Author Affiliations: Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China (Ni YB, Gao PJ, Wang D, Li Z and Zhu JY)

Corresponding Author: Ji-Ye Zhu, MD, Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China (Tel/Fax: +86-10-68310585; Email: gandanwk@vip.sina.com)

 

© 2015, Hepatobiliary Pancreat Dis Int. All rights reserved.

doi: 10.1016/S1499-3872(15)60328-9

Published online January 2, 2015.

Contributors: ZJY proposed the study. NYB and GPJ performed research and wrote the first draft. WD and LZ collected and analyzed the data. ZJY revised the manuscript. NYB and GPJ contributed equally to this research. All authors contributed to the design and interpretation of the study and to further draft. ZJY is the guarantor.

Funding: This study was supported by grants from the Health Industry Scientific Research Fund (201002015) and Beijing Medicine Research and Development Fund (2009-2029).

Ethical approval: Informed consent was obtained from each patient, and this study was approved by the ethics committee of Peking University People's Hospital.

Competing interest: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

BACKGROUND: Esophagogastric variceal hemorrhage is a life-threatening complication of portal hypertension. In this study, we compared the therapeutic effect of a novel surgical procedure, esophagogastric devascularization without splenectomy (EDWS), with the widely used modified esophagogastric devascularization (MED) with splenectomy for the treatment of portal hypertension.

 

METHODS: Fifty-five patients with portal hypertension were included in this retrospective study. Among them, 27 patients underwent EDWS, and the other 28 patients underwent MED. Patients' characteristics, perioperative parameters and long-term follow-up were analyzed.

 

RESULTS: The portal venous pressure was decreased by 20% postoperatively in both groups. The morbidity rate of portal venous system thrombosis in the EDWS group was significantly lower than that in the MED group (P=0.032). The 1- and 3-year recurrence rates of esophagogastric variceal hemorrhage were 0% and 4.5% in the EDWS group, and 0% and 8.7% in the MED group, respectively (P=0.631).

 

CONCLUSIONS: EDWS is a safe and effective treatment for esophagogastric varices secondary to portal hypertension in selected patients. Patients treated with EDWS had a lower complication rate of portal venous system thrombosis compared with those treated with conventional MED.

 

(Hepatobiliary Pancreat Dis Int 2015;14:276-280)

 

KEY WORDS: portal hypertension; esophagogastric devascularization without splenectomy; portal vein system thrombosis

 

 

Esophagogastric variceal hemorrhage is a serious life-threatening complication in patients with portal hypertension (PH). In 2007, the American Association for the Study of Liver Disease (AASLD) upgraded its recommendation for the treatment of PH. The treatment of varices and variceal hemorrhage depends on the clinical stage of PH, including drugs, endoscopic variceal ligation (EVL), transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation.^[1] In China, patients with PH have the option to undergo liver transplantation or esophagogastric devascularization to control acute bleeding and to prevent recurrent variceal hemorrhage, especially when EVL and TIPS fail or are contraindicated.^[2] Esophagogastric devascularization is a modified version of Sugiura procedure and is associated with a relatively low operative mortality and risk of later hemorrhage from gastric or recurrent esophageal varices.^[3] In selected patients, its outcome is comparable with that of liver transplantation.^[4]

 

Compared with other treatments, current esophagogastric devascularization is associated with higher rates of postoperative complications including portal venous system thrombosis (PVST), which indicates poor prognosis. Splenectomy is an essential component of current esophagogastric devascularization. In this procedure, perisplenic portosystemic communication branches are destroyed, which may increase the portal vein pressure. Furthermore, splenic vein thrombosis after splenectomy may extend to the portal vein and superior mesenteric vein, increasing the risk of re-bleeding.^[5] To reduce the incidence of PVST and to improve prognosis, we developed a novel surgical approach, esophagogastric devascularization without splenectomy (EDWS). The present retrospective study aimed to evaluate the outcomes in patients who underwent EDWS compared with those treated with modified esophagogastric devascularization (MED).

