HER2-positive metastatic colorectal cancer occurs in 2-4% of all colorectal cancers, about 5% in RAS wild-type colorectal cancer, and only 0.2-1.4% in RAS mutant colorectal cancer. The TRIUMPH trial was conducted in Japan for patients with HER2-positive colorectal cancer, and its results led to the approval of the combination therapy of pertuzumab and trastuzumab for the treatment of HER2-positive unresectable advanced or recurrent colorectal cancer that has progressed during chemotherapy in March 2022 in Japan. In the field of colorectal cancer, the development of new HER2-targeted drugs such as antibody-drug conjugates and bispecific antibodies is ongoing, and future developments are expected to be of interest.

Human epidermal growth factor receptor 2(HER2)positive breast cancer has been regarded as a poor prognosis breast cancer, but since the development of trastuzumab and various anti-HER2 drugs, the prognosis has significantly improved. Also, combining anti-HER2 drugs with chemotherapy as preoperative treatment, shows high ratings of pathological complete response(pCR). In terms of breast cancer, pCR is a prognosis predictive factor. As a result, in perioperative treatment for HER2 positive breast cancer, residual disease-guided approach which means to select postoperative treatment according to the response to preoperative chemotherapy has become the main stream. Furthermore, trastuzumab deruxtecan, which had been covered by insurance only for HER2 positive metastatic or recurrent breast cancer, was newly reimbursed for breast cancer with low HER2 expression at the end of March 2023, and the future movement is attracting attention.

Transsphenoidal surgery is the first-line treatment for most functioning pituitary neuroendocrine tumors(PitNETs). Medical therapies are usually chosen for patients with residual or refractory tumors after surgery or contraindications to surgery. Dopamine agonists(DA)are the first-line treatment for prolactinomas. Somatostatin analogs are the first line of therapy for GH- and TSH-producing PitNETs. In severe hypercortisolemia due to ACTH-producing PitNETs, adrenal enzyme inhibitors such as 11β-hydroxylase inhibitors should be started immediately, as marked hypercortisolemia leads to serious opportunistic infections. Pasireotide and DA are usually administered to treat mild hypercortisolemia. Based on the histological pattern of secretory granules, somatotroph, lactotroph, and corticotroph tumors can be divided into two subtypes: densely granulated and sparsely granulated. Densely granulated lactotroph tumors tend to be resistant to DA. In contrast, densely granulated somatotroph and corticotroph tumors express high levels of somatostatin receptors and are more responsive to somatostatin analogs. Since ACTH-producing PitNETs express SSTR5 without SSTR2, the second-generation somatostatin analog, pasireotide, is effective against ACTH-producing PitNETs.

Surgical treatment of craniopharyngioma still presents several challenges. The tumor recurs at a high rate when its removal is insufficient. However, total resection of the tumor has a high risk of complications owing to its proximity to the hypothalamus and the pituitary stalk. In addition, tumor control by radiation treatment is insufficient for long follow-up periods of over 10 years. Therefore, various treatments have been selected, ranging from partial tumor removal followed by radiation to total tumor removal, even if it involves sacrificing pituitary functions. In this article, we explain the surgical treatment with a focus on endoscopic endonasal surgery for craniopharyngiomas.

The major changes in the upcoming 5th edition of the "2022 WHO Classification of Endocrine and Neuroendocrine Tumors" include:(1)evolution of the nomenclature: from pituitary adenoma to pituitary neuroendocrine tumour(PitNET),(2)detailed subtyping of a PitNET based on the tumor lineage, cell type, and related characteristics,(3)endorsement of the routine use of immunohistochemistry for pituitary transcription factors(PIT1, TPIT, SF1, GATA3, and ER-alpha),(4)introduction of some additional clinicopathologically distinct PitNET subtypes,(5)introduction of the term "metastatic PitNET" to replace the previous terminology "pituitary carcinoma," and(6)unifying posterior lobe tumors, the family of pituicyte tumors that invariably express TTF1, et al. Currently, no widely agreed grading or staging systems for PitNETs exist. Prognosis varies by tumor subtype and certain tumor subtypes are recognized as more aggressive(high-risk PitNETs)than others. Potentially aggressive PitNETs should be identified on an individual basis upon considering the tumor subtype, proliferative potential, and tumor invasion assessment.

