Prognostic value of primary tumor sidedness in patients with non-metastatic IBD related CRC - Is it the exception to the rule?

BACKGROUND: Although primary tumor sidedness (PTS) has a known prognostic role in sporadic colorectal cancer (CRC), its role in Inflammatory Bowel Disease related CRC (IBD-CRC) is largely unknown. Thus, we aimed to evaluate the prognostic role of PTS in patients with IBD-CRC. METHODS: All eligible patients with surgically treated, non-metastatic IBD-CRC were retrospectively identified from institutional databases at ten European and Asian academic centers. Long term endpoints included recurrence-free (RFS) and overall survival (OS). Multivariable Cox proportional hazard regression as well as propensity score analyses were performed to evaluate whether PTS was significantly associated with RFS and OS. RESULTS: A total of 213 patients were included in the analysis, of which 32.4% had right-sided (RS) tumors and 67.6% had left-sided (LS) tumors. PTS was not associated with OS and RFS even on univariable analysis (5-year OS for RS vs LS tumors was 68.0% vs 77.3%, respectively, p = 0.31; 5-year RFS for RS vs LS tumors was 62.8% vs 65.4%, respectively, p = 0.51). Similarly, PTS was not associated with OS and RFS on propensity score matched analysis (5-year OS for RS vs LS tumors was 82.9% vs 91.3%, p = 0.79; 5-year RFS for RS vs LS tumors was 85.1% vs 81.5%, p = 0.69). These results were maintained when OS and RFS were calculated in patients with RS vs LS tumors after excluding patients with rectal tumors (5-year OS for RS vs LS tumors was 68.0% vs 77.2%, respectively, p = 0.38; 5-year RFS for RS vs LS tumors was 62.8% vs 59.2%, respectively, p = 0.98). CONCLUSIONS: In contrast to sporadic CRC, PTS does not appear to have a prognostic role in IBD-CRC.

Is the age at surgery in Crohn's disease clinically relevant? Differences and peculiarities: a wide single centre experience after long-term follow-up.

PURPOSE: The Montreal classification for Crohn's disease includes "age at diagnosis" as a parameter but few is reported about the age at surgery. The aim of this study is to evaluate the short- and long-term differences in the postoperative surgical outcome and disease behaviour, according to the age at the first surgery. METHODS: Patients consecutively operated for abdominal Crohn's disease during the period 1986-2012 at our centre were systematically analysed according to their age at first surgery. In our retrospective cohort, the age at first surgery ranged from 13 to 83 years, and patients were arbitrarily divided into four groups: ≤ 19 (G1), 20-39 (G2), 40-59 (G3) and ≥ 60 (G4) years old. RESULTS: In total, 1051 patients were included with a median follow-up time of 232 months. The four groups exhibited statistically significant differences in age at diagnosis, smoke habit, time between diagnosis and surgery, disease location and behaviour, history of perianal fistula or abscess, severe malnutrition requiring total parental nutrition before surgery, type of surgery, total length of resected bowel, median duration of hospitalization, incidence of abdominal recurrences and number of surgical recurrences. G1 displays an inverse linear trend with time in the severity of clinical characteristics when compared to G4 groups. On the contrary, the incidence of short-term complications, types of abdominal recurrence and presence of concomitant perianal disease did not vary among groups. In addition, at multivariate analysis, the age at surgery and the disease location were the only independent risk factors for abdominal surgical recurrence. CONCLUSION: Despite first surgery is extremely more frequent between 20 and 59 years, patients from G1 and G4 groups showed clinical differences and peculiarities when compared to the other age groups. The most indolent CD behaviour and occurrence of surgical recurrence was observed in patients having their first abdominal surgery in the elderly, while patients operated before the age of 19 experienced a more aggressive disease course.

Long-Term Follow-Up, Association between CARD15/NOD2 Polymorphisms, and Clinical Disease Behavior in Crohn's Disease Surgical Patients.

