Deep ulcers are associated with increased C-reactive protein in active ulcerative colitis.

BACKGROUND: Increased C-reactive protein (CRP) is used to diagnose and predict response to treatment in acute severe ulcerative colitis (UC). AIMS: To investigate the connection between CRP elevation and deep ulcers in UC. METHODS: Patients with active UC were enrolled in a multicenter prospective cohort and a retrospective cohort of consecutive patients undergoing colectomy from 2012 to 2019. RESULTS: Forty-one (9 (22%) with deep ulcers) patients were included in the prospective cohort: 4/5 (80%) patients with CRP > 100 mg/L, 2/10 (20%) patients with CRP between 30 and 100 mg/L and 3/26 (12%) patients with CRP < 30 mg/L had deep ulcers (p = 0.006). In the retrospective cohort [46 patients (31 (67%) with deep ulcers)], 14/14 (100%) patients with CRP > 100 mg/L, 11/17 (65%) patients with CRP between 30 and 100 mg/l and 6/15 (40%) patients with CRP < 30 mg/L had deep ulcers (p = 0.001). Positive predictive value of CRP > 100 mg/l for presence of deep ulcers was 80% and 100% in both cohorts, respectively. CONCLUSIONS: CRP elevation is a robust surrogate marker for presence of deep ulcers in UC. Elevated CRP or presence of deep ulcers could influence the choice of medical therapy in acute severe UC.

Intersphincteric resection for low rectal cancer: the risk is functional rather than oncological. A 25-year experience from Bordeaux.

AIM: There are few data evaluating the long-term outcomes of intersphincteric resection (ISR), especially the impact of inclusion of more juxtapositioned and intra-anal tumours on oncological and functional outcomes. We compared the oncological and functional results of patients treated by total mesorectal excision and ISR for low rectal cancer over a 25-year period. METHOD: This is a retrospective study from a single institution evaluating results of ISR over three periods: 1990-1998, 1999-2006 and 2007-2014. Patients treated by partial or total ISR, with or without neoadjuvant chemoradiotherapy, for low rectal cancer (≤ 6 cm from the anal verge) were included. We compared postoperative morbidity, quality of surgery and oncological and functional outcomes in the time periods studied. RESULTS: Of 813 patients operated on for low rectal cancer, 303 had ISR. Tumour stage did not differ; however, the distance of the tumour from the anorectal junction decreased from 1 to 0 cm (P < 0.001) and the distal resection margin shortened from 25 to 10 mm (P < 0.001) from 1990 to 2014. The postoperative morbidity and quality of surgery did not change significantly over time. The 5-year local recurrence (4.3% vs 5.9% vs 3.5%; P = 0.741) and disease-free survival (72% vs 71% vs 75%; P = 0.918) did not differ between the three time periods. Functional results improved during the last period; however, overall 42% of patients experienced major bowel dysfunction. CONCLUSION: Pushing the envelope of sphincter-saving resection in ultra-low rectal cancer reaching or invading the anal sphincter did not compromise oncological and functional outcomes. The main limitation of the ISR procedure appears to be functional rather than oncological, suggesting that bowel rehabilitation programmes should be developed.

Perioperative FOLFOX 4 Versus FOLFOX 4 Plus Cetuximab Versus Immediate Surgery for High-Risk Stage II and III Colon Cancers: A Phase II Multicenter Randomized Controlled Trial (PRODIGE 22).

BACKGROUND: Perioperative chemotherapy has proven valuable in several tumors, but not in colon cancer (CC). OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of perioperative chemotherapy in patients with locally advanced nonmetastatic CC. METHODS: This is a French multicenter randomized phase II trial in patients with resectable high-risk T3, T4, and/or N2 CC on baseline computed tomography (CT) scan. Patients were randomized to receive either 6 months of adjuvant FOLFOX after colectomy (control) or perioperative FOLFOX for 4 cycles before surgery and 8 cycles after (FOLFOX peri-op). In RAS wild-type patients, a third arm testing perioperative FOLFOX-cetuximab was added. Tumor Regression Grade (TRG1) of Ryan et al was the primary endpoint. Secondary endpoints were toxicity, perioperative morbidity, and quality of surgery. RESULTS: A total of 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped (lack of efficacy). The remaining 104 patients (control, n = 52; FOLFOX preop n = 52) represented our intention-to-treat population. In the FOLFOX perioperative group, 96% received the scheduled 4 cycles before surgery. R0 resection and complete mesocolic excision rate were 94% and 93%, respectively. Overall mortality and morbidity rates were similar in both groups. Perioperative FOLFOX chemotherapy did not improve major pathological response rate (TRG1 = 8%) but was associated with a significant pathological regression (TRG1-2 = 44% vs 8%, P < 0.001) and a trend to tumor downstaging as compared to the control group. CT scan criteria were associated with a 33% rate of overstaging in control group. CONCLUSIONS: Perioperative FOLFOX for locally advanced resectable CC is feasible with an acceptable tolerability but is not associated with an increased major pathological response rate as expected. However, perioperative FOLFOX induces pathological regression and downstaging. Better preoperative staging tools are needed to decrease the risk of overtreating patients.

