Circulating Exosomal MicroRNA Signature Predicts Peritoneal Metastasis in Patients with Advanced Gastric Cancer.

BACKGROUND: Despite a radical operation, about half of gastric cancer (GC) patients with advanced GC experience peritoneal metastasis (PM), and the patients with PM have a poor prognosis. However, because staging laparoscopy was a highly invasive procedure for patients, identification of PM using a liquid biopsy can be useful for patients with GC. METHODS: This study analyzed two genome-wide miRNA expression profiling datasets (GSE164174 and TCGA). The study prioritized biomarkers in pretreatment plasma specimens from clinical training and validation cohorts of patients with GC. The authors developed an integrated exosomal miRNA panel and established a risk-stratification model, which was combined with the miRNA panel and currently used tumor markers (CEA, CA19-9, CA125, and CA72-4 levels). RESULTS: The comprehensive discovery effort identified a four-miRNA panel that robustly predicted the metastasis with excellent accuracy in the TCGA dataset (area under the curve [AUC] 0.86). A circulating exosomal miRNA panel was established successfully with remarkable diagnostic accuracy in the clinical training (AUC 0.85) and validation (AUC 0.86) cohorts. Moreover, the predictive accuracy of the panel was significantly superior to that of conventional clinical factors (P < 0.01), and the risk-stratification model was dramatically superior to the panel and currently used clinical factors for predicting PM (AUC 0.94; univariate: odds ratio [OR] 77.00 [P < 0.01]; multivariate OR 57.71 [P = 0.01]). CONCLUSIONS: The novel risk-stratification model for predicting PM has potential for clinical translation as a liquid biopsy assay for patients with GC. The study findings highlight the potential clinical impact of the model for improved selection and management of patients with GC.

SF6 is a useful expander for post-pneumonectomy syndrome in the long-term course: a case report.

BACKGROUND: Post-pneumonectomy syndrome (PPS) is a rare but serious condition that can occur after pneumonectomy. It is characterized by a mediastinal shift towards the vacated hemithorax, which can potentially lead to respiratory failure. The management of PPS poses a clinical challenge, especially in the context of the limited availability of certain therapeutic devices due to regulatory restrictions in Japan. CASE PRESENTATION: A 36-year-old female with stage IB non-small cell lung cancer underwent left pneumonectomy. Approximately 2 years later, she developed dyspnea. After consulting with our hospital, subsequent imaging revealed an extreme mediastinal shift causing bronchial obstruction. Emergency thoracotomy and subsequent sulfur hexafluoride (SF6) injections were successfully used to manage her condition. Over the course of follow-up, the interval between SF6 injections was extended from 3 to 11 months, indicating an improvement in the intrathoracic condition. CONCLUSIONS: This case illustrates the efficacy of SF6 gas in treating PPS and in reducing the frequency of medical interventions. SF6 gas administration is safe and effective for the treatment of patients with PPS.

Local Recurrence of Rectal Cancer After Transanal Total Mesorectal Excision and Risk Factors: A Nationwide Multicenter Cohort Study in Japan.

Objective: To investigate the oncological outcomes after transanal total mesorectal excision (TaTME) for rectal cancer and risk factors for local recurrence (LR). Background: A high LR rate with a multifocal pattern early after TaTME has been reported in Norway and the Netherlands, causing controversy over the oncological safety of this technique. Methods: Twenty-six member institutions of the Japan Society of Laparoscopic Colorectal Surgery participated in this retrospective cohort study. A total of 706 patients with primary rectal cancer who underwent TaTME between January 2012 and December 2019 were included for analysis. The primary endpoint was the cumulative 3-year LR rate. Results: A total of 253 patients had clinical stage III disease (35.8%) and 91 (12.9%) had stage IV. Intersphincteric resection was performed in 318 patients (45.0%) and abdominoperineal resection in 193 (27.3%). There was 1 urethral injury (0.1%). A positive resection margin (R1) was seen in 42 patients (5.9%). Median follow-up was 3.42 years, and the 2- and 3-year cumulative LR rates were 4.95% (95% confidence interval: 3.50-6.75) and 6.82% (95% confidence interval: 5.08-8.89), respectively. A multifocal pattern was observed in 14 (25%) of 56 patients with LR. Tumor height from the anal verge, pathological T4 disease, pathological stage III/IV, positive perineural invasion, and R1 resection were significant risk factors for LR in multivariable analysis. Conclusions: In this selected cohort in which intersphincteric resection or abdominoperineal resection was performed in more than half of cases, oncological outcomes were acceptable during a median follow-up of more than 3 years.

