The Contribution of Muscle Innate Immunity to Uremic Cachexia.

Protein energy wasting (PEW) is a common complication both in chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Of note, PEW is one of the stronger predictors of morbidity and mortality in this patient population. The pathogenesis of PEW involves several mechanisms, including anorexia, insulin resistance, acidosis and low-grade inflammation. In addition, "sterile" muscle inflammation contributes to PEW at an advanced CKD stage. Both immune and resident muscle cells can activate innate immunity; thus, they have critical roles in triggering "sterile" tissue inflammation. Toll-like receptor 4 (TLR4) can detect endogenous danger-associated molecular patterns generated or retained in blood in uremia and induce a sterile muscle inflammatory response via NF-κB in myocytes. In addition, TLR4, though the activation of the NLRP3 inflammasome, links the sensing of metabolic uremic stress in muscle to the activation of pro-inflammatory cascades, which lead to the production of IL-1ß and IL-18. Finally, uremia-induced accelerated cell senescence is associated with a secretory phenotype that favors fibrosis in muscle. Targeting these innate immune pathways could lead to novel therapies for CKD-related PEW.

MicroRNAs differential expression profile in metastatic colorectal cancer: A pilot study with literature review.

BACKGROUND AND OBJECTIVES: Colorectal cancer is still one of the leading causes of cancer-related deaths worldwide and specific tools to improve disease assessment and treatment response are advocated. The aim of this study was to analyze miRNAs expression in metastatic and non-metastatic colorectal cancer, in order to identify reliable biomarkers suitable for prognosis, treatment and patient's monitoring. MATERIAL AND METHODS: Among 25 patients (mean age 71 ± 12 years; Female/Male: 12/13) submitted to laparoscopic colorectal resection between August 2017 and February 2019, miRNAs were extracted from fresh frozen tissues of solid tumors. Gene expression's analysis arising from microarray technology was performed. RESULTS: Pathological evaluation identified 15 metastatic patients (8 presenting with stage III and 7 with stage IV cancers) and 10 non-metastatic patients (4 presenting with stage I and 6 stage II cancers). Bioinformatic analysis of solid biopsies revealed 16 miRNAs (11 upregulated and 5 downregulated) differently expressed between metastatic and non-metastatic groups, with three miRNAs (miR-7515, miR-7109-5p and miR-6831-5p) never linked to colorectal cancer before. CONCLUSIONS: Our study showed an association between miRNAs and metastatic colorectal cancer, suggesting their potential role as biomarkers for tumor management, if confirmed by further studies.

Infections in patients with inflammatory bowel disease.

BACKGROUND/AIM: Inflammatory bowel diseases (IBD) are a group of conditions characterized by chronic inflammation of all or part of the digestive tract and primarily includes Ulcerative Colitis (UC) and Crohn's Disease (CD). This review has as target to summarize the complicated correlation between IBD and infections, which can affect patients' quality of life and increase substantially morbidity and mortality rates. RESULTS: Scientific evidence in recent years shows a growing recognition of the phenomenon although the association between these two aspects is not definitively clear. Despite the fact that our understanding of this linkage is still incomplete, it is easily deducible that infections can start whether it be the onset or the relapse of IBD. In addition to this, the course of the disease predisposes the patient to numerous infections caused by the drugs used to treat IBD and this also raises the risk of infection complications. CONCLUSIONS: Clinical trials have demonstrated that the combined use of immunomodulating agents may increase the risk of new infections. The infections might be intensified by an insufficient vaccination of adults with IBD. Physicians have to be aware of these risks and try to attenuate and treat them properly. KEY WORDS: Infections, Inflammatory bowel disease, Risk factors.

Surgical management of acute diverticulitis. An update based on our experience and literature data.

