Unveiling the HER2-low phenomenon: exploring immunohistochemistry and gene expression to characterise HR-positive HER2-negative early breast cancer.

PURPOSE: HER2-low breast cancer (BC) is a novel entity with relevant therapeutic implications, especially in hormone receptor (HR) positive BC. This study examines whether HER2 mRNA through the 21-gene assay, Oncotype DX (ODX), can refine the diagnosis of HER2-low and HER2-zero, obtained by immunohistochemistry (IHC). METHODS: Between Jan 2021 and Jan 2023, 229 consecutive HR-positive HER2-negative early BC (T1-3 N0-1) have been characterised by IHC and ODX. HER2 status by IHC was either zero (IHC-0) or low (IHC-1 + and IHC-2 + /ISH-negative) while HER2-zero was further divided into HER2-null (IHC-0) and HER2-ultralow (IHC-1-10%). HER2 gene expression by ODX was negative if lower 10.7. RESULTS: The distribution of HER2 IHC was as follows: 53.3% HER2-0, 29.25% HER2-1 + , and 17.5% HER2-2 + . The clinicopathological characteristics were similar in the three groups, with higher PgR-negative rate in HER2-zero (13.9% vs 3% vs 5%). The distribution of RS was homogeneous in the three groups with the median HER2 gene expression of 9.20 [IQR: 8.70-9.60]. HER2 gene expression gradually increased as the IHC score, with substantial overlap. After adjusting for confounders, HER2-1 + and HER2 2 + had a significant positive correlation between HER2 gene expression and IHC [OR 1.42, 95% CI 1.21 to 1.68, p < 0.001; OR 1.96, 95% CI 1.61 to 2.37, p < 0.001] compared to the HER2-zero group. HER2 gene expression did not differ between HER2-null and HER2-ultralow subgroups. CONCLUSION: Due to the substantial overlap, the HER2 gene expression is unable to properly distinguish HER2-low and HER2-zero IHC whose accurate identification is critical in the context of HER2-negative BC.

Isatuximab plus atezolizumab in patients with advanced solid tumors: results from a phase I/II, open-label, multicenter study.

BACKGROUND: The anti-CD38 antibody isatuximab is approved for the treatment of relapsed/refractory multiple myeloma, but there are no data on its efficacy in solid tumors. This phase I/II study (NCT03637764) assessed the safety and activity of isatuximab plus atezolizumab (Isa + Atezo), an anti-programmed death-ligand 1 (PD-L1) antibody, in patients with immunotherapy-naive solid tumors: epithelial ovarian cancer (EOC), glioblastoma (GBM), hepatocellular carcinoma (HCC), and squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Phase I assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and the recommended phase II dose (RP2D) of isatuximab 10 mg/kg intravenously (i.v.) every week for 3 weeks followed by once every 3 weeks + atezolizumab 1200 mg i.v. every 3 weeks. Phase II used a Simon's two-stage design to assess the overall response rate or progression-free survival rate at 6 months (GBM cohort). Interim analysis was carried out at 6 months following first dose of the last enrolled patient in each cohort. Pharmacodynamic biomarkers were tested for CD38, PD-L1, tumor-infiltrating immune cells, and FOXP3+ regulatory T cells (Tregs) in the tumor microenvironment (TME). RESULTS: Overall, 107 patients were treated (EOC, n = 18; GBM, n = 33; HCC, n = 27; SCCHN, n = 29). In phase I, Isa + Atezo showed an acceptable safety profile, no dose-limiting toxicities were observed, and RP2D was confirmed. Most patients experienced ≥1 treatment-emergent adverse event (TEAE), with ≤48.5% being grade ≥3. The most frequent TEAE was infusion reactions. The study did not continue to stage 2 based on prespecified targets. Tumor-infiltrating CD38+ immune cells were reduced and almost cleared after treatment. Isa + Atezo did not significantly modulate Tregs or PD-L1 expression in the TME. CONCLUSIONS: Isa + Atezo had acceptable safety and tolerability. Clinical pharmacodynamic evaluation revealed efficient target engagement of isatuximab via treatment-mediated reduction of CD38+ immune cells in the TME. Based on clinical data, CD38 inhibition does not improve responsiveness to PD-L1 blockade in these patients.

