Indications and waiting list priority for deceased donor liver transplantation in HIV/HCV co-infected hemophilic patients in Japan through contaminated blood product.

HIV/HCV co-infection from blood products for hemophilia has been a social problem in Japan. Liver transplantation (LT) is an important treatment option for hepatic failure and cirrhosis of the liver in co-infected patients, and appropriate indications for LT, especially organ form deceased donors, are required by society. The aim is to propose priority status for the waiting list for deceased donor (DD) LT in HIV/HCV co-infected patients in Japan based on medical and scientific considerations. Since 2009, we have been working on the subject in research projects under grants-in-aid for health and labour sciences research on AIDS measures provided by the Ministry of Health, Labour and Welfare (the Kanematsu project and Eguchi project). Our research showed that hepatic fibrosis is advanced in HIV/HCV co-infected Japanese patients, especially those with hemophilia who became infected from blood products at a faster rate than HCV mono-infected patients. In addition, those patients who developed portal hypertension had a poor prognosis at a young age. The results of our research contributed to increasing the priority score of those patients on the deceased donor liver transplantation (DDLT) waiting list in 2013 and to establishing a scoring system for DDLT corresponding to the Model for End-stage Liver disease (MELD) score in 2019. This paper introduces changes in priority and the current state of priority of the DDLT waiting list for HIV/HCV co-infected patients in Japan.

Wisteria floribunda agglutinin-positive human Mac-2-binding protein as a predictive marker of liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfected patients.

AIM: In human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfected patients, the progression of liver failure is reported to be more aggressive than that in HCV mono-infected patients. Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA+ -M2BP) is well recognized as a liver fibrosis glycobiomarker with a unique fibrosis-related glycoalteration. We analyzed HIV/HCV coinfected patients' M2BP levels as a possible marker for predicting liver fibrosis. METHODS: M2BP was measured in 31 HIV/HCV coinfected patients, and we analyzed the correlation between WFA+ -M2BP and several markers of fibrosis, liver function, and tumor markers. We compared the WFA+ -M2BP levels in HIV/HCV coinfected patients with those of HCV mono-infected patients by performing a propensity score matching analysis. RESULTS: In the HIV/HCV coinfected patients, the serum level of WFA+ -M2BP was well correlated with the markers type IV collagen, hyaluronic acid, and alpha-fetoprotein, but not protein induced by vitamin K absence-II. In the propensity score matching with HCV mono-infected patients, the WFA+ -M2BP levels were significantly higher in the HIV/HCV coinfected patients compared with the levels in the HCV mono-infected patients. CONCLUSION: In conclusion, WFA+ -M2BP might be a feasible predictive marker of fibrosis in HIV/HCV coinfected patients.

Relationship between various hepatic function scores and the formation of esophageal varices in patients with HIV/hepatitis C virus co-infection due to contaminated blood products for hemophilia.

AIM: It is reportedly difficult to accurately assess the liver reserve capacity of patients with HIV/hepatitis C virus (HCV) co-infection through contaminated blood products by the Child-Pugh (CP) classification. Therefore, we investigated a clinically applicable scoring system in determining the risk of esophageal varices in HIV/HCV co-infected patients, known as latent portal hypertension leading to esophageal varices. METHODS: Forty-three patients with HIV/HCV co-infection underwent clinical examinations, including endoscopy and assessment of hepatic reserve, in our department between 2009 and 2017. Child-Pugh score, the recently developed albumin-bilirubin (ALBI) grade, and the albumin-indocyanine green evaluation (ALICE) were compared to evaluate their diagnostic accuracy for the detection of esophageal varices using the area under the receiver operating characteristic curve (AUROC). RESULTS: The patients were all male hemophiliacs and were positive for both HIV and HCV antibodies, with a median age of 45 years (range, 29-66 years). Thirty-seven patients (84.1%) were classified as CP A at the examination. The comparison of AUROCs showed a superior diagnostic accuracy for ALICE (AUROC = 0.814) to detect esophageal varices. The positive prediction rate was the highest with ALICE if -2.325 was set, and the negative prediction rate was the highest with ALBI if -2.575 was set. The ALICE showed the highest accuracy compared to other two scores. CONCLUSION: The ALICE score was found to be the most valuable system for portal hypertension in HIV/HCV co-infected hemophilia patients. Because of its high specificity, ALICE for secondary surveillance could be used after other markers such as the aspartate aminotransferase to platelet ratio index and Fibrosis-4 index.

