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Abstract Background Histopathology by pathologists is essential in the diagnosis of non‐small cell lung cancer (NSCLC). However, auxiliary diagnostic procedures for malignant tumor have continued to evolve. Despite the poor prognosis of patients with NSCLC, the application of the latest procedures and technologies to the field of lung cancer has lagged. Mass spectrometry was used to detect trace amounts of peptides in human tissue with high accuracy. The aim of this study was to establish a method for diagnostic mass spectrometry to identify lymph node metastasis by detecting cytokeratin (CK)19, a useful biomarker in lung cancer. Methods We collected 81 lymph nodes with positive expression of CK19 in patients who underwent radical surgical resection in the Department of Thoracic Surgery at Iwate Medical University between May 2020 and December 2022. An X500R instrument was used for sample analysis. A positive result for lymph node metastasis as the detection at least two product ions (FGPGVAFR and ILGATIENSR) from CK19 was defined. Results Our study indicated a high diagnostic efficiency for mass spectrometry, with 87.5% sensitivity and 91.2% specificity. The mutual concordance of mass spectrometry methods and histopathological diagnosis was 90.1%. Conclusions Mass spectrometry offers high diagnostic accuracy and can be clinically applied to auxiliary diagnostic procedures for lymph node metastasis from NSCLC.

Abstract Inflammatory myofibroblastic tumor (IMT) is a rare disease that is considered an intermediate neoplasm, with the risk of recurrence and metastasis. Surgical treatment is the standard therapy for IMT, although there are only a few reports of surgery for lung metastasis of pulmonary IMT. We opine that surgical treatment might be effective not only for localized tumors, but also for cases of lung metastasis of IMT.

Abstract Background Segmentectomy with curative intention is occasionally performed for early non‐small cell lung cancer (NSCLC). However, a major problem has been pointed out, in that the rate of locoregional recurrence is higher after segmentectomy than after lobectomy. This study aimed to investigate differences in rates of lymph node metastasis between segment 6 and basal segment NSCLC as potential candidates for segmentectomy and to explore factors associated with locoregional recurrence of segmentectomy. Methods We retrospectively analyzed 461 patients with lower lobe NSCLC who underwent segmentectomy or lobectomy with mediastinal lymph node dissection between 2011 and 2021. Among these, 122 patients with clinical N0 NSCLC, diameter ≤ 20 mm, and consolidation tumor ratio >0.5 were analyzed. Results The 122 patients were divided into a segment 6 group (n = 51) and a basal segment group (n = 71). Frequency of lymph node metastasis was significantly higher in the segment 6 group (17.7%) than in the basal segment group (4.2%; p = 0.01). Metastases to lymph node station 7 were seen in five of 122 patients (4.1%). Hilar lymph node metastasis occurred in nine of 122 patients (7.4%). Notably, metastases to station 11, 11i and 11 s lymph nodes were the most frequent patterns for hilar lymph nodes (41.7%). Conclusions Station 11 lymph nodes are adjacent to the remaining lung segment or pulmonary artery in S6 segmentectomy or basal segmentectomy. Part of the NSCLC in segment 6 patients may thus be considered for lobectomy owing to the difficulty of complete dissection of station 11 lymph nodes.

Abstract Background Bleeding from the pulmonary artery (PA) can be fatal in video‐assisted thoracoscopic surgery (VATS) for lung cancer. We evaluated intraoperative PA injury and assessed precautions for thoracoscopic anatomic pulmonary resection. Methods We retrospectively analyzed a total of 1098 patients who underwent radical surgery for lung cancer utilizing complete VATS from January 2010 to December 2021. Results A total of 16 patients (1.5%) had PA injury during VATS, while hemostasis was performed by conversion to thoracotomy in eight patients (50.0%). Although there was a significantly greater operation time and blood loss for patients in the PA injury group (318.4 vs. 264.9 min, p = 0.001; 550.3 vs. 60.5 g, p ≤ 0.001, respectively), there was no significant different for the chest tube insertion duration and length of postoperative hospital stay (4.9 vs. 7.8 days, p = 0.157; 10.6 vs. 9.9 days, p = 0.136, respectively). There was a significant difference observed for the surgical procedure related to the left upper lobectomy in the PA injury group (43.8 vs. 18.8%, p = 0.012), with the primary causative PA determined to be the left anterior segmental PA (A3) (31.3%). Conclusions VATS is both feasible and safe for lung cancer treatment provided the surgeon performs appropriate hemostasis, although fatal vascular injury could potentially occur during VATS. Surgeons need to be aware of the pitfalls regarding PA dissection management.

