The Dutch-Belgian Registry of Stereotactic Body Radiation Therapy for Liver Metastases: Clinical Outcomes of 515 Patients and 668 Metastases.

PURPOSE: Although various studies have reported that stereotactic body radiation therapy (SBRT) for liver metastases has high local control rates and relatively low toxicity, most series included a small number of patients. We aimed to validate these outcomes in a large multi-institution patient cohort treated in accordance with a common protocol. METHODS AND MATERIALS: A shared web-based registry of patients with liver metastases treated with SBRT was developed by 13 centers (12 in the Netherlands and 1 in Belgium). All the centers had previously agreed on the items to be collected, the fractionation schemes, and the organs-at-risk constraints to be applied. Follow-up was performed at the discretion of the centers. Patient, tumor, and treatment characteristics were entered in the registry. Only liver metastases treated individually as independent targets and with at least 1 radiologic follow-up examination were considered for local control analysis. Toxicity of grade 3 or greater was scored according to the Common Terminology Criteria of Adverse Events (v4.03). RESULTS: Between January 1, 2013, and July 31, 2019, a total of 515 patients were entered in the web-based registry. The median age was 71 years. In total, 668 liver metastases were registered, and 447 were included for local control analysis. The most common primary tumor origin was colorectal cancer (80.3%), followed by lung cancer (8.9%) and breast cancer (4%). The most-used fractionation scheme was 3x18-20 Gy (36.0%), followed by 8x7.5 Gy (31.8%), 5x11-12 Gy (25.5%), and 12x5 Gy (6.7%). The median follow-up time was 1.1 years for local control and 2.3 years for survival. Actuarial 1-year local control was 87%; 1-year overall survival was 84%. Toxicity of grade 3 or greater was found in 3.9% of the patients. CONCLUSIONS: This multi-institutional study confirms the high rates of local control and limited toxicity in a large patient cohort. Stereotactic body radiation therapy should be considered a valuable part of the multidisciplinary approach to treating liver metastases.

Gallbladder Visualization in Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE: A Potential Mimicker of Hepatic Metastases.

Gallbladder visualization represents a rare incidental finding when using somatostatin receptor-targeted SPECT radiopharmaceuticals such as In-octreotide. We present the case of a 30-year-old man with pseudomyogenic hemangioendothelioma who underwent Ga-DOTATATE PET/CT for restaging of metastatic disease and subsequent treatment with peptide receptor radionuclide therapy with Lu-DOTATATE. Posttherapeutic SPECT/CT, but not pretherapeutic or posttherapeutic PET/CT, showed gallbladder visualization, evidencing Lu-DOTATATE excretion into the bile. This case highlights that biliary Lu-DOTATATE excretion may represent a rare mimicker of hepatic metastases and emphasizes the role SPECT/CT for precise anatomical correlation to avoid misinterpretation.

Reduce Adverse Effects of Laparoscopic Cholecystectomy with Pulse Width Modulated LED Light (625 nm, 76 Hz, 23% Duty Cycle).

OBJECTIVE: Reducing adverse effects in laparoscopic cholecystectomy (LCE) is important to avoid complications. After removal, the porta hepatis and gallbladder bed of liver were treated with pulse width modulated (PWM) red LED light with parameters λ = 625 ± 5 nm, full width at half maximum 17 nm, 76 Hz, duty cycle 23%, 15-30 mW/cm2, and 0.9-1.8 J/cm2. The changes of eight blood parameters were studied: red blood cell, hemoglobin, white blood cell, erythrocyte sedimentation rate (ESR), bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), and amylase. BACKGROUND DATA: Other current methods of reducing undesirable effects of LCE significantly affect surgery and are not commonly used in practice. MATERIALS AND METHODS: Before LCE, 263 patients were randomized into the control and test groups. Patients in the test group were treated with light radiated for 2 min during the surgery on the bed of the removed gallbladder and porta hepatis. Blood samples were taken before surgery and on the third day after surgery, studied, and compared by nonparametric statistical methods. RESULTS: The test group revealed significant reduction in postsurgery gain of levels of ALT, AST, and ESR compared with the control group. CONCLUSIONS: Treatment of the removed gallbladder bed and porta hepatis by red LED PWM radiation during LCE significantly reduces the adverse effects of surgery while increasing its time insignificantly and does not affect the surgical best practices deployed.

Gallbladder toxicity and high-dose ablative-intent radiation for liver tumors: Should we constrain the dose?

