Prognostic impact of osteosarcopenia in patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma.

BACKGROUND: We investigated the prognostic impact of osteosarcopenia, defined as the combination of osteopenia and sarcopenia, in patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma (PDAC). METHODS: The relationship of osteosarcopenia with disease-free survival and overall survival was analyzed in 183 patients who underwent elective pancreatic resection for PDAC. Computed tomography was used to measure the pixel density in the midvertebral core of the 11th thoracic vertebra for evaluation of osteopenia and in the psoas muscle area of the 3rd lumbar vertebra for evaluation of sarcopenia. Osteosarcopenia was defined as the simultaneous presence of both osteopenia and sarcopenia. The study employed a retrospective design to examine the relationship between osteosarcopenia and survival outcomes. RESULTS: Osteosarcopenia was identified in 61 (33%) patients. In the univariate analysis, disease-free survival was significantly worse in patients with male sex (p = 0.031), pathological stage ≥ III PDAC (p = 0.001), NLR, ≥ 2.71 (p = 0.041), sarcopenia (p = 0.027), osteopenia (p = 0.001), and osteosarcopenia (p < 0.001), and overall survival was significantly worse in patients with male sex (p = 0.001), pathological stage ≥ III PDAC (p = 0.001), distal pancreatectomy (p = 0.025), sarcopenia (p = 0.003), osteopenia (p < 0.001), and osteosarcopenia (p < 0.001). In the multivariate analysis, the independent predictors of disease-free survival were osteosarcopenia (p < 0.001) and pathological stage ≥ III PDAC (p = 0.002), and the independent predictors of overall survival were osteosarcopenia (p < 0.001), male sex (p = 0.006) and pathological stage ≥ III PDAC (p = 0.001). CONCLUSION: Osteosarcopenia has an adverse prognostic impact on long-term outcomes in patients undergoing pancreatic resection for PDAC.

Proposal for Prognosis-Oriented Definition of Borderline Resectable Hepatocellular Carcinoma.

BACKGROUND: Owing to advances in the multidisciplinary treatment of hepatocellular carcinoma (HCC), a conceptualization and definition for borderline resectable (BR) HCC, which carries a high risk of recurrence, is warranted. In this study, we aimed to define BR-HCC using a prognosis-oriented approach. METHODS: The study included an original cohort of 221 patients and an independent validation cohort of 181 patients who had undergone primary hepatic resection for HCC. To define oncological BR-HCC, we evaluated the risk factors for early recurrence beyond the Milan criteria within 1 year after hepatic resection using multivariable logistic regression models. Subsequently, we developed high-risk scores using the identified risk factors and defined BR-HCC. The utility of high-risk score was validated in the validation cohort. RESULTS: In the original cohort (HBV:HCV=20%:29%), recurrence beyond the Milan criteria within 1 year was observed in 28 patients (13%), with a 5-year survival rate of 25%. Multivariable analysis identified risk factors for recurrence beyond the Milan criteria within 1 year, including serum α-fetoprotein levels ≥ 12 ng/ml (p=0.02), tumor diameters > 5 cm (p=0.02), tumor number ≥ 3 (p=0.001), and macrovascular invasion (p=0.04). BR-HCC was defined as a tumor with two or more identified risk factors, and 42 patients (19%) were diagnosed with BR-HCC, with a 5-year survival rate of 51%. In the validation cohort, 45 (25%) patients had BR-HCC, with a 5-year survival rate of 42%. CONCLUSIONS: The prognosis-oriented definition of BR-HCC enabled us to identify patients who are susceptible to early unresectable recurrence and have poor survival after hepatic resection for HCC. For patients with BR-HCC, preoperative systemic therapy may be a viable option to improve post-resection outcomes.

Osteosarcopenia is a significant predictor of recurrence and the prognosis after resection for extrahepatic bile duct cancer.

