoplanin(+)-CAFs in metastatic lymph nodes had a shorter overall survival than those without podoplanin(+)-CAFs (P = 0.003). In multivariate analyses, podoplanin(+)-CAFs in metastatic lymph nodes were a significantly independent risk factor for a poor outcome (P = 0.007). CONCLUSIONS: Our study indicated that podoplanin(+)-CAFs in metastatic lymph nodes was a significant prognostic factor for overall survival among pathological N2 stage III adenocarcinoma patients.

Clinicopathological features and prognostic factors of adenocarcinoma of the esophagogastric junction according to Siewert classification: experiences at a single institution in Japan.

BACKGROUND: Treatment strategy for adenocarcinoma of the esophagogastric junction (AEG) remains controversial. The aims of this study are to evaluate results of surgery for AEG, to clarify clinicopathological differences according to the Siewert classification, and to define prognostic factors. METHODS: We retrospectively analyzed 179 consecutive patients with Siewert type I, II, and III AEG who underwent curative (R0) resection at the National Cancer Center Hospital East between January 1993 and December 2008. RESULTS: Patients with AEG were divided according to tumor: 10 type I (5.6%), 107 type II (59.8%), and 62 type III (34.6%). Larger, deeper tumors and nodal metastasis were more common in type III than type II tumors. No significant differences were seen in 5-year survival rates among the three types: type I (51.4%), type II (51.8%), and type III (62.6%). Multivariate analysis showed that depth of tumor and mediastinal lymph node metastasis were independent prognostic indicators. The recurrence rate for patients with mediastinal lymph node metastasis was 87.5%. The risk factors for mediastinal lymph node metastasis were length of esophageal invasion and histopathological grade. CONCLUSIONS: Mediastinal lymph node metastasis and tumor depth were significant and independent factors for poor prognosis after R0 resection for AEG. Esophageal invasion and histopathological grade were significant and independent factors for mediastinal lymph node metastasis.

Characteristic immunophenotype of solid subtype component in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinomas represent a morphologically heterogeneous tumor composed of an admixture of different histologic subtypes (lepidic, papillary, acinar, and solid subtype). The presence of a solid subtype component is reported to be associated with a poorer prognosis. The aim of this study was to evaluate the characteristic immunophenotype of the solid subtype component compared with the immunophenotypes of other components. METHODS: We analyzed the clinicopathological characteristics of stage I adenocarcinoma patients with predominant solid subtype disease. Furthermore, we immunostained adenocarcinomas with predominant lepidic, papillary, acinar, and solid subtype components (n = 23 each) for 10 molecular markers of tumor invasiveness and scored the results. RESULTS: Patients showing predominance of the solid subtype component (solid subtype adenocarcinoma) had a poorer prognosis than those showing predominance of the lepidic, papillary, or acinar component. Lymphovascular invasion was more often detected in solid subtype tumors than in others. The solid subtype component showed a significantly stronger staining intensity of laminin-5 expression than the lepidic, papillary, and acinar components (P < 0.001, P < 0.001, and P = 0.016, respectively). The fibronectin and vimentin expression levels were also significantly higher in the solid subtype component than in other components. This immunostaining character was validated by using mixed-subtype adenocarcinomas containing all four components in the same tumor. CONCLUSIONS: This study concluded that the solid subtype component in lung adenocarcinomas exhibit the invasive immunophenotype, including increased laminin-5 expression, compared with the other components, which may be associated with a poorer prognosis.

Clinicopathological features of stomach cancer with invasive micropapillary component.

