The efficacy and limitations of percutaneous endoscopic gastrostomy.

We analyzed 64 percutaneous endoscopic gastrostomy procedures performed by us between 1986 and 1990. Thirty patients had neurologic disease; 16 had head and neck cancers; eight had other malignancies; two had acquired immunodeficiency syndrome; and eight had other problems. Seven patients died within 30 days of complications (n = 4) or the primary illness (n = 3). Mean follow-up was 6 months; an additional patient died of aspiration and eight others died of their underlying illness. There were 19 complications (32%). Four wound complications occurred. Nine patients developed aspiration pneumonia within 3 days of the procedure, four of whom died in the hospital. Of the 24 patients with a history of aspiration, nine experienced aspiration during or after percutaneous endoscopic gastrostomy. Patients with a history of aspiration were more likely to have perioperative aspiration pneumonia, and patients who experienced aspiration were more likely to die.     

Regional muramyl tripeptide phosphatidylethanolamine administration enhances hepatic immune function and tumor surveillance

BACKGROUND: Immune status of the liver may affect growth of liver metastases. We analyzed the ability of muramyl tripeptide phosphatidylethanolamine (MTP-PE), an immunomodulatory bacterial cell wall analog, to stimulate Kupffer cells (KCs) and protect against tumor growth, with or without an immunosuppressive partial hepatectomy (PH). Impact of MTP-PE's route of administration on KC function was assessed. METHODS: Buffalo rats (n = 7 to 12/group) were treated with saline, 40 microg MTP-PE intraportally (portal) or intravenously (IV) and challenged with 5 x 10(5) hepatoma cells, and tumors counted on day 21. To assess MTP-PE's impact on KC stimulation in animals undergoing PH, a known stimulant of tumor cell growth, groups were treated with saline or MTP-PE and challenged with tumor and underwent 30% PH. KCs were harvested and analyzed for superoxide production. Statistical analysis was performed with Mann-Whitney U test or chi-square test. RESULTS: MTP-PE-treated animals had fewer tumor nodules than control animals (19 vs 184, P <.005). MTP-PE-portal animals had fewer nodules than MTP-PE-IV (2 vs 36, P <.05). MTP-PE treatment before PH resulted in fewer tumor nodules compared with control animals (192 vs 276, P <. 05). MTP-PE administration increased macrophage superoxide production (20.6 +/- 2 vs 11.9 +/- 1.1 nmol/10(6) cells, P <.005). CONCLUSIONS: MTP-PE improved KC function and decreased growth of microscopic tumor cells. MTP-PE's effects persist after an immunosuppressive hepatectomy. Portal administration was the most effective. MTP-PE administration may be useful as a neoadjuvant therapy for patients undergoing resection of liver malignancies.     

Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) of concurrent systemic oxaliplatin (Oxal) combinations plus hepatic arterial infusion (HAI) in patients with unresectable hepatic metastases from colorectal cancer. PATIENTS AND METHODS: Thirty-six patients (89% previously treated) with unresectable liver metastases were treated with concurrent HAI and systemic Oxal plus irinotecan (CPT-11; group A) or Oxal, fluorouracil (FU), and leucovorin (LV; group B). Systemic chemotherapy was administered every 2 weeks concurrent with 2 weeks of HAI floxuridine (FUDR) and dexamethasone (Dex) every 28 days. RESULTS: The MTD for patients in group A was Oxal 100 mg/m(2), CPT-11 150 mg/m(2), and FUDR 0.12 mg/kg x 30 mL divided by pump flow rate. The MTD for group B was Oxal 100 mg/m(2), LV 400 mg/m(2), and FU 1,400 mg/m(2) by continuous infusion over 48 hours, with the same FUDR dose as in group A. Grade 3 or 4 toxicities in groups A and B included diarrhea (24% and 20%), neutropenia (10% and 7%), neurotoxicity (24% and 20%), and bilirubin more than 3 mg/mL (5% and 7%, respectively). The complete and partial response rate totaled 90% for group A and 87% for group B. Median survival time was 36 and 22 months for groups A and B, respectively. Seven patients in group A were ultimately able to undergo liver resection. CONCLUSION: Combination therapy with HAI FUDR and Dex plus systemic Oxal combinations may be safely administered to patients with colorectal cancer. The high response rate (88%) and the possibility of conversion to resectability, despite disease progression on prior systemic regimens, suggest that these combinations should be evaluated in larger studies as first- or second-line therapy in patients with hepatic metastases from colorectal cancer.     

Multi-Center Analysis of Liver Transplantation for Combined Hepatocellular Carcinoma-Cholangiocarcinoma Liver Tumors

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Serial measurement of hepatic lipids during chemotherapy in patients with colorectal cancer: a 1H MRS study

Hepatic steatosis is a hallmark of chemotherapy‐induced liver injury. We made serial ¹H MRS measurements of hepatic lipids in patients over the time course of a 24‐week chemotherapeutic regimen to determine whether ¹H MRS could be used to monitor the progression of chemotherapy‐induced steatosis. Thirty‐four patients with stage III or IV colorectal cancer receiving 5‐fluorouracil, folinic acid and oxaliplatin (n = 21) or hepatic arterial infusion of floxuridine with systemic irinotecan (n = 13) were studied prospectively. ¹H MRS studies were performed at baseline and after 6 and 24 weeks of treatment. A ¹H MR spectrum was acquired from the liver during a breath hold and the ratio of fat to fat + water (FFW) was calculated to give a measure of hepatic triglycerides (HTGCs). The methodology was histologically validated in 18 patients and the reproducibility was assessed in 16 normal volunteers. Twenty‐seven patients completed baseline, 6‐week and 24‐week ¹H MRS examinations and one was censored. Thirteen of 26 patients (50%) showed an increase in FFW after completion of treatment. Six patients (23%) developed hepatic steatosis and two patients converted from steatosis to nonsteatotic liver. Patients whose 6‐week hepatic lipid levels had increased significantly relative to baseline also had a high probability of lipid elevation relative to baseline at the completion of treatment. Serial ¹H MRS is effective for the monitoring of HTGC changes during chemotherapy and for the detection of chemotherapy‐associated steatosis. Six of 26 patients developed steatosis during chemotherapy. Lipid changes were observable at 6 weeks. Copyright © 2012 John Wiley & Sons, Ltd.     