BACKGROUND: CARD15/NOD2 is the most significant genetic susceptibility in Crohn's disease (CD) even though a relationship between the different polymorphisms and clinical phenotype has not been described yet. The study is aimed at analyzing, in a group of CD patients undergoing surgery, the relationship between CARD15/NOD2 polymorphisms and the clinical CD behavior after a long-term follow-up, in order to identify potential clinical biomarkers of prognosis. METHODS: 191 surgical CD patients were prospectively characterized both for the main single nucleotide polymorphisms of CARD15/NOD2 and for many other environmental risk factors connected with the severe disease form. After a mean follow-up of 7.3 years, the correlations between clinical features and CD natural history were analyzed. RESULTS: CARD15/NOD2 polymorphisms were significantly associated with younger age at diagnosis compared to wild type cases (p < 0.05). Moreover, patients carrying a 3020insC polymorphism presented a larger Δ between diagnosis and surgery (p = 0.0344). Patients carrying an hz881 and a 3020insC exhibited, respectively, a lower rate of responsiveness to azathioprine (p = 0.012), but no difference was found in biologic therapy. Finally, the risk of surgical recurrence was significantly associated, respectively, to age at diagnosis, to familial CD history, to diagnostic delay, to arthritis, and to the presence of perioperative complications. CONCLUSIONS: 3020insC CARD15 polymorphism is associated with an earlier CD onset, and age at CD diagnosis < 27 years was confirmed to have a detrimental effect on its clinical course. In addition, the familiarity seems to be connected with a more aggressive postoperative course. Finally, for the first time, we have observed a lower rate of responsiveness to azathioprine in patients carrying an hz881 and a 3020insC.

Laparoscopic ileo-colic resection and right hemicolectomy for Crohn's disease and colon cancer: a preliminary comparative study on post-operative outcome.

Crohn's disease (CD) patients are generally considered at high risk of post-operative complications with respect to non-CD patients. The primary endpoint of this study is to compare early major complications rates between CD and colon cancer (CC) patients undergoing mini-invasive ileo-colic resections or right hemicolectomies. The secondary endpoint is to evaluate the role of pre-operative medication with anti-TNF as a possible risk factor for post-operative complications. An observational retrospective study was carried on patients who underwent mini-invasive ileocolic resections for CD and right hemicolectomies for CC at Digestive Surgery Unit and IBD Unit, Careggi Univeristy Hospital, from January 1, 2008, to June 1, 2019. Data collected included demographic and clinical informations, pre-operative anti-TNF use, major complications and mortality. Hundred and thirty-three mini-invasive ileocolic resections for CD and 131 mini-invasive right hemicolectomies for CC were included. Early major post-operative complications rates were 4.5% for CD patients and 3% for CC patients (p = 0.535). Anastomotic leak rates were 1.5% in both groups. There was no significant difference in mean length of stay; while, mean operation time was significantly longer in CD patients (p < 0.01). Pre-operative use of anti-TNF was not associated with a higher risk for early major post-operative complications in CD patients. In our institution, CD patients undergoing ileocolic resections or right hemicolectomies with a mini-invasive technique do not have a significantly higher risk of postoperative major complications with respect to CC patients, even when treated with anti-TNF agents within 3 months before surgery.

Preliminary study of short- and long-term outcome and quality of life after minimally invasive surgery for Crohn's disease: Comparison between single incision, robotic-assisted and conventional laparoscopy.

