Purely Endoscopic Evacuation of Intracranial Hematomas.

Cerebral hemorrhage is a frequent disease and one of the main causes of disabilities. Even in the case of cerebral hemorrhage, if there were a treatment that would improve the functional prognosis, the benefits would be immeasurable. Although there are limited reports with a high level of evidence in past studies, it has been found that surgery can be effective if a large amount of hematoma can be removed in a minimally invasive manner. Also, it has become clear that the control of bleeding becomes a problem when surgery is performed within 2 days after the onset of stroke and that the therapeutic time window might be longer. In Japan, since the introduction of the transparent sheath by Nishihara et al., endoscopic hematoma removal has been widely performed and has become the standard surgical procedure. The three basic equipment needed for this surgery are a rigid scope, a suction coagulator, and a transparent sheath. The key point of the surgery is to search for hematomas and bleeding points through a transparent sheath and coagulate the bleeding vessels. In this chapter, we will introduce surgical techniques using these devices, but it is important to carefully decide on surgical options by considering your own technique, the condition of each patient, and the devices available in the area.

Renal Immune-related Adverse Event of Pembrolizumab Masked by Pemetrexed.

A Japanese woman in her 60s developed a kidney injury 9 weeks after treatment with pemetrexed, carboplatin, and pembrolizumab for stage IV lung adenocarcinoma. A renal biopsy showed chronic tubulointerstitial damage with minimal focal interstitial inflammation, consistent with pemetrexed-induced nephropathy; thus, pemetrexed was withdrawn. However, the kidney injury continued to worsen. A repeated biopsy showed severe acute tubulointerstitial nephritis, suggestive of a pembrolizumab-induced immune-related adverse event (irAE). The worsening after pemetrexed discontinuation suggested that the irAE had already begun, as the first biopsy showed focal inflammation. This case suggests thatcombining immune checkpoints and chemotherapy requires considering concurrent drug-induced nephrotoxicity.

[Analysis of the Tumor Immune Microenvironment of Colorectal Cancer by Deep Learning-Based Imaging Cytometry].

The tumor immune microenvironment(TIME)of colorectal cancer contains indicators of unique therapeutic outcomes for each cancer patient. Deep learning-based imaging cytometry(DL-IC), which can obtain objective and reproducible cell- related information in tissue sections, has attracted attention as an analytical method for clarifying this indicator. This study demonstrates the validation process of Cu-Cyto, one of DL-IC, regarding cell identification accuracy. Acquisition of"spatial structure"information in TIME is useful for biomarker retrieval and contributes to precision oncology.

Deep Learning-based Image Cytometry Using a Bit-pattern Kernel-filtering Algorithm to Avoid Multi-counted Cell Determination.

BACKGROUND/AIM: In pathology, the digitization of tissue slide images and the development of image analysis by deep learning have dramatically increased the amount of information obtainable from tissue slides. This advancement is anticipated to not only aid in pathological diagnosis, but also to enhance patient management. Deep learning-based image cytometry (DL-IC) is a technique that plays a pivotal role in this process, enabling cell identification and counting with precision. Accurate cell determination is essential when using this technique. Herein, we aimed to evaluate the performance of our DL-IC in cell identification. MATERIALS AND METHODS: Cu-Cyto, a DL-IC with a bit-pattern kernel-filtering algorithm designed to help avoid multi-counted cell determination, was developed and evaluated for performance using tumor tissue slide images with immunohistochemical staining (IHC). RESULTS: The performances of three versions of Cu-Cyto were evaluated according to their learning stages. In the early stage of learning, the F1 score for immunostained CD8+ T cells (0.343) was higher than the scores for non-immunostained cells [adenocarcinoma cells (0.040) and lymphocytes (0.002)]. As training and validation progressed, the F1 scores for all cells improved. In the latest stage of learning, the F1 scores for adenocarcinoma cells, lymphocytes, and CD8+ T cells were 0.589, 0.889, and 0.911, respectively. CONCLUSION: Cu-Cyto demonstrated good performance in cell determination. IHC can boost learning efficiencies in the early stages of learning. Its performance is expected to improve even further with continuous learning, and the DL-IC can contribute to the implementation of precision oncology.

