Current surgical treatment of esophagogastric junction adenocarcinoma

The incidence of esophagogastric junction(EGJ)adenocarcinoma has shown an upward trend over the past several decades worldwide.In this article,we review previous studies and aimed to provide an update on the factors related to the surgical treatment of EGJ adenocarcinoma.The Siewert classification has implications for lymph node spread and is the most commonly used classification.Different types of EGJ cancer have different incidences of mediastinal and abdominal lymph node metastases,and different surgical approaches have unique advantages and disadvantages.Minimally invasive surgeries have been increasingly applied in clinical practice and show comparable oncologic outcomes.Endoscopic resection may be a good therapy for early EGJ cancer.Additionally,there is still a great need for well-designed,large RCTs to forward our knowledge on the surgical treatment of EGJ cancer.

Animal models of pancreatitis: Can it be translated to human pain study?

Chronic pancreatitis affects many individuals around the world,and the study of the underlying mechanisms leading to better treatment possibilities are important tasks.Therefore,animal models are needed to illustrate the basic study of pancreatitis.Recently,animal models of acute and chronic pancreatitis have been thoroughly reviewed,but few reviews address the important aspect on the translation of animal studies to human studies.It is well known that pancreatitis is associated with epigastric pain,but the understanding regarding to mechanisms and appropriate treatment of this pain is still unclear.Using animal models to study pancreatitis associated visceral pain is difficult,however,these types of models are a unique way to reveal the mechanisms behind pancreatitis associated visceral pain.In this review,the animal models of acute,chronic and un-common pancreatitis are briefly outlined and animal models related to pancreatitis associated visceral pain are also addressed.

Relationships of CDXs and apical sodium-dependent bile acid transporter in Barrett's esophagus

Barrett's esophagus (BE) is characterized by intestinal metaplasia with the differentiated epithelium replaced by another type of epithelium morphologically similar to normal intestinal epithelium. The metaplasia is preceded by bile and acid reflux into the esophagus. BE is a premalignant condition associated with increased risk of esophageal cancer, especially esophageal adenocarcinoma. The Caudal-related homeodomain transcription factors Caudal-related homeodomain transcription factor CDX1 and CDX2 are expressed exclusively in the small and large intestine, playing important roles in proliferation and differentiation of intestinal epithelial cells. Ectopic expression of CDX1 and CDX2 occurs in BE. The apical sodium-dependent bile acid transporter (ASBT) is expressed primarily in terminal ileum where it is a key factor for intestinal reabsorption of bile salts. In addition to upregulation of CDX1 and CDX2, ASBT expression is up-regulated in BE. Furthermore, both CDX1/CDX2 and ASBT expressions are down-regulated in high-grade esophageal dysplasia. The alteration of the above-mentioned factors calls for attention: what is the relationship between CDXs and ASBT aberrant expression in BE? In this commentary, we discuss this issue on basis of the recent study done by Ma et al .

Easy fixation effects the prevention of Peterson’s hernia and Roux stasis syndrome

BACKGROUND Laparoscopic distal gastrectomy(LDG)for gastric cancer has been progressed and popular in Japan,since it was first described in 1994.Several reconstruction methods can be adopted according to remnant stomach size,and balance of pros and cons.Roux-en-Y(R-Y)reconstruction is a one of standard options after LDG.Its complications include Petersen’s hernia and Roux stasis syndrome.Here we report our ingenious attempt,fixation of Roux limb and duodenal stump,for decreasing the development of Petersen’s hernia and Roux stasis syndrome.AIM To develop a method to decrease the development of Petersen’s hernia and Roux stasis syndrome.METHODS We performed ante-colic R-Y reconstruction after LDG.After R-Y reconstruction,we fixed Roux limb onto the duodenal stump in a smooth radian.Via this small improvement in Roux limb,Roux limb was placed to the right of the ligament of Treitz.This not only changed the anatomy of the Petersen’s defect,but it also kept a fluent direction of gastrointestinal anastomosis and avoided a cross-angle after jejunojejunostomy.31 patients with gastric cancer was performed this technique after R-Y reconstruction.Clinical parameters including clinicopathologic characteristics,perioperative outcomes,postoperative complication and follow-up data were evaluated.RESULTS The operative time was(308.0±84.6 min).This improvement method took about 10 min.Two(6.5%)patients experienced pneumonia and pancreatitis,respectively.No patient required reoperation or readmission.All patients were followed up for at least 3 year,and none of the patients developed postoperative complications related to internal hernia or Roux stasis syndrome.CONCLUSION This 10 min technique is a very effective method to decrease the development of Petersen’s hernia and Roux stasis syndrome in patients who undergo LDG.

