Risk factors for severe morbidity and definitive stoma after elective surgery for sigmoid diverticulitis: a multicenter national cohort study.

BACKGROUND: In the decision to perform elective surgery, it is of great interest to have data about the outcomes of surgery to individualize patients who could safely undergo sigmoid resection. The aim of this study was to provide information on the outcomes of elective sigmoid resection for sigmoid diverticular disease (SDD) at a national level. METHODS: All consecutive patients who had elective surgery for SDD (2010-2021) were included in this retrospective, multicenter, cohort study. Patients were identified from institutional review board-approved databases in French member centers of the French Surgical Association. The endpoints of the study were the early and the long-term postoperative outcomes and an evaluation of the risk factors for 90-day severe postoperative morbidity and a definitive stoma after an elective sigmoidectomy for SDD. RESULTS: In total, 4617 patients were included. The median [IQR] age was 61 [18.0;100] years, the mean ± SD body mass index (BMI) was 26.8 ± 4 kg/m2, and 2310 (50%) were men. The indications for surgery were complicated diverticulitis in 50% and smoldering diverticulitis in 47.4%. The procedures were performed laparoscopically for 88% and with an anastomosis for 83.8%. The severe complication rate on postoperative day 90 was 11.7%, with a risk of anastomotic leakage of 4.7%. The independent risk factors in multivariate analysis were an American Society of Anesthesiologists (ASA) score ≥ 3, an open approach, and perioperative blood transfusion. Age, perioperative blood transfusion, and Hartmann's procedure were the three independent risk factors for a permanent stoma. CONCLUSIONS: This series provides a real-life picture of elective sigmoidectomy for SDD at a national level. TRIAL REGISTRATION: Comité National Information et Liberté (CNIL) (n°920361).

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.

Colon sparing resection versus extended colectomy for left-sided obstructing colon cancer with caecal ischaemia or perforation: a nationwide study from the French Surgical Association.

AIM: It is not known whether patients with obstructive left colon cancer (OLCC) with caecal ischaemia or diastatic perforation (defined as a blowout of the caecal wall related to colonic overdistension) should undergo a (sub)total colectomy (STC) or an ileo-caecal resection with double-barrelled ileo-colostomy. We aimed to compare the results of these two strategies. METHOD: From 2000 to 2015, 1220 patients with OLCC underwent surgery by clinicians who were members of the French Surgical Association. Of these cases, 201 (16%) were found to have caecal ischaemia or diastatic perforation intra-operatively: 174 patients (87%) underwent a STC (extended colectomy group) and 27 (13%) an ileo-caecal resection with double-end stoma (colon-sparing group). Outcomes were compared retrospectively. RESULTS: In the extended colectomy group, 95 patients (55%) had primary anastomosis and 79 (45%) had a STC with an end ileostomy. In the colon-sparing group, 10 patients (37%) had simultaneous resection of their primary tumour with segmental colectomy and an anastomosis which was protected by a double-barrelled ileo-colostomy. The demographic data for the two groups were comparable. Median operative time was longer in the STC group (P = 0.0044). There was a decrease in postoperative mortality (7% vs 12%, P = 0.75) and overall morbidity (56% vs 67%, P = 0.37) including surgical (30% vs 40%, P = 0.29) and severe complications (17% vs 27%, P = 0.29) in the colon-sparing group, although these differences did not reach statistical significance. Cumulative morbidity included all surgical stages and the rate of permanent stoma was 66% and 37%, respectively, with no significant difference between the two groups. Overall survival and disease-free survival were similar between the two groups. CONCLUSION: The colon-sparing strategy may represent a valid and safe alternative to STC in OLCC patients with caecal ischaemia or diastatic perforation.

Elective surgery for tumours of the splenic flexure: a French inter-group (AFC, SFCD, FRENCH, GRECCAR) survey.