Standardized hybrid living donor hemihepatectomy in adult-to-adult living donor liver transplantation.

The aim of this study was to analyze the outcomes of the most updated version and largest group of our standardized hybrid (laparoscopic mobilization and hepatectomy through midline incision) living donor (LD) hemihepatectomy compared with those from a conventional laparotomy in adult-to-adult living donor liver transplantation (LDLT). Of 237 adult-to-adult LDLTs from August 1997 to March 2017, 110 LDs underwent the hybrid procedure. Preoperative and operative factors were analyzed and compared with conventional laparotomy (n = 126). The median duration of laparoscopic usage was 26 minutes in the hybrid group. Although there was improvement in applying this procedure over time from the beginning of the series of cases studied, blood loss and operative duration were still smaller and shorter in the hybrid group. There was no significant difference between the groups in the incidence of postoperative complications greater than or equal to Clavien-Dindo class III. There was no difference in recipient outcome between the groups. Our standardized procedure of hybrid LD hepatectomy is applicable and safe for all types of LD hepatectomies, and it enables the benefit of both the laparoscopic and the open approach in a transplant center without a laparoscopic expert. Liver Transplantation 24 363-368 2018 AASLD.

Pretransplant serum procalcitonin level for prediction of early post-transplant sepsis in living donor liver transplantation.

AIM: Infection is a frequent cause of in-hospital mortality after liver transplantation (LT). Elimination of possible risks in the pretransplant period, early diagnosis of post-transplant sepsis, and prompt treatment with antimicrobial agents are important. The objectives of this study were to analyze the impact of early post-transplant sepsis on outcomes and to clarify the value of predictive factors for early post-transplant sepsis. METHODS: The study included 136 patients who underwent initial living donor LT (LDLT) at our institute between April 2009 and December 2016. Sepsis was defined using the third international consensus criteria. The results of biochemical tests at the introduction of anesthesia before LDLT were collected for pretransplant evaluation. RESULTS: Post-transplant sepsis was found in 37 patients (27.2%). More patients had a pre-transplant serum procalcitonin (PCT) level >0.5 ng/mL in the sepsis group than in the non-sepsis group (11 [29.7%] vs 10 [10.1%]; P = 0.007). The 1-year survival rate in the sepsis group was significantly lower than in the non-sepsis group (53.8% vs 87.2%; P < 0.001). Multivariate analysis identified pretransplant serum PCT >0.5 ng/mL (odds ratio, 3.8; 95% confidence interval, 1.3-10.9; P = 0.01) as the only independent risk factor for post-transplant sepsis. CONCLUSIONS: Survival of patients with early post-transplant sepsis was poor and the incidence of sepsis was associated with the pretransplant serum PCT level. Re-evaluation of the general condition and rescheduling of LT should be considered in a patient with pretransplant serum PCT >0.5 ng/mL.

Aspartate transaminase-platelet ratio and Fibrosis-4 indices as effective markers for monitoring esophageal varices in HIV/hepatitis C virus co-infected patients due to contaminated blood products for hemophilia.

AIM: We examined the feasibility of the aspartate transaminase (AST)-platelet ratio index (APRI) and Fibrosis-4 (FIB4) score, which are well-established markers for liver fibrosis, as indicators for monitoring esophageal varices in patients who were co-infected with HIV and hepatitis C virus (HCV) due to contaminated blood products for hemophilia in Japan. METHODS: Forty-three HIV/HCV co-infected patients were enrolled. All were hemophilic men (median age 41 years; range, 29-66 years). We analyzed the correlations between fibrosis indices (APRI, FIB4) and various liver function tests, fibrosis markers, liver stiffness measured by acoustic radiation force impulse elastography, and the findings of gastrointestinal endoscopy. RESULTS: Both APRI and FIB4 were well correlated with several of the factors related to liver fibrosis and the existence of esophageal varices in the patients. The cut-off values for detecting esophageal varices estimated as the area under the receiver operating characteristic curve were 0.85 for APRI and 1.85 for FIB4. CONCLUSION: In patients co-infected with HIV/HCV due to contaminated blood products for hemophilia, APRI and FIB4 are effective for monitoring esophageal varices, even among patients who are apparently doing well with good liver function as Child-Pugh grade A.

