Laparoscopic Treatment of Gastric Duplication in a Child

Introduction: Gastric duplication is a rare congenital anomaly with an incidence of 4-8% of all gastrointestinal duplications; enteric duplications are ectopic cystic or tubular structures with a mucous and muscular tunics and they can be in contiguity/continuity with the intestinal lumen.1 Gastric duplication is often an occasional finding, associated to aspecific sintomatology for which pre-operative diagnosis is not univoque; differential diagnosis with other retroperitoneal diseases or mesenteric cysts can be difficult.1 (Run time 8min). Material and Methods: We present a case of a one-year-old child with a pre-natal ultrasound (US) finding of endo-abdominal cystic lesion. After birth, US scans showed an anechogenic-cyst of 33x28mm in the left upper quadrant, between stomach, spleen and kidney. The magnetic resonance confirmed the presence of the lesion (40x34mm), imprinting the posterior gastric wall, the spleen and the anterior side of left kidney. An esophagous-stomach-duodenum contrast study was also performed, showing the imprinting cyst on the great curvature close to the gastric fundus without communication with gastric lumen. On follow-up, the child underwent to periodic US scans and no growth or ultrasonographic changes were described. At 13-months, the diagnosis was still unclear and the patient underwent explorative laparoscopy with esophagous-gastric-duodenoscopy (EGDS). The preliminary EGDS showed a 35mm convexity on the posterior wall of gastric fundus with no evidence of orifice. A 5mm trans-umbilical trocar was placed and 5mm trocar in the epigastric region and 10-12mm trocar in the left side were positioned. At the abdominal exploration the cyst resulted to be in continuity with the posterior gastric wall on the superior third of the great curvature. The lesion was isolated from other tissues, but the postero-medial wall of neoformation appeared to be not dissociable and in continuity with the stomach; a complete resection of the cyst, using 45mm linear stapler, was performed including a small portion of the great gastric curvature. At the following intra-operative endoscopic control no more evidence of irregularity of the gastric wall was seen and the suture was assured. Results: The operative time was 140-minutes. No complications occurred and the blood loss was minimal. The patient started oral intake on 5’ post-operative-day and was discharged on 6’ post-operative-day. The histological examination confirmed the gastric nature of cyst. At 1-year of follow-up no recurrences were diagnosed and the child presents in good health with a regular growth. Conclusion: We can assume that laparoscopic surgery is the correct procedure for gastric duplication cysts, to get both definitive diagnosis and treatment, and the radical surgical excision represents the treatment of choice in order to avoid neoplastic degeneration of internal lining mucosa.2 Furthermore surgical laparoscopy appears to be a feasible and safe technique

a rare case of diaphragmatic hernia after cytoreductive surgery and hypertermic intraperitoneal chemotherapy

Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective therapeutic approach for selected patients with gastrointestinal and gynecological malignancies with peritoneal spread. The most frequent postoperative surgical complications are anastomotic leakage, digestive perforations, fistulas, intestinal obstruction, abscess and peripancreatitis. This report presents case of a patient with late postoperative diaphragmatic hernia after CRS and HIPEC. A 50- year-old woman previously treated with CRS and HIPEC for a pseudomyxoma peritonei was admitted to our unit with diagnosis of intestinal obstruction. At the CT scan a left diaphragmatic hernia involving the splenocolic flexure was found. Both stripping of the diaphragmatic peritoneum during CRS, sometimes combined with diaphragmatic resection and the heat of HIPEC might be responsible for such complication. The diaphragmatic hernia is rarely diagnosed after CRS and HIPEC. Surgical techniques for repair can be the direct suture of the defect or closure with synthetic or biological tissue, both are possible surgical techniques for repair with a good long term results