BACKGROUND: The treatment of acute diverticulitis is a matter of debate and has undergone significant changes. Currently the main focus of surgical treatment is a more conservative and less invasive management. AIMS AND METHODS: To focus the role of surgery in the treatment of acute diverticulitis, the Authors have conducted a review of the literature of the last two decades and have revised critically their own experience. RESULTS: The indications for elective surgery based on the number of episodes, the young age at diagnosis and the presence of risk factors such as immunosuppression, have to be overcome in favour of a more individual approach based on the severity of the disease. Similarly the presence of pneumoperitoneum is no longer a compelling indication for urgent surgery just as it was in the past. In the treatment of complicated diverticulitis with abscess (Hinchey I-II) is used more and more conservative treatments consisting of guided percutaneous drainage combined with antibiotics. Resection with primary anastomosis with or without diverting ileostomy is preferable to Hartmann's procedure in case of perforated diverticulitis with peritonitis (Hinchey III-IV), using the latter only in the case of comorbidities, severe sepsis, hemodynamic instability or longtime feculent peritonitis (Hinchey IV). Recently, laparoscopic peritoneal lavage was introduced in the treatment of diverticulitis. CONCLUSIONS: Thanks to the progress made in conservative and interventional treatment and laparoscopic surgery, an increasingly less invasive treatment is proposed in the management of acute diverticulitis. KEY WORDS: Acute diverticulitis, Laparoscopic surgery, Surgical treatment.

Crohn's disease and postoperative recurrence. The role of anastomotic configurations and the kono-s anastomosis.

BACKGROUND: The observation that in more than 90% of Crohn's disease patients the postoperative recurrences are located in the pre-anastomotic tract leads us to suppose that the anastomosis would play a role in the appearance of recurrences. AIM AND METHODS: To focus the role of different anastomotic configurations in the incidence of recurrences, the Authors have conducted a review of the literature of the last two decades and have revised critically their experience. RESULTS: The rate of recurrences seem to be lower in patients in whom the anastomotic configuration is such as to present a wide lumen; it seems that they are lower after stapled side-to-side anastomosis. The Kono-S anastomosis, recently introduced technique, seems to offer better results. CONCLUSIONS: The role of the various types of anastomosis remains uncertain. Further large-scale controlled trials with long term follow-up are needed. KEY WORDS: Anastomosis, Crohn's disease, Postoperative Recurrences.

Elective surgery for ulcerative colitis, ileo-rectal anastomosis or restorative proctocolectomy An Update.

BACKGROUND: Despite advances in the medical management of Ulcerative Colitis (UC), surgery is required in about a third of patients. AIMS AND METHODS: A review of the literature of the last 20 years was conducted in order to analyze the results of Ileo-Rectal Anastomosis (IRA) and of Ileal Pouch-Anal Anastomosis (IPAA) in the treatment of mild-to-moderate UC. Postoperative complications, functional results and the risk of cancer were analyzed in each of the two groups of patients. RESULTS: In IRA group postoperative morbidity is low, varying from 8 to 28%. The risk of urinary and sexual dysfunction are rare and fertility rates are higher, compared to IPAA. The cumulative probability of success (working IRA) is 84% at 5 years and 51-69% at 10 years. The postoperative morbidity of IPAA is higher; dehiscence and pelvic sepsis were observed respectively in 9.5% and in 5.5%. A sexual dysfunction is present in 3.4%. In 18.8% occurs pouchitis. The risk of failure of the pouch is 6.8% and increased to 8.5% after 5 years. The risk of cancer is higher after IRA than after IPAA, with a cumulative risk at 20 years of 6-14% and 4.2% respectively. DISCUSSION: The choice between IPAA or IRA is based upon patient's preference and clinical criteria (malignancy or sphincter injury). IPAA, intervention of choice, is burdened by a higher rate of complications, such as anastomotic leak with pelvic sepsis and subsequent functional pouch failure, pouchitis, infertility in young women, lesions of the pelvic nerves and portal vein thrombosis. There have been reports of cancer not only in the anal transitional zone, but also in the same pouch, either after mucosectomy that after stapled anastomosis. IRA is less invasive than IPAA and postoperative complications are lower. Does not require dissection of the pelvic and presents no risk of injury of the nerves of the urogenital sphere. The long-term results of the IRA are generally satisfactory and most of the patients stated that after the intervention improve both the health status and quality of life. CONCLUSION: Today IPAA is the gold standard. The IRA is indicated in selected patients where they meet the following requirements: normal sphincter tone, absence of severe perineal disease, rectum does not actively involved by the disease, absence of dysplasia or cancer. It is also indicated in patients who refuse an ileostomy and it can be proposed as a possible interim procedure in young women, because it does not need a pelvic dissection and because the risk of infertility is minimal or absent when compared to IPAA. Because the risk of cancer is higher, patients undergoing IRA must be adequately informed about the risk, as well as recurrent proctitis, also of cancer, and must fully understand the need for surveillance and accept at least annual endoscopy with rectal biopsies; if these conditions are not met, patients should not be candidates for IRA. KEY WORDS: IPAA, IRA, Surgical treatment, Ulcerative Colitis.