Fatal and extensive multiorgan hemorrhages in anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis: An autopsy case report.

INTRODUCTION: Anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) is an autoantigen associated with dermatomyositis (DM). Anti-MDA5 Ab-positive DM patients frequently exhibit clinically amyopathic dermatomyositis (CADM), and develop rapidly progressive interstitial lung disease (RPILD). Even with early detection and potent combination immunosuppressive therapy, anti-MDA5 Ab-positive DM patients have a poor prognosis. In the present case report, we present a rare autopsy case of a patient with anti-MDA5 Ab DM with RPILD who exhibited diffuse alveolar damage (DAD) patterning in lung specimens, and extensive hemorrhages in multiple organs. PATIENT CONCERNS: An 82-year-old Japanese man admitted with bacterial pneumonia was subsequently diagnosed with anti-MDA5 Ab-positive DM based on skin manifestations (mechanic's hand, ulcerated palmar papules, and flagellate erythema), myositis, interstitial pneumonia, and elevation of anti-MDA5 Ab titer. DIAGNOSIS: The patient was diagnosed with anti-MDA5 Ab DM, complicated with RPILD. INTERVENTIONS: The patient received potent immunosuppressive therapy consisting of pulse methylpredonisolone at a dose of 1000 mg for 3 days, followed by prednisolone at 60 mg/d, a 1000 mg pulse of intravenous cyclophosphamide (IVCY), and oral tacrolimus at 6 mg/d. Intravenous immunoglobulin (IVIG) at a dose of 400 mg/kg/d for 5 days was subsequently administered. OUTCOMES: Despite triple immunosuppressive therapy and IVIG, the patients' respiratory status deteriorated, and the patient died of respiratory failure on the twelfth day after admission. An autopsy revealed pulmonary DAD and multiorgan hemorrhages, including the left iliopsoas muscle, gastric and bowl mucosa, spleen, and left adrenal gland. LESSONS: Multiorgan hemorrhages may be a fatal complication in anti-MDA5 Ab DM patients.

Minute perivascular epithelioid cell (PEC) nests in the abdominal lymph nodes--a putative precursor of PEComa.

A perivascular epithelioid cell tumor (PEComa) is a peculiar growth defined as a mesenchymal tumor composed of histologically and immunohistochemically distinct perivascular epithelioid cells (PECs). Because neither normal counterparts nor precursor lesions of PEComa have been identified, we examined minute PEC nests, ranged from 0.8 mm to 10 mm, to investigate the possible origin of the PEComa. We examined a total of 80 677 para-aortic and pelvic lymph nodes that were systematically dissected from 1656 patients for gynecological malignancies. The identified lesions were confirmed immunohistochemically with multiple PEC markers, including smooth muscle actin, HMB45, melan-A, MiTF, ER and PgR. A total of 66 minute PEC nests were found in 21 patients (1.3% of the total population) with an average frequency of 3.1 lesions per patient. In cases of multiple involvement, 11 of 13 nests were located at the same level of multiple lymph node or on continuous levels. The lesions were preferentially distributed at the level of para-aortic and high pelvic lymph nodes. All nests were positive for actin and HMB45, whereas the other markers were positive with varying frequencies. The minute PEC nests may be associated with the possible normal counterpart of PEComas.

HNF4α as a marker for invasive mucinous adenocarcinoma of the lung.

