International Tailored Chemotherapy Adjuvant (ITACA) trial, a phase III multicenter randomized trial comparing adjuvant pharmacogenomic-driven chemotherapy versus standard adjuvant chemotherapy in completely resected stage II-IIIA non-small-cell lung cancer.

BACKGROUND: Several strategies have been investigated to improve the 4% survival advantage of adjuvant chemotherapy in early-stage non-small-cell lung cancer (NSCLC). In this investigator-initiated study we aimed to evaluate the predictive utility of the messenger RNA (mRNA) expression levels of excision repair cross complementation group 1 (ERCC1) and thymidylate synthase (TS) as assessed in resected tumor. PATIENTS AND METHODS: Seven hundred and seventy-three completely resected stage II-III NSCLC patients were enrolled and randomly assigned in each of the four genomic subgroups to investigator's choice of platinum-based chemotherapy (C, n = 389) or tailored chemotherapy (T, n = 384). All anticancer drugs were administered according to standard doses and schedules. Stratification factors included stage and smoking status. The primary endpoint of the study was overall survival (OS). RESULTS: Six hundred and ninety patients were included in the primary analysis. At a median follow-up of 45.9 months, 85 (24.6%) and 70 (20.3%) patients died in arms C and T, respectively. Five-year survival for patients in arms C and T was of 65.4% (95% CI (confidence interval): 58.5% to 71.4%) and 72.9% (95% CI: 66.5% to 78.3%), respectively. The estimated hazard ratio (HR) was 0.77 (95% CI: 0.56-1.06, P value: 0.109) for arm T versus arm C. HR for recurrence-free survival was 0.89 (95% CI: 0.69-1.14, P value: 0.341) for arm T versus arm C. Grade 3-5 toxicities were more frequently reported in arm C than in arm T. CONCLUSION: In completely resected stage II-III NSCLC tailoring adjuvant chemotherapy conferred a non-statistically significant trend for OS favoring the T arm. In terms of safety, the T arm was associated with better efficacy/toxicity ratio related to the different therapeutic choices in the experimental arm.

CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials.

Background: Central nervous system (CNS) metastases are common in patients with non-small-cell lung cancer (NSCLC). Osimertinib has shown systemic efficacy in patients with CNS metastases, and early clinical evidence shows efficacy in the CNS. To evaluate osimertinib activity further, we present a pre-specified subgroup analysis of CNS response using pooled data from two phase II studies: AURA extension (NCT01802632) and AURA2 (NCT02094261). Patients and methods: Patients with T790M-positive advanced NSCLC, who had progressed following prior epidermal growth factor receptor-tyrosine kinase inhibitor treatment, received osimertinib 80 mg od (n = 411). Patients with stable, asymptomatic CNS metastases were eligible for enrolment; prior CNS treatment was allowed. Patients with ≥1 measurable CNS lesion (per RECIST 1.1) on baseline brain scan by blinded independent central neuroradiology review (BICR) were included in the evaluable for CNS response set (cEFR). The primary outcome for this CNS analysis was CNS objective response rate (ORR) by BICR; secondary outcomes included CNS duration of response, disease control rate (DCR) and progression-free survival (PFS). Results: Of 128 patients with CNS metastases on baseline brain scans, 50 were included in the cEFR. Confirmed CNS ORR and DCR were 54% [27/50; 95% confidence interval (CI) 39-68] and 92% (46/50; 95% CI 81-98), respectively. CNS response was observed regardless of prior radiotherapy to the brain. Median CNS duration of response (22% maturity) was not reached (range, 1-15 months); at 9 months, 75% (95% CI 53-88) of patients were estimated to remain in response. Median follow-up for CNS PFS was 11 months; median CNS PFS was not reached (95% CI, 7, not calculable). The safety profile observed in the cEFR was consistent with the overall patient population. Conclusions: Osimertinib demonstrated clinically meaningful efficacy against CNS metastases, with a high DCR, encouraging ORR, and safety profile consistent with that reported previously. ClinicalTrials.gov number: NCT01802632; NCT02094261.

Subcutaneous fat loss is greater than visceral fat loss with diet and exercise, weight-loss promoting drugs and bariatric surgery: a critical review and meta-analysis.

