Insights from an Italian Delphi panel: exploring resistance to first-generation somatostatin receptor ligands and guiding second-line medical therapies in acromegaly management.

PURPOSE: First-line medical therapy for acromegaly management includes first-generation somatostatin receptor ligands (fgSRLs), but resistance limits their use. Despite international guidelines, the choice of second-line therapy is debated. METHODS: We aim to discuss resistance to fgSRLs, identify second-line therapy determinants and assess glycemia's impact to provide valuable insights for acromegaly management in clinical practice. A group of Italian endocrinologists expert in the pituitary field participated in a two-round Delphi panel between July and September 2023. The Delphi questionnaire encompassed a total of 75 statements categorized into three sections: resistance to fgSRLs therapy and predictors of response; determinants for the selection of second-line therapy; the role of glycemia in the therapeutic management. The statements were rated on a 6-point Likert scale. RESULTS: Fifty-nine (79%) statements reached a consensus. IGF-1 levels resulted central for evaluating resistance to fgSRLs, that should be defined considering also symptomatic clinical response, degree of tumor shrinkage and complications, using clinician- and patient-reported outcome tools available. Factors to be evaluated for the choice of second-line medical therapy are hyperglycemia-that should be managed as in non-acromegalic patients-tumor remnant, resistant headache and compliance. Costs do not represent a main determinant in the choice of second-line medical treatment. CONCLUSION: The experts agreed on a holistic management approach to acromegaly. It is therefore necessary to choose currently available highly effective second-line medical treatment (pegvisomant and pasireotide) based on the characteristics of the patients.

Isolated radial tears of the lateral meniscus midbody: a case series of professional athletes treated with outside-in repair.

PURPOSE: The main aim of the study is to assess clinical and functional outcomes of arthroscopic outside-in repair of isolated radial tears of the midbody of lateral meniscus in professional athletes and to evaluate the return to the sport activity after surgery. METHODS: A retrospective data collection on professional athletes with isolated complete lesion of the midbody of lateral meniscus, treated with arthroscopic outside-in repair was carried out. Outcome measures included functional assessment, Limb Symmetry Index (LSI) and Hamstring Quadriceps Ratio (HQR) and Lysholm score collected before surgery and at 4-month follow-up. Data on return to sport practice and re-injury were also retrieved. RESULTS: Fourteen patients satisfied the selection criteria. Full return to professional sport activity (Tegner 10) was registered in the 86% of the cohort at 4 months after the surgery. Functional testing of the athletes showed a return of the LSI and HQR to the pre-surgical condition, demonstrating a full recovery of the functional ability and muscle strength. Similarly, clinical evaluation through Lysholm score showed an improvement, reaching an average of 97.7 points at 4 months follow-up. CONCLUSION: A good functional recovery and a high rate of return to play has been observed in a population of professional athletes, at 4 months after outside-in repair.

Management of colorectal peritoneal metastases: Expert opinion.

When peritoneal metastases are diagnosed (strong agreement of experts): (i) seek advice from a multidisciplinary coordination meeting (MCM) with large experience in peritoneal disease (e.g. BIG RENAPE network); (ii) transfer (or not) the patient to a referral center with experience in hyperthermic intraperitoneal chemotherapy (HIPEC), according to the advice of the MCM. With regard to systemic chemotherapy (strong agreement of experts): (i) it should be performed both before and after surgery, (ii) for no longer than 6 months; (iii) without postoperative anti-angiogenetic drugs. With regard to cytoreductive surgery (strong agreement of experts): (i) Radical surgery requires a xiphopubic midline incision; (ii) no cytoreductive surgery via laparoscopy. With regard to HIPEC: HIPEC can be proposed for trials outside an HIPEC referral center (weak agreement between experts): (i) if surgery is radical; (ii) if the expected morbidity is "reasonable"; (iii) if the indication for HIPEC was suggested by a MCM, and; (iv) mitomycin is preferred to oxaliplatin (which cannot be recommended) for this indication.

What is the impact of neoadjuvant chemoradiation on outcomes in gastro-intestinal cancer?

