Journal of Integrative Oncology

Oxaliplatin (LOHP) and pegylated liposomal doxorubicin (PLD) are active single agents in recurrent ovarian cancer (ROC). In this phase II study we explored safety and activity of combined LOHP and PLD in the treatment of ROC. Eligible patients had had disease recurrence following a paclitaxel/ carboplatin regimen or following cisplatinum or non-platinum-based second line chemotherapy. Other eligibility criteria were a performance status ≤ 2 and a life expectancy > 3 months. Treatment consisted of 120 mg/m2 LOHP and 40 mg/m2 PLD, given over 2 days, every 3 weeks. Forty-six patients with ROC were entered into the study between 10/2001 and 10/2005; 67.5% of patients were platinum-sensitive. Toxicity was moderate, with grade 3 or 4 neutropenia in 2% of patients, and grade 2 PPE in 7% of patients. Overall response rate was 67.5%. Median progression-free survival (PFS) was 27.5 months, while median overall survival was 44 months. We conclude that LOHP and PLD are active in ROC, and can be safely administered in pre-treated patients

Recurrence after liver surgery for hepatocellular carcinoma (HCC) remains the major dismal event affecting patient’s overall survival (OS). Several studies on gene signature showed an association between MYC deregulation and poor prognosis. We aimed to analyze prognostic factors, including MYC status, for disease free survival (DFS) and OS, as well as to develop a new prognostic model for HCC able to predict the patient’s prognosis. Methods: Sixty-three patients who underwent liver resection for HCC from January 2006 to December 2009 in a single division of the Department of Surgery at the University of Verona were included into this study. Predictors of DFS and OS were identified using univariate and multivariate survival analysis. The prognostic ability of our model was compared using Harrell’s c-index to current clinical staging systems (AJCC/TNM 7th ed., BCLC and CLIP). Results: Predictors of DFS, in both univariate and multivariable analysis were number of HCC, serum AFP, and MYC status; these variables were included in a nomogram to predict DFS. Patients were classified into two groups (high- and low-risk group) according to their predicted 12-month risk of recurrence. Patients in low-risk group showed a 36-month DFS of 43% compared to 0% for high-risk group. Furthermore, patients in low-risk group presented a 36-month OS of 70% compared to 15% for high-risk group. Our model was included in AJCC/TNM 7th ed., BCLC and CLIP staging systems. When reclassified with our model, CLIP presented the highest predictive ability (c-index=73%) compared to the others staging-systems. Conclusions: We developed a prognostic model for DFS after hepatectomy for HCC, based on MYC gene status and clinical features (number of nodules and AFP serum level). Our new prognostic model could have important clinical applications in selecting those patients who might have major benefits from surgical resection.

Introduction: Basal cell carcinoma accounts for 80% of all non-melanoma skin cancer. Vismodegib is the hedgehog signaling pathway inhibitor, which has shown improved outcome in both locally advanced and metastatic basal cell carcinoma. There are, however, reports of cutaneous squamous cell carcinomas developing while on active treatment with vismodegib. We present a case of transition to squamous cell carcinoma after vismodegib treatment in a patient with a 10-year history of basal cell carcinoma.
Case presentation: 44-year-old Caucasian man with 10 year history of basal cell carcinoma on his left chest wall and left shoulder was treated with local resection and actively on vismodegib. He presented with enlarging and infected mass. He underwent left forequarter amputation of his left arm, shoulder and clavicle. Pathology reported basosquamous cell carcinoma with scapula invasion and axillary lymph node metastases. Staging was stage III T4N1M0. He continued on vismodegib post-operation. Three months after his amputation, the patient presented with a recurrent left shoulder mass with nonhealing surgical wound. Imaging revealed vascular invasion. Biopsy of the lesion was consistent with invasive squamous cell carcinoma with genomic profiling of PIK3R1, PTCH1 and STK11 gene mutations. At the patient’s request he was subsequently transferred to another facility for a second surgical opinion.
Conclusion: Biopsy and genetic analyses of basal cell carcinoma lesions should be considered in every case that has treatment plan for hedgehog signaling pathway inhibitor to evaluate for potential secondary squamous cell carcinoma growth. Further study is needed to confirm the mechanism of basal cell resistance to anti-smoothened therapy and eventual squamous cell carcinoma growth.

