Enhanced recovery protocol in esophagectomy, is it really worth it? A cost analysis related to team experience and protocol compliance.

Application of enhanced recovery protocols (ERP) in esophageal surgery seems to lead an advantage in terms of length of hospital staying and outcomes, but only few data exist on its cost effectiveness. Previous literature analyzed pre- and post-ERP groups, finding a cost reduction with the introduction of the pathway. We aimed to study the influence on costs of accumulating experience and compliance in an ERP group. Seventy-one patients have been treated at our institution from January 2014 to June 2017 with our ERP for Ivor-Lewis esophagectomy. Direct costs were divided into subcategories and were analyzed as a function of calendar year and compliance. Factor affecting costs were searched. Univariable analysis highlighted a significant reduction in costs over time. Increase in compliance led to a progressive cost reduction for each ERP item completed (€14 852-€11 045). While age was not found to significantly influence the cost (p = 0.341), complications seemed to nullify the effect of experience: the median was €11 507 in uncomplicated patients, and increased to €13 791 in Clavien-Dindo 3-4 (CD3-4) patients. Compliance and CD3-4 remained significant also in multivariable analysis, accomplished by quantile regression, while year of surgery lost its significance. Our results evidence how accumulating experience in ERP led to a cost reduction over time, which was mainly mediated by an increase in compliance. Indeed, compliance was the main factor in reducing ERP cost while CD3-4 complications were the most important factor in cost increasing, nullifying the benefit of compliance.

Morphometric evaluation of the linea alba in fresh corpses.

Purpose: Diastasis recti abdominis is an increase in the distance between the medial borders of the two rectus muscles. It is most often triggered after intra-abdominal pressure increases, such as postpartum or in obesity. Most publications are based on radiological studies or are done in certain subgroups, without unanimous reference values of the distance between the rectus abdominis or standardization. Methods: Forty-one cadavers were studied. Exclusion criteria: signs of abdominal trauma, major burns, presence of scar from previous abdominal surgery, clinical signs of abdominal hernia, and identification of hernia during cadaver dissection. Linea alba (LA) length, width, and thickness were measured with a flexible tape measure and digital caliper. Anatomical landmarks were established, and subdivisions were described based on them to compare the cadavers. Results: Sex and age had little effect on LA width, thickness, or length. Obesity (compared to normal weight) was the only variable that promoted an increase in the LA width (p < 0.01). The supraumbilical length varied with the total height of the evaluated cadavers (p < 0.01), but the infraumbilical length did not (p = 0.11). Conclusion: The general statistical results of this study, regarding the evaluation of LA measurements in cadavers, showed that ethnicity, sex, and age have little effect on the width, thickness, or length of the LA. LA width differed significantly with abdominal circumference.

Loss of function effect of RET mutations causing Hirschsprung disease.

We have introduced three Hirschsprung (HSCR) mutations localized in the tyrosine kinase domain of RET into the RET/PTC2 chimaeric oncogene which is capable of transforming NIH3T3 mouse fibroblasts and of differentiating pC12 rat pheochromocytoma cells. The three HSCR mutations abolished the biological activity of RET/PTC2 in both cell types and significantly decreased its tyrosine phosphorylation. By contrast, a rare polymorphism in exon 18 does not alter the transforming capability of RET/PTC2 or its tyrosine phosphorylation. These data suggest a loss of function effect of HSCR mutations which might act through a dominant negative mechanism. Our model system is therefore capable of discriminating between causative HSCR mutations and rare polymorphisms in the tyrosine kinase domain of RET.

Conducted healing to treat large skin wounds.

BACKGROUND: Improvement of the healing process to provide better aesthetical and functional results continues to be a surgical challenge. This study compared the treatment of skin wounds by means of conducted healing (an original method of treatment by secondary healing) and by the use of autogenous skin grafts. METHOD: Two skin segments, one on each side of the dorsum,were removed from 17 rabbits. The side that served as a graft donor site was left open as to undergo conducted healing (A)and was submitted only to debridement and local care with dressings. The skin removed from the side mentioned above was implanted as a graft (B) to cover the wound on the other side. Thus, each animal received the two types of treatment on its dorsum (A and B). The rabbits were divided into two groups according to the size of the wounds: Group 1 - A and B (4 cm2)and Group 2 - A and B (25 cm2). The healing time was 19 days for Group 1 and 35 days for Group 2. The final macro- and microscopic aspects of the healing process were analysed comparatively among all subgroups. The presence of inflammatory cells, epidermal cysts and of giant cells was evaluated. RESULTS: No macro- or microscopic differences were observed while comparing the wounds that underwent conducted healing and those in which grafting was employed, although the wounds submitted to conducted healing healed more rapidly. CONCLUSIONS: Conducted wound healing was effective for the treatment of skin wounds.

