Gastric and duodenal obstruction in patients with cholangiocarcinoma in the porta hepatis: increased prevalence after radiation therapy.

OBJECTIVE: Our objective was to study the imaging findings in patients who had gastric and duodenal obstruction as a long-term complication of cholangiocarcinoma and to determine if the obstruction was associated with radiation therapy. MATERIALS AND METHODS: Between 1973 and 1989, 96 patients had either curative resection or palliative stenting for cholangiocarcinoma involving the hepatic duct bifurcation. Sixty-three (66%) also received adjuvant radiation therapy ranging from 4960 to 7220 rad (cGy). Gastric outlet or duodenal obstruction or both developed subsequently in seven of the 63 patients treated with radiation therapy. Radiographic studies, including upper gastrointestinal series and CT, and medical and surgical records for these seven patients were retrospectively reviewed. RESULTS: Upper gastrointestinal series in the seven patients with obstruction showed narrowing of the lumen, deformity and enlargement of gastric and duodenal mucosal folds, and delayed gastric emptying. CT performed in five of the seven patients showed thickening of the wall of the gastric antrum and small bowel and retained food and fluid within the stomach. All seven patients required gastrojejunostomy; at surgery, dense adhesions and fibrosis were found, and it was not evident whether the obstruction was due to the tumor or to radiation fibrosis. However, because this complication was seen only after radiotherapy, it was presumed to be radiation fibrosis. CONCLUSION: Our experience suggests that radiation therapy increases the risk of postoperative gastric and duodenal obstruction in patients undergoing surgery for cholangiocarcinoma.

Analysis of failure after curative irradiation of extrahepatic bile duct carcinoma.

Thirty-four patients with subtotally resected or unresectable carcinoma of the extrahepatic bile ducts received radiation therapy; a minimum of 45 Gy (external beam) to the tumor and regional lymph nodes +/- 5-fluorouracil (5-FU). Seventeen patients received an external beam boost of 5 to 15 Gy to the tumor, and a specialized boost was used in the remaining 17 patients (iridium-192 transcatheter seeds in 10 and intraoperative radiation therapy [IORT] with electrons in seven). The median time to death in all 34 patients was 12 months (range, 4 to 98-months). The only patients who survived longer than 18 months were those either with gross total or subtotal resection before external irradiation (2 of 6) or who received specialized boosts (192Ir, 3 of 10; IORT, 3 of 7). Local failure was documented in 9 of 17 patients who received external beam irradiation alone +/- 5-FU, 3 of 10 patients who received an 192Ir boost, and 2 of 6 patients who received an IORT boost with curative intent.

Radiotherapy of cholangiocarcinoma: the roles for primary and adjuvant therapies.

A total of 22 patients with cholangiocarcinoma who had been treated with external radiotherapy between 1978 and 1989 were analyzed. Of the 22 patients, 18 had cancer of the hepatic hilus (Klatskin) and 4 had intrahepatic biliary cancer; all but 2 of the subjects had advanced disease. In all, 16 patients underwent primary irradiation for unresectable tumors, 4 were subjected to adjuvant irradiation after gross tumor resection, and 2 received preoperative irradiation followed by gross tumor resection. The mean initial irradiation dose was 52.0 Gy (range, 26-78 Gy). The TDF (time-dose-fractionation) for the entire course of radiotherapy ranged from 49 to 154 (mean, 100). The median survival of all patients was 10 months, and the cumulative 1-year survival value was 37.7%. The external radiotherapy proved to be effective in the treatment of cholangiocarcinoma in terms of palliation and survival.

[Combined moving strip whole liver irradiation and traditional Chinese medicine for large liver cancer].

This paper reports the result of large liver cancer treated by moving strip whole liver irradiation from 1980 to 1988. The 5-year survival rate was 30.83% +/- 7.77% and the median survival time was 25.8 months. Analysis of factors affecting prognosis showed: 1. The higher the midplane tissue irradiation dose, the longer the survival (P less than 0.001) and 2. Patients with greater than or equal to 8 less than 13 cm tumor diameter and/or greater than or equal to 50% less than 75% tumor/liver volume ratio had longer survival than those with greater than or equal to 13 cm diameter and/or greater than or equal to 75% tumor/liver volume ratio (P less than 0.001). Traditional Chinese medicine was indispensable as a supplement to this treatment. Both clinical and experimental study suggested that this technique could improve the patient's final outcome.

Variable low dose rate irradiation (131I-anti-CEA) and integrated low dose chemotherapy in the treatment of nonresectable primary intrahepatic cholangiocarcinoma.

