Elisabetta Nobili

Durable complete response of hepatocellular carcinoma after metronomic capecitabine.

Background Hepatocellular carcinoma (HCC) is a highly vascular tumor which is poorly responsive to standard systemic chemotherapy. Recently, various antiangiogenic targeted agents have shown promising activity at different levels of evidence in patients with advanced HCC, suggesting that such treatments might be effective. Case report Since chemotherapy administered with metronomic schedules inhibits angiogenesis, we treated a 64-year-old man with advanced HCC with metronomic capecitabine. After only two months of treatment the HCC nodules disappeared on ultrasonography. This finding was confirmed by a computed tomography scan. After more than three years the patient is still in treatment with minimal toxicity and maintains a complete remission. Conclusions Our case report suggests that metronomic capecitabine may be effective in advanced HCC patients while being also well tolerated. This is important, given the frequent comorbidities of HCC patients. Free full text available at www.tumorionline.it

Oxaliplatin-Based Chemotherapy in Advanced Neuroendocrine Tumors: Clinical Outcomes and Preliminary Correlation with Biological Factors

Purpose: The role of chemotherapy in low-/intermediate-grade neuroendocrine tumors (NETs) is still debated. We present the results of an Italian multicenter retrospective study evaluating activity and toxicity of oxaliplatin-based chemotherapy in patients with advanced NETs. Methods: Clinical records from 5 referral centers were reviewed. Disease control rate (DCR) corresponding to PR + SD (partial response + stable disease) at 6 months, progression-free survival (PFS), overall survival (OS) and toxicity were calculated. Ki67 labeling index, grade of differentiation and excision- repair-cross-complementing group 1 (ERCC-1) were analyzed in tissue tumor samples. Results: Seventy-eight patients entered the study. Primary sites were: pancreas in 46, gastrointestinal in 24, lung in 19 and unknown in 10% of patients. The vast majority were G2 (2010 WHO classification). Eighty-six percent of the patients were metastatic, and 87% were pretreated and progressive to previous therapies. Sixty-five percent of the patients received capecitabine/oxaliplatin (CAPOX), 6% gemcitabine/oxaliplatin (GEMOX), and 29% leucovorin/fluorouracil/oxaliplatin (FOLFOX-6). PR occurred in 26% of the patients, half of them with pancreatic NETs, and SD in 54%. With a median follow-up of 21 months, the median PFS and OS were 8 and 32 months with 70 and 45 events, respectively. The most frequent G3 toxicities were neurological and gastrointestinal. ERCC-1 immunohistochemical overexpression was positive in 4/28 evaluated samples, with no significant correlation with clinical outcome. Conclusion: This analysis suggests that oxaliplatin-based chemotherapy can be active with a manageable safety profile in advanced NETs irrespective of the primary sites and tumor grade. The 80% DCR and 8-month PFS could justify a prospective study in NETs with intermediate biological characteristics, especially with pancreatic primary tumors.

Impact of surgery on the development of duodenal cancer in patients with familial adenomatous polyposis

PurposePrecancerous duodenal lesions in patients with familial adenomatous polyposis can be detected with duodenoscopy and treatment may prevent the development of cancer. We proposed to determine the frequency, natural history, cumulative risk, and risk factors of the precancerous duodenal lesions in a series of patients diagnosed in northern Italy.MethodsA prospective, endoscopic, follow-up protocol was performed in 50 patients examined by gastroduodenoscopy at two years of interval or less. The presence and severity of precancerous lesions of the duodenal mucosa were evaluated by Spigelman score. Twenty-five patients (50 percent) had proctocolectomy and ileoanal anastomosis, 15 (30 percent) had colectomy and ileorectal anastomosis, and 5 (10 percent) had proctocolectomy and definitive ileostomy from 0 to 3 years before the admission to the surveillance program. All patients showed more than a thousand adenomas in the colorectal mucosa. No patients with attenuated polyposis were found.ResultsAt the first endoscopy, duodenal adenomas could be detected in 19 of 50 patients (38 percent), whereas at the end of the follow-up, 43 (86 percent) had duodenal lesions. The final mean Spigelman score increased during the follow-up period (P<0.001 respect to baseline values). No duodenal cancer could be detected. Eleven patients had or developed severe precancerous duodenal lesions (Stage IV) treated with endoscopic or surgical resection. The distribution of patients with Stage IV according to the surgery of the colon was: 2 of 25 treated with ileoanal anastomosis and 8 of 15 with ileorectal anastomosis (P=0.0024, Fisher’s exact test).ConclusionsPatients with familial adenomatous polyposis are at risk of significant neoplasia. The natural history of precancerous lesions might be related to surgical treatment of colorectal neoplasms.