BACKGROUND: The feasibility of minimally invasive approach for Crohn's disease (CD) is still controversial. However, several meta-analysis and retrospective studies demonstrated the safety and benefits of laparoscopy for CD patients. Laparoscopic surgery can also be considered for complex disease and recurrent disease. The aim of this study was to investigate retrospectively the effect of three minimally invasive techniques on short- and long-term post-operative outcome. PATIENTS AND METHODS: We analysed CD patients underwent minimally invasive surgery in the Digestive Surgery Unit at Careggi University Hospital (from January 2012 to March 2017). Short-term outcome was evaluated with Clavien-Dindo classification and visual analogue scale for post-operative pain. Long-term outcome was evaluated through four questionnaires: Short Form Health Survey (SF-36), Gastrointestinal Quality Of Life Index (GIQLI), Body Image Questionnaire (BIQ) and Hospital Experience Questionnaire (HEQ). RESULTS: There were 89 patients: 63 conventional laparoscopy, 16 single-incision laparoscopic surgery and 10 robotic-assisted laparoscopy (RALS). Serum albumin <30 g/L (P = 0.031) resulted to be a risk factor for post-operative complications. HEQ had a better result for RALS (P = 0.019), while no differences resulted for SF-36, BIQ and GIQLI. CONCLUSIONS: Minimally invasive technique for CD is feasible, even for complicated and recurrent disease. Our study demonstrated low rates of post-operative complications. However, it is a preliminary study with a small sample size. Further studies should be performed to assess the best surgical technique.

Multiplex gene expression profile in inflamed mucosa of patients with Crohn's disease ileal localization: A pilot study.

BACKGROUND: Crohn's disease (CD) is a complex disorder resulting from the interaction of genetic, environmental, and microbial factors. The pathogenic process may potentially affect any segment of the gastrointestinal tract, but a selective location in the terminal ileum was reported in 50% of patients. AIM: To characterize clinical sub-phenotypes (colonic and/or ileal) within the same disease, in order to identify new therapeutic targets. METHODS: 14 consecutive patients undergoing surgery for ileal CD were recruited for this study. Peripheral blood samples from each patient were collected and the main polymorphisms of the gene Card15/Nod2 (R702W, G908R, and 1007fs) were analyzed in each sample. In addition, tissue samples were taken from both the tract affected by CD and from the apparently healthy and disease-free margins (internal controls). We used a multiplex gene assay in specimens obtained from patients with ileal localization of CD to evaluate the simultaneous expression of 24 genes involved in the pathogenesis of the disease. We also processed surgery gut samples with routine light microscopy (LM) and transmission electron microscopy (TEM) techniques to evaluate their structural and ultrastructural features. RESULTS: We found a significant increase of Th17 (IL17A and IL17F, IL 23R and CCR6) and Th1 (IFN-γ) gene expression in inflamed mucosa compared to non-inflamed sites of 14 CD patients. DEFB4 and HAMP, two genes coding for antimicrobial peptides, were also strongly activated in inflamed ileal mucosa, suggesting the overwhelming stimulation of epithelial cells by commensal microbiota. IFN-γ and CCR6 were more expressed in inflamed mucosa of CD patients with ileal localization compared with patients with colonic localization suggesting a more aggressive inflammation process in this site. Morphological analysis of the epithelial lining of Lieberkün crypts disclosed enhanced release activity from goblet mucocytes, whereas the lamina propria contained numerous cells pertaining to various lines. CONCLUSION: We observed that the expression of ileal genes related to Th1 and Th17 activity is strongly activated as well as the expression of genes involved in microbiota regulation.

Analysis of Oxidative Stress-Related Markers in Crohn's Disease Patients at Surgery and Correlations with Clinical Findings.

Crohn' disease (CD) patients are at high risk of postoperative recurrence and new tools for the assessment of disease activity are needed to prevent long-term complications. In these patients, the over-production of ROS generated by inflamed bowel tissue and inflammatory cells activates a pathogenic cascade that further exacerbates inflammation and leads to increased oxidative damage to DNA, proteins, and lipids. We measured the products of protein/lipid oxidation and the total antioxidant capacity (ferric reducing ability of plasma, FRAP) in the serum of CD patients with severe disease activity requiring surgery with the aim to characterize their redox status and identify associations between oxidative stress-related markers and their clinical characteristics. At the systemic level, CD was associated with increased levels of protein and lipid oxidation products when compared to healthy volunteers, even though the FRAP values were similar. Advanced oxidation protein product (AOPP) levels showed the highest difference between patients and the controls (11.25, 5.02-15.15, vs. 1.36, 0.75-2.70, median, interquartile range; p < 0.0001) and the analysis of receiver operating characteristic (ROC) curves, indicated for AOPP, the best area under the curve (AUC) value for CD prediction. Advanced glycated end-products (AGEs) were also significantly higher in CD patients (p < 0.01), which is of interest since AOPP and AGEs are both able to activate the membrane receptor for advanced glycation end products (RAGE) involved in inflammatory diseases. Thiobarbituric acid reactive substance (TBARS) levels were significantly higher in CD patients with ileal localization and aggressive disease behavior, in smokers, and in patients suffering from allergies. In conclusion, our data indicate that circulating oxidative stress biomarkers may be attractive candidates as disease predictors as well as for clinical or therapeutic monitoring of CD. Our results also suggest that AOPP/AGEs and RAGE signaling may represent a pathogenic factor and a potential therapeutic target in CD.

