Transcatheter arterial chemoembolization for advanced hepatocellular carcinoma with inferior vena cava and right atrial tumors.

Advanced hepatocelluar carcinoma (HCC) with invasion of venous systems usually indicates not only a poor prognosis but also a contraindication for transcatheter arterial chemoembolization (TACE). This study evaluated the feasibility of TACE for advanced HCC with inferior vena cava (IVC) and right atrium (RA) tumors and, also, to search for the ideal embolization particle size. Twenty-six patients who had HCC invasion into the IVC included five patients with coexistent RA tumors that were treated with TACE. The chemoembolization method was cisplatin, doxorubicin, and mitomycin C mixed with Lipiodol and Ivalon. The selection of Ivalon particles was divided into two groups based on their size: (A) >180 microm, N = 9; and (B) 47-180 microm, N = 17. The overall response rate was 53.8% (14/26). Based on the response to TACE, the median survival period of the entire group was 4.2 months (range, 1.5 to 76.7 months). The median survival period of the 14 responders was 13.5 months (1.5-76.7 months), and that of the 12 nonresponders, 3.3 months (2.1 to 24.3 months) (p < 0.002). Comparing the two Ivalon particle sizes, the response rate was 12.5% (1/8 [corrected] patients) for group A and 72.2% [corrected] for group B (13/18 [corrected] patients) (p < 0.01). [corrected] No serious complication was observed post-chemoembolization. In conclusion, TACE is a safe and effective treatment for advanced HCC with IVC and RA tumors, and small Ivalon particles (47-180 microm) are superior to large ones (>180 microm).

Unresectable hepatocellular carcinoma treated with radiotherapy and/or chemoembolization.

The purpose of our study was to evaluate the outcome, patterns of failure, and toxicity for patients with unresectable hepatocellular carcinoma (HCC) treated with radiotherapy, transcatheter arterial chemoembolization (TACE), or combined TACE and radiotherapy. Forty-two patients with unresectable HCC were treated with combined radiotherapy and TACE (TACE+RT group, 17 patients), radiotherapy alone (RT group, 9 patients), or with TACE alone (TACE group, 16 patients). Mean dose of radiation was 46.9 +/- 5.8 Gy in a daily fraction of 1.8 to 2 Gy, directed only to the cancer-involved areas of the liver. TACE was performed with a combination of Lipiodol, doxorubicin, cisplatin, and mitomycin C, followed by Gelfoam or Ivalon embolization. Tumor size was smaller in the TACE group (mean: 5.4 cm) compared with the TACE+RT group (8.6 cm) and the RT group (13.1 cm) (P = 0.0003). The median follow-up was 24 months in the TACE+RT group, 28 months in the RT group, and 23 months in the TACE group. Survival was significantly worse for patients treated with radiotherapy alone due to the selection bias of patients with more advanced disease and compromised condition in this group. In contrast, the TACE+RT and TACE groups had comparable survival (two-year rates: TACE+RT 58%, TACE 56%, P = 0.69). The local control rate for the treated tumors was similar in the TACE+RT and TACE groups (P = 0.11). The intrahepatic recurrence outside the treated tumors was common and similar between these two groups (P = 0.48). The extrahepatic progression-free survival was significantly shorter for patients in the TACE+RT group than in the TACE group (two-year rates: TACE+RT 36%, TACE 100%, P = 0.002). Seven patients died from complications of treatment. Local radiotherapy may be added to treat patients with unresectable HCC, and the control of progression of the treated tumors was promising even in patients with large hepatic tumors. Survival of patients with combined TACE and radiotherapy was similar to that with TACE as the only treatment, while a significant portion of the patients treated with radiotherapy developed extrahepatic metastasis.

Safety and effectiveness of percutaneous fluoroscopic gastrostomy in cancer patients.