 

 

From January 2006 to December 2012, a total of 55 consecutive patients were treated either with EDWS or MED, and followed up at Peking University People's Hospital. Informed consent was obtained from each patient, and this study was approved by the ethics committee of Peking University People's Hospital. All the procedures were performed by general surgeons with extensive experience in hepatic resections. Inclusion criteria were as follows: 1) patients with acute esophagogastric variceal hemorrhage or a history of esophagogastric variceal hemorrhage; 2) recurrent esophagogastric variceal hemorrhage after repeated EVL or sclerotherapy; 3) patients who refused to undergo EVL, sclerotherapy, TIPS or liver transplantation; and 4) patients who were Child A or B. Exclusion criteria were: 1) preoperative imaging studies indicated that patient had portal vein thrombosis; 2) patients who were Child C; 3) patients who underwent hepatectomy, microwave ablation or radiofrequency ablation of hepatocarcinoma.

 

Both surgical procedures consist of devascularization of the proximal area of the lesser and the greater curvature of the stomach and the lower 6 cm of the esophagus, ligating all the perforating veins to the gastric and esophageal wall. The portal venous pressure (PVP) was measured through the branch of the right gastroepiploic vein. The esophagus was only transected in the patients with high risk signs of variceal hemorrhage which included medium/large varices or small varices that had red wale signs. An end-to-end anastomosis (EEA) autosuture stapling device was introduced in the distal esophagus through a small anterior gastrotomy. The EEA was performed 2 cm above the esophagogastric junction allowing concomitant transection and reanastomosis of the distal esophagus. In MED, splenectomy was performed concurrently. In EDWS, the splenic artery was ligated instead and splenocolic ligament was conserved.

 

Patients' general characteristics were collected, including age, Child-Pugh classification, and etiology of PH. Patients' platelet and white blood cell count, liver function and blood coagulation function were also collected on preoperative day 1 (baseline) and postoperative day 7 (POD 7). Surgical parameters were as follows: operation time, intraoperative blood loss, and preoperative and postoperative PVP. Postoperative hepatic insufficiency was defined as persistent hyperbilirubinemia (total bilirubin level >5 mg/dL) for more than 5 days after surgery.^[6] Long-term follow-up was conducted via phone or at an outpatient clinic.

 

Statistical analysis was performed using SPSS 15.0 (SPSS Inc., Chicago, IL, USA). Continuous data were expressed as mean±SD. Differences between the groups were analyzed with the independent-samples t test or the Chi-square test. Differences between preoperative and postoperative data within one group were analyzed with paired-samples t-test. A P value <0.05 was considered statistically significant.

 

 

Twenty-seven patients were treated with EDWS, among them 16 underwent esophageal transection concurrently. Twenty-eight patients underwent MED, and 8 of them underwent esophageal transection simultaneously. The platelet count of patients in both groups was less than normal, whereas the patients in the EDWS group showed a higher platelet count (P=0.035). Other parameters such as white blood cell count, hepatic function and coagulation function were comparable between the two groups (Table 1).

 

Postoperative PVP was decreased by nearly 20% of the baseline in both groups. However, this decrease did not reach a significant level compared with preoperative PVP. There was no significant difference in operation time and intraoperative blood loss between the EDWS and MED groups (Table 2).

 

The platelet count and white blood cell count of patients in the EDWS group were significantly lower than those of patients in the MED group at POD 7 (P<0.001, Table 3). In the EDWS group, the platelet count at POD 7 was relatively higher than that of the baseline, but there was no significant difference (P=0.129). In the MED group, however, the platelet count at POD 7 was significantly elevated (P<0.001). The white blood cell count at POD 7 was significantly elevated in both EDWS and MED groups (P<0.001). There was no significant difference in liver and coagulation functions between the two groups (Table 3).

