Background/Aims Hepatic cholangiocarcinomas are tumors with poor prognosis and with increasing incidence worldwide. The aim of the study was to compare morphological features and protein profiles of ...hilar and peripheral cholangiocarcinomas. Methods Clinicopathological data were collected from 111 cholangiocarcinomas (59 peripheral and 52 hilar). Protein expression, assessed on tissue samples using tissue microarray and protein array technologies, was compared between both types of tumors and with extrahepatic cholangiocarcinoma and hepatocholangiocarcinoma. Results Hilar cholangiocarcinomas were smaller in size (mean: 2.7 vs. 8 cm, p < 0.001), were more often well differentiated adenocarcinomas (65% vs. 36% well differentiated, p < 0.01) and carried out stronger perineural invasion (83% vs. 42%, p < 0.001) than peripheral cholangiocarcinomas. Regarding protein expression, hilar cholangiocarcinomas more often expressed MUC5AC (62% vs. 22%, p < 0.0001), Akt2 (54% vs. 27%, p < 0.001), CK8 (98% vs. 81%, p < 0.005) and annexin II (92% vs. 66%, p < 0.001). Interestingly, VEGF A expression was more frequently encountered in peripheral cholangiocarcinoma (69% vs. 25%, p < 0.0001) and correlated with increased vascular density. Using protein array antibody, we identified filamin A as significantly overexpressed (>2-fold) in peripheral cholangiocarcinomas. Conclusions Our results show that hilar and peripheral cholangiocarcinomas display specific protein profiles, especially regarding VEGF expression. This suggests a potential benefit for anti-angiogenic therapies in peripheral hepatic CCs.
Background A pathologic complete response (pCR) can be observed in up to 25% of patients after preoperative chemoradiotherapy for rectal cancer and is associated with an improved long-term prognosis. ...However, few data are available regarding the effect of pCR on postoperative morbidity. This study aimed to assess the impact of the pCR on postoperative outcomes after laparoscopic total mesorectal excision (TME). Methods A prospectively maintained database (2006−2011) was reviewed for all consecutive patients ( n = 143) undergoing laparoscopic TME for mid or low rectal cancer after neoadjuvant chemoradiotherapy. Postoperative data were compared for pCR-group and non-pCR-group. A pCR was defined as the absence of gross and microscopic tumor in the specimen, irrespective of the nodal status (ypT0). Results Thirty-three patients (23%) had a pCR. Median operating time was greatly shorter in the pCR-group (230 minutes, 180−360), compared with the non-pCR-group (240 minutes, 130−420, P = .02). Lymph node involvement was noted for 12% of the patients in the pCR-group and 33% of the patients in the non-pCR-group ( P = .91). Clavien Dindo grade 3 and 4 complications (6% vs 22%, P = .04), infection related morbidity (47% vs 76%, P = .04), and clinical anastomotic leakage rates (9% vs 29%, P = .02) were lesser in the pCR group compared with the non-pCR group. Mean duration of hospital stay was lesser in the pCR-group (9 vs 12 days, P = .01). Conclusion This study showed that Clavien Dindo grade 3 and 4 complications, including anastomosis leakage, and infection related complications rates were lesser in patients with pathologic complete response after RCT and laparoscopic TME for rectal cancer.
Aims
Neoadjuvant radiochemotherapy (RCT) followed by surgical resection is the treatment for locally advanced mid‐rectal or low rectal cancer. The aim of this study was to evaluate postoperative ...histological prognostic factors in a series of surgical specimens after neoadjuvant RCT.
Methods and results
One hundred and thirteen patients were included. Macroscopic and microscopic examinations were performed according to CAP recommendations, with additional criteria such as tumour budding, the presence of calcifications, and response to neoadjuvant therapy assessed according to Modified Rectal Cancer Regression Grade (m‐RCRG). The 3‐year disease‐free survival (DFS) was 67.6%. In univariate analysis, ypTN stage, tumour budding, circumferential margin, invaded margin and vascular and perineural invasion were prognostic factors. In multivariate analysis, the presence of calcifications (P = 0.04) and an involved circumferential margin (P = 0.03) were the only independent factors for worse DFS. mRCRG was not correlated with DFS. Among the 50 m‐RCRG1 tumours, DFS was better in ypT0 patients than in other ypT stages (P = 0.003).