BACKGROUND: Invasive micropapillary carcinoma has been recognized as a rare disease entity with aggressive tumor behavior. However, few reports have described invasive micropapillary carcinoma in the gastrointestinal tract, particularly its involvement in gastric cancer. METHODS: We retrospectively analyzed 930 patients diagnosed with gastric cancer who underwent gastrectomy, and we then histopathologically evaluated the existence of a regional invasive micropapillary component. Clinicopathological features were investigated in patients with an invasive micropapillary component and compared with such features in 100 patients with gastric adenocarcinoma, selected as stage-matched controls, who underwent gastrectomy during the same period. RESULTS: Of the 930 patients, 14 were histopathologically diagnosed with gastric cancer with a regional invasive micropapillary component. There were no significant differences in age, gender, tumor location, macroscopic type, or type of surgery between patients with an invasive micropapillary component and the pT-matched controls. Histopathologically, significant differences were observed in lymphatic infiltration, venous invasion, the percentage of cases with lymph node metastasis, and the median number of metastatic lymph nodes. The three-year disease-free and overall survival rates of patients with an invasive micropapillary component were 40.5 and 59.3%, respectively, compared with those for the stage-matched controls, which were 72.6 and 80.6%, respectively (p = 0.02 and 0.07). CONCLUSIONS: Patients with gastric cancer with a regional invasive micropapillary component showed marked cancer infiltration in the lymphatic pathway and poor prognosis after gastrectomy.

Differences between squamous cell carcinoma and adenocarcinoma of the lung: are adenocarcinoma and squamous cell carcinoma prognostically equal?

OBJECTIVE: We analyzed pulmonary squamous cell carcinoma and adenocarcinoma patient survival in our single institution database, to evaluate the relationship of histologic analysis to survival and tumor aggressiveness. METHODS: We reviewed 1856 consecutive patients with surgically resected pulmonary squamous cell carcinoma or adenocarcinoma regarding their clinicopathologic characteristics, overall survival and recurrence-free proportion. RESULTS: In squamous cell carcinoma patients, there were more elderly male smokers and more patients with T2-4 tumors, moderately/poorly differentiated tumors, lymph node metastasis or vascular invasion than in adenocarcinoma patients. In all patients and in pN0 patients, patients with squamous cell carcinoma showed significantly poorer overall survival than those with adenocarcinoma, but there were no statistically significant differences in the recurrence-free proportion between the two histologic types. There were statistically significantly more lung cancer-specific deaths in patients with adenocarcinoma than in patients with squamous cell carcinoma (P= 0.001). CONCLUSIONS: There were no differences in the development of recurrence between squamous cell carcinoma and adenocarcinoma of the lung, but considerable differences in overall survival were observed between the two histologic types. According to the stage grouping strategy of the TNM Classification for Lung and Pleural Tumours, these two histologic types need to be staged differently. This survival difference, however, may reflect the difference in patient background rather than in biologic aggressiveness between the two histologic types.

A pilot study of the technical and oncologic feasibility of thoracoscopic esophagectomy with extended lymph node dissection in the prone position for clinical stage I thoracic esophageal carcinoma.

BACKGROUND: Thoracoscopic esophagectomy in the prone position (TSEP) without thoracotomy is more invasive than right transthoracic esophagectomy (TTE). However, TTE and TSEP have not been compared in terms of technical and oncological feasibility for thoracic esophageal carcinomas of the same stage. METHODS: Fifty-nine patients with clinical stage I esophageal cancer underwent esophagectomy with three-field lymph node dissection from 2000 through 2010, 30 patients underwent right TTE through 2008, and 29 patients underwent TSEP from 2008 through 2010. TSEP was performed with four ports from 2008 through 2009 (13 patients) and with five ports--four conventional ports and a 5 mm camera port for the upper mediastinum--from 2009 (16 patients). We retrospectively evaluated the technical and oncologic feasibility of TSEP with extended lymph node dissection for clinical stage I thoracic esophageal carcinoma by comparing surgical outcomes between TTE and TSEP and examined the historical improvements and current status of TSEP, including port placement. RESULTS: All 29 patients who underwent TSEP with three-field lymph node dissection achieved complete resection, and in the 13 patients followed up for more than 1 year, there were no surgery-related postoperative deaths and no recurrence. No significant difference was found between TTE and TSEP in the mean number of dissected mediastinal lymph nodes, amount of blood loss, incidence of postoperative complications, mean postoperative hospital stay, or rate of complete resection or locoregional control, but the mean duration of thoracic procedure was significantly longer for TSEP than for TTE. For TSEP, the incidence of complications was lower and the postoperative hospital stay was shorter with five ports than with four ports. CONCLUSIONS: TSEP with extended lymphadenectomy is a feasible and appropriate surgical technique for clinical stage I thoracic esophageal carcinoma. We believe that its oncological feasibility for advanced esophageal carcinoma also will be demonstrated.

