PI3K-driven HER2 expression is a potential therapeutic target in colorectal cancer stem cells.

OBJECTIVE: Cancer stem cells are responsible for tumour spreading and relapse. Human epidermal growth factor receptor 2 (HER2) expression is a negative prognostic factor in colorectal cancer (CRC) and a potential target in tumours carrying the gene amplification. Our aim was to define the expression of HER2 in colorectal cancer stem cells (CR-CSCs) and its possible role as therapeutic target in CRC resistant to anti- epidermal growth factor receptor (EGFR) therapy. DESIGN: A collection of primary sphere cell cultures obtained from 60 CRC specimens was used to generate CR-CSC mouse avatars to preclinically validate therapeutic options. We also made use of the ChIP-seq analysis for transcriptional evaluation of HER2 activation and global RNA-seq to identify the mechanisms underlying therapy resistance. RESULTS: Here we show that in CD44v6-positive CR-CSCs, high HER2 expression levels are associated with an activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, which promotes the acetylation at the regulatory elements of the Erbb2 gene. HER2 targeting in combination with phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MEK) inhibitors induces CR-CSC death and regression of tumour xenografts, including those carrying Kras and Pik3ca mutation. Requirement for the triple targeting is due to the presence of cancer-associated fibroblasts, which release cytokines able to confer CR-CSC resistance to PI3K/AKT inhibitors. In contrast, targeting of PI3K/AKT as monotherapy is sufficient to kill liver-disseminating CR-CSCs in a model of adjuvant therapy. CONCLUSIONS: While PI3K targeting kills liver-colonising CR-CSCs, the concomitant inhibition of PI3K, HER2 and MEK is required to induce regression of tumours resistant to anti-EGFR therapies. These data may provide a rationale for designing clinical trials in the adjuvant and metastatic setting.

Comparative Study of the Initial Experience in Performing Robotic and Laparoscopic Right Hepatectomy with Technical Description of the Robotic Technique.

BACKGROUND: Despite potential benefits of robotic liver surgery, it is still considered a "development in progress" technique. METHODS: The outcomes of 14 patients undergoing robotic right hepatectomy were analyzed and compared with the results of 20 laparoscopic right hepatectomies consecutively performed by the same young surgeon. RESULTS: The overall mean operative time was less in robotic arm (425 ± 139 vs. 565.18 ± 183.73, p = 0.022) and the estimated blood loss was similar (335.15 ± 139.8 vs. 423.95 ± 205.15, p = 0.17); no blood transfusion was required. Two patients in robotic group and 5 in laparoscopic group (p = 0.454) underwent conversion to open surgery; the overall morbidity was 21.4 and 15% in studied arms, respectively (p = 0.634). Pathology reports showed a mean surgical margin of 26.02 ± 3.9 in robotic arm, 28.76 ± 4.6 for laparoscopic, (p = 0.079) and we achieved a R0 resection rate of 91.66 and 85%, respectively. Reoperation and 90-days mortality rate were both null in robotic arm. One patient in laparoscopic group was reoperated due to postoperative hemorrhage. One-year overall and disease free-survival rate were 92.3 and 84.6%, respectively in robotic arm and 90 and 85% in laparoscopic arm. CONCLUSIONS: Robotic right hepatectomy is a safe and feasible technique providing promising short-term outcomes and oncological results also in the initial phase of learning curve.

Minimally Invasive Video-Assisted Thyroidectomy: Analysis of Complications From a Systematic Review.