 

No perioperative mortality was observed in both groups. No patients had hepatic encephalopathy or hepatic insufficiency during hospitalization. The PVST morbidity rate was significantly higher in the MED group than in the EDWS group (35.7% vs 11.1%, P=0.032). No differences in the rates of other complications were observed (Table 4). Notably, postoperative hemorrhage resulting from stress or portal hypertensive gastropathy occurred in both groups (21.4% vs 14.8%, P=0.525), but no recurrent esophagogastric variceal hemorrhage was observed during hospitalization.

 

Twenty-two of the 27 patients (81.5%) in the EDWS group were followed up with a mean duration of 33.2 months (range 4-59). One patient died of liver failure 56 months after EDWS. In the MED group, the follow-up rate was 82.1% (23/28), with a mean follow-up time of 34.5 months (range 4-89). All the patients are alive.

 

The median RHFS was 50.4 months (95% CI: 45-56 months) in the EDWS group, with 1- and 3-year RHFS rates of 100% and 95.5%, respectively. In the MED group, the median RHFS was 60.1 months (95% CI: 44-76 months), with 1- and 3-year RHFS rates of 100% and 91.3%, respectively (Fig.). The difference was not significant between the EDWS and MED groups (P=0.631). Recurrent esophagogastric variceal hemorrhage was successfully controlled by conservative treatment, without using EVL, TIPS or surgery.

 

 

PH is the direct consequence of cirrhosis, resulting from distortion of liver vascular architecture by fibrosis and regenerative nodules, endothelial dysfunction and decreased nitric oxide bioavailability.^[7] Increased portal-pressure gradient above a certain level leads to development of collaterals at sites of communication between the portal and systemic circulations.^[8] In addition, splanchnic vasodilation and increased cardiac output increase portal venous flow, exacerbating PH.^[9] Esophagogastric varices are the most important collaterals, which rupture with rising portal pressure and portal venous flow, and constitute one of the major causes of death in PH.^[10] Therapies include ligation of portosystemic collaterals to prevent esophagogastric variceal bleeding.^[2] The Sugiura procedure is a landmark in the history of PH therapy. The procedure consists of extensive paraesophagogastric devascularization, esophageal transection, splenectomy, vagotomy and pyloroplasty. Separate thoracic and abdominal approaches were performed in one or two stages. In Japan, the 10-year survival rate was 72% in patients undergoing selective operation and the incidence of recurrent variceal bleeding was only 1.5%.^[11] The outcomes of the procedure outside Japan seem not as good as those in Japan with high complication and mortality rates, and these inconsistences may be due to diverse etiology and severity of cirrhosis, surgical experience and timing of intervention.^[12] The Sugiura procedure has since been modified, but without the improved results.^{[2, 12]}

 

Whether splenectomy was an essential component of esophagogastric devascularization has been debated in the annals of PH therapy. Currently, the modified esophagogastric devascularization surgery is widely used, and splenectomy is routinely performed to decrease the portal venous flow, to prevent esophagogastric variceal bleeding, and to maintain sufficient hepatic blood supply. The reported incidence of recurrent variceal bleeding was between 5% and 40%.^[13] Investigators proposed that the spleen in PH is afflicted with serious fibrosis and loss of function.^{[14, 15]}

 

However, postoperative complications of MED including PVST are associated with splenectomy.^[5] In the late 1990s, Orozco et al^[16] divided patients who underwent esophagogastric devascularization into two groups, depending on concomitant splenectomy. Significant differences were found in transfusion requirement and PVST, both favoring the group without splenectomy, whereas no differences were observed in re-bleeding, encephalopathy rate, and operation time or other postoperative complications between the two groups. Voros et al^[2] suggested that splenectomy was only performed in patients with severe hypersplenism, PVST, or for enlarged spleen. Other studies^{[14, 15]} proposed that splenectomy may exacerbate immune dysfunction in PH. However, few patients with severe hypersplenism underwent splenectomy, as symptom remission was achieved by partial splenectomy or partial splenic embolization. Therefore, we developed a novel procedure, EDWS, based on our 10 years' experience with MED. Our procedure preserved the spleen, the collaterals connecting the Retzius varices, the gastric coronary vein and spleen vein, ensuring that the spontaneous formation of these collaterals reduced the PVP. The spleen artery was ligated partially to reduce the portal blood flow. Our study showed that in patients undergoing EDWS, postoperative PVP was decreased by 20% of the baseline. The incidence of recurrent variceal bleeding in 1 year and 3 years after operation was 0% and 4.5%, respectively. The incidence of PVST in the EDWS group was significantly lower than that in the MED group. In general, EDWS in selected patients reduced the incidence of PVST and tended to reduce the recurrence of esophagogastric variceal bleeding.