Abstract Background Rapid intraoperative diagnosis for unconfirmed pulmonary tumor is extremely important for determining the optimal surgical procedure (lobectomy or sublobar resection). Attempts to diagnose malignant tumors using mass spectrometry (MS) have recently been described. This study evaluated the usefulness of MS and artificial intelligence (AI) for differentiating primary lung adenocarcinoma (PLAC) and colorectal metastatic pulmonary tumor. Methods Pulmonary samples from 40 patients who underwent pulmonary resection for PLAC (20 tumors, 20 normal lungs) or pulmonary metastases originating from colorectal metastatic pulmonary tumor (CRMPT) (20 tumors, 20 normal lungs) were collected and analyzed retrospectively by probe electrospray ionization‐MS. AI using random forest (RF) algorithms was employed to evaluate the accuracy of each combination. Results The accuracy of the machine learning algorithm applied using RF to distinguish malignant tumor (PLAC or CRMPT) from normal lung was 100%. The algorithms offered 97.2% accuracy in differentiating PLAC and CRMPT. Conclusions MS combined with an AI system demonstrated high accuracy not only for differentiating cancer from normal tissue, but also for differentiating between PLAC and CRMPT with a short working time. This method shows potential for application as a support tool facilitating rapid intraoperative diagnosis to determine the surgical procedure for pulmonary resection.

Abstract Background Pedunculated polyps are more likely to be amenable to complete resection than non-pedunculated early colorectal cancers and rarely require additional surgery. We encountered a patient with a pedunculated early colorectal cancer that consisted of poorly differentiated adenocarcinoma with lymphatic invasion. We performed an additional bowel resection and found nodal metastasis. Case presentation A 43-year-old woman underwent colonoscopy after a positive fecal occult blood test. The colonoscopist found a 20-mm pedunculated polyp in the descending colon and performed endoscopic resection. Histopathologic examination revealed non-solid type poorly differentiated adenocarcinoma. The lesion invaded the submucosa (3500 μm from the muscularis mucosa) and demonstrated lymphatic invasion. In spite of the early stage of this cancer, the patient was considered at high risk for nodal metastasis. She was referred to our institution, where she underwent bowel resection. Although there was no residual cancer after her endoscopic resection, a metastatic lesion was found in one regional lymph node. The patient is undergoing postoperative adjuvant chemotherapy, and there has been no evidence of recurrence 3 months after the second surgery. Conclusions Additional bowel resection is indicated for patients with pedunculated polyps and multiple risk factors for nodal metastasis, such as poorly differentiated adenocarcinoma and lymphatic invasion. We encountered just such a patient who did have a nodal metastasis; herein, we report her case history with a review of the literature.

Abstract Low‐grade fibromyxoid sarcoma (LGFMS) is a rare sarcoma subtype that most commonly arises in young adults. This tumor typically presents in the deep soft tissues of the proximal extremities or trunk as a painless mass. Although the most common site of LGFMS metastasis is the lung, it is rarely the primary site. Here, we report a case of primary pulmonary LGFMS. A 22‐year‐old asymptomatic man was referred to our hospital for investigation of a lung mass that had been discovered incidentally. Computed tomography (CT) showed a well‐defined mass 4.0 cm in diameter in the upper lobe of the right lung. Malignancy was suggested by focal uptake of 18F‐fluorodeoxyglucose positron‐emission tomography (18‐FDG‐PET). Following surgery, postoperative histological analysis of the resected specimen demonstrated LGFMS based on histological and immunohistological findings. In particular, mucin 4 showed diffuse positivity in the spindle‐shaped tumor cells. In conclusion, LGFMS can arise in the lungs, and physicians should consider this entity as a differential diagnosis for solitary lung mass in young adults.

