Novel mutation of transferrin receptor 2 causing hereditary hemochromatosis type 3 in a Japanese patient.

Hereditary hemochromatosis (HH) is recognized as a progressive iron-storage disorder, and leading to severe organ impairments, including liver cirrhosis. Hereditary hemochromatosis type 3 arises from mutations in the transferrin receptor 2 (TFR2) gene. However, HH type 3 is rare in Asia, and information regarding genetic mutations and associated phenotypes remains limited. Here, we reported the case of a Japanese patient with HH type 3, with a novel homozygous mutation of the TFR2 gene. A 69-year-old woman presented to our hospital with hand joint pain and was referred due to liver impairment. Viral hepatitis and autoimmune liver diseases were ruled out. However, the transferrin saturation was 92.2%, and the serum ferritin level was 1611.8 ng/mL. Additionally, abdominal computed tomography showed diffuse increased density of the liver parenchyma. Abdominal magnetic resonance imaging also suggested iron deposition. There is no history of prior treatments involving blood transfusions or iron agents. Her parents were involved in a consanguineous marriage, prompting genetic testing. She had a homozygous novel mutation, c.1337G>A (p.G446E), in the TFR2 gene. Serum hepcidin-25 level was decreased to 2.9 ng/mL. According to the American Society of Medical Genetics and Genomics guideline, the mutation was classified as likely pathogenic, leading to the diagnosis of HH type 3. Following phlebotomy, her arthritis resolved, and serum transaminase levels were normalized. This case marks the first demonstration of homozygous mutation, c.1337G>A (p.G446E), in the TFR2 gene in patients with HH type 3.

Prediction of Post-Gastrectomy Pancreatic Complications: A Preoperative Imaging Study Based on Computed Tomography.

BACKGROUND: Postoperative pancreas-related complications (PPRCs) are common after laparoscopic gastrectomy (LG) in patients with gastric cancer. We estimated the anatomical location of the pancreas on a computed tomography (CT) image and investigated its impact on the incidence of PPRCs after LG. METHODS: We retrospectively reviewed the preoperative CT images of 203 patients who underwent LG for gastric cancer between January 2010 and December 2017. From these images, we measured the gap between the upper edge of the pancreatic body and the root of the common hepatic artery. We evaluated the potential relationship between PPRCs and the gap between pancreas and common hepatic artery (GPC) status using an analysis based on the median cutoff value and assessed the impact of GPC status on PPRC incidence. We performed univariate and multivariate analyses to identify predictive factors for PPRC. RESULT: Postoperative pancreas-related complications occurred in 11 patients (5.4%). The median of the optimal cutoff GPC value for predicting PPRC was 0 mm; therefore, we classified the GPC status into two groups: GPC plus group and GPC minus group. Univariate analysis revealed that sex (male), C-reactive protein (CRP) > .07 mg/dl, GPC plus, and visceral fat area (VFA) > 99 cm2 were associated with the development of PPRC. Multivariate analysis identified only GPC plus as independent predictor of PPRC (hazard ratio: 4.60 [95% confidence interval 1.11-31.15], P = .034). CONCLUSION: The GPC is a simple and reliable predictor of PPRC after LG. Surgeons should evaluate GPC status on preoperative CT images before proceeding with laparoscopic gastric cancer surgery.

Clinical feasibility of the preoperative C-reactive protein-albumin-lymphocyte index to predict short- and long-term outcomes of patients with gastric cancer.

BACKGROUND: Gastric cancer (GC) is a major leading cause of cancer-related death worldwide. Systemic inflammation and the nutrition-based score are feasible prognostic markers for malignancies. Emerging evidence has also revealed the C-reactive protein-albumin-lymphocyte (CALLY) index to be a prognostic marker for several cancer types. However, its clinical significance to predict surgical and oncologic outcomes of patients with GC remains unclear. METHODS: We assessed the preoperative CALLY index in 426 patients with GC who received gastrectomy. RESULTS: A low preoperative CALLY index was significantly correlated to all well-established clinicopathologic factors for disease development, including an advanced T stage, the presence of venous invasion, lymphatic vessel invasion, lymph node metastasis, distant metastasis, and an advanced TNM stage. A low preoperative CALLY index was also an independent prognostic factor for overall survival (hazard ratio [HR], 2.64; 95 % CI, 1.66-4.2; P < .0001) and disease-free survival (HR, 1.76; 95 % CI, 1.01-3.05; P = .045). In addition, a low preoperative CALLY index was an independent predictive factor for postoperative surgical site infection (odds ratio, 2.64; 95 % CI, 1.42-4.89; P = .002). CONCLUSION: The preoperative CALLY index is valuable for perioperative and oncologic management of patients with GC.

