Intensified Total Neoadjuvant Therapy in Patients With Locally Advanced Rectal Cancer: A Phase II Trial.

AIMS: We assessed the efficacy and safety of total neoadjuvant therapy, including targeted agent plus FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) induction chemotherapy followed by intensified chemoradiotherapy (CRT) and surgical resection, in patients with locally advanced rectal cancer. MATERIALS AND METHODS: This was a single-arm, single-centre phase II trial. Eligible patients had non-metastatic locally advanced rectal adenocarcinoma. Based on Ras-BRAF status, patients were treated with bevacizumab (mutated Ras-BRAF) or panitumumab/cetuximab (wild-type Ras-BRAF) plus FOLFOXIRI regimen followed by oxaliplatin-5-fluorouracil-based CRT and surgery. The primary end point was pathological complete response rate. Secondary end points were toxicity, compliance, tumour downstaging, complete resection, surgical complications, local and distant failures and overall survival. The sample size was planned to expect an absolute 20% improvement in pathological complete response rate over historical literature data with an α error of 0.05 and a power of 80%. RESULTS: Between October 2015 and September 2019, 28 patients (median age 66 years) were enrolled. All patients had regional lymph node involvement at diagnosis. FOLFOXIRI plus bevacizumab was administered in 11 mutated Ras-BRAF patients, whereas the 17 wild-type Ras-BRAF patients received FOLFOXIRI plus panitumumab/cetuximab. Overall, total neoadjuvant therapy was well tolerated and 26 patients (92.9%) completed the programmed strategy. A complete response was achieved in nine cases (32.1%) and a nearly pathological complete response (ypT1 ypN0) in two patients (7.2%). There was no evidence of febrile neutropenia and no grade 4 adverse events were recorded. Radical resection was achieved in all cases. CONCLUSION: FOLFOXIRI plus targeted agent-based induction chemotherapy and intensified CRT before surgery showed promising clinical activity and was well tolerated in locally advanced rectal cancer patients. This phase II trial provides a strong rationale for phase III studies.

Criticism of learning curve in laparoscopic adrenalectomy: a systematic review.

BACKGROUND: Laparoscopic adrenalectomy (LA) has become the treatment of choice for benign adrenal lesions. Lateral Transperitoneal Laparoscopic Adrenalectomy (LTLA) is considered the gold standard. The number of LTLAs a surgeon must perform, in order to complete his learning curve, is not well defined in Literature. Moreover, the few papers dealing with the learning curve for LTLAs show controversial results and consider different evaluation parameters. METHODS: The systematic review has been carried out according to PRISMA statement. The literature search included PubMed and Scopus database. Hand searching of reference lists of previous review articles and relevant studies was also performed. The search string was "learning curve AND laparoscopic adrenalectomy". RESULTS: A total of 9 papers met the inclusion criteria out of 94 non duplicate citations. The aim of this systematic review is to provide a multidimensional evaluation by bringing into focus evaluation parameters of surgical performance, (operative time, intraoperative complications, conversion rate and blood loss), factors related to patient's pathology (side, size, adrenal pathology) and surgeon-specific properties. CONCLUSIONS: Operative time, intraoperative bleeding, intraoperative complications and conversion rate are the main parameters that have been considered for the achievement of learning curve, and for each there are discrepancies, mainly due to the relative rarity of adrenal tumors, and so for difficulties in obtaining approper analysis that could establish an effective learning curve. So, further evaluations in larger experience are needed.

The role of laparoscopic surgery in isolated adrenal metastasis: our personal experience.

BACKGROUND: Over the past 25 years, mini-invasive adrenalectomy has become the treatment of choice for most adrenal diseases, and even adrenal malignancies in selected cases. The aim of this retrospective evaluation is to assess the effectiveness of laparoscopic adrenalectomy as a treatment of choice for adrenal metastases. METHODS: From 2008 to 2018, 207 laparoscopic adrenalectomies have been performed in our Department of Surgery. Among these, in 12 cases the indication to adrenalectomy was metastatic adrenal lesion. RESULTS: The right adrenal gland was removed in 8 cases and the left adrenal gland in 4 cases. A complete resection (R0) was achieved in all patients. The median operative time was 130.6 ± 23.3 min. The median postoperative hospitalization was 3.5±2.0 days. Only one patient showed postoperative grade II complications, according to Clavien-Dindo classification. All patients underwent follow-up at 6-12-18 months without showing disease recurrence. There was no intra and perioperative mortality. Conversion to laparotomic surgery has never been performed. Mean tumor size was 2.4 cm ±1.6 cm. CONCLUSIONS: Laparoscopic adrenalectomy for metastasis permits to achieve similar results to the open approach in term of oncological outcomes, but gaining in terms of postoperative hospitalization, intra and post-operative complications as well a greater patient compliance.