Magnetic resonance imaging(MRI)is the preferred imaging technique for sellar and parasellar regions. In this study, we report our clinical experience with MRI for pituitary neuroendocrine tumors(PitNETs)with reference to histopathological findings through a review of the literature. Our previous study indicated that the three dimensional-spoiled gradient echo(3D-SPGR)sequence is suitable for evaluating sellar lesions on a postcontrast T1 weighted image(T1WI). This image demonstrates a defined relationship between the tumor and its surroundings, such as the normal pituitary gland, cavernous sinus, and optic pathway. This 3D-SPGR sequence is also suitable for detecting microtumors in corticotroph PitNETs. In somatotroph PitNETs, the signal intensity on T2WI is important to differentiate densely granulated tumors from sparsely granulated somatotroph tumors. In lactotroph PitNETs, distinct hypointense areas in the early phase on T2WI, possibly due to diffuse hemorrhage, indicate pronounced regression of invasive macroprolactinomas during cabergoline therapy.

Scientific advances have improved our understanding of the molecular pathological mechanisms underlying pituitary tumorigenesis, allowing us to analyze tumors in a more precise manner and to identify the tumors that have a greater risk of aggressive behavior at an earlier stage. Based on these molecular pathological findings, the classification of pituitary tumors has been revised over the last two decades to better describe their biological and clinical behavior and to identify prognostic markers of aggressiveness and poor prognosis. Understanding pituitary tumors at the molecular level has enabled increasingly targeted treatments with safety and efficacy validated in randomized trials. This paper reviews recent advances in the study of pituitary tumors, particularly pituitary endocrine tumors, and craniopharyngiomas, and describes potential therapies for pituitary tumors.

As the molecular pathology of pituitary cell development and the process of tumorigenesis in this organ continues to advance, it is recommended that pituitary neuroendocrine tumors(PitNETs)be classified based on three lineage-specific transcription factors(PIT1, Tpit, and SF1). In the hyperaging society of Japan, the number of cases traditionally classified as nonfunctioning PitNETs is increasing, and it is possible that some of these tumors may be associated with tumors that are known to exhibit aggressive behavior. The molecular pathological background of PitNET development is highly variable, and its pathogenesis in many cases remains unclear. As genomic analysis of PitNETs progresses, it is becoming increasingly clear that abnormalities in germline and somatic cell genomes contribute to our understanding of their etiology but do not explain most of them. Epigenetic modifications, such as deoxyribonucleic acid methylation and histone modifications(methylation and acetylation), are thought to be intricately related to tumorigenesis.

Pituitary tumors or tumors of the sella turcica include pituitary neuroendocrine tumors, Rathke's cleft cysts, craniopharyngiomas, tuberculum sellae, planum sphenoidale meningiomas, germ cell tumors, and hypophysitis. In addition, some rare tumors, such as pituicytomas, granular cell tumors, spindle cell oncocytomas, and chordomas or chondrosarcomas, arise from the parasellar regions. The treatment strategy is completely different for each lesion; therefore, accurate diagnosis is essential.

This report discusses the treatment and outcomes of three-port video-assisted thoracoscopic surgery (VATS) thymectomy for thymoma. We reviewed perioperative results of 159 thymoma cases( excluding thymic carcinoma) over 16 years. Thoracoscopic surgery was indicated for Masaoka stagesⅠ to Ⅲ, tumor diameter up to 12 cm, and resection of surrounding organs up to the lung, pericardium+reconstruction, internal thoracic artery and vein, left brachiocephalic vein, and phrenic nerve+reconstruction. The mean age of patients was 56.9±12.7, with 71 males and 88 females. The surgical approach was right-sided in 110 cases, left-sided in 47 cases, and bilateral in 2 cases. Total thymectomy was performed in 141 cases, with total thymectomy plus combined resection of other organs (lungs, pericardium, and phrenic nerve) ±reconstruction in 18 cases. The World Health Organization( WHO) classification( 5th edition) was type A/AB/B1/B2/B3/micronodular thymoma with lymphoid stroma (MNTLS) = 20/49/32/45/11/2, and Masaoka classification was stageⅠ/Ⅱ/Ⅲ=69/86/4. The three-port VATS technique offers several advantages, including its applicability to other surgeries, avoidance of contralateral thoracic cavity opening, safety in thymectomy without open conversion, and a mean postoperative hospital stay of 3 days.

