A case of Muir-Torre syndrome associated with mucinous hepatic cholangiocarcinoma and a novel germline mutation of the MSH2 gene

Muir-Torre syndrome (MTS) is a rare cancer-predisposing syndrome that is autosomal dominantly inherited and characterized by the development of sebaceous skin lesions (adenomas, epitheliomas, basaliomas and carcinomas). These lesions are typically associated with tumors that belong to the spectrum of hereditary nonpolyposis colorectal cancer (HNPCC) (i.e. tumors of the colorectum, endometrium, stomach or ovary). Biliary malignancy in association with MTS has only rarely been reported. We report a case of Muir-Torre syndrome associated with intrahepatic cholangiocarcinoma, a location not previously described, and associated with a novel missense mutation of the MSH2 gene (c.2026T>C), predicted to disrupt the function of the gen

Serrated polyps of the colorectum: is sessile serrated adenoma distinguishable from hyperplastic polyp in a daily practice?

The distinction between serrated polyps of the colon is complex, particularly between hyperplastic polyps (HP) and sessile serrated adenomas (SSA). Recent data show that SSA might be the precursors of serrated colonic cancers, underlining the necessity of identifying them. We characterized the demographic and pathologic characteristics of 102 serrated lesions among 321 polyps of the colorectum and determined if SSA can be microscopically distinguished from HP in biopsy material of a daily practice. There were 81 HP (79%) and 7 SSA (7%) of which one displayed low-grade dysplasia. Only six serrated polyps (6%) could not be correctly classified. The main architectural criteria for distinguishing SSA from HP is the serrated feature along the crypt axis and the rarity of undifferentiated cells in the lower third of the crypts. SSA was significantly more often located in the right colon and larger (median, 11 vs 4 mm) than HP. SSA are rare serrated polyps that can be distinguished from HP based on their morphology, location in the right colon, and larger size. One SSA of our series showed low-grade dysplasia supporting the concept that this lesion might be a precursor of serrated adenocarcinom

Evolution of intratumoral genetic heterogeneity during colorectal cancer progression

Evolution of intratumoral genetic heterogeneity during colorectal tumor progression has not been investigated so far. Multiple sample areas in colorectal adenocarcinoma at early and advanced stages and in metastases were studied for the well-known genetic alterations: K-ras and p53 point mutations and loss of heterozygosity (LOH) on chromosomes 5q and 18q. In primary colorectal cancers (CRCs), intratumoral genetic heterogeneity was more often observed in early than in advanced stages, at 90 and 67%, respectively. All but one of the advanced CRCs were composed of one predominant clone and other minor clones, whereas no predominant clone has been identified in half of the early cancers. At the early stage, the last events that were produced, the p53 mutation and LOH of 18q, were also the most heterogeneous. At the advanced stage, the LOH of 5q and 18q were the most frequent heterogeneous events (67 and 58%, respectively). The intratumoral heterogeneity for mutations was significantly reduced, from the early to the advanced stages (from 60 to 20% for K-ras and from 70 to 20% for p53). On the other hand, a quasi absence of intratumoral genetic heterogeneity was observed for K-ras and p53 in distant metastasis. In conclusion, colorectal adenocarcinomas are characterized by marked intratumoral genetic heterogeneity. A reduction of the intratumoral genetic heterogeneity for point mutations and a relative stability of the heterogeneity for allelic losses indicate that, during the progression of CRC, clonal selection and chromosome instability continue, while an increase cannot be prove

Long-term Outcome after Liver Resection for Hepatocellular Carcinoma Larger than 10 cm.

BACKGROUND: The purpose of the present study was to analyze long-term survival and disease-free survival after liver resection for giant hepatocellular carcinoma (HCC) ≥ 10 cm compared to HCC < 10 cm in diameter. The surgical approach in the treatment of giant HCC may achieve long-term survival and disease-free survival comparable to treatment of smaller lesions. METHODS: This retrospective analysis was a monocentric study conducted in a tertiary university center. It included 101 patients from 114 consecutive liver resections for HCC, separated into two groups: those with tumors less than 10 cm in diameter (small HCC; n = 79) and those with tumors larger than 10 cm (giant HCC; n = 22). The main outcome measures were overall five-year survival, five-year disease-free survival, recurrence rate, perioperative mortality at 30 days, surgical complication rate, and re-intervention rate. RESULTS: The two groups were homogeneously distributed, apart from cirrhosis, which was found more frequently in the group with small HCC (77 vs. 41 %; p = 0.0013). Both median survival (24 vs. 27 months; p = 0.0085) and overall 5-year survival (21 vs. 45; p = 0.04) were significantly poorer in the small HCC group compared to the giant HCC group. There were no differences en terms of recurrence rate, pattern, and timing. CONCLUSIONS: Liver resection for HCC larger than 10 cm is a valuable option in selected patients, one that provides overall survival and disease-free survival comparable to smaller lesions. Functional reserves of the liver, more than the size of the lesion, may be important in patient selection for surgical resection

A case of Muir-Torre syndrome associated with mucinous hepatic cholangiocarcinoma and a novel germline mutation of the MSH2 gene.

