High N6-methyladenosine-activated TCEAL8 mRNA is a novel pancreatic cancer marker.

N6-methyladenosine (m6A) is an RNA modification involved in RNA processing and widely found in transcripts. In cancer cells, m6A is upregulated, contributing to their malignant transformation. In this study, we analyzed gene expression and m6A modification in cancer tissues, ducts, and acinar cells derived from pancreatic cancer patients using MeRIP-seq. We found that dozens of RNAs highly modified by m6A were detected in cancer tissues compared with ducts and acinar cells. Among them, the m6A-activated mRNA TCEAL8 was observed, for the first time, as a potential marker gene in pancreatic cancer. Spatially resolved transcriptomic analysis showed that TCEAL8 was highly expressed in specific cells, and activation of cancer-related signaling pathways was observed relative to TCEAL8-negative cells. Furthermore, among TCEAL8-positive cells, the cells expressing the m6A-modifying enzyme gene METTL3 showed co-activation of Notch and mTOR signaling, also known to be involved in cancer metastasis. Overall, these results suggest that m6A-activated TCEAL8 is a novel marker gene involved in the malignant transformation of pancreatic cancer.

Comparative Study for Postoperative Initial Fixation Patterns of Two Different Types of Cementless Short Stem Using Three-Dimensional Templating Software.

Background: While cementless short stems have become popular in total hip arthroplasty (THA), Metha is a relatively recent development that differs from other short stems in its initial fixation concept of partial collum-sparing metaphyseal anchorage. The purpose of this study was to quantify the contact state between Metha and the femur. Additionally, we investigated the difference in contact points between Meta and Fitmore, which is one of the more popular curved short stems. Methods: We conducted a retrospective review of 42 hips that underwent THA using Metha and 41 hips using Fitmore. Stem-to-femur contact was evaluated by density mapping using a three-dimensional digital template system to quantify the contact condition according to the modified Gruen zone. The criterion for the stem-to-bone contact boundary was defined as a computed tomography value of 543 Hounsfield. Results: Quantitative evaluation of Metha according to the modified Gruen zones showed the ratio of surface area with high cortical contact in each zone. The results were 4.6% ± 5.7% in zone 1, 0.9% ± 2.3% in zone 2, 19.1% ± 12.9% in zone 3, 1.4% ± 3.2% in zone 5, 29.6% ± 16.4% in zone 6, and 25.1% ± 17.7% in zones 7. Evaluation of Fitmore for the same zones was as follows: 1.6% ± 2.4%, 18.5% ± 16.9%, 20.8% ± 17.4%, 12.7% ± 12.8%, 3.7% ± 5.8%, and 13.3% ± 10.3%. Comparing the two groups, the contact area was significantly greater for Metha in zones 1, 6 and 7 and Fitmore in zones 2 and 5 (p < 0.05). Conclusions: It is possible for Metha to achieve metaphyseal anchoring by contacting the cortical bone at the proximal femur, thus avoiding proximal offloading. To the best of our knowledge, no previous studies have quantitatively reported stem-to-cortical bone contact conditions in curved short stems.

Evaluation of patients with chronic obstructive pulmonary disease by maximal inspiratory pressure and diaphragmatic excursion with ultrasound sonography.

BACKGROUND: Decreased respiratory muscle strength and muscle mass is key in diagnosing respiratory sarcopenia. However, the role of reduced diaphragm activity, expressed as the maximal level of diaphragmatic excursion (DEmax), in diagnosing respiratory sarcopenia in patients with chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to characterize patients with COPD and low DEmax and maximal inspiratory pressure (MIP), a measure of inspiratory muscle strength, and assess the role of DEmax in respiratory sarcopenia. METHODS: Patients with COPD underwent spirometry, exercise tolerance (VO2peak) test, and MIP measurement. DEmax and sternocleidomastoid thickness at the maximal inspiratory level (TscmMIL) were assessed using ultrasound sonography. RESULTS: Overall, 58 patients with COPD (median age, 76 years; median %FEV1, 51.3 %) were included, 28 of whom showed a %MIP of ≥80 %, defined as having preserved MIP. Based on the %MIP of 80 % and median value of DEmax (48.0 mm) as thresholds, the patients were stratified into four groups: both-high (n = 18), %MIP-alone low (n = 11), DEmax-alone low (n = 10), and both-low (n = 19) groups. The both-low group exhibited the lowest %FEV1, Δinspiratory capacity, VO2peak, and TscmMIL, and these values were significantly lower than those of the both-high group. Except for %FEV1, these values were significantly lower in the both-low group than in the %MIP-alone low group despite adjusting DEmax level for body mass index. CONCLUSION: Measuring DEmax along with MIP can characterize patients with COPD, reduced exercise capacity, and decreased accessory respiratory muscle mass and can help diagnose respiratory sarcopenia.