Abstract Background Various types of preoperative chemoradiotherapy (CRT) have been established for rectal cancer; thus,Physicians will need to refine the selection of appropriate preoperative CRT for different patients since there are various treatment regimens. Oral tegafur-uracil (UFT) plus leucovorin (LV) is commonly used to treat rectal cancer in Japan. Oral chemotherapy offers patients many potential advantages. Since 2008, we have been performing preoperative CRT with intermittent oral UFT plus LV in locally advanced rectal cancer patients to prevent postoperative local recurrence. Here, in a retrospective analysis, we evaluated the efficacy and short-term outcomes of preoperative CRT with intermittent oral UFT plus LV. Methods We analyzed data from 62 patients with locally advanced rectal cancer, including 31 patients who underwent preoperative CRT between 2009 and 2013 (the CRT group) and 31 patients who were treated with surgery alone between 2001 and 2008 (the non-CRT group). Clinicopathologically, both groups included patients with rectal cancer at clinical tumor stages 3-4 or clinical node stages 0-3. In the CRT group, curative operations were performed ≥8 weeks after CRT. Patients were concomitantly treated with 2 cycles of oral UFT (300 mg/m2/day, days 1–14 and 29–42) plus LV (75 mg/day, days 1–14 and 29–42) and 45 Gy of radiotherapy. Chemotherapy was repeated every 28 days, followed by a 2-week break. Results The completion rate of CRT was high at 94% (n = 29/31). The downstaging rate of CRT was 61% (n = 19/31). The pathological complete response rate was 6.5% (n = 2/31). Significant differences were observed in the 3-year local recurrence rate between the two groups (P < 0.05). Conclusions Preoperative CRT with intermittent oral UFT plus LV appears to be a tolerable and effective treatment for Japanese patients with rectal cancer. A further investigation of a diversification of preoperative CRT for Japanese rectal cancer patients is required.

AST-120 (Kremezin) is used to treat progressive chronic kidney disease by adsorbing uremic toxin precursors produced by the gut microbiota, such as indole and phenols. Previously, we found that AST-120 decreased drug tolerance and virulence in Escherichia coli by adsorbing indole. Here, we show that AST-120 adsorbs phenazine compounds, such as pyocyanin, produced by Pseudomonas aeruginosa including multidrug-resistant P. aeruginosa strains, and suppresses pyocyanin-associated toxicity in A-549 (alveolar adenocarcinoma) and Caco-2 (colon adenocarcinoma) cells. Addition of fosfomycin, colistin and amikacin, which are often used to treat P. aeruginosa, inhibited the bacterial growth, regardless of the presence or absence of AST-120. These results suggest a further benefit of AST-120 that supports anti-Pseudomonas chemotherapy in addition to that of E. coli and propose a novel method to treat P. aeruginosa infection.

We explored the renal protective effects by a gut peptide, Ghrelin. Daily peritoneal injection with Ghrelin ameliorated renal damages in continuously angiotensin II (AngII)-infused C57BL/6 mice as assessed by urinary excretion of protein and renal tubular markers. AngII-induced increase in reactive oxygen species (ROS) levels and senescent changes were attenuated by Ghrelin. Ghrelin also inhibited AngII-induced upregulations of transforming growth factor-β (TGF-β) and plasminogen activator inhibitor-1 (PAI-1), ameliorating renal fibrotic changes. These effects were accompanied by concomitant increase in mitochondria uncoupling protein, UCP2 as well as in a key regulator of mitochondria biosynthesis, PGC1α. In renal proximal cell line, HK-2 cells, Ghrelin reduced mitochondria membrane potential and mitochondria-derived ROS. The transfection of UCP2 siRNA abolished the decrease in mitochondria-derived ROS by Ghrelin. Ghrelin ameliorated AngII-induced renal tubular cell senescent changes and AngII-induced TGF-β and PAI-1 expressions. Finally, Ghrelin receptor, growth hormone secretagogue receptor (GHSR)-null mice exhibited an increase in tubular damages, renal ROS levels, renal senescent changes and fibrosis complicated with renal dysfunction. GHSR-null mice harbored elongated mitochondria in the proximal tubules. In conclusion, Ghrelin suppressed AngII-induced renal damages through its UCP2 dependent anti-oxidative stress effect and mitochondria maintenance. Ghrelin/GHSR pathway played an important role in the maintenance of ROS levels in the kidney.

Mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome are disease that fulfilled criteria for diagnosis of Behcet's disease (BD) and relapsing polychondritis (RP). We report a 22-year-old Japanese woman presented with MAGIC syndrome and we described the clinicopathological characteristics of MAGIC syndrome based on a review of published cases from July 1985 to December 2015. In our case, the patient with oral aphthae, erythema nodosum, acne-like eruptions, uveitis, and polyarthritis fulfilled criteria for diagnosis of incomplete form of BD. The patient with uveitis, polyarthritis, and histological confirmation of chondritis also fulfilled criteria for diagnosis of RP. The patient was successfully treated with oral colchicine followed by prednisolone. The symptoms of MAGIC syndrome gradually disappeared, and the prednisolone dosage was gradually decreased and stopped. She has been in remission without active medication for a further 8 months. In the previous reports, some authors suggested that MAGIC syndrome was not a disease entity and might be RP occurring secondary to BD, another association of an autoimmune disease, or vasculitis with RP. However, the pathogenic association between MAGIC syndrome, BD, and RP is still unclear, and the number of reported cases of MAGIC syndrome is insufficient to establish a clear explanation. Therefore, further accumulation of data and careful observation of the clinical course are required to improve the understanding of MAGIC syndrome.