BACKGROUND: In an elective setting, there is no consensus regarding the type of colectomy that is best for patients with tumors of the splenic flexure: segmental left colectomy (or splenic flexure colectomy), left hemicolectomy or subtotal colectomy (or extended right hemicolectomy). In the United Kingdom, extended right hemicolectomy is preferred by surgeons. The aim of the present survey was to report on the practices in France for this particular tumor location. METHODS: Between 15/07/17 and 15/10/17, members of two French surgical societies [the French Association of Surgery (AFC) and the French Society of Digestive Surgery (SFCD)] and two French surgical cooperative groups [the French Federation of Surgical Research (FRENCH) and the French Research Group of Rectal Cancer Surgery (GRECCAR)] were solicited by email to answer an online anonymous questionnaire. RESULTS: A total of 190 out of 420 surgeons participated in this study (response rate 45%). The preferred procedure was splenic flexure colectomy (70%), followed by left hemicolectomy (17%) and subtotal colectomy (13%). The most used surgical approach was laparoscopy (63%), followed by laparotomy (31%) and hand-assisted laparoscopy (6%). Lymph node dissection was extended to the middle colic artery in 29% of splenic flexure colectomies and in 33% of left hemicolectomies. Twenty-nine percent of responders thought that tumors of the splenic flexure had a worse prognosis in comparison with other colonic sites, because of insufficient lymph node dissection (73%) or a more advanced stage (50%) at diagnosis. However, this opinion did not change the type of colectomy performed. CONCLUSIONS: There is a strong consensus in France to operate tumors of the splenic flexure with a splenic flexure colectomy and lymph node dissection limited to the left colic artery.

Influence of Molecular Status on Recurrence Site in Patients Treated for a Stage III Colon Cancer: a Post Hoc Analysis of the PETACC-8 Trial.

BACKGROUND: Recurrence patterns in stage III colon cancer (CC) patients according to molecular markers remain unclear. The objective of the study was to assess recurrence patterns according to microsatellite instability (MSI), RAS and BRAFV600E status in stage III CC patients. METHODS: All stage III CC patients from the PETACC-8 randomized trial tested for MSI, RAS and BRAFV600E status were included. The site and characteristics of recurrence were analyzed according to molecular status. Survival after recurrence (SAR) was analyzed. RESULTS: A total of 1650 patients were included. Recurrence occurred in 434 patients (26.3%). Microsatellite stable (MSS) patients had a significantly higher recurrence rate (27.2% vs. 18.7%, P = 0.02) with a trend to more pulmonary recurrence (28.8% vs. 12.9%, P = 0.06) when compared to MSI patients. MSI patients experienced more regional lymph nodes compared to MSS (12.9% vs. 4%, P = 0.046). In the MSS population, the recurrence rate was significantly higher in RAS (32.2%) or BRAF (32.3%) patients when compared to double wild-type patients (19.9%) (p < 0.001); no preferential site of recurrence was observed according to RAS and BRAFV600E mutations. Finally, decreased SAR was observed in the case of peritoneal recurrence or more than two recurrence sites. CONCLUSIONS: Microsatellite, RAS and BRAFV600E status influences recurrence rates in stage III CC patients. However, only microsatellite status seems to be associated with specific recurrence patterns. More than two recurrence sites and recurrence in the peritoneum were associated with poorer SAR.

Thirty-day mortality after emergency surgery for obstructing colon cancer: survey and dedicated score from the French Surgical Association.

AIM: The aim was to define risk factors for postoperative mortality in patients undergoing emergency surgery for obstructing colon cancer (OCC) and to propose a dedicated score. METHOD: From 2000 to 2015, 2325 patients were treated for OCC in French surgical centres by members of the French National Surgical Association. A multivariate analysis was performed for variables with P value ≤ 0.20 in the univariate analysis for 30-day mortality. Predictive performance was assessed by the area under the receiver operating characteristic curve. RESULTS: A total of 1983 patients were included. Thirty-day postoperative mortality was 7%. Multivariate analysis found five significant independent risk factors: age ≥ 75 (P = 0.013), American Society of Anesthesiologists (ASA) score ≥ III (P = 0.027), pulmonary comorbidity (P = 0.0002), right-sided cancer (P = 0.047) and haemodynamic failure (P < 0.0001). The odds ratio for risk of postoperative death was 3.42 with one factor, 5.80 with two factors, 15.73 with three factors, 29.23 with four factors and 77.25 with five factors. The discriminating capacity in predicting 30-day postoperative mortality was 0.80. CONCLUSION: Thirty-day postoperative mortality after emergency surgery for OCC is correlated with age, ASA score, pulmonary comorbidity, site of tumour and haemodynamic failure, with a specific score ranging from 0 to 5.

Elective subtotal colectomy with ileosigmoid anastomosis for colon cancer preserves bowel function and quality of life.