Changes of phasic and tonic smooth muscle function of jejunum in type 2 diabetic Goto-Kakizaki rats

AIM:To generate phasic and tonic stress-strain curves for evaluation of intestinal smooth muscle function in type 2 diabetic rats during active and passive conditions.METHODS:Seven diabetic Goto-Kakizaki(GK)male rats,32-wk old(GK group),and 9 age-matched normal Wistar rats(Normal group)were included in the study.Jejunal segments were distended up to a pressure of10 cm H2O in an organ bath containing 37℃Krebs solution with addition of carbachol(CA).The pressure and outer diameter changes were synchronously recorded.Passive conditions were obtained using calcium-free Krebs solution containing ethylene glycol tetraacetic acid and papaverine.Total phasic,tonic and passive circumferential stress and strain were computed from the diameter and pressure data with reference to the zero-stress state geometry.The active phasic and tonic stresses were defined as the total phasic and tonic stresses minus the passive stress.RESULTS:Diabetes increased jejunal mucosa and muscle layer thicknesses compared to the Normal group(mucosa,755.8±63.3 vs 633.1±59.1μm,P<0.01;muscle,106.3±12.9 vs 85.2±11.7μm,P<0.05).The pressure and stress thresholds were decreased in the GK group after CA application compared to distensions without CA application(pressure,1.01±0.07vs 1.99±0.19 cmH2O,P<0.01;stress,0.11±0.01vs 0.24±0.02 kPa,P<0.01).CA application did not change the pressure and stress threshold in the Normal group(pressure,2.13±0.32 vs 2.34±0.32 cm H2O,P>0.05;stress,0.25±0.03 vs 0.35±0.06 kPa,P>0.05).The amplitude of total phasic,total tonic,active phasic and active tonic circumferential stresses did not differ for the distensions without CA application between the GK group and the Normal group.However,the total phasic and total tonic stresses increased after CA application in the GK group compared those in the Normal group.When normalized to muscle layer thickness,the amplitude of active stresses before CA application was lowest in the GK group compared with the Normal group.No difference was found during CA application.CONCLUSION:The stress generated by intestinal muscle normalized to the muscle layer thickness was lowest in GK rats compared to normal rats whereas the response to CA stimulation was preserved.

Application of extended criteria donor grafts in liver transplantation for acute-on-chronic liver failure:A retrospective cohort study

BACKGROUND There is no consensus on the usage of extended criteria donor(ECD)grafts in liver transplantation(LT)for acute-on-chronic liver failure(ACLF)patients.AIM To summarize the experience of using ECD livers in ACLF-LT.METHODS A retrospective cohort study was conducted,enrolling patients who underwent LT at the First Affiliated Hospital of Sun Yat-Sen University from January 2015 to November 2021.The patients were divided into ECD and non-ECD groups for analysis.RESULTS A total of 145 recipients were enrolled in this study,of which ECD and non-ECD recipients accounted for 53.8%and 46.2%,respectively.Donation after cardiac death(DCD)recipients accounted for the minority compared with donation after brain death(DBD)recipients(16.6%vs 83.4%).Neither overall survival nor graft survival significantly differed between ECD and non-ECD and DCD and DBD recipients.ECD grafts were associated with a significantly higher incidence of early allograft dysfunction(EAD)than non-ECD grafts(67.9%vs 41.8%,P=0.002).Postoperative outcomes between DCD and DBD recipients were comparable(P>0.05).ECD graft(P=0.009),anhepatic phase(P=0.034)and recipient gamma glutamyltransferase(P=0.016)were independent risk factors for EAD.Recipient preoperative number of extrahepatic organ failures>2(P=0.015)and intraoperative blood loss(P=0.000)were independent predictors of poor post-LT survival.CONCLUSION Although related to a higher risk of EAD,ECD grafts can be safely used in ACLF-LT.The main factors affecting post-LT survival in ACLF patients are their own severe preoperative disease and intraoperative blood loss.