Diaphragm dome height on chest radiography as a predictor of dynamic lung hyperinflation in COPD.

Background and objective: Dynamic lung hyperinflation (DLH) can play a central role in exertional dyspnoea in patients with COPD. Chest radiography is the basic tool for assessing static lung hyperinflation in COPD. However, the predictive capacity of DLH using chest radiography remains unknown. This study was conducted to determine whether DLH can be predicted by measuring the height of the right diaphragm (dome height) on chest radiography. Methods: This single-centre, retrospective cohort study included patients with stable COPD with pulmonary function test, cardiopulmonary exercise test, constant load test and pulmonary images. They were divided into two groups according to the median of changes of inspiratory capacity (ΔIC=IC lowest - IC at rest). The right diaphragm dome height and lung height were measured on plain chest radiography. Results: Of the 48 patients included, 24 were classified as having higher DLH (ΔIC ≤-0.59 L from rest; -0.59 L, median of all) and 24 as having lower DLH. Dome height correlated with ΔIC (r=0.66, p<0.001). Multivariate analysis revealed that dome height was associated with higher DLH independent of % low attenuation area on chest computed tomography and forced expiratory volume in 1 s (FEV1) % predicted. Furthermore, the area under the receiver operating characteristic curve of dome height to predict higher DLH was 0.86, with sensitivity and specificity of 83% and 75%, respectively, at a cut-off of 20.5 mm. Lung height was unrelated to ΔIC. Conclusion: Diaphragm dome height on chest radiography may adequately predict higher DLH in patients with COPD.

Efficacy of Anterior Quadratus Lumborum Block and Pain After Total Hip Arthroplasty: A Randomized Controlled Trial.

BACKGROUND: Anterior quadratus lumborum block (AQLB) is one of the compartment blocks and has recently attracted attention as a new method of analgesia for postoperative hip surgery analgesia. This study aimed to compare the analgesic efficacy of AQLB in patients undergoing primary total hip arthroplasty (THA). METHODS: There were 120 patients undergoing primary THA under general anesthesia randomly allocated to receive a femoral nerve block (FNB) or an AQLB. The primary outcome was total morphine consumption over the initial 24-hour postoperative period. Secondary outcomes included the pain score evaluation while at rest and during active and passive motion over the 2 days following surgery and the manual muscle testing of the quadriceps femoris. The numerical rating scale (NRS) score was used for evaluating the postoperative pain score. RESULTS: There were no significant differences between the 2 groups concerning morphine consumption within 24 hours after surgery (P = .72). The NRS score at rest and passive motion were similar at all-time points (P > .05). However, there was a statistically significant difference in pain reported during the active motion for the FNB group compared to the AQLB (P = .04). No significant differences were found between the 2 groups concerning muscle weakness incidence. CONCLUSION: Both AQLB and FNB demonstrated adequate efficacy for postoperative analgesia at rest in THA. However, based on our study, whether AQLB is inferior or noninferior to FNB as an analgesic method for THA was inconclusive.

Difficult Preoperative Diagnosis of Suspected Metal Hypersensitivity in a Case with Early Failure of Bipolar Hemiarthroplasty.

Background: Metal hypersensitivity is a rare complication after total hip arthroplasty (THA), and no reliable diagnostic method for metal hypersensitivity to orthopedic metal implants has yet been established. Case report. A 57-year-old woman underwent hemiarthroplasty using a metal implant despite a skin allergy to metal jewelry. Two years after surgery, the patient developed early hemiarthroplasty failure and refractory erythema. Although the patient was clinically suspected to have a hypersensitivity to metal, the preoperative screening test was negative, and patient underwent revision surgery with cemented THA. Postoperatively, the erythema as well as her hip pain disappeared completely. Conclusion: Patients with clinically suspected metal hypersensitivity should undergo primary and revision total hip arthroplasty using hypoallergenic implants regardless of preoperative screening results.