Prognostic impact of the combination of p16INK4a, p21 and Immunoscore in rectal cancer.

BACKGROUND: The association between p16INK4a and p21, a marker of cellular senescence, and the Immunoscore, an immunological prognostic indicator, in rectal cancer patients undergoing curative surgery were investigated. METHODS: A total of 82 patients who underwent curative surgery for rectal cancer were evaluated. The resected specimens were analyzed for p16INK4a, p21, CD3 and CD8 expression by immunohistochemistry. Immunoscore was calculated on the basis of CD3 and CD8 expressions. The clinicopathological characteristics and long-term outcomes were evaluated. RESULTS: Among the 82 patients, 24 (29.3%) were p16INK4a-positive and 11 (13.4%) were p21-positive. The patients were classified into the following five Immunoscore groups (IS0-5). IS0, IS1 and IS2 were classified as the low Immunoscore group (45 patients, 54.9%) and IS3 and IS4 as the high Immunoscore group (37 patients, 45.1%). There was no significant difference in age, sex, body mass index, American Society of Anesthesiologists physical status, depth of invasion of the tumor, lymph node metastasis and histological classification of the tumor with p16INK4a or p21 expression or Immunoscore. p16INK4a-positive expression and low Immunoscore each showed a tendency to indicate poor prognosis of disease-free survival (DFS). Patients with the combination of p16INK4a and p21 positivity and with p16INK4a positivity and low Immunoscore showed significantly poor prognosis of DFS. Patients with p21 positive positivity and low Immunoscore tended to have worse DFS. CONCLUSIONS: p16INK4a, p21 and Immunoscore may be prognostic indicators of rectal cancer. The combination of them may provide more accurate prognostic prediction than either factor alone.

Feasibility of laparoscopic and endoscopic cooperative surgery for gastric gastrointestinal stromal tumor with tumor diameter of >5 cm.

BACKGROUND: Laparoscopic and endoscopic cooperative surgery (LECS) is an effective treatment for gastric gastrointestinal stromal tumors (GISTs). The utility of LECS for gastric GISTs of > 5 cm remains controversial. This study was performed to investigate the feasibility of LECS for gastric GISTs with a tumor diameter of >5 cm. METHODS: We analyzed 43 patients with gastric GISTs who underwent LECS or laparoscopic partial gastrectomy (Lap-Partial Gx). We compared the surgical outcomes of LECS versus Lap-Partial Gx and of LECS for a tumor diameter of > 5 versus ≤ 5 cm. RESULTS: In the comparison of LECS versus Lap-Partial Gx, there were no significant intergroup differences in the operative time or blood loss volume. The morbidity rate was similar between the groups. No postoperative mortality occurred in either group. In the comparison of LECS for a tumor diameter of > 5 versus ≤ 5 cm, there were no significant intergroup differences in operative time, or blood loss volume. The morbidity rate was similar between the > 5-cm and ≤ 5-cm groups (0.0% vs. 4.5%, respectively ; p = 0.56). Additionally, no recurrence or death occurred during follow-up in either group. CONCLUSION: LECS is a feasible option for gastric GISTs with a tumor diameter of > 5 cm. J. Med. Invest. 71 : 148-153, February, 2024.