Adenocarcinoma Arising from Perianal Fistulizing Crohn's Disease.

Perianal fistula is a very debilitating event and a cause of morbidity in patients with Crohn's disease (CD). Its malignant transformation is very rare with an incidence of around 0.004-0.7$. Presence of disease in the colon and rectum is the major risk factor for the development of a perianal fistula. In this report we show a case of adenocarcinoma arising from a perianal fistulizing CD. This type of tumor is highly aggressive, difficult to diagnose, and has a rather poor prognosis. The different neoplastic transformations and the different types of tumors that may appear in patients with CD, especially at the colorectal level or at the level of an eventual anastomosis, are to date well documented and described in the literature, while there is a lack of information and of treated cases concerning the occurrence of cancer at the level of a fistula. Due to the rarity of cases, we tried to identify the most frequent and important risk factors: sex, duration of disease, age at diagnosis, and the history of the fistula.

SECCA procedure for anal incontinence and antibiotic treatment: a case report of anal abscess.

BACKGROUND: Fecal Incontinence (FI) can seriously affect quality of life. The treatment of fecal incontinence starts conservatively but in case of failure, different surgical approaches may be proposed to the patient. Recently several not invasive approaches have been developed. One of these is the radiofrequency (RF) energy application to the internal anal sphincter. CASE PRESENTATION: We report a rare case of an anal abscess related to a SECCA procedure in a 66-year-old woman affected by gas and FI for twenty years. CONCLUSIONS: The complications post-SECCA procedure reported in literature are generally not serious and often self-limited, such as bleeding or anal pain. This is a case of an anal abscess. We suggest that this finding could consolidate the importance of administering antibiotic therapy to patients and to run a full course of at least 6 days rather than a short-term (24 h) therapy, with the aim to minimize the incidence of this complication.

Laparoscopic "double-port" splenectomy. A new minimally-invasive option in a giant spleen.

INTRODUCTION: In case of massive splenomegaly, laparoscopic splenectomy (LS) becomes challenging, uncomfortable and risky both for the surgeon and for the patient. As a consequence of ongoing research to obtain efficient and cheaper "scarless surgery", single-port technique and hand-assisted devices were developed and improved in this field. PRESENTATION OF CASE: We present the clinical case of a patient affected by idiopathic myelofibrosis (MF) and splenomegaly who was admitted to our Department to perform a splenectomy for a suspected 5-cm splenic lesion. DISCUSSION: The splenic longitudinal diameter measured 26 cm. The patient underwent splenectomy by laparoscopy, combining a single-port access and a gel-port device. The operation was completed laparoscopically. The operating time was 220 min and the estimate blood loss was 100 ml. The patient was discharged at 11 post-operative day in overall good conditions. Upon pathological analysis the splenic lesion was a localization of diffuse large B-cell Lymphoma in the context of MF. CONCLUSION: this novel "hybrid technique" of splenectomy, combining the advantages of reduced number of abdominal incisions of the single-port technique to those of the hand assistance, is feasible in massive splenomegaly with good results. Furthermore, the use of the sovrapubic retrieval incision as the introduction site for the hand assisted device is convincing, since it's useful for both tasks. Further studies with large casuistries are necessary to confirm the effectiveness of the technique.

Primary lymphoma of appendix presenting as acute appendicitis: A case report.

INTRODUCTION: Primary lymphomas of appendix are extremely rare tumors. The incidence is 0.015% of all gastrointestinal lymphomas. PRESENTATION OF CASE: We present a case of a 75 year-old male patient who presented with acute abdominal pain in the lower right quadrant and fever. DISCUSSION: The patient received laparotomic appendectomy. The definitive histopathological examination revealed the presence of diffuse large cell B-lymphoma of the appendix. The neoplasms of appendix usually manifest clinically with sign and symptoms of acute appendicitis from luminal obstruction (30-50%). Preoperative diagnosis is difficult and often occurs through histopathological examination. CONCLUSION: Primary appendiceal lymphoma is rare and there are no clear guidelines for therapy. Primary surgical resection followed by post-operative chemotherapy showed high efficacy. The histopathological examination of all appendectomy is essential.