Serial transverse enteroplasty (STEP) in case of short bowel syndrome: did we achieve our goal? A systematic review.

Surveys on Serial Transverse Enteroplasty (STEP) published in international literature (1 January 2003- 31 May 2021) were searched. Articles were included from 17 countries: 1/23 comparative and 22/23 cohort studies. STEP was performed on 308 patients: pediatrics, adults, and mixed ages. Pediatric group included 16 studies and the adult 6. Pre-STEP residual small bowell (SB) length for pediatrics and adults ranged from 18 to 26 cm and from 30 to 70 cm, respectively. Post-STEP increased SB length for pediatrics and adults ranged between 42 and 100% and 50% and 176%, respectively. For pediatrics, enteral autonomy was reached in 32.22% of cases, parenteral nutrition (PN) dependence was 36.11%, a repeated STEP procedure (Re-STEP) was needed in 17.22%, and a bowel transplant was performed in 6.11%. In adults, enteral autonomy was achieved in 52.38%, while PN dependence was 37.1%, and no Re-STEP or transplantation were required. For the mixed group, post-STEP bowel length increased from 2 to 50 cm, enteral autonomy was obtained in 43%, PN dependence was 57%, without reported Re-STEP or transplantation. Mortality rates were between 5.55% (pediatric) and 7.14% (adults). Preoperative length with preservation of ileocecal valve represented the main predictive factors to achieve enteral autonomy.

Intestinal-type mucinous ovarian carcinoma arising from a seromucinous precursor lesion.

OBJECTIVE: Mucinous ovarian carcinoma is a tumor with gastrointestinal differentiation, which is not associated with endometrial-type (endometriotic or seromucinous) precursors. Here, we describe a peculiar case of mucinous ovarian tumor with intestinal differentiation arising in a seromucinous lesion, which may represent a distinct entity. CASE PRESENTATION: A 58-year woman underwent surgery due to a 14.5-cm ovarian mass with lymph nodal, peritoneal, omental and colorectal involvement. Histological examination with ancillary immunohistochemical analysis has been performed. Histologically, the mass was a carcinoma with intestinal differentiation and expansile growth pattern, arising in a seromucinous cystadenoma with intestinal metaplasia. Both the carcinoma and the metaplasia showed loss of Müllerian markers (estrogen and progesterone receptors, PAX8) and positivity for intestinal-type markers (cytokeratin 20, CDX2). CONCLUSIONS: Our case may represent the ovarian counterpart of endometrial gastrointestinal-type carcinoma, which is an aggressive entity developing from gastrointestinal metaplasia of the endometrial epithelium. Acknowledging the existence of such entity might be relevant in terms of diagnosis and patient management.

A deep learning classifier for digital breast tomosynthesis.

PURPOSE: To develop a computerized detection system for the automatic classification of the presence/absence of mass lesions in digital breast tomosynthesis (DBT) annotated exams, based on a deep convolutional neural network (DCNN). MATERIALS AND METHODS: Three DCNN architectures working at image-level (DBT slice) were compared: two state-of-the-art pre-trained DCNN architectures (AlexNet and VGG19) customized through transfer learning, and one developed from scratch (DBT-DCNN). To evaluate these DCNN-based architectures we analysed their classification performance on two different datasets provided by two hospital radiology departments.DBT slice images were processed following normalization, background correction and data augmentation procedures. The accuracy, sensitivity, and area-under-the-curve (AUC) values were evaluated on both datasets, using receiver operating characteristic curves. A Grad-CAM technique was also implemented providing anindication of the lesion position in the DBT slice. RESULTS: Accuracy, sensitivity and AUC for the investigated DCNN are in-line with the best performance reported in the field. The DBT-DCNN network developed in this work showed an accuracy and a sensitivity of (90% ± 4%) and (96% ± 3%), respectively, with an AUC as good as 0.89 ± 0.04. Ak-fold cross validation test (withk = 4) showed an accuracy of 94.0% ± 0.2%, and a F1-score test provided a value as good as 0.93 ± 0.03. Grad-CAM maps show high activation in correspondence of pixels within the tumour regions. CONCLUSIONS: We developed a deep learning-based framework (DBT-DCNN) to classify DBT images from clinical exams. We investigated also apossible application of the Grad-CAM technique to identify the lesion position.