Aim of this review is to compare visceral and subcutaneous fat loss with all available strategies (diet and exercise, weight-loss promoting agents and bariatric surgery). Eighty-nine studies, all full papers, were analyzed to evaluate visceral and subcutaneous fat changes, measured through ultrasound, computerized tomography, magnetic resonance imaging and expressed as thickness, weight, area and volume. Studies were included in a meta-analysis (random-effects model). Intervention effect (absolute and percent changes of visceral and subcutaneous fat) was expressed as standardized mean differences, with 95% confidence intervals. Publication bias was formally assessed. The result was that subcutaneous fat was greater than visceral fat when measured as area, volume and weight, not as thickness; decrease of subcutaneous fat was greater than visceral fat when measured as area, volume and weight, not as thickness; percent decrease of visceral fat was always greater than percent decrease of subcutaneous fat, with no differences between different strategies. No intervention preferentially targets visceral fat. Basal visceral fat depots are smaller than basal subcutaneous fat depots. Visceral fat loss is linked to subcutaneous fat loss. With all strategies, percent decrease of visceral fat prevails on subcutaneous fat loss.

The association of financial difficulties with clinical outcomes in cancer patients: secondary analysis of 16 academic prospective clinical trials conducted in Italy.

BACKGROUND: Cancer may cause financial difficulties, but its impact in countries with public health systems is unknown. We evaluated the association of financial difficulties with clinical outcomes of cancer patients enrolled in academic clinical trials performed within the Italian public health system. PATIENTS AND METHODS: Data were pooled from 16 prospective multicentre trials in lung, breast or ovarian cancer, using the EORTC quality of life (QOL) C30 questionnaire. Question 28 scores financial difficulties related to disease or treatment in four categories from 'not at all' to 'very much'. We defined financial burden (FB) as any financial difficulty reported at baseline questionnaire, and financial toxicity (FT) as score worsening in a subsequent questionnaire. We investigated (i) the association of FB with clinical outcomes (survival, global QOL response [questions 29/30] and severe toxicity), and (ii) the association of FT with survival. Multivariable analyses were performed using logistic regression models or the Cox model adjusting for trial, gender, age, region and period of enrolment, baseline global QOL and, where appropriate, FB and global QOL response. Results are reported as odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CI). RESULTS: At baseline 26% of the 3670 study patients reported FB, significantly correlated with worse baseline global QOL. FB was not associated with risks of death (HR 0.94, 95% CI 0.85-1.04, P = 0.23) and severe toxicity (OR 0.90, 95% CI 0.76-1.06, P = 0.19) but was predictive of a higher chance of worse global QOL response (OR 1.35, 95% CI 1.08-1.70, P = 0.009). During treatment, 2735 (74.5%) patients filled in subsequent questionnaires and 616 (22.5%) developed FT that was significantly associated with an increased risk of death (HR 1.20, 95% CI 1.05-1.37, P = 0.007). Several sensitivity analyses confirmed these findings. CONCLUSION: Even in a public health system, financial difficulties are associated with relevant cancer patients outcomes like QOL and survival. CLINICAL TRIALS NUMBER: Any registered clinical trial number should be indicated after the abstract.

A phase II study on the efficacy and safety of procedural analgesia with fentanyl buccal tablet in cancer patients for the placement of indwelling central venous access systems.

BACKGROUND: Pain in cancer patients is often related to oncologic therapies and diagnostic procedures. The placement of fully implantable venous access systems is a very common procedure in oncology patients. Local anaesthesia is the method most commonly used to overcome pain related to this surgical procedure, but the local anaesthetic may be unable to completely eradicate all pain. This study investigates the effectiveness and safety of fentanyl buccal tablet (FBT), administered by OraVescent® technology, in reducing procedural pain related to the placement of indwelling central venous access systems (Ports) in opioid-naïve cancer patients. METHODS: Inpatients who required an indwelling vascular access (Port) were preoperatively assessed with a self-assessment questionnaire on anxiety and pain. A 100 µg FBT was administered 10 min before preparation of the operating field. A self-assessment scale for pain experienced during the procedure was administered at the end of the procedure. Vital signs and the presence of any side effects or bothersome symptoms were monitored during the procedure, at the end, and 4 h later. RESULTS: From October 2012 to June 2014, 65 patients were enrolled in the study. A total of 61 (93.9 %) patients perceived no or a little pain during the procedure. Four patients (6.2 %) reported a lot of pain. No patient reported very severe pain. This data is significant in terms of the lower than expected presence of pain (Fisher test p = 0.0018) as assessed in our previous experience without procedural analgesia. The most common side effects of FBT was drowsiness, experienced by 28 patients at the end of the procedure (43.1 %), significantly reduced (p < 0.01) to 8 patients after 4 h (12.5 %). Nausea was present in 6 cases at the end of the procedure (9.2 %) and in 7 cases 4 h later (10.9 %). Vomiting was present in 3 cases at the end (4.7 %) and in 2 other patients after 4 h (7.8 %). No significant change of vital parameters was observed between the baseline and the subsequent measurements in all patients studied. CONCLUSIONS: The significant improvement in the number of patients experiencing little or no pain, accompanied by a lower number of non-severe side effects, suggests that FBT is a valid, practical and safe method of procedural analgesia. It will be necessary to perform further studies, taking into account the need for standard antiemetic pre-medication to minimise the incidence of nausea and vomiting.

