K. E. F. Hobbs

A Comparison of Sclerotherapy with Staple Transection of the Esophagus for the Emergency Control of Bleeding from Esophageal Varices

We compared two procedures for the emergency treatment of bleeding esophageal varices in patients who did not respond to blood transfusion and vasoactive drugs. We randomly assigned 101 patients with cirrhosis of the liver and bleeding esophageal varices to undergo either emergency sclerotherapy (n = 50) or staple transection of the esophagus (n = 51). Four patients assigned to sclerotherapy and 12 assigned to staple transection did not actually undergo those procedures, but all analyses were made on an intention-to-treat basis. Total mortality did not differ significantly between the two groups; the relative risk of death for staple transection as compared with sclerotherapy was 0.88 (95 percent confidence interval, 0.51 to 1.54). Mortality at six weeks was 44 percent among those assigned to sclerotherapy and 35 percent among those assigned to staple transection. Complication rates were similar for the two groups. An interval of five days without bleeding was achieved in 88 percent of those assigned to staple transection and in 62 percent of those assigned to sclerotherapy after a single injection (P less than 0.01) and 82 percent after three injections. In only 2 of the 11 patients who received a third sclerotherapy injection was bleeding controlled for more than five days, and 9 died. We conclude that staple transection of the esophagus is as safe as sclerotherapy for the emergency treatment of bleeding esophageal varices and that it is more effective than a single sclerotherapy procedure. We currently recommend surgery after two injection treatments have failed.

Treatment of small hepatocellular carcinomas.

There is growing interest in screening to detect symptomless hepatocellular carcinoma (HCC), which should be easier to treat than symptomatic tumours. Combined alpha-fetoprotein and ultrasound monitoring can detect HCCs of 1 cm, and Lipiodol retention can be detected in tumours smaller than 1 cm. A number of treatment options are available. Surgical resection may be curative in selected patients with a single small tumour, but the cirrhotic patient is left with a diseased liver and the risk of tumour recurrence or death from underlying liver dysfunction. Orthotopic liver transplantation is a rational treatment for patients with decompensating cirrhosis and a small HCC, but it is expensive and necessitates immunosuppression. A variety of targeted or local therapies, either individually or in combination, can be used to treat HCC. These include percutaneous alcohol injection into an HCC, which may be an alternative to surgical resection. Tumour necrosis can be seen after targeted Lipiodol chemotherapy or radiotherapy. Transcatheter arterial embolisation selectively embolises the feeding artery, and can be combined with Lipiodol chemotherapy. Small tumours are thus amenable to treatment, even in patients who cannot have surgery. Screening and treatment for symptomless HCC seems justified, unless controlled trials teach us differently.

A prospective controlled study comparing brush and bile exfoliative cytology for diagnosing bile duct strictures.

Imaging of biliary strictures may suggest malignancy but cytology can provide a tissue diagnosis. The aim of this study is to compare the diagnostic value of brush cytology and bile cytology. Thirty two patients (20 males, 12 females, median age 66 years, range 31-84) with biliary strictures at endoscopic retrograde cholangio pancreatography (24) or percutaneous transhepatic cholangiography (8) had bile cytology and brush cytology. Brushings were taken using a modified Geenan cytology brush (6 Fr gauge, Wilson Cook) passed alongside a guide wire placed through the stricture. Bile was aspirated after insertion of an internal/external catheter or an endoprosthesis. Bile and brushings were examined by one experienced cytologist (AD) and was reported as positive or negative for malignant cells. Twenty nine patients had malignant strictures. Sixteen were confirmed by histology and 13 had malignancy suggested by clinical follow up. Three patients had resection of histologically benign strictures. The overall sensitivity of brush cytology (17 of 29 positive, 59%) was significantly greater than bile cytology (seven of 29 positive, 24%) (p < 0.01) as was the diagnostic accuracy (63 v 31%, p < 0.01). None of the patients had positive bile cytology with negative brush cytology. There were no procedure related complications and the average sampling time once the guide wire had been inserted was less than five minutes. It is concluded that brush cytology is more sensitive than bile cytology and with the technique described is safe and rapid.

Epirubicin-lipiodol chemotherapy versus 131iodine-lipiodol radiotherapy in the treatment of unresectable hepatocellular carcinoma

Background. Arterially administered iodized oil (Lipiodol) is selectively retained by hepatocellular carcinomas (HCCs), and has been used as a vehicle for delivery of therapeutic agents to these tumors. This study compared the efficacy of Lipiodol‐targeted epirubicin chemotherapy with Lipiodol‐131I radiotherapy.

Value of exfoliative cytology for investigating bile duct strictures.

The cause of a biliary tract stricture may be difficult to determine radiologically. Exfoliative biliary cytology was evaluated in 62 patients (median age 65 years, range 30-94) with biliary tract strictures presenting to the Hepatobiliary Unit between January 1984 and December 1989. Bile samples were taken during endoscopic retrograde cholangiopancreatography (ERCP) in 42 patients, percutaneous cholangiography in 14, and both in six. The site of stricturing was upper third of the bile duct in 43% (n = 27), middle third in 10% (n = six), and lower third in 47% (n = 29). Of the 47 patients with radiological appearances of a malignant stricture, 22 (47%) had histological confirmation by biopsy either under computed tomography guidance, at endoscopy, at operation, or at necropsy. Fourteen of the 47 patients had positive cytology (30%). In seven patients cytology alone established the presence of malignancy (15%) and in the other seven positive cytology was confirmed by histology. The addition of cytology to tissue biopsy therefore allowed malignancy to be confirmed in 29 of the 47 patients (62%). None of the 15 patients subsequently shown to have benign disease had positive cytology. Sensitivity of the technique was 30% and specificity 100%. Samples for exfoliative cytology are simple to obtain, the results are highly specific and should be a routine part of the investigation of biliary strictures.