Sternocleidomastoid Muscle Thickness Correlates with Exercise Tolerance in Patients with COPD.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have difficulties inhaling as the diaphragm becomes flattened and weakened due to lung hyperinflation. This weakened respiratory function is compensated for by the increased activity of the accessory respiratory muscles, such as the sternocleidomastoid muscle (SCM). OBJECTIVES: This study aimed to evaluate the difference in the SCM thickening fraction (SCM TF) of each respiratory phase (end-expiration, resting inspiration, and end-inspiration), as measured using ultrasonography (US), between patients with COPD and control subjects. We also evaluate the correlation between the SCM TF of each respiratory phase and exercise tolerance in patients with COPD. METHODS: Patients with COPD (n = 44) and age-matched controls (n = 20) underwent US for determination of the SCM TF. Ventilation parameters, including the peak oxygen uptake (peak VO2) and the change in the inspiratory capacity, were measured during cardiopulmonary exercise testing. The SCM thickness and TF was measured during end-expiration, resting breathing, and end-inspiration. RESULTS: The SCM was significantly thinner in patients with COPD than in controls at end-expiration. The increase in the SCM TF from end-expiration to end-inspiration in patients with COPD did not differ significantly from that in control subjects. In contrast, the SCM TF from end-expiration to resting inspiration was significantly greater in patients with COPD than in control subjects. The peak VO2 was strongly positively correlated with the SCM TF from end-expiration to end-inspiration in patients with COPD (r = 0.71, p < 0.01). CONCLUSIONS: The SCM may be thinner in patients with COPD than in controls. The SCM TF may also be associated with exercise tolerance.

[A Case of Advanced Gastric Cancer with Preoperative Liver Metastasis and Postoperative Adrenal Metastasis, That Obtained Long-Term Recurrence-Free Survival after Resection and Chemotherapy].

The case was a 70-year-old man of highly advanced gastric cancer with 2 liver metastases(S3, S8)and pancreatic invasion. Three courses of S-1 plus L-OHP(SOX therapy)were performed, and total gastrectomy and combined resection of the spleen and body and tail of the pancreas and partial resection of the liver S3 and S8 were performed after reduction of primary tumor and liver metastasis. S-1 therapy was continued for 1 year as postoperative adjuvant chemotherapy. Left adrenal metastasis was detected by CT, 1 year and 6 months after the operation. PET-CT revealed no other areas suspected of recurrence, so left adrenalectomy was performed through the retroperitoneal space. Radical resection was not achieved because adhesions and scarring from the previous surgery were severe. Paclitaxel plus Ramucirumab was started and after 10 courses, the disappearance of the tumor shadow was observed on enhanced CT, and PET-CT. Three years and 3 months after the initial surgery and 1 year and 8 months after resection of adrenal metastasis, the patient is alive without recurrence.

Treatment of Severe Hip Dysplasia with Leg Length Discrepancy Using Spherical Periacetabular Osteotomy.

Case. A 20-year-old woman with severe subluxation of the hip displayed a leg length discrepancy of approximately 20 mm. The proposed treatment was a spherical periacetabular osteotomy (SPO) for joint preservation and postoperative leg length maintenance. SPO is a novel periacetabular osteotomy procedure. At her 3-year follow-up, the patient had functional, pain-free motion and high satisfaction. In this case, the SPO technique was able to achieve satisfactory clinical results without further exacerbating the leg length discrepancy after surgery.

Pancreatic fibrosis by extracellular volume fraction using Contrast-enhanced computed tomography and relationship with pancreatic cancer.