A new lung adenocarcinoma classification was recently proposed by IASLC/ATS/ERS. In this classification, invasive mucinous adenocarcinoma (IMC) is placed in a new category because of its unique radiologic, morphologic, and genetic characteristics. Minimal cytologic atypia characterizes this tumor; thus, it is occasionally difficult to make a diagnosis with a biopsy specimen. We used immunohistochemistry to examine HNF4α expression in a tissue microarray consisting of 278 lung adenocarcinoma specimens. In addition, we analyzed the clinicopathologic features, including EGFR, KRAS, and ALK mutation status. HNF4α expression was detected in 33 of the 37 surgically resected IMCs. The tumor cells were uniformly labeled with the molecule in all of the corresponding biopsy specimens, whereas the normal cells were not. Although HNF4α was also expressed in other lung adenocarcinoma subtypes, those with HNF4α expression shared IMC features, including negative TTF-1 expression (P<0.001), positive CDX2 expression (P<0.001), positive KRAS mutation status (P=0.001), and negative EGFR mutation status (P<0.001). Although some ALK-positive adenocarcinomas showed IMC morphology, the tumors were negative for HNF4α, suggesting that they belonged to a different group of tumors. We found that HNF4α labeled all of the IMC tumors except the ALK-positive adenocarcinomas. Thus, HNF4α positivity could serve as a useful marker for overcoming the diagnostic difficulties caused by minimal nuclear atypia and sparse tumor cells in small biopsy samples. Because other adenocarcinoma subtypes with HNF4α expression share clinicopathologic features with IMC, these adenocarcinomas, especially the columnar cell type of acinar-predominant adenocarcinoma, might constitute a biological spectrum of IMC.

What does the CT angiography "spot sign" of intracerebral hemorrhage mean in modern neurosurgical settings with minimally invasive endoscopic techniques?

Hematoma expansion is correlated with morbidity and mortality for patients with intracerebral hemorrhage (ICH). Recent studies demonstrated that contrast extravasation on contrast-enhanced CT and small-enhancing foci, so-called spot signs, on CT angiography are associated with subsequent hematoma enlargement. Such radiological markers of ICH may have significant implications not only as a surrogate marker for hematoma expansion in medical hemostatic therapy but also as indication for surgery. In this article, a brief description of contrast extravasation and "spot sign" will be provided first. The findings of some of the important trials that shaped the current landscape of therapeutic interventions for ICH will then be reviewed. Many neurosurgeons have faced a significant dilemma since the Surgical Trial in Intracerebral Haemorrhage (STICH) trial was published. Under adverse circumstances, many neurosurgeons assume that minimally invasive surgical interventions are still likely to benefit some patients and will be more effective. Among future candidate strategies for ICH, the most promising is neuroendoscopic surgery with direct hemostatic devices, which attains direct local hemostasis at the sites of vascular rupture. It is plausible that ultra-early direct hemostatic surgery given in the emergency setting might reduce hematoma volume and rebleeding and improve outcome. Finally, a description of future avenues of minimally invasive surgery for ICH treatment and suggestions for the design of further studies using reliable predictor of hematoma expansion spot sign will be provided. Neuroendoscopic interventions are minimally invasive and are likely of benefit in hemostasis and hematoma removal. On the basis of these observations, the spot sign of ICH has sub-emergency surgical implications.

Is primary pulmonary meningioma a giant form of a meningothelial-like nodule? A case report and review of the literature.

Minute pulmonary meningothelial-like nodules (PMNs) are asymptomatic, small nodules that are occasionally detected in surgical or autopsy specimens. Recent improvements in tumor imaging and the increased use of computed tomography (CT) scans of the chest have led to the early detection of these pulmonary nodules in various clinical settings, often before surgery or health examinations. However, large PMNs have rarely been observed. In this study, we report a patient with a large PMN, which was almost identical to so-called 'primary pulmonary meningioma'. A CT scan of his chest revealed a small, well-circumscribed nodule. Immunohistochemical analysis of the tumor revealed that the tumor cells were positive for CD56, epithelial membrane antigen, and progesterone receptor. Given the similarity of these results to the staining pattern of minute PMNs in previous reports, we suggest that the primary pulmonary meningiomas reported to date are, in fact, a giant form of PMN.

A novel monoshaft bipolar cautery for use in endoscopic intracranial surgery. A short technical note.

