Robotic versus open Ivor-Lewis esophagectomy: A more accurate lymph node dissection without burdening the leak rate.

BACKGROUND: Robotic-assisted minimally invasive esophagectomy (RAMIE) combines the beneficial effects of minimally invasive surgery on postoperative complications, especially on pulmonary ones, with the safety of the anastomosis performed in open surgery. Moreover, RAMIE could allow a more accurate lymphadenectomy. METHODS: We reviewed our database to identify all patients with adenocarcinoma of the esophagus treated by Ivor-Lewis esophagectomy in the period January 2014 to June 2022. Patients were divided according to the thoracic approach into RAMIE and open esophagectomy (OE) groups. We compared the groups for early surgical outcomes, 90-day mortality as well as R0 rate, and the number of lymph nodes harvested. RESULTS: We identified 47 patients in RAMIE and 159 patients in the OE group. Baseline characteristics were comparable. Operative time was significantly longer for RAMIE procedures (p < 0.01); however, we did not observe the difference in overall (RAMIE 55.5% vs. OE 61%, p = 0.76) and severe complications rate (RAMIE 17% vs. OE 22.6%, p = 0.4). The anastomotic leak rate was 2.1% after RAMIE and 6.9% after OE (p = 0.56). We did not report the difference in 90-day mortality (RAMIE 2.1% vs. OE 1.9%, p = 0.65). In the RAMIE group, we observed a significantly higher number of thoracic lymph nodes harvested, with a median of 10 lymph nodes in the RAMIE group versus 8 in the OE group (p < 0.01). CONCLUSIONS: In our experience, RAMIE has morbimortality rates comparable to OE. Moreover, it allows a more accurate thoracic lymphadenectomy which results in a higher thoracic lymph nodes retrieval rate.

Poorly Cohesive Gastric Cancers Showing the Transcriptomic Hallmarks of Epithelial-Mesenchymal Transition Behave Aggressively.

HYPOTHESIS: Poorly cohesive (PC) gastric cancer (GC) exhibits variable clinical behavior, being extremely aggressive in most cases but more indolent at times. We hypothesized that the integrative genomic and gene expression characterization of a PC GC series could help identifying molecular subtypes with potential clinical implications. MATERIALS AND METHODS: 64 PC GCs were assessed for alterations in 409 genes and 30 cases were subjected to transcriptomic profiling of 20,815 genes. RESULTS: A median of 8.2 mutations per Mb (interquartile range 6.9-10.4) was found and a tumor mutational load >10 muts/Mb was significantly associated with patients' worse survival ( P =0.0024). The most frequent mutated genes were CDH1 and TP53 (each 32.8%) followed by PIK3CA (10.9%). In 15 samples (23.4%), at least 1 chromatin remodeling gene was mutated: KMT2D (5 cases); ARID1A and BAP1 (4 cases each); EZH2 , KMT2A , PBRM1 (1 case each). Eight samples (12.5%) had fusion genes involving CLDN18 gene. Gene expression profiling identified 4 different clusters: cluster A associated with epithelial to mesenchymal transition (EMT) signature; cluster B associated to proliferative signature and EMT; cluster C correlated to hedgehog signaling; cluster D showing no enrichment for any of the previous signatures. Notably, cluster A and B showed a worse prognosis compared with clusters C and D ( P =0.0095). CONCLUSION: integrated genomic and transcriptomic analysis suggest the existence of 4 molecular subtypes of PC GC with prognostic significance where EMT features are associated with a worse outcome.

Enhanced Recovery After Surgery can Improve Patient Outcomes and Reduce Hospital Cost of Gastrectomy for Cancer in the West: A Propensity-Score-Based Analysis.