Blue light irradiation inhibits the M2 polarization of the cancer-associated macrophages in colon cancer.

Recent studies have shown that blue light-emitting diode (LED) light has anti-tumor effects, suggesting the possibility of using visible light in cancer therapy. However, the effects of blue light irradiation on cells in the tumor microenvironment, including tumor-associated macrophages (TAMs), are unknown. Here, THP-1 cells were cultured in the conditioned medium (CM) of HCT-116 cells to prepare TAMs. TAMs were divided into LED-irradiated and control groups. Then, the effects of blue LED irradiation on TAM activation were examined. Expression levels of M2 macrophage markers CD163 and CD206 expression were significantly decreased in LED-irradiated TAMs compared with the control group. While control TAM-CM could induce HCT-116 cell migration, these effects were not observed in cells cultured in TAM-CM with LED irradiation. Vascular endothelial growth factor (VEGF) secretion was significantly suppressed in LED-exposed TAMs. PD-L1 expression was upregulated in HCT-116 cells cultured with TAM-CM but attenuated in cells cultured with LED-irradiated TAM-CM. In an in vivo model, protein expression levels of F4/80 and CD163, which are TAM markers, were reduced in the LED-exposed group. These results indicate that blue LED light may have an inhibitory effect on TAMs, as well as anti-tumor effects on colon cancer cells.

Number of Healthy Teeth Can Predict the Response of Rectal Cancer to Chemoradiotherapy: A Retrospective Study.

BACKGROUND: It has been reported that the oral and gut microbiomes are associated with the prognosis in patients who undergo surgery, chemotherapy, and radiation for colorectal cancer. This study is the first to identify a correlation between the number of healthy teeth, which is an oral health indicator, and the efficacy of preoperative chemotherapy for rectal cancer. METHODS: This retrospective single-center study included 30 patients who underwent radical surgery after preoperative chemoradiotherapy (CRT) between December 2013 and June 2021. The relationship between number of teeth before CRT and the efficacy of CRT, CRT-related adverse events, postoperative complications, and long-term postoperative outcomes was examined. RESULTS: The number of healthy teeth was significantly greater in patients with downstaging of their disease than in those without downstaging (P = .027) and in patients with a complete response according to the Response Evaluation Criteria in Solid Tumors than in those who did not have a complete response (P = .014). Patients were divided into two groups according to whether they had ≥15 teeth or ≤14 teeth. There was no significant between-group difference in CRT-related adverse events. The incidence of all postoperative complications and grade II postoperative complications tended to be higher in patients with ≥15 teeth (P = .071 and P = .092, respectively), as did the 5-year overall survival rate (P = .083) and the 5-year disease-free rate (P = .007). DISCUSSION: The number of healthy teeth predicted the response to preoperative CRT, postoperative complications, and the outcome of subsequent surgery in patients with rectal cancer.

Fulminant myocarditis during postoperative adjuvant chemotherapy for lung cancer with atezolizumab: a case report.

BACKGROUND: Postoperative adjuvant systemic therapy with atezolizumab for lung cancer has been reported to be effective. Although myocarditis is a rare immune adverse event associated with atezolizumab, it can have a serious course and should be treated with caution. We herein report a case of fulminant myocarditis during adjuvant systemic therapy with atezolizumab. CASE PRESENTATION: The patient was a 49-year-old Asian woman. She was diagnosed with pT2aN1M0 stage IIB (Programmed Death Ligand 1(PD-L1), 50%) after surgery for right upper lobe lung adenocarcinoma. Atezolizumab was administered following platinum-based adjuvant chemotherapy. On day 14, the patient was hospitalized because of deterioration in her general condition caused by fever. On day 16, she developed dyspnea, which worsened, and on day 17, she experienced shock. Blood tests, echocardiography, and cardiac catheterization were performed, and the patient was diagnosed with cardiogenic shock due to myocarditis. Initial measures did not improve the patient's shock state. The patient was transferred to hospital for the use of an assistive circulatory system. Pulse steroid therapy was administered, and myocarditis showed a tendency toward improvement. A retrospective review of the patient's history revealed a decreased lymphocyte count and an increase in the neutrophil/lymphocyte ratio, which may be useful for detecting severe immune-related adverse events. The troponin levels were elevated, but creatine phosphokinase level remained within the normal range. CONCLUSION: Myocarditis can be fatal due to the rapid progression of symptoms. Close follow-up, a prompt diagnosis, and therapeutic intervention are important. Decreased lymphocyte counts, increased neutrophil/lymphocyte ratios, and the measurement of multiple myocardial biomarkers are considered useful for the early diagnosis of myocarditis.