AIM: We report on our experience of elective subtotal colectomy and ileosigmoid anastomosis for colon cancer with focus on postoperative results, function and quality of life. METHOD: Between 1998 and 2011, 106 consecutive patients with colonic malignancy underwent this procedure electively. Function and quality of life (EORTC QLQ-C30) were evaluated retrospectively with questionnaires sent to all patients free of recurrence. RESULTS: There were 62 men and 44 women (mean age 63 years). Postoperative mortality and morbidity rates were 1.9 and 26.4%, respectively. Persistent ileus was the main early complication (16%). After a mean follow-up of 67 ± 36 months, 50 (78.1) out of 64 patients have been evaluated for function and quality of life. The mean number of bowel movements per 24 h was 3 ± 2 and significantly lower when the length of the remaining sigmoid colon was more than 15 cm (P = 0.049). Compared with a European reference population for EORTC QLQ-C30 results, our patients had significantly more diarrhoea (26 vs 3, P = 0.0002) but less pain (10 vs 25, P < 0.0001) and better global quality of life (77 vs 62, P < 0.0001). CONCLUSION: Elective subtotal colectomy for colon cancer is safe and associated with good function and quality of life. Ileosigmoid anastomosis should be discussed when extended colectomy is required, providing the rectosigmoid junction and its vascular supply can be oncologically preserved. For tumours located in the transverse colon or at the splenic flexure, this procedure may be the best surgical option.

FOxTROT2: innovative trial design to evaluate the role of neoadjuvant chemotherapy for treating locally advanced colon cancer in older adults or those with frailty.

Treating older adults with cancer is increasingly important in modern oncology practice. However, we currently lack the high-quality evidence needed to guide optimal management of this heterogeneous group. Principally, historic under-recruitment of older adults to clinical trials limits our understanding of how existing evidence can be applied to this group. Such uncertainty is particularly prevalent in the management of colon cancer (CC). With CC being most common in older adults, many patients also suffer from frailty, which is recognised as being strongly associated with poor clinical outcomes. Conducting clinical trials in older adults presents several major challenges, many of which impact the clinical relevance of results to a real-world population. When considering this heterogeneous group, it may be difficult to define the target population, recruit participants effectively, choose an appropriate trial design, and ensure participants remain engaged with the trial during follow-up. Furthermore, after overcoming these challenges, clinical trials tend to enrol highly selected patient cohorts that comprise only the fittest older patients, which are not representative of the wider population. FOxTROT1 was the first phase III randomised controlled trial to illustrate the benefit of neoadjuvant chemotherapy (NAC) in the treatment of CC. Patients receiving NAC had greater 2-year disease-free survival compared to those proceeding straight to surgery. Outcomes for older adults in FOxTROT1 were similarly impressive when compared to their younger counterparts. Yet, this group inevitably represents a fitter subgroup of the older patient population. FOxTROT2 has been designed to investigate NAC in a full range of older adults with CC, including those with frailty. In this review, we describe the key challenges to conducting a robust clinical trial in this heterogeneous patient group, highlight our strategies for overcoming these challenges in FOxTROT2, and explain how we hope to provide clarity on the optimal treatment of CC in older adults.

Computed Tomography Colonography Angiography (CTC-A) prior to colectomy for cancer: A new tool for surgeons.

The pre-operative work-up for non-metastatic colon cancer includes colonoscopy and thoraco-abdomino-pelvic computed tomography (CT) with intravenous (IV) contrast. Colonoscopic determination of the anatomical location of the tumor may be erroneous, particularly with a long redundant colon (dolichocolon), and the search for synchronous colon neoplasms is limited when the endoscope cannot traverse the tumor-bearing segment. While computed tomography colonography angiography (CTC-A) makes it possible to assess distant tumor metastasis, it remains limited for the assessment of loco-regional extension. CTC-A requires specific colonic preparation, controlled colonic insufflation with CO2, and an injection of IV contrast. CTC-A provides a 3-D view of the overall morphology of the colon and precisely localizes the site of the colonic tumor. Merging the images of the colon with those of mesenteric and colonic vessels provides a representation of anatomical vascular variations. This information could help the surgeon to better plan the colectomy. The use of two-dimensional images of CTC-A with sections perpendicular to the major axis of the tumor-bearing colonic segment can provide precise information on the degree of parietal extension and be useful in evaluating the value of neo-adjuvant chemotherapy.

Evaluation of serum VEGF levels in untreated erythrocytosis patients.