BACKGROUND: Data on ERAS for gastrectomy are scarce, and the majority of the studies come from Eastern countries. Patients in the West are older and suffer from more advanced tumors that impair their clinical condition and often require neoadjuvant treatment. This retrospective study assessed the feasibility and safety of an Enhanced Recovery After Surgery (ERAS) protocol for gastrectomy in a Western center. METHODS: We conducted a single-center study of 351 patients operated for gastric cancer: 103, operated from January 2015 to December 2016, followed the standard pathway, while 248, operated from January 2017 to December 2019, followed the ERAS program. The primary outcomes considered were length of hospital stay (LOS) and direct costs. Secondary outcomes were 90-day morbidity and mortality, readmission rate, and compliance with ERAS items. A propensity score (PS) was built on confounding variables. RESULTS: Compliance with ERAS items after the program was ≥ 70%. Univariable analysis evidenced a 2-day median reduction in LOS and a median cost reduction of €826 per patient in the ERAS group. PS-based multivariable analysis confirmed a significant, 2-day decrease in median LOS and a €1097 saving after ERAS introduction. Ninety-day mortality decreased slightly in ERAS group, while complications and readmissions did not change significantly. When complications were included in the multivariable analysis, ERAS retained its significance, although the effects on LOS and cost were blunted to a median reduction of 1 day and €775, respectively. CONCLUSIONS: ERAS for gastrectomy improved patients' recovery and reduced hospital costs without changes in morbidity, mortality, or readmission.

Pretreatment Primary Tumor Stage is a Risk Factor for Recurrence in Patients with Esophageal Squamous Cell Carcinoma Who Achieve Pathological Complete Response After Neoadjuvant Chemoradiotherapy.

BACKGROUND: Although pathological complete response (pCR) after multimodal treatment for esophageal cancer is associated to the best prognosis, recurrence may occur in 20-40% of cases. The present study investigated the recurrence pattern and predictive factors of recurrence after pCR in patients with esophageal cancer. METHODS: In this study, 427 patients received preoperative treatment for either esophageal squamous cell carcinoma (SCC) or adenocarcinoma at Verona University Hospital between 2000 and 2018. Of these, 145 patients (34%) achieved a pCR. Long-term prognosis, recurrence pattern, and risk factors for relapse in pCR patients were analysed. RESULTS: During a median follow-up of 52 months, 37 relapses (25.5%) occurred, mostly at distant level (n = 28). Nearly all locoregional relapses (8/9) were detected in SCC cases. The 5-year overall survival and cancer-related survival were 71.7% (95% confidence interval [CI] 62.6-78.9%) and 77.5% (95% CI 68.5-84.2%) respectively. Male sex, higher body mass index, and cT4 were significant risk factors for recurrence at univariate analysis. The multivariate analysis confirmed the role of cT4 as predictor of recurrence only in SCCs. CONCLUSIONS: Esophageal cancer recurs in about one-fourth of pCR cases. A fair number of local recurrences occurs in SCCs, but the main problem is the systemic disease control. According to our analysis, SCCs patients with cT4 stage have an increased risk to recur, so they should be managed differently by a personalized approach in terms of adjuvant treatment and follow-up.

Personalized therapeutic strategies in HER2-driven gastric cancer.

BACKGROUND: Trastuzumab is the only approved targeted therapy in patients with HER2-amplified metastatic gastric cancer (GC). Regrettably, in clinical practice, only a fraction of them achieves long-term benefit from trastuzumab-based upfront strategy. To advance precision oncology, we investigated the therapeutic efficacy of different HER2-targeted strategies, in HER2 "hyper"-amplified (≥ 8 copies) tumors. METHODS: We undertook a prospective evaluation of HER2 targeting with monoclonal antibodies, tyrosine kinase inhibitors and antibody-drug conjugates, in a selected subgroup of HER2 "hyper"-amplified gastric patient-derived xenografts (PDXs), through the design of ad hoc preclinical trials. RESULTS: Despite the high level of HER2 amplification, trastuzumab elicited a partial response only in 2 out of 8 PDX models. The dual-HER2 blockade with trastuzumab plus either pertuzumab or lapatinib led to complete and durable responses in 5 (62.5%) out of 8 models, including one tumor bearing a concomitant HER2 mutation. In a resistant PDX harboring KRAS amplification, the novel antibody-drug conjugate trastuzumab deruxtecan (but not trastuzumab emtansine) overcame KRAS-mediated resistance. We also identified a HGF-mediated non-cell-autonomous mechanism of secondary resistance to anti-HER2 drugs, responsive to MET co-targeting. CONCLUSION: These preclinical randomized trials clearly indicate that in HER2-driven gastric tumors, a boosted HER2 therapeutic blockade is required for optimal efficacy, leading to complete and durable responses in most of the cases. Our results suggest that a selected subpopulation of HER2-"hyper"-amplified GC patients could strongly benefit from this strategy. Despite the negative results of clinical trials, the dual blockade should be reconsidered for patients with clearly HER2-addicted cancers.

