Immune checkpoint inhibitors (ICIs) have shown remarkable efficacy in various malignancies, but their effectiveness in colorectal cancer is generally limited to MSI‒high tumors. We report a case of complete response in an MSI‒stable rectal cancer patient with para‒aortic lymph node metastasis treated with a sequential strategy involving targeted therapy and ICI. A 52‒year‒old woman underwent laparoscopic intersphincteric resection with bilateral lateral lymph node dissection for advanced lower rectal cancer, followed by adjuvant CAPOX. Two years postoperatively, para‒aortic lymph node metastasis was confirmed histologically. FOLFIRI plus cetuximab was initiated, resulting in marked regression of the nodes but without CEA normalization. Switching to FOLFIRI plus bevacizumab led to further CEA reduction. After 2 courses, nivolumab was added and CEA normalized. CEA levels rose again after completion of ICI, but continued FOLFIRI plus bevacizumab led to re‒normalization without radiologic progression. This case suggests that sequential treatment using cetuximab and bevacizumab may modulate the tumor microenvironment and enhance ICI response even in MSI‒stable colorectal cancer. Strategic immunomodulation could provide a promising option for ICI‒resistant tumors.

We report a case of a 51‒year‒old man who presented with right lower abdominal pain. On physical examination, a palpable, tender mass was detected in the right lower abdomen. Contrast‒enhanced computed tomography (CT) revealed a 15‒cm mass in the right lower abdominal wall, supplied by the right inferior epigastric artery, with internal hemorrhage and necrotic areas. Radiological findings were inconclusive for malignancy. As there was no evidence of distant metastasis or invasion into adjacent organs, the tumor was considered resectable, and surgical resection was performed. Histopathological examination confirmed the diagnosis of synovial sarcoma. Given the high risk of recurrence and metastasis associated with synovial sarcoma, adjuvant chemotherapy was administered postoperatively. The patient remains alive without recurrence 1 year after surgery.

We report a case of conversion surgery after nivolumab treatment and chemotherapy for metastatic gastric cancer. A 75‒year‒old man was diagnosed as advanced gastric cancer with peritoneal dissemination. The patient was judged as unresectable gastric cancer and received SOX+nivolumab treatment. After 8 courses of chemotherapy, the primary lesion and enlarged lymph nodes were reduced and abdominal small nodules were disappeared. Consequently, we performed staging laparoscopy followed by laparoscopic distal gastrectomy with D2 lymph node dissection as a conversion surgery. Histopathological diagnosis was ypT2N0M0CY0, and ypStage ⅠB. The patient has been recurrence‒free for 6 months.

We report a 58‒year‒old woman with Stage Ⅳb sigmoid colon cancer, presenting with hematochezia and lower abdominal pain, and diagnosed with over 15 liver metastases and para‒aortic lymph node (PALN) metastases. After laparoscopic sigmoid colectomy, FOLFOXIRI plus bevacizumab achieved marked liver tumor reduction and complete PALN response, enabling hepatic resection. Multiple recurrences were managed with repeated liver resections, PALN dissection, and chemoradiotherapy. Following fifth‒line of chemotherapy, oxaliplatin was reintroduced, and fruquintinib initiated, leading to 6 years and 3 months of survival. This case highlights multidisciplinary strategies for initially unresectable colorectal cancer.

We have experienced a case in which MSI‒high advanced cecum and ascending colon cancer was completely cured by surgery and immune checkpoint inhibitors (ICIs). CEA, which had been high before surgery, did not normalize after radical surgery and rose again 1 year later. Although no obvious relapse findings could be identified by imaging tests such as CT and PET and examination laparoscopy, an increase in CEA was observed, so it was judged that the residual tumor had a flare‒up, and pembrolizumab alone was started. After 3 cycles, CEA normalized and treatment was completed after a total of 9 doses. Currently, no recurrence has been observed and follow‒up is underway. If there is a high suspicion of a recurrence of MSI‒high colorectal cancer, ICI therapy was considered an option.