The donor advocacy team: a risk management program for living organ, tissue, and cell transplant donors.

BACKGROUND AND PURPOSE: Although the incidence of living donor death is low in Japan, statistics show one living liver donor death in more than 7000 living liver transplants. Thus, medical transplant personnel must recognize that the death of a living organ or tissue transplant donor can occur and develop an appropriate risk management program. METHODS AND RESULTS: We describe how Nagasaki University Hospital established and implemented a Donor Advocacy Team (DAT) program: a risk management program for initiation in the event of serious, persistent, or fatal impairment of an organ, tissue, or cell transplantation from a living donor. DISCUSSION: The purposes of the DAT program are as follows: 1. To disclose official information without delay. 2. To provide physical and psychological care to the patient experiencing impairment and their family. 3. To provide psychological care to the medical staff in charge of the transplant. 4. To standardize the responses of the diagnosis and treatment department staff and other hospital staff. 5. To minimize the damage that the whole medical transplantation system may suffer and leverage the occurrence for improvement. To address (1) and (5), actions, such as reporting and responses to the government, mass media, transplant-related societies, and organ transplant networks, have been established to ensure implementation.

Analysis of early relaparotomy following living donor liver transplantation.

We retrospectively analyzed the causes, risk factors, and impact of early relaparotomy after adult-to-adult living donor liver transplantation (LDLT) on the posttransplant outcome. Adult recipients who underwent initial LDLT at our institution between August 1997 and August 2015 (n = 196) were included. Any patients who required early retransplantation were excluded. Early relaparotomy was defined as surgical treatment within 30 days after LDLT. Relaparotomy was performed 66 times in 52 recipients (a maximum of 4 times in 1 patient). The reasons for relaparotomy comprised postoperative bleeding (39.4%), vascular complications (27.3%), suspicion of abdominal sepsis or bile leakage (25.8%), and others (7.6%). A multivariate analysis revealed that previous upper abdominal surgery and prolonged operative time were independent risk factors for early relaparotomy. The overall survival rate in the relaparotomy group was worse than that in the nonrelaparotomy group (6 months, 67.3% versus 90.1%, P < 0.001; 1 year, 67.3% versus 88.6%, P < 0.001; and 5 years, 62.6% versus 70.6%, P = 0.06). The outcome of patients who underwent 2 or more relaparotomies was worse compared with patients who underwent only 1 relaparotomy. In a subgroup analysis according to the cause of initial relaparotomy, the survival rate of the postoperative bleeding group was comparable with the nonrelaparotomy group (P = 0.96). On the other hand, the survival rate of the vascular complication group was significantly worse than that of the nonrelaparotomy group (P = 0.001). Previous upper abdominal surgery is a risk factor for early relaparotomy after LDLT. A favorable longterm outcome is expected in patients who undergo early relaparotomy due to postoperative bleeding. Liver Transplantation 22 1519-1525 2016 AASLD.

Does the development of chronic kidney disease and acute kidney injury affect the prognosis after living donor liver transplantation?

BACKGROUND AND AIMS: Chronic kidney disease (CKD) and acute kidney injury (AKI) have been discussed as complications following living donor liver transplantation (LDLT). The aim of this study was to clarify the relationships among CKD, AKI, and the prognosis after LDLT. METHODS: This study included 118 patients who underwent LDLT in our department. A low eGFR (<60 mL/min/1.73 m(2) ) was regarded to indicate CKD. AKI 1 and AKI 2 were characterized by an increase in the serum creatinine level of 0.5 and 1.0 mg/dL, respectively, within one wk after LDLT. We investigated the risk factors for and the relevance of CKD and AKI on the prognosis. RESULTS: AKI 1 was associated with sepsis and intra-operative bleeding (p = 0.0032, p = 0.001). AKI 2 was associated with sepsis and hepatitis C infection (p < 0.001, p = 0.027). A pre-operative eGFR of 60-89 and diabetes were the risk factors for the development of CKD in POY 2 (p = 0.018, p = 0.002). AKI 2, sepsis, and diabetes were the risk factors for the patient death within one yr after LDLT (p = 0.010, p = 0.002, p = 0.022). AKI 2 and sepsis were the risk factors for death within two yr after LDLT (p = 0.005, p = 0.018). CONCLUSIONS: Recognizing the risk factors and careful management for preventing both AKI and CKD may improve the prognosis of patients following LDLT.