Reduction of the emergency activity, during the Covid 19 Italian lockdown, what's the lesson to learn?

The COVID 19 pandemic was declared on the 9th of March 2020. The health crisis affected the whole world with a very high and unexpected number of infected people. The situation forced the declaration of lockdown and a worldwide health system reorganization. Surprisingly, the social distancing laws caused a reduction of urgent hospital activities not COVID 19 related. The aim of this manuscript is to analyze the reasons why fewer emergencies were described during the 2020 Italian lockdown. The Data reporting urgent Emergency Room (ER) activity, during the first three weeks of the Italian lockdown (Group 1), were analyzed and compared with the same period in 2019 (Group 2). During the study period in 2020, there was a 46,5% reduction in ER activity compared to that in 2019. Nevertheless, the hospitalization rate was higher in the 2020 then in 2019 (p<0.05). The present data showed that almost half of the basic ER activity araised from mild health problems that could be followed by territorial health services. The strengthening of territorial medical services would allow hospitals to handle critical situations more easily and to focus activity by reducing the waiting list.

Is there a relationship between physical performance and orchiectomy?

Bilateral orchiectomy is indicated for the treatment of patients with testicular cancer or advanced prostate tumours. The influence of hypogonadism on physical performance is still not known. The purpose of this work was to verify the effect of bilateral orchiectomy on physical performance. Sixteen rats were divided into two groups: Group 1 (Control), in which only skin incision and suture were made (n = 5) and Group 2, in which the rats were submitted to bilateral orchiectomy (n = 11). The animals ran on a treadmill at the speed of 20 m min(-1) until they were fatigued and felt once, during 10 s, when the experiment was interrupted. Time to running and weight of animals were verified. The results were compared using the Mann-Whitney test. There was no difference on time to running - minutes - (P = 0.14) and weight - grams - (P = 0.25) between the animals submitted to orchiectomy (100 ± 44 min and 359 ± 38 g) and the control Group (81 ± 40 min to run and 327 ± 25 g). Bilateral orchiectomy does not affect the physical performance of the rat.

Hypoandrogenism related to early skin wound healing resistance in rats.

The purpose of this study was to verify the effect of testosterone depletion on healing of surgical skin wounds at different ages and post-operative periods. Forty-four Wistar male rats were divided into four groups: Group 1Y (n = 11) - young control, sham-operated rats (30-day old); Group 1A (n = 10) - adult control, sham-operated rats (3 to 4-month old); Group 2Y (n = 10) - young rats after bilateral orchiectomy; and Group 2A (n = 11) - adult rats after bilateral orchiectomy. After 6 months, a linear incision was performed on the dorsal region of the animals. The resistance of the wound healing was measured in a skin fragment using a tensiometer, on the 7th and 21st post-operative days. The wound healing resistance was higher in Group 1Y than in Group 2Y after 7 days (P < 0.05). Wound healing resistance at 21 days was higher than at 7 days in all groups (P < 0.05). Late wound healing resistance was not different between young and adult rats. It is concluded that bilateral orchiectomy diminished the wound healing resistance only in young animals at the 7th post-operative day.

Laparoscopic transhiatal suture and gastric valve as a safe and feasible treatment for Boerhaave's syndrome: an Italian single center case series study.

