Selenia Casnedi

Sinusoidal Injury Increases Morbidity After Major Hepatectomy in Patients With Colorectal Liver Metastases Receiving Preoperative Chemotherapy

Objective:To investigate whether sinusoidal injury (SI) was associated with a worse outcome after hepatectomy in patients with colorectal liver metastases (CRLM). Background:Correlation between SI and oxaliplatin-based chemotherapy (OBC) was recently shown in patients with CRLM. However, it has yet to be fully clarified whether SI affects liver functional reserve and outcome after hepatectomy. Patients and Methods:Between 2003 and 2005, 90 patients with CRLM who underwent an elective hepatectomy after preoperative chemotherapies were included. Diagnosis of SI was established pathologically in the nontumoral liver parenchyma of the resected specimens, and perioperative data were assessed in these patients. Results:OBC was significantly associated with a higher incidence of SI. Preoperative indocyanine green retention rate at 15 minutes (ICG-R15) and postoperative value of total-bilirubin were significantly higher, and hospital stay was significantly longer in patients presenting with SI. Multivariate analysis showed that female gender, administration of 6 cycles or more of OBC, abnormal value of preoperative aspartate aminotransferase >36 IU/L, or abnormal value of preoperative ICG-R15 (>10%) were preoperative factors significantly associated with SI. Among patients undergoing a major hepatectomy, SI was significantly associated with higher morbidity and longer hospital stay. Conclusion:The present study suggests that SI resulted in a poorer liver functional reserve and in a higher complication rate after major hepatectomy. Therefore, female patients who received 6 cycles or more of OBC, or presenting with abnormal preoperative aspartate aminotransferase and ICG-R15 values should be carefully selected before deciding to undertake a major hepatectomy.

Clinicopathologic Study of 62 Acinar Cell Carcinomas of the Pancreas: Insights Into the Morphology and Immunophenotype and Search for Prognostic Markers.

Acinar cell carcinoma (ACC) of the pancreas is a very rare tumor that has various morphologic features, which may give rise to diagnostic difficulties. Because of its rarity, many clinicopathologic characteristics remain to be further elucidated, and prognostic factors are yet to be well established. With the aim of better characterizing this carcinoma and searching for prognostic indicators, we collected 62 ACCs and investigated the following parameters: site, size, local infiltration, node and distant metastases, architectural pattern, nuclear atypia, presence of necrosis, lymphovascular and perineural invasion, proliferation, BCL10, trypsin, carboxyl ester lipase, amylase, lipase, PDX1, cytokeratin 19 (CK19), CK7, p53, and &bgr;-catenin expression. Twelve cases showing >30% of endocrine cells were reclassified as mixed acinar-neuroendocrine carcinomas, whereas 1 tumor was reclassified as a mixed ductal-acinar carcinoma and was excluded from the statistical prognostic evaluations. BCL10 and trypsin were the most reliable immunohistochemical markers, whereas amylase and lipase were not. Surgery was statistically correlated with a better prognosis (P=0.0008). Among resected tumors there was no difference in survival between ACCs and mixed acinar-neuroendocrine carcinomas, and factors that significantly correlated with poor prognosis were size >6.5 cm (P=0.004), lymph node (P=0.0039) and distant (P=0.008) metastases, and UICC stage (P=0.009). Stage was the only independent prognostic factor at multivariable analysis, and the best prognostic discrimination was observed on grouping together stages I and II and grouping together stages III and IV, suggesting a simplification of the UICC staging for such cancers. In addition, vascular and perineural invasion and CK19 and p53 expression showed a trend for poor prognosis, not reaching statistical significance.

Sinusoidal obstruction syndrome compromises liver regeneration in patients undergoing two-stage hepatectomy with portal vein embolization.

PurposeSeveral factors have been reported to affect liver regeneration after portal vein embolization (PVE); however, the effect of sinusoidal obstruction syndrome (SOS) has not been evaluated. Therefore, we assessed the effect of SOS on liver regeneration after PVE in patients with multiple bilobar colorectal liver metastases scheduled to undergo two-stage hepatectomy (TSH) combined with PVE.MethodsThe subjects of this study were 78 patients prospectively scheduled to undergo TSH between December 1996 and August 2009. Archived formalin-fixed, paraffin-embedded nontumoral tissue samples were collected from the 1st- and 2nd-stage hepatectomies in 42 and 45 patients, respectively, and SOS and steatohepatitis were diagnosed pathologically. We analyzed the clinicopathological variables affecting liver regeneration after PVE.ResultsSinusoidal obstruction syndrome was diagnosed in 11 (26.2%) and 20 patients (44.4%) at the time of the 1st- and 2nd-stage hepatectomy, respectively. Patients with SOS at the 1st-stage hepatectomy had a significantly lower hypertrophy ratio of the future remnant liver (FRL) after PVE than patients without SOS (16.8 ± 24.0 vs 55.6 ± 32.5; P < 0.001). Multivariate logistic regression analysis revealed that SOS was an independent factor predicting lower FRL hypertrophy after PVE (Δ% FRL <20: hazard ratio 31.7, 95% confidence interval 2.84–355.12; P = 0.005). The incidence of postoperative transient liver failure after the 2nd-stage hepatectomy in patients presenting with SOS was higher than that in those without SOS, but the difference did not reach significance (25.0% vs 4.0%; P = 0.052). Steatohepatitis was confirmed at the 1st- and 2nd-stage hepatectomy in 6 (14.3%) and 3 (6.7%) patients, respectively.ConclusionSinusoidal obstruction syndrome inhibits FRL hypertrophy after PVE and induces postoperative liver failure. Therefore, an alternative strategy is needed to perform TSH safely in the presence of SOS.