Metastasis-directed stereotactic body radiation therapy in the management of oligometastatic head and neck cancer.

INTRODUCTION: Recently major efforts have been made to define the oligometastatic setting, but for head and neck cancer (HNC) limited data are available. We aimed to evaluate outcome of oligometastatic HNC treated with Stereotactic body radiotherapy (SBRT) as metastasis-directed therapy. MATERIALS AND METHODS: We analyzed patients treated with SBRT on a maximum of five oligometastases from HNC, in up to two organs. Concomitant treatment was allowed. End points were toxicity, local control of treated metastases (LC), progression-free survival (PFS) and overall survival (OS). RESULTS: 48 consecutive patients and 71 lesions were treated. With a follow-up of 20.2 months, most common primary tumors were larynx (29.2%) and salivary glands (29.2%), while common site of metastases was lung (59.1%). Median dose was 48 Gy (21-75) in 3-8 fractions. Treatment was well tolerated, with two patients reporting mild pain and nausea. LC rates at 1 and 2 years were 83.1% and 70.2%. Previous local therapy (HR 4.97; p = 0.002), oligoprogression (HR 4.07; p = 0.031) and untreated metastases (HR 4.19; p = 0.027) were associated with worse LC. PFS at 1 and 2 years were 42.2% and 20.0%. Increasing age (HR 1.03; p = 0.010), non-adenoid cystic carcinoma (HR 2.57; p = 0.034) and non-lung metastases (HR 2.20; p = 0.025) were associated with worse PFS. One- and 2-years OS were 81.0% and 67.1%. Worse performance status (HR 2.91; p = 0.049), non-salivary primary (HR 19.9; p = 0.005), non-lung metastases (HR 2.96; p = 0.040) were correlated with inferior OS. CONCLUSIONS: SBRT can be considered a safe metastasis-directed therapy in oligometastatic HNC. Efficacy of the treatment seems to be higher when administered upfront in the management of metastatic disease; however, selection of patients need to be improved due to the relevant risk of appearance of new metastatic site after SBRT.

A validated method to identify Echinococcus granulosus sensu lato at species level.

The zoonotic tapeworm Echinococcus granulosus sensu lato (s.l.) represents a species complex encompassing multiple causative agents of cystic echinococcosis, a neglected tropical disease affecting more than one million people in the world. At least eight genotypes, grouped in five species, are currently recognized within this species complex, and they differ in terms of relative public health impact. Here we present a molecular method that first identifies the common E. granulosus sensu stricto (s.s.) (genotypes G1 and G3) based on a PCR-RFLP assay, and can further identify the remaining species based on a multiplex PCR assay. We demonstrate the applicability of the method to DNA extracted from parasitic cyst material of human and animal origin, preserved in ethanol or frozen. The method has been developed and validated at the European Union Reference Laboratory for Parasites (EURLP), according to the ISO/IE 17025.

Lung cancer management: monitoring and treating resistance development in third-generation EGFR TKIs.