A correlation between the graft volume evaluation and the prognosis in consideration of hepatic "compliance" in living donor liver transplantation.

BACKGROUND/AIMS: The aim is to clarify the correlation between the hepatic compliance and prognosis of the patients who underwent LDLT. METHODOLOGY: Volumetry was performed using a 3D volume analyzer. The hepatic compliance was evaluated based on the difference between the estimated total liver volume in the arterial phase and venous phase (n=66). The correlations among the hepatic compliance, donor background factors and the recipient's prognosis were evaluated. RESULTS: Fourteen cases (21%) presented with a more than 5% increase in volume during the venous phase than in the arterial phase, and 12 of these recipients were still alive. There was a significant increase in death among recipients from donors age 60 years old and older (5/7, 71.4%, p<0.01). In these cases, the hepatic compliance was significantly different between the deceased cases and the surviving cases; while there was no hepatic compliance in the five deceased cases, favorable hepatic compliance was observed in two of the surviving cases (p<0.01). CONCLUSIONS: Hepatic compliance appears to exist. The poor prognosis of liver grafts in recipients from elderly donors may be attributable to hepatic compliance, and assessing the hepatic compliance may be useful for preoperative liver graft evaluation.

A hybrid method of laparoscopic-assisted open liver resection through a short upper midline laparotomy can be applied for all types of hepatectomies.

BACKGROUND: Although hepatectomy procedures should be designed to provide both curability and safety, minimal invasiveness also should be pursued. METHODS: We analyzed the data related to our method for laparoscopy-assisted open resections (hybrid method) through a short upper midline incision for various types of hepatectomies. Of 215 hepatectomies performed at Nagasaki University Hospital between November 2009 and June 2012, 102 hepatectomies were performed using hybrid methods. RESULTS: A hybrid method was applicable for right trisectionectomy in 1, right hemihepatectomy in 32, left hemihepatectomy in 29, right posterior sectionectomy in 7, right anterior sectionectomy in 1, left lateral sectionectomy in 2, and segmentectomy in 7 patients, and for a minor liver resection in 35 patients (12 combined resections). The median duration of surgery was 366.5 min (range 149-709) min, and the median duration of the laparoscopic procedure was 32 min (range 18-77) min. The median blood loss was 645 g (range 50-5,370) g. Twelve patients (12 %) developed postoperative complications, including bile leakage in three patients, wound infections in two patients, ileus in two patients, and portal venous thrombus, persistent hyperbilirubinemia, incisional hernia, local liver infarction each in one patient. There were no perioperative deaths. CONCLUSIONS: Our method of hybrid hepatectomy through a short upper midline incision is considered to be applicable for all types of hepatectomy and is a reasonable approach with no abdominal muscle disruption, which provides safe management of the hepatic vein and parenchymal resection even for patients with bilobular disease.

[Acoustic radiation force impulse elastography for liver disease staging in human immunodeficiency virus and hepatitis C virus co-infection].

BACKGROUND: Survival of human immunodeficiency virus (HIV)-infected patients has improved due to the widespread use of anti-retroviral therapy. However, mortality has increased when HIV-infected patients are co-infected with hepatitis C virus (HCV), and the liver disease in such patients is rapidly progressive compared with that in HCV monoinfected patients. Therefore, accurate staging of the liver disease is critical when determining appropriate treatment. AIM: To clarify the efficacy of acoustic radiation force impulse (ARFI) elastography for the evaluation of liver fibrosis and hepatic functional reserve in HIV/HCV co-infected patients. METHODS: The correlation of shear wave velocity (Vs), measured by ARFI elastography, with liver fibrosis or hepatic functional reserve was analyzed. RESULTS: Vs was significantly correlated with platelet count, splenic volume, hyaluronic acid, type IV collagen, and LHL15 (receptor index: uptake ratio of the liver to the liver plus heart at 15min) in 99mTc-GSA (technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin) scintigraphy. CONCLUSION: ARFI elastography was useful for the staging of liver disease in HIV/HCV co-infected patients and it facilitated minimally invasive and accessible evaluation of fibrosis and functional reserve.