Weekly docetaxel versus CMF as adjuvant chemotherapy for older women with early breast cancer: final results of the randomized phase III ELDA trial.

BACKGROUND: Evidence on adjuvant chemotherapy in older women with breast cancer is poor. We tested whether weekly docetaxel is more effective than standard chemotherapy. PATIENTS AND METHODS: We carried out a multicenter, randomized phase III study. Women aged 65-79, operated for breast cancer, with average to high risk of recurrence, were allocated 1 : 1 to CMF (cyclophosphamide 600 mg/m², methotrexate 40 mg/m², fluorouracil 600 mg/m², days 1, 8) or docetaxel (35 mg/m(2) days 1, 8, 15) every 4 weeks, for four or six cycles according to hormone receptor status. Primary end point was disease-free survival (DFS). A geriatric assessment was carried out. Quality of life (QoL) was assessed with EORTC C-30 and BR-23 questionnaires. RESULTS: From July 2003 to April 2011, 302 patients were randomized and 299 (152 allocated CMF and 147 docetaxel) were eligible. After 70-month median follow-up, 109 DFS events were observed. Unadjusted hazard ratio (HR) of DFS for docetaxel versus CMF was 1.21 [95% confidence interval (CI) 0.83-1.76, P = 0.32]; DFS estimate at 5 years was 0.69 with CMF and 0.65 with docetaxel. HR of death was 1.34 (95% CI 0.80-2.22, P = 0.26). There was no interaction between treatment arms and geriatric scales measuring patients' ability or comorbidities. Hematological toxicity, mucositis and nausea were worse with CMF; allergy, fatigue, hair loss, onychopathy, dysgeusia, diarrhea, abdominal pain, neuropathy, cardiac and skin toxicity were worse with docetaxel. One death was attributed to CMF and two to docetaxel. Increasing age, impairment in instrumental daily living activities, number of comorbidities and docetaxel treatment were independently associated with severe nonhematological toxicity. QoL was worse with docetaxel for nausea-vomiting, appetite loss, diarrhea, body image, future perspective, treatment side-effects and hair loss items. CONCLUSIONS: Weekly docetaxel is not more effective than standard CMF as adjuvant treatment of older women with breast cancer and worsens QoL and toxicity. CLINICALTRIALSGOV: NCT00331097.

Prevention of type 2 diabetes; a systematic review and meta-analysis of different intervention strategies.

AIM: Different intervention strategies can prevent type 2 diabetes (T2DM). Aim of the present systematic review and meta-analysis was to evaluate the effectiveness of different strategies. METHODS: Studies were grouped into 15 different strategies: 1: diet plus physical activity; 2: physical activity; 3-6: anti-diabetic drugs [glitazones, metformin, beta-cell stimulating drugs (sulphanylureas, glinides), alfa-glucosidase inhibitors]; 7-8: cardiovascular drugs (ACE inhibitors, ARB, calcium antagonists); 9-14 [diets, lipid-affecting drugs (orlistat, bezafibrate), vitamins, micronutrients, estrogens, alcohol, coffee]; 15: bariatric surgery. Only controlled studies were included in the analysis, whether randomized, non-randomized, observational studies, whether primarily designed to assess incident cases of diabetes, or performed with other purposes, such as control of hypertension, of ischemic heart disease or prevention of cardiovascular events. Appropriate methodology [preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement] was used. Seventy-one studies (490 813 subjects), published as full papers, were analysed to identify predictors of new cases of T2DM, and were included in a meta-analysis (random-effects model) to study the effect of different strategies. Intervention effect (new cases of diabetes) was expressed as odds ratio (OR), with 95% confidence intervals (C.I.s). Publication bias was formally assessed. RESULTS: Body mass index was in the overweight range for 13 groups, obese or morbidly obese in lipid-affecting drugs and in bariatric surgery. Non-surgical strategies, except for beta-cell stimulating drugs, estrogens and vitamins, were able to prevent T2DM, with different effectiveness, from 0.37 (C.I. 0.26-0.52) to 0.85 (C.I. 0.77-0.93); the most effective strategy was bariatric surgery in morbidly obese subjects [0.16 (C.I. 0.11,0.24)]. At meta-regression analysis, age of subjects and amount of weight lost were associated with effectiveness of intervention. CONCLUSIONS: These data indicate that several strategies prevent T2DM, making it possible to make a choice for the individual subject.

