A 75‒year‒old man consulted our hospital with abdominal pain and fever. He was diagnosed as abscess‒forming appendicitis by contrast‒enhanced computed tomography(CT), and underwent conservative treatment and CT‒guided drainage. CT‒guided drainage revealed no abscess. Follow‒up contrast‒enhanced CT and MRI revealed a diagnosis of appendiceal mucinous neoplasm and peritoneal pseudomyxoma. Hence, the treatment strategy was operation. Intraoperative findings revealed mucus deposits in the right paracolic gutter and around the liver. The mucus was examined cytologically, but no malignant findings were detected. An ileocecal resection was performed. The pathological diagnosis was high‒grade appendiceal mucinous neoplasm(HAMN). The patient was discharged without postoperative complications. The patient was alive and recurrence‒free, 12 months after surgery. We report this rare case with a review of the literature.

Non-muscle invasive bladder cancer(NMIBC)accounts for about 70% of bladder cancers, with most patients treated by TURBT followed by intravesical therapy according to recurrence risk.BCG is effective but BCG-unresponsive cases often require cystectomy.Recently, novel therapies including immune checkpoint inhibitors, drug-delivery devices, and gene therapy have emerged.This chapter reviews recent and ongoing phase Ⅲ trials in BCG-naïve NMIBC.

Primary squamous cell carcinoma of the small intestine is extremely rare, particularly in patients without adenocarcinoma components. Here, we report a case of a patient with primary small intestinal squamous cell carcinoma along with a brief literature review. The patient was a 70-year-old woman who was referred to our hospital after undergoing lower gastrointestinal endoscopy at another institution for abdominal pain and anemia, which revealed a suspected perforation of a sigmoid colon tumor. Computed tomography revealed a tumor that involved the sigmoid colon, small intestine, and left adnexa, as well as a para-aortic lymph node metastasis that infiltrated the left renal vein. A tumor marker analysis showed elevated SCC antigen levels, endoscopic examination revealed findings suggestive of infiltration from other organs into the sigmoid colon, and a biopsy confirmed squamous cell carcinoma. No findings suggestive of primary squamous cell carcinoma were identified during the systemic examination. Palliative exploratory laparotomy with tumor resection(partial small bowel, sigmoid colon, and left adnexal resection)was performed. The pathological diagnosis was consistent with primary small intestinal squamous cell carcinoma with no adenocarcinoma components detected. Chemotherapy was proposed to improve the patient's prognosis, but the patient opted for best supportive care and died of the primary cancer approximately 6 months after surgery.

An 81-year-old man was admitted with heart failure and severe anemia. He had undergone a right nephrectomy for renal cell carcinoma 25 years earlier. Abdominal CT revealed a transverse colon tumor. Colonoscopy showed a nearly circumferential lesion with submucosal tumor-like features. Laparoscopic transverse colectomy was performed, and the tumor was completely resected. Histopathological examination revealed a clear cell carcinoma consistent with recurrence of renal cell carcinoma. We report this rare case of late mesenteric recurrence 25 years after nephrectomy, along with a brief literature review.

A 76-year-old man with a history of chronic obstructive pulmonary disease(COPD)presented with exertional dyspnea and melena. Detailed examination revealed a 10-cm heterogeneous, contrast-enhancing mass on the posterior wall of the upper gastric body. Endoscopy showed a submucosal tumor-like elevation with ulceration. Biopsy of the ulcerative lesion indicated well-differentiated adenocarcinoma. Based on these findings, the coexistence of gastric gastrointestinal stromal tumor(GIST)and gastric cancer was clinically suspected. Considering the patient's poor general condition, partial gastrectomy of the upper gastric body was performed. Intraoperatively, a 12-mm white nodule was also found on the anterior wall of the lower gastric body and was enucleated simultaneously. Histopathological examination revealed discontinuous high- and low-grade GISTs, a 5-mm intramucosal well-differentiated adenocarcinoma, and the white nodule was diagnosed as a leiomyoma. Although adjuvant imatinib was initiated postoperatively, it was discontinued due to adverse effects. Peritoneal dissemination and liver metastases developed 4 years and 8 months after surgery, and the patient passed away 5 years and 6 months postoperatively. The coexistence of multiple gastric GISTs with early gastric cancer and gastric leiomyoma is extremely rare. We report this case with a brief review of the literature.