FIRST CASE OF LAPAROSCOPIC PARTIAL SPLENECTOMY IN A CHILD WITH HAMARTOMA: CASE REPORT AND REVIEW OF THE LITERATURE

INTRODUCTION To date, laparoscopic surgery has played a key role in the treatment of not only splenic hematologic pathologies but also solid ones. Hamartoma is a rare disease; only twenty percent of them are of pediatric relevance; it is a benign tumor, but radiological features never allow proper differentiation from malignant neoplasms. In children, hamartoma may be associated with other morbid conditions, such as sickle cell disease or other hematological alterations. PRESENTATION OF THE CASE We report a case of hamartoma in a 7-year-old child treated with partial laparoscopic splenectomy After a multidisciplinary evaluation, the indication of laparoscopic splenectomy was decided; upon evaluating the age of the patient and the affected spleen portion, a partial splenectomy was proposed. The histological examination during surgery was performed to exclude any form of malignancy. The intraoperative frozen section of the specimen was negative for malignancies, and a partial splenectomy was performed. DISCUSSION Surgery remains the first choice in the definitive treatment of solid lesions of the spleen; minimally invasive technique, namely, laparoscopy, has set itself as the technique of choice for surgical treatment. In this case, the possibility of obtaining an intraoperative pathological diagnosis by frozen section of the specimen, confirming the benign nature of the lesion, allowed the surgeon to decide in favor of a laparoscopic partial splenectomy. CONCLUSION Partial laparoscopic splenectomy can be considered a safe, effective and reproducible alternative in patients suffering from benign solid diseases, safeguarding the hematological functions of the organ itself in pediatric age

CYTOREDUCTIVE SURGERY AND HIPEC IN A 14 YEARS OLD PATIENT WITH PERITONEAL RECURRENCE OF ADENOCARCINOMA OF THE RIGHT COLON

Introduction Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is nowadays a feasible and effective treatment for peritoneal metastasis. We present a case of a 14 years old child with peritoneal metastasis from recurrent colorectal cancer. Presentation of case Colonoscopy and CT-scan were performed leading to the diagnosis of a stenosing adenocarcinoma of the right colon in 2015. Two pelvic lesions were found at the total body PET scan, suspected for peritoneal metastasis. Neoadjuvant chemotherapy was administered, and restaging CT-scan and magnetic resonance (MRI) highlighted a partial response. The patient underwent right laparoscopic hemicolectomy. The postoperative staging was T4 N1 G3. Seven months after the last cycle of adjuvant chemotherapy, CT-scan revealed two huge abdominal masses. The patient underwent explorative laparotomy and bilateral oophorectomy, positive for metastasis from colorectal cancer and peritoneal washing cytology was positive for neoplastic cells. A CT-scan was performed on December 2017 showed a suspect lesion below the anterior abdominal wall. The case was discussed at the tumour board and the indication for CRS and HIPEC was given. In January 2018 the child underwent complete CRS and HIPEC with no complications. No adjuvant chemotherapy was administered. After 11 months the follow up is negative for the recurrent disease. Discussion and Conclusion Cytoreduction and HIPEC can be performed even in children as a feasible and safe treatment with successful outcomes. As for adults, an appropriate multidisciplinary pre-operative work up and a correct cases selection is needed to have the best results even regarding the quality of life

CRISPR/Cas9-mediated deletion of Interleukin-30 suppresses IGF1 and CXCL5 and boosts SOCS3 reducing prostate cancer growth and mortality

Background Metastatic prostate cancer (PC) is a leading cause of cancer death in men worldwide. Targeting of the culprits of disease progression is an unmet need. Interleukin (IL)-30 promotes PC onset and development, but whether it can be a suitable therapeutic target remains to be investigated. Here, we shed light on the relationship between IL30 and canonical PC driver genes and explored the anti-tumor potential of CRISPR/Cas9-mediated deletion of IL30. Methods PC cell production of, and response to, IL30 was tested by flow cytometry, immunoelectron microscopy, invasion and migration assays and PCR arrays. Syngeneic and xenograft models were used to investigate the effects of IL30, and its deletion by CRISPR/Cas9 genome editing, on tumor growth. Bioinformatics of transcriptional data and immunopathology of PC samples were used to assess the translational value of the experimental findings. Results Human membrane-bound IL30 promoted PC cell proliferation, invasion and migration in association with STAT1/STAT3 phosphorylation, similarly to its murine, but secreted, counterpart. Both human and murine IL30 regulated PC driver and immunity genes and shared the upregulation of oncogenes, BCL2 and NFKB1, immunoregulatory mediators, IL1A, TNF, TLR4, PTGS2, PD-L1, STAT3, and chemokine receptors, CCR2, CCR4, CXCR5. In human PC cells, IL30 improved the release of IGF1 and CXCL5, which mediated, via autocrine loops, its potent proliferative effect. Deletion of IL30 dramatically downregulated BCL2, NFKB1, STAT3, IGF1 and CXCL5, whereas tumor suppressors, primarily SOCS3, were upregulated. Syngeneic and xenograft PC models demonstrated IL30's ability to boost cancer proliferation, vascularization and myeloid-derived cell infiltration, which were hindered, along with tumor growth and metastasis, by IL30 deletion, with improved host survival. RNA-Seq data from the PanCancer collection and immunohistochemistry of high-grade locally advanced PCs demonstrated an inverse association (chi-squared test, p = 0.0242) between IL30 and SOCS3 expression and a longer progression-free survival of patients with IL30(Neg)SOCS3(Pos)PC, when compared to patients with IL30(Pos)SOCS3(Neg)PC. Conclusions Membrane-anchored IL30 expressed by human PC cells shares a tumor progression programs with its murine homolog and, via juxtacrine signals, steers a complex network of PC driver and immunity genes promoting prostate oncogenesis. The efficacy of CRISPR/Cas9-mediated targeting of IL30 in curbing PC progression paves the way for its clinical use