BACKGROUND: Boerhaave's syndrome (BS) is a rare life-threating condition with poor prognosis. Unfortunately, due to its very low incidence, no clear evidences or definitive guidelines are currently available: in detail, surgical strategy is still a matter of debate. Most of the case series reports thoracic approach as the most widely used; conversely, transhiatal abdominal management is just described in sporadic case reports. In our center, the laparoscopic approach has been adopted for years: in the present study, we aim to show his feasibility by reporting the outcomes of the largest clinical series available to date. METHODS: Clinical records of patients admitted for BS to the General and Upper GI Surgery Division of Verona from February 2014 to December 2019 were retrospectively collected. Clinico-pathological characteristics, preoperative workup, surgical management, and outcomes were analyzed. RESULTS: Seven patients were admitted; epigastric/thoracic pain and vomiting were the most frequent symptoms at diagnosis. Laboratory findings were not specific; conversely, radiological imaging always revealed abnormal findings: particularly, CT had excellent sensitivity in detecting signs of esophageal perforation. All but one case had diagnostic workup and received surgery within 24 h. Every patient had laparoscopic transhiatal direct suture and gastric valve; 2 patients (28.6%) also needed a thoracoscopic toilette. Postoperative complications occurred in 4 patients (57%), but in only two of them (29%), the complication was severe according to Clavien-Dindo classification (both received thoracentesis or thoracic drainage for pleural effusion). Of note, no cases of postoperative esophageal leak were recorded. Postoperative mortality was 14% due to one patient who died for cardiovascular complications. Most of the patients (71.4%) were admitted to ICU after surgery (average length, 8.8 days); mean hospital stay was 14.7 days. No patients had readmissions. CONCLUSIONS: To our knowledge, this is the largest case series reporting laparoscopic management of BS. We show that laparoscopy is a safe and feasible approach associated with a shorter length of hospital stay when compared with clinical series in which thoracic approach had been chosen. Of note, laparoscopic management would be easily adopted by surgical centers treating benign gastro-esophageal junction entailing a proper management more widely.

Perianastomotic drainage in Ivor-Lewis esophagectomy, does habit affect utility? An 11-year single-center experience.

Anastomotic leakage (AL) is a deadly complication after Ivor-Lewis esophagectomy. The use of an anastomotic drainage (AD), to diagnose and to potentially treat the leakage, is still a widespread practice. At present, scientific literature is lacking in this topic and its use is based on each center experience. We performed a retrospective analysis of 239 consecutive patients who underwent an Ivor-Lewis esophagectomy in our Department from 01/01/2006 to 31/12/2017. Until 28/02/2014, a transthoracic anastomotic drainage was routinely placed in 119 patients (anastomotic-drain group). Drainage removal was planned on POD 5 after the resume of oral intake. In the remaining 120 cases, no drainage was placed (no anastomotic-drain group). We compared the two groups to assess whether the anastomotic drainage had an impact on the timing of the anastomotic leakage diagnosis and treatment. In our series, we observed 9 anastomotic leaks in the first group (7.6%) and 3 in the second one (2.5%). In the anastomotic-drain group, median time for leak diagnosis was 10 days, and notably, in seven cases, the anastomotic drainage was already removed. Considering all the patients who experienced an AL, a re-operation was mandatory in one case, while endoscopic treatment was chosen for five cases and conservative treatment was adopted in three cases. The median hospital length of stay in these patients was 31 days. In the no anastomotic-drain group, one patient with anastomotic leakage was treated conservatively and discharged after 34 days. The other two cases were re-operated and an esophageal prosthesis was placed in both cases, and these patients were discharged, respectively, on POD 28 and POD 38. Concluding, the role of the anastomotic drain in Ivor-Lewis esophagectomy is still unclear. There is a shortage of the literature on this topic and our experience shows that the anastomotic drain has a limited sensibility in AL diagnosis and cannot replace the clinical signs and symptoms. Moreover, the drain it is often removed before the leakage becomes visible. In selected patients with a less severe leak, the anastomotic drain can be an effective treatment, but often a percutaneous drainage, it is an effective alternative choice. In severe dehiscence with sepsis, a reoperation remains the mainstay to control the mediastinal contamination and to eventually treat the leakage.

In vitro activity of Acanthamoeba castellanii on human platelets and erythrocytes.

The effect of Acanthamoeba on human platelets and erythrocytes has not been fully elucidated. This paper reports that cell-free supernatants prepared from A. castellanii can activate human platelets, causing both a significant increase in the cytosolic free-calcium concentration and platelet aggregation. In addition, we demonstrated that platelet activation depends on the activity of ADP constitutively secreted into the medium by trophozoites. This study also showed that A. castellanii can affect human red blood cells, causing hemolysis, and provided evidence that hemolysis occurs in both contact-dependent and contact-independent ways; there are differences in kinetics, hemolytic activity, and calcium dependency between the contact-dependent and contact-independent mechanisms. Partial characterization of contact-independent hemolysis indicated that ADP does not affect the plasma membrane permeability of erythrocytes and that heat treatment of amoebic cell-free supernatant abolishes its hemolytic activity. These findings suggest that some heat-labile molecules released by A. castellanii trophozoites are involved in this phenomenon. Finally, our data suggest that human platelets and erythrocytes may be potential cell targets during Acanthamoeba infection.