Over the past decade, molecular biology techniques have identified numerous key genetic mutations in brain tumors. This has improved understanding of disease pathogenesis, and facilitated prognostic prediction, and the development of effective targeted molecular therapies. In 2021, the World Health Organization published the fifth edition of its classification of CNS tumors(WHO 5th), recommending a reporting format based on an integrated diagnosis combining histopathological and molecular genetic information. The classification of pediatric brain tumors has also advanced significantly, clarifying the disease backgrounds specific to childhood and differences in prevalence. The WHO 5th classification represents a significant advancement in selecting optimal treatments and recognizing patient groups that share similar clinical characteristics. However, some challenges remain for its implementation in routine clinical practice, including establishing access to molecular genetic testing. Herein, we reviewed the tumor types listed in the WHO 5th edition that predominantly affect children and adolescents, referring to recently published reports and concepts.

The patient was in her 50s, had received concurrent chemoradiotherapy for stage ⅢB cervical cancer approximately 19 years ago, and was in good health. She had an ileus 3 months earlier and underwent an experimental laparotomy 2 months before, which revealed cancerous peritonitis, as well as a biopsy of a tumor in the peritoneum. Histological examination revealed malignant peritoneal mesothelioma(MPM). The patient died 2 months postoperatively. Histological examination was the primary diagnostic method, supplemented by HE staining, immunostaining, and genetic testing, for establishing MPM diagnosis. MPM is an extremely rare secondary cancer following cervical cancer treatment.

Lung cancer remains one of the leading causes of cancer‒related mortality worldwide, underscoring the urgent need for innovative diagnostic and therapeutic approaches. The advent of immune checkpoint inhibitors(ICIs)has significantly transformed the treatment landscape, particularly for non‒small cell lung cancer(NSCLC). However, predictive biomarkers for ICI efficacy remain limited, with PD‒L1 expression, tumor mutational burden(TMB), and microsatellite instability providing only partial insight into therapeutic response. Recent attention has focused on tertiary lymphoid structures(TLS), ectopic lymphoid aggregates resembling secondary lymphoid organs that form in the tumor microenvironment. TLS are composed of B cells, T cells, dendritic cells, and other immune components, and play a central role in coordinating local antitumor immune responses. In NSCLC, the presence of TLS has been associated with favorable prognosis and improved response to ICIs, independent of PD‒L1 or TMB status. Moreover, emerging evidence suggests that the quality of TLS-such as the degree of maturation and the nature of infiltrating immune cells-may further influence immunotherapeutic outcomes. This review outlines the clinical significance of TLS in lung cancer, discussing their structure, function, and potential as novel biomarkers for stratifying patients undergoing immunotherapy. We also explore future directions including therapeutic strategies aimed at promoting TLS formation, such as vaccines or immune adjuvants, as well as the application of artificial intelligence and spatial omics technologies for the standardized evaluation and in‒depth characterization of TLS. As the integration of TLS analysis into clinical oncology evolves, a more precise and personalized approach to lung cancer immunotherapy may be realized.