Venous Thromboembolism and Port-Related Thrombosis in Metastatic Colorectal Cancer Patients: A Monocenter Experience

Venous thromboembolism (VTE) may occur during the natural history of neoplastic disease and is a common cause of mortality and morbidity in cancer patients. Major risk factors for VTE in cancer patients include surgery, immobilization, hospitalization, and the administration of granulopoietic and/or erythropoietic (stimulatory) agents. Chemotherapy is a supplementary independent risk factor for VTE and the use of central venous catheters (CVC) in clinical practice has increased the risk of thromboembolic events. We conducted a retrospective study to evaluate CVC-related thrombosis and the VTE rate in 145 consecutive metastatic colorectal cancer patients. We observed only 2 cases of symptomatic CVC- related thrombotic events (1.38%) and 10 cases of thromboembolic events (6.9%) in our series. Only surgery for metastases was found to be significantly related to the development of VTE, with an incidence of 16.1% vs. 4.4 in patients who did not undergo surgery (p = 0.037). In addition, a history of VTE seems to be a supplementary risk factor for CVC-related thrombosis (p = 0.055).

Autoimmune Pancreatitis Associated with High Levels of Chromogranin A, Serotonin and 5-Hydroxyindoleacetic Acid

We report a case of a male patient with autoimmune pancreatitis in whom biochemical examination revealed high plasma chromogranin A concentrations, histological demonstration of a small lymphocytic infiltrate and rapid decrease in size of the pancreatic mass following short-lasting therapy with methylprednisolone. To our knowledge, this is the first patient with autoimmune pancreatitis who had a simultaneous increase of serum chromogranin A levels, circulating and urinary serotonin concentrations and urine 5-hydroxyindoleacetic acid concentrations. This is one of the few cases of mass forming pancreatitis with small lymphocytic infiltrate found in a Caucasian patient and rapid decrease in size of the pancreatic mass following short-lasting therapy with methylprednisolone.

The safety and efficacy of enzalutamide in the treatment of advanced prostate cancer

ABSTRACT Introduction: Enzalutamide – a non-steroidal second-generation antiandrogen – represents an active treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) in both chemotherapy-naïve and docetaxel-pretreated settings, based on the demonstration of improved overall survival over placebo in two large phase III trials. Areas covered: The therapeutic landscape of mCRPC, narrowed to docetaxel until recently, encompasses now several treatments of a different nature (including androgen receptor targeting agents, taxanes, radiometabolic therapy, and immunotherapy), improving considerably the patients prognosis. However, direct comparisons between these agents still lack, raising the question of the optimal sequence of treatment. Expert commentary: We described in detail available data on clinical efficacy and safety of enzalutamide in different clinical settings (chemotherapy-naïve and -pretreated mCRPC patients), analyzing patients characteristics, the effects of enzalutamide on major clinical outcomes and its impact on patients quality of life. Finally, we briefly overviewed ongoing clinical trials evaluating potential active combinations, cross-resistance with other compounds, sequential strategies, and possible prognostic or predictive biomarkers.

Human Herpesvirus 6 Encephalitis Simulating Brain Metastases in a Patient with Advanced Small-Cell Lung Cancer

Background: The brain is a frequent site of metastases in small-cell lung cancer. Symptoms of cerebral involvement are headache, disorientation, nausea/vomiting and seizures. Case: A man with small-cell lung cancer developed a human herpesvirus 6 (HHV-6) meningoencephalitis with neurological symptoms that simulated brain involvement from the lung cancer. HHV-6 is a T cell lymphotropic virus which may be pathogenic in the immunocompromised host. HHV-6 remains latent after the first infection, and when the immune system is compromised it can reactivate. The treatment of HHV-6 infection is highly specific and the drugs recommended are the two antivirals, ganciclovir or foscarnet. Conclusion: In cancer patients neurologic symptoms are usually due to brain metastases. This case shows that in a cancer patient any aspecific neurologic symptom should be carefully evaluated in order to exclude a non-oncologic cause. This statement is particularly true if the therapies for the oncological and neurological diseases are effective.

Is adjuvant systemic chemotherapy after resection of metastases from colorectal cancer suitable