 

PVST refers to a thrombosis created in the portal venous system, including the main trunk, branches of the intrahepatic and extrahepatic portal veins (the splenic vein, the superior mesenteric vein, or the inferior mesenteric vein). It is a major complication of esophagogastric devascularization surgery. Occlusion of the main trunk of the portal and mesenteric veins, which is usually symptomatic, leads to variceal re-bleeding, ischemic intestinal necrosis, or hepatic failure. In contrast, splenic stump thrombosis or partial intrahepatic PVST may be asymptomatic and rarely associated with serious complications. Patients with postoperative PVST in the main trunk may forgo curative liver transplantation. The reported incidence of PVST after MED in hepatitis B cirrhosis-related PH is 13.4%-43.5%.^[17] Several clinical risk factors have been associated with postoperative PVST, including elevated postoperative platelet count, surgical techniques, hemodynamic changes in the splenic and portal veins, endothelial damage, postoperative release of procoagulant factors, and reduction of anticoagulant factors.^[18] Stamou et al^[19] reported that a rise in the platelet count of more than 650×10⁹/L one week after surgery was directly associated with the development of PVST. Zhou^[20] also suggested that the peak platelet count of more than 300×10⁹/L was a risk factor for PVST, whereas even prophylactic anticoagulants failed to reduce the risk of PVST at a peak platelet count exceeding 500×10⁹/L. In our study, partial remission of hypersplenism was achieved in the EDWS group. Postoperative platelet count in these patients was slightly elevated, which may contribute to the low incidence of postoperative PVST. This may also suggest that EDWS concurrently with partial ligation of the splenic artery partially remitted hypersplenism, and also avoided rapid elevation of postoperative platelet count and PVST formation. Simultaneously, endothelial damage and exposure of collagen fibers, caused by clamping or squeezing the splenic vein in MED, were high risk factors of PVST,^[21] which could be avoided by conserving the spleen in the novel EDWS.

 

In addition to the inherent limitations of this retrospective study, the study design did not facilitate the exploration of the flow index such as the velocity of the portal venous blood stream, an important factor predicting the outcome of EDWS.^{[17, 22]} The study was based on a limited number of patients, quite homogeneous clinically and demographically. A further prospective study should be conducted in a large population to confirm the precise surgical indications and contraindications of EDWS.

 

In conclusion, EDWS is safe and effective for esophagogastric varices secondary to PH in selected patients, especially when alternative treatments such as EVL, TIPS or liver transplantation are not available or effective. It is associated with a low risk of postoperative complications, especially PVST and recurrent esophagogastric variceal bleeding compared with MED.

 

 

1 Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W; Practice Guidelines Committee of the American Association for the Study of Liver Diseases; Practice Parameters Committee of the American College of Gastroenterology. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 2007;46:922-938. PMID: 17879356

2 Voros D, Polydorou A, Polymeneas G, Vassiliou I, Melemeni A, Chondrogiannis K, et al. Long-term results with the modified Sugiura procedure for the management of variceal bleeding: standing the test of time in the treatment of bleeding esophageal varices. World J Surg 2012;36:659-666. PMID: 22270986

3 Zhou GW. The choice of surgical module for the treatment of portal hypertension in the era of liver transplantation. Chin J Bases Clin General Surg 2013;20:10-12.