Conclusions
The presence of calcifications in the tumour bed is described for the first time as a prognostic factor in rectal cancer. The prognostic value of budding was demonstrated in this study after neoadjuvant RCT. ypT stage appears to be a more reliable predictor of oncological outcome than histological tumour regression grade, which needs to be standardized for better reproducibility.
Battistella M, Guedj N, Fallet‐Bianco C, Bodemer C, Brousse N & Fraitag S (2011) Histopathology59, 407–420
The histopathological spectrum of cutaneous meningeal heterotopias: clues and pitfalls
Aims: ... To describe the histopathological features of heterotopic cutaneous meningeal tissue.
Methods and results: Nineteen cases were collected between 1993 and 2010. Immunohistochemistry for epithelial membrane antigen (EMA), neuron specific enolase (NSE), S100, glial fibrillary acid protein (GFAP), progesterone receptor (PR), CD31, glucose transporter‐1 (Glut‐1), podoplanin and NKI‐C3 was performed. Lesions were congenital (100%) and presented as aplasia cutis with alopecia (63%) or lumps (37%), on the scalp (18 of 19) and sacral region. Resonance magnetic imaging revealed four underlying anomalies of the neuraxis. Histopathological analysis showed meningeal tissue arranged in four variably associated architectural patterns: fibrous (100%), pseudovascular (100%), cellular (68%) and pseudomyxoid (32%). Other features included collagen bodies (58%), calcifications (26%) and dermal melanocytes (32%). Heterotopic brain tissue or heterotopic ependymal cyst was associated in two cases. Arachnoidal cells expressed EMA and NSE, but not S100 protein, CD31 or GFAP. They expressed podoplanin (93%), especially in pseudovascular areas, NKI‐C3 (79%), and less frequently Glut‐1 (46%) and PR (30%).
Conclusions: Histopathological features of cutaneous meningeal heterotopias are various and sometimes misleading. Fibrous lesions should not be misdiagnosed as aplasia cutis. Podoplanin‐positive pseudovascular spaces represent the main pitfall and should not be diagnosed as lymphangioma. Correct diagnosis is confirmed by EMA and NSE coexpression within the lesion.
Metabolic syndrome (MS) is a newly identified risk factor in chronic liver disease (CLD) and hepatocellular carcinoma (HCC). The aim of this study was to analyze the pathological characteristics of ...HCC and nontumoral liver in patients with MS as the only risk factor for liver disease in comparison with those that developed in the course of other CLDs in order to provide further insight into the physiopathology of HCC associated with MS. HCC patients with features of MS as the only risk factor for liver diseases (MS group, n = 31) were compared to HCC patients with overt causes of CLD (CLD group, n = 81) or without causes of CLD (cryptogenic group, n = 16) who underwent surgical resection during the same period of time. Among the patients of the MS group, there were 30 males and 1 female. In comparison with the patients with HCC of the CLD group, the patients with MS were older (mean age: 67± 7 versus 59 ± 14 years, P < 0.01), and the background liver was significantly more often free of significant fibrosis (F0–F2: 65% in the MS group versus 26% in the CLD group, P < 0.001). In addition, HCCs associated with MS were more often well differentiated (65% versus 28%, P < 0.001). Five HCCs, all from the MS group, developed on a preexisting liver cell adenoma, with three of them showing typical histological features of telangiectatic adenoma. Conclusion: This study shows that HCCs in patients with features of MS as the only risk factor for liver disease have distinct morphological characteristics and mainly occur in the absence of significant fibrosis in the background liver. In addition, some of them arise through malignant transformation of a preexisting liver cell adenoma. (HEPATOLOGY 2009.)
The prognostic value of splenic vessel involvement in distal pancreatic adenocarcinoma remains controversial. The aim of the study was to assess its prognostic relevance in a large multicenter ...cohort.
Patients who underwent pancreatosplenectomy for distal pancreatic adenocarcinoma were identified from 5 pancreatic surgical centers. A pathology review of the surgical specimens was performed to assess splenic vessel involvement, defined as invasion of the vessel’s adventitia or deeper, and confirm the presence of splenic vein tumor thrombosis. Prognostic factors associated with overall and relapse-free survival were evaluated.