INTRODUCTION: Patients treated with third-generation EGFR TKIs will develop resistance to treatment at a certain point. Early detection of resistance occurrence could allow more options for treatment. AREAS COVERED: We discuss the development of third-generation EGFR TKIs, focusing on osimertinib and discuss the most common resistance mechanisms under evaluation. We also debate how this resistance can be detected; particularly we review the possible application of liquid biopsy in this scenario. Lastly we discuss available treatment options when resistance occurs, with an eye on ongoing trials and possible future developments. EXPERT OPINION: As resistance will ultimately develop, a strict instrumental follow-up as per international guidelines is required with the aim of detecting this resistance in an early phase. Detecting an oligoprogression could allow the integration of local ablative therapies while further delaying the need for a systemic therapy change. By exploiting the increasing potentiality of liquid biopsy, in the near future, physicians could be able to understand why a patient develops resistance and therefore can choose the best possible individualized treatment option.

When a mimicker wears strange faces: description of an osteogenic melanoma arising within an ovarian teratoma with focus on its late peritoneal relapse.

Secondary malignancies arising within mature teratomas are a rare event, originating from malignant transformation of the tissues derived from one of the three germ cell layers. Osteogenic melanoma is exceedingly rare histologic variant of malignant melanoma, in which the melanoma is associated to an osteogenic sarcoma component. To the best of our knowledge, first case of osteogenic melanoma arising within mature ovarian teratoma in a 30-year-old woman without evidence of a primary cutaneous or visceral melanoma. The present case showed an unusual morphological and immunohistochemical pattern and was incorrectly diagnosed as undifferentiated carcinoma. After a 15 years follow-up period, the patient presented a peritoneal recurrence histologically constituted by epithelioid cells with prominent osteoid formation and with immunohistochemical expression of melanocytic markers (S100, HMB-45). Heterozygote Mutation V600E/E complex has been detected in the BRAF exon 15 sequence. The case was then interpreted as osteogenic melanoma. The present case contributes to widen the spectrum of neoplasms derived from malignant transformation of ovarian teratomas and provides also new insights about the clinical behavior of osteogenic melanoma when arising outside its usual anatomical location.

The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.

Ubiquitin Proteasome System (UPS) is an adaptable and finely tuned system that sustains proteostasis network under a large variety of physiopathological conditions. Its dysregulation is often associated with the onset and progression of human diseases; hence, UPS modulation has emerged as a promising new avenue for the development of treatments of several relevant pathologies, such as cancer and neurodegeneration. The clinical interest in proteasome inhibition has considerably increased after the FDA approval in 2003 of bortezomib for relapsed/refractory multiple myeloma, which is now used in the front-line setting. Thereafter, two other proteasome inhibitors (carfilzomib and ixazomib), designed to overcome resistance to bortezomib, have been approved for treatment-experienced patients, and a variety of novel inhibitors are currently under preclinical and clinical investigation not only for haematological malignancies but also for solid tumours. However, since UPS collapse leads to toxic misfolded proteins accumulation, proteasome is attracting even more interest as a target for the care of neurodegenerative diseases, which are sustained by UPS impairment. Thus, conceptually, proteasome activation represents an innovative and largely unexplored target for drug development. According to a multidisciplinary approach, spanning from chemistry, biochemistry, molecular biology to pharmacology, this review will summarize the most recent available literature regarding different aspects of proteasome biology, focusing on structure, function and regulation of proteasome in physiological and pathological processes, mostly cancer and neurodegenerative diseases, connecting biochemical features and clinical studies of proteasome targeting drugs.

The use of radiation therapy for oligoprogressive/oligopersistent oncogene-driven non small cell lung cancer: State of the art.

Oncogene-driven non small cell lung cancer (NSCLC) is a distinct entity in thoracic oncology. The availability of effective target therapies, like EGFR inhibitors or ALK inhibitors, have revolutionized the prognosis of these patients. However, despite an initial response in the majority of patients, drug resistance ultimately occurs. In some cases, this resistance develops in few clonal cells (oligoprogression), so that a local ablation of these resistant deposits could allow to maintain the same systemic therapy and possibly to prolong patients' survival. For these purposes, stereotactic body radiation therapy (SBRT) is an ideal local ablative treatment, because it is effective, non invasive and with limited side effects. In this review, we aim to analyze available clinical data to verify whether SBRT can allow these patients to continue with existing target therapy longer, delay the switch to other systemic therapies and improve their outcome modifying the natural history of the disease.