4 Wang M, Wen TF, Yan LN, Li C, Zhang Y. Comparison on effects of liver transplantation and periesophagogastric devascularization with splenectomy for portal hypertension and cirrhosis with liver function of Child Grade A. Chin J Bases Clin General Surg 2013;20:18-23.

5 Leng XS. Current status and perspectives in the management of portal hypertension. Chin J Bases Clin General Surg 2013;20:1-3.

6 Kim SU, Ahn SH, Park JY, Kim do Y, Chon CY, Choi JS, et al. Prediction of postoperative hepatic insufficiency by liver stiffness measurement (FibroScan®) before curative resection of hepatocellular carcinoma: a pilot study. Hepatol Int 2008;2:471-477. PMID: 19669322

7 Iwakiri Y, Groszmann RJ. Vascular endothelial dysfunction in cirrhosis. J Hepatol 2007;46:927-934. PMID: 17391799

8 Groszmann RJ, Garcia-Tsao G, Bosch J, Grace ND, Burroughs AK, Planas R, et al. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med 2005;353:2254- 2261. PMID: 16306522

9 Iwakiri Y, Groszmann RJ. The hyperdynamic circulation of chronic liver diseases: from the patient to the molecule. Hepatology 2006;43:S121-131. PMID: 16447289

10 Garcia-Tsao G, Bosch J. Management of varices and variceal hemorrhage in cirrhosis. N Engl J Med 2010;362:823-832. PMID: 20200386

11 Sugiura M, Futagawa S. Esophageal transection with paraesophagogastric devascularizations (the Sugiura procedure) in the treatment of esophageal varices. World J Surg 1984;8:673-679. PMID: 6506734

12 Dagenais M, Langer B, Taylor BR, Greig PD. Experience with radical esophagogastric devascularization procedures (Sugiura) for variceal bleeding outside Japan. World J Surg 1994;18:222-228. PMID: 8042327

13 Henderson JM. Surgical treatment of portal hypertension. Baillieres Best Pract Res Clin Gastroenterol 2000;14:911-925. PMID: 11139346

14 Wang Y. Matters of right and wrong in splenectomy for portal hypertension. Chin J Hepatobiliary Surg 2006;12:577-578.

15 Xia SS. Careful selection of splenectomy should be emphasized for cirrhotic portal hypertension. Chin J Hepatobiliary Surg 2006;12:583-584.

16 Orozco H, Mercado MA, Martinez R, Tielve M, Chan C, Vasquez M, et al. Is splenectomy necessary in devascularization procedures for treatment of bleeding portal hypertension? Arch Surg 1998;133:36-38. PMID: 9438756

17 Zhang Y, Wen TF, Yan LN, Yang HJ, Deng XF, Li C, et al. Preoperative predictors of portal vein thrombosis after splenectomy with periesophagogastric devascularization. World J Gastroenterol 2012;18:1834-1839. PMID: 22553410

18 Lai W, Lu SC, Li GY, Li CY, Wu JS, Guo QL, et al. Anticoagulation therapy prevents portal-splenic vein thrombosis after splenectomy with gastroesophageal devascularization. World J Gastroenterol 2012;18:3443-3450. PMID: 22807615

19 Stamou KM, Toutouzas KG, Kekis PB, Nakos S, Gafou A, Manouras A, et al. Prospective study of the incidence and risk factors of postsplenectomy thrombosis of the portal, mesenteric, and splenic veins. Arch Surg 2006;141:663-669. PMID: 16847237

20 Zhou GW. Portal vein thrombosis after devascularization operation and its prevention. Chin J Gen Surg 2013;28:500-503.

21 Yang W, Hu YQ, Mo RX. Portal vein thrombosis developed in cirrhotic portal hypertensive patients after splenectomy and portaazygous devascularization. Chin J Gen Surg 2010;5:710-712.

22 Huard G, Bilodeau M. Management of anticoagulation for portal vein thrombosis in individuals with cirrhosis: a systematic review. Int J Hepatol 2012;2012:672986. PMID: 22778970