Only a few cases of malignant peripheral nerve sheath tumor (MPNST) associated with Von Recklinghausen’s disease or type I neurofibromatosis (NF-1) have so far been reported worldwide. We present a case of a 27 year old man with MPNST of the left thigh associated with NF-1. The diagnosis was based on clinical, radiological and histopathological evidence. He presented a large mass of thigh, deeply adhering, with the presence of collateral venous circulation. He also presented multiple café-au-lait spots, with a many neurofibromas. MRI of the hip and left thigh showed the presence of a bulky tissue process, badly limited, measuring 24,6×11×12 cm occupying the anterolateral and posterolateral lodge with an intermediate signal in T1, discreetly more intense in T2. The microscopic and immunohistochemical findings supported the final diagnosis of MPNST with mesenchymal differentiation. The staging was negative. Also, the diagnosis of NF-1 is held according to the presence of two NIH criteria. The decision of the multidisciplinary meeting was to make a neoadjuvant chemotherapy to surgery with a doublet of adriamycin and ifosfamide with surveillance for other tumor development or multisystem complications. The presence of a large mass on the path of a peripheral nerve requires a careful examination of the skin for signs evoking a von Recklinghausen disease.

Background: The levels of expression of Heparin binding-epidermal growth factor like growth factor (HB-EGF) mRNA in tumor tissues and normal tissues of the excised kidney were compared in order to clarify the role of HBEGF inrenal cell carcinoma (RCC) derived from the proximal tubule. Method: Normal and tumor tissues were collected from surgical specimens of 16 cases pathologically diagnosed with RCC. Total RNA was extracted from these samples, and the level of expression of HB-EGF mRNA was measured by real-time quantitative PCR using a TaqMan probe after reverse transcription. Glyceraldehyde phosphate dehydrogenase (GAPDH) was used as an internal standard. The expression levels of HB-EGF mRNA in normal and tumor tissues of the same case were compared, and statistical analysis was performed to evaluate the association between the expression level and various clinical-pathological factors in RCC. Results: Expression of HB-EGF mRNA was detected in 82% (13/16) of the normal tissues and 63% (10/16) of the tumor tissues. The expression level in the normal tissues was significantly 7-fold higher than that in the tumor tissues. No significant association was detected between the expression of HB-EGF mRNA and the clinical stage or prognosis of RCC. However, the pathological findings indicated that negative expression of ratio of HB-EGF was higher in RCC with more-advanced malignant progression. Conclusion: Our results indicated that it was unlikely that HB-EGF might play a role in determining the aggressiveness or clinical features in RCC. However, the decreased expression of HB-EGF mRNA in RCC tissues indicates that tumorigenesis of RCC may disrupt the normal regulatory system of HB-EGF.

Four HCC characteristics typically inform tumor behavior: maximum tumor size, number of nodules, portal vein thrombosis and serum AFP level. The sum of these parameters was recently published as an HCC Aggressiveness Index. We aimed to validate this index retrospectively in a larger and independent HCC cohort of 2706 Italian HCC patients, and to evaluate a possible relationship between the index and liver function parameters. The scores in the HCC Aggressiveness Index were again found to significantly relate to patient survival. Furthermore, in a multiple logistic regression model of the Aggressiveness Index score categories, there were significant differences in several liver parameter terciles amongst the score categories, suggesting a relationship of liver function to tumor aggressiveness. It was concluded that a prognostically significant Tumor Aggressiveness Index was validated and was found to be related to levels of some common liver function parameters.