Corrigendum: Gut and spleen anomalies associated with DYRK1A syndrome.

[This corrects the article DOI: 10.3389/fped.2022.936732.].

Under-reporting of subjective symptoms and its prognostic value: a pooled analysis of 12 cancer clinical trials.

BACKGROUND: Oncologists tend to under-report subjective symptoms during cancer treatment. This study describes the under-reporting rate of selected symptoms and explores its association with overall survival (OS). A secondary aim is to test the association of patient-reported symptoms with OS. PATIENTS AND METHODS: This is a post hoc analysis on data pooled from 12 randomized trials, promoted by the National Cancer Institute of Naples (Italy), enrolling patients between 2002 and 2019, with published primary analyses. Occurrence and grade of six side-effects (anorexia, nausea, vomiting, constipation, diarrhea and fatigue) reported by physicians were compared with corresponding symptoms reported by patients in quality-of-life (QoL) questionnaires. Under-reporting was defined as the rate of cases reported grade 0 by the physician while grade ≥1 by the patient. Prognostic value was tested in a multivariable model stratified by trial, including age, sex and performance status as confounders. A landmark threshold was defined for OS analyses. RESULTS: 3792 patients with advanced lung, ovarian, pancreatic, breast or colorectal cancer were pooled; 2603 (68.6%) were eligible having at least one toxicity assessment and one QoL questionnaire, before the first planned disease restaging. Concordance between physicians' and patients' reporting was low with Cohen's k coefficients ranging from 0.03 (fatigue) to 0.33 (vomiting). Under-reporting ranged from 52.7% (nausea) to 80.5% (anorexia), and was not associated with OS. Patient-reported anorexia, vomiting and fatigue ('a little' or more) were significantly associated with shorter OS. CONCLUSIONS: Under-reporting of treatment side-effects is frequent, but it does not affect OS. Patients' reported symptoms should be used for prognostic evaluation.

Association of CTLA-4 polymorphisms with improved overall survival in melanoma patients treated with CTLA-4 blockade: a pilot study.

CTLA-4 blockade with monoclonal antibodies can lead to cancer regression in patients with metastatic melanoma (MM). CTLA-4 gene polymorphisms may influence the response to anti-CTLA-4 antibodies although few data are available regarding this issue. We analyzed six CTLA-4 single nucleotide polymorphisms (-1661A > G, -1577G > A, -658C > T, -319C > T, +49A > G, and CT60G > A) in 14 Italian MM patients and 45 healthy subjects. We found a significant association between the -1577G/A and CT60G/A genotypes and improved overall survival (Pc < 0.006, Bonferroni corrected), further confirmed by the diplotype analysis (-1577 & CT60 GG-AA diplotype, p < 0.001). A positive trend toward an association between these genotypes and response to therapy was also observed.

Early structured surgical management plan for neonates with short bowel syndrome may improve outcomes.