Looking for a strategy in treating peritoneal gastric cancer carcinomatosis: an Italian multicenter Gastric Cancer Research group's analysis.

BACKGROUND: The present study provides a snapshot of Italian patients with peritoneal metastasis from gastric cancer treated by surgery in Italian centers belonging to the Italian Research Group on Gastric Cancer. Prognostic factors affecting survival in such cohort of patients were evaluated with the final aim to identify patients who may benefit from radical intent surgery. METHODS: It is a multicentric retrospective study based on a prospectively collected database including demographics, clinical, surgical, pathological, and follow-up data of patients with gastric cancer and synchronous macroscopic peritoneal metastases. Patients were surgically treated from January 2005 to January 2017. We focused on patients with macroscopic peritoneal carcinomatosis (PC) treated with upfront surgery in order to provide homogeneous evidences. RESULTS: Our results show that patients with peritoneal carcinomatosis cannot be considered all lost. Strictly selected cases (R0/R1 and P1 patients) could benefit from an aggressive surgical approach performing an extended lymphadenectomy and HIPEC treatment. CONCLUSION: The main result of the study is that GC patients with limited peritoneal involvement can have a survival benefit from a surgery with "radical oncological intent", that means extended lymphadenectomy and R0 resection. The retrospective nature of this study is an important bias, and for this reason, we have started a prospective multicentric study including Italian stage IV patients that hopefully will give us more answers.

Primary muscle involvement in a 15-year-old girl with the recurrent homozygous c.362dupC variant in FKBP14.

Kyphoscoliotic Ehlers-Danlos syndrome associated with FKBP14 (FKBP14-kEDS) is an ultrarare autosomal recessive disorder reported in less than 30 individuals so far. In its original description, emphasis was put on the mild muscle involvement. Further reports confirm that FKBP14-kEDS is distinguishable from primary muscle disorders by the lack of progressive muscle disease. We report a 15-year-old girl with FKBP14-kEDS as a result of the recurrent c.362dupC variant, who also showed severe involvement of the lower limb muscles. She never attained autonomous walking and presented significant lower limb weakness. Lower limb magnetic resonance imaging showed a pattern of multiple muscle involvement. Further musculoskeletal assessment revealed significant bone mass density reduction of the spine, unilateral congenital hip dysplasia, and occipitoatlantoaxial instability. This patient points out the existence of a wider phenotypic spectrum of FKBP14-kEDS to include early onset muscle disease.

Anthropometric characteristics of newborns with Prader-Willi syndrome.

This is a retrospective multicenter nationwide Italian study collecting neonatal anthropometric data of Caucasian subjects with Prader-Willi syndrome (PWS) born from 1988 to 2018. The aim of the study is to provide percentile charts for weight and length of singletons with PWS born between 36 and 42 gestational weeks. We collected the birth weight and birth length of 252 male and 244 female singleton live born infants with both parents of Italian origin and PWS genetically confirmed. Percentile smoothed curves of birth weight and length for gestational age were built through Cole's lambda, mu, sigma method. The data were compared to normal Italian standards. Newborns with PWS showed a lower mean birth weight, by 1/2 kg, and a shorter mean birth length, by 1 cm, than healthy neonates. Females with a 15q11-13 deletion were shorter than those with maternal uniparental maternal disomy of chromosome 15 (p < .0001). The present growth curves may be useful as further traits in supporting a suspicion of PWS in a newborn. Because impaired prenatal growth increases risk of health problems later in life, having neonatal anthropometric standards could be helpful to evaluate possible correlations between the presence or absence of small gestational age and some clinical and metabolic aspects of PWS.

Gastrocolic trunk of Henle and its variants: review of the literature and clinical relevance in colectomy for right-sided colon cancer.