Current role of open surgery in adrenal tumors.

AIM: The aim of this retrospective evaluation is to assess the current role of open adrenalectomy, in particular in cases of adrenocortical carcinoma (ACC). MATERIALS AND METHODS: From January 2009 to May 2019, 26 open out of 233 adrenalectomies were performed in our Academic Department. Open adrenalectomy was performed by the anterior approach. A midline abdominal incision or a subcostal surgical incision was used to reach the peritoneal cavity. The resection was defined R0 if the margins of the sample were negative for malignancy. RESULTS: Open adrenalectomy was performed in 26 patients: 10 men and 16 women with a mean age of 61±25.3 years and a mean BMI of 28.4±2.9. The right adrenal gland was removed in 15 cases Romaand the left in 11 cases.We reported 18 diagnosis of malignant pathology. The other diagnosis concerned 5 cases of pheochromocytoma, 1 case of Cushing's disease and 2 cases of hyperaldosteronism. Mean tumor size was 7.7±5.5. Mean operative time was 160 min (range=110-205 minutes). Mean postoperative stay was 7±2 days. Only 3 (10%) patient showed postoperative grade II complications, according to Clavien-Dindo classification. Midline abdominal incision was used in 18 patients, subcostalsurgical incision in 5 patients and bilateral subcostal surgical incision in 3 patients. 3 right nephrectomy was necessary to remove the entire tumor mass. An en bloc R0 tumor resection was accomplished in all cases.There was no intra and perioperative mortality. All patients recovered well from surgery. The mean follow-up period was 15 (range=6-48) months. CONCLUSION: In conclusion, our retrospective study points out the role of open adrenalectomy as the treatment of choice in selected cases with known or suspected malignant adrenal tumors and with size greater than 12 cm.

Second jejunal loop adenocarcinoma associated with celiac disease: the first case report.

INTRODUCTION: Jejunal adenocarcinoma is a very rare disease but the frequency of this rare carcinoma is higher in celiac patients. We report the first case report of a second jejunal loop adenocarcinoma associated with celiac disease. PRESENTATION OF CASE: A 47-year-old woman, with a history of celiac disease. Computerized tomographic scans of the abdomen and pelvis demonstrated a severe retroperitoneal lymphoadenopathy, para-aortic, inter-aorto-caval, porto-caval, posterior pancreaticoduodenal space, celiac trunk, lesser gastric curvature, lymph node grouping. The patient underwent digiunal resection and regional lymphadenectomy. Diagnosis was poorly differentiated jejunal adenocarcinoma, infiltrating subserosal adipose tissue, metastasing in five out of eight regional lymph nodes. U.I.C.C. 2017 grading = pT3 pN2 G3 R0; Stage IIIB. DISCUSSION: The jejunum accounts for 11-25% of small bowel adenocarcinoma, that accounts for less than 5% of gastrointestinal cancer, notwithstanding that 90% of the mucosa surface area of the digestive tract is made by small intestine. To the best of our knowledge, this is the first report on a second loop jejunal adenocarcinoma complicating celiac disease. In our study, the diagnosis of cancer was made by computed tomography (CT) of abdomen and the patient was operated. For the diagnosis of small bowel tumour, CT enteroclysis has a sensitivity of 85-95% and a specificity of 90-96%. Complete resection (RO) of the jejunal adenocarcinoma, with regional lymph nodes resection and jejuno-jejunal anastomosis should be performed. CONCLUSION: After curative surgical resections of small bowel adenocarcinoma, adjuvant chemo-therapy has not shown a clear benefit in retrospective studies. Preoperative Chemo-Radio-therapy and careful Imaging Staging are the first steps to planning surgery.

Preservation of left colic artery with lymph node dissection of IMA root during laparoscopic surgery for rectosigmoid cancer. Results of a retrospective analysis.