Assay of hydroxyl radicals generated by focused ultrasound.

Water sonolysis leads to the formation of hydroxyl radicals (OH*). Various techniques are used to detect the OH* production and thus to assess the level of ultrasound-mediated cavitation generated in vitro. In this study, we used terephthalic acid (TA) as an OH* trap. This method is based on the fluorescent properties of hydroxyterephthalic acid (HTA) formed by the reaction of TA with OH* and used as an indicator of the degree of inertial cavitation caused. The experimental system is comprised mainly of a focused piezoelectric ultrasound transmitter and a measurement cell containing 1X PBS/TA diluted solution. In the first part, we aimed to characterize the most appropriate experimental conditions (TA dosimeter solution, irradiation time) in order to optimize the resulting HTA fluorescence values. Then, we could determine that the HTA production increased with the level of the cavitation phenomenon caused by the acoustic power from which OH* production may be estimated.

Pain during and after-hernioplasty in raquidian or locorregional anesthesia by locking peripheral nerves.

PURPOSE: To analyze pain scores after surgery in a group of patients submitted to inguinal hernia repair under peripheral nerve block with local or spinal anesthesia. METHODS: Fifty patients were divided into two groups (both with 25 patients each). In the first group the patients were submitted to herniorrhaphy under peripheral block and local anesthesia (LG) and in the other group the patients were submitted to the same procedure under spinal anesthesia (RG). The pain was assessed using the international visual analog pain scale at four different moments. The analysis cost of the procedure was performed using the hospital's average final cost, without including medical expenses. RESULTS: The groups were homogeneous in relation to the epidemiological and clinical features. There was no significant difference between the pain in the intraoperative period and in the return visit for both groups (p = 0.17 and p = 0.18). In the immediate postoperative period, both groups reported no pain at all. In general, the RG reported a greater pain score (16% for RG and 12% for LG). Complications were more frequent in patients submitted to spinal anesthesia (40% versus 8%) (p = 0.008). The surgical time was higher in the LG (39.3 ± 9.2 min) versus (28.7 ± 7.5 min) (p = 0.01). The average final cost of the procedure was US$ 100.98 for the LG and US$ 166.19 for the RG (p = 0.00). CONCLUSION: The inguinal hernioplastia under local anesthesia plus sedation is a safe method, with a low incidence of complications, great acceptance by patients and less expensive.

SH2B1beta adaptor is a key enhancer of RET tyrosine kinase signaling.

The RET gene encodes two main isoforms of a receptor tyrosine kinase (RTK) implicated in various human diseases. Activating germ-line point mutations are responsible for multiple endocrine neoplasia type 2-associated medullary thyroid carcinomas, inactivating germ-line mutations for Hirschsprung's disease, while somatic rearrangements (RET/PTCs) are specific to papillary thyroid carcinomas. SH2B1beta, a member of the SH2B adaptors family, and binding partner for several RTKs, has been recently described to interact with proto-RET. Here, we show that both RET isoforms and its oncogenic derivatives bind to SH2B1beta through the SRC homology 2 (SH2) domain and a kinase activity-dependent mechanism. As a result, RET phosphorylates SH2B1beta, which in turn enhances its autophosphorylation, kinase activity, and downstream signaling. RET tyrosine residues 905 and 981 are important determinants for functional binding of the adaptor, as removal of both autophosphorylation sites displaces its recruitment. Binding of SH2B1beta appears to protect RET from dephosphorylation by protein tyrosine phosphatases, and might represent a likely mechanism contributing to its upregulation. Thus, overexpression of SH2B1beta, by enhancing phosphorylation/activation of RET transducers, potentiates the cellular differentiation and the neoplastic transformation thereby induced, and counteracts the action of RET inhibitors. Overall, our results identify SH2B1beta as a key enhancer of RET physiologic and pathologic activities.