149 patients underwent upfront surgery. Splenic vascular involvement was observed in 69 of them (46.3%). A parietal infiltration of the splenic artery or splenic vein was observed in 26 (17.5%) and 49 patients (32.8%), respectively. A pathologic tumor thrombosis of the splenic vein was identified in 22 patients (14.8%) and associated with larger tumors (>20 mm) (P = .023), more perineural (P = .017), and lymphovascular (P = .002) invasion, and more positive lymph node (P = .001). After a median follow-up of 50.8 months (95% confidence interval: 44.3–57.3), the cumulative 5-year overall and relapse-free survival were 46.2% and 33%, respectively. In multivariate analysis, in addition to lymph node metastasis (hazard ratio = 1.8; 95% confidence interval 1.1–3.1; P = .023) and perineural invasion (hazard ratio = 3.5; 95% confidence interval 1.3–9.7; P = .016), presence of splenic vein tumor thrombosis was the only splenic vascular involvement that affected independently the overall survival (HR = 2.3; 95% confidence interval 1.3–4.3; P = .006).
In resectable distal pancreatic adenocarcinoma, a pathologic tumor thrombosis of the splenic vein is an independent prognostic factor of overall survival. To define the perioperative oncological strategy, a preoperative evaluation of splenic vessel involvement and thrombosis is needed.
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Following ileal resection for Crohn's disease (CD), recurrence is very frequent. Although several clinical risk factors of recurrence have been identified, predicting relapse remains challenging. ...Performing an ileocolonoscopy within the first year after surgery is currently recommended to assess endoscopic recurrence and to adjust the treatment. We took advantage of a large prospective multicentric cohort to investigate the role of the ileal mucosa-associated microbiota in postoperative endoscopic recurrence.
Ileal mucosa-associated microbiota was analysed by 16S sequencing at the time of surgery and/or of endoscopic evaluation in 201 patients (288 samples in total) prospectively recruited in France.
Ileal mucosa-associated microbiota exhibits profound changes following surgery in CD. Compared with non-recurrence setting, endoscopic recurrence is associated with strong changes in ileal mucosa-associated microbiota that are highly reminiscent of those observed generally in ileal CD compared with healthy subjects with a reduction in alpha diversity, an increase in several members of the Proteobacteria phylum and a decrease in several members of the Lachnospiraceae and the Ruminococcaceae families within the Firmicutes phylum. At the time of surgery, we identified several bacterial taxa associated with endoscopic recurrence and that can better predict relapse than usual clinical risk factors.
Surgery has an important impact on ileal mucosa-associated microbiota. Postoperative endoscopic recurrence is associated with changes in microbiota composition and alpha diversity. The gut microbiota has the potential to predict postoperative evolution and recurrence.
We used the postoperative recurrence model to better understand the role of adherent and invasive
(AIEC) bacteria in Crohn's disease (CD), taking advantage of a well-characterised postoperative ...cohort.
From a prospective, multicentre cohort of operated patients with CD, AIEC identification was performed within the surgical specimen (M0) (N=181 patients) and the neoterminal ileum (n=119 patients/181) during colonoscopy performed 6 months after surgery (M6). Endoscopic postoperative recurrence was graded using Rutgeerts' index. The mucosa-associated microbiota was analysed by 16S sequencing at M0 and M6. Relative risks or ORs were adjusted on potential confounders.
AIEC prevalence was twofold higher within the neoterminal ileum at M6 (30.3%) than within the surgical specimen (14.9%) (p<0.001). AIEC within the neoterminal ileum at M6 was associated with higher rate of early ileal lesions (i1) (41.6% vs 17.1%; aRR 3.49 (95% CI 1.01 to 12.04), p=0.048) or ileal lesions (i2b+i3) (38.2% vs 17.1%; aRR 3.45 (95% CI 1.06 to 11.30), p=0.040) compared with no lesion (i0). AIEC within the surgical specimen was predictive of higher risk of i2b-endoscopic postoperative recurrence (POR) (aOR 2.54 (95% CI 1.01 to 6.44), p=0.049) and severe endoscopic POR (aOR 3.36 (95% CI 1.25 to 9.06), p=0.017). While only 5.0% (6/119) of the patients were AIEC-positive at both M0 and M6, 43.7% (52/119), patients with history of positive test for AIEC (M0 or M6) had higher risk of ileal endoscopic POR (aOR 2.32 (95% CI 1.01 to 5.39), p=0.048)), i2b-endoscopic postoperative recurrence (aOR 2.41 (95% CI 1.01 to 5.74); p=0.048) and severe endoscopic postoperative (aOR=3.84 (95% CI 1.32 to 11.18), p=0.013). AIEC colonisation was associated with a specific microbiota signature including increased abundance of
.
Based on the postoperative recurrence model, our data support the idea that AIEC are involved in the early steps of ileal CD.
NCT03458195.
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