[Organ preserving strategies for rectal cancer treatment]. / Stratégies de préservation d'organe dans le traitement des cancers du rectum.

For rectal cancers, the current standard of care consists of chemoradiation followed by radical surgery with total mesorectal excision. Oncologic results are good, especially regarding local recurrence rates, but at the cost of high morbidity rates and poor anorectal, urinary and sexual function results. Since chemoradiation yields 15 to 25% pathological complete response, the role of radical surgery is questioned for patients presenting with good response after chemoradiation and two organ preservation strategies have been offered: watch and wait strategy and local excision strategy. The aim of this review is to give the results of organ preservation after chemoradiotherapy series and to highlight different questions regarding initial patient's selection, complete clinical response definition, risk of mesorectal nodal involvement, follow-up modalities as well as oncologic and functional results.

Diagnosis of liver fibrosis by transient elastography (FibroScan) and non-invasive methods in Crohn's disease patients treated with methotrexate.

BACKGROUND: Methotrexate is an effective treatment in Crohn's disease, which may induce liver fibrosis with high cumulative doses. Transient elastography (FibroScan, Echosens, Paris, France) is a new non-invasive rapid, allowing assessment of liver fibrosis by measurement of liver stiffness. AIM: A prospective study to evaluate liver fibrosis with FibroScan and non-invasive biochemical methods in Crohn's disease patients treated with methotrexate. METHODS: Consecutive Crohn's disease patients had evaluation of liver fibrosis with non-invasive methods. Two subgroups of patients were compared: cumulative dose of methotrexate of more than 1500 mg (group 1) and naive for methotrexate (group 2). Liver biopsy was performed in patients with persistent liver enzyme abnormalities or FibroScan value >8.7 kPa. RESULTS: Fifty-four consecutive Crohn's disease patients were fully investigated (45 females, mean age 41 +/- 14 years). Median FibroScan values were similar in group 1 (n = 21) and in group 2 (n = 33), 5.5 and 4.5 kPa, respectively. FibroScan values were not correlated with the cumulative dose of methotrexate. CONCLUSION: In Crohn's disease patients treated with a high dose of methotrexate, significant liver fibrosis is rare and not accurately detected with liver enzymes abnormalities. FibroScan could be recommended and liver biopsy could be performed only with patients with high values and/or with chronic liver enzymes abnormalities.

The oncological safety of laparoscopic total mesorectal excision with sphincter preservation for rectal carcinoma.

BACKGROUND: Although experience of laparoscopic treatment of rectal carcinoma has been reported, there is no evidence of its oncological safety because most procedures included partial mesorectal excision or abdominoperineal excision and quality of surgery is lacking. The aim of this study was to assess the oncological results of laparoscopic total mesorectal excision with sphincter preservation for rectal carcinoma. METHODS: From 2000 to 2003, 144 patients underwent laparoscopic total mesorectal excision with low colorectal or coloanal anastomosis for mid and low rectal adenocarcinoma. There were 88 men and 56 women, with a median age of 65 years. The tumor was located at 5.5 cm (range 1-12) from the anal verge and was classified uT1T2 in 25 cases and uT3 in 119 cases. One hundred twenty patients received preoperative radiotherapy. RESULTS: Postoperative mortality and morbidity were 1% and 34% respectively. Conversion was 14% (n = 20). Macroscopic assessment of the specimen (n = 92) showed an intact mesorectum in 88% of the cases. The distal margin and the circumferential margin were safe in 98% and 94% of the cases, respectively. A complete microscopic excision, i.e., R0 resection, was achieved in 134 cases (93%). Pathological data were similar to those of an open match group. With a median follow-up of 18 months, there was no port-site recurrence and two patients had local recurrence (1.4%). The 3-year overall and disease- free survival rates were 89% and 77%, respectively. CONCLUSIONS: A high quality of surgical excision can be achieved by the laparoscopic dissection, suggesting that this approach in treatment of rectal carcinoma is oncologically safe.