PURPOSE: Little is known about the risk of gallbladder toxicity from hypofractionated (HFXRT) and stereotactic body radiation therapy (SBRT). We report on gallbladder toxicity and attribution to treatment in a prospective series of patients with primary and metastatic liver tumors receiving ablative-intent HFXRT and SBRT with protons. METHODS AND MATERIALS: We evaluated 93 patients with intact gallbladders enrolled in either of 2 trials investigating proton HFXRT and SBRT for primary and metastatic liver tumors from 2009 to 2014. Patients received 45 to 67.5 GyE in 15 fractions for primary liver tumors (n = 45) and 30 to 50 GyE in 5 fractions for metastatic tumors (n = 48). No gallbladder dose constraints were used at treatment, and gallbladder volumes and dose-volume histograms were created retrospectively. Attributable toxicity was defined as cholecystitis or perforation without preexisting gallbladder disease. Baseline factors were evaluated using Fisher exact test and the nonparametric K-sample test. RESULTS: At baseline, 25 patients had preexisting cholelithiasis and 15 underwent biliary stenting before or after RT. Median follow-up after treatment was 11.8 months (range, 0.1-59.2 months). Despite maximum gallbladder doses >70 GyE in 41%, >80 GyE in 31%, and >90 GyE in 13% (equieffective dose at 2 Gy [EQD2], α/ß = 3), there were no attributable cases of gallbladder toxicity. Two patients developed grade 3 and 4 cholecystitis 16 and 2 months after treatment, respectively, and both had a strong history of preexisting cholelithiasis and biliary stenting. These patients received relatively low gallbladder doses with mean doses of 0.02 GyE and 5.1 GyE (EQD2, α/ß = 3), well below the 17.1 GyE mean for the remaining cohort (range, 0-81.1 GyE, EQD2). CONCLUSIONS: We identified no relationship between gallbladder dose and toxicity and did not reach the maximum tolerated gallbladder dose in this cohort treated with high-dose radiation. We recommend not constraining dose to the gross tumor volume to protect the gallbladder during ablative HFXRT and SBRT.

Radiation-induced cholecystitis after hepatic radioembolization: do we need to take precautionary measures?

Controversy exists over the need to take precautionary measures during hepatic radioembolization to minimize the risk of radiation-induced cholecystitis. Strategies for a variety of clinical scenarios are discussed on the basis of a literature review. Precautionary measures are unnecessary in the majority of patients and should be taken only when single photon-emission computed tomography (CT; SPECT)/CT shows a significant concentration of technetium-99m macroaggregated albumin in the gallbladder wall. In this case report with quantitative SPECT analysis, it is illustrated how an adjustment of the catheter position can effectively reduce the absorbed dose of radiation delivered to the gallbladder wall by more than 90%.

Yttrium-90 radioembolization of malignant tumors of the liver: gallbladder effects.

OBJECTIVE: After (90)Y-microsphere radioembolization for unresectable hepatic neoplasms, the nearby gallbladder is susceptible to radiation-induced cholecystitis, an uncommon complication. The purpose of this study was to characterize the imaging findings after (90)Y radioembolization of the gallbladder and to assess the incidence of clinically significant radiation-induced cholecystitis. MATERIALS AND METHODS: Medical records were retrospectively reviewed for cholecystectomy after (90)Y treatment of 133 consecutively registered patients (76 men, 57 women; average age, 65 years). Thirty-four of the patients had primary and 99 had secondary liver neoplasms. The pretreatment and posttreatment cross-sectional images of 85 of the patients were available for review. RESULTS: Clinically significant radiation-induced cholecystitis occurred in 1 of the 133 patients (0.8%). After radioembolization, gallbladder imaging abnormalities were found in 84 of 85 patients (99%), but none was associated with clinically significant radiation-induced cholecystitis. CONCLUSION: The incidence of clinically significant radiation-induced cholecystitis was only 0.8% despite a high prevalence of gallbladder imaging abnormalities after (90)Y radioembolization. Therefore, in the postinterventional care of patients with abdominal pain after (90)Y radioembolization, even if imaging abnormalities of the gallbladder are identified, cholecystectomy should be reserved for patients in whom other causes of pain have been excluded.

[Assessment of the effectiveness of laser reflexotherapy in combined treatment of patients with chronic acalculous cholecystitis].

AIM: To study effects of laserpuncture in combined treatment of chronic non-calculous cholecystitis on motor function gallbladder, clinical symptoms. MATERIALS AND METHODS: 73 patients of chronic non-calculous cholecystitis were divided in to groups: 35 patients were received treated only by the means of standard therapy (the control group), 38 patients were received a course laserpuncture as part of complex treatment (the study group). RESULTS: Influence laser radiation on acupuncture points was found to induce positive therapeutic effect, such as: decrease the durations of clinical symptoms, correction of motor function gallbladder. CONCLUSION: Laserpuncture is an effective method of non-calculous cholecystitis treatment and can be included in relevant combined schemes.