Comparison of the short-term surgical outcomes of lateral lymph node dissection for low rectal cancer using a robotic-assisted transabdominal approach alone or supported by a transanal approach.

BACKGROUND: Lateral lymph node metastases are a major cause of local recurrence after surgery for advanced low rectal cancer. Lateral lymph node dissection (LLND) may reduce the risk of local recurrence in patients with suspected lateral lymph node metastasis. Recent reports have shown that robotic-assisted LLND can help to reduce the postoperative complication rate, such as urinary disturbance. Furthermore, with the advent of transanal total mesorectal excision, a novel LLND procedure that combines a transabdominal approach with a transanal approach has been reported. This study aimed to clarify the safety and feasibility of robotic-assisted LLND supported by a transanal approach for advanced low rectal cancer. METHODS: Thirty-nine patients diagnosed to have low rectal cancer between June 2019 and May 2023 were retrospectively enrolled and divided according to whether they underwent LLND via a robotic-assisted transabdominal approach alone (transabdominal group, n = 19) or in combination with a transanal approach (2team group, n = 20). The patient characteristics and short-term surgical outcomes were compared between the two groups. RESULTS: The total operation time was significantly shorter in the 2team group than in the transabdominal group (366 min vs. 513 min, P < 0.001), as was the time taken to perform unilateral LLND (64 min vs. 114 min, P < 0.001). Furthermore, there was significantly less intraoperative bleeding in the 2team group (30 mL vs. 80 mL, P = 0.004). There was no significant between-group difference in postoperative complications. The incidence of postoperative urinary disturbance was satisfactory at 5% in both groups. CONCLUSIONS: The operation time for LLND performed by a robotic-assisted transabdominal approach was shortened when supported by a transanal approach. The frequency of postoperative urinary disturbance was low in both groups. Therefore, robotic-assisted abdominal LLND supported by a transanal approach can be considered a promising treatment option for advanced low rectal cancer.

Preoperative evaluation to determine the difficulty of No. 6 lymphadenectomy in laparoscopic gastrectomy.

BACKGROUND: Laparoscopic gastrectomy (LG) requires a long learning curve because of the complicated surgical procedures. Infrapyloric (No. 6) lymph node dissection (LND) is one of the difficult procedures in LG, especially for trainees. This study investigated the impact of the prediction of the difficulty of No. 6 LND. METHODS: We retrospectively reviewed the preoperative computed tomography (CT) images and individual operative video records of 57 patients who underwent LG with No. 6 LND to define and predict the No. 6 LND difficulty. To evaluate whether prediction of the difficulty of No. 6 LND could improve surgical outcomes, 48 patients who underwent laparoscopic distal gastrectomy were assessed (30 patients without prediction by a qualified surgeon and 18 patients with prediction by a trainee). RESULTS: The anatomical characteristic that LND required > 2 cm of dissection along the right gastroepiploic vein was defined as difficulty of No. 6 LND. Of the 57 LG patients, difficulty was identified intraoperatively in 21 patients (36.8%). Among the several evaluated anatomical parameters, the length between the right gastroepiploic vein and the right gastroepiploic artery in the maximum intensity projection in contrast-enhanced CT images was significantly correlated with the intraoperative difficulty of No. 6 LND (p < 0.0001). Surgical outcomes, namely intraoperative minor bleeding, postoperative pancreatic fistula, and drain amylase concentration were not significantly different between LG performed by a trainee with prediction compared with that by a specialist without prediction. CONCLUSIONS: Preoperative evaluation of the difficulty of No. 6 LND is useful for trainees, to improve surgical outcomes.