BACKGROUND: Intraoperative hemorrhage is a critical issue in the endoscopic evacuation of intracerebral hemorrhage (ICH). Refined and dedicated endoscopic instruments for hemostasis are required. In this technical report, a hemostatic procedure using a monoshaft bipolar cautery is described. TECHNIQUE AND INSTRUMENTATION: The endoscope and monoshaft bipolar cautery are combined into a single-handed instrument, leaving the surgeon's other hand free to manipulate a suction cannula, and so a bimanual hemostatic device system - a combination of a monoshaft bipolar cautery and a multifunctional suction cannula - is obtained. RESULTS: Hemostasis was possible with the monoshaft bipolar cautery during endoscopic hematoma evacuation procedures. No intraoperative complications during hemostasis were apparent, nor were any apparent postoperative complications suggestive of inadvertent tissue damage. CONCLUSIONS: The present report describes the successful use of a monoshaft bipolar cautery and its application in a bimanual hemostatic device system.

Early recovery and better evacuation rate in neuroendoscopic surgery for spontaneous intracerebral hemorrhage using a multifunctional cannula: preliminary study in comparison with craniotomy.

Neuroendoscopy is a promising therapeutic option for spontaneous intracerebral hemorrhage (ICH). We sought to compare the clinical outcomes between neuroendoscopic surgery and craniotomy for spontaneous ICH. We retrospectively analyzed the clinical and radiographic data of 43 patients treated with 23 neuroendoscopic procedures (endoscopy group) and 20 microsurgical procedures (craniotomy group). Rebleeding rate, surgical complications, and/or death were identified as primary clinical endpoints during the 2-month postoperative follow-up period. Evacuation rate, Glasgow Coma Scale (GCS) score at day 7, and Glasgow Outcome Scale (GOS) score were compared as well. A composite primary endpoint was observed in 5 cases (11.6%), including 1 postoperative death in the endoscopy group (4.3%) and 4 postoperative deaths in the craniotomy group (20.0%). No rebleeding was observed in the endoscopy group. The evacuation rate was significantly higher in the endoscopy group compared with the craniotomy group (99.0% vs 95.9%; P < .01). Mean GCS score at day 7 was 12 for the endoscopy group and 9.1 for the craniotomy group (P < .05). The mean change in GCS score was +4.8 for the endoscopy group and -0.1 for the craniotomy group (P < .001). Our data indicate that in patients with ICH, endoscopic surgery is safe and feasible, and may promote earlier recovery. Our results warrant a future prospective, randomized, controlled efficacy trial.

Fluorescent in situ hybridization 1p/19q deletion/imbalance analysis of low-grade and atypical meningiomas.

The chromosomal 1p/19q state was analyzed in 16 low-grade meningiomas and 7 atypical meningiomas using fluorescent in situ hybridization (FISH) analysis. Chromosome 1p aberrations were observed in all atypical meningiomas, but in only one low-grade meningioma. Atypical meningiomas showed 19q deletion or imbalance, suggesting chromosomal instability of 19q. A small group of low-grade meningioma showed 19q aberrations. FISH 1p/19q deletion/imbalance analysis is a sensitive method for detecting chromosome aberrations of meningiomas and provides useful information for grading of meningiomas. Patients with low-grade meningioma with chromosomal instability of 1p/19q should be followed up carefully. Assessment of the chromosomal state by FISH might be of crucial importance in the clinical management of meningiomas.

Subcutaneous migration of distal ventriculoperitoneal shunt catheter caused by abdominal fat pad shift--three case reports.

Aberrant migration of a ventriculoperitoneal shunt catheter is an infrequent complication and the mechanism is unclear. We report three cases of subcutaneous migration of the distal catheter. The relationship between thick abdominal fat and catheter migration was suggested in all three cases. Abdominal radiography showed that the subcutaneous fat pad had slid down in the standing position, pulling the catheter out of the peritoneal cavity. We suggest the following mechanisms: Changing from the supine position to the standing position caused subcutaneous fat pad to slide down, the shifted fat pad pulled out the catheter from the peritoneal cavity, and anchoring prevents the catheter returning into the peritoneal cavity. Subcutaneous fat pad shift might act as a "windlass," resulting in coiling of the catheter in the subcutaneous tissue. During daily life, the peritoneal catheter was pulled out repeatedly and finally was coiled within the subcutaneous fat tissue. Placement of the catheter between the subcutaneous fat pad and the abdominal muscle wall will help to avoid this rare complication. This preventive measure is especially recommended for obese patients with a high risk of subcutaneous migration of the peritoneal catheter.