PURPOSE: To evaluate the safety and effectiveness of percutaneous fluoroscopic gastrostomy (PFG) in cancer patients. METHODS: We retrospectively analyzed the success rate, complication rate, and patient outcomes of PFG performed during a 15-month period in our hospital. The Cope type 10-French and 12-French self-retaining catheters were used for gastrostomy. RESULTS: Of the 113 PFG procedures requested during the study period, 112 (99.1%) were performed successfully; one procedure was cancelled because the nasogastric tube could not be passed through the obstructed esophagus. Thirty-day follow-ups were obtained for 92.0% of the procedures. Of the patients with at least 30 days of follow-up, eight (7.8%) died, but only two deaths (1.9%) were procedure-related. Major complications, including peritonitis and severe wound infection, occurred after eight procedures (7.8%). Minor complications, including superficial wound infection, tube fracture, leakage, severe pain, mild hemorrhage, and tube migration, occurred after 23 procedures (22.3%). The severity of pneumoperitoneum was significantly associated with the frequency of complications (p < 0.05). After placement of the gastrostomy, 68% of the patients maintained or increased their initial body weight; 28% lost 10% or less of their body weight; and 4% lost more than 10% of their body weight. CONCLUSIONS: PFG appears to be effective and relatively safe for long-term nutritional support in cancer patients.

Local radiotherapy with or without transcatheter arterial chemoembolization for patients with unresectable hepatocellular carcinoma.

PURPOSE: To evaluate the treatment outcome, patterns of failure, and prognostic factors for patients with unresectable hepatocellular carcinoma (HCC) treated with local radiotherapy alone or as an adjunct to transcatheter arterial chemoembolization (TACE). METHODS AND MATERIALS: From March 1994 to December 1997, 25 patients with unresectable HCC underwent local radiotherapy to a portion of the liver. Twenty-three patients were classified as having cirrhosis in Child-Pugh class A and 2 in class B. Mean diameter of the treated hepatic tumor was 10.3 cm. Mean dose of radiation was 46.9 +/- 5.9 Gy in a daily fraction of 1.8-2 Gy. Sixteen patients were also treated with Lipiodol and chemotherapeutic agents mixed with Ivalon or Gelfoam particles for chemoembolization, either before and/or after radiotherapy. Percutaneous ethanol injection therapy (PEIT) was given to one patient. All patients were monitored for treatment-related toxicity and for survival and patterns of failure. RESULTS: In a median follow-up period of 23 months, 11 patients were alive and 14 dead. The median survival duration from treatment was 19.2 months with a 2-year survival of 41%. Only 3 of 25 patients had local progression of the treated hepatic tumor. The recurrences were seen within the liver or extrahepatic. The 2-year local, regional, and extrahepatic progression-free survival rates were 78%, 46%, and 39%, respectively. The local control ranked the highest. Patients with Okuda Stage I disease had significantly longer survival than those with Stage II and III (p = 0.02). Patients with T4 disease (p = 0.02) or treated with radiotherapy alone (p = 0.003) had significantly shorter survival. T4 disease (p = 0.03) and pretreatment alpha-fetoprotein level of more than 200 ng/ml (p = 0. 03) were associated with significantly worse regional progression-free survival. A significant difference was observed in both regional progression-free survival (p = 0.0001) and extrahepatic progression-free survival (p = 0.005) between patients with and without portal vein thrombosis before treatment. The presence of satellite nodules had a significantly worse impact on regional progression-free survival (p = 0.04) and extrahepatic progression-free survival (p = 0.03). Patients with hepatic tumor more than 6 cm in diameter or portal vein thrombosis tended to have shorter survival. Radiation-induced liver disease (RILD) and gastrointestinal bleeding were the most common treatment-related toxicities. CONCLUSION: Radiotherapy is effective in the treatment of patients with unresectable HCC. Its effect appeared to be more prominent within the site to which radiation was given. The combination of TACE and radiation was associated with better control of HCC than radiation given alone, probably due to the selection of patients with favorable prognosis for the combined treatment. A dose-volume model should be established in the next phase of research in the treatment of unresectable HCC.