To effectively induce anti‒tumor immune responses, it is essential that tumor‒specific T cells are generated within the tumor microenvironment (TME), a process in which tumor‒draining lymph nodes (TDLNs) are thought to play a critical role. We have previously demonstrated that photoimmunotherapy targeting cancer‒associated fibroblasts (PIT‒CAF), which specifically targets the fibroblast activation protein (FAP), modulates the immune cell composition and function within the TME. In this study, we investigated the effects of CAFs and PIT‒CAF on tumor‒specific T cells in both the TME and TDLNs.

A female patient in her 70s, underwent laparoscopic right hemicolectomy for ascending colon cancer (pT4aN2aM0). Eight courses of post‒operative adjuvant chemotherapy with CapeOX were administered. However, 1 year and 5 months post‒surgery, liver metastasis was observed. Following 1 course of FOLFIRI therapy and 1 course of FOLFIRI+bevacizumab therapy, high‒frequency microsatellite instability (MSI‒H) was detected, and pembrolizumab therapy was initiated. CT imaging revealed necrotic changes in the metastatic lesion while stable disease (SD) was maintained. After completing 28 courses of pembrolizumab therapy over 1 year and 9 months, the treatment was temporarily discontinued. One year and 3 months after discontinuation, the CEA level was elevated and the tumor was enlarged. Pembrolizumab therapy was resumed, and 5 additional courses were administered. Subsequently, surgical resection of the liver metastasis revealed no residual tumor and pathological complete response was confirmed. The patient has remained recurrence‒free without further treatment.

Surgery is the basic treatment for oral cancer; however, post-operative oral function has a significant impact on daily life. Therefore, early detection of oral cancer during dental checkups is important. On remote islands without dentists, it is particularly desirable for oral surgeons to cooperate for the early detection of oral cancer, to perform surgery. The Kagawa Dental Association has been conducting remote island oral cancer examinations in cooperation with the Dept. of Oral and Maxillofacial Surgery, Faculty of Medicine, Kagawa University, for the early detection of oral cancer on remote islands with no dentists in Kagawa Prefecture. In this report, we describe our experience with the early detection of a rare mucoepidermoid carcinoma of the floor of the mouth during remote island oral cancer screening in the Kagawa Prefecture, with the cooperation of the local government and others.

The patient was a 63-year-old man at initial consultation. After pre-operative chemotherapy for advanced gastric cancer, he underwent distal gastrectomy. Eight months later, liver metastases appeared in segments 6 and 7. First-line chemotherapy with capecitabine plus cisplatin was administered, but the liver lesions worsened, and a para-aortic lymph node metastasis was observed. Second-line ramucirumab plus paclitaxel shrank the metastatic lesions without new lesions. Because he could not tolerate further combined chemotherapy, third-line nivolumab monotherapy was started 12 months after chemotherapy initiation. After 6 courses, grade 4 adrenal insufficiency developed, and nivolumab was discontinued. Nevertheless, all metastatic lesions had shrunk and showed peripheral calcification. Ramucirumab monotherapy was resumed (43 courses) based on the patient's clinical status. During this period, the liver metastases continued to decrease and became completely calcified;the para-aortic lymph node resolved. PET-CT showed no FDG accumulation in the liver, consistent with organized, tumor-free lesions. The recurrent disease was judged equivalent to a complete response (CR), and no further treatment was given. Subsequent CT scans showed ongoing shrinkage and gradual decalcification of the organized liver lesions. Thirty-five months after discontinuing ramucirumab, the lesions are cystic and the CR persists. Given the high microsatellite instability status and the timing of lesion shrinkage and calcification, nivolumab likely played the dominant role in achieving CR. Our review of the limited number of reported cases suggests that discontinuing nivolumab after CR in gastric cancer can be a valid option.

