John M. Richart

Spontaneous retroperitoneal and rectus muscle hemorrhage as a potentially lethal complication of cirrhosis.

Abstract: Aims/Background: Cirrhosis may be complicated by bleeding from varices at sites of porto‐systemic anastomosis and may be exacerbated by coagulopathy.

Metabolic Syndrome and Cardiovascular Disease after Hematopoietic Cell Transplantation: Screening and Preventive Practice Recommendations from the CIBMTR and EBMT

Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus, and all cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with the estimated prevalence of MetS being 31–49% amongst HCT recipients. While MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to review literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors.

High-Dose Interleukin-2 (HD IL-2) Therapy Should Be Considered for Treatment of Patients with Melanoma Brain Metastases

A retrospective review was performed on patients with stable melanoma brain metastases treated with HD IL-2 therapy (720,000 IU/kg per dose intravenously; 14 doses, 2 cycles per course, maximum 2 courses) from January 1999 to June 2011 at Saint Louis University. There were 5 men and 3 women; median age was 52.2 years (26.8–61.1 years). One patient started treatment with lung lesions only (after resection of melanoma brain disease) and experienced partial response. Seven patients had brain metastases at treatment initiation. Median overall survival (mOS) for entire cohort (n = 8) was 8.7 months (2.1 to 19.0 months). All patients with brain metastases at first dose (n = 7) showed progressive disease; mOS was 6.7 months (range 2.1–18.2 months) for this group. Patients received radiosurgery and whole brain radiation before and after HD IL-2 therapy. One patient had symptoms suggestive of neurotoxicity. A history of alcohol abuse was revealed during admission. The patients symptoms improved with initiation of an alcohol withdrawal protocol. In this analysis, patients with melanoma brain metastases received HD IL-2 without treatment-related mortality. We think that HD IL-2 should be considered as a treatment option in patients with melanoma brain metastases who are otherwise eligible for therapy.

Simultaneous Presence of t(2;8)(p12;q24) and t(14;18)(q32;q21) in a B-Cell Lymphoproliferative Disorder with Features Suggestive of an Aggressive Variant of Splenic Marginal-zone Lymphoma

We report a case of an aggressive variant of splenic marginal-zone lymphona (SMZL) with circulating villous lymphocytes. The karyotype of all examined cells had multiple structural and numerical abnormalities, including two lymphoma characteristic translocations, t(2;8)(p12;q24) and t(14;18)(q32;q21). Based on a literature review of cytogenetic aberrations of splenic lymphoma with villous lymphocytes (SLVL) and SMZL, this is apparently the first documentation of these two translocations in a case of SMZL, and could reflect the heterogeneity of the disorder.

Metabolic syndrome and cardiovascular disease following hematopoietic cell transplantation: screening and preventive practice recommendations from CIBMTR and EBMT

Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus and all cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with the estimated prevalence of MetS being 31–49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal of reviewing literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors.

Impact of Sequencing Targeted Therapies With High-dose Interleukin-2 Immunotherapy: An Analysis of Outcome and Survival of Patients With Metastatic Renal Cell Carcinoma From an On-going Observational IL-2 Clinical Trial: PROCLAIMSM

&NA; ProleukinR Observational Study to Evaluate the Treatment Patterns and Clinical Response in Malignancy (PROCLAIMSM) is the largest observational clinical database of high‐dose interleukin‐2 (HD IL‐2)‐treated patients in the US. Herein, the survival and outcome for patients with renal cell carcinoma receiving HD IL‐2 in sequence with targeted therapy are described. HD IL‐2 has an acceptable efficacy and safety profile in current clinical practice and remains a valuable therapy for patients with renal cell carcinoma. Background: This analysis describes the outcome for patients who received targeted therapy (TT) prior to or following high‐dose interleukin‐2 (HD IL‐2). Patients and Methods: Patients with renal cell carcinoma (n = 352) receiving HD IL‐2 were enrolled in ProleukinR Observational Study to Evaluate the Treatment Patterns and Clinical Response in Malignancy (PROCLAIMSM) beginning in 2011. Statistical analyses were performed using datasets as of September 24, 2015. Results: Overall, there were 4% complete response (CR), 13% partial response (PR), 39% stable disease (SD), and 43% progressive disease (PD) with HD IL‐2. The median overall survival (mOS) was not reached in patients with CR, PR, or SD, and was 15.5 months in patients with PD (median follow‐up, 21 months). Sixty‐one patients had prior TT before HD IL‐2 with an overall response rate (ORR) to HD IL‐2 of 19% (1 CR, 9 PR) and an mOS of 22.1 months. One hundred forty‐nine patients received TT only after HD IL‐2 with an mOS of 35.5 months. One hundred forty‐two patients had no TT before or after HD IL‐2, and mOS was not reached. The mOS was 8.5 months in PD patients who received HD IL‐2 without follow‐on TT and 29.7 months in PD patients who received follow‐on TT after HD IL‐2. Conclusions: HD IL‐2 as sole front‐line therapy, in the absence of added TT, shows extended clinical benefit (CR, PR, and SD). Patients with PD after HD IL‐2 appear to benefit from follow‐on TT. Patients who progressed on TT and received follow‐on HD IL‐2 experienced major clinical benefit. HD IL‐2 therapy should be considered in eligible patients.