A pilot study of three-dimensional conformal radiotherapy in unresectable hepatocellular carcinoma.

BACKGROUND: The purpose of this study was to determine the potential role of three-dimensional (3-D) conformal radiotherapy (RT) in treatment of unresectable hepatocellular carcinoma (HCC). METHODS: Thirteen patients were included in this study, which was conducted between 1993 and 1996. Nine patients (group A) were treated with 3-D conformal RT alone because of main portal vein thrombosis, inferior vena cava thrombosis, obstructive jaundice and failure of previous transcatheter arterial chemoembolization (TACE) to control the disease. The remaining four patients (group B) were treated with a combination of TACE and 3-D conformal RT. RESULTS: The greatest dimension of the main tumour in the whole group of patients ranged from 6 to 25 cm (median 15 cm). The radiation dose ranged from 40 to 60 Gy. The tumour response was evaluated by computed tomography scans of the liver 6-8 weeks after completion of radiotherapy. Partial response was observed in 58% of the patients (seven of 12) and minimal response in another 25% of patients (three of 12). One patient could not be evaluated because of the development of hepatic failure 1 month after completion of RT. All patients in group B lived for more than 1 year (range 16-40 months). In group A, one patient who had a large tumour (11 x 10 x 21 cm) with portal vein thrombosis was converted to become resectable after 45 Gy of radiation. The resection specimen revealed no residual cancer cells. This patient is alive longer than 15 months after treatment without the evidence of disease. CONCLUSIONS: Our experience indicates that HCC is more radiosensitive than it was traditionally expected. Three-dimensional reconstruction of tumour and surrounding organs helps to avoid excessive exposure of the liver and adjacent organs to RT and makes it a safer treatment modality for unresectable HCC. Our preliminary data show promise and are worthy of further study to explore the potential role of radiotherapy in the treatment strategy for HCC at various stages of involvement.

Two-phase study of hepatic artery vascular occlusion with microencapsulated cisplatin in patients with liver metastases from neuroendocrine tumors.

OBJECTIVE: We conducted a two-phase trial in which 100-micron polylactic acid microcapsules with a cisplatin payload (manufactured at our institution [the M. D. Anderson Cancer Center]) were used for hepatic artery occlusion therapy for symptomatic patients who had liver metastases from neuroendocrine tumors. SUBJECTS AND METHODS: Between January 1993 and December 1995, 20 patients with advanced, unresectable, symptomatic neuroendocrine tumors with liver metastases received repeated hepatic artery occlusion therapy using encapsulated cisplatin. The dose of encapsulated cisplatin was increased in a stepwise fashion. Selective angiography was used to occlude the portion of the hepatic vasculature that had the most metastases with encapsulated cisplatin microcapsules. In each patient, hepatic artery occlusion therapy was repeated in 6-8 weeks and responses were evaluated. Subsequent vascular occlusions were performed on the basis of the level of palliation achieved and the persistence of symptoms. RESULTS: Of the 20 patients, 17 patients had carcinoid tumors and three had islet cell tumors. The median percentage of liver replacement was approximately 50%. Fifteen of the 20 patients had received prior therapy and 17 patients had hormonal syndrome at the beginning of therapy. One patient had tumor bulk-related symptoms. Nineteen patients had elevated peptides markers that could be followed serially Six patients received encapsulated cisplatin at 50 mg/m2, four patients at 75 mg/m2, and 10 patients at 100 mg/m2 of body surface area. The median number of vascular occlusive procedures per patient was three. All patients were assessable for toxicity and 18 were assessable for response (the other two patients were not assessable because of loss of follow-up). The median follow-up time was 14 months. Twelve (67%) of 18 patients had a median reduction in symptoms of 50%. Eleven (73%) of 15 patients with elevated 24-hr-urine levels of 5-hydroxyindoleacetic acid had a median reduction of 64% for this symptom. We observed objective reduction in the tumors of 14 of the 18 patients. In six of the 14 patients, we noted a partial response. In eight, we observed a minor response. In four of the 18 patients, we noted no response. One treatment-related death resulted from hepatorenal syndrome. Other major complications included hepatic pain (100%), fever (100%), nausea (100%), and vomiting (95%). Also all patients had a transient elevation of liver enzymes. Five of the 20 patients died of disease during our study. CONCLUSION: Hepatic artery vascular occlusion therapy using encapsulated cisplatin is feasible, can palliate symptoms, and can produce biochemical and objective responses in liver metastases from neuroendocrine tumors. The maximum tolerated dose appears to be 100 mg/m2 of body surface area per treatment. Polylactic acid capsules have potential because they can incorporate multiple agents. With surface coating, such capsules can also be used to target specific receptors.

