The 2021 WHO classification of tumors of the central nervous system, 5th edition (WHO CNS 5) is built on the previous, revised 4th edition, published in 2016, which incorporated molecular information into the diagnosis of brain tumors for the first time, breaking with the century-old histogenetic classification. WHO CNS 5 also adopted a series of recommendations of "the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT)" that facilitates a consensus review of novel diagnostically relevant data and determines how such information can be fit into future CNS tumor classifications. In WHO CNS 5, the grading system was reformed to "grading within tumor types," and the tumor groups, especially diffuse gliomas, have been significantly restructured; the diffuse gliomas have been divided into the adult type and the pediatric type, the latter being subdivided into low-grade and high-grade gliomas. Based on molecular alterations, 22 novel tumor types are recognized, and some nomenclature has also been revised. The integrated, layered diagnosis of combining histology, grading, and molecular information was recommended to provide clinically relevant information.

Meningiomas, schwannomas, and pituitary adenomas are typically benign tumors of intracranial origin, but all of these tumors have a border with the surrounding tissue. The basic structure is a clear "boundary" between the tumor and its surroundings, with a thin membrane layer to create that separation. This layer of membrane is the boundary between the tumor and its surroundings and provides a space for the tumor to grow its cells, and can be viewed as the so-called "tumor capsule. Based on the relationship between the membrane structure of the tumor capsule and the surrounding normal tissues, we perform surgery to reduce surgical complications. We histologically evaluated three types of tumor capsules(meningioma, schwannoma, and pituitary adenoma)and compared the membrane structure of each tumor with that seen in clinical surgery.

The extended endoscopic endonasal approach(EEA)has been expanding in recent years with the development of instruments and surgical techniques. Basically, sela, extradural, and intranasal lesions such as pituitary tumor, craniopharyngioma, chordoma, chondrosarcoma, and cholesterol granuloma are indicated. Intradural lesions or lesions that extend laterally or downward to the craniocervical junction are more difficult to operate. In addition, cases of hard tumor with calcification of the tumor, cases in which the tumor involves important blood vessels, re-operative cases, and cases after radiotherapy are also difficult cases and should be considered preoperatively. In recent years, we have been trying to keep the nasal structures as much as possible without removing nasal structure, but in cases where the tumor has invaded and destroyed the nasal structures, extended EEA is necessary. The anatomy of the extended EEA is complicated and not common among neurosurgeons. In this chapter, we present the basic anatomy and surgical cases to be understood in extended EEA and explain the pitfalls.

Skull base surgery for malignant skull base disease is one of the most difficult surgeries. The success of the surgery depends on the harmonization of the excellent skills of the three departments: neurosurgery, otorhinolaryngology/head and neck surgery, and plastic surgery. In addition, it is necessary to perform complete resection, that is, resection in which the malignant tumor is removed along with some surrounding healthy tissue. It is known that there is a statistically significant difference between negative and positive resection margins. In the event of a positive resection margin, chemoradiation with high-dose cisplatin is standard for the most common squamous cell carcinomas.

While most meningiomas are histologically benign tumors, higher grade meningiomas classified as WHO grades 2 and 3 are not always amenable to the standard treatment. To accurately assess the biological characteristics and prognosis of the tumor, the WHO classification of meningiomas has been continuously revised based on the latest findings. This article describes the recent modifications of the WHO classification of meningiomas. In the 2021 WHO classification, molecular diagnosis was considered more important and it was integrated into the classification as a stand-alone criterion of some subtypes. As for treatment, surgical resection is the mainstay treatment for meningiomas of all WHO grades while the importance of radiation therapy should be emphasized, especially for skull base meningiomas, to balance the surgical risk and for functional preservation. Among the new surgical techniques, endoscopic resection of midline skull base meningiomas has been established over the last decades. In addition, several notable new insights to control high-grade meningiomas based on prospective observational studies are introduced in this article.

