Purpose: The best prognosis in hepatocellular carcinoma (HCC) can be achieved with surgical resection; however, the number of resected cases are limited due to advanced lesions or associated liver ...disease. The purpose of this study was to investigate the efficacy and toxicity of a prospective trial of combined transcatheter arterial chemoembolization (TACE) and local radiotherapy (RT) in unresectable HCC.
Methods and Materials: Patients with histologically proven unresectable HCC due to either advanced lesions or associated cirrhosis were eligible. From March 1992 to August 1994, 30 patients were entered into this study. TACE was performed with Lipiodol (5 ml) and doxorubicin (Adriamycin
™; 50 mg), followed by gelatin sponge particle (Gelfoam
™) embolization. Local RT was started within 7–10 days following TACE. Mean tumor dose was 44.0 ± 9.3 Gy in daily 1.8 Gy fractions. Response was assessed by computerized tomography (CT) scan 4–6 weeks following completion of the treatment and then at 1–3-month intervals. Survival was calculated from the start of TACE using the Kaplan–Meier method.
Results: An objective response was observed in 19 patients, giving a response rate of 63.3%. Distant metastasis occurred in 10 patients, with 8 in the lung only and 2 in both lung and bone. Survival rates at 1, 2, and 3 years were 67%, 33.3%, and 22.2%, respectively. Median survival was 17 months. There were 6 patients surviving more than 3 years. Toxicity included transient elevation of liver function tests in all patients, fever in 20, thrombocytopenia in 4, and nausea and vomiting in 1. There was no treatment-related death.
Conclusion: Combined TACE and local RT is feasible and tolerable. It gives a 63.3% response rate with median survival of 17 months. We feel that this regimen would be a new promising modality in unresectable HCC. Further study is required to compare the therapeutic efficacy of this regimen to TACE alone.
Purpose: The purpose of this study was to investigate the efficacy of local radiotherapy (RT) as a salvage treatment for unresectable hepatocellular carcinoma (HCC) patients who failed with ...transcatheter arterial chemoembolization (TACE).
Methods and Materials: Patients with unresectable HCC who had been treated with and eventually failed with TACE were eligible. The judgment of TACE failure was based on incomplete tumor filling of lipiodol-adriamycin mixture on either angiography or computed tomography (CT) scan. From January 1993 to December 1997, 27 patients were entered into this study. They had UICC Stage III (17) or IVA (10) disease, with a mean tumor size of 7.2 ± 2.9 cm. Local RT was done, with a mean tumor dose of 51.8 ± 7.9 Gy, in daily 1.8-Gy fractions using a 10- or 6-MV linear accelerator. Survival was calculated from both the diagnosis and the start of RT using the Kaplan-Meier method.
Results: An objective response was observed in 16 of 24 patients (66.7%) including 1 CR. Intrahepatic metastasis was noted outside the RT field in 10 patients (37.0%). Extrahepatic distant metastasis occurred in 4 patients. Survival rates at 1, 2, and 3 years were 85.2%, 58.1%, and 33.2%, respectively, from the diagnosis and 55.9%, 35.7%, and 21.4%, respectively, from the start of RT. The median survivals were 26 months from the diagnosis and 14 months from the start of RT. Acute toxicity involved alteration in liver function test (13 patients) and thrombocytopenia (2 patients). Subacute and chronic toxicity involved gastroduodenal ulcer (3 patients) and duodenitis (2 patients). There was no treatment-related death.
Conclusion: In unresectable HCC patients who failed with TACE, local RT induced a substantial tumor response of 66.7%, with a 3-year survival rate of 21.4% and a median survival time of 14 months. Toxicity was significant but manageable. Although we do not know if there is survival benefit through this treatment, local RT in these patients seems to be valuable as a salvage for TACE-failed HCC.
Patients presenting with dyspnea are common. Often times, patients carry previously anchored diagnoses, such as COPD, as a cause of their pulmonary symptoms. It is important, however, to perform a ...thorough history and physical examination in order to consider less common causes of dyspnea, such as in the case of this patient who was diagnosed with amyotrophic lateral sclerosis (ALS). The typical course for this disease process includes progressive limb and bulbar muscular weakness with eventual involvement of the respiratory musculature, ultimately leading to respiratory failure - the most frequent cause of death in ALS within 2 to 5 years of diagnosis.