The aim of this prospective study was to investigate the involvement of angiogenesis in the etiopathogenesis of the different classes of erythrocytosis (polycythemia vera PV, idiopathic erythrocytosis and secondary erythrocytosis). The angiogenic activity was evaluated by the assessment of the serum VEGF levels in 78 untreated erythrocytosis patients and 21 healthy subjects. The results indicated that VEGF was overproduced in advanced and untreated PV patients and at less degree, in early PV, a subgroup of idiopathic erythrocytosis, thus confirming an increased angiogenic activity. However, VEGF does not play an angiogenic role in secondary erythrocytosis.

How I treat stage II colon cancer patients.

Stage II colon cancer (CC) is probably one of the best prognosis gastrointestinal tumors seen in our consultations, but often takes a lot of time for physicians to determine appropriate treatment because of the limited benefit of adjuvant chemotherapy (CT) in these patients, together with the limited evidence in this situation. How to choose the best treatment for each individual patient is thus dependent on molecular (microsatellite instability/microsatellite stability status) and clinico-pathological features relevant enough to classify these tumors into low-, intermediate- and high-risk stage II disease and to choose an appropriate attitude for each of these subgroups. In practice, the first step in treatment decision making must be to assess the patient's status and comorbidities to see if the patient is eligible for an adjuvant treatment. Then, as fluoropyrimidines (FPs) are the corner stone of CC adjuvant treatment, screening for dihydropyrimidine dehydrogenase deficiency is mandatory in western countries. Finally, depending on the patient's characteristics and tumor risk stage, the strategy may be surveillance, adjuvant FP alone or oxaliplatin-based adjuvant CT. In the near future, new tools such as Immunoscore® (HalioDx; Luminy Biotech Enterprises, Marseille Cedex, France) and circulating tumor DNA may help to identify more precisely patients with minimal residual disease for more personalized adjuvant treatment approaches.

Combined first-stage hepatectomy and colorectal resection in a two-stage hepatectomy strategy for bilobar synchronous liver metastases.

BACKGROUND: This study assessed the feasibility and outcomes of combined colorectal and hepatic resection as the first step of two-stage hepatectomy in patients with bilobar synchronous colorectal liver metastases. METHODS: All patients with bilobar synchronous colorectal liver metastases who were considered for two-stage hepatectomy, combining resection of the primary tumour with the first stage of hepatectomy, between 2000 and 2008 were selected from a prospectively collected database at two institutions. Data were analysed retrospectively on an intention-to-treat basis. RESULTS: Thirty-three patients were studied. Twenty patients received neoadjuvant chemotherapy. Combined colorectal resection and clearance of left-sided liver metastases was the first-stage procedure in all but one patient, in whom right clearance was performed. In 17 patients right portal vein ligation was undertaken at the same time. No patient died. Two patients had anastomotic leakage. Interval chemotherapy was given to 25 patients, five of whom also had percutaneous portal vein embolization. Twenty-five patients had the second-stage hepatectomy, but not eight patients with disease progression. There was one postoperative death after the second stage, and eight patients experienced morbidity. Median follow-up from the first stage was 28.7 months. Overall and disease-free survival rates for patients who completed the procedure were 80 and 44 per cent respectively at 3 years, and 48 and 22 per cent at 5 years. CONCLUSION: In patients with bilobar synchronous colorectal liver metastases who are candidates for two-stage hepatectomy, combined resection of the primary tumour and first-stage hepatectomy reduces the number of procedures, optimizes chemotherapy administration and may improve outcome.

High prevalence of Foxp3 and IL17 in MMR-proficient colorectal carcinomas.