Endoscopic endonasal skull base surgery has become popular due to its minimally invasive nature to the patient and the development of various medical devices. The reason why it is considered less invasive is that it is possible to reach the anterior skull base lesion using the corridor of the nasal cavity and paranasal sinuses. The roles of the nasal sinuses include acting as breathing pathways, warming, humidifying, and filtering of inhaled air, olfaction, and being a resonant cavity, all of which are important for a comfortable life, and the loss of these functions reduces the quality of life. Therefore, to perform endoscopic endonasal skull base surgery in a minimally invasive and safe manner, it is necessary to understand the anatomy of the nasal sinuses to reach anterior skull base lesions while preserving nasal structures as much as possible. This article describes the normal local anatomy of the nasal cavity and the paranasal sinuses, as well as the surgical techniques, especially the anterior skull base approach and the pterygopalatine fossa approach, for endoscopic endonasal skull base surgery.

The patient was an 83-year-old woman with a history of breast cancer, distal right radial edge bone fracture, and cervical spine symptoms who had been diagnosed with an arachnoid cyst 9 years previously. She was examined by a nearby doctor, because of an approximately 1-year history of reduced verbal output; she also begun experiencing difficulties with walking. However, she was diagnosed with aging, a history of cervical spondylosis, and the effects of past fractures.At the time of this consultation, she was conscious and lucid, with mild right-sided hemiparesis, was unable to write, and had mild motor aphasia. Head magnetic resonance imaging revealed an arachnoid cyst (longer axis: 10 cm) in the left frontal lobe that did not take up contrast media. There was also a midline shift. The cause of the right hemiparesis and motor aphasia was probably compression of the left frontal lobe by the arachnoid cyst.We performed excision of the cyst wall by craniotomy and placed a cyst-peritoneal shunt under general anesthesia. At approximately one week after surgery, the patient was able to write and her motor aphasia improved. She was discharged 20 days after the operation.It is rare for an arachnoid cyst to increase in size after childhood. In the present case, surgical treatment led to a good outcome in an elderly patient with a symptomatic arachnoid cyst. Arachnoid cysts rarely increase in size. These cysts may become symptomatic in elderly people after lying clinically dormant for a long time.

A 79-year-old man was admitted to our hospital because of sudden onset of left ataxic hemiparesis. Brain MRI diffusion weighted images showed typical lacunar infarction on the right internal capsule. He had no risk factors of cerebrovascular disorder such as hypertension, diabetes mellitus, hyperlipidemia and arrhythmia. On admission, he had a slight fever and his laboratory data showed anemia, thrombocytopenia and elevation of CRP and LDH. Intravascular large B-cell lymphoma (IVLBCL) was suspected because the serum level of soluble IL-2 receptor was also elevated. Pathological diagnosis of IVLBCL was underwent by the skin biopsy from his senile hemangiomas. Although IVLBCL was known to demonstrate various CNS lesions, it is extremely rare to be manifested as a single lacunar infarction, and this case must be important for the differential diagnosis.

A 23-year-old man was referred to our department for chest abnormal shadow. Computed tomography (CT) of the chest revealed a well-defined 1.2 cm nodule in the S4 segment of the right middle lobe and a well-defined 1.8 cm nodule in the S10 segment of the right lower lobe. The patient was found to have a fracture in the left fifth rib due to the falling accident at playing snowboard, two months before. He was diagnosed with a benign tumor in the right middle lobe and the right lower lobe and was performed surgery. Thoracoscopy revealed a yellowish-brown tumor in the right middle lobe( S4) and a yellow-brown tumor in the right lower lobe( S10). Both lesions were diagnosed as clots by rapid intraoperative pathologic diagnosis. Histopathological diagnosis was an intrapulmonary hematoma.

In 21 of 47 mice, tumor development was initiated by intraperitoneal injection of one side population(SP)cell derived from a mouse ascites tumor and the host mice died of the ascites tumor. The SP cells were thought to be cancer stem-like cells. Examination by differential interference contrast microscopy revealed that the SP cells were smaller in size(ϕ 27.5µm), and had a higher N/C ratio, sparser and shorter microvilli on the cell surface, and significantly fewer mitochondria, as compared to the non-SP cells(ϕ 30.0µm). These findings could be related to the stemness of the SP cells.