The Ser/Thr-specific kinase, polo-like kinase 1 (Plk1), is a crucial eukaryotic cell cycle regulatory protein. Overexpression of this kinase is observed in many cancer cells and where it can be related to their aggressiveness. Dysfunction of Plk1 in cancer cells causes mitotic arrest and subsequent apoptosis. Accordingly, Plk1 is considered as a target for the development of anti-cancer agents. Plk1 has two domains, a catalytic kinase domain (KD) and a polo-box domain (PBD). PBD intramolecularly interacts with its KD and regulates Plk1 activity and localization. Therefore, in addition to the KD, the PBD is considered to be a potential drug target. We have been developing peptidic low-nanomolar-affinity PBD-binding inhibitors. However, these peptides do not show significant cytotoxicity, due to their low cell membrane permeability. To obtain cell-active Plk1 inhibitors, I applied a bivalent approach designed to simultaneously engage both KD and PBD regions of Plk1 for enhancing the potency, selectivity and lipophilicity. Here, I developed bivalent Plk1 inhibitors, in which the PBD-binding peptides are conjugated with the known KD-binding inhibitors BI2536 or wortmannin using PEG linkers. These bivalent inhibitors exhibit up to 100-fold enhanced Plk1 affinity relative to the best monovalent PBD-binding ligands, higher selectivity for tested kinases compared to BI2536, and significant cytotoxicity against HeLa cells.

The advent of novel anti-multiple myeloma (MM) agents has led to dramatic improvement in patient survival. Nevertheless, the majority of patients with MM have bone lesions, and destructive bone lesions significantly reduce quality of life. Progressive destructive bone lesions develop when osteoblast differentiation from bone marrow stromal cells is inhibited and osteoclasts are activated in the bone marrow microenvironment in patients with MM. Recent research has also shed light on the functions and roles of osteocytes, which account for the majority of bone cells. Since MM cells mainly invade the red marrow, bone lesions are often found in the skull, spine, and ilium, which contain red marrow. Imaging is essential for the diagnosis of MM bone lesions, and whole-body low-dose CT, whole-body MRI, and FDG-PET/CT have demonstrated utility. Furthermore, recent advances in anti-MM drugs have improved the prognosis of MM significantly, highlighting the importance of treating and managing MM bone lesions. This review will explain the molecular pathology and management of MM bone lesions.

We report a rare case of a solitary metastasis in which long-term complete remission was achieved with chemotherapy alone. An 81-year-old woman underwent a right hemicolectomy and D3 lymph node dissection for ascending colon cancer. Pathological findings showed type 2, 40×20 mm, tub2>muc, pT3, int, INF b, ly1, v0, pN1(1/32), pPM0, pDM0, and fStage Ⅲa. However, the patient chose not to undergo adjuvant chemotherapy and opted for further observation. Five months after the surgery, lymph node metastasis was observed near the right external iliac artery. Because the patient did not wish to undergo surgical treatment, SOX therapy was initiated. Owing to considerable side effects, the patient's treatment was switched to oral S-1. Gradually, the lesion disappeared, and the treatment was changed to UFT. The patient has maintained complete long-term remission for 10 years postoperatively. Here, we report this case along with a literature review.

A 65-years-old female was admitted to our hospital for treatment of fever and chest pain. Contrast-enhanced computed tomography (CT) revealed an anterior mediastinal tumor with a thickened wall, and right pleural effusion. Ten days after antibiotic therapy, the fever, chest pain and pleural effusion disappeared. Thymectomy was performed to confirm the diagnosis. Histopathologic diagnosis was type B2 thymoma with extensive necrotic area, Masaoka's stageⅠ. No recurrence has been observed for approximately two years since the surgery. Thymomas have a variety of pathological features such as cystic and hemorrhagic changes and necrosis. However, thymomas with extensive necrosis are very rare. We presented this case with a review of the literature.

A 67 year-old man consulted an urologist with the chief complaint of gross hematuria and discomfort in the urethral region. He was later diagnosed with malignant melanoma by transurethral biopsy. Urethrocystoscopy revealed lesions 3 cm peripherally from the sphincter muscle, and TUR of the urethra to the bladder neck revealed no malignant lesion in the prostatic area, urethra, or bladder. Radical penectomy was performed and the histopathologic diagnosis was pT2 malignant melanoma with negative urethral resection margins. At 9 months postoperatively, there was no evidence of recurrence or metastasis. Primary malignant melanoma of the urethra is an extremely rare disease with a poor prognosis for which no effective treatment has been established other than surgical resection. We report this case with discussion of the literature.