PURPOSE: This study examined the impact of osteosarcopenia on recurrence and the prognosis after resection for extrahepatic biliary tract cancer (EBTC). METHODS: We retrospectively analyzed 138 patients after resection for perihilar cholangiocarcinoma (11), distal cholangiocarcinoma (54), gallbladder carcinoma (30), or ampullary carcinoma (43). Osteosarcopenia is defined as the concomitant occurrence of osteopenia and sarcopenia. We investigated the relationship between osteosarcopenia and the overall survival (OS) and disease-free survival (DFS) in univariate and multivariate analyses. RESULTS: Osteosarcopenia was identified in 38 patients (27.5%) before propensity score (PS) matching. In the multivariate analysis, the independent recurrence factors were the prognostic nutrition index (p = 0.015), osteosarcopenia (p < 0.001), poorly differentiated adenocarcinoma (p = 0.004), perineural invasion (p = 0.002), and non-curability (p = 0.008), whereas the independent prognostic factors were prognostic nutrition index (p = 0.030), osteosarcopenia (p < 0.001), poorly differentiated adenocarcinoma (p = 0.007), lymphatic invasion (p = 0.018), and non-curability (p = 0.004). After PS matching, there was no significant difference in the variables between the patients with and without osteosarcopenia (n = 34 each). The 5-year DFS and OS after PS matching in patients with osteosarcopenia were significantly worse than in patients without osteosarcopenia (17.6% vs. 38.8%, p = 0.013 and 20.6% vs. 57.4%, p = 0.0005, respectively). CONCLUSIONS: Preoperative osteosarcopenia could predict the DFS and OS of patients after resection for EBTC.

The Impact of Fibrinogen to Prognostic Nutritional Index Rate on Prognosis of Pancreatic Ductal Adenocarcinoma.

INTRODUCTION: The aim of the present study was to evaluate the prognostic value of the ratio of serum fibrinogen to prognostic nutritional index (PNI; Fbg/PNI) in patients undergoing resection for pancreatic ductal adenocarcinoma. METHODS: A total of 140 patients who had undergone resection for pancreatic cancer were included. Patients were divided into two groups according to a Fbg/PNI ≥8.8 or <8.8. Survival data were analyzed using the log-rank test for univariate analysis and Cox proportional hazards for multivariate analysis. RESULTS: Fbg/PNI was a significant prognostic indicator in univariate analysis for overall survival (OS) and disease-free survival (DFS). Fbg/PNI retained significance in multivariate analysis for OS (hazard ratio, 1.81; 95% confidence interval, 1.19-2.77; P < .01) in addition to tumor differentiation and nodal involvement. Fbg/PNI was a significant independent prognostic indicator of poor DFS on multivariate analysis (hazard ratio, 1.54; 95% confidence interval, 1.05-2.26; P = .03). CONCLUSION: Preoperative Fbg/PNI is a novel significant independent prognostic indicator for OS and DFS following resection of pancreatic cancer with curative intent.

Dynamics of the prognostic nutritional index in preoperative chemotherapy in patients with colorectal liver metastases.

BACKGROUND: Identifying the prognostic indicators that reflect the efficacy of preoperative chemotherapy is necessary. In this study, we investigated the prognostic indicators targeting the systemic inflammatory response for the administration of preoperative chemotherapy in patients with colorectal liver metastases. METHODS: Data for 192 patients were retrospectively analyzed. The relationship between overall survival and clinicopathological variables, including biomarkers such as the prognostic nutritional index, was investigated in patients who underwent upfront surgery or preoperative chemotherapy. RESULTS: In the upfront surgery group, extrahepatic lesion (p=0.01) and low prognostic nutritional index (p < 0.01) were significant prognostic indicators, whereas a decrease in the prognostic nutritional index (p=0.01) during preoperative chemotherapy were independent poor prognostic factors in the preoperative chemotherapy group. In particular, a decrease in the prognostic nutritional index was a significant prognostic marker in patients aged <75 years (p=0.04). In patients with a low prognostic nutritional index aged <75 years, preoperative chemotherapy significantly prolonged overall survival (p=0.02). CONCLUSION: A decrease in the prognostic nutritional index during preoperative chemotherapy predicted overall survival of patients with colorectal liver metastases after hepatic resection, and preoperative chemotherapy may be effective for patients aged <75 years with a low prognostic nutritional index.

A novel self-assembling peptide hemostatic gel as rescue therapy for fistula bleeding after endoscopic ultrasound-guided hepaticogastrostomy.

The novel synthetic self-assembling peptide PuraStat has been approved for hemostasis in endoscopic procedures. Nakahara and colleagues describe their application of PuraStat for hemostasis of refractory fistula bleeding after endoscopic ultrasound-guided hepaticogastrostomy. The effective and technically easy procedure is a useful option when hemostasis cannot be achieved by other means.