Relationship between surgical trauma and albumin concentration in the postoperative period of digestive system operations.

AIM: Surgical trauma can provoke systemic alterations including changes in hepatic protein synthesis. Thus, it is important to point out the influence of this phenomenon on serum albumin concentration. The objective of the present work was to assess the effect of surgical trauma on serum albumin concentration during the immediate postoperative period in gastrointestinal procedures. METHODS: The study was conducted on 150 randomized adult patients submitted to elective major surgeries (Group 1) and to medium size surgeries (Group 2) of the gastrointestinal system, identified according to sex, age and skin color. Blood samples for the determination of serum albumin concentration were obtained on the day preceding and following the surgical procedure. RESULTS: There was a reduction in serum albumin both in Group 1 (P < 0.0001) and Group 2 (P < 0.0001), with no difference between sexes or patient skin colors for major surgeries. However, women showed a lower reduction in serum albumin than men in medium-sized surgeries. Also, the reduction of albumin was lower in black-skinned patients than in colored and lower in the latter than in white-skinned patients. With respect to age range, a greater reduction of albumin was observed in both groups among patients over 65 years, followed by younger patients (< 45 years) and by patients aged 45 to 65 years. CONCLUSION: Medium-sized and majors operations provoked an acute reduction in albuminemia, which was less intense among women, among the patients aged 45 to 65 years and among dark-skinned patients.

Morphology and healing resistance of abdominal wall after longitudinal and transversal laparotomy in rabbits.

AIM: The abdominal wall continues to be a topic of investigation for the evaluation of its healing in terms of morphology and resistance. In the present investigation, transverse and longitudinal laparotomies were studied comparatively. METHODS: Thirty rabbits were divided into two groups: Group 1 (n=10) longitudinal laparotomy, Subgroup 1A (n=5) suture of the anterior and posterior sheaths of the abdominal rectus muscle and of the peritoneum, Subgroup 1B (n=5) suture of the anterior sheath of the abdominal rectus muscle; Group 2 (n=20) transverse laparotomy, Subgroup 2A (n=5) suture of the anterior and posterior sheaths of the abdominal rectus muscle and of the peritoneum, Subgroup 2B (n=5) suture of only the anterior sheath of the abdominal rectus muscle, Subgroup 2C (n=5) suture of the abdominal rectus muscle and of its anterior sheath on a single plane, Subgroup 2D (n=5) repair of the posterior sheath of the abdominal rectus muscle together with the peritoneum, followed by suture of the abdominal rectus muscle complemented with suture of the anterior sheath of the same muscle. After 17 days, two peritoneal aponeurotic muscular segments of the scar were removed for the evaluation of resistance and of histological aspects. RESULTS: The resistance values detected for each group showed 1A>1B, 1A>2A and 1B>2B, and 2B>2C>2D>2A (P=0.014). Dehiscence, infections and adhesions were more frequent in Group 2. Histology revealed muscular degeneration and necrosis, with mature fibrous connective scar tissue replacing muscle tissue. CONCLUSION: Transverse muscle section causes greater muscle weakening and leaving the peritoneum open does not alter the resistance of the scar.

Influence of amine fluoride/stannous fluoride mouthwashes with and without chlorhexidine on secretion of proinflammatory molecules by peri-implant crevicular fluid cells.

AIM: Patients with dental implants need optimal plaque control. Peri-implantitis is an inflammation of soft and hard tissues around implants characterized by bone loss mediated by proinflammatory molecules such as IL-1beta, PGE(2), vascular endothelial growth factor (VEGF). The aim of this study was to evaluate the influence of amine fluoride/stannous fluoride (AmF-SnF(2)) vs chlorhexidine 0.12% (CHX) combined with Am-SnF(2) on IL-1beta, PGE(2) and EGF secretion by cells of crevicular peri-implant fluid. METHODS: Thirty patients with dental implants were included in this study. The test group used AmF-SnF(2) rinsing for 14 days, the control group used CHX rinsing during the first 7 days and AmF-SnF(2) during the following 7 days. Crevicular samples were collected using filter paper strips and assayed for level of IL-1beta, PGE(2) and VEGF with ELISA test. Data were analyzed with paired and unpaired t test. RESULTS: IL-1beta, VEGF and PGE(2) levels were significantly lower in test compared to control group. Comparing first with second week of treatment, a greater decrease of IL-1beta and VEGF was evident in sample group during the second week. There was a lower decrease of IL-1beta and VEGF during the entire treatment in control group. Differences of PGE(2) levels after 7 days in both the groups were not significant while there was a significant difference during the second week. CONCLUSION: The following data suggest that the use of AmF-SnF(2) could decrease the production of IL-1beta, PGE(2) and VEGF by inflammatory cells.AmF-SnF(2) could be an alternative to CHX mouth rinses in plaque control of patients with implants.