Carcinoid tumors: imaging procedures and interventional radiology.

The hypervascular nature of carcinoid tumors and their metastases allows a more aggressive role by the radiologist in diagnosis and interventional management. Double-contrast gastrointestinal studies still best define the primary neoplasms. Appendiceal tumors, the most frequent site of carcinoids, frequently escape radiologic detection until large enough to be discovered by computed tomography (CT). Superior mesenteric arteriography of the small bowel and cecum is useful when the scanning procedures are not revealing. The "spokewheel" configuration of the desmoplastic mesenteric masses and lymph node metastases are best seen by CT, whereas hepatic metastases can be demonstrated by CT, CT-angioportography (CTAP), ultrasonography (US), magnetic resonance imaging (MRI), and octreotide scintigraphy. Percutaneous needle biopsy with radiologic guidance confirms the diagnosis of carcinoid tumors and their metastases. Hepatic arteriography is frequently performed in preparation for hepatic embolization or chemoembolization. Hepatic vascular occlusion therapy, the procedure of choice for the management of inoperable carcinoid liver metastases, results in a partial response in at least 50% of patients and a mortality rate of 5%. Chemoembolization with microencapsulated cytotoxic agents and direct percutaneous ethanol injection should also be considered for the treatment of liver metastases.

A large lumen microcatheter for oncologic intervention.

A newly available Tracker-325 catheter (Target Therapeutics, Fremont, CA, USA), modified from the Tracker-18 catheter, has the same outer diameter but a larger lumen. This catheter was used in 15 patients during a 7-month period for superselective arterial catheterization when conventional catheters could not be placed successfully. Arterial embolization (n = 7), chemoembolization (n = 5), and chemoinfusion (n = 3), were performed. The increased luminal diameter of the Tracker-325 allowed an increased flow rate for diagnostic arteriography, accommodated larger embolic particles, and improved the ability to achieve a super-selective position.

Gastrointestinal leiomyosarcoma metastatic to the liver. Durable tumor regression by hepatic chemoembolization infusion with cisplatin and vinblastine.

BACKGROUND: Gastrointestinal leiomyosarcoma metastatic to the liver is considered most resistant to any combination of systemic chemotherapy containing doxorubicin and/or ifosphamide. METHODS: Fourteen patients with gastrointestinal leiomyosarcoma metastatic to the liver were treated with hepatic chemoembolization infusion consisting of polyvinyl alcohol sponge particles mixed with cisplatin powder (150 mg) followed by an intrahepatic arterial infusion of vinblastine (10 mg/m2). RESULTS: Ten major (> 50% regression) tumor responses were observed (70%) in patients lasting from 8 to 31+ months (median, 12 months) after an average of two hepatic chemoembolization procedures, usually 4 weeks apart. Transient side effects included right upper quadrant pain requiring narcotics, significant hepatic enzyme elevation, particularly of lactic dehydrogenase with a minimal increase in bilirubin, paralytic ileus requiring nasogastric suction up to 72 hours, urinary electrolyte losses (potassium+, magnesium++, sodium+) requiring supplements, and occasionally mild but transient leukopenia and thrombocytopenia. CONCLUSIONS: Hepatic chemoembolization infusion appears to induce a high rate of durable tumor response in patients with notoriously chemoresistant gastrointestinal leiomyosarcoma metastatic to the liver.