A comparison of postoperative pain between transumbilical and suprapubic incision in laparoscopic liver resection.

BACKGROUND: In laparoscopic liver resection, few reports have investigated the influence of type of incision on postoperative pain in laparoscopic liver resection. We therefore conducted the present study to clarify the difference in postoperative pain between two types of incision. METHODS: Nineteen patients who underwent laparoscopic lateral sectionectomy were enrolled. In 11 patients with a transumbilical incision and eight with a suprapubic incision, the operation duration, blood loss, length of incision, duration of intravenous fentanyl infusion immediately after surgery and rescue dosage, and period of regular oral nonsteroidal anti-inflammatory drugs were evaluated. RESULTS: There was no significant difference between the two groups in patients' background characteristics, operation time, or amount of blood loss. The length of suprapubic incision was significantly longer than the umbilical incision. Concerning the postoperative pain management, the duration of intravenous fentanyl administration was 1 day (1-2 days) for umbilical incisions and 1.5 days (1-2 days) for suprapubic incisions, showing no significant difference. Regarding the rescue dosage of fentanyl, the results were comparable between the groups. Regarding the postoperative duration of regular nonsteroidal anti-inflammatory drug administration, there was also no significant difference between the groups (transumbilical: 14 [5-35] days vs suprapubic: 8 [7-32]). CONCLUSIONS: Postoperative pain is comparable between umbilical and suprapubic incision in patients who underwent laparoscopic left lateral segmentectomy. In terms of postoperative pain, either a transumbilical incision or a suprapubic incision can be selected for specimen extraction.

A Single-site Interventional Study on the Contemporary Relevance of Braun Enteroenterostomy After Pancreaticoduodenectomy.

BACKGROUND/AIM: Braun enteroenterostomy following pancreaticoduodenectomy is a standard procedure. It has been reported to decrease bile reflux and vomiting, prevent reflux gastritis and delay gastric emptying (DGE). However, some reports suggest that the incidence of DGE is unaffected with this procedure. Therefore, in this study, we aimed to investigate whether Braun enteroenterostomy was effective after pancreaticoduodenectomy. PATIENTS AND METHODS: A total of 145 patients who underwent pancreaticoduodenectomy were enrolled and divided into 2 groups i.e., 51 patients with Braun enteroenterostomy (B group) and 94 patients without Braun enteroenterostomy (non-B group). We compared the perioperative data of the patients. Patients who reported postoperative symptoms underwent gastrointestinal endoscopic evaluation. RESULTS: The incidence of DGE was 7.4% (7/94) and 1.9% (1/51) in the non-B and B groups, respectively (p=0.36), with no significant difference between the groups. During follow-up, some patients reported symptoms including epigastralgia, nausea and melena. The incidence of these symptoms was 27.7% (26 patients; 26/94) and 23.5% (12 patients; 12/51) in non-B and B groups, respectively. Regarding gastrointestinal endoscopic findings, the incidence of anastomotic ulcer was 7.7% (2/26) and 16.7% (2/12) in non-B and B groups, respectively (p=0.40). Bile reflux incidence was 30.8% (8/26) and 0% (0/12) in non-B and B groups, respectively (p=0.03). CONCLUSION: Though Braun enteroenterostomy was related to bile reflux, it did not affect the incidence of anastomotic and gastric ulcers or DGE. Therefore, it may not be a necessary procedure after pancreaticoduodenectomy.

The Efficacy of Acoustic Radiation Force Impulse Elastography for Predicting Clinical Outcomes in Living Donor Liver Transplant.

