Dario Maggioni

“High or low Inferior Mesenteric Artery ligation in Laparoscopic low Anterior Resection: study protocol for a randomized controlled trial” (HIGHLOW trial)

BackgroundThe position of arterial ligation during laparoscopic anterior rectal resection with total mesorectal excision can affect genito-urinary function, bowel function, oncological outcomes, and the incidence of anastomotic leakage. Ligation to the inferior mesenteric artery at the origin or preservation of the left colic artery are both widely performed in rectal surgery. The aim of this study is to compare the incidence of genito-urinary dysfunction, anastomotic leak and oncological outcomes in laparoscopic anterior rectal resection with total mesorectal excision with high or low ligation of the inferior mesenteric artery in a controlled randomized trial.Methods/designThe HIGHLOW study is a multicenter randomized controlled trial in which patients are randomly assigned to high or low inferior mesenteric artery ligation during laparoscopic anterior rectal resection with total mesorectal excision for rectal cancer. Inclusion criteria are middle or low rectal cancer (0 to 12 cm from the anal verge), an American Society of Anesthesiologists score of I, II, or III, and a body mass index lower than 30. The primary end-point measure is the incidence of post-operative genito-urinary dysfunction. The secondary end-point measure is the incidence of anastomotic leakage in the two groups. A total of 200 patients (100 per arm) will reliably have 84.45 power in estimating a 20% difference in the incidence of genito-urinary dysfunctions. With a group size of 100 patients per arm it is possible to find a significant difference (α = 0.05, β = 0.1555). Allowing for an estimated dropout rate of 5%, the required sample size is 212 patients.DiscussionThe HIGHLOW trial is a randomized multicenter controlled trial that will provide evidence on the merits of the level of arterial ligation during laparoscopic anterior rectal resection with total mesorectal excision in terms of better preserved post-operative genito-urinary function.Trial registrationClinicalTrials.gov Identifier: NCT02153801Protocol Registration Receipt 29/5/2014.

ERAS Protocol Reduces IL-6 Secretion in Colorectal Laparoscopic Surgery: Results From a Randomized Clinical Trial.

Background: Enhanced Recovery After Surgery (ERAS) program applied to colorectal laparoscopic surgery is well known to reduce hospitalization improving short-terms outcomes. Its goal is to minimize the surgical stress response in order to maintain the physiological homeostasis altered by surgery. However, there is little knowledge about the involved dynamics in the reduction of the surgical stress that these programs allow. The primary aim of this study was to compare the level of immune and nutritional serum investigators across surgery in patients undergoing elective colorectal laparoscopic surgery within an ERAS protocol or according to a standard care program. Materials and Methods: One hundred forty patients undergoing major colorectal laparoscopic surgery were enrolled and randomized in 2 groups (70 per arm). Cortisol, C-reactive protein (CRP), white blood cell count, prolactin, interleukin (IL)-6 levels were collected preoperatively, 1, 3, and 5 days after surgery. Transferrin, prealbumin, albumin, and triglyceride level were collected preoperatively, 1 and 5 days after surgery. Short-term outcomes were also prospectively assessed. Results: IL-6 levels were lower in the ERAS group on 1, 3, and 5 days postoperatively (P<0.05). IL-6 levels in the enhanced group, differently from control group, returned to preoperative level 3 days after surgery. CRP level was lower in the enhanced group on day 1, 3, and 5 (P<0.05). There was no difference in cortisol and prolactin levels between groups. Prealbumin serum level was higher on day 5 (P<0.05) compared to standard group. Conclusions: ERAS protocol applied to colorectal laparoscopic surgery affects surgical stress response, decreasing IL-6 and CRP levels postoperatively and improving prealbumin postoperative synthesis.