Multimodal therapeutic strategies combining chemotherapy, radiation therapy and surgery have been shown to be feasible and to have a positive impact on outcomes by decreasing the risk of locoregional recurrence and often by increasing overall survival. The advantages of neoadjuvant chemo(radio)therapy include optimal tumor control combined with better tolerance and compliance to treatment while also increasing the number of candidates for surgery. Whereas indications for neoadjuvant therapy are increasing, its impact on surgical treatment and postoperative outcomes are not well-known. Surgeons frequently believe that chemo(radio)therapy may amplify intraoperative difficulties, thereby increasing postoperative morbidity and mortality. The aim of this review was to report the state of the art regarding: (i) the role of chemo(radio)therapy; (ii) its impact on surgical indications and modalities; and (iii) its impact on postoperative outcomes for the most frequently encountered gastro-intestinal cancers, i.e. esophageal, rectal, pancreatic, and anal canal cancer.

Right post-traumatic diaphragmatic hernia with liver and intestinal dislocation.

Right diaphragmatic hernia is an uncommon injury following abdominal trauma. A case of delayed right post-traumatic diaphragmatic hernia is presented. The patient referred us with wheezing and cough since 1 month. A chest-abdominal computed tomography scan demonstrated a large diaphragmatic defect with liver and intestinal dislocation. The patient underwent surgical intervention with diaphragmatic repair. No complications were observed during admission and follow-up is actually negative for recurrence.

Black esophagus: acute esophageal necrosis, clinical case and review of literature.

Black esophagus is a rare, multifactorial disease. A case of acute black esophagus following pancreatic resection is presented. The patient referred us with a specific gastrointestinal bleeding. An esophagogastroduodenoscopy confirmed the diagnosis. We performed conservative treatment with complete esophageal re-epithelization and negative follow-up for stenosis or necrosis relapse.

Circulating tumor cells and circulating tumor DNA: What surgical oncologists need to know?

As a result of recent progress in detection techniques, circulating tumor DNA (ctDNA) and circulating tumor cells (CTC) can now be accurately detected in the blood of most cancer patients. While these new biomarkers can provide a better understanding of key biological mechanisms underlying cancer growth and dissemination, they also open up a wide range of possible clinical applications in medical oncology, radiation oncology and surgical oncology. In this review, we summarize the results obtained with ctDNA and CTC together with their potential future clinical applications in the field of surgical oncology, with particular focus on the perioperative setting of various types of cancer. These applications include, but are not limited to, cancer screening, early diagnosis, prognostic assessment, evaluation and management of preoperative systemic or local therapies, post-surgical detection of minimal residual disease and early detection of cancer relapse.

Enhanced recovery after gastro-intestinal surgery: The scientific background.

Enhanced recovery programs (ERP) are without any doubt a major innovation in the care of surgical patients. This multimodal approach encompasses elements of both medical and surgical care. The goal of this in-depth review is to analyze the surgical aspects of ERP, underlining the scientific rationale behind each element of ERP after surgery and in particular, the role of mechanical bowel preparation before colorectal surgery, the place of minimal access surgery, the utility of nasogastric tube, abdominal drainage, bladder catheters and early re-feeding. Publication of factual data has allowed many dogmas to be discarded.

Diffuse malignant peritoneal mesothelioma: Evaluation of systemic chemotherapy with comprehensive treatment through the RENAPE Database: Multi-Institutional Retrospective Study.

PURPOSE: Diffuse malignant peritoneal mesothelioma (DMPM) is a severe disease with mainly locoregional evolution. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the reported treatment with the longest survival. The aim of this study was to evaluate the impact of perioperative systemic chemotherapy strategies on survival and postoperative outcomes in patients with DMPM treated with curative intent with CRS-HIPEC, using a multi-institutional database: the French RENAPE network. PATIENTS AND METHODS: From 1991 to 2014, 126 DMPM patients underwent CRS-HIPEC at 20 tertiary centres. The population was divided into four groups according to perioperative treatment: only neoadjuvant chemotherapy (NA), only adjuvant chemotherapy (ADJ), perioperative chemotherapy (PO) and no chemotherapy before or after CRS-HIPEC (NoC). RESULTS: All groups (NA: n = 42; ADJ: n = 16; PO: n = 16; NoC: n = 48) were comparable regarding clinicopathological data and main DMPM prognostic factors. After a median follow-up of 61 months, the 5-year overall survival (OS) was 40%, 67%, 62% and 56% in NA, ADJ, PO and NoC groups, respectively (P = 0.049). Major complications occurred for 41%, 45%, 35% and 41% of patients from NA, ADJ, PO and NoC groups, respectively (P = 0.299). In multivariate analysis, NA was independently associated with worse OS (hazard ratio, 2.30; 95% confidence interval, 1.07-4.94; P = 0.033). CONCLUSION: This retrospective study suggests that adjuvant chemotherapy may delay recurrence and improve survival and that NA may impact negatively the survival for patients with DMPM who underwent CRS-HIPEC with curative intent. Upfront CRS and HIPEC should be considered when achievable, waiting for stronger level of scientific evidence.