Osteosarcopenia predicts poor prognosis for patients with intrahepatic cholangiocarcinoma after hepatic resection.

PURPOSE: The concept of osteosarcopenia, which is concomitant osteopenia and sarcopenia, has been proposed as a prognostic indicator for cancer patients. The aim of this study was to evaluate the prognostic significance of osteosarcopenia in patients with intrahepatic cholangiocarcinoma (IHCC). METHODS: The subjects of this retrospective study were 41 patients who underwent hepatic resection for IHCC. Osteopenia was assessed with pixel density in the mid-vertebral core of the 11th thoracic vertebra and sarcopenia was assessed by the psoas muscle areas at the third lumbar vertebra. Osteosarcopenia was defined as the concomitant occurrence of osteopenia and sarcopenia. We analyzed the association of osteosarcopenia with disease-free and overall survival and evaluated clinicopathologic variables in relation to the osteosarcopenia. RESULTS: Eighteen (44%) of the 41 patients had osteosarcopenia. Multivariate analysis identified osteosarcopenia (hazard ratio 3.38, 95% confidence interval: 1.49-7.68, p < 0.01) as an independent predictor of disease-free survival, and age ≥ 65 years (p = 0.03) and osteosarcopenia (hazard ratio 6.46, 95% confidence interval: 1.76-23.71, p < 0.01) as independent predictors of overall survival. CONCLUSIONS: Preoperative osteosarcopenia may be a predictor of adverse prognosis for patients undergoing hepatic resection for IHCC, suggesting that preoperative management to maintain muscle and bone intensity could improve the prognosis.

Clinical outcomes and predictors of technical failure of endoscopic transpapillary gallbladder drainage in acute cholecystitis.

BACKGROUND AND AIMS: Endoscopic transpapillary gallbladder drainage (ETGBD) has been performed as an alternative therapy against cholecystectomy in patients with acute cholecystitis. To date, few studies have reported the safety, efficacy, and factors affecting ETGBD. We evaluated the clinical outcomes and predictors of technical failure of ETGBD. METHODS: Patients with acute cholecystitis who underwent ETGBD were retrospectively reviewed, and consecutive patients were included in the study. The technical success rate, clinical success rate, adverse events, and the predictors associated with the technical failure of ETGBD were investigated. RESULTS: A total of 242 patients were enrolled in the study. The technical success rate of ETGBD and clinical success rate of technically successful ETGBD cases were 87% and 93%, respectively. We experienced cystic duct injury in 24 patients as an ETGBD-related adverse event, and pancreatitis in 12 patients as an endoscopic retrograde cholangiopancreatography-related adverse event. Multivariate analysis indicated that cystic duct injury was the independent predictor associated with the technical failure of ETGBD (odds ratio, 11; 95% confidence interval, 3.9-29; p < 0.001). CONCLUSIONS: ETGBD was a safe and effective treatment method for acute cholecystitis with acceptable adverse events. There was no predictor based on the information from patient characteristics; however, cystic duct injury was associated with the technical failure of ETGBD.

The significance of osteosarcopenia as a predictor of the long-term outcomes in hepatocellular carcinoma after hepatic resection.

BACKGROUND: Frailty, represented by sarcopenia and osteopenia, has been associated with worse survival after hepatectomy in patients with hepatocellular carcinoma. Recently, the concept and term "osteosarcopenia" have been proposed, which has been associated with worse outcome in several malignancies. METHODS: This study included 227 patients who underwent elective hepatic resection for hepatocellular carcinoma. Osteopenia was evaluated with computed tomographic measurement of pixel density in the midvertebral core of the 11th thoracic vertebra. The skeletal muscle index (SMI) was evaluated with psoas muscle areas at the third lumbar vertebra. Osteosarcopenia was defined as the concomitant occurrence of osteopenia and low SMI. We retrospectively investigated the relationship between osteosarcopenia and disease-free and overall survival. RESULTS: Osteosarcopenia was identified in 27 (12%) of the patients. Multivariate analysis showed that osteosarcopenia (P < .001), C-reactive protein-to-albumin ratio ≥0.02 (P = .002), and stage ≥III (P ≤ .001) were independent predictors of disease-free survival, while osteosarcopenia (P < .001), Child-Pugh grade B (P = .002), C-reactive protein-to-albumin ratio ≥0.02 (P = .001), low SMI (P ≤ .001), and stage ≥III (P ≤ .001) were independent predictors of overall survival. CONCLUSION: Preoperative osteosarcopenia may be a prognostic factor in patients with hepatocellular carcinoma after hepatic resection. Our results suggests that the preoperative maintenance of skeletal muscle and bone density may potentially improve prognosis.