BACKGROUND AND AIMS: Colorectal cancer (CRC) harbours different types of DNA alterations, including microsatellite instability (MSI). Cancers with high levels of MSI (MSI-H) are considered to have a good prognosis, probably related to lymphocyte infiltration within tumours. The aim of the present study was to characterise the intratumoural expression of markers associated with the antitumour immune response in mismatch repair (MMR)-proficient (MSS) colon cancers. METHODS: Ninety human colon cancers (T) and autologous normal colon mucosa (NT) were quantified for the expression of 15 markers of the immune response with quantitiative reverse transcription-PCR (qRT-PCR). mRNA expression levels were correlated with MMR status. Immunohistochemistry (IHC) was performed using both interleukin 17 (IL17) and CD3 antibodies. RESULTS: Expression of cytotoxic markers (FasL, granzyme B and perforin), inflammatory cytokines (IL1beta, IL6, IL8, IL17 and transforming growth factor beta (TGFbeta)) and a marker of regulatory T cells (forkhead box P3 (Foxp3)) was significantly higher in tumours than in autologous normal tissues. Adjusting for MMR status, higher tumoural expression of both granzyme B and perforin was associated with the MSI-H phenotype, and the perforin T/NT ratio was higher in MSI-H tissues than in MSS tissues. Higher tumoural expression of Foxp3, IL17, IL1beta, IL6 and TGFbeta was associated with the MSS phenotype, and the IL17 T/NT ratio was higher in MSS tissues than in MSI-H tissues as assessed by both qRT-PCR and IHC. CONCLUSIONS: Immune gene expression profiling in CRC displayed different patterns according to MMR status. Higher Foxp3, IL6, TGFbeta and IL17 expression is a particular determinant in MMR-proficient CRC. These may be potential biomarkers for a new prognostic "test set" in sporadic CRCs.

Imatinib: Major photocatalytic degradation pathways in aqueous media and the relative toxicity of its transformation products.

Imatinib (IMA) is a highly potent tyrosine kinase inhibitor used as first-line anti-cancer drug in the treatment of chronic myeloid leukemia. Due to its universal mechanism of action, IMA also has endocrine and mutagenic disrupting effects in vivo and in vitro, which raises the question of its environmental impact. However, to date, very little information is available on its environmental fate and the potential role of its transformation products (TPs) on aquatic organisms. Given the IMA resistance to hydrolysis and direct photolysis according to the literature, we sought to generate TPs through oxidative and radical conditions using the AOPs pathway. Thus, the reactivity of the cytotoxic drug IMA in water in the presence of OH and h+ was investigated for the first time in the present work. In this regard, a non-targeted screening approach was applied in order to reveal its potential TPs. The tentative structural elucidation of the detected TPs was performed by LC-HRMSn. The proposed approach allowed detecting a total of twelve TPs, among which eleven are being described for the first time in this work. Although the structures of these TPs could not be positively confirmed due to lack of standards, their chemical formulas and product ions can be added to databases, which will allow their screening in future monitoring studies. Using the quantitative structure-activity relationship (QSAR) approach and rule-based software, we have shown that the detected TPs possess, like their parent molecule, comparable acute toxicity as well as mutagenic and estrogenic potential. In addition to the in silico studies, we also found that the samples obtained at different exposure times to oxidative conditions, including those where IMA is no longer detected, retained toxicity in vitro. Such results suggest further studies are needed to increase our knowledge of the impact of imatinib on the environment.

Quantification of very low-abundant proteins in bacteria using the HaloTag and epi-fluorescence microscopy.

Cell biology is increasingly dependent on quantitative methods resulting in the need for microscopic labelling technologies that are highly sensitive and specific. Whilst the use of fluorescent proteins has led to major advances, they also suffer from their relatively low brightness and photo-stability, making the detection of very low abundance proteins using fluorescent protein-based methods challenging. Here, we characterize the use of the self-labelling protein tag called HaloTag, in conjunction with an organic fluorescent dye, to label and accurately count endogenous proteins present in very low numbers (<7) in individual Escherichia coli cells. This procedure can be used to detect single molecules in fixed cells with conventional epifluorescence illumination and a standard microscope. We show that the detection efficiency of proteins labelled with the HaloTag is ≥80%, which is on par or better than previous techniques. Therefore, this method offers a simple and attractive alternative to current procedures to detect low abundance molecules.

Surgical management of obstructive left colon cancer at a national level: Results of a multicentre study of the French Surgical Association in 1500 patients.