Clinical implications of C-reactive protein-albumin-lymphocyte (CALLY) index in patients with esophageal cancer.

PURPOSE: The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel inflammatory nutritional biomarker. This study aimed to investigate the potential clinical significance and oncological prognostic role of the preoperative CALLY index in patients with esophageal cancer. METHODS: We analyzed the preoperative CALLY index in 146 patients with esophageal cancer. The CALLY index and clinicopathological variables were analyzed by the Mann-Whitney U test, and associations between the CALLY index and survival outcomes were analyzed by Kaplan-Meier analysis and log-rank tests. Univariate and multivariate analyses of prognostic variables were conducted using Cox proportional hazards regression. RESULTS: A lower preoperative CALLY index was significantly correlated with patient age, advanced T stage, presence of lymph node metastasis, neoadjuvant therapy, lymphatic invasion, and advanced stage classification. The preoperative CALLY index decreased significantly in a stage-dependent manner. Patients with esophageal cancer with a low CALLY index had poorer overall survival, disease-free survival than those with a high CALLY index. Multivariate analysis showed that a low CALLY index was an independent prognostic factor for overall survival, disease-free survival and an independent predictor of postoperative surgical site infection. CONCLUSIONS: Preoperative CALLY index is a useful marker to guide the perioperative and postoperative management of patients with esophageal cancer.

Japanese Society of Medical Oncology clinical guidelines: Molecular testing for colorectal cancer treatment, 5th edition.

Molecular testing to determine optimal therapies is essential for managing patients with colorectal cancer (CRC). In October 2022, the Japanese Society of Medical Oncology published the 5th edition of the Molecular Testing Guideline for Colorectal Cancer Treatment. In this guideline, in patients with unresectable CRC, RAS/BRAF V600E mutational and mismatch repair tests are strongly recommended prior to first-line chemotherapy to select optimal first- and second-line therapies. In addition, HER2 testing is strongly recommended because the pertuzumab plus trastuzumab combination is insured after fluoropyrimidine, oxaliplatin, and irinotecan in Japan. Circulating tumor DNA (ctDNA)-based RAS testing is also strongly recommended to assess the indications for the readministration of anti-EGFR antibodies. Both tissue- and ctDNA-based comprehensive genomic profiling tests are strongly recommended to assess the indications for targeted molecular drugs, although they are currently insured in patients with disease progression after receiving standard chemotherapy (or in whom disease progression is expected in the near future). Mutational and mismatch repair testing is strongly recommended for patients with resectable CRC, and RAS/BRAF V600E mutation testing is recommended to estimate the risk of recurrence. Mutational and mismatch repair and BRAF testing are also strongly recommended for screening for Lynch syndrome. Circulating tumor DNA-based minimal residual disease (MRD) testing is strongly recommended for estimating the risk of recurrence based on clinical evidence, although MRD testing was not approved in Japan at the time of the publication of this guideline.

Promoter methylation levels of microRNA-124 in non-neoplastic rectal mucosa as a potential biomarker for ulcerative colitis-associated colorectal cancer in pediatric-onset patients.

PURPOSE: To determine the methylation level of the miR-124 promoter in non-neoplastic rectal mucosa of patients with pediatric-onset ulcerative colitis (UC) to predict UC-associated colorectal cancer (UC-CRC). METHODS: Between 2005 and 2017, non-neoplastic rectal tissue specimens were collected from 86 patients with UC, including 13 patients with UC-CRC; cancer tissues were obtained from the latter group. The methylation status of the miR-124 promoter was quantified using bisulfite pyrosequencing and compared between pediatric- and adult-onset UC patients. RESULTS: Patients with pediatric-onset UC experienced a significantly shorter disease duration than those with adult-onset UC. The levels of miR-124 promoter methylation in non-neoplastic rectal mucosa were positively correlated with the age at the diagnosis and duration of UC. The rate of increase in miR-124 methylation was accelerated in patients with pediatric-onset UC compared to those with adult-onset UC. Furthermore, the miR-124 methylation levels in non-neoplastic rectal mucosa were significantly higher in patients with UC-CRC than in those with UC alone (P = 0.02). A receiver operating characteristic analysis revealed that miR-124 methylation in non-neoplastic tissue discriminated between patients with pediatric-onset UC with or without CRC. CONCLUSION: miR-124 methylation in non-neoplastic rectal mucosa may be a useful biomarker for identifying patients with pediatric-onset UC who face the highest risk of developing UC-CRC.