Previous experience using 131I anti-CEA antibody, which irradiates at a variable low dose rate in combination with a multimodality treatment program, has demonstrated acceptable toxicity and response in primary intrahepatic cholangiocarcinoma. In attempting to improve therapy, Cis-platin was added to the prior regimen. Induction therapy was unchanged. One month later, chemotherapy was given (doxorubicin, 15 mg, 5-fluorouracil, 500 mg, plus Cis-platin, 20 mg/M2) followed the next day by outpatient administration of 20 mCi 131I anti-CEA by i.v. bolus. Five days later, 10 mCi was administered. The latter regimen (chemotherapy plus 20 + 10 mCi 131I anti-CEA) was repeated every 2 months using polyclonal antibodies derived from different species (rabbit, pig, baboon, and horse). Twenty-four patients (29% with prior chemotherapy and/or metastases) were prospectively treated according to this regimen. Toxicity was limited to hematologic toxicity and was manifested by thrombocytopenia and leukopenia (17% and 4% grade 4, respectively, according to RTOG toxicity criteria). Tumor remission was evaluated by CT volumetric analysis and demonstrated a 14% response rate for the induction portion of therapy, 24% for the radioimmunoglobulin portion of treatment, and 50% remission rate when all subsequent tumor volumes were compared to the pre-treatment volume (entire program). The median survival for the entire group of patients was 10.1 months. This result is superior to previously reported trials and, in comparison to our previous study (10.1 vs 6.5 months median survival), further advancement in protocol design appears to have been made. In view of the rarity of this disorder, a randomized trial is not possible and strict statistical analyses cannot be made. The mechanism of 131I-anti-CEA variable low dose irradiation and chemotherapy interaction is discussed as well as further potential modifications for treatment improvement.

Radiotherapy of bile duct carcinoma using intracatheter 198Au grains.

Eight patients with bile duct carcinoma were treated with radiotherapy using intracatheter 198Au grains. The intracatheter 198Au grains in an inner tube were inserted into a percutaneous transhepatic catheter. A plastic tip was placed between these grains to improve spatial and temporal dose allocation. This method and 192Ir wire irradiation resemble each other closely in dose distribution, but the former has the following advantages over the latter. 1) The number of 198Au grains used can be changed quite easily in accordance with the length of the stenosis. 2) The half-life of 198Au is about 2.7 days, and a dose of 25-40 Gy at 1.0 cm from the source is delivered over this period. The medical staff can protect themselves from radioactivity when the sources are withdrawn after brachytherapy. 3) 192Ir wire is not used very frequently in spite of its long half-life (74 days) because bile duct carcinoma is uncommon. 4) In Japan, 198Au grains can be purchased on a weekly basis, so treatment plans can be easily made. The eight patients also received external irradiation and the median survival after onset of radiotherapy was 7.9 months. There have been few systemic or local complications.

Radiotherapy of postoperative residual tumor of bile duct carcinoma.

The case of a patient with bile duct carcinoma who had a postoperative residual tumor treated with high-dose-rate intraluminal brachytherapy (HDRIBT) following external radiotherapy is presented. Following radiotherapy, he has been alive and well without signs of recurrence for two years and eleven months as of this writing. HDRIBT following external irradiation is recommended for the treatment of postoperative small residual tumors of the bile duct.

Treatment of cancers involving the liver and porta hepatis with external beam irradiation and intraarterial hepatic fluorodeoxyuridine.

A Phase I/II clinical trial was designed for patients with malignancies of the liver and porta hepatis. This protocol employed three concepts: a) boost treatment to gross tumor within the liver for selected patients, determined by the dose-volume histogram (DVH) of the normal liver that would be irradiated by boost treatment; b) concurrent use of intraarterial hepatic 5-fluorodeoxyuridine (FdUrd) as a radiosensitizer; and c) hyperfractionation (1.5 Gy fractions given bid greater than 4 hr apart). This report describes the results of treatment of the first 33 patients entered onto this study, with a minimum follow-up of 1 year. Twenty patients received only whole liver irradiation (33 Gy). Thirteen patients were treated with whole liver irradiation (30 Gy) plus a 15 Gy (6 patients) or 30 Gy (7 patients) boost (total 45 Gy and 60 Gy to the tumor, respectively). Forty-eight percent of the evaluable patients (14/29) had an objective response, based on CT scan. The median duration of response was 8 months. The chief toxicities were fatigue, nausea, gastritis, and diarrhea, which were less than or equal to grade 2 in severity. Two patients developed mild radiation hepatitis which was treated successfully with diuretics. These data suggest that the treatment of intrahepatic malignancies can be guided by the concept of DVH analysis of the normal liver to allow the safe administration of doses of radiation that are potentially tumoricidal and are well above those that would be predicted to be tolerable for the whole liver.

Does additive radiotherapy after hilar resection improve survival of cholangiocarcinoma? An analysis in sixty-four patients.

Between September 1983 and January 1990, 64 patients with Klatskin tumors were treated with resective therapy in the Academic Medical Centre Amsterdam. Twenty-nine patients received postoperative adjuvant radiotherapy, 22 patients were treated with resective therapy only and there were 13 postoperative deaths. The longterm results in the patients treated with or without adjuvant radiotherapy were retrospectively assessed. Three patients had a curative resection. Comparison of both therapeutic modalities demonstrated a statistically significant difference in survival (P less than 0.001) in favour of the patients who were treated with additive radiotherapy. The radiotherapy was generally well tolerated.