Antral exfoliative cytology for the detection of Helicobacter pylori in the stomach

AIM: To evaluate the efficacy of antral exfoliative cytology method in the diagnosis of Helicobacter pylori (H pylori)infection in the stomach.METHODS: Fifty patients were submitted to upper digestivetract endoscopy due to complaints of dyspepsia. Thematerial for exfoliative cytology was obtained by extensive brushing of the gastric antral mucosa and Papanicolaou stain was used to identify the bacteria. The authors also performed gastric biopsies to collect material for urease tests and histologic studies, with hematoxylin-eosin and fucsin stains in order to identify the microorganism. The gold standard used to detect the presence of H pylori was an analysis of the combined results from the gastric biopsies by urease test and histological method. RESULTS: Antral exfoliative cytology method exhibited 90.3% sensitivity, 66.6% specificity, accuracy of 81.6%, positive predictive value of 82.3% and negative predictive value of 80.0%, in this population with a prevalence of 63.3%.CONCLUSION: Antral exfoliative cytology was demonstrated to be a sensitive, accurate and easy to perform method for investigating H pylori infection in the stomach.

Gastric cancer with soft tissue metastasis of the abdominal wall:a case report

Abdominal wall metastasis of gastric cancer(GC)is a very rare occurrence in the clinic setting.We recently diagnosed and treated a patient with abdominal wall metastasis of GC and we hope to provide some helpful guidance on the clinical diagnosis and treatment of this disease.A 49-year-old male patient with GC was admitted to our hospital(Dalian Municipal Central Hospital,Dalian,China)complaining of left upper abdominal wall mass.Physical examination and regular laboratory blood tests showed no obvious abnormalities.Ultrasound and CT of the abdomen showed a subcutaneous solid mass in the abdominal wall.Radical gastrectomy was performed on February 27,2019,six months after it was first noticed by the patient.Pathological examination and immunohistochemistry showed GC with abdominal metastasis.Postoperative radiotherapy or chemotherapy was not pursued after the second operation and no recurrence or metastasis has been noted so far.GC with abdominal metastasis is very rare and can be easily missed or misdiagnosed.For metastasis to a single site in the abdominal wall,surgical resection,which is recommended,may improve patient outcomes.

Metastatic stomach lymphoepithelioma-like carcinoma and immune checkpoint inhibitor therapy:A case report

BACKGROUND Pulmonary lymphoepithelioma-like carcinoma(PLELC)is a rare type of nonsmall-cell lung cancer.Stomach lymphoepithelioma-like carcinoma(LELC)metastasis secondary to PLELC has not been reported recently.CASE SUMMARY A 64-year-old female was admitted to our hospital for a regular gastroscopy examination with a 6-year history of surgical resection for left PLELC.Positron emission tomography/computed tomography suggested high accumulation of 18F-fludeoxyglucose in the gastric cardia region.Upper gastrointestinal endoscopy confirmed a large mass at the stomach fundus.Immunohistochemistry(IHC)of the biopsy suggested metastatic stomach LELC.Proximal gastrectomy showed that this 6.5 cm×5.0 cm mass was located in the stomach fundus near the cardia.Histopathological examination showed a poorly differentiated carcinoma with prominent lymphoplasmacytic infiltration.IHC demonstrated that the tumor was positive for CK(AE1/AE3),p63,p40,p53,Ki-67(70%),and EGFR(3+)and negative for CK7,CK20,Her2,and CD10.In situ hybridization analysis showed positive staining Epstein-Barr virus-encoded RNA.Tumor programmed cell death ligand 1(PD-L1)expression score was 98%,and the combined positive score was 100,with no evidence of microsatellite instability.Thus,the patient was unequivocally diagnosed with metastatic stomach LELC secondary to pulmonary LELC.After discharge,this patient underwent PD-1 inhibitor treatment(toripalimab,240 mg)every 3 wk for ten cycles,and she has had no tumor recurrence.CONCLUSION For gastric LELC metastasis,PD-1 inhibitor therapy could become a new therapeutic approach,though there is still no evidence from large data sets to support this.