Arterial complications from long-term hepatic artery chemoinfusion catheters: evaluation with CT.

OBJECTIVE: The purpose of this study was to define CT changes in the common hepatic artery and the porta hepatis caused by complications of long-term placement of a catheter in the hepatic artery for infusion of chemotherapeutic agents via a surgically implanted pump or port. MATERIALS AND METHODS: We retrospectively reviewed abdominal CT scans of 115 patients before and after placement of a catheter into a hepatic artery for chemoinfusion, with special attention to the common hepatic artery and the porta hepatis. The changes seen on CT scans were correlated with clinical findings and other imaging findings (arteriography and radionuclide scanning) in patients who had symptoms related to catheters and pumps, including pain during treatment, persistent pain without apparent cause, or occlusion of the catheter. RESULTS: CT scans of 20 patients (17%) showed changes along the common hepatic artery. Five had rounded, low-density fluid collections around the tip of the catheter, believed to be caused by extravasation of chemotherapeutic agents or heparin. Five had well-defined soft-tissue densities along the hepatic artery, where the tip of the catheter was located; these were thought to be caused by dissection of the artery with periarterial fibrosis. Ten had poorly defined areas of low density along the vessel, which may have been caused by periarterial edema, arteritis, or extravasation of the chemotherapeutic agents. Two patients had pain on injection through the device, but no changes were seen on CT scans. Fourteen of 16 patients who had symptoms related to infusion catheters had CT changes in the porta hepatis. CONCLUSION: Fluid collections and soft-tissue densities around the tip of the catheter and along the hepatic artery seen on CT scans of patients who had surgical placement of catheters for chemoinfusion should be recognized as possible complications from the treatment and lead to further study to confirm the diagnosis.

Intraperitoneal catheters: percutaneous placement with fluoroscopic guidance.

PURPOSE: The authors reviewed their experience with percutaneous placement of catheters into the peritoneal cavity for the administration of intraperitoneal chemotherapy to determine if their approach resulted in a lower complication rate than the reported 12%-16% rate and to demonstrate the technical advantages over surgically placed catheters. PATIENTS AND METHODS: Seventy-six patients with gastrointestinal or gynecologic malignancies underwent 152 procedures during a 20-month period. The catheters were used to deliver antineoplastic agents and, in some patients, to drain ascites. Catheter insertion was performed with local anesthesia and a modified Seldinger technique. A 5-F catheter was used in 89% of procedures; in the remainder, the catheter was of a larger caliber. RESULTS: The procedure was successful in 145 (95%) instances and failed in seven (5%) attempts because of peritoneal adhesions. The catheters remained in place for less than 2 days in 56%, 2-10 days in 25%, and more than 10 days in 19% of patients. One catheter remained in place for 15 weeks. Complications occurred in seven procedures (5%). Four cases of mild peritonitis responded to a brief course of intravenously administered antibiotics, and severe pain in two patients required premature catheter removal. A single case of inadvertent transcolonic catheter placement occurred without adverse sequelae to the patient. CONCLUSIONS: Intraperitoneal catheterization can be performed with local anesthesia by using a simple technique with a very low complication rate. The catheters can remain in place for prolonged periods without significant risks.

In vivo microscopy of the liver after injection of Lipiodol into the hepatic artery and portal vein in the rat.

The route, distribution and clearance of intraarterially administered Lipiodol in the liver has been the subject of much speculation. The hepatic microcirculation was therefore studied by in vivo microscopy after injection of Lipiodol into the hepatic artery and the portal vein in rats. After intraarterial injection, Lipiodol rapidly entered the portal branches through arterio-portal communications. Lipiodol also passed through the sinusoids from the portal into the hepatic veins and then into the systemic circulation. Sinusoidal congestion occurred when the oil droplets filled the liver microcirculation and resolved as the oil was cleared. It is of clinical significance to note the passage of the oil into the systemic circulation after arterial injection.