BACKGROUND: In children with short bowel syndrome, maximal adaptation of the bowel after extensive resection is thought to occur during the first 2 years of life. The aim of the present study was to review children with short bowel syndrome from two intestinal rehabilitation centers, comparing those undergoing lengthening procedures <365 days of age (early) versus those whose lengthening procedure was carried out >365 days of age (late). METHODS: Retrospective data collection was performed from January 2004 to December 2010 in Manchester, UK, and from December 2006 to December 2010 in Brussels, Belgium. Both medical centers follow a similar intestinal rehabilitation program (IRP). Data collected included population demographics, bowel length preoperatively and postoperatively, age at operation, parenteral nutrition (PN), central access, and complications. RESULTS: Complete data were available for eight children who underwent lengthening surgery at <365 days of age, and six who underwent the procedure at >365 days of age. Diagnoses were similar. Groups were matched for gestation and birthweight, with no statistical difference in preoperative and postoperative bowel lengths. The mean duration of PN postoperatively was 378 days in the early cohort and 589 days in the late cohort. This trended toward statistical significance (p = 0.071). Full enteral autonomy was achieved at 17 months (early) and 59 months (late) (p = 0.01). Patients in the early group required fewer central lines than those operated on later (p = 0.035). CONCLUSIONS: Enrolling children into an IRP involving early (<365 days of age) lengthening surgery allows a shorter postoperative time to allow weaning to full enteral nutrition, as well as fewer central lines. Both outcomes provide benefits for the child and family, allowing an earlier return to normal life.

The predictive and prognostic role of single nucleotide gene variants of PD-1 and PD-L1 in patients with advanced melanoma treated with PD-1 inhibitors.

Background: Despite having revolutionized the treatment paradigm for advanced melanoma, not all patients benefit from immune checkpoint inhibitor therapy. To date, there are no predictive biomarkers for response or the occurrence of immune-related adverse events (irAEs) to programmed cell death protein 1 (PD-1) inhibitors. Our aim was to investigate the predictive and prognostic role of single nucleotide variants (SNVs) of genes involved in the PD-1 axis. Methods: We analysed, in metastatic melanoma patients treated with nivolumab or pembrolizumab, five PD-1 SNVs, namely PD1.3 G>A (rs11568821), PD1.5 C>T (rs2227981), PD1.6 G>A (rs10204525), PD1.7 T>C(rs7421861), PD1.10 C>G (rs5582977) and three programmed death-ligand 1 (PD-L1) SNVs: +8293 C>A (rs2890658), PD-L1 C>T (rs2297136) and PD-L1 G>C (rs4143815). Association of SNV genotypic frequencies with best overall response to PD-1 inhibitors and development of irAEs were estimated through a modified Poisson regression. A Cox regression modelling approach was applied to evaluate the SNV association with OS. Results: A total of 125 patients with advanced melanoma were included in the analysis. A reduction in irAEs risk was observed in patients carrying the PD-L1 +8293 C/A genotype compared with those carrying the C/C genotype (risk ratio = 0.45; 95% CL 0.22-0.93; P = 0.031). A trend for a reduction in irAEs was also observed with the PD1.5 T allele (risk ratio = 0.70, 95% confidence limits 0.48-1.01 versus C allele). None of the SNVs was associated with response to therapy. Finally, a survival benefit was observed in patients harbouring the PD1.7 C/C genotype (hazard ratio = 0.37; 95% confidence limits 0.14-0.96; P = 0.028) in the homozygous model. Conclusions: Our study showed that PD-1.5 and PD-L1 +8293 SNVs may play a role as a predictive biomarker of development of irAEs to PD-1 inhibitors. PD1.7 SNV may also be associated with a reduction of the risk of death, although further translational research is needed to confirm these results.

Bone effect of adjuvant tamoxifen, letrozole or letrozole plus zoledronic acid in early-stage breast cancer: the randomized phase 3 HOBOE study.

BACKGROUND: To measure bone mineral density (BMD) reduction produced by letrozole as compared with tamoxifen and the benefit of the addition of zoledronic acid. PATIENTS AND METHODS: A phase 3 trial comparing tamoxifen, letrozole or letrozole+zoledronic acid in patients with hormone receptor-positive early breast cancer was conducted; triptorelin was given to premenopausal patients. Two comparisons were planned: letrozole versus tamoxifen and letrozole+zoledronic acid versus letrozole. Primary end point was the difference in 1-year change of T-score at lumbar spine (LTS) measured by dual energy X-ray absorptiometry scan. RESULTS: Out of 483 patients enrolled, 459 were available for primary analyses. Median age was 50 (range 28-80). The estimated mean difference (95% confidence interval [CI]) in 1-year change of LTS was equal to -0.30 (95% CI -0.44 to -0.17) in the letrozole versus tamoxifen comparison (P<0.0001) and to +0.60 (95% CI +0.46 to +0.77) in the letrozole+zoledronic acid versus letrozole comparison (P<0.0001). Bone damage by letrozole decreased with increasing baseline body mass index in premenopausal, but not postmenopausal, patients (interaction test P=0.004 and 0.47, respectively). CONCLUSIONS: In the HOBOE (HOrmonal BOne Effects) trial, the positive effect of zoledronic acid on BMD largely counteracts damage produced by letrozole as compared with tamoxifen. Letrozole effect is lower among overweight/obese premenopausal patients.