A 68-year-old woman presented to the hospital with recurrent episodes of dyspnea and carbon dioxide retention. She has a history of type II diabetes, hyperlipidemia, hypertension, cervical stenosis, and chronic obstructive pulmonary disease (COPD) requiring home oxygen therapy. Her medications included the following COPD regimen: short acting anticholinergic/beta agonist inhaler, mucolytic, steroid, long acting beta agonist nebulizers, and a Trilogy adaptive servo-ventilation device for nighttime breathing assistance. In the ED, workup showed pH 7.34, pCO2 95mmHg, and HCO3 of 50mmHg; chest x-ray was significant for mild hyperexpansion. On examination, she had mild proximal upper extremity weakness, bilateral thenar atrophy, and a nasal voice. She was in the ICU for 24-48 hours for intensive positive pressure therapy because of her severe carbon dioxide retention.
Bedside pulmonary function testing was consistent with a restrictive process, and she was diagnosed with obesity hypoventilation. However, her BMI was only 39, and given her history of weakness and thenar atrophy, we were concerned for a neurologic process. Neurology found fibrillations with insertion and prominent fasciculations within the proximal right upper limb muscles on needle electromyography. Ultrasound examination with phrenic nerve stimulation showed reduced recruitment of large, complex motor unit potentials in both hemidiaphragms and intercostal muscles. With this constellation of symptoms, ALS was diagnosed. Other possible diagnoses were ruled out with neuroimaging, serologic, and cerebrospinal fluid studies.
Progressive dyspnea as the major presenting symptom of ALS is exceedingly rare, occurring in less than 1% according to literature. It is important to keep ALS in the differential diagnosis in patients who present with progressive dyspnea and restrictive lung disease on pulmonary function testing because this diagnosis has significant prognostic difference compared to other entities such as obesity hypoventilation syndrome.
Identification of the risk factors and the high-risk groups which are most vulnerable is critical in COVID-19 disease management at a population level. Evaluating the efficacy of vaccination against ...infections is necessary to determine booster vaccination strategies for better protection in high-risk groups. In this study, we recruited 158 mRNA-vaccinated individuals during the Delta wave of SARS-CoV-2 infections in Singapore and examined the antibody profiles of infected individuals. We found that, despite high exposure due to communal living conditions in proximity, 4% of individuals (6/158) had PCR-confirmed infections and 96% (152/158) remained uninfected. Time-course analysis of the antibody profile at the start and the end of quarantine period showed Delta-specific boosting of anti-spike antibody response in 57% of the uninfected individuals (86/152). In the remaining 43% of the uninfected individuals (66/152) with no Delta-specific antibody boost, we found a higher Delta-specific antibody response at the start of quarantine period, which correlated with higher Delta pseudovirus neutralizing capacity. Our findings indicate that a higher basal variant-specific antibody response in the mRNA-vaccinated individuals contributes to better protection against infections by the new emerging SARS-CoV-2 variants.
Objectives/Hypothesis: The objectives were to measure the degree of trismus induced after radiation therapy for nasopharyngeal cancer and assess its progress over time.
Study Design: A prospective, ...single‐armed measurement study with long‐term follow‐up.
Methods: Seventeen patients with nasopharyngeal cancer treated between 1997 and 1999 were studied. Patients were given radiation therapy with bilateral parallel‐opposing ports of 45 Gy, 25 fractions, then with a reduced volume to 68.4 to 70.2 Gy. The end point was the degree of trismus, which was measured by serial changes of the maximal interincisal distance (MID) at various specified time points before, during, and after radiation therapy.