Poor pathogenetic role of luminal obstruction in the development of appendicitis: A case report.

RATIONALE: In developed countries, the incidence of acute appendicitis is about 95 cases out of 100,000 per year, being one of the most common urgencies in general surgery worldwide. However, its pathogenesis is still poorly understood. Direct luminal obstruction (by a fecalith, lymphoid hyperplasia, or impacted stool) is reported to be the primary and principal cause of acute appendicitis. PATIENT CONCERNS: During October 2016 a 58-year-old woman was operated because of a clinical recurrence of Crohn's disease. At surgery, performed through single incision laparoscopy, we observed an exceptional finding. DIAGNOSES: Despite a previous ileo-cecal resection, the appendix was still present and vascularized by small vessels within the mesoappendix connected to the neo-terminal ileum mesentery; it was about 5 cm long and macroscopically not inflamed even if its base was clearly no longer connected with the cecum. OUTCOMES: The patient underwent ileo-colic resection with en-bloc removal of the appendix. With a narrow metallic stylet probe we carefully tried to enter the appendix lumen through the opposite side from its fundus but we were not able to enter it before cutting the wall with scissors. Pathological examination confirmed the Crohn's disease recurrence affecting the small bowel and the appendix lumen obstructed in the presence of a fecalith but without any sign of inflammation. LESSONS: This finding seems to highlight the poor pathogenetic role of luminal obstruction in the development of acute appendicitis.

New perspectives on the long-term outcome of segmental colectomy for Crohn's colitis: an observational study on 200 patients.

BACKGROUND AND AIMS: Surgical management of Crohn's colitis represents one of the most complex situations in colorectal surgery. Segmental colectomy (SC) and total abdominal colectomy with ileorectal anastomosis (TAC-IRA) are the most common procedures, but there are few available data on their long-term outcome. The aim of the present study was to analyze the long-term outcome of patients who underwent segmental colectomy for Crohn's colitis, with regard to the risk for total abdominal colectomy. METHODS: In this observational, monocentric, retrospective analysis, we analyzed patients who received a segmental colectomy for Crohn's colitis at our institution. The database was updated by asking patients to complete a questionnaire by telephone or at the outpatient clinic. Only patients followed up at our Hospital were included. Patients were followed up by a specialized multidisciplinary team (IBD Unit). The primary endpoint was the interval between segmental colectomy and, when performed, total abdominal colectomy. RESULTS: Between 1973 and 2014, 200 patients underwent segmental colectomy for Crohn's colitis. The median follow-up was 13.5 years (interquartile range [IQR] 7.8-21.5). Overall, 62 patients (31%) had a surgical recurrence, of these, 42 (21%) received total abdominal colectomy. At multivariate analysis, the presence of ≥ 3 sites (HR = 2.47; 95% CI 1.22-5.00; p = 0.018) and perianal disease (HR = 3.23; 95% CI 1.29-8.07; p = 0.006) proved to be risk factors for total abdominal colectomy. CONCLUSIONS: The risk for surgical recurrence after SC for Crohn's colitis is acceptable. We recommend a bowel-sparing policy for the treatment of Crohn's colitis in any case in which the extent of the disease at the moment of surgery makes the conservative approach achievable.

Totally robotic intracorporeal side-to-side isoperistaltic strictureplasty for Crohn's disease.