Surgery for mediastinal and chest wall tumors requires various approaches, including open and thoracoscopic, depending on the size and localization of the tumor. While robotic surgery for anterior mediastinal tumors has become a standardized approach, the approaches for tumors of the superior, middle, and posterior mediastinum, in particular, have not been generalized. Our institution introduced robotic surgery in 2017 and has performed 785 robot-assisted surgeries until November 2022. In this report, we describe our clinical experience with robotic surgery for mediastinal tumors, which required an atypical approach, as well as a case of hybrid robot-assisted extended surgery combined with an open chest procedure for lung cancer with chest wall invasion.

The patient was a 27-year-old male. In December 2020, he was diagnosed with a primary extragonadal germ cell tumor of the retroperitoneum with inferior vena caval (IVC) involvement. After 3 courses of bleomycin, etoposide and cisplatinum and 3 courses of paclitaxel, ifosfamide and cisplatin, the serum human chorionic gonadotropin (hCG) level remained abnormally low. He was referred to our department after follow-up for 2 months. Since the hCG level continued to decrease during follow-up, we decided to perform marker-positive surgery. He underwent retroperitoneal lymph node dissection. We also resected a part of the IVC wall and tumor in the IVC. The serum hCG level was normalized at 5 days after surgery. Pathological examination revealed only necrotic tissue. Immunohistochemistry showed hCG positive in the necrotic tissue.

A 79-year-old woman underwent colonoscopy that revealed a 30-mm-sized nodular, mixed-type, lateral spreading tumor-granular in the lower rectum. Endoscopic submucosal dissection was performed, and the pathological findings indicated a mostly adenoma-type tumor with synaptophysin, cluster of differentiation 56-positive, and chromogranin A-negative associated with neuroendocrine carcinoma. Surgical resection was performed owing to vascular invasion, and the lymph node metastasis of the endocrine carcinoma component was observed. Thus, we reported a rare case of the coexistence of adenoma and neuroendocrine carcinoma.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has improved survival for patients with hematological malignancy, especially for those highly at risk of relapse. However, disease relapse after allo-HSCT remains the most common cause of treatment failure and death, even with conventional chemotherapy and donor lymphocyte infusion. Disease relapse in allo-HSCT can be reduced via pre-emptive treatment based on measurable residual disease and maintenance therapy for patients at high risk of relapse as promising treatment strategies. Recently, the development of novel agents and cellular therapies with high antitumor activity and less toxicity, which can be used in the post-transplant setting, has increased their clinical applications in the therapeutic approach. This review examines the current landscape and future strategies for maintenance therapy, mainly for AML and ALL after allo-HSCT.

Classic Hodgkin lymphoma (cHL) is one of the common subtypes of malignant lymphoma in Western countries. Although patients with HL showed unsatisfactory results in the 1960s, the clinical development in radiotherapy and chemotherapy based on several clinical trials over the last 50 years has made cHL a curable disease with a favorable outcome. As a result, late-onset treatment-related toxicities such as second primary malignancies and cardiac events are thought to be a significant issue especially in early-stage patients. To minimize the toxic effects while maximizing the antitumor efficacy, several clinical trials to evaluate response-adapted strategies using interim PET scans and novel agents, such as brentuximab vedotin (BV) and/or immune checkpoint inhibitor (ICI) are currently underway. In this review, the author summarizes currently available data on PET-adapted and BV and/or ICI-containing therapies for untreated cHL, and discusses their future prospects in cHL treatment.

Rituximab treatment significantly improved the outcomes of diffuse large B-cell lymphoma (DLBCL). A central nervous system (CNS) relapse remains a serious and fatal event for patients with DLBCL; therefore, the clinical question of the optimal treatment regimen for reducing the risk of CNS relapse remains unknown. The CNS-International Prognostic Index was identified as a predictive model for CNS relapse. No factors can completely predict CNS relapse although several reports regarding high-risk factors for CNS relapse have been reported. In practice, intrathecal methotrexate (MTX) and high-dose MTX therapy have been used for CNS prophylaxis. Unfortunately, evidence of the optimal therapy for CNS prophylaxis in patients with DLBCL remains lacking. This study aimed to review CNS relapse assessment and discuss study results with clinical impacts on CNS prophylaxis treatment strategies in DLBCL.