Background: Several recent studies have reported that patients with metastatic colorectal cancer (CRC) whose primary tumor is located in left side of the colon have more favorable responses to anti-epidermal growth factor receptor (EGFR) antibody therapy than those with right-sided tumors. However, the mechanism for this phenomenon is unknown.Methods: Fifty-two cases of primary CRC with liver metastases were analyzed in this retrospective study. The mRNA levels of 19 signal transduction genes in both primary tumor and liver metastases were measured by real-time reverse transcription polymerase chain reaction. The purposes of this study were (1) to determine the correspondence between signal transduction gene expressions in primary tumors and corresponding liver metastases, and (2) to determine whether expression levels of these genes differ by primary tumor location.Results: mRNA expression levels of 14 of 19 signal transduction genes, including PTEN, ERBB2, MET, HGF, AREG, and EREG, showed significant correlations between the primary tumor and corresponding liver metastases. When the mRNA levels of the primary tumors were compared by tumor location, only PTEN mRNA expression differed significantly between left and right-sided CRC (median PTEN expression: left 1.00 vs. right 1.68; p = 0.017). When rectal cancers were separated from left-sided colon cancers, PTEN mRNA levels increased progressively from rectum to right-sided colon (median; rectum 0.84, left colon 1.23, right colon 1.68, p = 0.013). PTEN mRNA expression in liver metastases also differed significantly according to primary tumor location (median; left 0.92 vs. right 1.27, p = 0.048). There was no difference in overall survival between patients with high versus low levels of PTEN mRNA (p = 0.59).Conclusions: Our data suggest that the PIK3/AKT/mTOR pathway is more active in left- than right-sided CRC, which provides a possible explanation for the fact that efficacy of anti-EGFR therapy differs by location of primary tumor. [ABSTRACT FROM AUTHOR]

de Garengeot hernia is a rare subtype of a femoral hernia with incarceration of the appendix. This type of hernia usually presents with therapeutic dilemmas, especially because of the risk of surgical site infection (SSI). Our patient was a 74-year-old woman with a bulging mass and tenderness in the right inguinal area. Computed tomography revealed an incarcerated appendix, with appendicitis in the femoral hernia. Laparoscopic appendectomy was initially performed, followed by hernioplasty via the anterior approach to prevent properitoneal contamination. Some authors have recently reported cases successfully treated by laparoscopy. However, this type of hernia has a higher risk for SSI, compared with the risk involved in usual hernioplasty. Therefore, selection of the appropriate surgical approach to prevent wound infection is important, especially in the presence of appendicitis. We would like to highlight the usefulness of hybrid surgery, laparoscopic appendectomy and hernioplasty via the anterior approach to prevent SSIs. [ABSTRACT FROM AUTHOR]

Noda epileptic rats (NERs) present with clinico-pathological manifestations reminiscent of human generalized tonic-clonic epilepsy. Thus, this strain of rat has been a model of primary, generalized, tonic-clonic epilepsy. However, the infrequency of seizures in these rats makes the assessment of antiepileptic drugs (AEDs) difficult. Therefore, traditional AEDs have only been tested in NERs against audiogenic seizures evoked by weekly acoustic priming from 3 to 22 weeks of age or by using the kindling procedure in adult animals. Adult NERs are susceptible to changes in their environment, such as bedding replacement or unpleasant sensory stimuli. In the present study, traditional AEDs-phenobarbital (PB) and sodium valproate (VPA)-were evaluated against seizures evoked by strong environmental stimuli in mature NERs that had not been previously primed. The number of animals presenting with seizures decreased in a dose-dependent manner following administration of either PB (dose range 1.0-5.0 mg/kg) or VPA (50 and 100 mg/kg). Consequently, the utility of NERs as a model of generalized tonic-clonic epilepsy was confirmed. This type of protocol can be used to further evaluate AEDs and test effects of chronic administration of AEDs. [ABSTRACT FROM AUTHOR]