PURPOSE: This study aimed to assess the relationship between pancreatic fibrosis measured by the extracellular volume fraction (ECV) using contrast-enhanced computed tomography (CT) and the histologic pancreatic fibrosis fraction and investigate the relationship between pancreatic fibrosis and pancreatic cancer. METHOD: The study included 88 consecutive patients (48 males, 40 females; median age, 69 years; range, 17-89 years); 47 had pancreatic cancer, and 41 had other diseases. Fifty-two cases were evaluated pathologically for pancreatic fibrosis. The histologic pancreatic fibrosis fraction was quantified using image analysis software in nontumorous pancreatic tissue at the resection stump using 2-µm-thick Azan-stained slides. Two board-certified radiologists measured ECV in the pancreatic parenchyma at an estimated transection line. The correlation between histologic pancreatic fibrosis fraction and ECV was investigated, and whether the ECV value could be used as a biomarker for pancreatic cancer was investigated. RESULTS: The histologic pancreatic fibrosis fraction was significantly correlated with the ECV (r = 0.64, P < 0.01). Pancreatic fibrosis evaluated by ECV was higher in pancreatic cancer patients than in other patients (P < 0.01). On receiver-operating characteristic curve analysis, the ECV had good diagnostic accuracy for the development of pancreatic cancer (cut-off value 32.8%; sensitivity 61.0%, specificity 85.1%). ECV was identified on multivariate analysis as an independent risk factor for pancreatic cancer (odds ratio 1.16; P < 0.01). CONCLUSIONS: Extracellular volume fraction was strongly related to the histologic pancreatic fibrosis fraction, which was independently associated with pancreatic cancer. Thus, extracellular volume fraction is an imaging biomarker that reflects the progression of pancreatic fibrosis and may potentially help predict the development of pancreatic cancer, although further investigation will be needed.

Establishment of a reference single-cell RNA sequencing dataset for human pancreatic adenocarcinoma.

Single-cell RNA sequencing (scRNAseq) has been used to assess the intra-tumor heterogeneity and microenvironment of pancreatic ductal adenocarcinoma (PDAC). However, previous knowledge is not fully universalized. Here, we built a single cell atlas of PDAC from six datasets containing over 70 samples and >130,000 cells, and demonstrated its application to the reanalysis of the previous bulk transcriptomic cohorts and inferring cell-cell communications. The cell decomposition of bulk transcriptomics using scRNAseq data showed the cellular heterogeneity of PDAC; moreover, high levels of tumor cells and fibroblasts were indicative of poor-prognosis. Refined tumor subtypes signature indicated the tumor cell dynamics in intra-tumor and their specific regulatory network. We further identified functionally distinct tumor clusters that had close interaction with fibroblast subtypes via different signaling pathways dependent on subtypes. Our analysis provided a reference dataset for PDAC and showed its utility in research on the microenvironment of intra-tumor heterogeneity.

Exophthalmos associated with chronic progressive external ophthalmoplegia.

PURPOSE: Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial disease characterized by slowly progressive ptosis and limitations in ocular motility. Although exophthalmos is not considered to be a common feature of CPEO, this study focused on the incidence of exophthalmos in patients with CPEO. STUDY DESIGN: Retrospective observational case series METHODS: We reviewed the clinical charts of patients who received a diagnosis of CPEO sometime during the period between January 2010 and December 2018. CPEO was diagnosed on the basis of detection of a deletion of mitochondrial DNA (mtDNA) from saliva, buccal mucosa, or extraocular muscle specimens obtained during strabismus surgery. Horizontal MRI/CT images or Hertel ophthalmometry was used in determining exophthalmos. RESULTS: Seven patients (4 males) were identified. The mean age at diagnosis was 32.6 years (range 13-53 years). mtDNA deletion mutations were detected in the buccal mucous membrane DNA in 5 patients and in the saliva and extraocular muscle DNA in 2 patients. MRI/CT was recorded in 6 patients, four of whom showed exophthalmos (cases 1-4), and case 5 was determined as exophthalmos on the basis of a Hertel ophthalmometer reading. Exophthalmos was bilateral in 4 of the patients (cases 1, 2, 4, and 5) and unilateral in 1 patient (case 3). Exophthalmos was the chief concern of 2 of the patients; however, it was not clinically significant in the other patients. CONCLUSIONS: Although exophthalmos may not be recognized by either the patient or the clinician, it may be one of the common features of CPEO. A large multiethnic study should be performed.

Cancer metabolism challenges genomic instability and clonal evolution as therapeutic targets.

Although cancer precision medicine has improved diagnosis and therapy, refractory cancers such as pancreatic cancer remain to be challenging targets. Clinical sequencing has identified the significant alterations in driver genes and traced their clonal evolutions. Recent studies indicated that the tumor microenvironment elicits alterations in cancer metabolism, although its involvement in the cause and development of genomic alterations has not been established. Genomic abnormalities can contribute to the survival of selected subpopulations, recently recognized as clonal evolution, and dysfunction can lead to DNA mutations. Here, we present the most recent studies on the mechanisms of cancer metabolism involved in the maintenance of genomic stability to update current understanding of such processes. Sirtuins, which are NAD+-dependent protein deacetylases, appear to be involved in the control of genomic stability. Alterations of deleterious subpopulations would be exposed to selective pressure for cell survival. Recent studies indicated that a new type of cell death, ferroptosis, determines the survival of clones and exert cancer-restricting or -promoting effects to surrounding cells in the tumor microenvironment. Suppressing genomic instability and eliminating deleterious clones by cell death will contribute to the improvement of cancer medicine. Furthermore, the elucidation of the mechanisms involved is seen as a bridgehead to the pharmacologic suppression of such refractory cancers as pancreatic cancer.