Clinical severity and molecular characteristics of circulating and emerging rotaviruses in young children attending hospital emergency departments in France.

Group A rotavirus (RVA) is the leading cause of acute gastroenteritis in young children worldwide. A prospective surveillance network has been set up to investigate the virological and clinical features of RVA infections and to detect the emergence of potentially epidemic strains in France. From 2009 to 2014, RVA-positive stool samples were collected from 4800 children <5 years old attending the paediatric emergency units of 16 large hospitals. Rotaviruses were then genotyped by RT-PCR with regard to their outer capsid proteins VP4 and VP7. Genotyping of 4708 RVA showed that G1P[8] strains (62.2%) were predominant. The incidence of G9P[8] (11.5%), G3P[8] (10.4%) and G2P[4] (6.6%) strains varied considerably, whereas G4P[8] (2.7%) strains were circulating mostly locally. Of note, G12P[8] (1.6%) strains emerged during the seasons 2011-12 and 2012-13 with 4.1% and 3.0% prevalence, respectively. Overall, 40 possible zoonotic reassortants, such as G6 (33.3%) and G8 (15.4%) strains, were detected, and were mostly associated with P[6] (67.5%). Analysis of clinical records of 624 hospitalized children and severity scores from 282 of them showed no difference in clinical manifestations or severity in relation to the genotype. The relative stability of RVA genotypes currently co-circulating and the large predominance of P[8] type strains may ensure vaccine effectiveness in France. The surveillance will continue to monitor the emergence of new reassortants that might not respond to current vaccines, all the more so as all genotypes can cause severe infections in infants.

Radiofrequency ablation and surgical resection of liver metastases from uveal melanoma.

BACKGROUND: The resection of liver metastasis from uveal melanoma (LMUM) remains controversial. In this study, we evaluated treatment with radiofrequency ablation (RFA) for liver metastases alone or in combination with surgical liver resection. METHODS: A total of 72 patients with LMUM were evaluated in this study. Of these, 57 patients underwent surgical resection (S) while 15 patients had RFA ± S. Clinicopathologic factors were evaluated in terms of recurrence and survival using Chi-square and log-rank tests, respectively. RESULTS: We studied 22 metastases treated by RFA. There were no statistically significant differences between the groups in terms of median age of onset, synchronous nature of the metastases, time from primary tumour treatment to liver metastasis, diameter of the largest metastasis, presence of liver miliary disease, and the type of liver resection. There was a statistically lower number of liver metastases and more bilobar metastases in the RFA group than in the S group. The median overall survival after liver surgery was 27 months in group S and 28 months in the RFA group ± S. The median disease-free survival was 10 months in group S and 7 months in the RFA group ± S. There were no statistically significant differences in the median overall survival and disease-free survival between groups. CONCLUSIONS: The results of this retrospective analysis show that RFA can be used to treat liver metastases to spare the hepatic parenchyma. RFA ± liver surgery and liver surgery alone demonstrate similar survival times.

Professional risks when carrying out cytoreductive surgery for peritoneal malignancy with hyperthermic intraperitoneal chemotherapy (HIPEC): A French multicentric survey.

BACKGROUND: Over the last two decades, many surgical teams have developed programs to treat peritoneal carcinomatosis with extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Currently, there are no specific recommendations for HIPEC procedures concerning environmental contamination risk management, personal protective equipment (PPE), or occupational health supervision. METHODS: A survey of the institutional practices among all French teams currently performing HIPEC procedures was carried out via the French network for the treatment of rare peritoneal malignancies (RENAPE). RESULTS: Thirty three surgical teams responded, 14 (42.4%) which reported more than 10 years of HIPEC experience. Some practices were widespread, such as using HIPEC machine approved by the European Community (100%), individualized or centralized smoke evacuation (81.8%), "open" abdominal coverage during perfusion (75.8%), and maintaining the same surgeon throughout the procedure (69.7%). Others were more heterogeneous, including laminar flow air circulation (54.5%) and the provision of safety protocols in the event of perfusate spills (51.5%). The use of specialized personal protective equipment is ubiquitous (93.9%) but widely variable between programs. CONCLUSION: Protocols regarding cytoreductive surgery/HIPEC and the associated professional risks in France lack standardization and should be established.

