Hyogo Prefectural Cancer Center

In this nationwide retrospective study, we sought to evaluate the oncologic and functional outcomes and safety of transoral surgery (TOS) for hypopharyngeal and laryngeal squamous cell carcinomas in Japan and to clarify the appropriate indications for various TOS modalities. Data were obtained from the Head and Neck Cancer Registry of Japan. Patients who underwent transoral or endoscopic resection between 2011 and 2016 were selected. Detailed clinical information was collected from 55 institutions using web-based case report forms. Surgical modalities analyzed included endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), endoscopic laryngopharyngeal surgery (ELPS), transoral laser microsurgery (TLM), and transoral videolaryngoscopic surgery (TOVS). In total, 1825 patients were included (hypopharyngeal cancer, 62.5 %; laryngeal cancer, 37.5 %). Most cases (77.5 %) were T1 or lower, and 90.8 % were Stage II or earlier. TLM is predominantly used for glottic cancers, ELPS/ESD for superficial hypopharyngeal lesions, and TOVS for more advanced tumors, reflecting distinct indications for each modality. The 5-year disease-specific survival (DSS), recurrence-free survival (RFS), and overall survival (OS) were 97.1 %, 84.3 %, and 85.4 %, respectively. The laryngeal preservation rate was 98.2 %. Tracheostomy was performed in 5.0 % of cases, mainly for airway protection; major complications, including pneumonia (2.4 %), hemorrhage (1.1 %), fistula formation (0.4 %), and vocal cord fixation (2.6 %), occurred in <3 % of patients. Postoperative functional outcomes were favorable, with persistent dysphagia (Functional Outcome Swallowing Scale stage ≥ 3) in 1.6 % and tube feeding dependence in 1.8 %. Non-robot-assisted TOS demonstrated excellent oncologic control and functional preservation of the larynx with low complication rates in early-stage hypopharyngeal and laryngeal cancers. Each surgical modality has distinct indications depending on the tumor site, depth of invasion, and institutional expertise. These findings support the use of TOS as a safe and effective treatment option for selected patients. Further procedural standardization and data accumulation are required to refine the indications and facilitate their broader adoption in clinical practice.

The recommendation to discontinue low-dose aspirin (LDA) during the periprocedural period of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) remains controversial in patients at low thrombotic risk. If continuation of LDA does not increase bleeding risk, gastric ESD could be safely performed under sustained antiplatelet effects, benefiting patients. This study aimed to evaluate whether continuation of LDA is noninferior to discontinuation regarding ESD-related bleeding risk in patients with low thrombotic risk. Patients with gastric mucosal neoplasms and low thrombotic risk who were taking LDA were eligible. Participants were randomly assigned to either the discontinuation or continuation group. No prophylaxis was performed except for cauterizing exposed vessels at the ulcer base. The primary end point was the incidence of ESD-related major bleeding. A total of 551 patients were enrolled. In the modified intent-to-treat analysis, the incidence of ESD-related major bleeding (95%) was 7.6% (4.8-11) in the discontinuation group (n = 276) and 10% (6.9-14) in the continuation group (n = 275), yielding a risk difference of 2.5% (-2.3 to 7.4). The upper limit of the 2-sided 90% confidence interval (6.6%) exceeded the predefined noninferiority margin (Δ5%, P = 0.157). The per-protocol analysis supported this negative result, with a risk difference of 4.4% (-0.5 to 9.5). Two patients in the continuation group developed cerebral infarction. The noninferiority of LDA continuation over discontinuation for ESD-related major bleeding in gastric ESD was not demonstrated. Therefore, discontinuation of LDA during the periprocedural period is recommended for patients with low thrombotic risk (UMIN000013177).