A comparison of treatment and outcomes of perihilar cholangiocarcinoma between Eastern and Western centers

Background

Perihilar cholangiocarcinoma (PHC) often requires extensive surgery which is associated with substantial morbidity and mortality. This study aimed to compare an Eastern and Western PHC cohort in terms of patient characteristics, treatment strategies and outcomes including a propensity score matched analysis.

Angiographic identification of extrahepatic perfusion after hepatic arterial pump placement: implications for surgical prevention

Background

Hepatic arterial infusion (HAI) chemotherapy is an effective treatment for patients with liver malignancy. Extrahepatic perfusion (EHP) after HAI pump placement requires correction prior to starting chemotherapy. The aim of this study was to define the origin of arterial branches causing EHP in order to determine if alterations in surgical technique during pump placement might prevent EHP.

Methods

A prospectively maintained, single-centre HAI database was reviewed for all patients (2008–2011) with EHP. The origin of arterial branches causing EHP was classified anatomically and patient outcomes were analysed.

Results

Of the 327 patients with pumps implanted, 24 evidenced EHP. The arterial branch responsible for EHP perfused the duodenum, pancreas and/or stomach. The branch responsible for EHP arose from the proper hepatic artery (PHA), 1^st, 2^nd, or 3^rd order hepatic artery branches in 7, 10, 5 and 2 patients, respectively. The majority of branches beyond the PHA causing EHP (13/17) originated from the right hepatic artery. In 18 patients, aberrant branches were successfully treated with embolization.

Conclusion

These findings provide the anatomic basis for prevention of up to one-third of the cases of EHP intra-operatively, decreasing the number of patients who will require additional procedures for correction of EHP post-operatively.     

Intraductal papillary neoplasm of the bile duct: A biliary equivalent to intraductal papillary mucinous neoplasm of the pancreas?

Intraductal papillary neoplasm of the bile duct (IPNB) is a variant of bile duct carcinoma characterized by intraductal growth and better outcome compared with the more common nodular-sclerosing type. IPNB is a recognized precursor of invasive carcinoma, but its pathogenesis and natural history are ill-defined. This study examines the clinicopathologic features and outcomes of IPNB. A consecutive cohort of patients with bile duct cancer (hilar, intrahepatic, or distal) was reviewed, and those with papillary histologic features identified. Histopathologic findings and immunohistochemical staining for tumor markers and for cytokeratin and mucin proteins were used to classify IPNB into subtypes. Survival data were analyzed and correlated with clinical and pathologic parameters. Thirty-nine IPNBs were identified in hilar (23/144), intrahepatic (4/86), and distal (12/113) bile duct specimens between 1991 and 2010. Histopathologic examination revealed 27 pancreatobiliary, four gastric, two intestinal, and six oncocytic subtypes; results of cytokeratin and mucin staining were similar to those of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Invasive carcinoma was seen in 29/39 (74%) IPNBs. Overall median survival was 62 months and was not different between IPNB locations or subtypes. Factors associated with a worse median survival included presence and depth of tumor invasion, margin-positive resection, and expression of MUC1 and CEA. Conclusion: IPNBs are an uncommon variant of bile duct cancer, representing approximately 10% of all resectable cases. They occur throughout the biliary tract, share some histologic and clinical features with IPMNs of the pancreas, and may represent a carcinogenesis pathway different from that of conventional bile duct carcinomas arising from flat dysplasia. Given their significant risk of harboring invasive carcinoma, they should be treated with complete resection. (HEPATOLOGY 2012).     

Operative procedures for unresectable pancreatic cancer: does operative bypass decrease requirements for postoperative procedures and in-hospital days?

Background

The optimal surgical management of patients found to have unresectable pancreatic cancer at open exploration remains unknown.

Methods

Records of patients who underwent non-therapeutic laparotomy for pancreatic cancer during 2000–2009 and were followed until death at Memorial Sloan–Kettering Cancer Center, New York, were reviewed.

Results

Over the 10-year study period, 157 patients underwent non-therapeutic laparotomy. Laparotomy alone was performed in 21% of patients; duodenal bypass, biliary bypass and double bypass were performed in 11%, 30% and 38% of patients, respectively. Complications occurred in 44 (28%) patients. Three (2%) patients died perioperatively. Postoperative interventions were required in 72 (46%) patients following exploration. The median number of inpatient days prior to death was 16 (interquartile range: 8–32 days). Proportions of patients requiring interventions were similar regardless of the procedure performed at the initial operation, as were the total number of inpatient days prior to death. Patients undergoing gastrojejunostomy required fewer postoperative duodenal stents and those undergoing operative biliary drainage required fewer postoperative biliary stents.

Conclusions

In this study, duodenal, biliary and double bypasses in unresectable patients were not associated with fewer invasive procedures following non-therapeutic laparotomy and did not appear to reduce the total number of inpatient hospital days prior to death. Continued effort to identify unresectability prior to operation is justified.