Peritoneal carcinomatosis-like implants of extramedullary hematopoiesis. An insolite occurrence during splenectomy for myelofibrosis.

INTRODUCTION: Primary myelofibrosis (MF) is a myeloproliferative neoplasm that results in debilitating constitutional symptoms, splenomegaly, and cytopenias. In patients with symptomatic splenomegaly, splenectomy remains a viable treatment option for MF patients with medically refractory symptomatic splenomegaly that precludes the use of ruxolitinib. CASE PRESENTATION: We present the clinical case of a patient who was admitted to our Department to perform a splenectomy in MF as a therapeutic step prior to an allogeneic stem cell transplantation (ASCT). A laparotomic splenectomy and excision of whitish wide-spread peritoneal and omental nodulations was performed. There were no operative complications and the surgery was completed with minimal blood loss. The histopathological exam revealed an extramedullary hematopoiesis in both spleen and peritoneal nodules. CONCLUSION: In primary myelofibrosis it must always be kept in mind the possible presence of peritoneal implants of extramedullary hematopoiesis and ascites of reactive genesis. We report a rare case of peritoneal carcinomatosis-like implants of extramedullary hematopoiesis found at splenectomy for MF.

Splenectomy for E. coli abscess: A case report with a difficult preoperative diagnosis and unclear pathogenesis.

INTRODUCTION: Isolated splenic abscess is a rare clinical condition and remains a diagnostic dilemma. Clinical presentation is non-specific and the diagnosis is often delayed. Ultrasonography and CT scan are the gold standard. The treatment is still controversial: antibiotic therapy, percutaneous drainage (PCD) or splenectomy. CASE PRESENTATION: We present the clinical case of a patient, admitted to our Department because of abdominal pain, without fever. The preoperative radiological assesment showed three intrasplenic liquid collections, whose differential diagnosis was made between hematic collection and abscess. The treatment was splenectomy. The samples of collected liquid were positive for Escherichia Coli. CONCLUSION: In case of splenic abscess, splenectomy is the best therapeutic choice. The other therapeutical options like antibiotic therapy and PCD, can be used only in particular cases, but without the same efficacy.

Stapled Mesh Reinforcement Technique (SMART) to Prevent Parastomal Hernias: Our Initial Experience and Review of the Literature.

Parastomal hernia is one of the most common stoma related complication, with the correlated risk of incarceration, obstruction, and strangulation. The incidence is high (30-50%) and depends on the length of follow up. Different surgical options for repairing are defective with a 25-70% failure and recurrence rate. Prevention of parastomal hernia with mesh reinforcement seems to be effective. Three available trials are recruiting patients: Prism (with matrix porcine prothesis), Prevent (with preperitoneal polypropylene mesh), and the stapled polypropylene mesh stoma reinforcement technique (SMART). We performed the SMART procedure in six patients undergoing definitive colostomy. Our cases show that the procedure is rapid (duration range 15-20 minutes), cost effective (500 euro), and safe (in our experience, there are no post-surgical complications that are procedure-related). A long term follow-up and a higher number of patients will give us confirmation of the initial hopeful results.

Post-operative recurrence in Crohn's disease. Critical analysis of potential risk factors. An update.

INTRODUCTION: Crohn's disease is associated with high rates of postoperative recurrence. At 10 years after surgery a high percentage of patients suffer recurrence (as many as 75% and above) and many of these (up to 45%) require re-intervention. The aim of the study was to identify, amongst the various "potential predictive factors", those which today should be considered "real risk factors" for postoperative recurrence. METHODS: A review of literature of the last 30 years was carried out. A medical literature search was conducted using Medline, Embase, Ovid Journals, Science Direct, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews. Potential risk factors related to the patient, disease, type of surgery and pharmacological treatment were analyzed. RESULTS: According to most Authors predictive factors, in addition to smoke, are also represented by an extent of disease superior to 100 cm and by absence of postoperative pharmacological treatment. Moreover, according to "the second European evidence-based Consensus on the diagnosis and the management of Crohn's disease: Special situations", localization of disease in the colon, penetrative behavior of disease, extensive small bowel resection and prior intestinal surgery should also be considered predictive factors. CONCLUSIONS: The high incidence of postoperative recurrence in Crohn's disease mandates a strict follow up (clinical, laboratory and instrumental monitoring). Identifying patients with increased risk would enable physicians to plan a surveillance program and to implement a rational therapeutic prophylaxis.