Unusual Giant Pre-Sacral Multicystic Schwannoma: A Case Report and Differential Diagnosis

Background: Schwannomas are generally benign neoplasms arising from the nerve sheath. Presacral schwannomas are very rare entities and difficult to diagnose, representing less than 15% of all retrorectal space tumors. Benign schwannoma sometimes displays degenerative changes, such as cyst formation, calcification, hemorrhage, and hyalinization. Usually these degenerations are partially seen in the tumors. Objective: To point out that presacral schwannoma can display markedly multilocular cystic degeneration. Case Report: We present this unique case of a 24-year-old man diagnosed with an unusually large pure multilocular cystic schwannoma, which is revealed by digestive, urinary, and nonspecific neurological symptoms. The patient was successfully treated with radical surgery via an anterior approach leading to the recovery of symptoms. Discussion and Conclusion: This tumor was unusual in its totally multicystic appearance and its resemblance to a wide spectrum of lesions that can occur in the pre-sacral space, such as hydatid and developmental cysts. Preoperative diagnosis is essential to prevent major neurological deficits during surgical intervention.

Lower Bifidobacteria counts in both duodenal mucosa-associated and fecal microbiota in irritable bowel syndrome patients

AIM: To determine the composition of both fecal and duodenal mucosa-associated microbiota in irritable bowel syndrome (IBS) patients and healthy subjects using molecular-based techniques. METHODS: Fecal and duodenal mucosa brush samples were obtained from 41 IBS patients and 26 healthy subjects. Fecal samples were analyzed for the composition of the total microbiota using fluorescent in situ hybridization (FISH) and both fecal and duodenal brush samples were analyzed for the composition of bif idobacteria using real-time polymerase chain reaction. RESULTS: The FISH analysis of fecal samples revealed a 2-fold decrease in the level of bifidobacteria (4.2 ± 1.3 vs 8.3 ± 1.9, P < 0.01) in IBS patients compared to healthy subjects, whereas no major differences in other bacterial groups were observed. At the species level, Bifidobacterium catenulatum levels were significantly lower (6 ± 0.6 vs 19 ± 2.5, P < 0.001) in the IBS patients in both fecal and duodenal brush samples than in healthy subjects.CONCLUSION: Decreased bifidobacteria levels in both fecal and duodenal brush samples of IBS patients compared to healthy subjects indicate a role for microbiotic composition in IBS pathophysiology.

Helicobacter pylori and EBV in gastric carcinomas:Methylation status and microsatellite instability

AIM:To verify the methylation status of CDH1, DAPK, COX2, hMLH1 and CDKN2A genes and to evaluate their association with Helicobacter pylori (H. pylori)-cagA+ and Epstein Barr virus (EBV) infections in gastric adenocarcinomas.METHODS: Methylation-specific PCR (MSP) assay was performed in 89 primary gastric carcinomas (intestinal and diffuse types). Microsatellite instability (MSI) analysis was performed using the BAT26 primer set and PCR products were analyzed with the ABI PRISM 3100 Genetic Analyzer using Genescan 3.7 software (Applied Biosystems). Detection of H. pylori and genotyping were performed by PCR, using specifi c primers for ureaseC and cagA genes. The presence of EBV was assessed by in situ hybridization. Statistical analyses were performed using the χ2 or Fisher's exact test.RESULTS: The most frequent hypermethylated gene was COX-2 (63.5%) followed by DAPK (55.7%), CDH1 (51%), CDKN2A (36%) and hMLH1 (30.3%). Intestinal and diffuse adenocarcinomas showed different methylation profiles and there was an association between methylation of E-CDH1 and H. pylori-cagA+ in the intestinal adenocarcinoma type. MSI was correlated with hMLH1 methylation. There was an inverse correlation between DAPK hypermethylation and MSI.CONCLUSION: We found a strong association between CDH1 methylation and H. pylori-cagA+ in intestinal-type gastric cancer, association of MSI and better prognosis and an heterogeneous COX-2 overexpression.