Efficacy of thalidomide as immunosuppressor in heterotopic heart transplantation.

BACKGROUND: Based on its anti-inflammatory and immunosuppressive effects, thalidomide has been used for the treatment of dermatologic diseases and of graft-versus-host reaction in patients submitted to bone marrow transplantation. The present study evaluated the immunosuppressive action of thalidomide alone or in combination with cyclosporine on the prevention of rejection of heterotopic cardiac allograft in rabbits. METHOD: Fifty rabbits were used, 25 of them as donors and 25 as receivers. The animals that received the graft were divided into five groups (n = 5): Group 1 (control)--non-immunosuppressed animals, Group 2 (animals immunosuppressed with cyclosporine at the dose of 10 mg/kg/day), Group 3 (animals immunosuppressed with thalidomide at the dose of 100 mg/kg/day), Group 4 (animals immunosuppressed with cyclosporine at the dose of 5.0 mg/kg/day), and Group 5 (animals immunosuppressed with cyclosporine at the dose of 5.0 mg/kg/day in combination with thalidomide at the dose of 50 mg/kg/day). The medications were administered through an orogastric catheter starting on the day before the transplant. The hearts were implanted in the abdomen and the graft vessels were anastomosed with abdominal aorta and cava. RESULTS: The combination of thalidomide and cyclosporine showed the lowest histopathological rejection score (p < 0.05). Thalidomide administered alone or in combination with cyclosporine was effective against rejection, increasing the survival (p < 0.01) of animals submitted to heterotopic heart transplantation in an abdominal position. CONCLUSIONS: Thalidomide may be considered as an adjuvant immunosuppressive drug that can be useful in transplantation.

The effect of surgical procedures on serum albumin concentration.

PURPOSE: To assess the effect of surgical trauma on serum albumin concentration during the immediate postoperative period. METHODS: 200 consecutive adult patients submitted to elective major surgeries (Group 1) and to medium size surgeries (Group 2) were identified according to gender, age and skin color. Blood samples for the determination of serum albumin concentration were obtained on the day preceding and the one following the surgical procedure. Pre- and postoperative albumin data were compared by the paired t test. The gender was compared by the Student t test. The skin color and the age were compared by the repeated measured one-way ANOVA and the Tukey-Kramer tests. The level of significance was set at P < 0.05. RESULTS: There was a reduction in serum albumin in Group 1 (p < 0.0001) and Group 2 (p < 0.0001), with no difference between gender or skin colors for major surgeries. However, women showed a lower reduction than men in serum albumin in medium-sized surgeries. In medium-sized surgeries, black patients had the lowest reduction in albuminemia. The greater reduction in albuminemia occurred in patients older than 65 years old. CONCLUSION: Medium-sized and majors operations provoked an acute reduction in albuminemia, which was more intense in aged white men.

Increased apoptosis, Huntingtin inclusions and altered differentiation in muscle cell cultures from Huntington's disease subjects.

Mutated huntingtin (htt) is ubiquitously expressed in tissues of Huntington's disease (HD) patients. In the brain, the mutated protein leads to neuronal cell dysfunction and death, associated with formation of htt-positive inclusions. Given increasing evidence of abnormalities in HD skeletal muscle, we extensively analyzed primary muscle cell cultures from seven HD subjects (including two unaffected mutation carriers). Myoblasts from presymptomatic and symptomatic HD subjects showed cellular abnormalities in vitro, namely mitochondrial depolarization, cytochrome c release, increased caspase-3, -8, and -9 activities, and defective cell differentiation. Another notable feature was the formation of htt inclusions in differentiated myotubes. This study helps to advance current knowledge about the downstream effects of the htt mutation in human tissues. Further applications may include drug screening using this human cellular model.