BACKGROUND: Nowadays, minimally invasive video-assisted thyroidectomy (MIVAT) is considered a safe and effective option. However, its complication rate has not been specifically discussed yet. The aim of this systematic review was enrolling a large number of studies to estimate early and late complications (transient and definitive, uni- and bilateral laryngeal nerve palsy; transient and definitive hypocalcemia; cervical hematoma; hypertrophic or keloid scar) of MIVAT compared with conventional technique. METHODS: The review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria in PubMed and Embase. Search terms were "minimally invasive," "video-assisted," and "thyroidectomy." We enrolled randomized clinical trials, nonrandomized trials, and noncontrolled trials. RESULTS: Thirty-two articles were considered suitable. Complication rate of MIVAT was quite similar to conventional technique: only one randomized trial found a significant difference concerning overall skin complication, and a single trial highlighted hypocalcemia significantly increased in MIVAT, concerning serologic value only. No difference concerning symptomatic nor definitive hypocalcemia was found. CONCLUSIONS: We can confirm that MIVAT is a safe technique. It should be adopted in mean-high-volume surgery centers for thyroidectomy, if a strict compliance with indication was applied.

Robotic pancreatic surgery: old concerns, new perspectives.

BACKGROUND: Described for the first time in 2003, the robotic pancreatic surgery shows interesting results. The evaluation of post-operative outcomes is necessary once we describe an innovative surgical approach. METHODS: We have performed a retrospective analysis of a prospectively maintained database on robotic pancreatic surgery including malignant and benign indications for surgery. RESULTS: A total of 50 consecutive patients underwent robotic pancreatic surgery (26 pancreatico duodenectomy and 24 distal pancreatectomy) between January 2012 and July 2015 in a single centre. The overall operative time was 425 (390-620) min. In a subgroup of highly selected malignant tumours, we were able to achieve 88% of R0 resection with robotic approach. A number of lymphnodes rose significantly with growing experience (p = .025). The overall major complication rate (15%), as well as pancreatic fistula rate (16%) were acceptable. The two-year overall survival for the whole group was 65%. CONCLUSION: The robotic pancreatic surgery in a highly selected group of patients seems safe and feasible. The cost-effectiveness and long-term oncologic outcomes need further investigations.

Bactibilia in diseases of the biliary tract and pancreatic gland in patients older than 80 years: a STROBE-retrospective cohort study in a teaching hospital in Italy.

Bile is a lipid-rich sterile solution produced in the liver that can be infected resulting in bactibilia. A higher incidence of postoperative infectious complications has been seen in patients with bactibilia. Recently, gram-negative bacteria have been linked to a tumor-associated inflammatory status. This study is a retrospective cohort study of 39 patients, who are over 80 years of age only (53.85% males and 46.15% females), hospitalized with diseases of the biliopancreatic system in one teaching hospital in Italy from January 2011 to December 2012 with a follow-up of 5 years. The most common biliary diseases after surgery were pancreatic head cancer (p < 0.0001) and gallbladder cancer (p = 0.0051), while the most common bacteria in the bile were E. coli (p = 0.0180) and Pseudomonas spp. (p < 0.0001). Uni- and multivariate linear correlation analysis revealed that patients with pancreatic head cancer had low survival times compared to patients with other diseases. Moreover, the bacterium type was a positive predictor of survival time compared to other variables. Our data confirm E. coli as a pathogen in patients with gallbladder and pancreatic cancer. Although the influence of bactibilia in developing surgical complications is limited, we consider that its composition is crucial to properly address the antibiotic treatment in biliary tract infections, especially in the elderly.

Vacuum-Assisted Wound Closure with Mesh-Mediated Fascial Traction Achieves Better Outcomes than Vacuum-Assisted Wound Closure Alone: A Comparative Study.