A 34‒year‒old woman presented with a pelvic tumor in the Douglas pouch during her first pregnancy, initially suspected to be a desmoid tumor and managed subsequently. Biopsy during cesarean section in her second pregnancy confirmed aggressive angiomyxoma (AAM). Postpartum tumor growth prompted a 16‒month course of gonadotropin‒releasing hormone agonist therapy (leuprorelin acetate, 1.88 mg every 4 weeks), which reduced tumor size from 20×13 cm to 10×7.5 cm after 12 doses. However, adverse effects, such as fatigue and nausea occurred, and further tumor shrinkage was minimal, necessitating surgical intervention. A left posterior sacral approach allowed complete tumor resection while preserving the rectum, reproductive organs, and autonomic nerves. AAM is a rare tumor of the pelvis or external genitalia in young women. Although surgical excision remains the primary treatment, no standardized approach exists. This case demonstrates the role of preoperative hormone therapy in significantly reducing tumor size, thereby facilitating complete excision with organ preservation, and underscore its potential role in AAM management.

A large mass in the liver was incidentally observed on abdominal ultrasonography of a 75‒year‒old female during health surveillance. Computed tomography (CT) and magnetic resonance imaging revealed a tumor (φ>12 cm) in the medial segment of the liver. A liver biopsy was performed, and the tumor was histopathologically diagnosed as a neuroendocrine tumor (NET) G1. 18F‒fluorodeoxyglucose positron emission tomography‒CT (PET‒CT) and somatostatin receptor scintigraphy (SRS) revealed concomitant uptake in the hepatic tumor and no abnormal uptake in other organs; thus, the tumor was diagnosed as a primary hepatic NET (PHNET). Radical resection required right trisectionectomy of the liver, with little future remnant liver volume. The radical resection was performed 3 weeks post portal embolization. There were no surgical complications or obvious recurrence for 1 year post‒surgery. PHNETs are extremely rare and are difficult to diagnose using routine imaging modalities. PET‒CT and SRS are useful to exclude the presence of extrahepatic lesions and histopathological examination is required to diagnose PHNETs. Surgical resection is the first‒line treatment for PHNETs and even if the PHNET is large, a favorable prognosis can be achieved with radical resection.

We describe the cases of 4 patients with breast cancer who developed an allergy to fosnetupitant (Pro‒NETU). Case 1: A 67‒year‒old woman with breast cancer and bone metastasis received premedication that included Pro‒NETU. Minutes after administration, she complained of flushing, tachycardia, and dyspnea. Administration was discontinued. Minutes after discontinuation, the patient's symptoms were alleviated. She experienced no further complaints of such symptoms, and her premedication subsequently excluded Pro‒NETU. Case 2: A 50‒year‒old woman with early stage breast cancer received premedication that included Pro‒NETU. Minutes after administration, she complained of flushing, dyspnea, and drowsiness. Administration was discontinued. Minutes after discontinuation, her symptoms ameliorated. Case 3: A 41‒year‒old woman with early stage breast cancer received premedication that included Pro‒NETU. Minutes after administration, she complained of flushing, tachycardia, and dyspnea. Administration was thus discontinued, and she received an H2‒blocker and corticosteroid. Minutes after discontinuation, her symptoms were alleviated. Case 4: A 50‒year‒old woman with early stage breast cancer received premedication that included Pro‒NETU. Minutes after administration, she complained of flushing and tachycardia. Administration was discontinued. Minutes after discontinuation, her symptoms ameliorated. Fosaprepitant did not cause these allergies. The patients in cases 2, 3, and 4 had known allergies to docetaxel, and the cause of allergy in case 4 was unknown. Polysorbate 80, contained in docetaxel, fosaprepitant, and Pro‒NETU, was suspected to be the cause of allergy in cases 1, 2, and 3.