Metabolic control and risk of hypoglycaemia during the first year of intensive insulin treatment in type 2 diabetes: systematic review and meta-analysis.

AIM: Aim of this study was to analyse clinical correlates of HbA1c, and of overall, nocturnal, and severe hypoglycaemia, through direct-weighted regressions, as well as the effect of different insulin regimens and insulin analogues, through meta-analysis. METHODS: Appropriate methodology (PRISMA statement) was used. Sixty-seven randomized studies, published as full papers were analysed to identify predictors of both HbA1c and hypoglycaemia; studies were included in a meta-analysis to study the effect of different insulin regimens or insulin analogues on HbA1c and hypoglycaemia during the first year of insulin treatment in type 2 diabetes patients. RESULTS: Final HbA1c, change of HbA1c, hypoglycaemia, nocturnal hypoglycaemia and severe hypoglycaemia were associated with intensity of treatment. Final HbA1c was higher with basal than with twice-a-day or prandial, and with twice-a-day than with prandial regimen, with opposite figures for hypoglycaemia. Within basal regimens, detemir and glargine were similar to NPH insulin on HbA1c, with less hypoglycaemia and nocturnal hypoglycaemia; within prandial regimens, new analogues were more effective than regular insulin on HbA1c, and induced less hypoglycaemia. The effect of glargine on HbA1c and on hypoglycaemia vanished with increasing number of insulin injections. CONCLUSION: Metabolic control and hypoglycaemia are associated with intensity of treatment. Basal regimens have a reduced effect on metabolic control, but are associated with lower frequency of hypoglycaemia. Newer analogues, short- and long-acting, yield better control and less hypoglycaemia than older analogues.

Short bowel syndrome: a practical pathway leading to successful enteral autonomy.

BACKGROUND: Short bowel syndrome is a multisystemic disorder that results from the loss of a significant amount of small bowel. The goal of treatment in these patients is to achieve complete enteral autonomy while minimizing complications. Our unit has 30 years of experience in the management of short gut patients. During the past decade, our results have improved significantly, especially in children with severe short bowel syndrome. This brief communication looks at the algorithm presently used in our unit. METHODS: In this communication, the principles in management of short bowel syndrome in our unit are discussed. In addition, our algorithm is published for the first time. A brief summary of our results is provided. RESULTS: Twenty-seven children were enrolled from 2000 to 2009. In this cohort, two patients died because of significant liver disease: one after having two liver and bowel transplants. Overall, survival stands at 92%. All had autologous gastrointestinal reconstruction, and 19 patients underwent bowel lengthening (longitudinal intestinal lengthening and tailoring). The median residual length of bowel of this subgroup at first operation was 25 cm in those who had their gut measured. Two patients were lost to follow-up. Two patients remain on supplemental total parenteral nutrition (TPN), with an overall 91% of surviving patients off TPN at a median of 6 months after reconstruction. CONCLUSIONS: We believe this improvement is related to the development-over many years-of a structured pathway for managing these patients.

Case Report: Gut and spleen anomalies associated with DYRK1A syndrome.

DYRK1A syndrome has been extensively studied primarily with regard to neurologic and other phenotypic features such as skeleton and craniofacial alterations. In the present paper, we aim to highlight unusual anomalies associated with a DYRK1A mutation: a 17-year-old female patient with language and cognitive delay, microcephaly, and an autistic disorder, who was operated upon for spleen torsion with anomalous gut fixation.

Conservative management of posterior tracheal wall injury by endoscopic stent placement in children: Preliminary data of three cases.

The management of tracheal wall lacerations is debated. Current treatments are mainly derived by the experience on adults and include conservative or surgical treatments depending on the clinical condition of the patient. We report our preliminary data with removable tracheal stents in 3 children with tracheal tears and respiratory failure. If performed in specialized centers with appropriate endoscopic and clinical follow-up, airway stents can be considered a valid and safe conservative treatment for tracheal tears and an alternative to intubation or tracheostomy. Further studies are needed to compare different therapeutic options and better define the management and duration of stent treatment.

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.