BACKGROUND: Open abdomen (OA) permits the application of damage control surgery principles when abdominal trauma, sepsis, severe acute peritonitis and abdominal compartmental syndrome (ACS) occur. METHODS: Non-traumatic patients treated with OA between January 2010 and December 2015 were identified in a prospective database, and the data collected were retrospectively reviewed. Patients' records were collected from charts and the surgical and intensive care unit (ICU) registries. The Acosta "modified" technique was used to achieve fascial closure in vacuum-assisted wound closure and mesh-mediated fascial traction (VAWCM) patients. Sex, age, simplified acute physiology score II (SAPS II), abdominal compartmental syndrome (ACS), cardiovascular disease (CVD) and surgical technique performed were evaluated in a multivariate analysis for mortality and fascial closure prediction. RESULTS: Ninety-six patients with a median age of 69 (40-78) years were included in the study. Sixty-nine patients (72%) underwent VAWCM. Forty-one patients (68%) achieved primary fascia closure: two patients (5%) were treated with VAWC (37 median days) versus 39 patients (95%) who were treated with VAWCM (10 median days) (p = 0.0003). Forty-eight patients underwent OA treatment due to ACS, and 24 patients (50%) survived compared to 36 patients (75%) from the "other reasons" group (p = 0.01). The ACS group required longer mechanical ventilator support (p = 0.006), length of stay in hospital (p = 0.005) and in ICU (p = 0.04) and had higher SAPS II scores (p = 0.0002). CONCLUSIONS: The survival rate was 62%. ACS (p = 0.01), SAPS II (p = 0.004), sex (p = 0.01), pre-existing CVD (p = 0.0007) and surgical technique (VAWC vs VAWCM) (p = 0.0009) were determined to be predictors of mortality. Primary fascial closure was obtained in 68% of cases. VAWCM was found to grant higher survival and primary fascial closure rate.

Correction to: Vacuum-Assisted Wound Closure with Mesh-Mediated Fascial Traction Achieves Better Outcomes than Vacuum-Assisted Wound Closure Alone: A Comparative Study.

In the original article the credit line for the reuse of Fig. 1 from an article published in the open access journal, World Journal of Emergency Surgery is missing.

From Illusion to Reality: A Brief History of Robotic Surgery.

PURPOSE: Robotic surgery is currently employed for many surgical procedures, yielding interesting results. METHODS: We performed an historical review of robots and robotic surgery evaluating some critical phases of its evolution, analyzing its impact on our life and the steps completed that gave the robotics its current popularity. RESULTS: The origins of robotics can be traced back to Greek mythology. Different aspects of robotics have been explored by some of the greatest inventors like Leonardo da Vinci, Pierre Jaquet-Droz, and Wolfgang Von-Kempelen. Advances in many fields of science made possible the development of advanced surgical robots. Over 3000 da Vinci robotic platforms are installed worldwide, and more than 200 000 robotic procedures are performed every year. CONCLUSION: Despite some potential adverse events, robotic technology seems safe and feasible. It is strictly linked to our life, leading surgeons to a new concept of surgery and training.

Pulmonary Laser Metastasectomy by 1318-nm Neodymium-Doped Yttrium-Aluminum Garnet Laser: A Retrospective Study About Laser Metastasectomy of the Lung.

BACKGROUND: The lungs are among the first organ affected by remote metastases from many primary tumors. The surgical resection of isolated pulmonary metastases represents an important and effective element of therapy. This is a retrospective study about our entire experience with pulmonary resection for metastatic cancer using 1318-nm neodymium-doped yttrium-aluminum garnet laser. METHOD: In this single-institution study, we retrospectively analyzed a group of 209 patients previously treated for primary malignant solid tumors. We excluded 103 patients. The number and location of lesions in the lungs was determined using chest computed tomography and positron emission tomography-computed tomography. Disseminated malignancy was excluded. All pulmonary laser resections are performed via an anteroaxillary muscle-sparing thoracotomy. All lesions were routinely removed by laser with a small (5-10 mm) margin of the healthy lung. Patients received systematic lymph node sampling with intraoperative smear cytology of sampled lymph nodes. RESULTS: Mortality at 2 years from the first surgery is around 20% (10% annually). This value increases to 45% in the third year. The estimated median survival for patients who underwent the first surgery is reported to be approximately 42 months. CONCLUSION: Our results show that laser resection of lung metastases can achieve good result, in terms of radical resection and survival, as conventional surgical metastasectomy. The great advantage is the possibility of limiting the damage to the lung. Stapler resection of a high number of metastases would mutilate the lung.

Arterial stiffness, endothelial and cognitive function in subjects with type 2 diabetes in accordance with absence or presence of diabetic foot syndrome.