PURPOSE: Acoustic radiation force impulse (ARFI) elastography is widely used for evaluating liver fibrosis. Here we evaluated the efficacy of ARFI elastography for estimating graft quality and clinical outcomes in living donor liver transplant (LDLT). METHODS: We retrospectively evaluated the cases of 87 LDLT donors who preoperatively underwent ARFI elastography at Nagasaki University Hospital between August 2010 and June 2016. We analyzed whether the velocity of shear wave (Vs) obtained by ARFI elastography affected the regeneration rate of each donor's remnant liver and the 1-year survival rate of the recipients. RESULTS: There were no significant correlations between Vs value and the donors' age. Only 1 donor (1.1%) showed significant fibrosis, F2 (portal fibrosis with few septa) in zero-biopsy. The 7 donors (8.0%), including 1 case, showed a high Vs value (> 1.33) that was equal to F2, although there was no abnormal pathologic finding except in 1 case. In those cases, the regeneration rate of the remnant liver after hepatectomy was significantly lower compared to other cases. The 1-year survival rate of the recipients paired with the high-Vs donors was also significantly poorer than that of the other cases (high-Vs: 57.1%, others: 84.2%, P = .04). CONCLUSIONS: ARFI elastography might be an effective examination for the preoperative evaluation of the graft quality in LDLT.

Long-term culture of rat hepatocytes using human amniotic membrane as a culture substrate.

Amniotic membrane is attracting attention as a new material for regenerative medicine. We herein report that the culture of primary rat hepatocytes on human amniotic membrane maintained their morphology and their production of albumin for at least two months. Human amniotic membrane was collected during planned cesarean section and kept frozen until usage. Primary rat hepatocytes were plated on human amniotic membrane. Hepatocytes accumulated as colonies on amniotic membrane, and their rat albumin level was maintained for two months. Their three-dimensional structure on extracellular matrix, which is abundant in amniotic membranes might influence the maintenance of the hepatocyte-specific function.

Prevention of delayed gastric emptying after living donor left hepatectomy.

BACKGROUND: Delayed gastric emptying (DGE) is uncomfortable complication after left hepatectomy. The aim of this study is to show our strategy to prevent DGE after living donor left hepatectomy. METHODS: The cases were divided into 3 groups as without any prevention (control group), prevented DGE with putting omentum between the liver and pylorus (O group), and with putting a Seprafilm (S group). The incidence of DGE and the CT finding 1 month after surgery were retrospectively compared between the groups. RESULTS: The incidence of DGE was significantly decreased in O and S group than control group (P < 0.05, Fisher's test). In S group, fluid collection along the cutting surface of the liver was observed on CT significantly more than other groups, but the incidence of bile leakage was adversely less in S groups than other groups, meaning that collected fluid in S group were presumed as the ascites without bile. CONCLUSION: Omentum patching and Seprafilm were equally effective to prevent DGE after living donor left hepatectomy, and Seprafilm might be better because it is more physiologic.

Pancreaticoduodenectomy can be indicated for elderly patients: risk prediction using the estimation of physiologic ability and surgical stress (E-PASS) system.

BACKGROUND: Pancreaticobiliary malignant diseases are primarily treated by surgical resection. However, the surgical indications for elderly patients, especially for pancreaticoduodenectomy (PD), must be carefully considered due to patient compliance. Whether PD can contribute to better prognoses in elderly patients remains unclear. Therefore, we aimed to evaluate the complications, compliance, and survival of elderly and non-elderly patients who underwent PD in our department. METHODS: We retrospectively analyzed 282 patients who underwent PD from 2000 to 2017 and divided them into non-elderly (aged ≤ 79 years, n = 238) and elderly (aged ≥ 80 years, n = 44) groups. The estimation of physiologic ability and surgical stress (E-PASS) system was used to evaluate morbidity and mortality using preoperative risk score (PRS), surgical stress score (SSS), and comprehensive risk score (CRS). RESULTS: Preoperative risk score was higher in the elderly group than in the non-elderly group, although SSS and CRS were similar. No significant differences were detected in the occurrence of postoperative complications. In the elderly group, CRS was higher in patients with complications than in those without. Long-term outcomes evaluated by overall and disease-specific survival were not significantly different. CONCLUSIONS: In the elderly patients, E-PASS especially CRS can predict the occurrence of complications. The safety and prognoses of elderly patients after PD are comparable with those of non-elderly patients.

Aberrant common hepatic artery from the left gastric artery and with no connection to the gastroduodenal artery: Risky vascular anomaly in gastrectomy.

Knowledge of anatomical variations of the celiac axis is important in upper abdominal surgery. Aberrant common hepatic artery originating from the left gastric artery without connecting the gastroduodenal artery is extremely rare. Preoperative vascular anatomy assessment using reconstructions of CT images may be useful for safe surgical procedure.