Role of stromal PD-L1 expression in colorectal liver metastasis.

BACKGROUND AND AIM: The outcomes of immune checkpoint blockade for colorectal cancer (CRC) treatment are unsatisfactory. Furthermore, the efficacy of immune checkpoint blockade for liver metastasis of various cancer is poor. Here, we investigated the relationship between stromal programmed death-ligand 1 (PD-L1) expression and the prognosis of patients with colorectal cancer liver metastasis (CRLM). METHODS: The present study enrolled 84 CRLM patients who underwent surgery (R0) for CRC. Immunohistochemistry was performed to analyze stromal PD-L1 expression in CRLM. RESULTS: Stromal PD-L1 was expressed in 52.3% of CRLM samples, which was associated with fewer not optimally resectable metastases (p = 0.04). Stromal PD-L1 also tended to associate with a lower tumor grade (p = 0.08). Stromal PD-L1-positive patients had longer overall survival (p = 0.003). Multivariate analysis identified stromal PD-L1 expression (p = 0.008) and poorer differentiation (p < 0.001) as independent prognostic indicators. Furthermore, stromal PD-L1 expression was correlated to a high number of tumor-infiltrating lymphocytes (TILs). Stromal PD-L1- and low TIL groups had shorter OS than stromal PD-L1 + and high TIL groups (46.6% vs. 81.8%, p = 0.05) Stromal PD-L1-positive patients had longer disease-free survival (DFS) (p = 0.03) and time to surgical failure (p = 0.001). Interestingly, stromal PD-L1 expression was positively related to the desmoplastic subtype (p = 0.0002) and inversely related to the replacement subtype of the histological growth pattern (p = 0.008). CONCLUSIONS: Stromal PD-L1 expression may be a significant prognostic marker for CRLM.

Conversion surgery after successful response to chemotherapy (S-1 + oxaliplatin + nivolumab) in a patient with stage IV gastric cancer with peritoneal metastasis (P1, CY1): a case report.

We here present a case report of a patient with Stage IV gastric cancer with peritoneal metastasis (P1, CY1) who underwent conversion surgery after a successful response to chemotherapy (S-1 + oxaliplatin + nivolumab). The patient was a woman in her 60 s. Her chief complaint was epigastric pain. Upper gastrointestinal endoscopy showed Type 4 advanced carcinoma on the lesser curvature of the gastric body. Biopsy showed Group 5 (poorly differentiated adenocarcinoma) and HER2 was negative. Staging laparoscopy revealed seeding in the round ligament of the liver (P1) and adenocarcinoma cells in ascites (CY1). Ten courses of chemotherapy (S-1 + oxaliplatin + nivolumab) were administered, after which contrast-enhanced computed tomography showed that the primary tumor had shrunk and seeding was no longer detectable. Upper gastrointestinal endoscopy revealed scar-like changes. A second staging laparoscopy revealed that ascites cytology was negative and a biopsy of the round ligament of the liver showed no malignant cells (P0, CY0). Conversion surgery comprising laparoscopic total gastrectomy with D2 lymph node dissection and resection of the round ligament of the liver was performed. The postoperative course was uneventful. Histopathological examination of the resected specimen revealed no tumor cells in the gastric mesentery or the round ligament of the liver. The pathological diagnosis was gastric cancer [M, U, L, Less, Ant, Post, type4, T3(SS), N0, M0 (H0, P0, CY0), ypStage IIA]. Adjuvant chemotherapy (S-1) was commenced. The patient is still alive 7 months later with no evidence of recurrence.

