Radiation segmentectomy for curative intent of unresectable very early to early stage hepatocellular carcinoma (RASER): a single-centre, single-arm study.

BACKGROUND: Unresectable solitary very early to early stage hepatocellular carcinoma is managed with ablation for curative intent. Radiation segmentectomy is a treatment option that delivers radioactive 90yttrium (90Y)-bound microspheres transarterially to a segment of liver. The aim of this study was to assess the safety and efficacy of radiation segmentectomy in patients with unresectable hepatocellular carcinoma deemed unfavourable for ablation. METHODS: RASER was a single-centre, single-arm study that included adults (>18 years) with solitary hepatocellular carcinoma with unfavourable location for ablation, without metastasis or macrovascular invasion. Eligibility criteria included measurable disease 3 cm or less in diameter, Child-Pugh score A-B7, an Eastern Cooperative Oncology Group score of 0, and adequate haematological and organ function. The primary endpoint was target tumour response measured by mRECIST. Patients were followed up with imaging and office visits for up to 24 months. The trial is registered with ClinicalTrials.gov (NCT03248375), and is completed. FINDINGS: Individuals were enrolled between Aug 3, 2016, and April 4, 2019, and the last patient follow-up occurred on March 31, 2021. Of the 44 individuals assessed for eligibility, 29 patients were included in the study. Initial target lesion complete response was observed in 24 (83%) of 29 patients, and partial response was observed in five (17%) of patients. All patients had an initial objective response and 26 (90%) individuals had a sustained complete response. Four (14%) patients had grade 3 leukopenia and two (7%) had grade 3 thrombocytopenia. There were two (7%) non-laboratory-related grade 3 adverse events (one arterial injury and one ascites). The most frequent (>10% patients) grade 1 or 2 adverse events were fatigue (nine [31%]); nausea, vomiting, or anorexia (seven [24%]); abdominal discomfort (six [21%]), leukopenia (nine [31%]), thrombocytopenia (four [14%]), increased alkaline phosphatase (four [14%]), increased alanine or aspartate aminotransferase (four [14%]), increased bilirubin (four [14%]), and decreased albumin (six [21%]). There was one death that was not treatment related. INTERPRETATION: Radiation segmentectomy was efficacious, with a low proportion of high-grade adverse events in patients with unresectable very early to early stage hepatocellular carcinoma with suboptimal location for ablation. These results suggest that radiation segmentectomy should be further investigated as a potential curative treatment option for well selected patients. FUNDING: Boston Scientific.

The usefulness of distal splenorenal shunt in children with portal hypertension for the treatment of severe thrombocytopenia and leukopenia.

BACKGROUND: In the current era of transplantation and therapeutic endoscopy, the role of the distal splenorenal shunt (DSRS) for portal hypertension (PH) has diminished. We reviewed the outcome of the use of DSRS in children to determine the usefulness of this operation. METHODS: In the follow-up course for PH from 1987 to 2006, 15 patients who developed severe thrombocytopenia (platelet count <50 x 10(3)/mm(3)) and/or leukopenia (WBC count <3000/mm(3)) with normal liver function were referred for DSRS. Primary diagnosis was portal vein thrombosis (N=10) and congenital hepatic fibrosis (N=5). Platelet, WBC count, liver function test, and spleen size were checked before and after DSRS. Shunt patency was accessed postoperatively. Operative morbidity, mortality, and long-term outcomes were measured. RESULTS: Platelet count and WBC count increased in individual patients. Mean value of each count increased significantly after DSRS (p=0.002, .004, respectively). Spleen size decreased significantly (N=7, p=0.018). Shunt patency rate was 100%. There was one postoperative complication and no postoperative mortality. Two patients developed portopulmonary hypertension. No patients underwent subsequent transplantation or endoscopic treatment for gastroesophageal varices after DSRS. CONCLUSIONS: DSRS is an effective and reliable procedure for children with PH and is still useful for selected pediatric patients.

Splenectomy for non-Hodgkin's lymphoma.

Splenomegaly is a common occurrence in the course of non-Hodgkin's lymphoma (NHL), sometimes leading to development of bulk symptoms or cytopenias. Splenomegaly may also be the primary manifestation of NHL. We reviewed our experience with diagnostic and therapeutic splenectomy for NHL over the past 3 years. In July of 1991, a prospective database had been established to evaluate elective splenectomy for hematologic disease; of 58 patients, 12 had NHL. Splenectomy was performed for diagnostic purposes, correction of cytopenias, and relief of bulk symptoms. Most patients had more than one indication for splenectomy. Operative hemorrhage requiring transfusion was seen only in patients with massive splenomegaly (> 1,500 g). Median postoperative hospital stay was 4 days. There was no operative mortality or major morbidity. Minor morbidity was seen in 17% of patients. A favorable hematologic response was seen in 80% of cytopenias at the 3-month postoperative interval. Splenectomy is safe and effective in appropriately selected patients with NHL.