Late-stage elderly patients have low tolerance to chemotherapy, and they have difficulties when they are treated with standard chemotherapy. We report a case of a late-stage elderly patient who had a long-term response to UFT/UZEL/bevacizumab( Bev)therapy for lung metastasis after surgery for early-stage colon cancer. He was 82-years-old and underwent laparoscopy-assisted sigmoid colectomy for sigmoid colon cancer at another hospital. The pathological diagnosis was pT1b, ly1, v0, N0, M0, pStage Ⅰ. Six months after the surgery, a small nodule was noted in the middle lobe of the right lung. It grew five months later and was definitely diagnosed as lung metastasis. Considering his physical condition and tumor size, we opted to introduce less invasive chemotherapy instead of standard chemotherapy. UFT/UZEL/Bev was started 14 months after surgery. Although he required dose reduction due to anorexia, he safely continued the treatment with partial response (PR), which was maintained for 2 years and 6 months. While UFT/UZEL/Bev has no convincing evidence, it may be an option for vulnerable patients, especially those with non-life-threatening disease.

Oral uracil and tegafur plus Leucovorin(UFT/LV)therapy is one of the standard adjuvant chemotherapies for colorectal cancer, and is widely used without any serious adverse events. Herein, we describe a case of UFT/LV-induced acute liver failure in a 75-year-old woman who underwent laparoscopic sigmoidectomy for sigmoid colon cancer. She was diagnosed with advanced colon cancer and lymph node metastasis by postoperative histopathological analysis, and adjuvant chemotherapy was initiated. After 30 days of commencing the therapy, the patient visited our hospital with complaints of severe diarrhea and difficulty in food intake. The apparent cause of these symptoms was unclear on computed tomography(CT), and mild liver damage was revealed in blood test results. The hepatic disorder gradually progressed after the hospitalization, and the condition was diagnosed as acute hepatic insufficiency. Additionally, obvious atrophy of the liver parenchyma and significant ascites were confirmed on CT. Two months later, the platelet count decreased markedly, but fortunately, no bleeding occurred. There has been no recurrence since 2 years after the surgery without any additional adjuvant therapy.

A 66-year-old woman underwent total mastectomy with level Ⅰ and Ⅱ axillary lymph node dissection for right breast cancer in July 2007. The pathology results indicated the presence of T2N0M0 invasive ductal carcinoma(tubule forming type), that was estrogen receptor-positive and human epidermal growth factor 2-negative. She received postoperative adjuvant therapy with oral anastrozole(ANA)for 5 years. Eleven years after surgery, at the age of 77 years, a chest X-ray examination during a routine health checkup identified a mass shadow in the right lung. Further investigation revealed bilateral multiple lung metastases due to breast cancer recurrence. Histological examination of a tissue obtained by computed tomography(CT)-guided lung biopsy confirmed that the histological type and subtype were identical to those found in the initial surgery. Hence, endocrine therapy with ANA plus CDK4/6 inhibitor was started in November 2018. However, the first CDK4/6 inhibitor, palbociclib, caused severe myelosuppression even when the dose was reduced by 2 levels. Therefore in January 2019, the patient was switched to abemaciclib, with the dose reduced by 1 level initially and then reduced by 2 levels from August 2019. In June 2019, new multiple lung metastases appeared, and the patient was switched from ANA to fulvestrant, after which complete response was achieved in 6 months. CT in June 2021 showed no recurrence, and the patient(now 80-year-old)continues to take abemaciclib plus fulvestrant therapy.

A 52-year-old male was diagnosed with cT4N3M1b, cStage Ⅳ adenocarcinoma of the lung, and underwent 6 courses of pemetrexed(PEM), carboplatin(CBDCA), and bevacizumab(Bev)therapy, followed by 4 courses of PEM/Bev maintenance therapy. Due to the deterioration of his condition, 4 courses of pembrolizumab(Pembro)therapy were administered as second- line therapy, but the treatment was discontinued due to disease progression. Third-line therapy with docetaxel(DTX)/ ramucirumab(Rmab)was administered, resulting in a partial response, but discontinued due to adverse events. Finally, fourth-line therapy with atezolizumab(Atezo)was initiated. After 6 courses of Atezo therapy, partial response was achieved, and the tumor continued to shrink for 3 years. The aim of the treatment strategy for both PD-1 and PD-L1 antibody drugs is to suppress T-cell exhaustion, and if either drug fails, the other drug may theoretically fail. However, in this case, the PD-L1 antibody drug was effective against non-small cell lung cancer that had shown resistance to PD-1 antibody drugs, suggesting that even if a patient becomes resistant to PD-1 antibody drugs, PD-L1 antibody drugs may result in effective outcomes.