Cartilage tissues regulate systemic aging via ectonucleotide pyrophosphatase/phosphodiesterase 1 in mice.

Aging presents fundamental health concerns worldwide; however, mechanisms underlying how aging is regulated are not fully understood. Here, we show that cartilage regulates aging by controlling phosphate metabolism via ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1). We newly established an Enpp1 reporter mouse, in which an EGFP-luciferase sequence was knocked-in at the Enpp1 gene start codon (Enpp1/EGFP-luciferase), enabling detection of Enpp1 expression in cartilage tissues of resultant mice. We then established a cartilage-specific Enpp1 conditional knockout mouse (Enpp1 cKO) by generating Enpp1 flox mice and crossing them with cartilage-specific type 2 collagen Cre mice. Relative to WT controls, Enpp1 cKO mice exhibited phenotypes resembling human aging, such as short life span, ectopic calcifications, and osteoporosis, as well as significantly lower serum pyrophosphate levels. We also observed significant weight loss and worsening of osteoporosis in Enpp1 cKO mice under phosphate overload conditions, similar to global Enpp1-deficient mice. Aging phenotypes seen in Enpp1 cKO mice under phosphate overload conditions were rescued by a low vitamin D diet, even under high phosphate conditions. These findings suggest overall that cartilage tissue plays an important role in regulating systemic aging via Enpp1.

The IL-17-IL-17RA axis is required to promote osteosarcoma progression in mice.

Osteosarcoma is rare but is the most common bone tumor. Diagnostic tools such as magnetic resonance imaging development of chemotherapeutic agents have increased the survival rate in osteosarcoma patients, although 5-year survival has plateaued at 70%. Thus, development of new treatment approaches is needed. Here, we report that IL-17, a proinflammatory cytokine, increases osteosarcoma mortality in a mouse model with AX osteosarcoma cells. AX cell transplantation into wild-type mice resulted in 100% mortality due to ectopic ossification and multi-organ metastasis. However, AX cell transplantation into IL-17-deficient mice significantly prolonged survival relative to controls. CD4-positive cells adjacent to osteosarcoma cells express IL-17, while osteosarcoma cells express the IL-17 receptor IL-17RA. Although AX cells can undergo osteoblast differentiation, as can patient osteosarcoma cells, IL-17 significantly inhibited that differentiation, indicating that IL-17 maintains AX cells in the undifferentiated state seen in malignant tumors. By contrast, IL-17RA-deficient mice transplanted with AX cells showed survival comparable to wild-type mice transplanted with AX cells. Biopsy specimens collected from osteosarcoma patients showed higher expression of IL-17RA compared to IL-17. These findings suggest that IL-17 is essential to maintain osteosarcoma cells in an undifferentiated state and could be a therapeutic target for suppressing tumorigenesis.

Transthyretin amyloid deposition in ligamentum flavum (LF) is significantly correlated with LF and epidural fat hypertrophy in patients with lumbar spinal stenosis.

Lumbar spinal stenosis (LSS) is a degenerative disease characterized by intermittent claudication and numbness in the lower extremities. These symptoms are caused by the compression of nerve tissue in the lumbar spinal canal. Ligamentum flavum (LF) hypertrophy and spinal epidural lipomatosis in the spinal canal are known to contribute to stenosis of the spinal canal: however, detailed mechanisms underlying LSS are still not fully understood. Here, we show that surgically harvested LFs from LSS patients exhibited significantly increased thickness when transthyretin (TTR), the protein responsible for amyloidosis, was deposited in LFs, compared to those without TTR deposition. Multiple regression analysis, which considered age and BMI, revealed a significant association between LF hypertrophy and TTR deposition in LFs. Moreover, TTR deposition in LF was also significantly correlated with epidural fat (EF) thickness based on multiple regression analyses. Mesenchymal cell differentiation into adipocytes was significantly stimulated by TTR in vitro. These results suggest that TTR deposition in LFs is significantly associated with increased LF hypertrophy and EF thickness, and that TTR promotes adipogenesis of mesenchymal cells. Therapeutic agents to prevent TTR deposition in tissues are currently available or under development, and targeting TTR could be a potential therapeutic approach to inhibit LSS development and progression.