Frozen section accurately allows pathological characterization of endometrial cancer in patients with a preoperative ambiguous or inconclusive diagnoses: our experience.

BACKGROUND: The aim of this study was to assess the agreement rate between intraoperative evaluation (IOE) and final diagnosis (FD) in a series of surgically resected endometrial carcinoma (EC), with a preoperative ambiguous or inconclusive diagnosis by endometrial biopsies and imaging. METHODS: A retrospective study was performed selecting patients who underwent surgery with IOE for suspected EC at our institution from 2012 to 2018. A K coefficient was determined with respect to the histotype, tumor grade, myometrial infiltration and cervical involvement. RESULTS: Data analysis has been performed on 202 women. The IOE evaluation was distributed as Endometrioid (n = 180) and Non-Endometrioid (n = 22). The comparison between the frozen section (FS) and the definitive histological subtype showed an overall agreement rate of 93,07% (k = 0.612) and an agreement of 97.2% for Endometrioid vs 59% for Non-Endometrioid tumors. The FIGO system grading was the same in 91,1% of patients, none was upgraded and in 8,9% downgraded. Observed agreements were 89,11% and 95,54% for myometrial and cervical involvement, respectively. CONCLUSIONS: The good agreement between intraoperative grading, myometrial invasion and their histological definition on permanent sections highlights that FS is a good predictor for surgical outcome, in particular in presence of a preoperative ambiguous or inconclusive diagnostic evaluation.

Significant chronic airway abnormalities in never-smoking HIV-infected patients.

OBJECTIVES: The aim of the study was to describe chronic lung disease in HIV-infected never-smokers by looking at clinical, structural and functional abnormalities. METHODS: This comparative cross-sectional study included 159 HIV-infected never-smoking patients [mean (± standard deviation) age 54.6 ± 9.1 years; 13.2% female; 98.1% with undetectable viral load] and 75 nonmatched never-smoking controls [mean (± standard deviation) age 52.6 ± 6.9 years; 46.7% female]. We examined calcium scoring computer tomography (CT) scans or chest CT scans, all with a lung-dedicated algorithm reconstruction, to assess emphysema and airway disease (respiratory bronchiolitis and/or bronchial wall thickening), tested pulmonary function using spirometry, lung volumes and the diffusion lung capacity of carbon monoxide (DLCO), and assessed respiratory symptoms using the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT). RESULTS: Twenty-five (17.2%) of the HIV-infected patients versus two (2.7%) of the controls had a CAT score > 10. Only 5% of the HIV-infected patients showed FEV1% < 80%, and 25% had DLCO < 75% of the predicted value. Based on the CT scans, they had increased prevalences, compared with the controls, of airway disease (37% versus 7.9%, respectively) and emphysema (18% versus 4%, respectively), with more severe and more frequent centrilobular disease. After correction for age, sex and clinical factors, HIV infection was significantly associated with CAT > 10 [odds ratio (OR) 7.7], emphysema (OR 4), airway disease (OR 4.5) and DLCO < 75% of predicted (OR 4). CONCLUSIONS: Although comparisons were limited by the different enrolment methods used for HIV-infected patients and controls, the results suggest that never-smoking HIV-infected patients may present with chronic lung damage characterized by CT evidence of airway disease. A minority of them showed respiratory symptoms, without significant functional abnormalities.

Hemangioma of the umbilical cord with associated amnionic inclusion cyst: two uncommon entities occurring simultaneously.

This corrects the article DOI: 10.32074/1591-951X-26-17.

Hemangioma of the umbilical cord with associated amnionic inclusion cyst: two uncommon entities occurring simultaneously.