Acceptable toxicity after stereotactic body radiation therapy for liver tumors adjacent to the central biliary system.

PURPOSE: To evaluate biliary toxicity after stereotactic body radiation therapy (SBRT) for liver tumors. METHODS AND MATERIALS: Among 297 consecutive patients with liver tumors treated with SBRT of 35 to 50 Gy in 5 fractions, patients who were irradiated with >20 Gy to the central biliary system (CBS), including the gallbladder, and had follow-up times >6 months were retrospectively analyzed. Toxicity profiles, such as clinical symptoms and laboratory and radiologic data especially for obstructive jaundice and biliary infection, were investigated in relation to the dose volume and length relationship for each biliary organ. RESULTS: Fifty patients with 55 tumors were irradiated with >20 Gy to the CBS. The median follow-up period was 18.2 months (range, 6.0-80.5 months). In the dose length analysis, 39, 34, 14, and 2 patients were irradiated with >20 Gy, >30 Gy, >40 Gy, and >50 Gy, respectively, to >1 cm of the biliary tract. Seven patients were irradiated with >20 Gy to >20% of the gallbladder. Only 2 patients experienced asymptomatic bile duct stenosis. One patient, metachronously treated twice with SBRT for tumors adjacent to each other, had a transient increase in hepatic and biliary enzymes 12 months after the second treatment. The high-dose area >80 Gy corresponded to the biliary stenosis region. The other patient experienced biliary stenosis 5 months after SBRT and had no laboratory changes. The biliary tract irradiated with >20 Gy was 7 mm and did not correspond to the bile duct stenosis region. No obstructive jaundice or biliary infection was found in any patient. CONCLUSIONS: SBRT for liver tumors adjacent to the CBS was feasible with minimal biliary toxicity. Only 1 patient had exceptional radiation-induced bile duct stenosis. For liver tumors adjacent to the CBS without other effective treatment options, SBRT at a dose of 40 Gy in 5 fractions is a safe treatment with regard to biliary toxicity.

Prophylactic embolization of the cystic artery before radioembolization: feasibility, safety, and outcomes.

PURPOSE: To evaluate the safety and efficacy of two different methods of proximal cystic artery embolization in patients undergoing yttrium-90 radioembolization. MATERIALS AND METHODS: Forty-six patients had cystic artery embolization performed immediately before yttrium-90 radioembolization, either by using Gelfoam pledgets (n = 35) or coils (n = 11). Clinical symptomatology during the admission and angiographic findings at 1-month follow-up were retrospectively reviewed. Rates of collateralization or recanalization of the cystic artery were compared, as well as the frequency of postprocedural abdominal pain and need for cholecystectomy. RESULTS: Technical success was achieved in all patients, and there were no procedural complications related to cystic artery embolization. Of the 11 coil-embolized patients, 5 (45%) demonstrated collateralization of the cystic artery at 1 month, and 1 (9%) demonstrated recanalization of the cystic artery. Of the 35 Gelfoam-embolized cases, 2 (6%) had collateralized at 1 month, and 14 (40%) had recanalized. Two patients (one from each group) had self-limited right upper quadrant pain after the procedure, and one patient in the coil embolization group required cholecystectomy. CONCLUSION: Proximal cystic artery embolization is safe and feasible and may be performed during liver-directed embolotherapy to minimize the exposure of the gallbladder to particulate, chemoembolic, or radioembolic agents.

[The application of pulsed infrared laser radiation with autoresonant amplification for the treatment of patients with acute viral hepatitis B].

A group of 59 patients presenting with acute viral hepatitis B was available for examination. A single course of pulsed infrared laser irradiation with autoresonant amplification resulted in the improvement of clinical conditions of the patients and normalization of ALAT activity, total and direct bilirubin levels.

Intracholecystic fat herniation in traumatic gallbladder perforation: a case report.

Gallbladder injuries from blunt trauma are uncommon and are also challenging to diagnose both clinically and radiologically. We present a case of intracholecystic fat herniation as a computed tomographic sign of gallbladder perforation.

[Effects of laser reflex therapy on a motor function of the gall bladder and physical properties of bile in patients with chronic acalculous cholecystitis].

AIM: To study effects of laser puncture in combined treatment of chronic non-calculous cholecystitis on motor function of the gallbladder, bile physical characteristics and clinical symptoms. MATERIAL AND METHODS: 73 patients with chronic non-calculous cholecystitis were divided into two groups: 35 patients received standard therapy alone (control group) and 38 patients were exposed to laser puncture as a component of combined treatment. RESULTS: Laser radiation on acupuncture points has a positive therapeutic result, i.e. shorter clinical symptoms, correction of motor function of the gallbladder and bile physical characteristics. CONCLUSION: Laser puncture is an effective method of acalculous cholecystitis treatment and can be included in relevant combined schemes.

