Treatment Of Bile Duct Carcinoma Research Articles

Progress of diagnosis and treatment of cholangiocarcinoma

Due to the high degree of malignancy and low surgical resection rate of cholangiocarcinoma, as well as the immaturity of postoperative adjuvant chemotherapy and targeted therapy drugs, the mortality rate of patients with cholangiocarcinoma is high and the long-term prognosis is poor. With the improvement of clinical diagnosis and treatment, preoperative evaluation and surgical technique, the diagnosis and treatment of cholangiocarcinoma have made some progress. The early stage of cholangiocarcinoma is lack of specific manifestations, so the patient has lost the opportunity of R0 resection when diagnosed. Early diagnosis can improve the patient′s R0 resection and long-term survival after surgery. The diagnostic accuracy can be improved by contrast enhanced ultrasound, enhanced magnetic resonance, positron emission tomography PET, etc. Dominated by comprehensive therapy in the treatment of bile duct carcinoma, strive for R0 resection for resectable cholangiocarcinoma, distant metastasis occurred after bile duct carcinoma can be combined with new adjuvant chemotherapy according to the review situation decides whether it is feasible to surgery, postoperative chemotherapy, molecular targeted therapy, body directional radiation therapy, and other comprehensive solutions in order to improve the long-term survival rate. This article reviews the recent progress in the pathogenesis, diagnosis and treatment of cholangiocarcinoma. Key words: Bile duct neoplasms; Diagnosis; Therapeutic uses

Synergic effect of photodynamic therapy using talaporfin sodium with conventional anticancer chemotherapy for the treatment of bile duct carcinoma

BackgroundPhotodynamic therapy (PDT) is an effective laser treatment for locally treating advanced bile duct carcinoma (BDC). The study objective was to evaluate the synergic effect of PDT using a new photosensitizer, talaporfin sodium (Laserphyrin), in combination with conventional anticancer drug treatments. MethodsThe range of the necrotic area, the percentage of apoptosis-positive cells, the vascular endothelial growth factor expression quantification, and the proliferating cell nuclear antigen–labeling index, as treatment effects, were examined in the BDC cell line (NOZ) in vitro and in vivo (4-wk-old male BALB/c mice). ResultsTumor viability was determined by an in vitro MTS assay. PDT with a single treatment of 5-fluorouracil, gemcitabine, oxaliplatin, and cis-diamminedichloroplatinum showed a significantly lower viability compared with the control or the PDT-alone group (P<0.05). Furthermore, administering PDT combined with two anticancer drugs showed a further decline in the tumor viability. A treatment of PDT combined with oxaliplatin and gemcitabine showed the least viability (P<0.05). Thus, this regimen was administered in the in vivo study. The tumor necrotic area, apoptosis positivity, and the vascular endothelial growth factor expression rate were higher in the PDT with anticancer drugs group compared with those of the other groups (P<0.05). The proliferating cell nuclear antigen–labeling index results in the PDT with the anticancer drugs group were significantly lower than those of the other groups (P<0.05). ConclusionsA treatment of PDT combined with gemcitabine and oxaliplatin showed the best synergic effect for necrosis, apoptosis, and cytostatic alterations for the treatment of BDC.

Experimental Evaluation of Microwave Antenna for Thermal Treatment of Bile Duct Carcinoma

A thermal treatment method that involves the use of an endoscope equipped with a microwave antenna is recognized as a new therapeutic method for treating bile duct carcinomas. In this treatment, the antenna is inserted into the bile duct through the papilla of Vater noninvasively using the forceps channel of the endoscope, and then, the part of the bile duct that has to be treated is locally heated. The antenna consists of a flexible coaxial cable, and microwave energy is radiated from the antenna slot at the tip. We have evaluated the heating performance of the antenna by heating the extracted organs using the antenna. In order to investigate the effectiveness and safety of this thermal treatment for clinical use, we carried out an animal experiment for evaluating the operability and robustness of the antenna and studying whether the temperature of the bile duct could be increased to 42°C without any tissue coagulation around the antenna slot under the blood flow condition. In the experiment, first, we inserted the antenna into the bile duct invasively by passing it through the duodenum. Next, we used X-ray images to adjust the position of an optical fiber thermosensor such that the distance between the slot of the antenna and the point at which the temperature was measured was not very large. As a result of the measurement, when an input power of 15 W was supplied to the antenna and the irradiating microwave was in the on state for 20 s and off state for 5 s, the temperature could be maintained at 42°C without any tissue coagulation by using the antenna for 30 min. The measured temperature position was located at the distance of 4.8 mm from the antenna slot. In addition, it was confirmed that the antenna was sufficiently robust, as it did not break down during the experiment. Therefore, we concluded that the antenna is suitable for use in thermal therapy. Further, we also analyze by using numerical simulation, in which the blood flow rate was 2.33×10-5 m3/kg•s, where the simulation results agreed well with the experimental results. Since the value of the blood flow rate was not quite different with the reference, the result was considered reasonable. Therefore the analytical model employed in this study can be used for improving the antenna structure and evaluating the therapeutic modality.