[Pudendal hernia of the labia]. / Hernie de la grande lèvre.

A case of hernia is reported with a brief review of perineal hernia.

Technical and oncological feasibility of laparoscopic total mesorectal excision with pouch coloanal anastomosis for rectal cancer.

AIM: The aim of this study was to evaluate the technical and oncological feasibility of laparoscopic total mesorectal excision (TME) with coloanal anastomosis for mid and low rectal cancer. METHODS: During a 2-year period, 50 patients underwent laparoscopic TME with coloanal anastomosis for rectal carcinoma located at a median of 4.5 (range 2-11) cm from the anal verge. Pre-operative radiotherapy was used in 46 patients. Intersphincteric dissection was combined with the laparoscopic procedure to achieve sphincter preservation. RESULTS: Conversion to a laparotomy was necessary in six patients. Postoperative mortality and morbidity were 2% and 28%, respectively. Morbidity was lower in patients operated on during the second part of the study, who had extraction of the rectal specimen through a small laparotomy incision, than in those operated on during the first part of the study when removal of the specimen was by transanal extraction. Oncological quality of excision was safe in 44 patients with intact or almost intact rectal fascia in 88% and R0 resection in 90%. At a median follow-up of 18 months, there was no local or port-site recurrence. CONCLUSION: This study confirms our preliminary results of oncological feasibility of laparoscopic TME with sphincter preservation for mid and low rectal cancer, and showed that morbidity can be decreased by using a standardized surgical procedure.

Laparoscopic intersphincteric resection with coloplasty and coloanal anastomosis for mid and low rectal cancer.

BACKGROUND: The feasibility of laparoscopic rectal resection in patients with mid or low rectal cancer was studied prospectively with regard to quality of mesorectal excision, autonomic pelvic nerve preservation and anal sphincter preservation. METHODS: Laparoscopic rectal excision was performed in 32 patients (21 men) with rectal carcinoma located 5 cm from the anal verge. Most patients had T3 disease and received preoperative radiotherapy. The surgical procedure was performed 6 weeks after radiotherapy and included total mesorectal excision, intersphincteric resection, transanal coloanal anastomosis with coloplasty and loop ileostomy. RESULTS: Three patients needed conversion to a laparotomy. Postoperative morbidity occurred in ten patients, related mainly to coloplasty. Macroscopic evaluation showed an intact mesorectal excision in 29 of 32 excised specimens; microscopically, 30 of the 32 resections were R0. Sphincter preservation was achieved in 31 patients. The hypogastric nerves and pelvic plexuses were identified and preserved in 24 of the 32 patients. Sexual function was preserved in ten of 18 evaluable men. CONCLUSION: A laparoscopic approach can be considered in most patients with mid or low rectal cancer.

Intrahepatic HCV RNA loads in 37 HIV-HCV co-infected patients with controlled HIV infection.

Serum and intrahepatic hepatitis C virus (HCV) RNA were measured in 37 HIV-HCV co-infected patients with controlled human immunodeficiency virus (HIV) infection and correlated with clinical, biological, and histological parameters. Thirty-seven interferon-naive patients underwent liver biopsy. HCV-induced activity (A) and fibrosis (F) were evaluated with METAVIR score. The 37 patients included had HIV plasma loads < 10,000 copies/ml, CD4(+) count > 250/microl. All the patients but two were receiving antiretroviral treatment. Liver tissue and sera were used for measurement of HCV RNA by the Cobas Amplicor HCV Monitor. All patients had serum and liver HCV RNA, and both levels were correlated (r = 0.47; P = 0.003). Intrahepatic HCV load did not depend on age, sex, duration of HCV infection, CD4(+), HCV genotype, or fibrosis. AST levels correlated with intrahepatic HCV load (r = 0.52; P = 0.001). Patients with METAVIR A1/A2 had significantly lower levels of liver HCV-RNA than were found in patients with METAVIR A3 (P = 0.026). Highly active antiretroviral therapy (HAART) including protease inhibitors(PI)-treated patients had significantly lower intrahepatic HCV load (P = 0.04). A weak but significant correlation between serum and liver HCV RNA was found. The amount of hepatic HCV RNA was correlated with AST levels, histological activity, but not with HCV genotype or fibrosis. The immune improvement associated with PI regimens could help reduce HCV load, supporting a protective effect of PI-induced immune restoration.

Immunohistochemical detection of hcv in cirrhosis, dysplastic nodules, and hepatocellular carcinomas with parallel-tissue quantitative RT-PCR.