A 60-year-old man diagnosed with sigmoid colon cancer was admitted to our hospital. A CT scan revealed multiple liver metastases. The patient was administered 15 courses of FOLFIRI chemotherapy and 15 courses of FOLFIRI plus Cmab chemotherapy. After this treatment, multiple liver metastases disappeared, and laparoscopic resection of the sigmoid colon was performed. Two months later, a recurrent lesion was found in the liver segment(S1), and 5 courses of FOLFIRI plus Cmab chemotherapy were performed. Although the CEA level decreased, the tumor size remained unchanged. Therefore, partial resection of the liver was performed, followed by 18 courses of FOLFIRI chemotherapy. After that, the patient was followed for a year without chemotherapy. However, about 1 year later, recurrence was observed in liver segments S5 and S6. A right lobectomy was performed for these 2 lesions, and then 16 more courses of FOLFIRI chemotherapy were performed. The chemotherapy was discontinued, and the patient was then followed up as an outpatient without chemotherapy; there has been no recurrence.

Multiple myeloma (MM) is characterized by genomic instability, which causes multiple genetic and chromosomal alterations and leads to disease progression and therapeutic resistance. Overlapping mechanisms, including defective genome repair machinery such as the loss of TP53 activity, as well as chromosomal segregation error represented by the abnormality of mitotic checkpoint kinases such as BUB1, cell cycle dysregulation, and tumor environment, cause structural and numerical chromosomal abnormalities. Cytogenetic abnormalities are important prognostic factors, and they are also linked to the use of proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and the BCL2 inhibitor venetoclax. We developed new diagnostic modalities for chromosomal analysis to improve the sensitivity and convenience of chromosomal diagnosis. The immunophenotyped-suspension-multiplex (ISM)-fluorescence in situ hybridization (FISH) can use imaging flow to examine three IGH-related chromosomal translocations at the same time. We also created a new FISH method called amplified FISH (amFISH) to detect microdeletion involving narrow chromosomal regions (approximately<100 kb), such as the microdeletions of 1p32 (CDKN2C) or of 14q32 (TRAF3), by using a fluorescent antibody to amplify the signals of small probes. Even in the era of clinical sequencing, these convenient modalities may hasten the cytogenetics-oriented therapeutic approach for MM.

Chronic myeloid leukemia (CML) is a hematological malignancy characterized by the Philadelphia (Ph) chromosome, which is formed by a t (9;22)(q34;q11) translocation. The aberrant activation of the ABL1 tyrosine kinase is caused by the BCR::ABL1 fusion gene on the Ph chromosome, leading to significant leukemic cell proliferation. CML is typically diagnosed in the chronic phase with few clinical symptoms and progresses to a blast crisis within years. CML acquires additional genetic abnormalities on top of BCR::ABL1 fusion during clonal evolution. ASXL1 mutations are found in the chronic phase, with a frequency of approximately 20%, whereas other mutations are rare. Most blast crisis cases have additional genetic abnormalities, including frequent ASXL1 and RUNX1 mutations. Recent studies have revealed that a subset of these genetic mutations affects the sensitivity of tyrosine kinase inhibitors to leukemic cells as well as patient prognosis, indicating applications for patient stratification and individualized treatment.

Acute myeloid leukemia (AML) is a heterogeneous disease, and the accumulation of various chromosomal and genetic abnormalities is considerably involved in its pathogenesis and prognosis. Recently, the disease classification based on molecular abnormalities and novel molecular-targeting therapies has been developed. In Europe and the United States, several agents have been approved for AML and incorporated into guidelines as the standard treatment depending on comorbid genetic mutations combined with conventional chemotherapy or monotherapy since 2017. The combination therapy of FLT3 inhibitor midostaurin and intensive chemotherapy has improved the prognosis of patients with FLT3-ITD-positive AML, which has been considered a poor prognosis for a long period. In addition to small-molecule compounds, various novel therapies for AML are under clinical investigation, including antibody therapies targeting CD47 and TIM-3, bispecific antibodies, and CAR-T-cell therapies. Considering the treatment strategies with diverse therapeutic modalities, the pathogenesis and clonal selection process of refractory AML, including the surrounding environment of residual leukemia cells, should be clarified. The combination of new therapies and chemotherapies is highly expected to improve the prognosis of patients with AML in the near future.