Surgical Antibiotic Prophylaxis: A Proposal for a Global Evidence-Based Bundle.

In the multimodal strategy context, to implement healthcare-associated infection prevention, bundles are one of the most commonly used methods to adapt guidelines in the local context and transfer best practices into routine clinical care. One of the most important measures to prevent surgical site infections is surgical antibiotic prophylaxis (SAP). This narrative review aims to present a bundle for the correct SAP administration and evaluate the evidence supporting it. Surgical site infection (SSI) prevention guidelines published by the WHO, CDC, NICE, and SHEA/IDSA/APIC/AHA, and the clinical practice guidelines for SAP by ASHP/IDSA/SIS/SHEA, were reviewed. Subsequently, comprehensive searches were also conducted using the PubMed®/MEDLINE and Google Scholar databases, in order to identify further supporting evidence-based documentation. The bundle includes five different measures that may affect proper SAP administration. The measures included may be easily implemented in all hospitals worldwide and are based on minimal drug pharmacokinetics and pharmacodynamics knowledge, which all surgeons should know. Antibiotics for SAP should be prescribed for surgical procedures at high risk for SSIs, such as clean-contaminated and contaminated surgical procedures or for clean surgical procedures where SSIs, even if unlikely, may have devastating consequences, such as in procedures with prosthetic implants. SAP should generally be administered within 60 min before the surgical incision for most antibiotics (including cefazolin). SAP redosing is indicated for surgical procedures exceeding two antibiotic half-lives or for procedures significantly associated with blood loss. In principle, SAP should be discontinued after the surgical procedure. Hospital-based antimicrobial stewardship programmes can optimise the treatment of infections and reduce adverse events associated with antibiotics. In the context of a collaborative and interdisciplinary approach, it is essential to encourage an institutional safety culture in which surgeons are persuaded, rather than compelled, to respect antibiotic prescribing practices. In that context, the proposed bundle contains a set of evidence-based interventions for SAP administration. It is easy to apply, promotes collaboration, and includes measures that can be adequately followed and evaluated in all hospitals worldwide.

Acute left colonic diverticulitis in the emergency setting: from diagnosis to treatment.

Acute left colonic diverticulitis (ALCD) is a common clinical condition encountered by physicians in the emergency setting. Clinical presentation of ALCD ranges from uncomplicated acute diverticulitis to diffuse fecal peritonitis. ALCD may be diagnosed based on clinical features alone, but imaging is necessary to differentiate uncomplicated from complicated forms. In fact, computed tomography scan of the abdomen and pelvis is the highest accurate radiological examination for diagnosing ALCD. Treatment depends on the clinical picture, the severity of patient's clinical condition and underlying comorbidities. Over the last few years, diagnosis and treatment algorithms have been debated and are currently evolving. The aim of this narrative review was to consider the main aspects of diagnosis and treatment of ALCD.

A Proposal for a Classification Guiding the Selection of Appropriate Antibiotic Therapy for Intra-Abdominal Infections.

Adequately controlling the source of infection and prescribing appropriately antibiotic therapy are the cornerstones of the management of patients with intra-abdominal infections (IAIs). Correctly classifying patients with IAIs is crucial to assessing the severity of their clinical condition and deciding the strategy of the treatment, including a correct empiric antibiotic therapy. Best practices in prescribing antibiotics may impact patient outcomes and the cost of treatment, as well as the risk of "opportunistic" infections such as Clostridioides difficile infection and the development and spread of antimicrobial resistance. This review aims to identify a correct classification of IAIs, guiding clinicians in the selection of the best antibiotic therapy in patients with IAIs.

Colorectal surgery in Italy during the Covid19 outbreak: a survey from the iCral study group.