PURPOSE: Venous vascular anatomy of the right colon presents a high degree of variability. Henle's Gastrocolic Trunk is considered an important anatomical landmark by colorectal surgeons. The classical description concerns a bipod vascular structure or tripod, but several variants are associated to it. The aim of this study is to merge the most updated literature on the anatomy knowledge of the Gastrocolic Trunk by evaluating all possible variants, as well as to underline its surgical importance due to its topographical relationships. METHODS: Twelve studies describing the anatomy of the gastrocolic trunk were selected, each of them dealing with a more or less extensive series of cases. A distinction was drawn between the gastropancreatic trunk, devoid of the colonic component, and the gastrocolic trunk; and then the frequency of the different resulting variants was reported. The data obtained from cadavers and radiological studies were analyzed separately. RESULTS: The Gastrocolic Trunk is found in 74% of cadaver studies, and in 86% of radiological studies. Its most frequent configuration is represented by the union of right gastroepiploic vein + anterior superior pancreaticoduodenal vein + superior right colic vein, respectively, 32.5% and 42.5%, followed by the right colic vein which replaces (26.9%, 12.3%) or is added (10%, 20.1%) to the superior right colic vein. CONCLUSIONS: The superior right colic vein joins the right gastroepiploic vein and the anterior superior pancreaticoduodenal vein thus forming, in most cases, the gastrocolic trunk. The anatomical knowledge of vascular structures forms the basis for both the interpretation of preoperative radiological images and the surgical procedure itself, despite the considerable anatomical variability of tributaries.

Surgical Treatment of Symptomatic Aortic Aneurysm in a Patient with Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis: Case Report and Review of the Literature.

Vasculitis is an heterogeneous group of syndromes, which shares inflammation of blood vessel wall as the main feature. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a necrotizing vasculitis, with few or no immune deposits, predominantly affecting small vessels (i.e., capillaries, venules, arterioles, and small arteries), associated with ANCAs specific for myeloperoxidase or proteinase 3. Clinical manifestations may be heterogeneous but an involvement of lungs and kidneys frequently occurs. AAV of large vessels is a very rare condition whose standard therapy is medical approach. Surgical revascularization has been described in selected patients after medical failure or in emergent settings. We report the case of a patient affected by symptomatic infrarenal aortic aneurysm related to AAV, who underwent in-situ reconstruction by means of cryopreserved homograft.

Ileostomy reversal with handsewn techniques. Short-term outcomes in a teaching hospital.

INTRODUCTION: Fecal diversion is considered an effective procedure to protect bowel anastomosis at high risk for leak. Some concerns exist regarding the risk for a significant morbidity associated to ileostomy creation itself and moreover to its closure. Surgical expertise and closure techniques are considered potential factors influencing morbidity. Aim of the study is to present a single-institution experience with ileostomy closures, in a teaching hospital, whereas ileostomy reversal is mainly performed by young residents. METHODS: A prospective database was investigated to extract data of patients who underwent loop ileostomy closure between January 2005 and December 2014. Ileostomy reversion was always realized in a handsewn fashion, performing either a direct closure (DC) or a resection plus end-to-end anastomosis (EEA). Postoperative morbidity was graded according to Clavien-Dindo classification. Outcomes after DC and EEA were compared by Fisher's exact test and Wilcoxon rank-sum test. RESULTS: Two hundred ninety-eight patients were included. Ileostomy reversal was performed by EEA in 236 patients (79.19 %) and by DC in 62 patients (20.81 %). Surgery was performed with a peristomal access in 296 cases (99.33 %). Incidence of anastomotic leak was 0.67 % (2/298). Overall reoperation rate was 0.34 % (1/298). Short-term overall morbidity rate was 20.47 %; but major complications (≥ grade III) occurred in only one patient (0.34 %). Mortality was nil. No significant differences in postoperative morbidity were found between the DC and EEA group. CONCLUSION: Loop ileostomy reversal is a safe procedure, associated to a low major morbidity and excellent results, even if performed with a handsewn technique by supervised trainee surgeons.

Cancer recurrence following conversion during laparoscopic colorectal resections: a meta-analysis.