Simplifying the dosimetry of carbon-11-labeled radiopharmaceuticals.

UNLABELLED: A two time-point sacrifice method is proposed as an alternative to conventional multiple time-point sacrifice methods to determine the organ cumulated activity of 11C-labeled radiopharmaceuticals. METHODS: Rat biodistribution data for 10 11C-labeled radiopharmaceuticals were analyzed to determine organ cumulated activity. Data were obtained at four sacrifice intervals 2-5 min, 10-15 min, 30-45 min and 1-1.5 hr postinjection. The organ absorbed dose per unit administered radioactivity (mGy/MBq) was calculated using all four data points and combinations of limited data. The objective was to determine if a limited sampling technique would provide sufficient accuracy in estimating absorbed dose. RESULTS: Residence times calculated using two time-points acquired during the first half-life of 11C were either equivalent or positively biased compared to using all sacrifice times. Overall, 87% of the residence times assessed were conservative compared to the multipoint method. For bladder organs, a consistent negative bias was observed with the reduced sacrifice method. CONCLUSION: Analysis of animal biodistributions using a reduced sacrifice protocol provides results in good agreement with and generally conservative to results using all sacrifice intervals. Correction factors are required for the urinary bladder and gallbladder when using the simplified technique due to bias. The bladder was often the limiting organ in determining human administered activity.

[The correction of functional disorders of the bile-secreting system by using laser radiation]. / Korrektsiia funktsional'nykh narushenii zhelchevyvodiashchei sistemy s pomoshch'iu lazernogo izlucheniia.

He-Ne laser irradiation of biologically active points and infrared laser irradiation of the liver were employed to improve gallbladder and sphincter functions, bile production and biochemistry, respectively, in a total of 57 patients with biliary dyskinesia presenting as hypokinetic dyskinesia of the gallbladder, hyperkinetic dyskinesia of the sphincter of Oddi or the combination of the two affections. Simultaneous use of the two kinds of laser irradiation appreciably shortens treatment duration, abolishes biliferous dysfunction, reestablishes physiological balance of bile components in case of its initial lithogenic potential.

Comparison of a pulsed dye laser and electrohydraulic lithotripsy on porcine gallbladder and common bile duct in vitro.

With the advent of minimal access biliary procedures there is a need for a safe intracorporal lithotripsy technique that can be used through small flexible endoscopes. Currently, the two techniques available are electrohydraulic lithotripsy and laser induced shock wave lithotripsy. In this study we compare the effect of a 504 nm coumarin pulsed dye laser and electrohydraulic lithotripsy on in vitro porcine gallbladder and common bile duct. Electrohydraulic lithotripsy at the lowest energy the generator would deliver caused perforation of both tissues in only a few pulses when a 1.9-F probe was placed in direct contact with the tissue. Energy from a 504 nm coumarin pulsed dye laser delivered through a 320-microns fiber placed in light contact with the tissue caused an energy-dependent perforation after 50 pulses in from none to 44% of tissues. It was also found that there was a higher incidence of perforation in more vascular than non-vascular tissue. When the EHL probe and the laser fiber were held 1-2 mm from the tissue surface, discharge of each resulted in no perforation. On histological examination of the tissues, the perforations were found to be very small with laser lithotripsy and considerably larger with the electrohydraulic lithotripsy. It was felt that laser lithotripsy in the clinical situation was likely to be much safer than electrohydraulic lithotripsy.

[Possibilities of the treatment of biliary dyskinesia by laser irradiation]. / Vozmozhnosti lecheniia diskinezii zhelchevyvodiashchikh putei s pomoshch'iu lazernogo izlucheniia.

The examination of 68 patients with biliary dysfunction determined hypokinesia of the gallbladder in 40, sphincter of Oddi spasm in 15 and combination of the two conditions in 13 patients. Blood biochemical indices showed no differences in patients with biliary dyskinesia compared to normal subjects except for alkaline phosphatase levels elevated in 35.3% of patients. This suggests the development of biliary hypertension and cholestasis. All the patients demonstrated disturbed colloid stability of the bile, in those with combined dyskinesia it became lithogenic. Helium-neon and semiconductor laser radiation of biologically active points and the hepatic region, respectively, improved the patients' performance status. The pain and dyspepsia discontinued. The function of the gallbladder and sphincter of Oddi recovered. Positive changes occurred in the blood and bile biochemistry. Laser therapy promoted bilirubin and bile cholesterol decrease. Cholic acid concentration grew, lithogenic characteristics of the bile returned to normal. It is inferred that laser therapy of biliary dyskinesia proved effective.