Remnant tissue enhances early postoperative biomechanical strength and infiltration of Scleraxis-positive cells within the grafted tendon in a rat anterior cruciate ligament reconstruction model.

When ruptured, ligaments and tendons have limited self-repair capacity and rarely heal spontaneously. In the knee, the Anterior Cruciate Ligament (ACL) often ruptures during sports activities, causing functional impairment and requiring surgery using tendon grafts. Patients with insufficient time to recover before resuming sports risk re-injury. To develop more effective treatment, it is necessary to define mechanisms underlying ligament repair. For this, animal models can be useful, but mice are too small to create an ACL reconstruction model. Thus, we developed a transgenic rat model using control elements of Scleraxis (Scx), a transcription factor essential for ligament and tendon development, to drive GFP expression in order to localize Scx-expressing cells. As anticipated, Tg rats exhibited Scx-GFP in ACL during developmental but not adult stages. Interestingly, when we transplanted the flexor digitorum longus (FDP) tendon derived from adult Scx-GFP+ rats into WT adults, Scx-GFP was not expressed in transplanted tendons. However, tendons transplanted from adult WT rats into Scx-GFP rats showed upregulated Scx expression in tendon, suggesting that Scx-GFP+ cells are mobilized from tissues outside the tendon. Importantly, at 4 weeks post-surgery, Scx-GFP-expressing cells were more frequent within the grafted tendon when an ACL remnant was preserved (P group) relative to when it was not (R group) (P vs R groups (both n = 5), p<0.05), and by 6 weeks, biomechanical strength of the transplanted tendon was significantly increased if the remnant was preserved (P vsR groups (both n = 14), p<0.05). Scx-GFP+ cells increased in remnant tissue after surgery, suggesting remnant tissue is a source of Scx+ cells in grafted tendons. We conclude that the novel Scx-GFP Tg rat is useful to monitor emergence of Scx-positive cells, which likely contribute to increased graft strength after ACL reconstruction.

Prognostic impact of frailty after gastrectomy in elderly gastric cancer patients.

BACKGROUND: Frailty plays a crucial role in cancer patients who have received surgery in this recent aging society. We aimed to investigate frailty as a prognostic factor in elderly gastric cancer (GC) patients who underwent curative gastrectomy. METHODS: We analyzed 86 elderly (over 75 years old) GC patients who underwent curative gastrectomy. Patients were assigned to two groups;frailty group (n=29) and no-frailty group (n=57). Clinicopathological values were compared between the two groups. RESULTS: The OS rate of the frailty group was significantly poorer than that of the no-frailty group (5-yr OS rate;frailty group 52.49% vs. no-frailty group 74.87%, p<0.05). Multivariate analysis of the OS showed that frailty tended to be significant prognostic factor (p=0.09). The DFS rate of the frailty group was significantly poorer than that of the no-frailty group (5-yr DFS rate;frailty group 42.30% vs. no-frailty group 71.55%, p<0.05). Multivariate analysis of the DFS showed that frailty tended to be significant prognostic factor (p=0.14). CONCLUSION: We identified the clinical impact of frailty prognostic factor for elderly GC patients who underwent gastrectomy. J. Med. Invest. 70 : 423-429, August, 2023.

A machine learning-based scoring system and ten factors associated with hip fracture occurrence in the elderly.