Abstract We analyzed the differences in bacterial composition between 475 Japanese patients with advanced gastric cancer (median age 70 years, median BMI 20.0) and 106 healthy individuals using a comprehensive metagenome shotgun analysis. Among the patients with advanced gastric cancer, 71% were male, 37.% patients had relapsed, and 55.5% previously underwent gastrectomy. Bifidobacterium , Anaerostipes , and Parabacteroides were predominant in healthy individuals, whereas Streptococcus , Lactobacillus , and Odoribacter were predominant in patients with advanced gastric cancer. Additionally, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that butanoate and pyruvate metabolism was enriched in healthy individuals, whereas factors such as ABC transporters and ribosomes were enriched in patients with advanced gastric cancer. Clustering analysis broadly classified patients with advanced gastric cancer and healthy individuals into two clusters; however, clustering using pathway data enabled a clearer classification of patients with advanced gastric cancer and healthy individuals than clustering using flora analysis. Moreover, healthy individuals showed higher bacterial flora diversity than patients with advanced gastric cancer. Thus, we successfully identified the molecular characteristics of microbial genera and functional pathways in the gut of patients with advanced gastric cancer. Our results suggest that fecal metagenomic shotgun sequencing analysis can be used to detect gastric cancer.

Modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) and nab-paclitaxel + gemcitabine are recommended as first-line treatments for metastatic pancreatic cancer. S-1, irinotecan, and oxaliplatin (S-IROX) demonstrated activity in a phase Ib trial in this population. Therefore, these three regimens were directly compared. This randomized phase II/III trial was performed at 45 centers in Japan. Eligible patients age 20-75 years with an Eastern Cooperative Oncology Group performance status of 0 or 1 and pathologically confirmed metastatic or recurrent pancreatic cancer were randomly assigned (1:1:1) to receive mFOLFIRINOX (oxaliplatin 85 mg/m2 over 2 hours, irinotecan 150 mg/m2 over 90 minutes, l-leucovorin 200 mg/m2 over 2 hours, each once daily on day 1, and fluorouracil 2,400 mg/m2 over 46 hours on days 1-3, every 2 weeks), S-IROX (oxaliplatin 85 mg/m2 over 2 hours, irinotecan 150 mg/m2 over 90 minutes on day 1, and S-1 80 mg/m2/day administered orally twice daily on days 1-7, every 2 weeks), or nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m2) on days 1, 8, and 15 every 4 weeks. The primary end point was overall survival (OS). A total of 527 patients were enrolled, with 426 included in the planned interim analysis. The median OS was 14.0 months (hazard ratio [HR], 1.31 [95% CI, 0.97 to 1.77]) and 13.6 months (HR, 1.35 [95% CI, 1.00 to 1.82]) in the mFOLFIRINOX and S-IROX groups, respectively, as compared with 17.1 months in the nab-paclitaxel + gemcitabine group. The predictive probability of achieving superiority in the final analysis was <1% in both groups. Thus, the trial was terminated owing to its futility. Grade 3 to 4 anorexia was more frequent in the mFOLFIRINOX (23.3%) and S-IROX (27.5%) groups than in the nab-paclitaxel + gemcitabine group (5.0%). Neither mFOLFIRINOX nor S-IROX appeared to be superior compared with nab-paclitaxel + gemcitabine as the first-line treatment for metastatic or recurrent pancreatic cancer.

We report two cases of folliculosebaceous poroma (holocrine poroma) harboring gene rearrangements involving members of the p21-activated kinase (PAK) family. Both tumors were composed of small poroid cells with ductal and sebaceous differentiation and demonstrated strong nuclear GATA3 expression on immunostaining. In one case, fluorescence insitu hybridization (FISH) demonstrated a PAK2 rearrangement; in the other, a PAK3 rearrangement was identified. Although GATA3 has been proposed as a useful marker to distinguish clonal seborrheic keratosis from hidroacanthoma simplex, its strong expression in PAK2/PAK3-rearranged folliculosebaceous poromas suggests limited specificity in this differential context. Notably, to our knowledge, this represents the first reported case of a benign poroma harboring a PAK3 rearrangement. These findings support a role for PAK gene fusions that may contribute to sebaceous differentiation in folliculosebaceous poroma and underscore the molecular heterogeneity of poromas.