Long-term outcomes of endoscopic transpapillary gallbladder drainage using a novel spiral plastic stent in acute calculus cholecystitis.

BACKGROUND: Endoscopic transpapillary gallbladder stenting (EGBS) is considered for patients with contraindications to early surgery for acute calculus cholecystitis. However, evidence regarding the long-term outcomes of EGBS is insufficient to date. The aim of the study was to evaluate the feasibility of EGBS as a bridge to or alternative to surgery when there are contraindications. METHODS: We reviewed the cases of patients who underwent EGBS using a novel spiral-shaped plastic stent for acute calculus cholecystitis between January 2011 and December 2019. We retrospectively evaluated the long-term outcomes of EGBS using a novel spiral-shaped plastic stent. RESULTS: Forty-nine patients were included. The clinical success rate of EGBS was 97%. After EGBS, 25 patients (surgery group) underwent elective cholecystectomy and 24 patients did not (follow-up group). In the surgery group, the median period from EGBS to surgery was 93 days. There was a single late adverse event with cholecystitis recurrence. In the follow-up group, the median follow-up period was 236 days. Late adverse events were observed in eight patients, including recurrence of cholecystitis (four patients), duodenal penetration by the distal stent end (two patients), and distal stent migration (two patient). In the follow-up group, the time to recurrence of biliary obstruction was 527 days. CONCLUSIONS: EGBS with a novel spiral-shaped plastic stent is safe and effective for long-term acute calculus cholecystitis. There is a possibility of EGBS to be a bridge to surgery and a surgical alternative for acute calculus cholecystitis in patients with contraindications to early cholecystectomy.

Significant impact of cachexia index on the outcomes after hepatic resection for colorectal liver metastases.

Introduction: The purpose of this study was to investigate the relation between preoperative cachexia index (CXI) and long-term outcomes in patients with colorectal liver metastases (CRLM) after hepatic resection. Method: In all,118 patients who underwent hepatic resection for CRLM were analyzed retrospectively. The relationship between CXI and the long-term outcomes in patients after hepatic resection was investigated. CXI was calculated based on preoperative skeletal muscle index, serum albumin level, and neutrophil-lymphocyte ratio. Results: The multivariate analysis showed that extrahepatic lesion (hazard ratio [HR] 2.86, 95% confidence interval [CI] 1.48-5.53, P < .01) and high CXI (HR 0.44, 95% CI 0.20-0.98, P = .04) were independent and significant predictors of disease-free survival. Moreover, extrahepatic lesion (HR 2.32, 95% CI 1.03-5.22, P = .04), high CXI (HR 0.17, 95% CI 0.05-0.57, P < .01), and curability R 1 or 2 (HR 3.29, 95% CI 1.23-8.78, P = .02) were independent and significant predictors of overall survival. Conclusion: CXI is a useful prognostic factor for disease-free survival and overall survival after hepatic resection in CRLM patients.

Clinical significance of cachexia index in patients with hepatocellular carcinoma after hepatic resection.