Minor and potentially toxic trace elements in milk and blood serum of dairy donkeys.

The aim of this trial was to study the concentration of Ti, V, As, Rb, Sr, Mo, Cd, Cs, and Pb in donkey milk and blood serum. One hundred twelve individual milk and blood serum samples were collected from 16 lactating donkeys (Martina-Franca-derived population; 6 to 12 yr old; 3 to 7 parities; average live weight 205.4kg; 32 to 58 d after foaling at the beginning of the trial) during a 3-mo-long experiment. The samples were analyzed for the aforementioned elements by inductively coupled plasma-mass spectrometry. Feedstuff and drinking water were also analyzed for the investigated elements. Data were processed by ANOVA for repeated measures. Average milk concentrations (±SD) of Ti, Rb, Sr, Mo, Cs, and Pb were 77.3 (±7.7), 339.1 (±82.1), 881.7 (±270.4), 4.5 (±1.6), 0.49 (±0.09), and 3.2 (±2.7) µg/L, respectively. More than 80% of samples were below the limit of detection for V, As, and Cd in milk and for Cd, and Pb in blood serum. The lower bound calculated for milk V, As, and Cd was 0.03µg/L for the 3 elements, the upper bound was calculated at 0.23, 0.10, and 0.31µg/L and the maximum value was observed at 0.54, 0.15, and 0.51µg/L, respectively. The average milk concentrations of Ti, Rb, Sr, Mo, and Cs were 600, 458, 346, 16, and 294%, respectively, than those of blood serum. Yet, Cs concentrations were in the same order of magnitude in milk and serum. Moderate to strong positive and significant correlation coefficients were observed between milk and blood serum concentrations for Ti, Rb, Sr, and Cs. The effect of the stage of lactation was significant for all the investigated elements in milk and blood serum, but most of the elements showed only small changes or inconsistent trends, and only the concentrations of Rb and Sr showed decreasing trends both in milk and blood serum. The relationship between milk and blood serum element concentrations indicates that the mammary gland plays a role in determining the milk concentrations of Mo, Ti, Rb, Sr, Mo, and Cs. In the current experimental conditions, in agreement with the low levels in drinking water and feedstuff, donkey milk concentration of potentially toxic elements was very low and did not raise health concerns for human consumption.

Prospective study of surveillance testing for metastasis in 100 high-risk uveal melanoma patients.

Despite advances in the local treatment of UM, half of patients develop metastases typically to the liver with poor survival. Microscopic complete surgical resection (R0) of liver metastases improves survival in high selected patients. Early identification of high-risk patients might allow detection of asymptomatic metastases, and increase R0 liver surgery rate. From October 2006 to December 2009, we conducted a prospective study to detect early minimal lesions with 6-monthly liver function tests (LFTs) and liver MRI in 100 high-risk patients. High risk was defined by primary tumor clinical or genomic criteria: thickness>8mm or diameter>15 mm, or extra-scleral extension, or monosomy 3 by FISH or aCGH. With a median follow-up of 49 months, the 5-year metastasis-free survival and overall survival were 47 and 33%, respectively. Of the 60 patients who became metastatic, 50 (83%) had exclusive liver metastasis. LFTs screening had no sufficient accurary, but biannual MRI showed high predictive value to detect metastasis and select patients eligible for curative surgery: 25/50 underwent laparotomy and among them, 8/25 (32%) had a R0 surgery. Median survival after metastasis was 14 months, mean survival reached 40 months in the R0 resected population. Six-monthly liver MRI screening is recommended in patients with large tumors or genomic high risk in order to detect early patient candidates to complete resection of liver metastases.

Response to dual HER2 blockade in a patient with HER3-mutant metastatic breast cancer.

BACKGROUND: HER3 activating mutations have been shown in preclinical models to be oncogenic and ligand-independent, but to depend on kinase-active HER2. PATIENTS AND METHODS: Whole-exome sequencing of the primary HER2-negative breast cancer and its HER2-negative synchronous liver metastasis from a 46-year-old female revealed the presence of an activating and clonal HER3 G284R mutation. RESULTS: HER2 dual blockade with trastuzumab and lapatinib as third-line therapy led to complete metabolic response in 2 weeks and confirmed radiological partial response after 8 weeks. Following the resection of the liver metastasis, the patient remains disease-free 40 weeks after initiation of the HER2 dual blockade therapy. Immunohistochemical analysis demonstrated a substantial reduction of phospho-rpS6 and phospho-AKT in the post-therapy biopsy of the liver metastasis. DISCUSSION: This is the first-in-man evidence that anti-HER2 therapies are likely effective in breast cancers harboring HER3 activating mutations.