PURPOSE: Surgical management of obstructive left colon cancer (OLCC) is controversial. The objective is to report on postoperative and oncological outcomes of the different surgical options in patients operated on for OLCC. METHODS: From 2000-2015, 1500 patients were treated for OLCC in centers members of the French Surgical Association. Colonic stent (n=271), supportive care (n=5), palliative derivation (n=4) were excluded. Among 1220 remaining patients, 456 had primary diverting colostomy (PDC), 329 a segmental colectomy (SC), 246 a Hartmann's procedure (HP) and 189 a subtotal colectomy (STC) as first-stage surgery. Perioperative data and oncological outcomes were compared retrospectively. RESULTS: There was no difference between the 4 groups regarding gender, age, BMI and comorbidities. Postoperative mortality and morbidity were 4-27% (PDC), 6-47% (SC), 9-55% (HP), 13-60% (STC), respectively (P=0.005). Among the 431 living patients after PDC, 321 (70%) patients had their primary tumour removed. Cumulative mortality and morbidity favoured PDC (7-39%) and SC (6-40%) compared to HP (1-47%) and STC (13-50%) (P=0.04). At the end of follow-up definitive stoma rates were 39% (HP), 24% (PDC), 10% (SC), and 8% (STC) (P<0.0001). Five-year overall and disease-free survival was: SC (67-55%), PDC (54-48%), HP (54-37%) and STC (48-49%). After multivariate analysis, SC and PDC were associated with better prognosis compared to HP and STC. CONCLUSION: In OLCC, SC and PDC are the two preferred options in patients with good medical conditions. For patients with severe comorbidities PDC should be recommended, reserving HP and STC for patients with colonic ischaemia or perforation complicating malignant obstruction.

Chemotherapy has also an effect on primary tumor in colon carcinoma.

BACKGROUND: This study characterizes the histological effect of chemotherapy (CT) on primary colonic tumors. METHODS: Between 2000 and 2006, 38 patients with stage IV colon cancer underwent resection of the primary, after chemotherapy (CT group, n = 16) or without preoperative CT (control group, n = 22). For all primary tumors, histological analysis included: fibrosis, acellular necrosis, acellular mucin pools, lymphoplasmacytic infiltration, and changes at tumor surface. Tumor regression grade (TRG) was determined by the amount of residual tumor cells and was graded from 1 to 5. RESULTS: No patient had complete histological response. Major histological tumor regression (TRG2) was observed in 70% of patients treated by CT and none of the not treated patients (P < 0.0001). Fibrosis, acellular necrosis, and surface changes were significantly increased in the CT group. TRG in the primary was comparable to the TRG in the corresponding liver metastases for 7/9 patients who underwent both colonic and hepatic resection after CT. CONCLUSION: CT induces major histological response in 70% of colon cancers. Response to CT in the primary and the corresponding liver metastases are correlated. These results support a policy of initial CT management for stage IV colon cancer and may warrant future studies of neoadjuvant CT in locally advanced colon carcinomas.

Robot-assisted laparoscopic mesh repair of incisional hernias with exclusive intracorporeal suturing: a pilot study.

BACKGROUND: The da Vinci robot laparoscopic incisional hernia repair with intracorporeal suturing may offer an alternative to transabdominal sutures and tackers. METHODS: From 2003 to 2005, 11 patients (median age, 71 years; median body mass index [BMI], 28) with small and medium-sized incisional hernias (median fascial defect, 19.6 cm2) were treated with the da Vinci robot system using intracorporeal mesh fixation with interrupted sutures. This pilot study aimed to assess the feasibility and report the morbidity with special reference to postoperative pain and long-term recurrence. RESULTS: The median operative time was 180 min. There was no conversion to open or standard laparoscopy and no postoperative mortality. The overall morbidity rate was 27%. One patient underwent reoperation on postoperative day 3 for peritonitis secondary to small bowel injury. The median visual analog pain score on postoperative day 1 was 3. Seven patients (63%) needed parenteral paracetamol until postoperative day 2. The median hospital stay was 3 days. During a median follow-up period of 25 months, no patient experienced recurrent hernia. One patient had a trocar-site herniation at 6 months. No patient experienced chronic suture site pain or discomfort. CONCLUSION: This is the first report of robot-assisted laparoscopic incisional hernia with exclusive intracorporeal suturing for mesh fixation in humans. The findings show that this technique is feasible and may not be associated with chronic postoperative pain. Further evaluation is needed to assess the benefit to the patient, but this investigation may be the basis for a future, prospective, randomized study.

[Colorectal carcinogenesis. 2. Underlying epigenetic and genetic alterations and molecular classification of colorectal cancers]. / Carcinogenèse colorectale. 2. Mécanismes génétiques et épigénétiques de la progression tumorale et calssification moléculaire des cancers colorectaux.

Gene alterations which have been implicated in colorectal carcinogenesis are characterized by three major mechanisms: chromosomal instability, microsatellite instability, and epigenetic mechanisms (i.e., CpG island hypermethylation). Progress in understanding of these genetic and epigenetic instabilities has led to advances in the individualization and characterization of more homogeneous sub-groups of colorectal tumors with regard to progression, prognosis and response to therapy.