BACKGROUND: The COVID19 pandemic had a deep impact on healthcare facilities in Italy, with profound reorganization of surgical activities. The Italian ColoRectal Anastomotic Leakage (iCral) study group collecting 43 Italian surgical centers experienced in colorectal surgery from multiple regions performed a quick survey to make a snapshot of the current situation. METHODS: A 25-items questionnaire was sent to the 43 principal investigators of the iCral study group, with questions regarding qualitative and quantitative aspects of the surgical activity before and after the COVID19 outbreak. RESULTS: Two-thirds of the centers were involved in the treatment of COVID19 cases. Intensive care units (ICU) beds were partially or totally reallocated for the treatment of COVID19 cases in 72% of the hospitals. Elective colorectal surgery for malignancy was stopped or delayed in nearly 30% of the centers, with less than 20% of them still scheduling elective colorectal resections for frail and comorbid patients needing postoperative ICU care. A significant reduction of the number of colorectal resections during the time span from January to March 2020 was recorded, with significant delay in treatment in more than 50% of the centers. DISCUSSION: Our survey confirms that COVID19 outbreak is severely affecting the activity of colorectal surgery centers participating to iCral study group. This could impact the activity of surgical centers for many months after the end of the emergency.

International consensus on the diagnosis and management of dumping syndrome.

Dumping syndrome is a common but underdiagnosed complication of gastric and oesophageal surgery. We initiated a Delphi consensus process with international multidisciplinary experts. We defined the scope, proposed statements and searched electronic databases to survey the literature. Eighteen experts participated in the literature summary and voting process evaluating 62 statements. We evaluated the quality of evidence using grading of recommendations assessment, development and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 33 of 62 statements, including the definition and symptom profile of dumping syndrome and its effect on quality of life. The panel agreed on the pathophysiological relevance of rapid passage of nutrients to the small bowel, on the role of decreased gastric volume capacity and release of glucagon-like peptide 1. Symptom recognition is crucial, and the modified oral glucose tolerance test, but not gastric emptying testing, is useful for diagnosis. An increase in haematocrit >3% or in pulse rate >10 bpm 30 min after the start of the glucose intake are diagnostic of early dumping syndrome, and a nadir hypoglycaemia level <50 mg/dl is diagnostic of late dumping syndrome. Dietary adjustment is the agreed first treatment step; acarbose is effective for late dumping syndrome symptoms and somatostatin analogues are preferred for patients who do not respond to diet adjustments and acarbose.

A proposal for a comprehensive approach to infections across the surgical pathway.

Despite evidence supporting the effectiveness of best practices in infection prevention and management, many healthcare workers fail to implement them and evidence-based practices tend to be underused in routine practice. Prevention and management of infections across the surgical pathway should always focus on collaboration among all healthcare workers sharing knowledge of best practices. To clarify key issues in the prevention and management of infections across the surgical pathway, a multidisciplinary task force of experts convened in Ancona, Italy, on May 31, 2019, for a national meeting. This document represents the executive summary of the final statements approved by the expert panel.

Nebivolol induces, via ß3 adrenergic receptor, lipolysis, uncoupling protein 1, and reduction of lipid droplet size in human adipocytes.

OBJECTIVES: Most ß-blockers may induce weight gain, dysglycemia, and dyslipidemia. Nebivolol is a third-generation ß1-blocker with vasodilating properties mediated by ß3 adrenergic receptors (ß3AR). We investigated whether nebivolol is able to induce ß3AR-mediated lipolysis, uncoupling protein 1 (UCP1), and size-reduction in human adipocytes. METHODS: Human visceral (n = 28) and subcutaneous adipose tissue (n = 26) samples were used to obtain differentiated subcutaneous and visceral preadipocytes. Adipocytes were used to verify the effects of nebivolol onlipolysis, uncoupling protein 1 (UCP1) and other genes of the thermogenic program. RESULTS: Lipolysis was induced by isoproterenol and specific ß3AR agonist, as expected,and also by nebivolol at 100 nmol/l and by its L-enantiomer at 10 nmol/l (P < 0.01). Nebivolol-mediated lipolysis was blocked by SR59230A, a specific ß3AR antagonist, suggesting that nebivolol acts through ß3AR in human adipocytes. Interestingly, in human adipocytes, nebivolol activated UCP1, PPARγ coactivator-1α (PGC-1α) and cytochrome c (CYCS) gene expression in a p38 MAPK-dependent manner. Using propranolol (ß1 and ß2 antagonist) together with nebivolol we showed that the induction of these genes was still present suggesting again ß3AR activation. Moreover, nebivolol significantly reduced the diameter of lipid droplets in cultured adipocytes. CONCLUSION: In summary, nebivolol, through ß3AR, is able to induce lipolysis and promote thermogenic and mitochondrial genes. The induction of lipolysis and the thermogenic program could explain the reduction of lipid droplets size. In conclusion, the lower dysmetabolic effects of nebivolol in humans may depend on its ß3 agonist activity and the consequent induction of thermogenic program in human adipocytes.