BACKGROUND: Cancer cachexia has been associated with unfavorable outcomes in several malignancies. The cachexia index (CXI), which consists of skeletal muscle, inflammation, and nutritional status, has been proposed as a novel biomarker of cachexia. Therefore, we here investigated prognostic value of the CXI in patients with hepatocellular carcinoma (HCC) after hepatic resection. METHODS: The study comprised 213 patients who had undergone primary hepatic resection for HCC between 2008 and 2018. First, the skeletal muscle index (SMI) was calculated as the area of the psoas muscle at the third lumbar vertebra/(the height)2. The CXI was then calculated by the following formula: SMI x serum albumin level/neutrophil-to-lymphocyte ratio (NLR). We retrospectively investigated the relationship between the CXI and disease-free survival as well as overall survival. RESULTS: In multivariate analyses, female (p < 0.01), hepatitis B surface antigen-positivity (p < 0.01), preoperative serum alpha-fetoprotein level ≥20 ng/mL (p = 0.01), preoperative serum protein induced by vitamin K absence or antagonist-II level ≥200 mAU/mL (p = 0.02), multiple tumors (p < 0.01), macrovascular invasion (p = 0.04), type of resection (p < 0.01), and low CXI (p = 0.03) were significant predictors of disease-free survival, while Child-Pugh grade B (p < 0.01), poor tumor differentiation (p = 0.05), multiple tumors (p = 0.01), macrovascular invasion (p = 0.04), NLR (p = 0.04), and low CXI (p < 0.01) were significant predictors of overall survival. In the subgroup analysis of advanced T stage, the CXI was associated with both disease-free (p < 0.01) and overall survival (p = 0.06). CONCLUSIONS: The CXI can be a prognostic indicator in patients with HCC after hepatic resection, suggesting the importance of comprehensive biomarker which includes skeletal muscle, inflammation, and nutritional status.

Well-differentiated liposarcoma causing non-islet cell tumor hypoglycemia.

Non-islet cell tumor hypoglycemia (NICTH) is a paraneoplastic syndrome that causes severe hypoglycemia. The tumor involved produces high-molecular-weight insulin-like growth factor-II (IGF-II). NICTH can be caused by various benign and malignant tumors. However, NICTH due to liposarcoma (LPS) is rare. A 38-year-old man was brought to the hospital emergency department with complaints of vomiting and unconsciousness. His abdomen was distended, and a large tumor was palpable. He had severe hypoglycemia that required continuous glucose infusion. Radiological examination revealed a large 40-cm mass that filled the abdominal cavity, and LPS of the mesentery was suspected. Laboratory data showed low levels of insulin, C-peptide, and IGF-I concentrations. Subsequently, an LPS-induced NICTH was suspected. Complete resection of the tumor and the encased small intestine was performed. The pathological diagnosis was well-differentiated liposarcoma (WDLPS). The Western immunoblot showed that the high-molecular-weight IGF-II confirmed in the serum preoperatively, had almost disappeared postoperatively. Based on these findings, NICTH caused by a WDLPS was diagnosed. The postoperative course was uneventful. In the last 4 years since the primary operation, the patient had not experienced further hypoglycemia symptoms. Here, we report a case of NICTH caused by a large WDLPS. NICTH should be considered in patients with both severe hypoglycemia and large tumors. In these cases, appropriate treatment including semi-urgent surgery should be provided.

Living donor liver transplantation for idiopathic portal hypertension with focal nodular hyperplasia.

The patient was a 61-year-old woman with a history of diabetes mellitus who had undergone ileocecal resection for ascending colon carcinoma 5 years earlier, followed by a postoperative adjuvant chemotherapy with XELOX (capecitabine + oxaliplatin). During follow-up, the liver gradually atrophied, and radiological imaging showed suspicious findings of 20 × 14 mm hepatocellular carcinoma (HCC) in the right lobe of the liver. The patient also underwent endoscopic variceal ligation for the esophageal varices. She was referred to our hospital for living donor liver transplantation (LDLT) due to decompensated liver cirrhosis with HCC. The patient did not have hepatitis B or C, and history of alcohol, suggesting that her liver cirrhosis was caused by a non-alcoholic steatohepatitis. The Child-Pugh score was 10 points (class C) and the Model for End-Stage Liver Disease (MELD) score was 8 points. The possibility of HCC could not be ruled out, and LDLT was performed. Postoperative pathological examination revealed idiopathic portal hypertension (IPH), and the mass lesion was diagnosed as focal nodular hyperplasia (FNH). The postoperative course was uneventful and the patient was discharged on postoperative day 14. This is the first case of liver transplantation for IPH with FNH.

Conversion surgery for undifferentiated carcinoma with osteoclast-like giant cells of the pancreas: a case report.

