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Resection of Hepatocellular Carcinoma in Patients Otherwise Eligible for Transplantation

Introduction The incidence of hepatocellular carcinoma (HCC) in the United States has increased 75% in the last decade. Liver transplantation is gaining acceptance for the treatment of early HCC, even in patients with adequate liver function. The objective of this study was to determine the long-term outcome of patients with early HCC who would have been candidates for transplantation but were treated instead with partial hepatectomy. Methods From August 1989 to November 2001, 611 patients with HCC were evaluated at our institution and entered into a prospective database. There were 180 (29%) patients who underwent partial hepatectomy, of whom 36 (20%) satisfied the currently accepted criteria for transplantation: 2 or 3 lesions each ≤ 3 cm in size or a solitary tumor ≤ 5 cm. Survival was determined by Kaplan-Meier analysis. Results Median tumor size was 3.5 (range, 1.8–5) cm and the median number of lesions was 1 (range, 1–3). Patients had pathologically confirmed cirrhosis of the liver in 78% (28/36) of cases, and 86% had normal liver function (Child class A). Perioperative morbidity was 25%, the median length of hospital stay was 8 (range, 4–24) days, and there was 1 (2.8%) perioperative death. At a median follow-up of 35 months for survivors, the 1-, 3-, and 5-year overall survival was 85%, 74%, and 69%, respectively, with a median survival of 71 months. The 5-year disease-free survival was 48% with a median of 52 months. Conclusions Partial hepatectomy in patients with early HCC who are otherwise eligible for transplantation can be performed with minimal morbidity and can achieve comparable 5-year survival to that reported for liver transplantation. Resection should be considered the standard therapy for patients with HCC who have adequate liver reserve.

Long-term results with resection of radiation-induced soft tissue sarcomas.

Introduction:Radiation therapy is increasingly used as adjuvant treatment of many childhood and adult malignancies. Radiation-induced sarcoma is a well recognized if uncommon event. The objective of this study is to determine the prevalence and long-term outcome for patients who develop radiation-induced sarcomas. Methods:From July 1982 to December 2001, 4884 adult patients with sarcoma were admitted and treated at our institution and recorded in a prospective database. There were 123 (2.5%) patients who had radiation-induced soft tissue sarcomas. Survival was determined by Kaplan-Meier analysis. Patient, tumor, and treatment characteristics were tested for their prognostic significance by log rank and the Cox proportional hazards model. Results:The median interval between radiation and development of sarcoma was 103 (6 to 534) months. In 114 patients with radiation-induced sarcoma who underwent curative resection, the 5-year actuarial survival was 41%, with a median survival of 48 months at a median follow-up of 36 months for survivors. The most common malignancy for which radiation was used was breast cancer (29%), followed by lymphoma (16%) and prostate cancer (15%). Malignant fibrous histiocytoma (23%) was the most common histologic diagnosis, followed by fibrosarcoma (15%) and angiosarcoma (15%). High-grade tumors (n = 85; 79%), age > 60 years (n = 61; 50%), and gross positive resection margin (n = 36; 32%) were predictive of poor sarcoma-specific survival on univariate and multivariate analysis. Conclusions:The increasing utilization of adjuvant radiation therapy, especially for early-stage breast cancer mandates long-term follow-up to detect radiation-induced sarcoma. Surgical resection remains the primary therapy, but 5-year survival remains ∼40%.

Venous Identity Is Lost but Arterial Identity Is Not Gained During Vein Graft Adaptation

Objectives—Ephrin ligands and Eph receptors are signaling molecules that are differentially expressed on arteries and veins during development. We examined whether Eph-B4, a venous marker, and Ephrin-B2, an arterial marker, are regulated during vein graft adaptation in humans and aged rats. Methods and Results—Eph-B4 transcripts and immunodetectable protein are downregulated in endothelial and smooth muscle cells of patent vein grafts in both humans and in aged rats, whereas Ephrin-B2 transcripts and protein are not strongly induced. Other markers of arterial identity, including dll4 and notch-4, are also not induced during vein graft adaptation in aged rats. Because VEGF-A is upstream of the Ephrin–Eph pathway, and expression of VEGF-A is induced only at early time points after exposure of the vein to the arterial environment, we inhibited VEGF-A in vein grafts using an siRNA-based approach. Vein grafts treated with siRNA directed against VEGF-A demonstrated a thicker intima-media containing α-actin, consistent with arterialization, but did not contain Eph-B4 or Ephrin-B2. Conclusions—Venous identity is preserved in the veins of aged animals, but is lost during adaptation to the arterial circulation; arterial markers are not induced. Markers of vessel identity are plastic in adults and their selective regulation may mediate vein graft adaptation to the arterial environment in aged animals and humans.