Fibroblast growth factor receptor 2b (FGFR2)-overexpressing advanced gastric cancer (AGC) is associated with poor prognosis and limited treatment options. Bemarituzumab, which selectively binds to FGFR2b, is being investigated in combination with chemotherapy as a first-line treatment. Dual inhibition of the vascular endothelial growth factor-vascular endothelial growth factor receptor and FGF-FGFR pathways may improve the survival of FGFR2b-positive AGC through synergistic inhibition of angiogenesis and the downstream signals for tumor proliferation. The WJOG18524G trial (RAINBIRD) is a single-arm, multicenter phase II trial to evaluate the safety and efficacy of bemarituzumab in combination with paclitaxel plus ramucirumab in patients with FGFR2b-positive AGC who are intolerant or refractory to first-line fluoropyrimidine-based chemotherapy. The main inclusion criteria are unresectable or metastatic FGFR2b-positive gastric adenocarcinoma, refractoriness or intolerance to fluoropyrimidine-based chemotherapy, measurable lesions, and performance status of 0 or 1. The primary endpoint is the objective response rate, which is assessed by a blinded independent central review. Translational research is planned to explore the predictive biomarkers and mechanisms of resistance to bemarituzumab by sequencing tumor DNA (PleSSiSion-Neo) and circulating tumor DNA (Guardant360), which are collected at multiple time points.

Hidradenoma can exhibit several cell types, including clear cells, polyhedral eosinophilic cells, squamoid cells, mucinous cells, oxyphilic (oncocytic) cells, and transitional (intermediate) cells. However, sebocytes have not yet been described in hidradenoma. Here, we present a case of CRTC1::MAML2-positive hidradenoma with sebaceous differentiation. In addition, this tumor had two cell-type layers that were morphologically similar to apocrine glandular cells and myoepithelial cells throughout the lesion. A 66-year-old male presented with a 20 mm nodule on his upper lip with a 3-year history. Histopathological examination revealed a multinodular tumor adherent to the overlying epidermis. No surrounding salivary glands were seen. The tumor consisted of eosinophilic ductoglandular cells surrounded by basaloid cells at the outer periphery. Numerous sebocytes were scattered throughout the tumor. Severe nuclear atypia or mitotic figures were not observed. Immunohistochemical examination showed no expression of α-smooth muscle actin, calponin, and S100 protein in the tumor cells. Adipophilin highlighted scattered sebocytic tumor cells. Immunoexpression of MLH1, PMS2, MSH2, and MSH6 was preserved. MAML2 break-apart fluorescence insitu hybridization revealed frequent split signals. Sanger sequencing revealed a CRTC1(e1)::MAML2(e2) fusion. Based on this report, hidradenoma should be included in the differential diagnosis of cutaneous adnexal tumors with sebaceous differentiation other than sebaceous adnexal tumors. In addition, sebocytes should be added to the list of tumor cell types in hidradenoma.

As indications for segmentectomy in small lung cancers expand, accurate preoperative computed tomography (CT) evaluation has become increasingly important. Irregularly shaped tumors require objective measurement techniques. This study assessed new segmentectomy criteria for early-stage non-small-cell lung cancer (NSCLC) using three-dimensional (3D) CT tumor volume. In total, 200 segmentectomies and 691 lobectomies for clinical stage 0/IA NSCLC were retrospectively analyzed. Preoperative 3D-CT was performed to measure total tumor volume and solid component volume. To assess the predictive value of solid component volume and solid component ratio for recurrence and mortality, the receiver operating characteristic (ROC) curves for the segmentectomy and lobectomy groups were plotted individually. Based on the cut-off values derived from the ROC curves in the segmentectomy group, all cases were stratified into four categories ("volume high risk + ratio high risk", "volume high risk + ratio low risk", "volume low risk + ratio high risk", "volume low risk + ratio low risk"). Recurrence-free survival was analyzed using the log-rank test. The cutoff values were 2063.4 mm3 and 28.3% for segmentectomy and 4705.0 mm3 and 73.0% for lobectomy. A significant difference in the 5-year recurrence-free survival between segmentectomy and lobectomy was found only in the volume high-risk + ratio high-risk category (48.1% vs. 66.9%). This exploratory analysis suggests that 3D-CT tumor quantification may aid in refining segmentectomy criteria; however, external validation is necessary before clinical application.