Successful management following combined thoracic endovascular aortic repair and minimally invasive esophagectomy for primary aortoesophageal fistula: A case report.

Aortoesophageal fistula (AEF) is a rare but life-threatening pathology. We report a case of a primary AEF that was successfully managed with temporary thoracic endovascular aortic repair (TEVAR) and esophagectomy with video-assisted thoracoscopic surgery. A 73-year-old man was transferred to the emergency department with a complaint of hematemesis. A computed tomography scan identified an AEF due to aortic aneurysm. We placed a stent using TEVAR for the purpose of hemodynamic stasis, and the operation was performed 23 h after admission. Right video-assisted thoracoscopic esophagectomy (VATS-E) was chosen, and a cervical esophagostomy and a feeding gastrostomy tube was constructed. Infection had been effectively controlled postoperatively. Four months after the first operation, we performed esophageal reconstruction. At the 70-month follow-up examination, the patient had no signs of mediastinitis. VATS-E immediately after hemostabilization by TEVAR is useful management for primary AEF.

A Circulating Panel of circRNA Biomarkers for the Noninvasive and Early Detection of Pancreatic Ductal Adenocarcinoma.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies. Delayed manifestation of symptoms and lack of specific diagnostic markers lead patients being diagnosed with PDAC at advanced stages. This study aimed to develop a circular RNA (circRNA)-based biomarker panel to facilitate noninvasive and early detection of PDAC. METHODS: A systematic genome-wide discovery of circRNAs overexpressed in patients with PDAC was conducted. Subsequently, validation of the candidate markers in the primary tumors from patients with PDAC was performed, followed by their translation into a plasma-based liquid biopsy assay by analyzing 2 independent clinical cohorts of patients with PDAC and nondisease controls. The performance of the circRNA panel was assessed in conjunction with the plasma levels of cancer antigen 19-9 for the early detection of PDAC. RESULTS: Initially, a panel of 10 circRNA candidates was identified during the discovery phase. Subsequently, the panel was reduced to 5 circRNAs in the liquid biopsy-based assay, which robustly identified patients with PDAC and distinguished between early-stage (stage I/II) and late-stage (stage III/IV) disease. The areas under the curve of this diagnostic panel for the detection of early-stage PDAC were 0.83 and 0.81 in the training and validation cohorts, respectively. Moreover, when this panel was combined with cancer antigen 19-9 levels, the diagnostic performance for identifying patients with PDAC improved remarkably (area under the curve, 0.94) for patients in the validation cohort. Furthermore, the circRNA panel could also efficiently identify patients with PDAC (area under the curve, 0.85) who were otherwise deemed clinically cancer antigen 19-9-negative (<37 U/mL). CONCLUSIONS: A circRNA-based biomarker panel with a robust noninvasive diagnostic potential for identifying patients with early-stage PDAC was developed.

Clinical Significance of the Preoperative Inflammatory Burden Index in Esophageal Cancer.

INTRODUCTION: The inflammatory burden index (IBI) serves as a prognostic marker for several cancers. Here, we evaluated the predictive value of preoperative IBI associated with the surgical and oncological outcomes of patients with esophageal cancer (EC). METHODS: The IBI was formulated as C-reactive protein × neutrophil/lymphocyte. We retrospectively analyzed preoperative IBI of 147 EC patients receiving esophagectomy between 2008 and 2018. Cox proportional hazards models and multivariable logistic regression were employed to identify independent risk factors of surgical site infection and prognosis. RESULTS: Increased preoperative IBI significantly correlated with higher tumor stage. Patients with high IBI experienced shorter overall survival (p = 0.0002) and disease-free survival (p = 0.002) compared with those with low IBI. In the adjusted Cox proportional hazards regression models, increased IBI served as an independent prognostic factor for overall survival (hazard ratio, 3.56; 95% confidence interval, 1.79-7.34; p = 0.0003) and disease-free survival (hazard ratio, 3.03; 95% confidence interval, 1.60-5.92; p = 0.007). Multivariable analysis identified preoperative high IBI which served as an independent risk factor for overall surgical site infection (odds ratio, 2.53; 95% confidence interval, 1.00-6.38; p = 0.049). CONCLUSION: Preoperative IBI may serve as a useful predictor of prognosis and surgical site infection of patients with EC after esophagectomy.