Results: During the 9 weeks of radiation therapy there was no significant change of MID (normalized MID ranged from 99.8% to 97%). The rate of decrease during this period was 1.3% per month. After radiation therapy there was a rapid decrease of MID between 1 and 9 months (normalized MID values at 1 and 9 mo were 95.5% ± 3.1% and 74.2% ± 5.7%, respectively). The rate of decrease during this period was dramatic (2.4%/mo). One year after radiation therapy, the rate of decrease became slower but was still measurable (0.2%/mo for the period from 12 to 24 mo). For the period from 24 to 48 months. the rate dropped to 0.1% per month. By the end of 48 months, normalized MID was 67.8% ± 7.6%.
Conclusion: By means of measurement over a period of time, it was found that patients with nasopharyngeal cancer had a mean decrease in initial interincisal distance of 32% at 4 years after radiotherapy. The trismus process evolved at different rates. It was rapid at 1 to 9 months after radiation therapy, then became slower and protracted over later years.
During the natural course of hepatitis B virus (HBV) infection, the long-term clinical and histological outcomes following spontaneous hepatitis B surface antigen (HBsAg) seroclearance remain ...unclear.
Between 1984 and 2003, 49 (9.5%) out of 432 inactive HBsAg carriers had no detectable level of circulating HBsAg. Fifteen of 49 patients had undergone paired peritoneoscopic liver biopsies.
During a mean follow-up period of 19.6 months after HBsAg seroclearance, 5 of 49 (10.2%) patients were noted to have HCC. Liver cirrhosis (
P=0.040), a history of perinatal infection (
P=0.005) and long-standing duration (at least 30 years) of HBsAg positivity (
P=0.002) were associated with a significantly higher risk of developing HCC. Despite HBsAg seroclearance, HBV DNA was detected in the liver tissues from all 15 patients who underwent paired liver biopsies. Necroinflammation was significantly ameliorated (
P<0.0001). On the other hand, amelioration of the fibrosis score did not reach a statistically significant level (
P=0.072). Interestingly, aggravation of liver fibrosis was evident in 2 patients (13.3%) including one who had rapidly progressed to overt cirrhosis.
In patients with spontaneous HBsAg seroclearance, necroinflammation was markedly improved and liver fibrosis was unchanged or regressed despite occult HBV infection. However, HCC developed in a minority of cases.
Purpose
: Dose escalation using three-dimensional conformal radiotherapy (3D-CRT) is based on the hypothesis that increasing the dose can enhance tumor control. This study aimed to determine whether ...a dose-response relationship exists in local radiotherapy for primary hepatocellular carcinoma (HCC).
Methods and Materials
: One hundred fifty-eight patients were enrolled in the present study between January 1992 and March 2000. The exclusion criteria included the presence of an extrahepatic metastasis, liver cirrhosis of Child class C, tumors occupying more than two-thirds of the entire liver, and a performance status on the Eastern Cooperative Oncology Group scale of more than 3. Radiotherapy was given to the field, including the tumor, with generous margin using 6- or 10-MV X-rays. The mean radiation dose was 48.2 ± 7.9 Gy in daily 1.8-Gy fractions. The tumor response was assessed based on diagnostic radiologic examinations, including a computed tomography scan, magnetic resonance imaging, and hepatic artery angiography 4–8 weeks after the completion of treatment. Liver toxicity and gastrointestinal complications were evaluated.
Results
: An objective response was observed in 106 of 158 (67.1%) patients. Statistical analysis revealed that the total dose was the most significant factor associated with the tumor response. The response rates in patients treated with doses <40 Gy, 40–50 Gy, and >50 Gy were 29.2%, 68.6%, and 77.1%, respectively. Survivals at 1 and 2 years after radiotherapy were 41.8% and 19.9%, respectively, with a median survival time of 10 months. The rate of liver toxicity according to the doses <40 Gy, 40–50 Gy, and >50 Gy was 4.2%, 5.9%, and 8.4%, respectively, and the rate of gastrointestinal complications was 4.2%, 9.9%, and 13.2%, respectively.
Conclusions
: The present study showed the existence of a dose-response relationship in local radiotherapy for primary HCC. Only the radiation dose was a significant factor for predicting an objective response. The results of this study showed that 3D-CRT can theoretically be used for treating primary HCC.
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