To investigate the efficacy and toxicity of adjuvant chemotherapy(AC)in elderly patients with Stage Ⅲ colorectal cancer(CRC).

The subject was a man in his late 70s who was seeing a family physician for diabetes and dyslipidemia on an outpatient basis. A routine medical checkup revealed liver dysfunction, prompting an abdominal ultrasound. As a result, a large hepatic tumor was discovered, prompting a thorough examination. The patient was diagnosed with hepatocellular carcinoma and multiple liver metastases, as well as tumor shadows that could indicate pulmonary metastases, after a thorough examination at our hospital. Due to the patient not having viral hepatitis or any drinking history and had formerly been confirmed as having fatty liver, a diagnosis of cirrhosis and hepatocellular carcinoma caused by NASH (nonalcoholic steatohepatitis) was given. A Child-Pugh score of 5 (A) and modified albumin-bilirubin (mALBI) grade 2 were used to maintain liver function. As a result, a 12-mg/day Lenvatinib treatment regimen was initiated. From the 6th day of the start of oral administration, the patient developed right hypochondralgia and loss of appetite. Blood samples showed increased levels of liver enzymes and inflammatory reaction, requiring hospitalization for closer examination. Intratumoral hemorrhage from hepatocellular carcinoma was discovered by dynamic CT scans. The patient's general condition was stable, and an angiogram was performed on the 3rd day of admission. As a result, persistent extravasation was discovered, necessitating transcatheter arterial embolization (TAE) treatment of the lesion for tumor vessel embolization. Thereafter, transient deterioration of the liver function occurred but an immediate improvement was seen. The patient was discharged without a recurrence of hemorrhage. An outpatient follow-up was performed, with blood test results indicating that liver function was maintained with a Child-Pugh score of 6 (A), and a dynamic CT showing that intratumoral hemorrhage was under control, allowing for readministration. Readministration of Lenvatinib was started at 4mg/day, one level lower, because the patient's body weight had dropped below 60kg. There are few reports on Lenvatinib-induced intratumoral hemorrhage, and this is a unique case worthy of reporting, with previous literary references, in which the entire process from intratumoral hemorrhage to readministration of Lenvatinib after embolization treatment has been documented.

Intraductal papillary mucinous carcinoma (IPMC) arising from the heterotopic pancreas is rare. A case of IPMC metastasis from the jejunal heterotopic pancreas was described. The heterotopic pancreas could be the source of the submucosal tumor-like lesion found in the small intestine with an elevated carbohydrate antigen (CA) 19-9 level. A 60-year-old woman was admitted to the hospital with pulmonary thromboembolism and anemia. The level of CA19-9, a tumor marker, was found to be 211.8U/ml. A tumor in the jejunum was discovered using contrast-enhanced computed tomography. There were also a number of hepatic tumors found. A submucosal tumor-like lesion in the jejunum was discovered during an enteroscopy, and a biopsy revealed it to be an adenocarcinoma. Partial resection of the jejunum was performed to control hemorrhage. Histopathology revealed an invasive IPMC arising from a heterotopic pancreas (Heinrich type II) and chemotherapy with gemcitabine and nab-paclitaxel was initiated. There have only been three cases of invasive IPMC from a heterotopic pancreas reported, and this is the first one to include chemotherapeutic treatment of distant metastasis.

A 43-year-old woman was suffering from epigastric pain. Her gastroscopy revealed polyposis of the stomach, and her biopsy revealed a hyperplastic polyp. During the 18-month follow-up, the polyps proliferated, and the patient was referred to our institute for further investigation and treatment. A juvenile gastric polyposis diagnosis was made. She refused to have the surgery despite the fact that it was necessary due to the anemia and hypoalbuminemia she was experiencing. Endoscopic biopsy results revealed gastric cancer at a follow-up visit 2 years and 3 months later; thus, a laparoscopic total gastrectomy was performed. Pathological examination revealed adenocarcinomas that were scattered and well-differentiated, with hyperplastic polyps in the background. No lymph node metastasis was found. Despite the fact that juvenile gastric polyposis is a pathologically benign disease, there have been numerous case reports of surgery being performed due to anemia, hypoalbuminemia, or gastric cancer associated with the disease. When gastric cancers are discovered in cases of juvenile gastric polyposis, they are usually in an early stage, making them a good candidate for laparoscopic total gastrectomy.