High-flow arteriovenous fistula in X-linked Alport syndrome: a case report.

Most male X-linked Alport syndrome patients with COL4A5 nonsense mutations experience end-stage kidney failure by 30 years old. Although there is no definition of high-flow arteriovenous fistula, access blood flows greater than 2000 mL/min might predict the occurrence of high-output heart failure. A 50-year-old Japanese man had suffered from proteinuria at 4 years old and sensorineural hearing loss and a lenticular lens at 20 years old. He had started to receive hemodialysis treatment due to end-stage kidney disease at 22 years old. A genetic test confirmed a novel hemizygous nonsense variant COL4A5 c.2980G > T (p.Gly994Ter), and he was diagnosed with X-linked Alport syndrome. COL4A5 c.2980G > T was considered "pathogenic" according to the American College of Medical Genetics and Genomics guidelines and in vitro experiments. Shortness of breath on exertion was exaggerated, his brachial artery blood flow was over 4,236-4,353 mL/min, his cardiac output was 5,874 mL/min, and he needed radial artery banding at 51 years old. After radial artery banding surgery, the brachial artery blood flow decreased to 987-1,236 mL/min, and echocardiography showed a cardiac output at 5100 mL/min with improved E' and E/E'. His shortness of breath on exertion improved gradually. Although rare, high-output heart failure due to high-flow arteriovenous fistula should be kept in mind as a complication in X-linked Alport syndrome patients, and our patient was successfully treated with radial artery banding surgery.

Extraction of a metallic susceptor after accidental ingestion of the heated tobaccostick TEREA™: a case report.

BACKGROUND: Tobacco ingestion is widely known to cause nicotine toxicity, which may result in severe symptoms. Two heated tobacco sticks, called TEREA™ and SENTIA™, were launched in 2021 by Philip Morris International (New York, NY, USA), and their ingestion is associated with a risk of bowel injury because they contain a partially pointed metallic susceptor. However, this risk is not well known to the general public or healthcare providers. To increase awareness of this risk, we herein report a case involving extraction of a metallic susceptor after ingestion of the heated tobacco stick TEREA™. CASE PRESENTATION: A 7-month-old girl presented to the emergency department of a nearby hospital because she was suspected to have accidentally swallowed heated tobacco. Although she presented with no symptoms related to nicotine poisoning, abdominal X-ray examination revealed a metal object in her stomach. According to a statement released by the Japan Poison Information Center, the TEREA™ heated tobacco stick contains a metallic susceptor with a rectangular shape and sharp corners. The patient was transferred to our department because of the risk of bowel injury, and upper gastrointestinal endoscopy was performed. No cigarettes were found by endoscopic observation; however, a metallic susceptor was located in the second part of the duodenum. We grasped it with biopsy forceps and carefully removed it using an endoscope with a cap attached to the tip. The post-endoscopic course was uneventful. CONCLUSIONS: Some patients who ingest heated tobacco sticks might be exposed not only to the effects of nicotine but also to physical damage caused by a metallic susceptor. Infants and toddlers especially could swallow these sticks, therefore tobacco companies need to make the problem more public. Clinicians also should alert the problem, and pay attention to this risk in the clinical setting.

Double inferior vena cava, an uncommon but relevant anatomical anomaly in surgery for lower rectal cancer: a report of two cases.