Balanced irrigation-suction technique with a multifunctional suction cannula and its application for intraoperative hemorrhage in endoscopic evacuation of intracerebral hematomas: technical note.

OBJECTIVE: Endoscopic evacuation of intraoperative hemorrhage is proving to be increasingly useful and effective. For general agreement that endoscopic evacuation has advantages over craniotomy, secure hemostatic procedures are crucial. TECHNIQUE: This technical note focuses on hemostatic procedures for managing intraoperative hemorrhage. Handling of the multifunctional suction cannula and its application for balanced irrigation-suction are fully explained in this report. RESULTS: Nearly complete evacuation of hematoma was achieved in all 15 cases. In 9 cases of intraoperative arterial bleeding, secure hemostatis has been accomplished. No surgical complications or rebleeding occurred. CONCLUSION: Even careful atraumatic evacuation of a hematoma can sometimes result in intraoperative hemorrhage. Repeated irrigation and point suctioning may be necessary to keep the operating field clear. A multifunctional suction cannula would be useful for maintaining irrigation and suction balance. Coagulation of a bleeding artery can be performed under clear visualization. A balanced irrigation-suction technique results in secure hemostasis.

FISH 1p/19q deletion/imbalance for molecular subclassification of glioblastoma.

Glioblastoma is the most malignant and frequent of the glial tumors. A minor fraction of glioblastoma may contain areas showing oligodendroglioma-like tumor cell differentiation. Several authors have described such tumors as glioblastoma with oligodendroglial component (GBMO). GBMO may represent the ultimate level of malignancy in the oligodendroglial lineage. The oligodendroglial component and combined loss of chromosomal arm 1p and 19q in glioblastoma indicate increased survival. In our study, we analyzed 1p and 19q status in a series of 12 glioblastoma and 8 oligodendroglial tumors using fluorescence in situ hybridization (FISH) on paraffin-embedded tissues. In each case, hybridization status was classified as deletion, imbalance, polysomy, amplification, or normal pattern. Other genetic alterations such as CDKN2A (p16), RB, and EGFR were also assessed. On histological review, 2 of 12 glioblastoma (16.7%) were classified as GBMO. Chromosome 1p/19q deletion was detected in 3 of 12 glioblastomas (25%). In contrast, all 8 oligodendroglial tumors showed 1p/19q deletion. All GBMO had 19q deletion with imbalance, whereas 1 of 10 ordinary glioblastoma (10%) demonstrated 19q deletion with imbalance. All but 1 ordinary glioblastoma (90%) showed CDKN2A (p16) deletion, but no GBMO displayed this alteration. Our results indicate that GBMO may be a distinct subtype of glioblastoma harboring a characteristic molecular profile. FISH on paraffin-embedded specimens is a useful method for subclassification of glioblastoma.

Concomitant cerebral infarction and intraventricular hemorrhage in moyamoya disease. Case report.

Moyamoya disease is categorized as either ischemic or hemorrhagic type, and the pathogenesis of this disease is unknown. In this paper, the authors report on a patient with moyamoya disease who suffered concomitant cerebral infarction and intraventricular hemorrhage (IVH). Endoscopic removal of the intraventricular hematoma and ventricular drainage were both performed. The patient did not experience further ischemic complications. Patients with moyamoya disease have intracranial hemodynamic insufficiency. Adequate control of intracranial pressure and removal of the intraventricular hematoma is important to prevent progression of cerebral infarction and hydrocephalus. To the authors' knowledge, this is the first report of concomitant cerebral infarction and IVH, or true mixed-type moyamoya disease. A possible pathogenesis of this rare condition is discussed.