Primary follicular lymphoma of the prostate is extremely rare, with this case representing only the 13th reported in the English literature. This report includes a review of the literature and details of a case in a 75-year-old male with concurrent primary follicular lymphoma and adenocarcinoma of the prostate. The patient was referred to our department due to prostate enlargement observed on CT and complaints of a decreased urinary stream. His PSA level was elevated at 8.9 ng/ml. MRI showed a PI-RADS category 4 lesion in the right peripheral zone of the prostate, with an estimated prostate volume of 60 ml. A transrectal prostate biopsy identified adenocarcinoma in two cores from the right base and one from the left apex, leading to a diagnosis of prostate cancer cT2aN0M0. Subsequently, the patient underwent robotic-assisted laparoscopic radical prostatectomy. Pathological findings confirmed adenocarcinoma in the right and left lobes (pT2a, pN0, EPE0, SV0, LVl1, RM0) and identified concurrent primary follicular lymphoma within the anterior fibromuscular stroma, which was positive for CD20, CD10 and Bcl-2. A complete clinical investigation, including an 18F-fluorodeoxyglucose positron emission tomography scan and bone marrow biopsy, revealed no involvement of other sites, and the patient was ultimately diagnosed with Ann Arbor stage IE lymphoma. No additional treatment was administered, and the patient has been followed up regularly. At six months postoperatively, there was no evidence of recurrence of either prostate cancer or lymphoma.

The treatment of recurrent or metastatic cervical cancer has entered a new era, with immune checkpoint inhibitors now being used as first-line standard of care options. Meanwhile, there is a lack of second-line and subsequent treatment options that can adapt to this changing treatment landscape, highlighting the need for the development of new treatments with novel mechanisms of action. Tisotumab vedotin (recombinant) is an antibody-drug conjugate (ADC) consisting of tisotumab, an anti-human tissue factor (TF) monoclonal antibody (IgG1κ), the microtubule inhibitor monomethyl auristatin E (MMAE), and a valine-citrulline linker. When the linker is cleaved by a protease in a tumor cell, MMAE is released to induce cell cycle arrest and apoptosis via disruption of the microtubular network. In non-clinical studies, tisotumab vedotin demonstrated concentration-dependent cytotoxic and anti-tumor activities. Tisotumab vedotin also mediated antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) activities. In a global Phase III study of tisotumab vedotin as second- or third-line therapy in patients with recurrent or metastatic cervical cancer (Study SGNTV-003/innovaTV 301), the drug demonstrated higher efficacy than the investigator's choice of chemotherapy. Although some eye-related adverse events occurred as unique toxicities, the safety profile of tisotumab vedotin was generally manageable. The results of analysis in the Japanese subpopulation of the SGNTV-003 (innovaTV 301) study were consistent with those of the overall population. Based on these results, tisotumab vedotin received regulatory approval in Japan in March 2025 for the indication of "advanced or recurrent cervical cancer that has progressed after cancer chemotherapy".

The tumor microenvironment (TME) includes immune cells, cancer-associated fibroblasts (CAFs), endothelial cells, pericytes, and more. Previously, these non-cancer cells were considered inactive components in cancer pathology. However, it has become evident that these cells and their secretions play crucial roles in cancer progression. To unravel the complexity of the TME and elucidate its mechanisms, microphysiological systems (MPS) have gained attention. An MPS is defined as "a microscale cell culture platform for in vitro modeling of functional features of a specific tissue or organ of human or animal origin", allowing for the control of the chemical or physical conditions of the TME and the analysis of the responses of cancer cells and surrounding cells. In recent years, the incorporation of vascular networks into tumor MPS has enabled more accurate assessments of the dynamics within the TME. This review provides an overview of the latest research on cancer MPS with vascular networks and the cellular and molecular dynamics within the TME.