BACKGROUND: Endothelial dysfunction is an early marker of cardiovascular disease so endothelial and arterial stiffness indexes are good indicators of vascular health. We aimed to assess whether the presence of diabetic foot is associated with arterial stiffness and endothelial function impairment. METHODS: We studied 50 subjects with type 2 diabetes mellitus and diabetic foot syndrome (DFS) compared to 50 diabetic subjects without diabetic foot, and 53 patients without diabetes mellitus, by means of the mini mental state examination (MMSE) administered to evaluate cognitive performance. Carotid-femoral pulse wave velocity (PWV) and augmentation index (Aix) were also evaluated by Applanation tonometry (SphygmoCor version 7.1), and the RH-PAT data were digitally analyzed online by Endo-PAT2000 using reactive hyperemia index (RHI) values. RESULTS: In comparison to diabetic subjects without diabetic foot the subjects with diabetic foot had higher mean values of PWV, lower mean values of RHI, and lower mean MMSE. At multinomial logistic regression PWV and RHI were significantly associated with diabetic foot presence, whereas ROC curve analysis had good sensitivity and specificity in arterial PWV and RHI for diabetic foot presence. CONCLUSIONS: Pulse wave velocity and augmentation index, mean RHI values, and mean MMSE were effective indicators of diabetic foot. Future research could address these issues by means of longitudinal studies to evaluate cardiovascular event incidence in relation to arterial stiffness, endothelial and cognitive markers.

The prevalence of post-thyroidectomy chronic asthenia: a prospective cohort study.

PURPOSE: Chronic asthenia (CA) is complained by some patients that have undergone thyroid surgery. We evaluate its impact in patients undergoing unilateral or bilateral thyroidectomy, the trend during a 1-year follow-up, and the possible risk factors. METHODS: A prospective, cohort study was carried out on 263 patients scheduled for thyroidectomy from 2012 and 2014. Exclusion criteria were as follows: Graves' disease, malignancies requiring radioiodine therapy, post-surgical hypoparathyroidism, laryngeal nerve palsy, abnormal pre- and post-operative thyroid hormone levels, and BMI outside the normal range. Demographics; smoking and alcoholism addiction; cardiac, pulmonary, renal, and hepatic failure; diabetes; anxiety; and depression were recorded. The Brief Fatigue Inventory (BFI) was used to evaluate CA and its possible association with these comorbidities 6 and 12 months after thyroidectomy. RESULTS: One hundred seventy-seven patients underwent total thyroidectomy (TT), 54 hemithyroidectomy (HT). Thirty-two patients were not recorded because of the onset of exclusion criteria. In the 6 months after thyroidectomy, in the TT group, 64 patients (36.16%) reported an impairment in the BFI score and only 1 in the TL group. The mean BFI score changed from 1.663(±1.191) to 2.16 (±11.148) in the TT group, from 1.584 (±1.371) to 1.171 (±1.093) in the TL group (p < 0.001). No further significant variations in BFI were reported 1 year after surgery. CONCLUSIONS: CA worsened after TT, but not after HT. Apart from operative procedure itself, no other risk factor was found be significantly associated with post-thyroidectomy asthenia. Further investigation is needed to determine the causes of CA.

"Relaparoscopic" management of surgical complications: The experience of an Emergency Center.

BACKGROUND/AIM: Laparotomy has been the approach of choice for re-operations in patients with surgical complications. The aim of this retrospective analysis was to evaluate the feasibility and the safety of laparoscopic approach for the management of general abdominal surgery complications. MATERIALS AND METHODS: We report a retrospective review of 75 patients who underwent laparoscopic evaluation for postoperative complications over a 4-year period. Primary outcomes (resolution rate by exclusive laparoscopic approach, conversion rate, further surgery rate) and secondary outcomes (mortality, hospitalization, prolonged ileus, wounds problems and median operative time) were evaluated. RESULTS: Sixty-six patients (88 %) were managed with laparoscopic approach without conversion; of these, sixty-three patients (84 %) had no more or further complications and were discharged from hospital between 4 ± 3 days after "second-look" surgery; three patients (4 %) developed postoperative complications requiring a third surgery. Nine cases (12 %) underwent conversion in open surgery after laparoscopic approach. Two elderly patients (2.7 %) died in intensive care unit, because of multi-organ failure syndrome. Median time elapsed between an intervention and another was about 2.5 ± 9.5 days. Mean operative time was 90 ± 150 min. Postoperative hospital stay was between 4.5 and 18 days. DISCUSSION AND CONCLUSION: Laparoscopy has begun to be the preferred method to manage postoperative problems, but only few reports are available actually. Our experience in "relaparoscopic" management of surgical complications seems to suggest that laparoscopy "second look" is an effective tool after open or laparoscopic surgery for the management of postoperative complications and it may avoid diagnostic delay and further laparotomy and related problems.