INTRODUCTION: Evidence regarding long-term oncological outcomes following conversion to open surgery (COS) during laparoscopic colorectal resection (LCR) is controversial. The aim of this study is to assess the impact on cancer recurrence of a failed laparoscopic attempt. METHODS: MEDLINE, Scopus and ISI Web of Knowledge databases were searched for articles reporting data on cancer recurrence in patients undergoing completed LCR and COS. Data were pooled by fixed or random effect modeling, according to the presence of heterogeneity. Primary outcomes were local recurrence (LR) and distance recurrence (DR). RESULTS: Seven studies involving 2493 patients (completed LCR, n 2201 and COS, n 292) were included. The pooled analysis showed that COS resections have an higher risk of LR (OR 1.97, 95% CI 1.14-3.42, p = 0.1); no difference was found in DR (OR 1.09, 95% CI 0.67-1.77, p = 0.71). However, an higher rate of T4 tumor was present in the converted group (OR 2.62, 95% CI 1.71-4, p = 0.0). Subgroup analysis including studies with T stage matched populations showed no significant statistical difference in LR rate; however, a trend toward higher recurrence was still clear. CONCLUSION: There is no consistent evidence that a failed laparoscopic attempt does not result in a poorer oncological outcome; therefore, a careful selection of patients for LCR for cancer is required.

Ventral mesh rectopexy versus conventional suture technique: a single-institutional experience.

AIMS: Anterior mesh rectopexy is a novel surgical technique for the treatment of complete rectal prolapse, a common disorder in female elderly patients. Aim of the study was to evaluate functional outcomes after ventral mesh rectopexy and conventional suture rectopexy. PATIENTS AND METHODS: Forty patients have been enrolled in this prospective study. Patients were divided into two groups: 20 patients (group A) had a conventional suture rectopexy with a standard technique and 20 patients (group B) underwent an anterior mesh rectopexy. Each patient had a clinic and defecographic diagnosis of full-thickness rectal prolapse, which was further investigated with manometry and clinical questionnaires (Wexner Constipation and Incontinence Score, Rome III criteria). Postoperative outcomes were evaluated through clinical questionnaires, a rigid rectosigmoidoscopy and a defecography, 1 year after surgery. RESULTS: Preoperative Wexner constipation score was greater than 15 in all the patients (21 in group A and 22 in group B); median postoperative score was 15 in group A and 11 in group B, and the difference was significant. Median preoperative incontinence score was 11 in group A and 12 in group B; median postoperative score was 9 in group A and 6 in group B. Three patients experienced recurrence in group A and only 1 patient in group B. CONCLUSION: Ventral mesh rectopexy is feasible, safe and effective for the treatment of full-thickness rectal prolapse in a well-fit geriatric population. Better functional results have been achieved compared with conventional suture technique with a trend toward a lower recurrence rate.

The long-term effects of stillbirth on women with and without gestational diabetes: a population-based cohort study.

AIMS/HYPOTHESIS: The aim of this study was to estimate the incidence of type 2 diabetes (primary objective) and hospitalisation for cardiovascular events (secondary objective) in women with previous gestational diabetes mellitus (GDM) and in those with normal glucose tolerance (NGT) in pregnancy, and to evaluate the role of stillbirth in differentiating the risks. METHODS: This was a population-based cohort study using administrative data and involving 12 local health authorities. Women with GDM (n = 3,851) during the index period from 2002 to 2010 were propensity matched with women with NGT (n = 11,553). Information was collected on type 2 diabetes development and hospitalisation for cardiovascular events. RESULTS: During a median follow-up of 5.4 years, the incidence rate per 1,000 person-years of type 2 diabetes was 2.1 (95% CI 1.8, 2.5) in women without GDM and 54.0 (95% CI 50.2, 58.0) among women with GDM and pregnancy at term (incidence rate ratio [IRR] 26.9; 95% CI 22.1, 32.7 compared with NGT and pregnancy at term). A history of stillbirth increased the risk of type 2 diabetes development by about twofold, irrespective of GDM status. No significant interaction between stillbirth and GDM on type 2 diabetes risk was found. GDM was associated with a significantly higher risk of cardiovascular events compared with NGT (IRR 2.4; 95% CI 1.5, 3.8). CONCLUSIONS/INTERPRETATION: Pregnancy complicated by GDM and ending in stillbirth represents an important contributory factor in determining type 2 diabetes development. Women with GDM are at a high risk of future cardiovascular events. Women with pregnancy complicated by GDM and stillbirth deserve careful follow-up.