Long term results of the Bicontact D stem in dysplastic osteoarthritis: a 10-15 year follow-up study.

PURPOSE: The purpose of the present study was to investigate the results of total hip arthroplasty (THA) using the Bicontact D stem with a minimum 10 year follow-up that focused on patients with developmental dysplasia of the hip (DDH). METHODS: One hundred five patients with osteoarthritis due to DDH who underwent primary THA were included in this study. The mean final follow-up period was 12.7 ± 1.2 years (range 10-15 years). All cases were evaluated both clinically and radiographically, and Kaplan-Meier survivorship was determined as stem revision for any reason as the end point. RESULTS: Modified Harris hip score averaged 89.0 ± 1.1 (range 60-98) at the final follow-up. The survivorship was 99.0% (95% confidence interval 93.4-99.9%) at 15.0 years, and only one hip with a well-fixed stem required stem revision due to recurrent dislocations. Cortical hypertrophy (CH) was observed in 40 of 105 hips (38.1%), and stress shielding (SS) progressed to grade 3 or 4 in six hips (6 of 105 hips: 5.7%) during the study period. Among the six hips with progressed SS, Dorr type C proximal femoral geometry was seen in five hips. CONCLUSION: This study of 105 THAs using the Bicontact D stem that focused on DDH patients with a minimum 10 year follow-up period achieved satisfactory clinical and radiological outcomes. Dorr type C proximal femoral geometry could be considered a risk factor for progressed SS.

Diaphragmatic excursion is correlated with the improvement in exercise tolerance after pulmonary rehabilitation in patients with chronic obstructive pulmonary disease.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD), the maximum level of diaphragm excursion (DEmax) is correlated with dynamic lung hyperinflation and exercise tolerance. This study aimed to elucidate the utility of DEmax to predict the improvement in exercise tolerance after pulmonary rehabilitation (PR) in patients with COPD. METHODS: This was a prospective cohort study. Of the 62 patients with stable COPD who participated in the outpatient PR programme from April 2018 to February 2021, 50 completed the programme. Six-minute walk distance (6MWD) was performed to evaluate exercise tolerance, and ultrasonography was performed to measure DEmax. Responders to PR in exercise capacity were defined as patients who demonstrated an increase of > 30 m in 6MWD. The receiver operating characteristic (ROC) curve was used to determine the cut-off point of DEmax to predict responses to PR. RESULTS: Baseline levels of forced expiratory volume in 1 s, 6MWD, maximum inspiratory pressure, DEmax and quadriceps muscle strength were significantly higher, and peak dyspnoea of modified Borg (mBorg) scale score was lower in responders (n = 30) than in non-responders (n = 20) to PR (p < 0.01). In multivariate analysis, DEmax was significantly correlated with an increase of > 30 m in 6MWD. The area under the ROC curve of DEmax to predict responders was 0.915, with a sensitivity and specificity of 83% and 95%, respectively, at a cut-off value of 44.9 mm of DEmax. CONCLUSION: DEmax could adequately predict the improvement in exercise tolerance after PR in patients with COPD.

Revision Total Hip Arthroplasty due to Catastrophic Osteolysis Caused by Massive Chronic Expanding Hematoma.

An 84-year-old woman who underwent bilateral cementless total hip arthroplasty (THA) for dysplastic osteoarthritis 22 years ago was subjected to analysis. A huge soft-tissue mass was revealed in her left medial thigh. Plain radiographs of the left hip joint revealed severe osteolysis around the stem, cup, and ischium. Magnetic resonance imaging showed a 25 × 14-cm multilobulated mass with a thick-walled pseudocapsule. Two-stage surgery was performed with resection of the mass followed by a subsequent revision THA. The mass was diagnosed as a chronic expanding hematoma through gross and histologic findings. Two years after the revision THA, there was no recurrence of a hematoma. Two-stage revision THA was useful for definitive diagnosis, and good functional recovery was obtained after surgery.