BACKGROUND: During sigmoid or rectal cancer surgery, dissection of lymph-nodes at the origin of inferior mesenteric artery is mandatory. Nevertheless, ligation of the origin of IMA should compromise blood supply to left colon and affect anastomosis. The aim of this retrospective evaluation is to compare high IMA ligation and low IMA ligation with preservation of LCA and skeletonization of the origin of IMA during laparoscopic colorectal resection. METHODS: All 120 patients included were affected by clinically M-0 sigmoid or rectal cancer. A laparoscopic colorectal resection with low or high ligature of IMA was performed. Low ligation was carried out with lymphadenectomy of the arterial root. Patients were divided in 2 groups according to type of treatment: Group A, high IMA ligation (N=65), Group B, low ligation with lymphadenectomy of IMA root (N=55). RESULTS: Preoperatively 59 patients had stage I, 42 patients had stage II  and 19 patients had stage III tumor. A mean of 20.3 +/- 4.5 lymph nodes were removed in group A patients and 18.9 +/- 9.1 in group B patients, and this difference was not statistically significant. Operative time, intraoperative and postoperative complication rates were not different between the two group. CONCLUSIONS: Low IMA ligation combined with lymph-node dissection at its origin is safe and effective, not time consuming and not associated to increased risk of complications and nerve damage. This technique can be considered as alternative to standard high IMA ligation in selected patients.

A Pilot Study on an Integrated Service Based on Wearable Textile Platforms to promote Workers Wellness at Workplace.

This paper describes a study performed in the frame of Wearables project and reports preliminary results. Objective of the study was the implementation of an integrated service finalized to increase employees' well-being through the investigation on the correlation between daily working activity and the observed physical parameters. The project monitored 28 volunteers employed in the field of waste collection (at the Amey's contract with Wolverhampton City Council), for a total of 275 data acquisition sessions. The study has been performed using sensing textiles, to collect objective work-correlated parameters during daily activity, aiming at the acquisition of objective indicators for an improved wellbeing. Physical parameters like heart rate, energy expenditure and heart rate activity-zones distribution have been evaluated from data acquired during normal working activity. The service produced encouraging results both in terms of monitoring individual subjects and in identifying trends correlated to different roles or tasks covered by workers. Also in term of usability and acceptability the system showed interesting potentialities, proving how wearable technologies can trigger innovative approaches and open new prospective in the growing field of workplace wellness.

Right pneumothorax secondary to colonoscopic perforation: a case.

AIM: The purpose of this study is to determine the anatomical aspects, mechanisms, risk factors and appropriate management of development of pneumothorax during a routine colonoscopy. CLINICAL CASE: We report a case of an accidental bowel wall injury during diagnostic colonoscopic with consequent pneumoperitoneum; this was followed by expansion of gas through diaphragmatic fenestration perhaps congenital, in right pleural cavity causing pneumothorax. DISCUSSION: Rarely, colonic perforation during colonoscopy can occur into the extraperitoneal space, thus leading to the passage and diffusion of air along the fascial planes and large vessels, possibly causing pneumoretroperitoneum, pneumomediastinum, pneumopericardium, pneumothorax, and subcutaneous emphysema. The combination of intraperitoneal and extraperitoneal perforation has also been reported. Pneumothorax following a colonoscopy sigmoid perforation is an extremely rare but severe and often lifethreatening complication. CONCLUSION: If the patient develops dyspnea and pneumoderma during or after this procedure, a chest radiogram or thoracoabdominal CT should be taken for diagnostic purposes. Urgent treatment, starting with chest tube insertion(s) and laparotomy or laparoscopy could be lifesaving.

Diagnostic, therapeutic and health-care management protocol in thyroid surgery: a position statement of the Italian Association of Endocrine Surgery Units (U.E.C. CLUB).

PURPOSE: The diagnostic, therapeutic and health-care management protocol (Protocollo Gestionale Diagnostico-Terapeutico-Assistenziale, PDTA) by the Association of the Italian Endocrine Surgery Units (U.E.C. CLUB) aims to help treat the patient in a topical, rational way that can be shared by health-care professionals. METHODS: This fourth consensus conference involved: a selected group of experts in the preliminary phase; all members, via e-mail, in the elaboration phase; all the participants of the XI National Congress of the U.E.C. CLUB held in Naples in the final phase. The following were examined: diagnostic pathway and clinical evaluation; mode of admission and waiting time; therapeutic pathway (patient preparation for surgery, surgical treatment, postoperative management, management of major complications); hospital discharge and patient information; outpatient care and follow-up. RESULTS: A clear and concise style was adopted to illustrate the reasons and scientific rationales behind behaviors and to provide health-care professionals with a guide as complete as possible on who, when, how and why to act. The protocol is meant to help the surgeon to treat the patient in a topical, rational way that can be shared by health-care professionals, but without influencing in any way the physician-patient relationship, which is based on trust and clinical judgment in each individual case. CONCLUSIONS: The PDTA in thyroid surgery approved by the fourth consensus conference (June 2015) is the official PDTA of U.E.C. CLUB.

Enhanced Soluble Serum CD40L and Serum P-Selectin Levels in Primary Aldosteronism.