Umbilical cord hemangioma is an uncommon benign vascular neoplasm arising from the free segment of the umbilical cord, distinct from placental and fetal insertion, and is thought to originate from endothelial cells of the umbilical vessels. Cystic changes in the umbilical cord rarely occur as a consequence of the damage to the amnionic surface of the cord caused by the presence of the hemangioma. Until now, a total of 8 cases of umbilical cord hemangioma associated with cystic changes in the umbilical cord have been reported in the literature, however, among these cases, only one showed an associated cyst derived from inclusion of the amniotic epithelium, and the remaining seven cases consisted of hemangiomas with associated pseudocyst of the umbilical cord. We herein report a case of umbilical cord hemangioma with an associated amnionic epithelial inclusion cyst. Clinicopathological features and differential diagnostic considerations are also discussed.

Impact of cardiovascular/diabetic comorbidity on conversion rate during laparoscopic cholecystectomy for acute cholecystitis: a multi-center study on early versus very delayed approach.

BACKGROUND: The impact of diabetes and cardiovascular comorbidity on laparoscopic cholecystectomy has been long debated, evaluating them as risk factors for conversion to an open procedure especially in patients with acute cholecystitis: an "early" procedure, as suggested by 2013 Tokyo guidelines, has been compared to a "very delayed" one in patients under anticoagulant/antiplatelet therapy or treated for diabetes and referred by medical wards to surgery after the acute period. METHODS: We selected 240 patients operated for acute cholecystitis by laparoscopy over the last 4 years at St. Orsola University Hospital-Bologna and Umberto I University Hospital-Rome, comparing 98 diabetic/cardiovascular patients versus 142 subjects as control group: the selection was based on operative timing, "early" (73 patients treated within 3 days) and "very delayed" (167 patients operated after 6 weeks). RESULTS: In the "early" subgroup there was no difference comparing diabetic/cardiovascular patients (31 pts) versus control group (42 pts) while in the "very delayed" subgroup among diabetic/cardiovascular patients (67 pts) there was significantly male predominance, ASA III/IV prevalence and less positive imaging findings versus control group (100 pts). In both subgroups, the conversion rate was significantly higher for diabetic/cardiovascular patients ("early"=25.8% and "very delayed"=8.95%) compared to control groups ("early"=4.76% and "very delayed"=1%), showing a trend (p=0.058) towards an increased conversion rate in the early approach among diabetic/cardiovascular group. CONCLUSIONS: Our study showed a significantly increased conversion rate to an open cholecystectomy for diabetic/cardiovascular patients affected by cholecystitis, especially within 3 days by the acute episode.

Colocutaneous fistula through ulcerative colitis and cancer to the pyoderma gangrenosum: a never-ending story for a single patient. Case report.

BACKGROUND: Inflammatory bowel diseases may be associated with many extraintestinal complications, that in some cases can represent the first onset of these disorders. In particular during the course of the disease, Ulcerative Colitis develops extraintestinal manifestations very frequently. One of the rarest is pyoderma gangrenosum, a noninfectious neuthrophilic dermatosis, that can involve most commonly legs but also other parts of the skin or mucosas. It can be idiopathic or associated with gammopathies, vasculitis, chronic arthritis or, like in our case, with inflammatory bowel disease and malignancies. CASE PRESENTATION: A 38-year-old man was referred to our Department with a colo-cutaneous fistula in the left quadrant of abdominal wall. In the anamnesis he reported a trauma during a soccer match three weeks before. Through a CT scan and endoscopy with biopsy an inflammatory bowel disease with a segmental colitis and stenosis was diagnosed. After medical therapy, an initial radiological drainage and a period of parenteral nutrition, he underwent a left hemicolectomy. Despite the previous endoscopic biopsy the histopathological examination put in evidence not only inflammatory disease (in particular Ulcerative Colitis) but also a colorectal tumor pT4pN0. After the full recovery before chemotherapy he has developed on the chest and on the abdomen some painful nodules, with central necrosis, one of those in contact with one of the ribs. Through TC and RM it was impossible to understand the precise nature of these skin lesions. With biopsy a pyoderma gangrenosum was diagnosed and treated until complete resolution. DISCUSSION AND CONCLUSION: Management of inflammatory bowel diseases can be a true challenge, not only for the intestinal manifestations, but also for all the other features not related to gut. In some cases the same patient can develop many complications, such as malignancies or rare cutaneous diseases. Despite the initial surprise for such a weird evolution in a same patient, from fistula to inflammatory disease to cancer and finally to pyoderma gangrenosum, to face every single complication following consolidated diagnostic and pathological paths has been the correct strategy for controlling the disease.