Hip fractures are fragility fractures frequently seen in persons over 80-years-old. Although various factors, including decreased bone mineral density and a history of falls, are reported as hip fracture risks, few large-scale studies have confirmed their relevance to individuals older than 80, and tools to assess contributions of various risks to fracture development and the degree of risk are lacking. We recruited 1395 fresh hip fracture patients and 1075 controls without hip fractures and comprehensively evaluated various reported risk factors and their association with hip fracture development. We initially constructed a predictive model using Extreme Gradient Boosting (XGBoost), a machine learning algorithm, incorporating all 40 variables and evaluated the model's performance using the area under the receiver operating characteristic curve (AUC), yielding a value of 0.87. We also employed SHapley Additive exPlanation (SHAP) values to evaluate each feature importance and ranked the top 20. We then used a stepwise selection method to determine key factors sequentially until the AUC reached a plateau nearly equal to that of all variables and identified the top 10 sufficient to evaluate hip fracture risk. For each, we determined the cutoff value for hip fracture occurrence and calculated scores of each variable based on the respective feature importance. Individual scores were: serum 25(OH)D levels (<10 ng/ml, score 7), femoral neck T-score (<-3, score 5), Barthel index score (<100, score 3), maximal handgrip strength (<18 kg, score 3), GLFS-25 score (≥24, score 2), number of falls in previous 12 months (≥3, score 2), serum IGF-1 levels (<50 ng/ml, score 2), cups of tea/day (≥5, score -2), use of anti-osteoporosis drugs (yes, score -2), and BMI (<18.5 kg/m2, score 1). Using these scores, we performed receiver operating characteristic (ROC) analysis and the resultant optimal cutoff value was 7, with a specificity of 0.78, sensitivity of 0.75, and AUC of 0.85. These ten factors and the scoring system may represent tools useful to predict hip fracture.

The remaining teres minor and subscapularis may contribute to preventing superior migration of the humeral head and progression of osteoarthritic change in rotator cuff tears.

Background: Superior migration of the humeral head is common in large and massive rotator cuff tears (RCTs). Humeral heads migrate superiorly according to an increase in the RCT size; however, the relevance of the remaining cuff has not been elucidated. This study investigated the relation between superior migration of the humeral head and the remaining rotator cuff, especially the teres minor (TM) and subscapularis (SSC), in RCTs involving tears and atrophy of the infraspinatus (ISP). Methods: Plain anteroposterior radiographic and magnetic resonance imaging examinations were performed on 1345 patients between January 2013 and March 2018. A total of 188 shoulders with tears of the supraspinatus and ISP with atrophic ISP were evaluated. Gradings of superior migration of the humeral head and osteoarthritic change were evaluated using the acromiohumeral interval, Oizumi classification, and Hamada classification on plain anteroposterior radiographs. The cross-sectional area of the remaining rotator cuff muscles was evaluated using oblique sagittal magnetic resonance imaging. The TM was classified as hypertrophic (H) and normal and atrophic (NA). The SSC was classified as nonatrophic (N) and atrophic (A). All shoulders were classified as groups A (H-N), B (NA-N), C (H-A), and D (NA-A). Age- and sex-matched patients with no cuff tears were also enrolled (control). Results: The acromiohumeral intervals of the control group and groups A-D were 11.4 ± 2.4, 9.5 ± 3.8, 7.8 ± 4.1, 7.2 ± 4.0, and 5.4 ± 3.5 mm (84, 74, 64, 21, and 29 shoulders, respectively), with significant differences between groups A and D (P < .001) and groups B and D (P = .016). Grade 3 of the Oizumi classification and grades 3, 4, and 5 of the Hamada classification were significantly higher in group D than in others (P < .001). Conclusion: The group showing hypertrophic TM and nonatrophic SSC prevented significantly migration of the humeral head and cuff tear osteoarthritis compared to the group showing atrophic TM and SSC in posterosuperior RCTs. The findings indicate that the remaining TM and SSC may prevent superior migration of the humeral head and progression of osteoarthritic change in RCTs. In treating patients with large and massive posterosuperior RCTs, the status of the remaining TM and SSC muscles should be assessed.