Primary aldosteronism (PA) is one of the most frequent forms of secondary hypertension, associated with atherosclerosis and higher risk of cardiovascular events. Platelets play a key role in the atherosclerotic process. The aim of the study was to evaluate the platelet activation by measuring serum levels of soluble CD40L (sCD40L) and P-selectin (sP-selectin) in consecutive PA patients [subgroup: aldosterone-secreting adrenal adenoma (APA) and bilateral adrenal hyperplasia (IHA)], matched with essential hypertensive (EH) patients. The subgroup of APA patients was revaluated 6-months after unilateral adrenalectomy. In all PA group, we measured higher serum levels of both sP-selectin (14.29±9.33 pg/ml) and sCD40L (9.53±4.2 ng/ml) compared to EH patients (9.39±5.3 pg/ml and 3.54±0.94 ng/ml, respectively; p<0.001). After removal of APA, PA patients showed significant reduction of blood pressure (BP) values, plasma aldosterone (PAC) levels and ARR-ratio, associated with a significant reduction of sP-selectin (16.74±8.9 pg/ml vs. 8.1±3.8 pg/ml; p<0.01) and sCD40L (8.6±1 ng/ml vs. 5.24±0.94 ng/ml; p<0.001). In PA patients, we found a significant correlation between sP-selectin and sCD40L with PAC (r=0.52, p<0.01; r=0.50, p<0.01, respectively); this correlation was stronger in APA patients (r=0.54; p<0.01 r=0.63; p<0.01, respectively). Our results showed that PA is related to platelet activation, expressed as higher plasma values of sCD40L and sP-selectin values. Surgical treatment and consequent normalization of aldosterone secretion was associated with significant reduction of sCD40L and sP-selectin values in APA patients.

Epicardial Fat Thickness and Primary Aldosteronism.

Primary aldosteronism (PA) is associated with increased cardiovascular risk and left ventricle (LV) changes. Given its peculiar biomolecular and anatomic properties, excessive epicardial fat, the heart-specific visceral fat depot, can affect LV morphology. Whether epicardial fat can be associated with aldosterone and LV mass (LVM) in patients with PA is unknown. We performed ultrasound measurement of the epicardial fat thickness (EAT) in 79 consecutive newly diagnosed patients with PA, 59 affected by bilateral adrenal hyperplasia (IHA), 20 aldosterone-producing adenoma (APA), and 30 patients with essential hypertension (low renin hypertension) (EH). The 3 groups did not differ by age, sex distribution, body mass index (BMI), waist circumference (WC), or blood pressure values. EAT showed a trend of increase in both APA and IHA groups when compared to patients with EH (8.3±1.8 vs. 7.9±1.3 vs. 7.8±2 mm, respectively). EAT was significantly correlated with indexed LVM in the IHA group (r=0.35, p<005), better than BMI or WC were. Interestingly, EAT was highly associated with plasma aldosterone concentrations (PAC) and PAC/plasma renin activity (PRA) (PAC/PRA) in the APA group (p=0.58, p=0.37, p<0.01, for both), whereas BMI and WC were not. EAT was also correlated with PRA in the IHA group (p=-0.28, p<0.05). Our study indicates a novel and interesting interaction of EAT with PA, independent of obesity, abdominal fat and blood pressure control. EAT can locally affect LVM, at least in patients with IHA. Further studies in larger population will be required to confirm these findings.

Primary aldosteronism with concurrent primary hyperparathyroidism: clinical case load in a single centre.

OBJECTIVE: Primary aldosteronism (PA) represents the main cause of endocrine secondary arterial hypertension in which aldosterone production is inappropriately elevated. Primary hyperparathyroidism (PHPT) is an endocrine disease characterized by hypercalcemia due to overproduction of parathyroid hormone (PTH). Although these two endocrine pathologies are secondary to hypertension in middle aged population, the occurrence of the PHPT in PA patients has rarely reported in the literature. The aim of the study was to describe some PA patients with concurrent PHPT, referred in a tertiary center of arterial hypertension. PATIENTS: We performed a retrospective study. In particular, the registry of 306 patients with PA seen in our center since 2004 was examined and revealed 8 patients (2.6%) with concurrent PHPT. CONCLUSIONS: There are several possible explanations for the association of these two endocrine disorders, including the combination was a random finding that PA inheres PHPT or vice versa.

First Experimental Characterization of Microwave Emission from Cosmic Ray Air Showers.