Nuclear factor-κB predicts outcome in locally advanced rectal cancer patients receiving neoadjuvant radio-chemotherapy.

BACKGROUND: NF-κB expression has been shown to be responsible for resistance to antineoplastic agents. AIMS: The aim of our study was to investigate the importance of NF-κB expression as prognostic factor in locally advanced rectal cancer patients receiving neoadjuvant radiochemotherapy. METHODS: We retrospectively analysed the immunoreactivity for NF-κB in patients with locally advanced rectal cancer who underwent neoadjuvant treatment (chemotherapy and/or radiotherapy) in our Institution between March 2003 and June 2006. RESULTS: Seventy-four consecutive patients were enrolled into this study. Immunohistochemistry analysis for NF-κB was performed both in biopsies and in primary tumour samples. NF-κB was considered positive when at least 1% of the tumour cells showed nuclear positivity. A significant correlation between a positive NF-κB nuclear expression, both in biopsies and in tumour samples, and a worse overall survival was observed. Moreover, median time to progression was significantly shorter in the NF-κB-positive subgroup of patients. CONCLUSION: Globally, our findings seem to suggest that NF-κB could represent an important parameter able to predict the outcome in patients receiving neoadjuvant treatment for rectal cancer. It also could be useful in order to select patients to receive adjuvant chemotherapy, intensifying the adjuvant therapy and, in the next future, obviating the use of drugs involving NF-κB system in their mechanism of action in NF-κB-positive patients.

Human dedifferentiated adipocytes show similar properties to bone marrow-derived mesenchymal stem cells.

Mature adipocytes are generally considered terminally differentiated because they have lost their proliferative abilities. Here, we studied the gene expression and functional properties of mature adipocytes isolated from human omental and subcutaneous fat tissues. We also focused on dedifferentiated adipocytes in culture and their morphologies and functional changes with respect to mature adipocytes, stromal-vascular fraction (SVF)-derived mesenchymal stem cells (MSCs) and bone marrow (BM)-derived MSCs. Isolated mature adipocytes expressed stem cell and reprogramming genes. They replicated in culture after assuming a fibroblast-like shape and expanded similarly to SVF- and BM-derived MSCs. During the dedifferentiation process, mature adipocytes lost their lineage gene expression profile, assumed the typical mesenchymal morphology and immunophenotype, expressed stem cell genes and differentiated into multilineage cells. Moreover, during the dedifferentiation process, we showed changes in the epigenetic status of mature adipocytes, which led dedifferentiated adipocytes to display a similar DNA methylation condition to BM-derived MSCs. Like SVF- and BM-derived MSCs, dedifferentiated adipocytes were able to inhibit the proliferation of stimulated lymphocytes in coculture while mature adipocytes stimulated their growth. Furthermore, dedifferentiated adipocytes maintained the survival and complete differentiation characteristic of hematopoietic stem cells. This is the first study that in addition to characterizing isolated and dedifferentiated adipocytes also reports on the immunoregulatory and hematopoietic supporting functions of these cells. This structural and functional characterization might have clinical applications of both mature and dedifferentiated adipocytes in such fields, as regenerative medicine.

The timing of surgery for resectable metachronous liver metastases from colorectal cancer: Better sooner than later? A retrospective analysis.