Development and Multicenter Validation of a Novel Immune-Inflammation-Based Nomogram to Predict Survival in Western Resectable Gastric and Gastroesophageal Junction Adenocarcinoma (GEA): The NOMOGAST

Background. More than 50% of operable GEA relapse after curative-intent resection. We aimed at externally validating a nomogram to enable a more accurate estimate of individualized risk in resected GEA. Methods. Medical records of a training cohort (TC) and a validation cohort (VC) of patients undergoing radical surgery for c/uT2-T4 and/or node-positive GEA were retrieved, and potentially interesting variables were collected. Cox proportional hazards in univariate and multivariate regressions were used to assess the effects of the prognostic factors on OS. A graphical nomogram was constructed using R software’s package Regression Modeling Strategies (ver. 5.0-1). The performance of the prognostic model was evaluated and validated. Results. The TC and VC consisted of 185 and 151 patients. ECOG:PS > 0 (p < 0.001), angioinvasion (p < 0.001), log (Neutrophil/Lymphocyte ratio) (p < 0.001), and nodal status (p = 0.016) were independent prognostic values in the TC. They were used for the construction of a nomogram estimating 3- and 5-year OS. The discriminatory ability of the model was evaluated with the c-Harrell index. A 3-tier scoring system was developed through a linear predictor grouped by 25 and 75 percentiles, strengthening the model’s good discrimination (p < 0.001). A calibration plot demonstrated a concordance between the predicted and actual survival in the TC and VC. A decision curve analysis was plotted that depicted the nomogram’s clinical utility. Conclusions. We externally validated a prognostic nomogram to predict OS in a joint independent cohort of resectable GEA; the NOMOGAST could represent a valuable tool in assisting decision-making. This tool incorporates readily available and inexpensive patient and disease characteristics as well as immune-inflammatory determinants. It is accurate, generalizable, and clinically effectivex

Microsatellite and RAS/RAF Mutational Status as Prognostic Factors in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Background Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) leads to prolonged survival for selected patients with colorectal (CRC) peritoneal metastases (PM). This study aimed to analyze the prognostic role of micro-satellite (MS) status and RAS/RAF mutations for patients treated with CRS. Methods Data were collected from 13 Italian centers with PM expertise within a collaborative group of the Italian Society of Surgical Oncology. Clinical and pathologic variables and KRAS/NRAS/BRAF mutational and MS status were correlated with overall survival (OS) and disease-free survival (DFS). Results The study enrolled 437 patients treated with CRS-HIPEC. The median OS was 42.3 months [95% confidence interval (CI), 33.4-51.2 months], and the median DFS was 13.6 months (95% CI, 12.3-14.9 months). The local (peritoneal) DFS was 20.5 months (95% CI, 16.4-24.6 months). In addition to the known clinical factors, KRAS mutations (p = 0.005), BRAF mutations (p = 0.01), and MS status (p = 0.04) were related to survival. The KRAS- and BRAF-mutated patients had a shorter survival than the wild-type (WT) patients (5-year OS, 29.4% and 26.8% vs 51.5%, respectively). The patients with micro-satellite instability (MSI) had a longer survival than the patients with micro-satellite stability (MSS) (5-year OS, 58.3% vs 36.7%). The MSI/WT patients had the best prognosis. The MSS/WT and MSI/mutated patients had similar survivals, whereas the MSS/mutated patients showed the worst prognosis (5-year OS, 70.6%, 48.1%, 23.4%; p = 0.0001). In the multivariable analysis, OS was related to the Peritoneal Cancer Index [hazard ratio (HR), 1.05 per point], completeness of cytoreduction (CC) score (HR, 2.8), N status (HR, 1.6), signet-ring (HR, 2.4), MSI/WT (HR, 0.5), and MSS/WT-MSI/mutation (HR, 0.4). Similar results were obtained for DFS. Conclusion For patients affected by CRC-PM who are eligible for CRS, clinical and pathologic criteria need to be integrated with molecular features (KRAS/BRAF mutation). Micro-satellite status should be strongly considered because MSI confers a survival advantage over MSS, even for mutated patients

