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5. Biliary decompression promotes Kupffer cell recovery in obstructive jaundice
SOCIETY FOR SURGERY OF THE ALIMEYTARY ~ ~~_ -.____ _~~_ TRACT _____~
..--5. Biliary Decompression Promotes Kupffer Cell Recovery in Obstructive Jaundice
6. Hepatic Resection for Metastatic Neuroendocrine Cancers
Clements WDB, McCaigue M, Erwin P, Hall&y I, Rowlands BJ Departments of Surgery Queen’s University, Institute of Clinical Science Belfast, Northern Ireland
Florencia Que, David M. Nagomey Mayo Clinic Rochester, Minnesota
Jaundiced patients undergoing surgical procedures have an increased risk of complications and death Gram negative sepsis constitutes the bulk of the morbidity and mortality. Depressed Kupffer cell clearance capacity (KCCC) predisposes jaundiced patients to endotoxaemia and its sequele. Biliary decompression remains the main tberapeutic strategy in obstructive jaundice. We investigated the efficacy of internal (ID) and external biliary drainage (ED) on KCCC. ID and ED were established by way of a choledochoduodenostomy and choledochovesical fistula, respectively. Method: Wistar Rats (250-300 g) were assigned to one of 6 groups--Sham operated, Bile duct ligation (BDL) for 3 weeks, and Sham operated for BDL for 3 weeks followed by a further 21 days of ID or ED. KCCC was measured using an isolated hepatic perfusion technique with FIX-labeled latex particles (0.75 u) as the test probe. Plasma was assayed for bilirubin, endotoxin and anticore glycolipid antibody (ACGA) was assayed for bilimbin, endotoxin and anticore glycolipid antibody (ACGA) concentrations. Results: Jaundiced rats had reduced KCCC (P
ACGA W Con@-4
168 * 12.3'340.3i60' 1.2 * 0.3 120.2i8.5 2.3 il.1 108 f 15.6 2.7 i0.8 140 i 16.5 3.3 + 1.5 110.6io7.2 2.7* 0.9 115.4zt10.9
En&toxin k/mU
KCCC (%I
100 + 51.1' 14.6zt1.8 7.1 i2.5 38.5 il.4 2.9 zt1.7 34.4 zt2 3.7 zt2.5 40.1 f 3.4 3.7 zt2.6 33.9 zt1.9+ 7.5i6.2 42.9il.6
Dataas mean * SEM. ('P
Hepatic resection for metastatic disease has proven efticacious in carefully selected patients, but such an approach for patients with metastatic neuroendocrine (NE) cancers remains unclear. We have shown that some patients with advanced NE tumors benefit from hepatic resection through relief of endocrinopatbies and prolonged survival and response correlates with the extent of resection (Surgery 1990, 108: 96-100). To further define the indications and predictors of survival for hepatic resection for metastatic NE cancers, we examined our updated experience. Methods: The records of 66 patients undergoing hepatic resection for me&static NE cancer between March 1984, and January 1993, were retrospectively reviewed. Survival was calculated by the Kaplan-Meier method and associations with survival were determined by the log-rank test. Results: There were 41 women and 25 men with a mean age of 56 yrs. Indications for resection were 46 carcinoid tumors and 20 islet cell cancers - 7 gnlcagonomas, 5 polyfunctional tumors, 5 nonfunctional tumors, 2 gastrinomas, and 1 insulinoma. Only 14 patients had solitary me&stases. Thirty-five patients had nonanatomic hepatic resections and 3 1 had lobar or extended lobar resections. Primary tumors were resected concurrently in 36 patients. All gross hepatic metastases were resected in 24 patients. Mean follow-up was 2.2 yrs (range: 5 days to 9.4 yrs). Mortality was 1.5% and morbidity was 24%. Median survival was not reached. Overall survival at 3 yrs was 8 1%. Survival was not different between tumor types (carcinoid-82% versus islet cell-80%) or for patients with complete versus incomplete resection (95% versus 75%). Clinical endocrinopathies were relieved in 53 of 60 (88%) symptomatic patients. Gf 32 patients with recurrent symptoms, mean duration of symptomatic relief was 1.2 years. Hormonal tumor markers were reduced in 43 of 61 patients with available data. Cnrrently, 17% of patients remain free of disease. Conclusion: Hepatic resection of NE metastases is associated with both prolonged survival and relief of endocrinopathies. Broader application of the approach in patients with metastatic gastrointestinal NE cancers is warranted.
Conclusions: These data support the hypothesis that endotoxaemia and its mediated effects are integral in the patbophysiology of jaundice. Furthermore, a short period of internal biliary drainage is a useful therapeutic strategy in restoring Kupffer cell function and negating systemic endotoxaemia and consequent complications in biliary obstruction.