Hepatitis C virus is a major risk factor for hepatocarcinogenesis in humans. In situ detection of the virus in early sequential lesions of hepatocarcinogenesis could provide information about the role of the virus in the transformation and promotion process. Parallel in situ detection of HCV proteins and RNA in human tissues were performed in 55 posthepatitis C cirrhosis, 17 dysplastic nodules (DN), and 25 hepatocellular carcinomas (HCC), using immunohistochemistry and tissue quantitative RT-PCR. A consistent cytoplasmic hepatocellular staining was obtained in 73% of cirrhosis cases (with or without HCC) and in 55% DN cases. A few tumoral hepatocytes were unambiguously stained in 28% HCC. The percentage of positive cells and the intensity of immunostaining significantly decreased from cirrhosis to HCC through DN, whereas there was no difference in the prevalence of positivity or the number of viral copies between cirrhosis and HCC using tissue-quantitative RT-PCR. Finally, RT-PCR levels were found parallel with the immunostaining in cirrhosis but not in HCC. These results suggest that HCV protein synthesis may persist but be down-regulated during sequential hepatocarcinogenesis. A putative role of HCV proteins on cell proliferation and differentiation during the early steps of carcinogenesis cannot therefore be excluded.

Cytokeratin 7 and 20 expression in cholangiocarcinomas varies along the biliary tract but still differs from that in colorectal carcinoma metastasis.

In the liver, the immunostaining of cytokeratins (CK) 7 and 20 has been used to distinguish usual peripheral cholangiocarcinomas (CC) and colorectal carcinoma metastasis (CRM). However, other subtypes of CC are not infrequent and may be particularly difficult to distinguish from CRM by histology and even immunohistochemistry. Therefore, 48 CC from different locations, either peripheral (n = 19), or nonperipheral, that is, from the large intrahepatic bile ducts, the hilum, and the extrahepatic bile ducts (n = 29), and with different cytoarchitectural patterns were tested for CK7 and CK20 and compared with 31 CRM. CC were positive for CK7 and CK20 in 96% and 70%, respectively, whatever the architecture and differentiation of the tumor. The labeling index (LI) of CK7 in CC was always high, whereas it was low or moderate for CK20. CK20-positive phenotype was significantly more frequent in nonperipheral than in peripheral CC (82% vs 47%; p = 0.007). CRM were all positive for CK20 with a high LI, and mostly negative (81%) for CK7. In conclusion, (1) the CK immunoprofile of CC varies according to the location of the tumor in the biliary tract, peripheral CC being more often CK7+/CK20-, and nonperipheral ones CK7+/CK20+; and (2) a decision tree based on CK20 LI and CK7 positivity allows the distinction of CRM and CC, even for the nonperipheral type.

Recurrence and accelerated progression of hepatitis C following liver transplantation.

The patient described had recurrent hepatitis C following OLT. This hepatitis appeared early postOLT and progressed to fibrosing cholestatic hepatitis, a severe form of HCV recurrence. Factors such as genotype 1, high viral load and severe damage on the first postOLT biopsy may indicate a more severe outcome. We have hypothesized that, in parallel to what is known for hepatitis B, this rare form of recurrence was linked to a high expression of virus C proteins in the liver graft. Severe form of hepatitis C recurrence should be treated early with the best currently available treatment which is a combination of IFN and ribavirin. Large series of patients with comparable virological, histological and immunological inclusions criteria are necessary to evaluate the efficacy of this treatment.

[Three deceptive cases of intrahepatic metastases of colorectal origin with endobiliary growth, simulating cholangiocarcinoma. Importance of immunostaining of cytokeratin 7 and 20]. / Trois cas trompeurs de métastases intrahépatiques d'origine colorectale à développement endobiliaire, simulant un cholangiocarcinome. Intérêt de l'immunomarquage des cytokératines 7 et 20.

Malignant tumors of the liver with intrabiliary growth are rare, except for some cholangiocarcinomas. Metastases with intrabiliary growth, whatever their origin, are rare. Moreover, colorectal metastasis can be particularly difficult to distinguish morphologically from some cholangiocarcinomas. We report 3 cases of late colorectal metastasis with intrabiliary growth, presenting as cholangiocarcinomas of the large ducts. Immunostaining with cytokeratins 7 and 20 attested the diagnostic and pointed out the spreading pattern of colorectal metastasis within biliary ducts. This study illustrates the capacity, probably underestimated, for colorectal metastasis to develop in the lumen of bile ducts and emphasizes the relevance of cytokeratin 7 and 20 immunostainings in such cases.