A Gelatin-Thrombin Matrix Topical Hemostatic Agent (Floseal) in Combination With Harmonic Scalpel Is Effective in Patients Undergoing Total Thyroidectomy: A Prospective, Multicenter, Single-Blind, Randomized Controlled Trial.

BACKGROUND: Hemostasis during thyroidectomy is essential; however, the safest, most efficient, and most cost-effective way to achieve this is unclear. This randomized, multicenter, single-blind, prospective study evaluated the efficacy and safety of using different hemostatic approaches in patients undergoing total thyroidectomy. METHODS: Patients aged ≥18 to 70 years were randomized to Floseal + a harmonic scalpel (HS), Floseal alone, HS alone, or standard total thyroidectomy. Primary endpoint was 24-hour drain output. Secondary endpoints included surgery duration and complications. RESULTS: Two hundred and six patients were randomized to Floseal + HS (n = 52), Floseal alone (n = 54), HS alone (n = 50), and standard total thyroidectomy (n = 50). The 24-hour drain output was lower in the Floseal + HS group compared with standard thyroidectomy. Floseal + HS also had a shorter surgery time (P < .0001) versus the other 3 treatments. CONCLUSION: Floseal + HS can be effective at reducing postsurgical drain output and provides a complementary hemostatic approach in patients undergoing total thyroidectomy.

Technical characteristics can make the difference in a surgical linear stapler. Or not?

BACKGROUND: Anastomotic leak (AL) after gastrointestinal surgery is a severe complication associated with relevant short- and long-term sequelae. Most of the anastomosis are currently performed with a surgical stapler that is required to have appropriate characteristics to guarantee good performances. The aim of our study was to evaluate, in the laboratory, pressure resistance and tensile strength of anastomosis performed with different surgical linear staplers, available in the market. MATERIALS AND METHODS: We have been studying three linear staplers, with diverse cartridges and staple heights, of three different companies, used for gastrointestinal anastomosis and gastric or intestinal closure. We performed 50 anastomosis for each device, with the pertinent different cartridges, on fresh pig intestine, for a total of 350 anastomosis, then injected saline solution and recorded the pressure that provokes a leak on the staple line. There were no statistically significant differences between the mean pressure necessary to induce an AL in the various instruments (P > 0.05). For studying the tensile strength, we performed a total of 350 anastomosis with the different linear staplers on a special strong paper (Tyvek), then recorded the maximal tensile force that could open the anastomosis. RESULTS: There were no statistically significant differences between the different staplers about the strength necessary to open the staple line (P > 0.05). CONCLUSIONS: we demonstrated that different linear staplers of three companies available in the market give comparable anastomotic pressure resistance and tensile strength. This might suggest that small dissimilarities between different devices are not involved, at least as major parameters, in AL etiology.

Biologic response of inguinal hernia prosthetics: a comparative study of conventional static meshes versus 3D dynamic implants.