Selective use of splenectomy after liver transplantation in children.

In a series of 106 pediatric liver transplantations, five patients were identified with recurrent rejection who could not tolerate the addition of azathioprine (Aza) to their immunosuppressive therapy because of leukopenia. Splenectomy was performed posttransplantation to allow the use of Aza. The number and severity of rejection episodes were compared before and after splenectomy in these patients. In addition, presplenectomy and postsplenectomy rejection frequencies were compared with rejection frequencies in 35 patients who did not require splenectomy and had at least 1 1/2 years of follow-up. Mild, moderate, and severe rejection episodes were defined by the treatment (mild, steroid bolus only; moderate, steroid recycle; and severe, monoclonal antibodies or Minnesota antilymphocyte globulin) required to produce complete resolution. There was a mean of 342 +/- 111 days from transplantation to splenectomy and a mean of 674 +/- 109 days of follow-up after splenectomy. Follow-up in the control group was 934 +/- 44 days. After splenectomy, the average platelet count increased from 78 +/- 15 to 514 +/- 113 (P = .020) and white blood cell count increased from 3.2 +/- 0.6 to 16.7 +/- 2.7 (P = .010). Splenectomy permitted the implementation of Aza therapy in one patient who previously was not a candidate because of hypersplenism and allowed uncomplicated Aza therapy in four patients who became severely leukopenic during previous Aza trials. All five patients who underwent splenectomy demonstrated a statistically significant (P less than .05) decrease in the total number of rejection episodes. Rejection frequency after splenectomy was no different from the rejection frequency in patients who did not require splenectomy (P = .682).(ABSTRACT TRUNCATED AT 250 WORDS)

Hematologic (cytopenic) manifestations of Wilson's disease (hepatolenticular degeneration).

The records of 54 consecutive patients with Wilson's disease seen at the Mayo Clinic from 1952 through early 1977 were reviewed to determine the frequency fo hematologic abnormalaties in their evaluation. Leukopenia and thrombocytopenia sometimes have been ascribed to treatment with D-penicillamine and its toxicity; however, we have found cytopenia to be a frequent finding in the presenting laboratory data of patients with Wilson's disease. Twenty-eight patients (52%) had thrombocytopenia and 16 of these patients (30% of the total) also had leukopenia. Severe, acute, intermittent hemolytic episodes were the initial and only presenting complaint of one patient. Six of the patients with significant cytopenias had splenectomy, and in all cases the peripheral blood counts returned to normal values. Long-term treatment with D-penicillamine improved the hepatic and neurologic dysfunction in most patients; however, the cytopenias remained unchanged except in three patients (treated 2, 5, and 10 years).

Hypersplenism in Hodgkin's disease: a report of three cases presenting with cytopenias.

A review of the last seventy-eight consecutive cases of Hodgkin's disease seen at our hospital revealed that two presented several hematologic cytopenias. These two cases and a similar case first seen at an associated hospital revealed pancytopenia in two and leukopenia in the third. All responded to splenectomy with hematologic improvement. All met the criteria for hypersplenism. This report illustrates that Hodgkin's disease can present cytopenias due to hypersplenism, and that early splenectomy can lead to hematologic improvement and tolerance of subsequent chemotherapy.

[Familial Wilson's disease: copper induced hemolysis, hypersplenism and hyperpigmentation as the main symptoms]. / Familiärer Morbus Wilson: kupferinduzierte Hämolyse, Hyperspleniesyndrom und Hyperpigmentation als Leitsymptome

Wilson's disease was diagnosed in a 16-year-old adolescent who presented with signs of hypersplenism due to cirrhosis, with marked hyperpigmentation of both lower legs and neurological disturbances. In view of progressive thrombocytopenia and leukocytopenia, splenectomy was performed during therapy with penicillamine later in the course, and the result was good. The patient's 12-year-old sister was found to have a hepatic form of Wilson's disease with typical biochemical findings. During the initial hospitalization a severe, spontaneous copper-induced hemolysis was noted. Another sister probably has a presymptomatic form of the disease. The parents are healthy but heterozygote carriers with regard to biochemical findings. The importance is stressed of hypersplenism, hyperpigmentation of the legs and especially of acute hemolysis in infancy as pointers in the diagnosis of Wilson's disease. Further diagnostic and therapeutic aspects are discussed.