A man in his 60s presented with jaundice. He was diagnosed with BR pancreatic head cancer with SMV infiltration. He underwent subtotal stomach-preserving pancreaticoduodenectomy(SSPPD)and SMV resection. He had an uneventful postoperative course and was discharged on day 13. Pathology revealed T4N1(3/28)M0, Stage Ⅳa. After adjuvant chemotherapy, a solitary left lung nodule was detected 2 years and 6 months postoperatively. It was diagnosed as recurrence. After chemotherapy, thoracoscopic partial lung resection was performed 3 years and 6 months postoperatively. Three months later, another solitary nodule was found in the left lung. Thus, a second thoracoscopic partial lung resection was performed 6 years and 1 month postoperatively to remove the lung metastasis. There has been no recurrence since, and the patient has achieved long-term survival of over 9 years after the initial surgery. This is a rare case of long-term survival after 2 metastasis resections, which we report with a brief literature review.

The case was a 68-year-old woman who presented with a complaint of an abdominal mass. She was diagnosed with the retroperitoneal liposarcoma. In the initial surgery, the primary tumor was resected together with the right colon involved. Since the histological type was the dedifferentiated type, imaging tests were performed every 10 weeks. After all there were seven local recurrences and one recurrence of lung metastasis, and each time the tumor relapsed, a combined resection of surrounding organs were repeated. At the time of the eighth recurrence, she requested chemotherapy. But her illness progressed. Five and a half years after the initial surgery, she passed away. The only effective treatment for retroperitoneal liposarcoma is surgical resection, but the prognosis varies depending on the histological type. The dedifferentiated type is a disease that often has a poor prognosis due to repeated local recurrence and inoperability. In this case, we report with a literature review on a case in which we were able to detect a recurrence in a state that was resectable by performing imaging tests at short intervals for dedifferentiated liposarcoma, and we were able to achieve long-term survival through 8 surgeries.

A 52-year-old man presented with a postoperative abdominal ultrasound of left renal cell carcinoma, which revealed a dilated main pancreatic duct in the pancreatic body tail. A 15 mm tumor was noted in the pancreatic head-neck region on CT, and was diagnosed as invasive pancreatic cancer on EUS-FNA. The tumor was diagnosed as resectable pancreatic head-body cancer, and after neoadjuvant chemotherapy, a subtotal stomach-preserving pancreaticoduodenectomy was performed. Postoperative histopathology showed well-differentiated adenocarcinoma, TS1(9 mm), T1bN0M0, Stage Ⅰ, preoperative chemotherapy efficacy was Grade 2, and R0 resection was obtained. At the same time, a 4 mm-sized nodule was found in the center of the pancreatic head, far from the primary pancreatic cancer, and was diagnosed as renal cell carcinoma intrapancreatic metastasis. He received 4 courses of S-1 therapy as postoperative adjuvant chemotherapy for pancreatic cancer, and is alive 23 months postoperatively without recurrence. The coexistence of primary pancreatic cancer and pancreatic metastasis of renal cell carcinoma is extremely rare, and we report this case with a review of the literature.

A 72-year-old man complained of right lower abdominal pain. A CT scan showed an acute appendicitis. Laparoscopic appendectomy was performed. Histopathological examination of the resected specimen identified goblet cell adenocarcinoma(GCA), predominantly extending through the muscularis propria of the appendix. The tumor invaded into the serosal tissue. Subsequently, robotic-assisted ileocecal resection with D3 lymphadenectomy was performed. The final pathological diagnosis was GCA(pT3N0M0, pStage ⅡA). GCA of the appendix is a rare entity that exhibits characteristics of both carcinoid and adenocarcinoma. We report this as a relatively rare and significant case, accompanied by a review of relevant literatures.