BACKGROUND: Undifferentiated carcinoma with osteoclast-like giant cells (UCOGCs) is a rare subtype of pancreatic cancer (PC), and its clinicopathological characteristics are still unclear. Herein, we report a case of initially unresectable UCOGC that was successfully resected after FOLFIRINOX therapy. CASE PRESENTATION: A 63-year-old man was referred to us for evaluation of a pancreatic mass detected by computed tomography (CT) during a medical checkup. Computed tomography showed a 7.5-cm tumor located in the pancreatic head and body, which involved the common hepatic artery (CHA), gastroduodenal artery (GDA), and main portal vein (PV) with tumor thrombus. UCOGC was suspected by endoscopic ultrasonography-guided fine needle aspiration, and the patient was diagnosed with unresectable locally advanced pancreatic cancer. After ten cycles of FOLFIRINOX, the tumor size decreased to 3 cm and the tumor thrombus in the main portal trunk had disappeared in the follow-up CT scan. However, the patient experienced severe adverse drug reactions, including neutropenia and liver dysfunction. Therefore, we performed pancreatoduodenectomy with portal vein resection. The pathological diagnosis was UCOGC with a negative tumor margin. He was treated with FOLFIRINOX, and remains recurrence-free for 6 months after surgery. CONCLUSIONS: We experienced a case undergoing conversion surgery for unresectable UCOGC, which resulted in R0 resection. FOLFIRINOX could be a possible regimen to achieve conversion surgery for UCOGC.

Technique of straightening the guidewire using a balloon catheter for successful endoscopic transpapillary gallbladder stenting.

Video 1The technique of straightening the guidewire, looped in the neck of the gallbladder because of segmental adenomyomatosis, using a balloon catheter during endoscopic transpapillary gallbladder stent placement.

Visceral disseminated varicella-zoster virus infection in an immunocompetent host.

Varicella-zoster virus (VZV) can cause visceral disseminated VZV infection in immunocompromised patients. We experienced visceral disseminated VZV infection in an immunocompetent host. A 78-year-old woman visited our hospital complaining of abdominal pain that had persisted for 7 days. On day 3 after admission, a skin rash with blisters appeared mainly on her head and trunk that was diagnosed as generalized zoster via rapid skin VZV diagnostic kit. Esophagogastroduodenoscopy showed gastric erosions, and VZV was detected by real-time polymerase chain reaction testing of the gastric mucosal biopsy specimen. Computed tomography imaging also revealed pancreatitis and colitis, and she was diagnosed as having visceral disseminated VZV infection involving multiple organs. She was treated with acyclovir intravenously, after which her skin rash and abdominal pain disappeared. Because visceral disseminated VZV infection can occur in immunocompetent patients, this disease should be considered in patients with unexplained inflammatory lesions of the gastrointestinal tract or pancreas.

Double-guidewire technique for endoscopic transpapillary gallbladder stenting.

Highlight Endoscopic transpapillary gallbladder stenting is effective for acute cholecystitis with high surgical risk. However, looping of the guidewire in the cystic duct sometimes impedes placement of the stent. Nakahara and colleagues present a case of successful endoscopic transpapillary gallbladder stenting after straightening the looped guidewire using a double-guidewire technique.

Efficacy of endoscopic large balloon dilation extended for 2 minutes in bile duct stone removal: A multicenter retrospective study.

BACKGROUND/PURPOSE: There is no evidence regarding the optimal balloon dilation time during endoscopic papillary large balloon dilation (EPLBD). The study aim was to evaluate the efficacy of 2-minute extended balloon dilation for EPLBD. METHODS: Two hundred and five patients who underwent EPLBD during endoscopic retrograde cholangiopancreatography (ERCP) for bile duct stones at three tertiary centers were included in the analysis. Clinical outcomes and the adverse events were compared between the 0-minute group (n = 94, balloon deflated immediately after waist disappearance) and the 2-minute group (n = 111, balloon dilation maintained for 2 minutes after waist disappearance). The risk factors of post-ERCP pancreatitis (PEP) after EPLBD were assessed. RESULTS: There were no significant differences in the stone removal rates and hospitalization periods between the two groups. However, the total ERCP procedure time was significantly shorter in the 2-minute group (40.6 vs 48.9 min, P = .03). The incidence of PEP was 7.4% in the 0-minute group and significantly lower at 0.9% in the 2-minute group (P = .04). Multivariate analysis identified without 2-minute extended EPLBD as a significant risk factor of PEP (OR: 9.9, P = .045). CONCLUSIONS: Extension of EPLBD for 2 minutes helped prevent PEP and shortened the procedure time.