Small Bowel Perforation Caused by Pancreaticojejunal Anastomotic Stent Migration after Pancreaticoduodenectomy for Periampullary Carcinoma

CONTEXT Pancreaticoduodenectomy is the gold standard for patients with resectable periampullary carcinoma. The protection of the anastomosis by positioning of an intraluminal stent is a technique used to lower the frequency of anastomotic fistulas. However the use of anastomotic stents is still debated and stent related complications are reported. CASE REPORT A fifty-three-year old male underwent pancreaticoduodenectomy (PD) for a T2N0 periampullary carcinoma with a pancreaticojejunal (duct to mucosa) anastomosis protected by a free floating 6 Fr Nelaton stent in the Wirsung duct. Twenty-three months after surgery the patient accessed Emergency Department for severe abdominal pain associated to temperature, high white blood cell count and an significant increase in C reactive protein. Method Abdominal CT scan shown the presence of a tubular stent in the mesogastrium/lower right quadrant. No evident free intra-abdominal air was detected. The patient was submitted to explorative laparotomy. After debridement for localized peritonitis the Nelaton trans anastomotic stent was found in the abdomen. There was no evidence of bowel perforation, but intestinal loops covered with fibrin and suspect for impending perforation were resected. CONCLUSION There is a lack of evidence about the true rate of post-operative complications related to pancreatic stenting. We believe that in patients presenting with abdominal pain or peritonitis that previously underwent PD with stent-guided pancreaticojejunal anastomosis, the hypothesis of stent migration should at least be taken into consideration.

Laparoscopic Left Hemicolectomy for Colon Cancer in Peritoneal Dialysis Patients: A Valid and Safe Surgical Technique to Ensure Peritoneal Dialysis Survival

A laparoscopic approach represents an effective alternative to open surgery in patients undergoing peritoneal dialysis (PD). In these patients, conventional thinking provides for removal of the peritoneal catheter during left colon resections because of higher risk of patient contamination and peritonitis. The present paper describes 3 cases of laparoscopic left hemicolectomy for colon cancer performed in PD patients without complications and without peritoneal catheter removal, leading to subsequent early PD resumption. Three normotype PD patients affected by early-stage sigmoid colon adenocarcinoma (T1-T2, M0, N0) underwent integrated surgical and nephrological management to reduce peritoneum stress, infective risk and postoperative complications. The day before surgery, patients were shifted to isovolumetric hemodialysis through tunneled central venous catheter. All patients underwent laparoscopic left hemicolectomy without Tenckhoff catheter removal. The postoperative period was uneventful, with concomitant antibiotic prophylaxis until the fifth day after surgery. Flushing of the PD catheter was performed twice a week postoperatively. Peritoneal dialysis was recovered 4 weeks after surgery in 2 cases with a well-maintained dialytic adequacy. One patient did not proceed to PD due to improvement of renal function after surgery. In selected PD patients, a minimally invasive surgical approach combined with careful nephrological management may represent a valid and safe strategy to treat early-stage colon cancer, avoiding PD drop-out.