BACKGROUND: The benefit of preoperative chemotherapy in patients with initially resectable liver metastases from colorectal cancer is still a matter of debate. AIMS: We aim to evaluate the role of neoadjuvant chemotherapy on the outcome of patients with colorectal cancer metachronous liver metastases undergoing potentially curative liver resection. METHODS: One-hundred four patients were available for analysis. Tested variables included age, sex, primary tumour TNM stage, location and grading, the number of liver metastases, monolobar or bilobar location, interval time between liver metastases diagnosis and liver resection, Fong Clinical Risk Score (CRS). Neoadjuvant chemotherapy was administered according to the FOLFOX4 regimen. RESULTS: Forty-four patients underwent liver resection without receiving neoadjuvant chemotherapy (group A); 60 patients received neoadjuvant chemotherapy (group B). At univariate analysis, only the time of liver resection seemed to affect overall survival: patients in group A showed a median survival time significantly superior to that of patients in group B (48 vs. 31 months; p=0.0358). CONCLUSIONS: Our findings suggest that, when feasible, resection of liver metastases should be considered as an initial approach in this setting. Further studies are needed to better delineate innovative therapeutic strategies that may lead to an improved outcome for colorectal cancer patients with surgically resectable liver metastases.

Vulvo-perineal reconstruction with a reverse sensitive rectus abdominis salvage flap in a multirecurrent anal carcinoma.

Reconstructive options after vulvectomy is preferably performed using fasciocutaneous flaps. If the defect is very large, the use of vertical rectus abdominis myocutaneous (VRAM) flap is recommended. We report a case of a patient affected by multirecurrent anal carcinoma, treated by chemotherapy, radiotherapy and surgery several times, until an extended abdominoperineal resection of Miles was performed. Since other surgical options were no more available, a primary reverse VRAM flap reconstruction was harvested, together with an end-to-end nerve anastomosis between the cutaneous ramus of the 8th intercostal nerve and the superior branch of the pudendal nerve to achieve sensibility. Encouraging results, without actual recurrence of the disease, were obtained.

Primary carcinoid tumour of the kidney. A case report and review of the literature.

Carcinoid tumours are known to occur frequently in the gastrointestinal and respiratory tracts. A primary carcinoid tumour of the kidney is an extremely rare entity and only 40 cases have been reported in the literature. As a consequence, very little is known about its real histogenesis, and its prognosis and clinicopathological patterns are not precisely defined. We report a case of primary carcinoid tumour of the kidney found in a middle-aged woman treated by nephrectomy, along with a thorough review of the literature concerning this kind of neoplasm.

[Extraordinary role of self-expanding metal stent (SEMS) in the malignant colorectal obstruction: different care in two cases]. / Lo straordinario impatto del Wallstent nelle occlusioni neoplastiche del colon: il differente impiego in due casi clinici.

The colorectal cancer presents with bowel obstruction in 10%-30% of patients. Established treatment of this evolutive condition, until 15 years ago, was emergency surgery. Primary resection with or without ileostomy, staged resection, Hartmann's procedure, or definitive colostomy are the therapeutical options. There is ongoing controversy on the best procedure to apply, because the choice depends on the patient's condition, age, electrolyte imbalances, nutritional status, obstructional grade, comorbidity and surgeon's attitude. However, the obstruction and the emergency operation add risk of complications and mortality instead of elective surgery. The efficacy of self-expanding metal stent to solve the obstruction had recently changed the management of malignant luminal obstruction: it is safe, effective, with very low mortality, low morbidity and also cheap. In the inoperable cases it represents the first line therapy avoiding the colostomy. In the operable patients, instead of two-step surgery, the SEMS had to be preferred because is a one-time and election surgery and avoid colostomy too, even if temporary. SEMS versus emergency primary surgery, without randomized and controlled study, allows a safer single-staged surgery. Finally it improves the quality of life avoiding colostomy, and reducing operative risk. We present two different use of SEMS: the palliation in inoperable patient and the "bridge to surgery" in critical obstructed patient.

[Non-operative management of blunt abdominal injuries]. / Ii trattamento non operativo dei traumi addominali chiusi.