[Dermo-hypodermitis caused by group B Streptococcus in infants under 3 months of age: A retrospective study in two hospitals]. / Dermo-hypodermites à streptocoque du groupe B chez les nourrissons de moins de 3 mois : étude rétrospective dans deux centres hospitaliers.

BACKGROUND: Very few studies describe group B streptococcal dermo-hypodermitis in newborns. OBJECTIVES: To describe the incidence, clinical characteristics, and course of group B streptococcal dermo-hypodermitis in infants less than 3 months old. PATIENTS AND METHODS: Infants under 3 months of age, hospitalized for group B streptococcal dermo-hypodermitis at Robert Debré University Hospital, Paris, France, and at Orsay Hospital, Orsay, France, between January 2002 and August 2013, were included in a retrospective study. RESULTS: Five infants were included in this study. All the infections occurred late. Dermo-hypodermitis accounted for 7% of the overall late-onset group B streptococcal infections during the same period. Four patients were male and had a risk factor of maternal-fetal infection (prematurity/hypotrophy). Four patients had specific clinical signs of dermo-hypodermitis with septic shock features on admission. One patient had meningitis and associated parotitis. Group B Streptococcus was isolated from blood culture of all patients. Serotype III Streptococcus was identified in four cases. The duration of intravenous antibiotic therapy varied from 7 to 23 days and the total duration of antibiotic therapy was between 14 and 44 days. The progression was favorable for all the infants, with no recurrence. CONCLUSION: Dermo-hypodermitis in infants under 3 months of age is rare but could be an early indicator of group B streptococcal bacteremia and/or sepsis. Early diagnosis of this severe complication and appropriate antibiotic therapy are critical.

Treatment of Leaks Following Sleeve Gastrectomy by Endoscopic Internal Drainage (EID).

BACKGROUND: Leaks are considered one of the major complications of laparoscopic sleeve gastrectomy (LSG) with a reported rate up to 7 %. Drainage of the collection coupled with SEMS deployment is the most frequent treatment. Its success is variable and burdened by high morbidity and not irrelevant mortality. The aim of this paper is to suggest and establish a new approach by endoscopic internal drainage (EID) for the management of leaks. METHODS: Since March 2013, 67 patients presenting leak following LSG were treated with deployment of double pigtail plastic stents across orifice leak, positioning one end inside the collection and the other end in remnant stomach. The aim of EID is to internally drain the collection and at the same time promote leak healing. RESULTS: Double pigtails stent were successfully delivered in 66 out of 67 patients (98.5 %). Fifty patients were cured by EID after a mean time of 57.5 days and an average of 3.14 endoscopic sessions. Two died for event not related to EID. Nine are still under treatment; five failure had been registered. Six patients developed late stenosis treated endoscopically. CONCLUSIONS: EID proved to be a valid, curative, and safe mini-invasive approach for treatment of leaks following SG. EID achieves complete drainage of perigastric collections and stimulates mucosal growth over the stent. EID is well tolerated, allows early re-alimentation, and it is burdened by fewer complications than others technique. Long-term follow-up confirms good outcomes with no motility or feeding alterations.

Bilateral simultaneous femoral neck fracture mimicking abdominal pain in a cerebral palsy patient.

Simultaneous bilateral femoral neck fractures are unusual lesions, generally associated with an underlying condition which causes impaired bone mineralization, triggered by an increased bone stress. We present a 24-year-old cerebral palsy patient, who was previously evaluated in another institution due to inability to walk, interpreted as abdominal pain. No alteration in blood analysis or abdominal X-rays was found. As no response to treatment was observed, a new abdominal X-ray was taken, which incidentally depicted bilateral medial femoral neck fracture. He was referred to our practice after a resection arthroplasty was offered in another institution. After admission, bilateral one-stage THA was performed. Several reports emphasize bone disease as a major precipitating factor, and there is an increased incidence of hip fractures in chronic epilepsy, renal osteodystrophy, and chronic steroid use. Femoral head resection has been proven to be effective in immobilized patients, whereas this was not a reasonable option in this patient who presented walking ability. Despite the treatment election, primary care physicians should be aware of and alert to the possibility of fractures in patients with neurological disorders and calcium metabolism alterations. Late diagnosis of orthopedic injuries in this type of patients may lead to permanent disability.