(Therapy-related?) large bowel acute ischemia in thalidomide-treated patient

Dear Editor: Thalidomide is used in the treatment of haematologic disorders such as multiple myeloma and primary myelofibrosis (PM) for its anti-angiogenic activity and modulation of cytokines such as TNF alpha. From 2000 to 2002, some studies were published in which patients treated with high doses of thalidomide (100 mg/day) had a significant improvement in splenomegaly, anemia and thrombocytopenia. However, at high doses of medicine, important adverse events happened that led to the discontinuation of therapy in more than 50% of cases in just 3 months. In 2003, Mesa et al. proposed the combination of low doses of thalidomide (50 mg/day) with prednisone. Actually this combination leads to a more lasting clinical and molecular response. However, the association between drug treatments with anti-angiogenic properties and the onset of thrombotic events is well known in literature. Among the medications mentioned, thalidomide has been repeatedly described in relation to these events, whether venous or arterious. Clark et al. have collected a series of 27 thrombotic–embolic events (particularly deep venous thrombosis and pulmonary embolism). Deep venous thrombosis is usually observed when the drug is administered in combination with dexamethasone, doxorubicin or melphalan in patients not previously treated. Therefore, in cases of treatment with thalidomide, an appropriate screening for risk of thromboembolism and prophylactic anticoagulant therapy are mandatory and appropriate. In this regard, we point to your attention a dramatic example which occurred recently in our institute. A 79-year-old woman was known since 1993 for chronic myeloproliferative neoplasm (PM) who was initially treated with oncocarbide. Since 2008, the patient required transfusion for pancytopenia with progressive splenomegaly in the absence of leakage from the gastrointestinal tract (in particular platelets count was always <40,000/dl). It was therefore proposed in the month of October, 2010, treatment with thalidomide (50 mg/day) combined with low doses of prednisone (12.5 mg/day) and prophylaxis with warfarin (PT-INR target treatment was <1.5). The patient had no previous history of venous thrombosis, and we verified no significant congenital or acquired abnormalities associated with thrombosis such as protein C, protein S, antithrombin III and thrombomodulin. After 40 days of initiation of therapy, the patient came under observation for an “acute abdomen”. Colonscopy and total body computed tomography (CT) were performed. Colonoscopy in the right colon wall showed the presence of a large, haemorrhagic, partially necrotic, 10-cm diameter lesion. CT at the same site documented a significant thickening of the wall and suffering attributable to ischemic oedema. It was also incidentally revealed the presence of pathologic tissue in the paravertebral region (posterior mediastinum and retroperitoneum) with densitometric Dr. Pagni and Dr. Moltrasio equally contributed to the management of the paper. F. Pagni (*) : F. Moltrasio :C. Di Bella :B. E. Leone Department of Pathology, Desio Hospital, Desio, Italy e-mail: petala.83@tiscali.it

Surgical Stress Response and Enhanced Recovery after Laparoscopic Surgery - A systematic review

Background: Enhanced Recovery Program (ERP) is a multimodal perioperative protocol. Its feasibility and benefits on short term outcomes have been widely reported. These well described improvements, like shorter length of stay and early resumption of bodys functions, represent the consequence of an attenuated surgical stress response (SSR). When this response is uncontrolled, it leads to postoperative complications and poor long-term outcomes. SSR can be easily monitored through the analyses of mediators in the bloodstream. Available evidences do not achieve to tell if ERP allows a measurable surgical stress reduction. In this review, we searched for papers investigating the surgical stress response and ERP applied to elective mini-invasive procedures, in order to better understand the level of evidence regarding the effectiveness of ERP in minimizing the surgical stress response. Materials and Methods: A systematic review of published literature was performed using PubMed, Cochrane, EMBASE and Google Scholar database, following the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Included studies concerned SSR analysis in ERP patients undergoing laparoscopic surgery through different surgical specialties. Eight studies with a total of 632 patients were included. Results: The three steps of SSR, endocrine, inflammatory and nutritional were all reported in the papers included in this review. Results showed no powerful evidence of difference in endocrine phase while an attenuated inflammatory response was reported for ERP patients when Interleukin-6 (IL-6) and C Reactive Protein (CRP) were dosed. Nutritional status was also preserved as albumin, pre-albumin and transferrin had better values in these patients. Conclusions: ERP applied to different types of laparoscopic surgery has a role in reducing SSR. This can be shown by the analysis of mediators such as IL-6, CRP and nutritional markers.

Laparoscopic Surgery in Patients on Peritoneal Dialysis: A Review of the Literature:

Peritoneal dialysis (PD) is an effective renal replacement therapy for the treatment of end-stage renal disease. Patients on PD undergoing abdominal open surgery often fail to resume PD. Laparoscopic surgery has recently become a serious alternative to open surgery in patients on PD to treat different abdominal pathologies. However, only a few studies have reported successful procedures without Tenckhoff catheter removal. The aim of this review is to describe how a laparoscopic technique can allow PD patients to deal with abdominal surgery without shifting to hemodialysis. Only 50 cases of laparoscopic surgical intervention in PD patients have been published to our knowledge. These case series largely concern laparoscopic cholecystectomies, appendectomies, nephrectomies, colectomies, and bariatric procedures. The reported cases show how laparoscopic surgery can be accepted as a valid option for several abdominal surgical procedures in patients on PD with good outcomes and early resumption of PD.