Accreditation for colorectal cancer surgery in Italy. Preliminary results of a new program in a district hospital.

Accreditation for colorectal (CR) cancer surgery has become a major issue in Italy. This study aimed to analyze the early results of a newly structured program for the treatment of CR cancer in a rural district hospital. Between 2017 and 2018, a total of 214 consecutive patients underwent a CR procedure for malignancy. There were 113 men and 101 women of a mean age of 74 years. Primary CR adenocarcinoma was diagnosed in 210 patients (98%). The incidence of stage I, II, III, and IV disease was 26%, 31%, 24%, and 19% respectively. Hospital volume increased tenfold compared to previous years. Anatomical resection was performed in 204 patients. Right-sided resection and resection of the transverse colon or left angle were performed in 76 (37%) and 14 (7%) patients, respectively. A restorative left sided CR resection was performed in 80 patients (39%), whereas Hartmann procedure and Miles abdominal-perineal resection were performed in 27 (13%) and 6 (3%) patients, respectively. Total colectomy with ileorectal anastomosis was performed in one patient, and two more patients underwent atypical resection. Emergency cecostomy was performed in 15 patients and a colic endoprosthesis was implanted in one patient for obstruction and seven underwent resection afterwards. Laparoscopic resection was performed in 118 patients (57.8%), and the conversion rate was 2%. Overall morbidity, reintervention, and mortality rates were 24.6%, 3,7%, and 3.2%, respectively. The incidence of AL was 4.6%, and two patients died of the consequences of it after right hemicolectomy. Five more elderly patients died for non-surgical related medical complications. The median hospital stay was ten days, and early unplanned readmission rate was 2%. Hospital and surgeon requirements, in terms of minimum volume, organization, and surgical outcome were fulfilled. A rural district hospital can become a tertiary referral center for the surrounding districts without imposing unreasonable travel burdens for patients. CR surgery represents a capital investment for the hospital administration since it shows the effectiveness and quality of care.

Early versus delayed approach in cholecystectomy after admission to an emergency department. A multicenter retrospective study.

BACKGROUND: Discussion regarding the timing of cholecystectomy for acute cholecystitis is still ongoing. This study evaluates the outcomes of patients who underwent surgery for acute cholecystitis after emergency admission at St. Orsola University Hospital of Bologna and Umberto I Hospital La Sapienza University of Rome. PATIENTS AND METHODS: . We performed a retrospective study on 464 patients who underwent cholecystectomy for acute cholecystitis. We divided patients in three groups based on the time elapsed between the onset of symptoms and surgery: within 72 hours (Group A), between 72 hours and 6 weeks (Group B) and after 6 weeks (Group C). We performed both univariate and multivariate statistical analysis on the data collected. RESULTS: The best results were in Group C, with significant differences with the others two groups: higher rates of laparoscopic technique (93% of cases), no mortality, better morbidity and shorter hospital stay. On the contrary, no significant differences were observed between Groups A and B: laparoscopic cholecystectomy 67% vs 66%, morbidity (Clavien-Dindo III-IV) 5% vs 5%, mortality 2% vs 1%, hospital stay 6,6 vs 5,6 days. Conversion rate was 11% in Group A, 18% in Group B and 4% in Group C. CONCLUSION: Our experience shows better results for cholecystectomies performed after 6 weeks from the onset of symptoms, while earlier cholecystectomies have worse outcomes regardless if they are performed before or after 72 hours from the onset of symptoms.