Over the past three decades, non-operative management has been shown to be an effective therapeutic option in hemodynamically stable patients. We retrospectively reviewed the last 7 years of our experience with the non-operative management of blunt abdominal traumas. From January 1998 to July 2005, 123 patients with blunt abdominal traumas and injuries to the spleen, liver and pancreas were admitted to our hospital. Fifty-eight of them (47.2%) were submitted to non-operative management; 5 (8.6%) presented associated splenic and hepatic injuries. We performed non-operative treatment for 27 splenic injuries (33.7% of all splenic injuries), 32 hepatic injuries (62.7% of all hepatic injuries) and 3 pancreatic injuries (75% of all pancreatic injuries). There was no mortality and no complications. We submitted one haemodynamically stable patient who presented a grade V hepatic injury and "contrast pooling" at abdominal CT scan to angiography and transarterial embolisation; this patient was successfully managed non-operatively. The overall success rate of non-operative management was 98.5%. The only non-operative management failure was a patient with both splenic and hepatic injuries. The success rate for injuries to the spleen was 96.3%, to the liver 96.9% and to the pancreas 100%. We conclude that hemodynamically stable patients suffering intra-abdominal injury can be safely managed non-operatively.

[Solid pseudopapillary tumor of the pancreas. A report of 3 cases and a review of the literature]. / Tumore solido pseudopapillare del pancreas. A proposito di 3 casi e revisione della letteratura.

Solid pseudopapillary tumours of the pancreas (SPTP) are a distinct clinico-pathological entity that differs from the other cystic pancreatic neoplasms in the young age of onset, the almost exclusive incidence in the female sex and the low degree of malignancy. SPTP is a rare neoplasm that has shown a progressive increase of incidence, passing from 0.17%-2.7% of all exocrine tumours of the pancreas in the 1980's, to 6% in recent reports in 2003. In addition, it accounts for about 5% of cystic neoplasms of the pancreas. With the present paper, in the world literature, updated to August 2005, 887 cases have been described in 248 articles. The histogenesis of these epithelial neoplasms remains uncertain though it is likely that they originate from pluripotent immature pancreatic cells. The tumour is generally of large size and invariably presents a capsule. The diagnosis in most cases is based on compressive symptoms, pain or finding of a palpable mass, while in about 20% of the patients the finding is occasional during abdominal imaging performed for other pathologies. CT and MR are not always sufficient to differentiate with certainty between this type of tumour and other cystic neoplasms of the pancreas such as pseudocysts, parasitic cysts and congenital cysts. Cytological examination in most cases permits the diagnosis of SPTP. The malignancy of these neoplasms is attenuated and local with capsular invasion, lymp-node spread and, only rarely, liver and peritoneal metastases. The surgical treatment has to be radical since the malignancy can only be defined by postoperative histological examination. The treatment consists of three possible options: duodenocephalopancreatectomy, intermediate pancreatectomy, and distal pancreatectomy with or without splenectomy. Intraoperative histological examination is mandatory for the diagnostic confirmation and for the evaluation of negativity of the pancreatic resection margins. Survival after radical resection is excellent. Moreover, in forma metastasizing to the liver an aggressive attitude may be still curative and assure longer survival. The Authors report their experience with three female patients with an average age 18 years (28,19 and 8 years) operated on between 1995 and 2000 for SPTP. Two of the patients were asymptomatic and the finding of the tumour was occasional. The third patient presented jaundice and abdominal pain. The average diameter of the tumours was 6 cm (4, 7 and 7 cm). In all three cases tumour marker values (CEA, Ca19-9, alphaFP) were normal. Only in one case was the preoperative diagnosis correct. The surgical treatment depended on the location of the neoplasms: for the two tumours in the head, in one case an enucleoresection was performed in relation to an exophytic location, while, in the other, a duodenocephalopancreatectomy was performed. In the somatopancreatic tumour a distal splenopancreatectomy was performed. Only in one case (the DCP) the capsule and the surrounding parenchyma were infiltreted by neoplasm. In all cases there was immunohistochemical positivity for alpha1-antitrypsin and for neuron-specific enolase. Neither mortality nor operative morbidity were observed. Follow-up with CT found no relapses in any of the three patients after 5, 7 and 10 years, respectively, after the operation.