Dynamic molecular changes associated with epithelial-mesenchymal transition and subsequent mesenchymal-epithelial transition in the early phase of metastatic tumor formation.

Metastatic tumor formation via vessel route begins with cancer cell extravasation from vessel lumen, migration into the connective tissue surrounding vessels, and invasion into target organ parenchyma. Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) have been recognized to play an important role in metastatic process, however, how and where these biological changes take place in the early phase of metastatic tumor development has never been clarified. We morphologically evaluated 34 small intrapulmonary metastases formed after cancer cell extravasation from lymphatics (lymphogenic metastasis) and 40 formed in the absence of extravasation (aerogenous metastasis) in human specimens and found that isolated or small clusters of invasive cancer cells (tumor budding) were frequently observed in lymphogenic metastasis (24/34; 71%), but were never observed within aerogenous metastasis. We immunostained 34 lymphogenic metastases for 13 molecular markers of EMT and MET and scored the immunostaining intensity of cancer cells floating in lymphatic vessels (LVs), migrating into the connective tissue surrounding vessels [bronchovascular bundle (BVB)], and growing in lung parenchyma (LP). Cancer cells within BVBs stained more weakly for E-cadherin (p < 0.001), ß-catenin (p < 0.001), and Geminin (p < 0.001) and more strongly for MMP-7 (p = 0.046) and Laminin-5 γ2 (p = 0.037) than tumor cells in LVs. However, cancer cells in LP exhibited resurgent E-cadherin (p = 0.011), ß-catenin (p < 0.001), and Geminin (p = 0.037) expression and reduced MMP-7 (p = 0.038) and Laminin-5 γ2 (p = 0.001) expression in comparison with cancer cells in BVBs. Our results suggested that in the early phase of metastatic tumor formation cancer cells undergo dynamic phenotypic change associated with EMT and subsequent MET.

Clinicopathological characteristics of primary lung adenocarcinoma predominantly composed of goblet cells in surgically resected cases.

Primary lung adenocarcinomas predominantly composed of goblet cells (APGC) are relatively rare, and the clinicopathological characteristics have remained unclear. The aim of this study was to clarify the clinicopathological characteristics of APGC. We selected adenocarcinoma with a goblet cell-type component of ≥ 90% from 2228 cases of surgically resected primary lung adenocarcinoma. The clinicopathological characteristics of APGC (46 cases) were analyzed. APGC showed a significantly higher rate of tumor location on the left side, in the lower lobe and pathological stage I, when compared with the other types of adenocarcinoma. Furthermore, APGC displayed a lower frequency of central fibrosis, plural invasion, pulmonary metastasis, lymphatic permeation, and vascular invasion. APGC showed local recurrence in two of 46 cases (4.3%) and no incidents of distant metastasis. When compared with non-mucinous bronchioloalveolar adenocarcinomas (non-mucinous BAC) without central fibrosis, APGC without central fibrosis, corresponding to mucinous BAC, showed a significantly higher rate of tumor location on the left side and in the lower lobe. In conclusion, APGC formed a distinct subset and should be considered separately from lung adenocarcinoma based on frequent involvement of the left and lower lung and lack of central fibrosis.

Centrally located adenocarcinoma with endobronchial polypoid growth: clinicopathological analysis of five cases.