Primary thyroid lymphoma: Can the diagnosis be made solely by fine-needle aspiration?

BackgroundPrimary malignant lymphoma fo the thyroid accounts for <5% of all thyroid malignancies and is primarily treated with chemotherapy and external beam radiation. With the advent of modern immunophenotypic analyses, fine-needle aspiration (FNA) can potentially obviate the need for surgical procedures.MethodsTo investigate the utility of FNA, data from 23 consecutive patients with primary malignant thyroid lymphoma evaluated at the Johns Hopkins Hospital from July 1985 to April 2000 were analyzed.ResultsPatients were categorized into two groups: those diagnosed before 1993 (group 1, n=12) and those diagnosed after 1993 (group 2, n=11). Although patients in group 1 were slightly older, there were no other differences between the groups with regard to sex, tumor grade, or tumor stage. Although no patient in group 1 was successfully diagnosed by FNA alone, seven patients (63%) in group 2 were diagnosed solely by FNA (P=.019, χ2 analysis). Therefore, all 12 patients in group 1, but only 4 of 11 patients in group 2, required open surgical biopsy.ConclusionsPrimary thyroid lymphoma is an uncommon malignancy usually treated nonsurgically once the diagnosis is established. In most patients with malignant lymphoma of the thyroid, FNA, should obviate the need for open surgical biopsy.

Surgery and ablative therapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, responsible for an estimated one million deaths annually. The incidence in the United States has steadily increased over the past two decades. Although HCC has historically had a dismal prognosis, it is now being detected earlier as a result of improved radiologic imaging and surveillance. This affords the opportunity to treat patients with curative intent, and may improve survival. Partial hepatectomy and transplantation each provide potentially curative therapy for selected patients with HCC. Transplantation is indicated when there is severe underlying liver dysfunction. Local ablative therapy, such as ethanol injection, hepatic artery embolization, and radiofrequency ablation, offer palliation for patients when surgery is not feasible. The rational application of the myriad of therapies to a patient with HCC is designed to maximize both quality of life and survival.

Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer.

Background:Modifications of FOLFIRINOX are widely used despite the absence of prospective data validating efficacy in metastatic disease (metastatic pancreatic cancer (MPC)) or locally advanced pancreatic cancer (LAPC). We conducted a multicentre phase II study of modified FOLFIRINOX in advanced pancreatic cancer to assess the impact of dose attenuation in MPC and efficacy in LAPC.Methods:Patients with untreated MPC or LAPC received modified FOLFIRINOX (irinotecan and bolus 5-fluorouracil reduced by 25%). Adverse events (AEs) were compared with full-dose FOLFIRINOX. Response rate (RR), median progression-free survival (PFS) and median overall survival (OS) were determined.Results:In total, 31 and 44 patients with LAPC and MPC were enrolled, respectively. In MPC, efficacy of modified FOLFIRINOX was comparable with FOLFIRINOX with RR 35.1%, OS 10.2 months (95% CI 7.65–14.32) and PFS 6.1 months (95% CI 5.19–8.31). In LAPC, efficacy was notable with RR 17.2%, resection rate 41.9%, PFS 17.8 months (95% CI 11.0–23.9) and OS 26.6 months (95% CI 16.7, NA). Neutropenia (P<0.0001), vomiting (P<0.001) and fatigue (P=0.01) were significantly decreased. [18F]-Fluorodeoxyglucose positron emission tomography imaging response did not correlate with PFS or OS.Conclusions:In this first prospective study of modified FOLFIRINOX in MPC and LAPC, we observed decreased AEs compared with historical control patients. In MPC, the efficacy appears comparable with FOLFIRINOX. In LAPC, PFS and OS were prolonged and support the continued use of FOLFIRINOX in this setting.