The development of bowel-sparing techniques (strictureplasties) for extended stricturing Crohn's disease (CD) and the increased use of minimally invasive surgery (wound sparing) represent the two most important improvements in inflammatory bowel disease surgery from the origin. Nevertheless, the minimally invasive approach for extended stricturing forms is usually avoided primarily because of difficulties in performing complex intracorporeal sutures. We describe a totally intracorporeal robotic ileocecal resection with a yet described modified side-to-side isoperistaltic strictureplasty for an extended ileocecal CD. The strictureplasty was 6 cm long including the stricture in its middle part. Adopting this approach, the preserved small bowel was about 10 cm longer. Operative time was about 4 h, with a blood loss of about 50 ml. The patients' post-operative course was uneventful, enteral nutrition started at post-operative day 2 and gradual oral food intake from day 3. She was discharged on post-operative day 6. Histology confirmed a stricturing CD, and the patient is recurrence free at 34 months' follow-up. Our report suggests that robotic-assisted intracorporeal strictureplasty is feasible and that robotics could represent an interesting instrument for allowing the intersection between minimally invasive and bowel-sparing surgery for CD.

Pylephlebitis and Crohn's disease: A rare case of septic shock.

INTRODUCTION: Troncular pylephlebitis, defined as septic thrombophlebitis of the portal vein, is usually secondary to suppurative infection from the regions drained by the portal system. Therefore, pylephlebitis can occur from the portal vein main tributaries. The occurrence of mesenteric pylephlebitis in Crohn's disease is extremely rare. PRESENTATION OF CASE: We describe a case of septic shock due to mesenteric pylephlebitis in a 47 years old male affected with Crohn's disease. The patient was admitted to the emergency department after he had been complained from 3h of a peri-umbilical abdominal pain associated to fever and shivering quickly followed by a severe hypotension. His medical history included histologically confirmed ileal Crohn's disease diagnosed 4 years before and treated with mesalamine only. Computed tomography scan confirmed the mesenteric pylephlebitis diagnosis. After medical therapy with antibiotics and systemic nutrition, the patient was successfully operated to treat his ileal Crohn's disease. DISCUSSION: In our case, the quick onset of a septic shock was not due to a peritonitis complicating a Crohn's disease, but to a rare condition not needing an urgent surgical resolution. This report shows that, even in Crohn's disease, once diagnosis is performed, antibiotic therapy associated to enteral and parenteral nutrition can lead to a complete clinical remission of mesenteric pylephlebitis, mandatory to perform an elective surgery. CONCLUSION: This case highlights the importance of promptly considerate and treat mesenteric pylephlebitis in presence of a septic shock in a Crohn's disease patient who is not showing clinical signs of peritonitis.

Safer intestinal invagination for a solid pancreatico-jejunal anastomosis in presence of a soft texture pancreatic remnant and non-dilated duct.

Pancreatico-jejunal anastomosis after pancreatoduodenectomy still represents the Achilles' heel of the procedure: the failure of this anastomosis is relatively common and it is the main cause of post-operative morbidity and mortality. Studies have described different reconstruction strategies for the control of the development of post-operative pancreatic fistula, but the strategy to obtain a safer pancreatico-jejunal anastomosis is still far from satisfaction. We report a novel variation of the invagination technique based on preliminary clinical experience in 8 patients who underwent pancreatico-jejunal anastomosis after pancreatoduodenectomy in our hepatobiliopancreatic center from 2008 to 2014. The variation could obtain a safer intestinal invagination for a solid pancreatico-jejunal anastomosis even in the presence of soft pancreatic remnant.

A multidisciplinary approach to desmoid tumors. When intra-abdominal fibromatosis degenerates into an abscess, which is the right treatment?