Despite improvements in prosthetics and surgical techniques, the rate of complications following inguinal hernia repair remains high. Among these, discomfort and chronic pain have become a source of increasing concern among surgeons. Poor quality of tissue ingrowth, such as thin scar plates or shrinking scars-typical results with conventional static implants and plugs-may contribute to these adverse events. Recently, a new type of 3D dynamically responsive implant was introduced to the market. This device, designed to be placed fixation-free, seems to induce ingrowth of viable and structured tissue instead of regressive fibrotic scarring. To elucidate the differences in biologic response between the conventional static meshes and this 3D dynamically responsive implant, a histological comparison was planned. The aim of this study was to determine the quality of tissue incorporation in both types of implants excised after short, medium, and long periods post-implantation. The results showed large differences in the biologic responses between the two implant types. Histologically, the 3D dynamic implant showed development of tissue elements more similar to natural abdominal wall structures, such as the ingrowth of loose and well-hydrated connective tissue, well-formed vascular structures, elastic fibers, and mature nerves, with negligible or absent inflammatory response. All these characteristics were completely absent in the conventional static implants, where a persistent inflammatory reaction was associated with thin, hardened, and shrunken fibrotic scar formation. Consequently, as herniation is a degenerative process, the 3D dynamic implants, which induce regeneration of the typical groin components, seem to address its pathogenesis.

Dynamic inguinal hernia repair with a 3d fixation-free and motion-compliant implant: a clinical study.

Static solutions for highly motile structures such as the groin seem to represent a procedural incongruence. Another important issue in prosthetic hernia repair is related to the poor quality of tissue ingrowth within conventional flat meshes and plugs. These are all static, passive devices, and thus do not move in synchrony with the natural movements of the groin. In the literature there is a clear understanding of how conventional prostheses used for inguinal hernia repair are incorporated by rigid fibrotic tissue. The term "scar plate" well emphasizes this occurrence. The ingrowth of this kind of stiff fibrotic scar leads to mesh shrinkage and to the reduction of the mesh surface area. This is considered a significant cause of recurrence and discomfort. With this in mind, the need for a more physiologic procedure to further decrease complications and recurrences in inguinal hernia repair due to implant design seems obvious. This report shows how, by eliminating invasive fixation and improving the quality of tissue ingrowth within the implant, it is possible to reduce complications. To achieve these results, a new type of 3D dynamic (inherent recoil), self-retaining implant has been developed. This newly designed implant was previously implanted in the porcine model, showing excellent outcomes. Of note were the quality of tissue ingrowth and the near absence of shrinkage, even a long time after implantation. The present study describes the outcome of this device used in open inguinal hernia repair in 91 patients having direct and indirect inguinal hernia. In this patient cohort, evaluations were made for; operation length, intraoperative complications, late complications such as seroma, infection, chronic pain, and pain assessment through VAS score. Patient follow-up was made at 1 and 2 weeks, and 1, 3, 6, 12, and 36 months. Ultrasound scans were performed for the detection of any possible implant dislodgment, shrinkage, and implant incorporation. The results of this study demonstrate that by using a purposefully designed 30 geometric implant expulsion forces can be switched into gripping forces, avoiding the need for traumatic fixation. This eliminates the typical complications related to mesh fixation such as bleeding, hematoma, chronic pain, and tissue tearing, often resulting in mesh dislodgement and recurrence. This new 30 implant results in open hernia repair procedures being safer, faster, and easier.

Multiple Ipsilateral Inguinal Hernias: More Frequent Than Imagined, If Undetected Source of Discomfort, Pain, and Re-interventions.