BACKGROUND: Double inferior vena cava (DIVC) is rare and usually detected incidentally. DIVC may be associated with several anatomical variants of the retroperitoneal and pelvic veins. These variants can pose a clinical problem during colorectal surgery. We present two patients with lower rectal cancer who also had a DIVC. CASE PRESENTATION: Case 1 was a 72-year-old man with advanced lower rectal cancer (T3N0M0) who underwent robot-assisted low anterior resection after neoadjuvant therapy. A DIVC was detected on preoperative computed tomography (CT). During the operation, a presacral vein was injured while mobilizing the rectum and hemostasis could not be achieved. We converted to open surgery and packed the pelvic cavity for hemostasis. Retrospective analysis suggested the injured vein arose from an interiliac vein of the presacral pelvic venous plexus. Case 2 was a 50-year-old woman with lower rectal cancer (T3N0M0), immune thrombocytopenic purpura, and a DIVC. Although preoperative three-dimensional CT angiography showed no obvious pelvic vein abnormalities, a short course of preoperative radiotherapy was delivered to avoid lateral pelvic lymph node dissection. Chemotherapy was deferred owing to her thrombocytopenic disease. Laparoscopic abdominoperineal resection was performed meticulously to minimize bleeding and achieve rapid hemostasis. No intraoperative complications occurred. CONCLUSION: DIVC is often accompanied by venous malformations that may pose a problem when mobilizing the mesorectum from the retroperitoneum. Preoperative assessment of pelvic vessel anatomy using three-dimensional CT is essential in patients with a DIVC who undergo rectal surgery.

Robot-assisted laparoscopic abdominoperineal resection for anal canal cancer associated with Crohn's disease: A case report.

A 37-year-old man with Crohn's disease (CD) and a history of abdominal surgery was diagnosed with anal canal cancer. Robot-assisted laparoscopic abdominoperineal resection was performed and the patient was discharged without any postoperative complications. Recently, minimally invasive surgery for CD patients has grown in popularity. However, there have been few studies of robotic surgery for CD patients with anal canal cancer. To the best of our knowledge, we present the first report of a patient with CD-associated anal canal cancer who underwent robot-assisted laparoscopic abdominoperineal resection.

The role of miR-21 as a predictive biomarker and a potential target to improve the effects of chemoradiotherapy against head and neck squamous cell carcinoma.

This study aimed to clarify whether circulating miR-21 represents a predictive biomarker in patients with head and neck squamous cell carcinoma (HNSCC) undergoing chemoradiotherapy, and to investigate the effect of miR-21 inhibitor for chemoradiation in human SCC cells. Plasma samples were obtained from 22 patients with HNSCC and 25 non-cancer volunteers. Plasma miR-21 expression was measured using real-time quantitative reverse transcription polymerase chain reaction. The effects of miR-21 inhibitor in human SCC cells were investigated by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry and western blot analysis. As a result, plasma miR-21 expression was higher in HNSCC patients than in control patients (P < 0.001). Seven patients with recurrence showed significantly higher plasma miR-21 than the 15 patients without recurrence. And high miR-21 expression group showed poor overall survival. Moreover, miR-21 inhibition significantly enhanced cisplatin- or radiation-induced apoptosis. Western blot analysis suggested the programmed cell death 4 protein as a potential target of miR-21 in relation to apoptosis. In conclusion, this study provides new insights into the role of miR-21 as a predictive biomarker for HNSCC treated with chemoradiotherapy and suggests a potential target to improve the effects of chemoradiotherapy against HNSCC.

Pretreatment Lymphocyte to C-Reactive Protein Ratio: An Independent Predictor of Overall Survival in Metastatic Hormone-Naïve Prostate Cancer Patients.

INTRODUCTION: The purpose of this study was to investigate the clinical value of combination of systematic inflammatory factors in predicting the outcomes of primary androgen deprivation therapy (ADT) plus first-generation antiandrogen treatment in metastatic hormone-naïve prostate cancer (mHNPC) patients. MATERIALS AND METHODS: A total of 361 consecutive mHNPC patients from the discovery (n = 165) and validation (n = 196) cohorts were analyzed. All patients received primary ADT with surgical castration or pharmacologic castration accompanied by first-generation antiandrogens. We evaluated the prognostic impact of pretreatment lymphocyte to C-reactive protein ratio (LCR) on overall survival (OS) in both cohorts. RESULTS: The median follow-up in the discovery and validation cohorts was 43.4 and 50.9 months, respectively. In the discovery cohort, low LCR (using an optimal cutoff threshold of 14,025) was significantly correlated with poor OS compared with high LCR (P < .001). Multivariate analysis revealed that the biopsy Gleason score and LCR were independent prognostic factors for OS. In the validation cohort, low LCR was also significantly correlated with poor OS compared with high LCR (P = .001). A multivariate analysis revealed that the extent of disease on bone scan grade, lactate dehydrogenase, and LCR were all independent predictors of OS. CONCLUSIONS: Pretreatment low LCR is an independent predictor of poor OS in mHNPC patients. This may be informative in predicting the susceptible patients' developing worse outcomes after being treated with primary ADT plus first-generation antiandrogen.