We report the first direct measurement of the overall characteristics of microwave radio emission from extensive air showers. Using a trigger provided by the KASCADE-Grande air shower array, the signals of the microwave antennas of the Cosmic-Ray Observation via Microwave Emission experiment have been read out and searched for signatures of radio emission by high-energy air showers in the GHz frequency range. Microwave signals have been detected for more than 30 showers with energies above 3×10^{16} eV. The observations presented in this Letter are consistent with a mainly forward-directed and polarized emission process in the GHz frequency range. The measurements show that microwave radiation offers a new means of studying air showers at E≥10^{17} eV.

Recurrent laryngeal nerve palsy and substernal goiter. An Italian multicenter study.

The aim of this retrospective multicenter study was to verify whether the substernal goiter and the type of surgical access could be risk factors for recurrent laryngeal nerve palsy during total thyroidectomy. Between 1999-2008, 14,993 patients underwent total thyroidectomy. Patients were divided into three groups: group A (control; n=14.200, 94.7%), cervical goiters treated through collar incision; group B (n=743, 5.0%) substernal goiters treated by cervical approach; group C (n=50, 0.3%) in which a manubriotomy was performed. Transient and permanent unilateral palsy occurred significantly more frequently in B+C vs. A (P≤.001) and in B vs. A (P≤.001). Transient bilateral palsy was significantly more frequent in B+C vs. A (P≤.043) and in C vs. A (P≤.016). Permanent bilateral palsy was significantly more frequent in B+C vs. A (P≤.041), and in B vs. A (P≤.037). Extension of the goiter into the mediastinum was associated to increased risk of recurrent nerve palsy during total thyroidectomy.

Fournier's gangrene: early diagnosis. How to diagnose, how to manage it.

Fournier's gangrene (FG) is a rare surgical emergency and a life-threatening condition with a rapidly progressive gangrene defined as a necrotizing fasciitis of the perineal or genital areas leading to septic shock and death if untreated. Risk factors are diabetes, immune compromise, obesity, drug use, or genital trauma. Patients are treated by incision and drainage. Aim of the study is to analyze cases of early manifestations of FG and consider aspect of diagnosis based on clinical presentation and the importance of precocious surgical treatment. We had experience of early lesions of FG in 22 cases. We report three cases in which the initial clinical presentation was typical of precocious signs referable to FG. Foley catheter was used in all cases, no diverting colostomy was performed. The patients were treated by artificial i.v. feeding. No extensive demolition of perineal tissues were operated, neither plastic surgery was required. Antibiotic therapy combined to surgical treatment with incision and drainage were performed in all cases. Admission in the intensive care unit was effective when indicated. No mortality was registered in all 22 cases of the series. FG is rare, severe condition requiring a multidisciplinary approach. An early diagnosis and an aggressive surgical treatment, improved by antibiotic therapy, hyperbaric oxygen therapy and proper wound care are the key points of FG management. In selected patients, colostomy or cystostomy must be considered when simple catheterization is not sufficient. Severe cases must be therefore referred to high-volume and specialized centres with specialist professional and intensive care facilities.

Diagnostic, therapeutic and healthcare management protocols in parathyroid surgery: II Consensus Conference of the Italian Association of Endocrine Surgery Units (U.E.C. CLUB).

AIM: To update the Diagnostic-Therapeutic-Healthcare Protocol (Protocollo Diagnostico-Terapeutico-Assistenziale, PDTA) created by the U.E.C. CLUB (Association of the Italian Endocrine Surgery Units) during the I Consensus Conference in 2008. METHODS: In the preliminary phase, the II Consensus involved a selected group of experts; the elaboration phase was conducted via e-mail among all members; the conclusion phase took place during the X National Congress of the U.E.C. CLUB. The following were examined: diagnostic pathway and clinical evaluation; mode of admission and waiting time; therapeutic pathway (patient preparation for surgery, surgical treatment, postoperative management, management of major complications); hospital discharge and patient information; outpatient care and follow-up. CONCLUSIONS: The PDTA for parathyroid surgery approved by the II Consensus Conference (June 2013) is the official PDTA of the U.E.C. CLUB.

Daily-life monitoring of stroke survivors motor performance: the INTERACTION sensing system.

The objective of the INTERACTION Eu project is to develop and validate an unobtrusive and modular system for monitoring daily life activities, physical interactions with the environment and for training upper and lower extremity motor function in stroke subjects. This paper describes the development and preliminary testing of the project sensing platform made of sensing shirt, trousers, gloves and shoes. Modular prototypes were designed and built considering the minimal set of inertial, force and textile sensors that may enable an efficient monitoring of stroke patients. The single sensing elements are described and the results of their preliminary lab-level testing are reported.