Clinical significance of hepatic artery variations originating from the superior mesenteric artery in abdominal tumor surgery

Background Hepatic artery variations are frequent clinical characteristic course of variant hepatic arteries originating providing instructions for abdominal tumor surgery. occurrences. The aim of this study was to investigate the from the superior mesenteric artery for the purpose of Methods The course of variant hepatic arteries originating from the superior mesenteric artery was studied in 400 patients with liver cancer confirmed by digital subtraction angiography （DSA） and multi-slice spiral computed tomography angiography （MSCTA）, and 86 patients with gastric cancer confirmed by preoperative MSCTA between June 2008 and June 2010 in the First Affiliated Hospital of Guangxi Medical University. Results Hepatic artery variations originating from the superior mesenteric artery were noticed in 49 liver cancer patients and 14 gastric cancer patients （total 63 cases）, with a variation rate of 12.96%, including two cases （3.17%） where the hepatic arteries ran along the anterior pancreas, and 61 cases （96.83%） where the hepatic arteries ran along the posterior pancreas. Conclusions Hepatic artery variations originating from the superior mesenteric artery present as two types： the pre-pancreas type and the post-pancreas type with the latter predominating. This finding is of clinical significance in abdominal tumor surgeries where clearance of portal lymph nodes is needed.

Primary gastric adenosquamous carcinoma: a case report and literature review

Primary gastric adenosquamous carcinoma (GASC) is exceedingly rare. It accounts for less than 1% of all gastric cancers. In this report, we describe our pathological findings along with a review of the literature to improve our understanding of the disease and reduce misdiagnosis, as well as to provide evidence for its treatment and prognosis. A 49-year-old male patient was admitted to our hospital (Dalian Municipal Central Hospital, Dalian, China) with a complaint of epigastric pain that had persisted for half a month. Physical examination, regular laboratory blood tests, and computed tomography revealed no obvious abnormalities. Gastroscopy revealed ulcers in the lower part of the stomach, and pathological assessment revealed adenocarcinoma. Radical gastrectomy was performed, and the folinic acid, fluorouracil, oxaliplatin (FOLFOX) chemotherapy regimen was administered postoperatively. Pathological assessment of the mass revealed a protruding tumor measuring 1.5 × 1.5 × 0.7 cm in the lower part of the stomach. The tumor infiltrated through the full wall of the stomach. This was confirmed by immunohistochemical (IHC) staining for cytokeratin (CK)(+), villin (-), p63 (++), and high-molecular-weight CK (+++). The patient remains alive with no recurrence more than seven years after surgery. Primary GASC is a rare malignant neoplasm. The diagnostic criteria for GASC mainly depend on the clinical, radiographic, and histopathological findings. Pathological assessment and IHC staining can be utilized to confirm the diagnosis. Radical gastrectomy plus postoperative chemotherapy containing the FOLFOX regimen is effective for treating GASC and might contribute to long-term survival.

Increased colon transit time and faecal load in irritable bowel syndrome

BACKGROUND Irritable bowel syndrome(IBS)is a bowel disorder involving abdominal pain or discomfort along with irregularity of stool form and passage frequency.The pathophysiology is poorly understood and seems to be multifactorial.Investigations of possible causes of IBS have included only a few colonic transit studies and no simultaneous determination of the colonic faecal content.AIM To compare colon transit time and faecal load between IBS-patients and healthy control subjects.METHODS The study included 140 patients with IBS,with a mean age of 50.0 years.The control group comprised 44 healthy persons with a mean age of 43.4 years,who were selected at random from the National Civil Register.Both the patient group and the control group underwent a marker study to measure colon transit time(CTT)and to calculate a faecal loading score.The patient group underwent treatment with a combined prokinetic regime,after which their CTT and faecal loading were reassessed.Analyses were performed to compare measurements between the control group and the patient group before and after treatment.RESULTS Compared to healthy controls,IBS-patients exhibited a significantly prolonged mean CTT(45.48 h vs 24.75 h,P=0.0002)and significantly greater mean faecal loading scores in all colonic segments(P<0.001).Among IBS patients,we found no significant differences between the 48 h and 96 h radiographs.Among patients exhibiting increased CTT and faecal loading,approximately half exhibited a palpable mass in the right iliac fossa.After intervention with a prokinetic treatment,the mean CTT among IBS patients was reduced from 45.48 h to 34.50 h(P=0.091),with the post-treatment CTT not significantly differing from the CTT among control subjects(P=0.095).The faecal loading score among IBS patients did not significantly differ before and after treatment(P=0.442).The posttreatment faecal loading score in IBS patients remained significantly higher compared to that in controls(5.3 vs 4.3,P=0.014).After treatment,half of the IBSpatients were relieved of bloating,while the majority no longer experienced abdominal pain and achieved a daily consistent stool.CONCLUSION IBS-patients exhibited prolonged CTT and heavier faecal loading.These assessments may aid in diagnosis.Faecal retention may contribute to IBS symptoms,which can be treated using a prokinetic regime.