Muir-Torre syndrome (MTS) is a rare cancer-predisposing syndrome that is autosomal dominantly inherited and characterized by the development of sebaceous skin lesions (adenomas, epitheliomas, basaliomas and carcinomas). These lesions are typically associated with tumors that belong to the spectrum of hereditary nonpolyposis colorectal cancer (HNPCC) (i.e., tumors of the colorectum, endometrium, stomach or ovary). Biliary malignancy in association with MTS has only rarely been reported. We report a case of Muir-Torre syndrome associated with intrahepatic cholangiocarcinoma, a location not previously described, and associated with a novel missense mutation of the MSH2 gene (c.2026T > C), predicted to disrupt the function of the gene

Primary clear cell sarcoma of the ileum: an uncommon and misleading site

A clear cell sarcoma, arising primarily in the ileum of a 35-year-old man, is reported. Histologically, the neoplasm infiltrated the full thickness of the intestinal wall. It consisted of strands and sheets of round to spindle-shaped cells with clear to eosinophilic cytoplasm, vesicular nuclei and prominent nucleoli. Vascular invasion was present at diagnosis. Tumour cells expressed S-100 protein, melan-A and tyrosinase. They were negative for HMB45, CD117, cytokeratins, epithelial membrane antigen, smooth muscle actin, desmin, CD31, CD34, chromogranin and synaptophysin. Reverse transcription-polymerase chain reaction analysis performed on paraffin-embedded tissue showed EWS-ATF1 fusion transcripts representative of the t(12;22) (q13;q12) clear cell sarcoma reciprocal translocation. The patient, who developed liver metastases 2 months after diagnosis, died of disease at 15 months. This case demonstrates that the gastrointestinal tract is a potential site for primary clear cell sarcoma of soft tissues, and, furthermore, that cytogenetics and/or molecular techniques play a central role in the diagnosi

Preoperative rectal cancer staging with phased-array MR

<p>Abstract</p> <p>Background</p> <p>We retrospectively reviewed magnetic resonance (MR) images of 96 patients with diagnosis of rectal cancer to evaluate tumour stage (T stage), involvement of mesorectal fascia (MRF), and nodal metastasis (N stage).</p> <p>Our gold standard was histopathology.</p> <p>Methods</p> <p>All studies were performed with 1.5-T MR system (Symphony; Siemens Medical System, Erlangen, Germany) by using a phased-array coil. Our population was subdivided into two groups: the first one, formed by patients at T1-T2-T3, N0, M0 stage, whose underwent MR before surgery; the second group included patients at Tx N1 M0 and T3-T4 Nx M0 stage, whose underwent preoperative MR before neoadjuvant chemoradiation therapy and again 4-6 wks after the end of the treatment for the re-staging of disease.</p> <p>Our gold standard was histopathology.</p> <p>Results</p> <p>MR showed 81% overall agreement with histological findings for T and N stage prediction; for T stage, this rate increased up to 95% for pts of group I (48/96), while for group II (48/96) it decreased to 75%.</p> <p>Preoperative MR prediction of histologically involved MRF resulted very accurate (sensitivity 100%; specificity 100%) also after chemoradiation (sensitivity 100%; specificity 67%).</p> <p>Conclusions</p> <p>Phased-array MRI was able to clearly estimate the entire mesorectal fat and surrounding pelvic structures resulting the ideal technique for local preoperative rectal cancer staging.</p

Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preoperative pelvic radiotherapy in patients with locally advanced rectal cancer

This multicentre phase II study evaluated the efficacy and safety of preoperative capecitabine plus oxaliplatin and radiotherapy (RT) in patients with locally advanced rectal cancer (T3/T4 rectal adenocarcinoma with or without nodal involvement). Treatment consisted of one cycle of XELOX (capecitabine 1000 mg m−2 bid on days 1–14 and oxaliplatin 130 mg m−2 on day 1), followed by RT (1.8 Gy fractions 5 days per week for 5 weeks) plus CAPOX (capecitabine 825 mg m−2 bid on days 22–35 and 43–56, and oxaliplatin 50 mg m−2 on days 22, 29, 43 and 50). Surgery was recommended 5 weeks after completion of chemoradiotherapy. The primary end point was pathological complete tumour response (pCR). Sixty patients were enrolled. In the intent-to-treat population, the pCR rate was 23% (95% CI: 13–36%). 58 patients underwent surgery; R0 resection was achieved in 57 (98%) patients, including all 5 patients with T4 tumours. Sphincter preservation was achieved in 49 (84%) patients. Tumour and/or nodal downstaging was observed in 39 (65%) patients. The most common grade 3/4 adverse events were diarrhoea (20%) and lymphocytopaenia (43%). Preoperative capecitabine, oxaliplatin and RT achieved encouraging rates of pCR, R0 resection, sphincter preservation and tumour downstaging in patients with locally advanced rectal cancer

High Expression of Testes-Specific Protease 50 Is Associated with Poor Prognosis in Colorectal Carcinoma

Testes-specific protease 50 (TSP50) is normally expressed in testes and abnormally expressed in breast cancer, but whether TSP50 is expressed in colorectal carcinoma (CRC) and its clinical significance is unclear. We aimed to detect TSP50 expression in CRC, correlate it with clinicopathological factors, and assess its potential diagnostic and prognostic value. = 0.009).Our data demonstrate that TSP50 is a potential effective indicator of poor survival for CRC patients, especially for those with early-stage tumors