THE AMERICAN JOURNAL OF SURGERY
VOLUME 167 APRIL 1994
445
..--5. Biliary Decompression Promotes Kupffer Cell Recovery in Obstructive Jaundice
6. Hepatic Resection for Metastatic Neuroendocrine Cancers
Clements WDB, McCaigue M, Erwin P, Hall&y I, Rowlands BJ Departments of Surgery Queen’s University, Institute of Clinical Science Belfast, Northern Ireland
Florencia Que, David M. Nagomey Mayo Clinic Rochester, Minnesota
Jaundiced patients undergoing surgical procedures have an increased risk of complications and death Gram negative sepsis constitutes the bulk of the morbidity and mortality. Depressed Kupffer cell clearance capacity (KCCC) predisposes jaundiced patients to endotoxaemia and its sequele. Biliary decompression remains the main tberapeutic strategy in obstructive jaundice. We investigated the efficacy of internal (ID) and external biliary drainage (ED) on KCCC. ID and ED were established by way of a choledochoduodenostomy and choledochovesical fistula, respectively. Method: Wistar Rats (250-300 g) were assigned to one of 6 groups--Sham operated, Bile duct ligation (BDL) for 3 weeks, and Sham operated for BDL for 3 weeks followed by a further 21 days of ID or ED. KCCC was measured using an isolated hepatic perfusion technique with FIX-labeled latex particles (0.75 u) as the test probe. Plasma was assayed for bilirubin, endotoxin and anticore glycolipid antibody (ACGA) was assayed for bilimbin, endotoxin and anticore glycolipid antibody (ACGA) concentrations. Results: Jaundiced rats had reduced KCCC (P
ACGA W Con@-4
168 * 12.3'340.3i60' 1.2 * 0.3 120.2i8.5 2.3 il.1 108 f 15.6 2.7 i0.8 140 i 16.5 3.3 + 1.5 110.6io7.2 2.7* 0.9 115.4zt10.9
En&toxin k/mU
KCCC (%I
100 + 51.1' 14.6zt1.8 7.1 i2.5 38.5 il.4 2.9 zt1.7 34.4 zt2 3.7 zt2.5 40.1 f 3.4 3.7 zt2.6 33.9 zt1.9+ 7.5i6.2 42.9il.6
Dataas mean * SEM. ('P
Hepatic resection for metastatic disease has proven efticacious in carefully selected patients, but such an approach for patients with metastatic neuroendocrine (NE) cancers remains unclear. We have shown that some patients with advanced NE tumors benefit from hepatic resection through relief of endocrinopatbies and prolonged survival and response correlates with the extent of resection (Surgery 1990, 108: 96-100). To further define the indications and predictors of survival for hepatic resection for metastatic NE cancers, we examined our updated experience. Methods: The records of 66 patients undergoing hepatic resection for me&static NE cancer between March 1984, and January 1993, were retrospectively reviewed. Survival was calculated by the Kaplan-Meier method and associations with survival were determined by the log-rank test. Results: There were 41 women and 25 men with a mean age of 56 yrs. Indications for resection were 46 carcinoid tumors and 20 islet cell cancers - 7 gnlcagonomas, 5 polyfunctional tumors, 5 nonfunctional tumors, 2 gastrinomas, and 1 insulinoma. Only 14 patients had solitary me&stases. Thirty-five patients had nonanatomic hepatic resections and 3 1 had lobar or extended lobar resections. Primary tumors were resected concurrently in 36 patients. All gross hepatic metastases were resected in 24 patients. Mean follow-up was 2.2 yrs (range: 5 days to 9.4 yrs). Mortality was 1.5% and morbidity was 24%. Median survival was not reached. Overall survival at 3 yrs was 8 1%. Survival was not different between tumor types (carcinoid-82% versus islet cell-80%) or for patients with complete versus incomplete resection (95% versus 75%). Clinical endocrinopathies were relieved in 53 of 60 (88%) symptomatic patients. Gf 32 patients with recurrent symptoms, mean duration of symptomatic relief was 1.2 years. Hormonal tumor markers were reduced in 43 of 61 patients with available data. Cnrrently, 17% of patients remain free of disease. Conclusion: Hepatic resection of NE metastases is associated with both prolonged survival and relief of endocrinopathies. Broader application of the approach in patients with metastatic gastrointestinal NE cancers is warranted.
Conclusions: These data support the hypothesis that endotoxaemia and its mediated effects are integral in the patbophysiology of jaundice. Furthermore, a short period of internal biliary drainage is a useful therapeutic strategy in restoring Kupffer cell function and negating systemic endotoxaemia and consequent complications in biliary obstruction.
THE AMERICAN JOURNAL OF SURGERY
VOLUME 167 APRIL 1994
445