Sclerosing cholangitis: palliation with percutaneous cholangioplasty.

Fourteen patients with sclerosing cholangitis underwent percutaneous cholangioplasty and stent placement with balloon-angioplasty and biliary-drainage catheters. There was initial clinical improvement in 13 of the 14 patients; one patient did not improve and died 1 month after the procedure. One of the 13 survivors developed encephalopathy and received a liver transplant 9 months after cholangioplasty; during the 9 months before transplantation, serum bilirubin and alkaline phosphatase levels returned to normal, and pruritus decreased. Restenosis of a duct following stent removal prompted repeat cholangioplasty in five of the 13 patients. Four of these five patients benefited from repeat cholangioplasty, and the fifth underwent liver transplantation 10 months after the second cholangioplasty. The other seven of the 13 survivors became either asymptomatic (n = 3) or less symptomatic than before cholangioplasty (n = 4) and did not require repeat cholangioplasty or liver transplantation during 10-42 months of follow-up.

The development of hepatobiliary cancer in a carrier of Salmonella typhus.

A case of Salmonella enteritis which resulted in a chronic typhoid carrier state is reported. The recurrent cholangitis progressed to sclerosing cholangitis, with subsequent development of cholangiocarcinoma. Although epidemiological studies demonstrate an increased risk of developing hepatobiliary cancer in chronic typhoid carriers, a documented case has never been reported.

Duodenocaval fistula: case report and literature review.

Duodenocaval fistulae are rare but may well be the source of gastrointestinal hemorrhage with associated sepsis in patients undergoing surgery and subsequently receiving radiation to the right upper abdomen. Management of these fistulae may be challenging. Diagnosis usually requires a high index of suspicion, particularly in post irradiated patients.

The geometry of triple-balloon dilation.

Triple-balloon dilation (TBD) of a variety of luminal structures has been successfully, though infrequently, used. A mathematical model is presented for the selection of balloon sizes, and equations and tables are derived that allow the user to estimate more accurately the size of balloons needed for TBD of structures with large lumina. With TBD, an approximately circular lumen can be formed. Also, TBD allows smaller, higher-pressure balloons to be used instead of single, low-pressure, large balloons. However, multiple puncture sites may be required for TBD.

Sheath needle for liver biopsy in high-risk patients.

Addition of an outer plastic sheath to a standard biopsy needle allows fluoroscopically monitored embolization of the biopsy site and needle tract with gelatin particles, thus reducing the risk of postbiopsy hemorrhage. This method has been used instead of the transjugular technique to perform liver biopsies in 22 patients considered to be at high risk for hemorrhage from biopsy performed with conventional techniques. A specimen adequate for diagnosis was obtained in 21 of the 22 patients. No patient exhibited clinical signs of postbiopsy hemorrhage.

Percutaneous vascular intervention after surgical shunting for portal hypertension.

Twenty percutaneous transluminal angioplasty (PTA) procedures and 13 percutaneous venous embolization (PVE) procedures were performed in 23 patients who either had or were at risk for the development of recurrent bleeding, hepatic encephalopathy, or both after surgical shunt placement for portal hypertension. PTA, performed in 12 patients with significant shunt stenoses, resulted in reduction or elimination of gradients in all patients; rebleeding has occurred in only one patient. Complications consisted of one fatal rupture of a mesocaval interposition vein graft and one balloon rupture requiring surgical removal. PVE, performed in 11 patients, resulted in measurable improvement in four of seven encephalopathic patients and temporary control in the two patients with intractable bleeding. Three patients underwent PVE prophylactically. PTA of graft strictures is a valuable treatment modality. Embolization may be helpful in selected cases of hepatic encephalopathy.