Cytoprotective Mechanism of the Novel Gastric Peptide BPC157 in Gastrointestinal Tract and Cultured Enteric Neurons and Glial Cells

Dear Editor,Body protection compound (BPC) 157 is a stable gastric pentadecapeptide. Predrag Sikiric’s team has carried out many investigations of its cytoprotective effects in different organs and tissues (1, 2)Their evidence indicates that BPC157 has potent cytoprotection in neural injury and gastrointestinal (GI) ulcers. Nevertheless.

Artificial intelligence system of faster region-based convolutional neural network surpassing senior radiologists in evaluation of metastatic lymph nodes of rectal cancer

Background: An artificial intelligence system of Faster Region-based Convolutional Neural Network (Faster R-CNN) is newly developed for the diagnosis of metastatic lymph node (LN) in rectal cancer patients. The primary objective of this study was to comprehensively verify its accuracy in clinical use. Methods: Four hundred fourteen patients with rectal cancer discharged between January 2013 and March 2015 were collected from 6 clinical centers, and the magnetic resonance imaging data for pelvic metastatic LNs of each patient was identified by Faster R-CNN. Faster R-CNN based diagnoses were compared with radiologist based diagnoses and pathologist based diagnoses for methodological verification, using correlation analyses and consistency check. For clinical verification, the patients were retrospectively followed up by telephone for 36 months, with post-operative recurrence of rectal cancer as a clinical outcome;recurrence-free survivals of the patients were compared among different diagnostic groups, by methods of Kaplan-Meier and Cox hazards regression model. Results: Significant correlations were observed between any 2 factors among the numbers of metastatic LNs separately diagnosed by radiologists, Faster R-CNN and pathologists, as evidenced by rradiologist-Faster R-CNN of 0.912, rPathologist-radiologist of 0.134, and rPathologist-Faster R-CNN of 0.448 respectively. The value of kappa coefficient in N staging between Faster R-CNN and pathologists was 0.573, and this value between radiologists and pathologists was 0.473. The 3 groups of Faster R-CNN, radiologists and pathologists showed no significant differences in the recurrence-free survival time for stage N0 and N1 patients, but significant differences were found for stage N2 patients. Conclusion: Faster R-CNN surpasses radiologists in the evaluation of pelvic metastatic LNs of rectal cancer, but is not on par with pathologists.

A novel nomogram individually predicting disease-specific survival after D2 gastrectomy for advanced gastric cancer

Background:Few studies have shown nomograms that may predict disease-specific survival(DSS)probability after curative D2 gastrectomy for advanced gastric cancer(AGC),particularly among Chinese patients.This study sought to develop an elaborative nomogram that predicts long-term DSS for AGC in Chinese patients.Methods:A retrospective study was conducted on 6753 AGC patients undergoing D2 gastrectomy between January 1,2000 and December 31,2012 from three large medical hospitals in China.We assigned patients from Sun Yat-sen University Cancer Center to the training set,and patients from the First Affiliated Hospital of China Medical University and Tianjin Medical University Cancer Hospital to two separate external validation sets.A multivariate survival analysis was performed using Cox proportional hazards regression model in a training set,and a nomogram was constructed.Harrell’s C-index was used to evaluate discrimination and calibration plots were used to validate similarities between survival probabilities predicted by the nomogram model and actual survival rates in two validation sets.Results:The multivariate Cox regression model identified age,tumor size,location,Lauren classification,lymphatic/venous invasion,depth of invasion,and metastatic lymph node ratio as covariates associated with survival.In the training set,the nomogram exhibited superior discrimination power compared with the 8th American Joint Com-mittee on Cancer TNM classification(Harrell’s C-index,0.82 vs.0.74;P<0.001).In two validation sets,the nomogram’s discrimination power was also excellent relative to TNM classification(C-index,0.83 vs.0.75 and 0.81 vs.0.74,respec-tively;P<0.001 for both).After calibration,the nomogram produced survival predictions that corresponded closely with actual survival rate.Conclusions:The established nomogram was able to predict 3-,5-,and 10-year DSS probabilities for AGC patients.Validation revealed that this nomogram exhibited excellent discrimination and calibration capacity,suggesting its clinical utility.