Cardiac 18F­FDG uptake and new­onset rectal cancer.

The present study aimed to investigate the factors affecting the cardiac uptake of 18F-fluorodeoxyglucose (18F-FDG) during 18F-FDG positron emission tomography (PET) for new-onset rectal cancer and new-onset colon cancer (ascending, transverse, descending, sigmoid colon cancer) and to examine the association between the cardiac uptake of 18F-FDG and prognosis. The participants were diagnosed with new-onset rectal cancer and new-onset colon cancer (ascending, transverse, descending, sigmoid cancer) at the Iga City General Hospital (Iga, Japan) between January 1, 2013, and March 31, 2018, and underwent an 18F-FDG PET scan for pretreatment staging. The relationship between cardiac maximum standard uptake value (SUVmax), the presence/absence of distant metastasis and prognosis was examined. A total of 26 patients (14 men and 12 women) aged 72.0±10 years with new-onset rectal cancer were selected for the study. No patients had multiple simultaneous cancers. The median cardiac SUVmax was 3.8 and 2.5 in patients with no distant metastasis and distant metastasis, respectively, revealing a statistically significant difference (P<0.01). The median tumor volume on PET-computed tomography (CT) images was 7,815 cm2 and was 66,248 cm2 in patients with no distant metastasis and distant metastasis, respectively, revealing a statistically significant difference (P<0.01). Echocardiography findings revealed no significant difference between patients with and without distant metastasis. The correlation coefficient between cardiac SUVmax and total tumor volume on PET/CT images (primary + lymph + distant metastases) was statistically significant (r=-0.42, P=0.03). Analysis of the association between the occurrence of distance metastasis and cardiac SUVmax as a continuous variable gave a statistically significant result [hazard ratio (HR): 0.30, 95% confidence interval (CI): 0.09-0.98, P=0.045]. Receiver operating characteristic analysis showed a cardiac SUVmax of 2.6 with an area under the curve of 0.86 for determining the presence of distant metastasis (95% CI: 0.70-1.00). The median observation time was 56 months, and nine patients died during observation. Analysis of the association between the overall survival and cardiac SUVmax (cutoff: 2.6) showed 95% CI: 0.01-0.45 and HR: 0.06 (P<0.01); that between the overall survival and total tumor volume on PET images showed 95% CI: 1.00-1.00 and HR: 1.00 (P<0.01); and that between the overall survival and presence of distant metastasis showed 95% CI: 1.72-116.4 and HR: 14.1 (P<0.01). Furthermore, 25 patients (16 men and nine women) aged 71.4±14.2 years with new-onset colon cancer were selected for the study. Analysis of new-onset colon cancer revealed no statistically significance between the cardiac SUVmax and distant metastasis.

[Stage â £ Gastric Cancer with Long Term Survival by Conversion Surgery-A Case Report].

A 78-year-old man presenting with a chief complaint of discomfort was found to have advanced gastric cancer invading pancreatic body, and with the metastasis of paraaortic lymph node(No. 16). After 3 courses of the S-1 plus oxaliplatin regimen, CT scan showed the disappearance of invasion to pancreatic body, and the No. 16 lymph node. Then total gastrectomy(D2+No. 19+No. 16a1+No. 16a2), Roux-en-Y reconstruction and cholecystectomy were undergoing. Histological assessment for treatment response showed Grade 1a, and we finally diagnosed gastric cancer: MU, Post, type 2, 30×20 mm, tub1>por1, ypT3, ypN1, ycM0, ypStage ⅡB. The postoperative course was uneventful, and the patient was discharged from the hospital on postoperative day 19. S-1 as adjuvant chemotherapy was performed for 12 months, and no recurrence was recognized for 5 years and 9 months after operation.