INTRODUCTION: Desmoid tumors are rare benign tumors that originates in the fibrous sheath or musculo-aponeurotic structure. Histologically benign, they tends to invade locally and to be recurrent. PRESENTATION OF CASE: We report a rare case of an intra-abdominal desmoid tumor in a patient affected by familial adenomatous polyposis, which degenerated into abscess. Male, 38 years, was hospitalized for abdominal pain, bowel obstruction and fever. The computed tomography showed a big dishomogeneous mass occupying the whole mesentery with internal massive liquefaction. The mass extended from the epigastrium for 13cm up to L3. On the right mesogastric side a solid, thick mass of about 2cm, with a length of 4.5cm, was identified; it was not cleavable from the wall and from some of the loops. We decided to perform a computed tomography-guided percutaneous drainage. Two hundred ml of purulent necrotic material was aspirated, and washing with antibiotic solution was carried out. Cytological examination of fluid drainage showed histiocytes and neutrophils. At follow-up, the patient's clinical condition had improved. An abdominal ultrasound showed a substantial reduction in the diameter of the mass. DISCUSSION: Diagnosis and treatment of desmoids tumor in patients with familial adenomatous polyposis may be difficult, especially when desmoids are located intra-abdominally and in the mesentery. Seldom will desmoid tumors be complicated by abscess formation. CONCLUSION: The management of desmoids tumors is not easy and the choice of the best treatment may be difficult due to the different possible anatomical presentations.

Radiofrequency on the liver remnant after liver resection to reach the haemostasis not otherwise achievable with conventional techniques.

INTRODUCTION: During liver resection, in same case of inflamed, steatotic or neo-vascularized liver parenchyma, reaching of haemostasis on the liver resection surface could be very difficult for the surgeon because of the presence of fragile tissue that does not allows the proper placement of stitches, and the conventional method fail. PRESENTATION OF CASE: The authors describe a novel technique in which, after a formal liver resection, liver haemostasis is achieved using radiofrequency energy on the resected surface. A patient affected by a hystiocytic sarcoma localized on the VI-V and IVa segments was scheduled for liver resection. During the resection a diffuse bleeding from the resected surface started with little success obtained with conventional method. So we decided to use the coagulative necrosis generated by the radiofrequency, using a cool type cluster needle, hand-piece with 3 needle, bending 2 needles in a way resembling a "fork", to reach a complete and definitive haemostasis. DISCUSSION: Haemostasis remains a critical issue in liver surgery not only for the catastrophic effect of haemorrhage but also because it is correlated to complications rate and to survival. The coagulative necrosis generated by the radiofrequency could be used to facilitate the creation of a necrotic plane to be transacted. CONCLUSION: The use of the radiofrequency energy, delivered through needles, is suggested when the conventional techniques fail to reach a proper haemostasis after a liver resection or, to consider its use, prior to resect the liver in presence of fragile parenchyma.

Colorectal cancer and Crohn's colitis: clinical implications from 313 surgical patients.

BACKGROUND: The relation between Crohn's colitis (CC) and colorectal cancer is still controversial. Several case reports and retrospective studies have shown that patients with Crohn's disease (CD) have a 6- to 20-fold higher risk to develop CRC than does the normal population. The extent of disease (extensive colitis), presence of anal fistula, age > 40 years, strictures, and length of disease >10 years may be important determinants for increasing risk. Despite this evidence, other population-based studies have shown no increased risk of colon or rectal cancer. The aim of this study was to investigate retrospectively factors that may predict the development of cancer. METHODS: We searched the histopathologic database of the Digestive Surgery Unit at Careggi University Hospital for CC patients (January 1987 to September 2011) and identified 313 patients with CC who underwent surgery. RESULTS: There are 11 (3.5 %) of adenocarcinomas. Multivariate analysis showed disease duration (p = 0.001), age at CD diagnosis (p = 0.002), distal localization (p = 0.045), and penetrating disease (p = 0.041) to be risk factors. Multivariate analysis showed that 40 patients who had undergone previous immunosuppressive therapy had a significant risk of developing CRC (p = 0.026). CONCLUSIONS: Crohn's colitis patients who require surgery are at higher risk for developing CRC, particularly those whose disease duration is >10 years, have distal localization, age at diagnosis was <40 years, and have penetrating disease. Previous immunosuppressive therapy should be better investigated. We recommend surgery for any patient presenting with colonic strictures.