Lung adenocarcinomas that exhibit endobronchial polypoid growth and arise from the central portion of the respiratory tree are extremely rare and their clinicopathological features are not well understood. We report the clinicopathological characteristics of five cases of centrally located adenocarcinomas. Histologically, in three cases (cases 1, 2, and 3) the tumor had a papillary, acinar, and solid structure. In the other two cases (cases 4 and 5) histological examination revealed a mucin-filled glandular and cystic structure resembling mucoepidermoid carcinoma, although the lesions lacked a squamoid cell component. Immunohistochemical staining revealed that the tumor cells in all five cases were positive for MUC1 and Cytokeratin 7. The tumor cells in cases 4 and 5 were positive for MUC5AC and MUC6, and the expression pattern in these two cases was similar to that of mucoepidermoid carcinoma of the lung. Our findings allowed us to identify two distinct subtypes of centrally located adenocarcinomas with distinct morphological and immunohistochemical characteristics; these should provide new insight into the pathogenesis of central adenocarcinoma of the lung.

Successful Hemispherotomy in a Patient with Encephalopathy with Continuous Spikes and Waves during Sleep Related to Neonatal Thalamic Hemorrhage: A Case Report with Intracranial Electroencephalogram Findings.

Neonatal thalamic hemorrhage is a strong risk factor for developing encephalopathy with continuous spikes and waves during sleep (ECSWS), even when not accompanied by widespread cortical destruction. The efficacy and indication of resective epilepsy surgery in such patients has not yet been reported. A 4-year-old boy was diagnosed with ECSWS based on strong epileptiform activation during sleep and neurocognitive deterioration. He had a history of left thalamic hemorrhage related to a straight sinus thrombosis during the newborn period. He presented with daily absence seizures that were refractory to medical treatment. At age 5, he underwent intracranial electroencephalogram (EEG) recording using depth and subdural strip electrodes placed in the left thalamus and over bilateral cortex, respectively. Interictal and ictal epileptiform discharges were observed in the thalamus, always preceded by discharges in the left or right parietal lobe. Left hemispherotomy successfully normalized the EEG of his unaffected hemisphere and extinguished his seizures. This is the first case report documenting resective epilepsy surgery in a patient with ECSWS due to neonatal thalamic injury without widespread cerebral destruction. Based on intracranial EEG findings, his injured thalamus did not directly generate the EEG abnormalities or absence seizures on its own. Patients with ipsilateral neonatal thalamic injury and even mild lateralized cortical changes may be candidates for resective or disconnective surgery for ECSWS.

Efficacy of long-term adrenocorticotropic hormone therapy for West syndrome: A retrospective multicenter case series.

OBJECTIVES: Long-term adrenocorticotropic therapy (LT-ACTH), which consisted of 2-4 weeks of daily injections of adrenocorticotropic hormone (ACTH) and subsequent months of weekly injections, was tried for relapsed West syndrome (WS) or other intractable epilepsies in small case reports. Our aim was to explore the efficacy of LT-ACTH for preventing WS relapse, as well as the prevalence of its adverse events. METHODS: This is a retrospective, nationwide, multicenter case series of patients with WS who underwent LT-ACTH. Clinical information of the patients and protocol of LT-ACTH were collected from participating institutes in this study. We defined clinical response to ACTH as achievement of hypsarrhythmia and epileptic spasms resolution. Patients who responded to daily ACTH injections were identified and assessed whether they experienced WS relapse during/after the weekly ACTH injection period. The outcome was measured by the nonrelapse rate at 24 months after daily ACTH injections using the Kaplan-Meier method. RESULTS: Clinical information of 16 children with WS was analyzed. The median age at LT-ACTH initiation was 14.5 months (range: 7-68 months). Thirteen (81%) patients had previously undergone conventional ACTH treatment. The LT-ACTH regimens comprised a median of 16 days of daily injections (range: 11-28 days) and 10 months of weekly injections (range: 3-22 months). Seven patients experienced WS relapse during/after subsequent weekly ACTH period, and the nonrelapse rate at 24 months after daily injections was estimated at 60.6% (95% confidence interval: 32.3%-80.0%). Height stagnation, hypertension, and irritability were observed; lethal adverse events were not reported. SIGNIFICANCE: Our study firstly explored the efficacy of LT-ACTH for preventing WS relapse. LT-ACTH might be a treatment option for patients with relapsed or intractable WS; however, we note that our study is limited by its small sample size and the lack of an appropriate control group.