Targeted molecular therapies (cetuximab and bevacizumab) do not induce additional hepatotoxicity: preliminary results of a case-control study.

AIMS To analyse the effects of the preoperative targeted molecular therapy (cetuximab (cetu) or bevacizumab (beva)) on non-tumorous liver parenchyma, and the clinical and biological outcome after liver resection for colorectal liver metastases (CLM). METHODS Between January 2005 and December 2007, 36 patients receiving preoperatively cetu (n = 15) or beva (n = 21) were, respectively, matched to a control group of patients who did not receive targeted molecular therapy. They were matched on the basis of age, gender, body mass index, extent of hepatectomy, and type and number of neoadjuvant chemotherapy. Liver function tests, postoperative outcome and histopathology of the resected liver were compared. RESULTS There was no mortality. Postoperative morbidity and perioperative bleeding rates were similar in both groups. In the beva group, liver function tests showed higher serum bilirubin level on postoperative day (POD) 1 (p = 0.001) and POD 3 (p = 0.01), higher serum aspartate aminotransferase on POD 1 (p = 0.004), and lower prothrombin time on POD 5 (p = 0.02). In both groups, cetu and beva, the postoperative peaks of gamma-glutamyl transpeptidase and alkaline phosphatase were statistically higher than in the control groups. Interestingly, the prevalence of sinusoidal injury and fibrosis was lower in patients receiving cetu (p = 0.04), while the prevalence of steatohepatitis was lower in patients receiving beva (p = 0.04). CONCLUSION The addition of beva or cetu to the neoadjuvant chemotherapy regimens does not appear to increase the morbidity rates after hepatectomy for CLM. The pathological examination did not show additional injury to the non-tumorous liver parenchyma.

Breast Metastasis as the First Clinical Manifestation of Ileal Neuroendocrine Tumor. A Challenging Diagnosis with Relevant Clinical Implications

Ileal neuroendocrine tumors are slow-growing grade 1 or, more rarely, grade 2 neuroendocrine tumors which, however, are frequently metastatic to regional lymph nodes and the liver. A few cases of ileal neuroendocrine tumors that are metastatic to the breast have also been reported in the medical literature. The knowledge of this uncommon clinical presentation is of great importance because it needs to be differentiated from primary breast carcinomas with neuroendocrine features, which represent completely different entities with a different therapeutic approach. The diagnosis of a breast metastasis from an ileal neuroendocrine tumor and its distinction from a well-differentiated primary neuroendocrine tumor of the breast is a challenging task for clinicians and pathologists. This workup is particularly difficult when the breast lesion is the first sign of malignancy. In the present paper, we describe the clinicopathological features of an ileal neuroendocrine tumor first presenting with a breast metastasis in a 50-year-old woman and we discuss the key diagnostic features for the differential diagnosis with primary well-differentiated neuroendocrine tumor of the breast. Moreover, we have reviewed the medical literature to give the reader a comprehensive overview on this topic.

Sarcome primitif du pancréas avec métastases hépatiques : place d’une chirurgie radicale ?

Pancreatic leiomyosarcomas are a rare neoplasm that accounts for 1/1000 of pancreatic cancers. In the literature, 23 cases of pancreatic leiomyosarcoma have been reported and the majority being diagnosed on autopsy. It has never been reported any radical curative surgery in presence of synchronous hepatic metastasis. We reported a case of a patient affected by a primitive pancreatic leiomyosarcoma with bilobar hepatic metastasis, who underwent distal splenopancreatectomy associated with the resection of multiple liver metastases.

c-MYC amplification and c-myc protein expression in pancreatic acinar cell carcinomas. New insights into the molecular signature of these rare cancers

The molecular alterations of pancreatic acinar cell carcinomas (ACCs) and mixed acinar-neuroendocrine carcinomas (MANECs) are not completely understood, and the possible role of c-MYC amplification in tumor development, progression, and prognosis is not known. We have investigated c-MYC gene amplification in a series of 35 ACCs and 4 MANECs to evaluate its frequency and a possible prognostic role. Gene amplification was investigated using interphasic fluorescence in situ hybridization analysis simultaneously hybridizing c-MYC and the centromere of chromosome 8 probes. Protein expression was immunohistochemically investigated using a specific monoclonal anti-c-myc antibody. Twenty cases had clones with different polysomies of chromosome 8 in absence of c-MYC amplification, and 5 cases had one amplified clone and other clones with chromosome 8 polysomy, while the remaining 14 cases were diploid for chromosome 8 and lacked c-MYC amplification. All MANECs showed c-MYC amplification and/or polysomy which were observed in 54% pure ACCs. Six cases (15.3%) showed nuclear immunoreactivity for c-myc, but only 4/39 cases showed simultaneous c-MYC amplification/polysomy and nuclear protein expression. c-myc immunoreactivity as well as c-MYC amplification and/or chromosome 8 polysomy was not statistically associated with prognosis. Our study demonstrates that a subset of ACCs shows c-MYC alterations including gene amplification and chromosome 8 polysomy. Although they are not associated with a different prognostic signature, the fact that these alterations are present in all MANECs suggests a role in the acinar-neuroendocrine differentiation possibly involved in the pathogenesis of MANECs.