Some problems that should be paid attention to in diagnosis and treatment of bile duct carcinoma

Some problems that should be paid attention to in diagnosis and treatment of bile duct carcinoma

Estimation of heating performances of a coaxial-slot antenna with endoscope for treatment of bile duct carcinoma

Hyperthermia is one of the modalities for cancer treatment, utilizing the difference of thermal sensitivity between tumor and normal tissue. Up to now, the authors have been studying various coaxial-slot antennas for microwave hyperthermia. A coaxial-slot antenna aiming at intracavitary heating for bile duct carcinoma has been especially developed. In this paper, heating performances of such an antenna are estimated for the actual treatments. As a result of the investigations, the possibility of this treatment by use of the proposed coaxial-slot antenna could be confirmed

Conservative and interventional endoscopic therapy of biliary tract carcinoma

Endoscopic therapy is central to the palliative treatment of bile duct carcinoma. In obstructive jaundice, biliary drainage has few complications and relieves symptoms reliably. It can prevent further complications and is indispensable to the treatment of cholangitis. The principal drawback of biliary stents is stent occlusion and cholangitis. Prophylactic antibiotics were not proven to be effective. Technical details concerning material, number and location of stents await further clarification. Photodynamic therapy is an emerging adjunct to palliative therapy of biliary cancer. Preoperative biliary drainage in obstructive jaundice is not warranted as a routine intervention. It may be indicated, though, as preoperative bridging or to allow liver function to recover before major hepatic surgery. Finally, stenting of postoperative bile duct stenosis is gaining increasing acceptance.

Retrograde portography of the right caudate lobe via the middle hepatic vein.

Hepatobiliary resection with caudate lobectomy has been conducted in the surgical treatment of bile duct carcinoma of the hepatic hilus. However, insufficient attention has been paid to the anatomy of the right portion of the caudate lobe, and techniques to visualize the portal branches of the right caudate lobe (P1r) have not been reported. Contrast medium was injected into the dorso-caudal branches of the middle hepatic vein (MHV) and images were obtained by digital subtraction venography. Retrograde portography of the P1r was achieved in 64 (84%) out of 76 cases. The mean number of visualized branches was 2.1 (137 out of 64) and the P1r coursed beyond the trunk of the MHV in 36 (56%) out of the 64 cases. Contrast medium flowed into the right portal vein from 59 P1r branches in 32 cases and into the left portal vein in 20 cases. No complications were encountered. Retrograde portograms of the P1r may provide valuable information not previously available to surgeons operating on the caudate lobe.

Diagnosis and non-surgical treatment of bile duct carcinoma: developments in the past decade.

In the past decade, ultrasonography and magnetic resonance cholangiography have become useful modalities for the screening of bile duct cancer. Intraductal ultrasonography, using a thin-caliber (2.0 to 2.4 mm in diameter) and high-frequency (15 to 20 MHz) probe, has become a promising modality in assessing locoregional staging. For interventional therapy of unresectable bile duct carcinoma, metallic stents also became an excellent modality. However, tumor ingrowth and overgrowth into the mesh of stents are problems to be solved, and external radiation therapy is widely conducted to control the tumor. To improve the limitations of external radiation, brachytherapy, photodynamic therapy, and microwave coagulation therapy are conducted. However, these modalities are available in only a limited number of institutions even now. To predict the prognosis of the patients, approaches using molecular biology must be established.

Distribution and pharmacokinetics of Photofrin in human bile duct cancer.

Prognosis of patients with bile duct tumors is mostly poor due to late diagnosis and a lack of adequate curative and palliative treatment modalities. To evaluate the potential of photodynamic therapy (PDT) as a novel and alternative treatment approach, we have investigated the uptake and tumor-specific localization of the photosensitizer Photofrin in human biliary tract neoplasms. We have quantified the distribution and the pharmacokinetics of Photofrin in normal and tumor tissue biopsies of the human bile duct by quantitative fluorescence microscopy and digital image analysis of cryosections. Fluorescence intensities (expressed as a percentage of a standard) are 19.0 +/- 11.4% and 25.2 +/- 12.7% for tumors and 10.9 +/- 2.9% and 13.2 +/- 9.1% (mean +/- SD) for normal bile duct tissue at 24 h (n = 5) and 48 h (n = 8) after Photofrin administration (2 mg kg-1 i.v.), respectively, and decrease afterwards in normal bile duct tissue over the period of investigation (4-35 days). The ratios of fluorescence in tumor versus normal tissue are found to be 1.7 +/- 0.7 and 2.3 +/- 1.2 (mean +/- SD) at days one and two after Photofrin administration, respectively. Thus, Photofrin preferentially accumulates in bile duct neoplasms, reaching peak values during the first two days. These data suggest that laser irradiation should be performed within this period after Photofrin injection to achieve tumor selectivity of PDT for effective treatment of bile duct carcinoma.