Expression of P-glycoprotein and C-MOAT in human hepatocellular carcinoma: detection by immunostaining.

P-Glycoprotein and C-MOAT are important hepatic transport proteins which play a role in handling anticancer drugs. Hepatocellular carcinoma is a common hepatic malignancy that is relatively resistant to chemotherapeutic drugs. We therefore studied the expression of these two transport proteins in liver sections from hepatocellular carcinoma by immunohistochemistry and compared the reactivity to that in other liver conditions, including cirrhosis and dysplasia. We studied 53 sections from 17 liver specimens and found that the majority of samples stained positively for both P-glycoprotein and C-MOAT; however, the degree of staining was less in HCC and hepatic adenoma than in liver adjacent to HCC or in cirrhosis or dysplastic nodules. HCC with a compact pattern had less staining than those with acinar, scirrhous, or trabecular patterns. The location of both P-glycoprotein and C-MOAT staining was a function of the liver lesion present. Thus, most tissues without hepatocellular carcinoma showed foci of globular canalicular staining, whereas a delicate linear pattern of canalicular staining was most common overall. We conclude that expression of P-glycoprotein and C-MOAT, as detected by qualitative immunohistochemical evaluation are little affected by the development of HCC and therefore are probably of little clinical significance for management of malignancy.

Complete metastasectomy after high-dose interleukin-2 (HD IL-2) therapy for melanoma

Meeting abstracts Our aim was to describe our experience with surgery after High-dose Interleukin-2 (HD IL-2) therapy in patients who were eligible for complete metastasectomy after treatment. A retrospective chart review was performed on patients with metastatic melanoma seen at Saint Louis

Lichenoid reaction as a potential immune response marker of intratreatment histological response during successful vismodegib treatment for a giant basal cell carcinoma.

We report an 83 year‐old patient with a 13 × 7.5 cm2 basal cell carcinoma (BCC) successfully treated with the combination of vismodegib and minimal surgery. On Day 109, a 0.9 cm papule suspicious for residual BCC was seen centrally within a large pink atrophic plaque. This lesion was excised; pathology confirmed BCC with negative surgical margins. Simultaneously, suspecting noncontiguous histologic response, we performed 21 biopsies at the periphery of the pretreatment tumor location. Seventeen (17/21, 81%) revealed lichenoid dermatitis. No tumor was seen on any. We believe the lichenoid dermatitis observed is a novel finding for two reasons. First, it may be considered a marker of a positive intratreatment response. This may help guide clinicians on the optimal treatment duration of vismodegib to maximize efficacy and mitigate side effects. Second, we think it suggests an additional mechanism of vismodegib action, possibly via local immune effects. Further investigations are warranted.

Coexistent metastatic melanoma of the kidney with unknown primary and renal cell carcinoma

In this report, we present an African-American female patient who presented with haematuria to her primary care physician. The symptoms persisted and coexistent metastatic spindle cell-type melanoma of the kidney and renal cell carcinoma were discovered on further evaluation. No primary site for melanoma was identified. Despite aggressive treatment with ipilimumab, the patients disease progressed quickly. The patient opted for palliative care and was referred to a hospice. Coexistent melanoma and renal cell carcinoma is exceedingly rare. Melanoma itself is rare in the African-American population. However, when it does present, it usually is at an advanced stage, as was the case in our patient. Since no primary tumour site for melanoma was found and the diagnosis was made after the tumour had metastasised, we think this case highlights the importance of cutaneous cancer surveillance in the non-Caucasian population. Earlier identification of melanoma in this population will help to improve outcomes.