Tumor response evaluation after neoadjuvant chemotherapy in locally advanced gastric adenocarcinoma: a prospective, multi-center cohort study

Background To verify the prognostic value of the pathologic and radiological tumor response after neoadjuvant chemotherapy in the treatment of locally advanced gastric adenocarcinoma. Methods A total of 67 patients with locally advanced gastric cancer (clinical ≥ T2 or nodal disease and without evidence of distant metastases) underwent perioperative chemotherapy (ECF or ECX regimen) from December 2009 through June 2015 in two surgical units. Histopathological and radiological response to chemotherapy were evaluated by using tumor regression grade (TRG) (Beckers criteria) and volume change assessed by CT. Results Fifty-one (86%) patients completed all chemotherapy scheduled cycles successfully and surgery was curative (R0) in 64 (97%) subjects. The histopathological analysis showed 19 (29%) specimens with TRG1 (less than 10% of vital tumor left) and 25 (37%) patients had partial or complete response (CR) assessed by CT scan. Median disease free survival (DFS) and overall survival (OS) were 25.70 months (range, 14.52-36.80 months) and 36.60 months (range, 24.3-52.9 months), respectively. The median follow up was 27 months (range, 5.00-68.00 months). Radiological response and TRG were found to be a prognostic factor for OS and DFS, while tumor histology was not significantly related to survival. Conclusions Both radiological response and TRG have been shown as promising survival markers in patients treated with perioperative chemotherapy for locally advanced gastric cancer. Other predictive markers of response to chemotherapy are strongly required.

Genito-Urinary Function and Quality of Life after Elective Totally Laparoscopic Sigmoidectomy after at Least One Episode of Complicated Diverticular Disease According to Two Different Vascular Approaches: the IMA Low Ligation or the IMA Preservation.

The arterial ligation during elective laparoscopic sigmoidectomy for diverticular disease can affect genito-urinary function injuring the superior hypogastric plexus, and can weaken the distal colonic stump arterial perfusion. Ligation of the inferior mesenteric artery distal to the left colic artery or the complete preservation of the inferior mesenteric artery can therefore be compared in terms of preservation of the descending sympathetic fibres running along the aorta to the rectum resulting in a different post operative genito urinary function. From January 2015 to March 2016, 66 patients underwent elective laparoscopic sigmoidectomy for diverticular disease among two enrolling hospitals. In one centre 35 patients underwent laparoscopic sigmoidectomy with the ligation of the inferior mesenteric artery distal to the left colic artery (low ligation). In the other centre 31 patient were operated on the same procedure with complete inferior mesenteric artery preservation (IMA preservation). There was no difference in terms of major complication occurred, first passage of stool and length of hospital stay between the two groups. Time of surgery was significantly shorter in LL group compared to IMA preserving group and intra operative blood loss was significantly lower in the LL group. There were no differences in the genito urinary function between the two group pre operatively, at 1 and 9 months post operatively. Genito urinary function did not significantly change across surgery in each groups. The low ligation and the IMA preserving vascular approach are safe end feasible techniques in elective laparoscopic sigmoidectomy for diverticular disease. They both prevent from genito-urinary post-operative disfunction and allow good post operative quality of life. The low ligation approach is related to shorter operative time and slower intra operative blood loss.

An Entirely Echo-Guided Technique for Totally Implantable Access Port Positioning

Percutaneous central vascular venous access to allow positioning of a totally implantable access port (TIAP) is a widely employed procedure. An open issue is the need to find an ionizing radiation free technique which allows a safe and correct positioning of the device. Echo-guided vein puncture is currently accepted as the best method for decreasing major immediate complications. We describe an entirely echo-based method for the insertion and assessment of correct placement of the totally implantable access ports (TIAP). 20 TIAPs with the described technique have been placed. TIAP can be safely positioned by entirely echo-guided technique avoiding ionizing radiation imaging.