Application of endoscopic microwave coagulation to the treatment of bile duct carcinoma

Endoscopic microwave coagulation therapy (EMCT) was applied to female patients aged 79 and 82 with obstructive jaundice due to lower bile duct carcinoma, because of their refusal pancreatoduodenectomy (PD). A single 10-second exposure of microwave (50W, 2450 MHz) was delivered 15 to 20 times during each treatment to the cancerous tissue using a monopoler shielded wire electrode under guidance of a percutaneous cholangioendoscopy. Treatment was repeated a total of three or six times at intervals of 1 week, and an expandable metallic stent was placed after recanalization of bile duct and negative tests for cancer cells. Supplementary radiation therapy (50.4Gy) was performed after EMCT, and no complications were encountered. Patients have subsequently lived well for 15 and 14 months without jaundice. These results indicate that EMCT for patients with lower bile duct cancer and high operative risk might be an effective alternative for PD.

Does bile spillage during an operation present a risk for peritoneal metastasis in bile duct carcinoma?

Whether bile spillage during operation presents a risk for peritoneal metastasis in the treatment of bile duct carcinoma was studied in 15 patients (12 with bile duct cancer, 3 with cancer of the papilla of Vater) who had all undergone a pancreatoduodenectomy. Preoperative bile was sampled through a percutaneous transhepatic biliary drainage catheter. Nine patients with bile duct cancer and one with cancer of the papilla of Vater showed positive bile cytology. The operative bile was obtained at the hepatic duct stump after a resection of the tumor-bearing bile duct. The operative bile in 10 patients with positive preoperative bile was found to be positive, while that in the five patients with negative preoperative bile was negative. Thus, the specificity of operative bile was identified as 100%. Moreover, in five patients with preoperative positive bile, saline irrigation of intrahepatic bile duct after a full recovery of hepatic bile revealed cancer cells to remain in the intrahepatic biliary trees. The viability of preoperative bile was 61%-97% with 1 x 10(4)-2.4 x 10(5) tumor cells, whereas there was a 41%-97% viability with 7.6 x 10(4)-10.4 x 10(5) tumor cells in the operative or irrigated bile. Accordingly, the patients with preoperative positive bile are thus suggested to be at high risk of inducing peritoneal metastasis due to the inadvertent spillage of hepatic bile at the time of resection of a bile duct tumor.

86 Intralumenal brachytherapy in the treatment of bile duct carcinoma

86 Intralumenal brachytherapy in the treatment of bile duct carcinoma

Surgical Treatment of 724 Carcinomas of the Gallbladder Results of the French Surgical Association Survey

The objective of this study was to evaluate the benefit of an aggressive approach to gallbladder carcinoma on long-term survival. Recent studies have shown that an aggressive surgical treatment of bile duct carcinoma can be associated with a surprising long-term survival. However, recent data on gallbladder carcinoma are not available. Data were obtained from a questionnaire sent to 73 institutions in France, Europe, and overseas, and they were analyzed retrospectively. The review included an analysis of patient sex and age, associated hepatobiliary diseases, symptoms and signs, diagnostic tests, operative management, pathology reports, and survival. Seventy-eight per cent of the patients were women, and 22% were men (p < 0.001). Gallstones were present in 86% of the cases. Four per cent of the patients had Tis stage lesions, 11% had T1 to T2 stage lesions, and 85% had T3 to T4 stage lesions (p < 0.001). Pain was the most frequent symptom (77%). Twenty-three per cent of the patients underwent curative operations, and 77% had a palliative treatment (25% of the patients underwent exploratory laparotomy). Exploratory laparotomy was followed by the highest mortality rate (66%), and older patients (> 70 years) had a higher operative risk (p < 0.04). The overall median survival was 3 months, and long-term survival correlated with the cancer stage (Tis, > 60 months; T1 to T2, > 22 months, and T3 to T4, 2 to 8 months). No differences were observed among the different surgical procedures adopted. No progress has been made in the last 10 years in the treatment of gallbladder malignancies.

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.

Intracatheter hyperthermia and iridium-192 radiotherapy in the treatment of bile duct carcinoma

We report a case of a patient with locally advanced bile duct carcinoma treated with 4500 cGy external beam radiotherapy, followed 3 weeks later by intracatheter 915 MHz microwave hyperthermia and radiotherapy delivered through a biliary U-tube placed at the time of surgery. Heating was to 43–45°C for 1 hour followed immediately by intracatheter Iridium-192 seeds to deliver 5000 cGy over a 72 hour period. Prior to treatment, a thermal dosimetry study in phanton was conducted, using the same type of U-tube catheter tubing as in the patient. Orthogonal X rays of the patient's porta hepatis region were used to reconstruct the catheter geometry in the phantom. Proper insertion depth was determined thermographically to obtain maximum heating at the center of the tumor. The maximum SAR was 8.8 watts per kilogram per watt input. During the treatment, the average power applied was 30 W. Six months after therapy, the patient is asymptomatic. Although alkaline phosphatase, SGOT and SGPT have remained elevated, bilirubin has returned to normal and computerized tomographic scans and cholangiograms remain stable. A duodenal ulcer developed after therapy and is healing well with conservative medical management. This case demonstrates that hyperthermia applied through biliary drainage catheters is technically feasible and clinically tolerated. We believe the use of intracatheter hyperthermia in conjunction with external and/or intracatheter radiotherapy in selected patients with unresectable bile duct carcinomas warrants further study.