EXPRESSION OF BETA-2-MICROGLOBULIN ON HEPATOCYTES AFTER LIVER TRANSPLANTATION

The distribution of beta 2-microglobulin was studied by an immunoperoxidase method in paraffin sections from sixteen serial graft liver biopsy samples taken after liver transplantation from four patients who had received transplants for advanced primary biliary cirrhosis. Mild to moderate acute rejection was diagnosed in three of the patients. Expression of beta 2-microglobulin on hepatocyte membranes was greater during rejection, and tended to fall after the rejection episode. However, a few hepatocytes continued to display beta 2-microglobulin on their cell membranes. Rejection was characterised histologically by infiltration of portal tracts with lymphoid cells, and cholestasis. Enhanced display of beta 2-microglobulin on hepatocytes probably reflects display of HLA A, B, and C antigens and may be associated with increased susceptibility of the affected cells to T-lymphocyte-mediated immune attack.

Selective Regional Chemotherapy of Unresectable Hepatic Tumours Using Lipiodol

Over a 30 month period from 1987 to 1990, selective hepatic cannulation under fluoroscopic control was performed in 57 consecutive patients with primary and secondary malignancies of the liver. Fifty-three patients were subsequently treated using intra-arterial Lipiodol emulsified with epirubicin. The tumours treated were hepatocellular carcinoma (n = 35), metastatic adenocarcinoma (n = 14), intrahepatic cholangiocarcinoma (n = 3) and leiomyosarcoma (n = 1). For hepatocellular carcinoma the cumulative survival was 38% at one year; the median survival was 12.2 months for Stage I, 6.3 months for Stage II and 0.9 months for Stage III tumours. In metastatic disease the cumulative survival was 63% at one year. These data suggest that targeted intra-arterial chemotherapy with Lipiodol-epirubicin is a useful palliative therapy for patients with Stage and II HCC, and that a controlled trial of this treatment should be undertaken.

Staple-line erosion : a common source of recurrent bleeding following stapled oesophageal transection

Recurrent bleeding after stapled oesophageal transection was studied in 73 patients with cirrhosis transected for acute variceal bleeding. The most frequent source of bleeding was partial or total circumferential oesophageal erosion at the transection: staple‐line erosion. This lesion occurred in 36 (49 per cent) patients and was the source of rebleeding in 29 (40 per cent) patients with 54 episodes. Rebleeding in 22 (30 per cent) patients was due to varices in nine (12 per cent), peptic ulcer in six (8 per cent), gastric erosions in two (3 per cent) and unknown sources in five (7 per cent), accounting for 33 episodes. The mean(s.e.m.) blood transfusion requirement for bleeding from staple‐line erosions was 1.5(0.25) units per bleed versus other sources, 6.5(1.0) units per bleed (P < 0.001). Staple‐line erosion was present at the first postoperative endoscopy in 11 (15 per cent) patients but the time to appearance varied widely. The lesion was more common in patients with Pughs grade A liver disease at the time of transection, reflecting the increased survival rate of these patients. Staple‐line erosion is a common source of minor recurrent bleeding following stapled oesophageal transection.

Selective radionuclide localisation in primary liver tumours (pilot study).

The therapeutic potential of 131I-Lipiodol was investigated in 8 patients with cholangiocarcinoma (CCA) and 15 patients with hepatocellullar carcinoma (HCC). Patients received one or two doses of 131I-Lipiodol via hepatic arterial injection. The mean total administered activity was 668 (SD 325) MBq in CCA and 953 (SD 477) MBq in HCC. One patient with CCA retained 131I-Lipiodol. The cumulative radiation dose was 9.6 Gy to tumour, 6.4 Gy to liver and 1.5 Gy to lung. The patient remained asymptomatic with no evidence of tumour 30 months from the start of treatment, whereas the remaining 7 patients exhibited tumour progression. The mean survival in CCA was 11.6 (SD 14.5) months. All 15 patients with HCC retained 131I with tumour: liver ratios of up to 30:1. The mean cumulative radiation dose was 34.7 (SD 32.4) Gy to tumour, 3.3 (SD 1.5) Gy to liver and 4.4 (SD 2.3) Gy to lung. The mean dose per administered activity was 3.8 (SD 4.1) cGy/MBq. Partial response (reduction in tumour size > 50%) was observed in 6 patients (40%). The mean survival was 7.1 (SD 6.0) months. 131I-Lipiodol can deliver highly selective internal irradiation to foci of HCC with evidence of objective response and may be the treatment of choice for patients with cirrhosis and a small tumour.

Duodeno-jejunal varicosities following extrahepatic portal vein thrombosis.

A 31 year old man, under investigation for melena, was found at endoscopy to have varicosities at the site of a duodeno-jejunostomy which had been performed for duodenal atresia when he was three days old. Angiography revealed an occluded portal vein with an extensive collateral circulation. At laparotomy some of the collateral vessels were found to pass through the anastomotic site and directly into the left lobe of the liver. The portal pressure was found to be minimally elevated. Resection of the anastomotic segment was performed with reconstruction using a Roux en Y jejunal loop. Bleeding from collateral vessels passing through an anastomosis site in a patient with extrahepatic portal vein thrombosis has not previously been reported.