The article reports the incidence of multiple inguinal protrusions in the same groin in a patient collect who underwent open hernia repair. Multiple ipsilateral inguinal hernias compose an almost neglected topic that, if not identified during hernia repair, could lead to unclear discomfort, pain, and reoperation. A collect of 100 consecutive open anterior inguinal hernia procedures was analyzed. The patients were divided into two subsets-A: patients with a single protrusion and B: patients with more than one protrusion simultaneously arising from the inguinal floor. The single hernias from cohort A and the multiple hernias from cohort B were further categorized using the Nyhus classification system. Eighty-eight single unilateral hernias were detected and 12 multiple inguinal hernias were ipsilaterally arising from the same groin. Nine percent of the multiple protrusions were double (three double indirect and six in combination direct + indirect). Three patients (3%) presented with triple protrusions; of those two individuals, one had a combination of double indirect, one had a direct hernia, and the third patient showed a tricomponent protrusion (hernia of the fossa supravescicalis + hernia of the fossa inguinalis media + indirect hernia). These numbers demonstrate that multiple ipsilateral inguinal hernias are more frequent than imagined. If undiscovered during a herniorrhaphy, the "forgotten" protrusion may generate unclear groin pain requiring reoperation. Consequently, is to envisage that many re-interventions will likely involve false "recurrences." Therefore, during hernia repair, more attention and adhesiolysis is essential during inspection of the inguinal floor. In fact, a careful exposure of the anatomical structures of the groin could be very advantageous in properly managing such conditions. This kind of surgical approach can help to prevent patient's discomfort and re-interventions.

European Initial Hands-On Experience with HEMOPATCH, a Novel Sealing Hemostatic Patch: Application in General, Gastrointestinal, Biliopancreatic, Cardiac, and Urologic Surgery.

Topical hemostatic agents that can seal tissues and assist in the coagulation cascade of patients undergoing surgery have been readily available for several decades. Using either synthetic or animal/plant-derived materials, these agents represent a powerful tool to reduce postoperative bleeding complications in cases where mechanical or energy-driven hemostasis is not possible or insufficient. Recently, a novel sealing hemostatic patch, HEMOPATCH (Baxter International, Deerfield, IL), was developed. The device is a thin and flexible patch consisting of a specifically-formulated porous collagen matrix, coated on one side with a thin protein-binding layer. This gives the patch a dual mechanism of action, in which the two components interact to achieve hemostasis by sealing off the bleeding surface and initiating the body's own clotting mechanisms. Here we present a series of case reports that outline the quick, effective hemostatic sealing of HEMOPATCH in a variety of clinical applications, including solid organ, gastrointestinal, biliopancreatic, endocrine, cardiovascular, and urologic surgeries. Essentially a feasibility study, these reports demonstrate how HEMOPATCH can be applied to seal almost any bleeding surface encountered during a range of procedures. Our results show that the device is eminently capable in both via laparotomy and laparoscopic approaches, and in patients with impaired coagulation or highly variable anatomies. In conclusion, our cases document the ease-of-use, application, and immediate hemostatic effect of the patch across a broad range of surgical settings and paves the way for future randomized clinical trials with more extensive follow-up.

Oligo-antigenic diet in the treatment of chronic anal fissures. Evidence for a relationship between food hypersensitivity and anal fissures.

OBJECTIVES: Patients with chronic constipation due to food hypersensitivity (FH) had an elevated anal sphincter resting pressure. No studies have investigated a possible role of FH in anal fissures (AFs). We aimed to evaluate (1) the effectiveness of diet in curing AFs and to evaluate (2) the clinical effects of a double-blind placebo-controlled (DBPC) challenge, using cow's milk protein or wheat. METHODS: One hundred and sixty-one patients with AFs were randomized to receive a "true-elimination diet" or a "sham-elimination diet" for 8 weeks; both groups also received topical nifedipine and lidocaine. Sixty patients who were cured with the "true-elimination diet" underwent DBPC challenge in which cow's milk and wheat were used. RESULTS: At the end of the study, 69% of the "true-diet group" and 45% of the "sham-diet group" showed complete healing of AFs (P<0.0002). Thirteen of the 60 patients had AF recurrence during the 2-week cow's milk DBPC challenge and 7 patients had AF recurrence on wheat challenge. At the end of the challenge, anal sphincter resting pressure significantly increased in the patients who showed AF reappearance (P<0.0001), compared with the baseline values. The patients who reacted to the challenges had a significantly higher number of eosinophils in the lamina propria and intraepithelial lymphocytes than those who did not react to the challenges. CONCLUSIONS: An oligo-antigenic diet combined with medical treatment improved the rate of chronic AF healing. In more than 20% of the patients receiving medical and dietary treatment, AFs recurred on DBPC food challenge.