Is Systemic Chemotherapy Useful in Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Colorectal Peritoneal Metastases? A Propensity-Score Analysis

Purpose: Multimodal treatment of colorectal (CRC) peritoneal metastases (PM) includes systemic chemotherapy (SC) and surgical cytoreduction (CRS), eventually with hyperthermic intraperitoneal chemotherapy (HIPEC), in select patients. Considering lack of clear guidelines, this study was designed to analyze the role of chemotherapy and its timing in patients treated with CRS-HIPEC. Methods: Data from 13 Italian centers with PM expertise were collected by a collaborative group of the Italian Society of Surgical Oncology (SICO). Clinicopathological variables, SC use, and timing of administration were correlated with overall survival (OS), disease-free survival (DFS), and local (peritoneal) DFS (LDFS) after propensity-score (PS) weighting to reduce confounding factors. Results: A total of 367 patients treated with CRS-HIPEC were included in the propensity-score weighting. Of the total patients, 19.9% did not receive chemotherapy within 6 months of surgery, 32.4% received chemotherapy before surgery (pregroup), 28.9% after (post), and 18.8% received both pre- and post-CRS-HIPEC treatment (peri). SC was preferentially administered to younger (p = 0.02) and node-positive (p = 0.010) patients. Preoperative SC is associated with increased rate of major complications (26.9 vs. 11.3%, p = 0.0009). After PS weighting, there were no differences in OS, DFS, or LDFS (p = 0.56, 0.50, and 0.17) between chemotherapy-treated and untreated patients. Considering SC timing, the post CRS-HIPEC group had a longer DFS and LDFS than the pre-group (median DFS 15.4 vs. 9.8 m, p = 0.003; median LDFS 26.3 vs. 15.8 m, p = 0.026). Conclusions: In patients with CRC-PM treated with CRS-HIPEC, systemic chemotherapy was not associated with overall survival benefit. The adjuvant schedule was related to prolonged disease-free intervals. Additional, randomized studies are required to clarify the role and timing of systemic chemotherapy in this patient subset

Taller de concordancia en la evaluación de imágenes capilaroscópicas

Introducción: la capilaroscopia es un método no invasivo que permite observar la microvasculatura en el área periungueal. Los resultados informados pueden ser altamente variables entre distintos observadores. A lo largo del tiempo surgieron métodos cuantitativos y semicuantitativos para mejorar la reproducibilidad. Objetivos: conocer el nivel de acuerdo intra e interobservador al informar los diferentes patrones capilaroscópicos en individuos con diferente nivel de entrenamiento. Materiales y métodos: estudio de corte transversal. Participaron médicos reumatólogos especialistas y en formación que habían realizado previamente un curso virtual de capacitación en capilaroscopia. Recibieron 40 imágenes capilaroscópicas proyectadas en una presentación de PowerPoint y debían responder a través de un cuestionario digital. Se evaluó la concordancia de respuestas intra e interobservador. Resultados: se encontró un alto nivel de concordancia global con un kappa 0,66 IC 95% (0,63-0,70) p<0,0000. También en otros grupos como reumatólogos en formación: kappa 0,65 IC 95% (0,60-0,71) p=0,0000, y médicos reumatólogos: kappa 0,67 IC 95% (0,62-0,72) p=0,0000. Conclusiones: el nivel de concordancia encontrado fue globalmente alto, independientemente del nivel de entrenamiento de los profesionales, y de ser o no reumatólogo. La concordancia fue superior cuando se comparó a quienes tenían más de 4 años de experiencia en la realización de videocapilaroscopia

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease