S. Rohr

The treatment of incisional and abdominal hernia with a prosthesis in potentially infected tissues — A series of 47 cases

SummaryThe aim of this study was to assess the infective risks involved in the placement of a non-absorbable prosthesis in the abdominal wall, in the treatment of abdominal hernias. Two groups of patients were compared over the period 1985 to 1995. Group A (N=47) received non-absorbable (Mersilene) prostheses, placed in a potentially infected area (Altemeier class 2, 3 and 4). Group B (N=47, Altemeier class 1) comprised a similar group of patients to those in group A. The prostheses were usually placed in the retro-muscular prefascial plane. Antibiotics were given either prophylactically or therapeutically, according to the degree of sepsis surrounding the operation. The length of hospital stay was longer in group A (15.6 ± 9 as against 10 ± 6 days. p=0,0006). There were two deaths in group A and none in group B (not significant). The general complication rate was 23.7% in group A as against 8.5% in group B (p=0.016). There was no significant difference between the two groups in regard to surgical complications (group A 23.7%, group B 21.3%). The infection rate in the abdominal wall was 10.6% and 6.4% in groups A and B respectively (not significant). There was only one patient with a prosthetic infection (in group A) requiring revision. We conclude that the use of non-absorbable prostheses placed in the retromuscular prefascial space may be more widely employed, in the course of potentially contaminated intra-abdominal surgery of Altemeier class 2.

Allelotyping analyses of synchronous primary and metastasis CIN colon cancers identified different subtypes

In colorectal cancer, the molecular alterations that lead to metastasis are not clearly established, probably because of their high genetic complexity. To identify combinations of genetic changes involved in tumor progression and metastasis, we focused on chromosome instable (CIN) colon cancers. We compared by allelotyping of 33 microsatellites, the genomic alterations of 38 primary colon tumors with the synchronously resected matched liver metastases (CLM). We observed that (i) the number of patients with alterations at certain loci did not differ significantly between the whole primary tumor and the paired CLM, (ii) a group of patients had fewer alterations in the metastasis when compared with the matched primary tumor. A 2‐way hierarchical unsupervised clustering of the allelotyping data revealed 2 tumor subtypes that have different levels of CIN (CIN‐High, CIN‐Low). Both subtypes have a minimal common set of alterations at chromosomes 8p, 17p and 18q, but does not include alteration at 5q or mutation at K‐Ras. These 2 subtypes were also observed using a collection of 104 independent primary CIN colon tumors. In addition, we found a third subtype, consisting of tumors with a very low number of alterations not associated with specific loci (CIN‐Very Low). We found that colon carcinogenesis may require a minimal set of alterations and that, in contrast to the current hypothesis, the level of CIN does not correlate with tumor progression. Therefore, our results suggest that metastasis potential could be present at very early stages of tumor development.

A role for chromogranin A (4-16), a vasostatin-derived peptide, on human colonic motility. An in vitro study

The hypothesis that CgA-derived peptides may be involved in mechanisms modulating motility was tested. Human colonic smooth muscles were studied using an organ bath technique. Acetic acid (AA) effects were characterized on spontaneous mechanical activities (SMA) and on responses to transmural nerve stimulation (NS). AA induced a significant decrease in tone and abolished SMA; this effect was insensitive to either TTX or L-NAME/apamin. The AA-induced inhibitory effects were significantly reduced in the presence of CgA4-16. This effect was insensitive to TTX or L-NAME/apamin. Furthermore, AA-induced effects were blocked in the presence of BAYK8644 and CgA4-16 together. The inhibitory effect of nifedipine was delayed in the presence of CgA4-16. NS induced a triphasic response. Only the excitatory components were reduced in the presence of AA. This effect was dose-related and remained unchanged in the presence of CgA4-16 alone, but was blocked in the presence of simultaneous administration of CgA4-16 and L-NAME/apamin. AA application induced inhibition of human colon motility in vitro. This effect may be mediated through an action on L-type calcium channels. CgA4-16 may display a protective role, which prevents the inhibition of motility due to AA to occur, by acting on both smooth muscle and afferent terminals.

KRAS and BRAF mutations are prognostic biomarkers in patients undergoing lung metastasectomy of colorectal cancer

Background:We evaluated KRAS (mKRAS (mutant KRAS)) and BRAF (mBRAF (mutant BRAF)) mutations to determine their prognostic potential in assessing patients with colorectal cancer (CRC) for lung metastasectomy.Methods:Data were reviewed from 180 patients with a diagnosis of CRC who underwent a lung metastasectomy between January 1998 and December 2011.Results:Molecular analysis revealed mKRAS in 93 patients (51.7%), mBRAF in 19 patients (10.6%). In univariate analyses, overall survival (OS) was influenced by thoracic nodal status (median OS: 98 months for pN−, 27 months for pN+, P<0.0001), multiple thoracic metastases (75 months vs 101 months, P=0.008) or a history of liver metastases (94 months vs 101 months, P=0.04). mBRAF had a significantly worse OS than mKRAS and wild type (WT) (P<0.0001). The 5-year OS was 0% for mBRAF, 44% for mKRAS and 100% for WT, with corresponding median OS of 15, 55 and 98 months, respectively (P<0.0001). In multivariate analysis, WT BRAF (HR: 0.005 (95% CI: 0.001–0.02), P<0.0001) and WT KRAS (HR: 0.04 (95% CI: 0.02–0.1), P<0.0001) had a significant impact on OS.Conclusions:mKRAS and mBRAF seem to be prognostic factors in patients with CRC who undergo lung metastasectomy. Further studies are necessary.

Analysis of Allelic Imbalance in Patients With Colorectal Cancer According to Stage and Presence of Synchronous Liver Metastases

ObjectiveTo investigate the relationship between number and location of allelic imbalances (AI) and local tumor progression according to Astler-Coller classification. Summary Background DataSpontaneous errors in DNA replication (i.e., allelic imbalance or microsatellite instability) have been suggested to play an important role in carcinomatous transformation as reflecting alterations of gene function. MethodsOne hundred two consecutive patients with colorectal carcinoma undergoing surgical resection were included in this study. Patients were distributed according to the Astler-Coller classification as stages A (n = 7), B1 (n = 15), B2 (n = 24), C (n = 31), and D (n = 25). Fluorescent polymerase chain reaction was performed on frozen tumor, normal colon mucosa, and blood DNA at 35 microsatellite markers. Allelic imbalance frequency was compared with tumor staging. ResultsThe percentage of AI was significantly higher in stage D than in A/B1 and B2. In addition, the percentage of AI was significantly higher in 10 synchronous colorectal liver metastases than in stage A/B1 and B2 tumors. However, the allelotyping revealed a subgroup of A/B1 tumors with a high AI frequency. Statistical analysis showed that the presence of AI at microsatellites D1S305, D2S138, D3S1282, D17S790, and D22S928 presented a significantly positive correlation with stages. ConclusionThe frequency of AI significantly correlates with tumor progression of colorectal cancer. Primary tumors with synchronous colorectal liver metastases showed a higher percentage of AI, suggesting that a frequency of AI greater than 35% with this selection of markers indicates a high risk of local progression and of development of metastases.

In Vivo Topoisomerase I Inhibition Attenuates the Expression of Hypoxia-Inducible Factor 1α Target Genes and Decreases Tumor Angiogenesis

Topoisomerase I is a privileged target for widely used anticancer agents such as irinotecan. Although these drugs are classically considered to be DNA-damaging agents, increasing evidence suggests that they might also influence the tumor environment. This study evaluates in vivo cellular and molecular modifications induced by irinotecan, a topoisomerase I-directed agent, in patient-derived colon tumors subcutaneously implanted in athymic nude mice. Irinotecan was given intraperitoneally at 40 mg/kg five times every 5 d, and expression profiles were evaluated at d 25 in tumors from treated and untreated animals. Unexpectedly, the in vivo antitumor activity of irinotecan was closely linked to a downregulation of hypoxia-inducible factor-1α (HIF1A) target genes along with an inhibition of HIF1A protein accumulation. The consequence was a decrease in tumor angiogenesis leading to tumor size stabilization. These results highlight the molecular basis for the antitumor activity of a widely used anticancer agent, and the method used opens the way for mechanistic studies of the in vivo activity of other anticancer therapies.

δ-Opioid receptor agonists inhibit neuromascular transmission in human colon

The present study was undertaken to investigate the possible role of delta-opioid receptors in the neuroregulation of human colonic motility by using a superfusion model. Spontaneous mechanical activity and responses to electrical transmural nerve stimulation of both longitudinal and circular muscle strips from the human sigmoid colon were studied. Exogenously added delta-opioid receptor agonists did not modify spontaneous contractile activities of either type of strip. Nerve stimulation induced a triphasic response composed of an initial contraction followed by a relaxation and an off-contraction. This response was mediated by cholinergic excitatory nerves and non-adrenergic, non-cholinergic excitatory and inhibitory nerves. [Met5]Enkephalin and the synthetic delta-opioid receptor agonist [D-Pen2,D-Pen5]enkephalin (DPDPE) significantly decreased the amplitude of the initial contraction and of the off-contraction. The effects of both delta-opioid receptor agonists were reduced in the presence of either the delta-opioid receptor antagonist, ICI 174864, or another delta-opioid receptor antagonist, naltrindole. ICI 174864 prevented neither the effects of a natural kappa-opioid receptor agonist, dynorphin-(1-13) nor those of the mu-opioid receptor agonist, PL017. Therefore, these data suggest that delta-opioid receptors might be involved in the neuroregulation of smooth muscle of human colon and may mediate inhibition of cholinergic and non-cholinergic excitatory transmission within the myenteric plexus.

Isolated microcytic anemia disclosing a unicentric Castleman disease: The interleukin-6/hepcidin pathway?

Castleman disease (CD) is a rare lymphoproliferative disorder of uncertain origin. Anemia is commonly reported and is related to an inflammatory mechanism. Occasionally an autoimmune hemolytic anemia appears as the leading clinical feature. Three histological types have been differentiated, a hyaline-vascular type (HV), a plasma cell type (PC), and a mixed type. Clinically CD is separated into unicentric (localized) or multicentric (generalized) forms. The former is most frequently of HV type (80-90%), affecting a single lymph node. The PC type is encountered in 10-20% of the unicentric CD and in almost all of the multicentric cases. Numerous systemic manifestations have been described usually associated with PC type. An isolated and markedly microcytic anemia revealing a unicentric CD has never been reported in English literature. Recent data concerning iron metabolism, interleukin-6 and hepcidin provide interesting clues to understand the particular microcytic anemia of CD.

Les résultats à long terme de la fundoplicature par laparoscopie dans le traitement du reflux gastro-œsophagien

Introduction. – The aim of this study was to evaluate the long term efficacy of laparoscopic treatement of gastroesophageal reflux disease (GERD). Patient and methods. – Between 1st January 1992 and 31 December 1996, 161 patients underwent complete or partial laparoscopic fundoplication for a symptomatic GERD. One hundred and twenty three patients were submitted to Nissen-Rossetti fundoplication, 26 patients to Nissen fundoplication and 12 patients to a partial posterior Toupet fundoplication.141 patients were evaluated at 3 months, 2-years and 5-years. Since undergoing the operation, four patients died of unrelated causes, 16 patients could not be contacted for follow up (10%). pH monitoring and oesophageal manometry were performed preoperatively and at 3 months postoperatively. The patients were evaluated 2 and 5-years after surgery by specific phone questionnaire. Results. – There was no mortality, the morbidity rate was 1.2% and the conversion rate was 5%. Incidence of dysphagia 3 months after surgery was 23.4%, and 5-years after 12%; 12% of patients had recurrent symptoms at 5 years. Conclusion. – The overall satisfaction rate at 5 years was 91.4%. Nissen-Rossetti fundoplication seems to have better results at 5-years regarding postoperative dysphagia and symptoms recurrence.

Management of Common Bile Duct Stones by Laparoscopic Cholecystectomy and Endoscopic Sphincterotomy: Pre-, Per- or Postoperative Sphincterotomy?

Background/Aims: The aim of this study was to evaluate the treatment of common bile duct stones (CBDS) by endoscopic sphincterotomy (ES) and laparoscopic cholecystectomy (LC), ES being performed either pre-, per- or postoperatively. Methods: Between January 1990 and June 1997, 386 patients with a median age of 60 (range 18–92) years were treated for suspected or confirmed CBDS. The CBDS were uncomplicated in 264 cases (70%) but associated with a complication in 122 cases (30%), namely, cholangitis (69 cases) or acute pancreatitis (53 cases). ES combined with LC was carried out in 233 cases (60%): ES was preoperative (sequential treatment in two stages) in 197 cases (51%); peroperative in 30 cases (7%), or postoperative in 6 cases (2%). Laparoscopic extraction was performed in 58 cases (15%) and conventional surgery in 82 cases (21%). Results: With respect to sequential treatment, endoscopic retrograde cholangiography showed the presence of CBDS in 117 cases (60%) and preoperative ES allowed the release of the CBDS in 82% of these cases. The complication rate of sequential treatment was 8% (15 cases) after ES and 7% (13 cases) after LC, with 1 death (0.5%). A peroperative ES performed after LC enabled evacuation of the CBDS in 28 cases (93%) without any complications or mortality. Postoperative ES was successful in 100% of cases with residual lithiasis in 16% (1 case) and a complication rate of 16% (1 case). Conclusion: Along with conventional surgery and laparoscopic extraction, ES combined with LC represents an effective alternative in the management of CBDS. Since it can be performed peroperatively, it allows a one-stage, minimally invasive treatment of most uncomplicated CBDS.