Interventional radiology of the biliary tract. Intraductal radiation.

One palliative method of treating patients with a high duct cholangiocarcinoma is the use of 192Ir wire. This is placed through the tumor, which has been previously intubated, and delivers a high local dose of radiation. The mean survival time in 30 patients treated with intraductal radiation was 16.8 months, an improvement compared to surgical bypass or endoscopic and radiologic drainage procedures.

The role of radiotherapy in the treatment of bile duct carcinoma.

Forty-two patients with irresectable bile duct carcinoma (n = 31) or with microscopic evidence of tumor rest after aggressive surgery for bile duct carcinoma (n = 11) were given radiotherapy consisting intentionally of external-beam therapy and intraluminal 192Iridium (192Ir) wire application(s) following bile drainage procedures. The treatment was well tolerated; complications were mainly infectious and related to the success of the drainage. A median survival of 10 months was achieved for the group as a whole. Patients treated following microscopically incomplete resection survived longer than patients with an irresectable tumor (15 vs 8 months median survival, p = 0.06). Gross lymph node involvement also proved to be a prognostic factor.

Management of proximal cholangiocarcinomas by surgical resection and radiotherapy.

Ninety-six patients with proximal cholangiocarcinomas were managed surgically. Fifty-three patients (55 percent) were resected, 39 curatively (41 percent), and 43 (45 percent) underwent palliative stenting. The preoperative placement of Ring catheters and the operative use of silastic transhepatic biliary stents greatly facilitated the surgical management of these lesions. Sixty-three patients (66 percent) also received postoperative radiotherapy. Hospital mortality was 4 percent (four deaths). Hospital mortality was 2 percent after resection (1 of 53 patients) and 7 percent after palliative stenting (3 of 43 patients). All deaths resulted from sepsis. One, 3, 5, and 10-year survivals for the entire group were 49 percent, 12 percent, 5 percent, and 2 percent, respectively. One, 3, 5, and 10-year survivals in the resected group (66 percent, 21 percent, 8 percent, and 4 percent, respectively) were superior to those in the stented group (27 percent, 6 percent, 0 percent, and 0 percent, respectively). Radiotherapy appeared to significantly extend survival in those patients undergoing palliative stenting, but not in those undergoing resection. We conclude that surgical resection of proximal cholangiocarcinomas can be performed safely and that it significantly prolongs survival. Further improvement in long-term survival will depend on advances in adjuvant therapy.

Endoscopic management of inoperable cholangiocarcinoma using iridium-192.

We report a well tolerated endoscopic technique of administering intraluminal radiotherapy to 14 patients with inoperable cholangiocarcinoma, in which the iridium-192 wire source was inserted down a nasobiliary catheter placed within a previously inserted endoscopic biliary prosthesis, thus allowing bile flow to continue during treatment. Radiotherapy was commenced 2 weeks after biliary decompression, when the median serum bilirubin level had fallen from 213 to 34 mumol/l. A total radiation dose of 6000 cGy at 0.5 cm from the source was administered over a median of 85 h (range 77-116 h). In four patients there was a transient increase in serum bilirubin during iridium treatment and, in two cases (14 per cent), this was associated with mild cholangitis. Both cases resolved rapidly once the iridium wire and nasobiliary catheter were removed. The median hospital stay after treatment was 2.5 days (range 0-28 days). The late complications associated with stent blockage were minimized by routinely changing stents at 4-6 monthly intervals; ten of the patients have so far undergone from one to five (median three) stent changes. Five patients have died at 3.6-8.2 months (median 4.8 months) following iridium treatment; four had extensive type III hilar lesions at diagnosis. Nine patients are still alive at 5.4-31.0 months (median 16.4 months). The overall median survival after iridium therapy is 10.5 months. This technique of endoscopic biliary decompression before internal iridium administration minimizes complications by allowing biliary drainage during treatment. The role of this treatment in patients with inoperable cholangiocarcinoma awaits the results of randomized, controlled trials.

Hilar cholangiocarcinoma associated with clonorchiasis.

Pathologic and epidemiologic evidence support the relationship between the liver fluke Clonorchis sinensis and the development of bile duct cancer. We report here a case of cholangiocarcinoma in a Laotian immigrant originally diagnosed with clonorchiasis. This case demonstrates the importance of early recognition and treatment of this disease to prevent subsequent morbidity and mortality. Diagnosis and treatment of clonorchiasis as well as the possible modes of cancer induction are discussed.

Absence of fatty replacement in radiation damaged liver: CT demonstration.

Computed tomography from two patients with chronic radiation-induced hepatic damage demonstrates focal sparing within the radiation portal from otherwise diffuse fatty infiltration.