3654 Background: In patients affected by metastatic colorectal cancer surgical resection of metastases improves the overall survival (OS) and represents the only potentially curative therapy in spite of the high 2 years-recurrence rate of disease. Adjuvant chemotherapy via hepatic arterial infusion (HAI) after resection of liver metastases has shown its efficacy in terms of disease free survival (DFS) but not for OS. On the contrary, the role of adjuvant systemic chemotherapy after metastases resection (ASCMR) was rarely investigated in randomised trials. This retrospective analysis has considered the role of ASCMR on DFS in patients submitted to radical resection of lung or liver metastases (synchronous or metachronous at first recurrence) from colorectal cancer between June 1996 and January 2003 in our centre. METHODS 48 patients were eligible; 32 received ASCMR (M19; F 13) and 16 did not receive any therapy (M 8; F 8). ASCMR used regimens were: 9 pts Mayo clinic (mean number of infusion 6,2 range 3-12); 10 pts Folfox-4 (6,2 range 3-11); 4 pts Folfiri (6,5 range 5-9); 9 pts De Gramont (6,5 range 6-10).The characteristics of patients and lesions are reported in Tab 1 Results: Results are reported in Tab 1 Conclusions: The features of the disease in the two groups of patients (treated with ASCMR and not) are not different. DFS is statistically higher for patients submitted to ASCMR (in particular for lung metastases). In conclusions the adjuvant systemic chemotherapy after resection of metastases from colorectal cancer could prolong DFS, but large prospective studies are needed to define overall survival. [Figure: see text] No significant financial relationships to disclose.

Liver metastases from prostate cancer at 11C-Choline PET/CT: a multicenter, retrospective analysis

AimDuring our daily clinical practice using 11C-Choline PET/CT for restaging patients affected by relapsing prostate cancer (rPCa) we noticed an unusual but significant occurrence of hypodense hepatic lesions with a different tracer uptake. Thus, we decided to evaluate the possible correlation between rPCa and these lesions as possible hepatic metastases.Materials and methodsWe retrospectively enrolled 542 patients diagnosed with rPCa in biochemical relapse after a radical treatment (surgery and/or radiotherapy). Among these, patients with a second tumor or other benign hepatic diseases were excluded. All patients underwent 11C-Choline PET/CT during the standard restaging workup of their disease. We analyzed CT images to evaluate the presence of hypodense lesions and PET images to identify the relative tracer uptake. In accordance to the subsequent oncological history, five clinical scenarios were recognized [Table 1]: normal low dose CT (ldCT) and normal tracer distribution (Group A); evidence of previously unknown hepatic round hypodense areas at ldCT with normal rim uptake (Group B); evidence of previously known hepatic round hypodense areas at ldCT stable over time and with normal rim uptake (Group C); evidence of previously known hepatic round hypodense areas at ldCT, in a previous PET/CT scan, with or without rim uptake and significantly changing over time in terms of size and/or uptake (Group D); evidence of hepatic round hypodense areas at ldCT with or without rim uptake confirmed as prostate liver metastases by histopathology, triple phase ceCT, ce-ultra sound (CEUS) and clinical/biochemical evaluation (Group E). We evaluated the correlation with PSA level at time of scan, rim SUVmax and association with local relapse or non-hepatic metastases (lymph nodes, bone, other parenchyma).ResultsFive hundred and forty-two consecutive patients were retrospectively enrolled. In 140 of the 542 patients more than one 11C-choline PET/CT had been performed. A total of 742 11C-Choline PET/CT scans were analyzed. Of the 542 patients enrolled, 456 (84.1%) had a normal appearance of the liver both at ldCT and PET (Group A). 19/542 (3,5%) belonged to Group B, 13/542 (2.4%) to Group C, 37/542 (6.8%) to Group D and 18/542 (3.3%) to Group E. Mean SUVmax of the rim was: 4.5 for Group B; 4.2 for Group C; 4.8 for Group D; 5.9 for Group E. Mean PSA level was 5.27 for Group A, 7.9 for Group B, 10.04 for Group C, 10.01 for Group D, 9.36 for Group E. Presence of positive findings at 11C-Choline PET/CT in any further anatomical area (local relapse, lymph node, bone, other extra hepatic sites) correlated with an higher PSA (p = 0.0285). In both the univariate and multivariate binary logistic regression analyses. PSA, SUVmax of the rim, local relapse, positive nodes were not associated to liver mets (Groups D-E) (p > 0.05). On the contrary, a significant correlation was found between the presence of liver metG (group D-E) and bone lesions (p= 0.00193).ConclusionOur results indicate that liver metastases in relapsing prostate cancer may occur frequently. The real incidence evaluation needs more investigations. In this case and despite technical limitations, Choline PET/CT shows alterations of tracer distribution within the liver that could eventually be mistaken for simple cysts but can be suspected when associated to high trigger PSA, concomitant bone lesions or modification over time. In this clinical setting an accurate analysis of liver tracer distribution (increased or decreased uptake) by the nuclear medicine physician is, therefore, mandatory.

Role of Guided - Fine Needle Biopsy of the Pancreatic Lesion

A variety of uncommon types of pancreatic carcinoma have been described, including acinar, adenosquamous, anaplastic, papillary, mucinous and microadenocarcinomas, each of which composes less than 5% of the total. All of these have similarly poor prognoses and are treated in a similar fashion. Also uncommon are mucinous cystic neoplasms (cystadenoma/cystadenocarcinoma) of the pancreas, which occur most frequently in the middle-aged women, and these are tipically located in the tail of the pancreas.