Extra-abdominal fibromatosis: Clinical and therapeutic considerations based on an illustrative case.

Extra-abdominal fibromatosis is a rare, benign disease that is characterized by a local but not metastatic invasivity. In particular, desmoid tumors of the chest wall represent only 10-20% of all deep fibromatoses. The disease occurs more often in females and has a higher incidence between puberty and the fourth decade of life. The present study reports the case of a 34-year-old female who came to our attention due to a voluminous mass in the right subcostal region. The magnetic resonance imaging of the upper abdomen confirmed the presence of a neoplasm localized between the anterior hepatic margin and the right costal plane. Through a right subcostal laparotomy, the voluminous 95×45×94-mm neoplasm was excised. Histological examination showed evidence consistent with extra-abdominal fibromatosis. The patient has not shown recurrence of the disease for 4 years since the surgery. Overall, radical surgery with disease-free resection margins is the prime treatment option for this disease. Other therapeutic options, such as radiotherapy, hormonal therapy or treatment with imatinib mesylate, can also be considered in certain cases.

The SIC-GIRCG 2013 Consensus Conference on Gastric Cancer.

The topic chosen by the Board of the Italian Society of Surgery for the 2013 annual Consensus Conference was gastric cancer. With this purpose, under the direction of 2 chairmen, 36 experts nominated by the Regional Societies of Surgery and by the Italian Research Group for Gastric Cancer (GIRCG) participated in an experts consensus exercise, preceded by a questionnaire and mainly held by telematic vote, in accordance with the rules of the Delphi method. The results of this Consensus Conference, presented to the 115th National Congress of the Italian Society of Surgery, and approved in plenary session, are reported in the present paper.

A multidisciplinary approach to short bowel syndrome.

Short bowel syndrome is a complex clinical picture, characterized by signs and symptoms of malabsorption and subsequent malnutrition, which often occurs after extensive bowel resections. Short bowel syndrome's treatment must begin together with the planning of the first surgery, especially for disease that may need multiple interventions. Patients with short bowel should be individually managed because they all are different in diagnosis, length of the remaining bowel and in psychosocial characteristics. For all these reasons, a multidisciplinary approach between the various specialists is therefore needed.

Laparoscopic bridging vs. anatomic open reconstruction for midline abdominal hernia mesh repair [LABOR]: single-blinded, multicenter, randomized, controlled trial on long-term functional results.

BACKGROUND: Re-approximation of the rectal muscles along the midline is recommended by some groups as a rule for incisional and ventral hernia repairs. The introduction of laparoscopic repair has generated a debate because it is not aimed at restoring abdominal wall integrity but instead aims just to bridge the defect. Whether restoration of the abdominal integrity has a real impact on patient mobility is questionable, and the available literature provides no definitive answer. The present study aims to compare the functional results of laparoscopic bridging with those of re-approximation of the rectal muscle in the midline as a mesh repair for ventral and incisional abdominal defect through an "open" access. We hypothesized that, for the type of defect suitable for a laparoscopic bridging, the effect of an anatomical reconstruction is near negligible, thus not a fixed rule. METHODS AND DESIGN: The LABOR trial is a multicenter, prospective, two-arm, single-blinded, randomized trial. Patients of more than 60 years of age with a defect of less than 10 cm at its greatest diameter will be randomly submitted to open Rives or laparoscopic defect repair. All the participating patients will have a preoperative evaluation of their abdominal wall strength and mobility along with volumetry, respiratory function test, intraabdominal pressure and quality of life assessment.The primary outcome will be the difference in abdominal wall strength as measured by a double leg-lowering test performed at 12 months postoperatively. The secondary outcomes will be the rate of recurrence and changes in baseline abdominal mobility, respiratory function tests, intraabdominal pressure, CT volumetry and quality of life at 6 and 12 months postoperatively. DISCUSSION: The study will help to define the most suitable treatment for small-medium incisional and primary hernias in patients older than 60 years. Given a similar mid-term recurrence rate in both groups, if the trial shows no differences among treatments (acceptance of the null-hypothesis), then the choice of whether to submit a patient to one intervention will be made on the basis of cost and the surgeon's experience. TRIAL REGISTRATION: Current Controlled Trials ISRCTN93729016.