Hepatocellular carcinoma: A comprehensive overview of surgical therapy

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with a rising incidence in the United States. The increase in medical and locally ablative therapies have improved prognosis, however surgery, either liver resection or transplantation, remains the mainstay of therapy. An increased understanding of liver anatomy, improved imaging modalities and refinements of surgical technique have all led to improved outcomes after surgery. Both resection and transplantation may be used in a complementary manner. Resection remains the treatment of choice for HCC when feasible. Liver transplantation, which removes both the tumor and the underlying diseased liver offers excellent outcomes in patients that meet the Milan criteria. While both these modalities have relatively well defined roles, the treatment of these patients must be tailored individually, using a multidisciplinary approach, to maximize survival, quality of life and allocation of scarce organs. J. Surg. Oncol. 2014 110:712–719.

Laparoscopic repair of iatrogenic diaphragmatic hernia following radiofrequency ablation for hepatocellular carcinoma

Radiofrequency ablation (RFA) is commonly used for treating unresectable hepatic malignancies. Some commonly associated complications of RFA include fever, symptomatic pleural effusion, abscess, hepatoma and hepatic insufficiency. Here, we report a case of diaphragmatic hernia in a patient following RFA for hepatic malignancy with cirrhosis.

Multiple gastrointestinal stromal tumors and synchronous ileal carcinoids

Background A 74-year-old African-American male presented with a 3-day history of hematemesis and melena. The patient reported no abdominal pain, constitutional symptoms, bright red blood per rectum, constipation, or diarrhea. His physical examination and medical history were unremarkable except for benign prostatic hypertrophy. An esophagogastroduodenoscopy showed a 3 × 2 × 2cm smooth round mass in the cardia, 2 cm distal to the gastroesophageal junction. Biopsy of the mass revealed an ulcerated tumor composed of spindle cells. Immunohistochemistry showed positive staining for a number of biochemical markers, including KIT, Ki-67 and smooth muscle actin, but was negative for the markers S100 and desmin. A gastric-wedge resection revealed an ulcerated 4.5cm mass in the stomach, and exploration of the abdomen revealed two ileal carcinoid tumors, jejunal diverticula and reactive mesenteric lymphadenopathy.Investigations Esophagogastroduodenoscopy, biopsy, CT scan, immunohistochemistry, DNA microarray analysis and quantitative reverse transcriptase-PCR.Diagnosis Multiple gastrointestinal stromal tumors occurring concomitantly with ileal carcinoids.Management Gastric-wedge resection and segmental resection.

Intermedin is overexpressed in hepatocellular carcinoma and regulates cell proliferation and survival

Angiogenesis is one of the hallmarks of tumor growth and metastasis. Identification of tumor angiogenic factors has been a critical component in understanding cancer biology and treatment. Intermedin (IMD) has been reported to promote angiogenesis in a rat ischemic model and human umbilical vascular endothelial cells. Our study sought to determine the role of IMD in human hepatocellular carcinoma tumor progression. High IMD mRNA expression levels were observed in human hepatocellular carcinoma tumors, even in early stage disease, by real‐time RT‐PCR. Immunohistochemical analysis of hepatocellular carcinoma clinical samples demonstrated that the tumor regions were significantly more immunoreactive for IMD than adjacent benign liver. Inhibition of IMD expression using RNA interference reduced cell proliferation in SK‐Hep‐1 and SNU‐398 cells. Blockage of IMD signaling using either an antagonist peptide or a neutralizing antibody inhibited growth in a dose‐dependent manner with concomitant induction of apoptosis, causing cleavage of caspase‐8 and downregulation of Gli1 and Bcl2. Conversely, addition of IMD active peptide increased the phosphorylation level of extracellular signal‐regulated kinase. Thus, IMD might play an important role in cell proliferation and survival of hepatocellular carcinoma. Our data suggests that IMD is a potential biomarker and therapeutic target for hepatocellular carcinoma. (Cancer Sci, doi: 10.1111/j.1349‐7006.2012.02341.x, 2012)