Next-generation sequencing clarified why first-line treatment with osimertinib was ineffective in an autopsied case of EGFR-mutated lung squamous cell carcinoma.

Epidermal growth factor receptor (EGFR)-mutated squamous cell carcinoma (SCC) is less common than adenocarcinoma. The third-generation EGFR-tyrosine kinase inhibitor, osimertinib, is effective in EGFR-mutated lung adenocarcinoma, but its efficacy in EGFR-mutated lung SCC is unclear. The patient was an 83-year-old male. He was diagnosed with SCC of the lung, and molecular analysis revealed that the tumor was positive for EGFR exon19 deletion. He was treated with osimertinib 80 mg/day. No adverse events were observed, but after 18 days of therapy, he complained of dyspnea, and a computed tomography scan showed enlarged lung cancer. The case was categorized as a progressive disease. The patient died 3 weeks later. The autopsy findings confirmed the diagnosis of lung SCC, with morphology and immunohistochemical staining identical to the tumor obtained by bronchoscopy. Next-generation sequencing showed the presence of TP53 R158L, CDK6, and KRAS amplifications. The current case report shows that next-generation sequencing can explain why osimertinib is ineffective in EGFR-mutated SCC.

Prognostic potential of METTL3 expression in patients with gastric cancer.

Methyltransferase-like 3 (METTL3) is a crucial component of the m6A methyltransferase complex, which serves pivotal roles in tumor progression. The present study investigated the prognostic significance of METTL3 expression in gastric cancer (GC). The expression levels of METTL3 were assessed by immunohistochemistry in formalin-fixed paraffin-embedded (FFPE) tissue specimens from 158 patients with GC. Propensity score matching (PSM) analysis was performed to clarify its prognostic potential. METTL3 gene expression was also investigated in fresh frozen specimens from another independent cohort of 57 patients with GC to establish its clinical relevance. Knockdown of METTL3 by small interfering RNA transfection was performed to evaluate its function in vitro. METTL3 expression was significantly higher in cancerous tissues compared with in corresponding normal mucosa (P<0.0001), and high METTL3 expression was an independent prognostic factor for overall and disease-free survival in the FFPE cohort of patients with GC. PSM analysis revealed that elevated METTL3 expression was significantly associated with poor survival outcomes, which was subsequently validated in another cohort of fresh frozen specimens. Knockdown of METTL3 inhibited proliferation, invasion, migration and anoikis resistance in GC cells. In conclusion, METTL3 expression may be used as a clinically feasible prognostic marker and could serve as a potential therapeutic target in patients with GC.

The effect of preoperative rehabilitation on the prevention of postoperative ileus in colorectal cancer patients.

PURPOSE: Previous research suggests that the preoperative rehabilitation of colorectal cancer patients can reduce postoperative ileus. However, the evidence is insufficient and further research is warranted. This study aimed to investigate whether short-term preoperative rehabilitation, both on an outpatient and inpatient basis, can reduce the incidence of postoperative ileus after colorectal cancer surgery. METHODS: This was a retrospective cohort study that drew on data from multicenter electronic medical records. Patients with stage 1-3 colorectal cancer who underwent surgery and postoperative rehabilitation were included. The incidence of postoperative ileus was compared between patients who received short-term preoperative rehabilitation and those who did not. Propensity score adjustment using inverse probability weighting and subgroup analysis by type of surgery was performed. RESULTS: Four thousand seventy-six eligible patients (43.4% female; mean age 75.1 ± 10.9 years) were included; 1914 (47.0%) received short-term preoperative rehabilitation. The preoperative rehabilitation group had a significantly lower incidence of postoperative ileus than the no preoperative rehabilitation group (pre-adjustment: 5.5% vs. 9.9%, p < 0.001; post-adjustment: 5.2% vs. 9.0%, p < 0.001). Therefore, preoperative rehabilitation was significantly associated with a lower incidence of postoperative ileus (OR: 0.554, 95% CI: 0.415-0.739, p < 0.001). In an adjusted analysis of surgery type subgroups, the incidence of postoperative ileus was significantly lower in the preoperative rehabilitation group for all types of surgery. CONCLUSION: Our study showed that short-term preoperative rehabilitation for patients with stage 1-3 colorectal cancer, both with inpatients and outpatients, significantly reduces the incidence of postoperative ileus.