Epidermal growth factor receptor (EGFR) mutations are among the most common genetic alterations in non‒small cell lung cancer (NSCLC), with ex19del and ex21L858R being the most prevalent. Ex19del correlates with better outcomes of EGFR tyrosine kinase inhibitors (EGFR‒TKIs) than L858R. The RELAY phase Ⅲ study showed that ramucirumab plus erlotinib as first‒line therapy provided similar progression‒free survival for both mutations. Preclinical studies using NSCLC cell line PC9 (ex19del) and its CRISPR‒engineered subline PC9EX21 (ex21L858R mutations) were conducted to explore the molecular basis of these clinical observations and assess the impact of these mutations on cell biology and responses to EGFR‒TKI and ramucirumab. PC9 and PC9EX21 cells had similar morphology, but PC9EX21 cells were larger, grew slower, had greater migratory potential, and exhibited delayed tumor formation in vivo. Fluorescence‒activated cell sorting analysis showed lower EGFR and higher human epidermal growth factor receptor 2 (HER2)/HER3 expression in PC9EX21, with vascular endothelial growth factor receptor 2 mRNA levels 8‒times higher than ex19del. Transcriptomic profiling and multiplex proteomics identified significant gene expression differences (receptor tyrosine kinase) and altered signaling pathways in PC9EX21. Ramucirumab enhanced erlotinib's anti‒proliferative effect in PC9EX21 but had a limited effect in ex19del. These findings highlight key biological differences between ex19del and L858R mutations, emphasizing the need for personalized treatment strategies in NSCLC.

Tertiary lymphoid structures(TLS)are gaining attention as sites for anti‒tumor immune responses. They are observed in gynecological tumor tissues, including common gynecological cancers such as endometrial, cervical, and ovarian cancers. The distribution and maturity of TLS, along with molecular genetic factors and patient prognosis, are being studied. Enhancing anti‒cancer treatment is anticipated by efficiently inducing TLS within the tumor microenvironment. Specifically, based on basic research aimed at reactivating anti‒tumor immunity within TLS, numerous clinical trials are underway for novel combined therapies targeting TLS‒positive cancers. These trials involve optimal combinations of immune checkpoint inhibitors, immune‒activating molecules, chemotherapy, and radiotherapy to induce TLS. This has led to the development of new cancer treatment strategies.

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.

Immune checkpoint inhibitors(ICI)have significantly improved treatment outcomes for advanced gastric cancer by enhancing anti‒tumor responses through increased activity of tumor‒infiltrating CD8+ T cells. This highlights the critical role of the immune microenvironment, drawing recent attention to tumor‒associated lymphoid structures(TLS). TLS, characterized by clusters of B cells, has been associated with favorable prognoses in various cancer types. Our research has demonstrated that TLS is present in gastric cancer tissue and correlates with improved survival outcomes and better responses to ICI treatment. Furthermore, we found that TLS promotes the infiltration of CD8+ T cells and the generation of tissue‒resident memory T cells. Advancing research on TLS holds promising potential for further improving treatment outcomes in the future.

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.

A woman in her 70s. In May, a pancreatic tumor was detected during a medical checkup, and she visited the Department of Gastroenterology of our hospital. She had no subjective symptoms, but she was diagnosed with primary pancreatic cancer and multiple bone metastases. She was undergoing outpatient chemotherapy. In November of the same year, she became aware of numbness in the right cheek area and was referred to our department. Neurologically, abnormal sensation in the area of the second branch of the right trigeminal nerve was observed. Head computed tomography (CT)/MRI showed a mass lesion in the right Meckel's cave, and FDG-PET showed multiple bone lesions as well as abnormal accumulation in the right Meckel's cave. Based on the above, we diagnosed the patient with numb cheek syndrome due to metastasis of pancreatic cancer to Meckel's cave. Neurologists should be aware that numb cheek syndrome can occur in association with an underlying malignancy.

A 73-year-old man was referred to our hospital for abnormal shadow. Chest computed tomography (CT) showed a tumor with a cavity in S10 of the left lung. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed the accumulation in the tumorous lesion of the cavity wall. Although the culture of the lavage fluid was positive for acid-fast bacilli and polymerase chain reaction (PCR) was positive for M. intracellulare, coexistence of cancer could not be denied. Therefore, he underwent surgery. Histopathological findings showed squamous cell carcinoma adjacent to epithelioid cell granulomatous lesion of nontuberculous mycobacteriosis.