Impact of One-Carbon Metabolism-Driving Epitranscriptome as a Therapeutic Target for Gastrointestinal Cancer.

One-carbon (1C) metabolism plays a key role in biological functions linked to the folate cycle. These include nucleotide synthesis; the methylation of DNA, RNA, and proteins in the methionine cycle; and transsulfuration to maintain the redox condition of cancer stem cells in the tumor microenvironment. Recent studies have indicated that small therapeutic compounds affect the mitochondrial folate cycle, epitranscriptome (RNA methylation), and reactive oxygen species reactions in cancer cells. The epitranscriptome controls cellular biochemical reactions, but is also a platform for cell-to-cell interaction and cell transformation. We present an update of recent advances in the study of 1C metabolism related to cancer and demonstrate the areas where further research is needed. We also discuss approaches to therapeutic drug discovery using animal models and propose further steps toward developing precision cancer medicine.

Radiological Evaluation of the Relationship Between Cortical Hypertrophy and Stress Shielding After Total Hip Arthroplasty Using a Cementless Stem.

BACKGROUND: Unloading of the proximal medial femoral cortex is usually associated with an increased bone strain at the distal part of the prosthesis, which may cause distal femoral cortical hypertrophy (CH). The objective of this study was to determine the factors that may be considered a predisposition to distal femoral CH and its effect on the stress shielding (SS) or durability of the fixation of the stem. METHODS: A total of 240 total hip arthroplasties were performed between January 2006 and December 2016, with all hips implanted with a Bicontact stem. The minimum follow-up period was more than 2 years, and the mean follow-up period was 7.2 years. The radiographic outcome was assessed on an anteroposterior hip radiograph. CH and SS were assessed on postoperative radiographs in the Gruen zone. We defined CH that appeared in zone 3 or 5 as 'the focal type' and defined CH that appeared in zones 2, 3, 4, 5, and 6 as 'the diffuse type.' SS followed the procedures from the Engh classification. RESULTS: CH was found in 72 hips (30% of the 240 hips), the focal type was found in 23 hips (9.6% of the 240 hips), and the diffuse type was found in 49 hips (20.4% of the 240 hips). SS was found in 41 hips (17.1% of 240 hips), including 32 hips with SS, which was found after the development of CH. One hip was from the focal-type CH and 31 hips were from the diffuse-type CH. SS, which is typically found in Engh classification types 1 and 2 developed in 13 hips, and SS, which is widely seen in Engh classification types 3 and 4 developed in 19 hips. All 19 hips with progressed SS were found after the diffuse-type CH had developed. In addition, among the 19 hips with progressed SS, Dorr type A was found in 0 hips, Dorr type B in 8 hips, and Dorr type C in 11 hips. CONCLUSIONS: According to the results of our radiological evaluation, development of the diffuse-type CH after total hip arthroplasty using Bicontact stems is one of the critical causes of the later development of SS and could be predicted to progress to SS. To prevent the development of the diffuse-type CH, the indication to choose a Bicontact stem for a Dorr type C with osteoporotic bone should be considered.

Immuno-Surgical Management of Pancreatic Cancer with Analysis of Cancer Exosomes.

Exosomes (EXs), a type of extracellular vesicles secreted from various cells and especially cancer cells, mesenchymal cells, macrophages and other cells in the tumor microenvironment (TME), are involved in biologically malignant behaviors of cancers. Recent studies have revealed that EXs contain microRNAs on their inside and express proteins and glycolipids on their outsides, every component of which plays a role in the transmission of genetic and/or epigenetic information in cell-to-cell communications. It is also known that miRNAs are involved in the signal transduction. Thus, EXs may be useful for monitoring the TME of tumor tissues and the invasion and metastasis, processes that are associated with patient survival. Because several solid tumors secrete immune checkpoint proteins, including programmed cell death-ligand 1, the EX-mediated mechanisms are suggested to be potent targets for monitoring patients. Therefore, a companion therapeutic approach against cancer metastasis to distant organs is proposed when surgical removal of the primary tumor is performed. However, EXs and immune checkpoint mechanisms in pancreatic cancer are not fully understood, we provide an update on the recent advances in this field and evidence that EXs will be useful for maximizing patient benefit in precision medicine.