Risk of appendiceal neoplasm after interval appendectomy for complicated appendicitis: A systematic review and meta-analysis.

BACKGROUND: Non-operative management is often the treatment of choice in cases of complicated appendicitis and routine interval appendectomy is not usually recommended. Actually, recent studies show an alarming number of appendiceal neoplasms following interval appendectomy. The aim of this study is to evaluate the prevalence of appendiceal neoplasms and their histological types after interval appendectomy for complicated appendicitis in adults. METHODS: A comprehensive literature search of the PubMed, Scopus and Web of Science databases was conducted according to the PRISMA statement. Studies reporting appendiceal neoplasm rates after interval appendectomy and histopathological characteristics were included. The most recent World Health Organization (WHO) classification of malignant tumours was considered. A pooled prevalence analysis for both prevalence and pathology was performed. RESULTS: A total of eight studies was included: seven retrospective series and one randomized controlled trial. The pooled prevalence of neoplasms after interval appendectomy was 11% (95% CI 7-15; I2 = 37.5%, p = 0.13). Appendiceal mucinous neoplasms occurred in 43% (95% CI 19-68), adenocarcinoma in 29% (95% CI 6-51), appendiceal neuroendocrine neoplasm in 21% (95% CI 6-36), globet cell carcinoma in 13% (95% CI -2-28), adenoma or serrated lesions in 20% (95% CI -0-41) of cases. CONCLUSION: The risk of appendiceal neoplasm in patients treated with interval appendectomy for complicated appendicitis is 11%; mucinous neoplasm is the most common histopathological type. Further studies should investigate this association in order to clarify the biological pathway and clinical implications.

Prognostic factors in Krukenberg tumor.

BACKGROUND: Krukenberg tumor (KT) is a rare secondary ovarian tumor. Little is known about clinicopathologic factors affecting prognosis in KT. OBJECTIVE: To assess the prognostic value of clinicopathologic factors in KT through a systematic review and meta-analysis. METHODS: Electronic databases were searched from their inception to February 2019 for studies assessing the association of clinicopathologic factors with overall survival in KT. Pooled hazard ratio (HR) was calculated for each factor; a p value < 0.05 was considered significant. RESULTS: Twenty-three studies with 1743 patients were included. A decreased overall survival was significantly associated with peritoneal involvement (HR 1.944; p = 0.003), ascites (HR 2.055; p = 0.034), synchronous presentation (HR 1.679; p = 0.034) and increased serum CEA levels (HR 1.380; p = 0.010), but not with age > 50 (HR 0.946; p = 0.743), menopausal status (HR 1.565; p = 0.204), gastric origin (HR 1.600; p = 0.201), size > 5 cm (HR 1.292; p = 0.119), size > 10 cm (HR 0.925; p = 0.714), bilateral ovarian involvement (HR 1.113; p = 0.347), non-peritoneal extaovarian metastases (HR 1.648; p = 0.237), liver metastases (HR 1.118, p = 0.555), predominant signet ring cell morphology (HR 1.322; p = 0.208) and levels of CA125 (HR 0.933; p = 0.828) and CA19.9 (HR 0.996; p = 0.992). CONCLUSION: Peritoneal involvement, synchronous presentation, ascites and increased serum CEA levels appear as unfavorable prognostic factors in KT and might affect the patient management.

Treatments and overall survival in patients with Krukenberg tumor.

BACKGROUND: Krukenberg tumor (KT) is a rare secondary ovarian tumor, primarily localized at the gastrointestinal tract in most cases. KT is related to severe prognosis due to its aggressiveness, diagnostic difficulties and poor treatment efficacy. Several treatments have been used, such as cytoreductive surgery (CRS), adjuvant chemotherapy (CT) and/or hyperthermic intraperitoneal chemotherapy (HIPEC). To date, it is still unclear which treatment or combination of treatments is related to better survival. OBJECTIVE: To assess the most effective therapeutic protocol in terms of overall survival (OS). METHODS: A systematic review of the literature was performed by searching MEDLINE, Scopus, EMBASE, ClinicalTrial.gov, OVID, Web of Sciences, Cochrane Library, and Google Scholar for all studies assessing the association of treatments with OS in KTs. The effectiveness of each treatment protocol was evaluated by comparing the OS between patients treated with different treatment protocols. RESULTS: Twenty retrospective studies, with a total sample size of 1533 KTs, were included in the systematic review. Therapeutic protocols used were CRS in 18 studies, CT in 13 studies, HIPEC in 7 studies, neoadjuvant CT in 2 studies, and some combinations of these in 6 studies. Seven studies showed that CRS significantly improved OS compared to other treatments or association of treatments without it. 11 studies showed that CRS without residual (R0 CRS) had a significantly better OS than CRS with residual (R + CRS). Five studies showed that CT significantly improved OS, but other five showed it did not. Two studies showed that HIPEC in association with CRS improved OS, while another study showed that efficacy of HIPEC was comparable to CT. Two studies evaluated neoadjuvant CT, but results were conflicting. CONCLUSION: CRS and in particular R0 CRS are the treatments showing the clearest results in improving OS in KT patients. Results about CT are conflicting. HIPEC appears effective both alone and in combination with CRS, and also related to fewer adverse effect than CT. The usefulness of neoadjuvant CT is still unclear. The association of R0 CRS with HIPEC seems to be the most effective and safe therapeutic protocol for KT patients.

The Madrid Posterior Component Separation: An Anatomical Approach for Effective Reconstruction of Complex Midline Hernias.

Introduction: In recent years, Posterior Component Separation (PCS) with the Madrid modification (Madrid PCS) has emerged as a surgical technique. This modification is believed to enhance the dissection of anatomical structures, offering several advantages. The study aims to present a detailed description of this surgical technique and to analyse the outcomes in a large cohort of patients. Materials and Methods: This study included all patients who underwent the repair of midline incisional hernias, with or without other abdominal wall defects. Data from patients at three different centres specialising in abdominal wall reconstruction was analysed. All patients underwent the Madrid PCS, and several variables, such as demographics, perioperative details, postoperative complications, and recurrences, were assessed. Results: Between January 2015 and June 2023, a total of 223 patients underwent the Madrid PCS. The mean age was 63.4 years, with a mean BMI of 33.3 kg/m2 (range 23-40). According to the EHS classification, 139 patients had a midline incisional hernia, and 84 had a midline incisional hernia with a concomitant lateral incisional hernia. According to the Ventral Hernia Working Group (VHWG) classification, 177 (79.4%) patients had grade 2 and 3 hernias. In total, 201 patients (90.1%) were ASA II and III. The Carolinas Equation for Determining Associated Risks (CeDAR) was calculated preoperatively, resulting in 150 (67.3%) patients with a score between 30% and 60%. A total of 105 patients (48.4%) had previously undergone abdominal wall repair surgery. There were 93 (41.7%) surgical site occurrences (SSO), 36 (16.1%) surgical site infections (SSI), including 23 (10.3%) superficial and 7 (3.1%) deep infections, and 6 (2.7%) organ/space infections. Four (1.9%) recurrences were assessed by CT scan with an average follow-up of 23.9 months (range 6-74). Conclusion: The Madrid PCS appears to be safe and effective, yielding excellent long-term results despite the complexity of abdominal wall defects. A profound understanding of the anatomy is crucial for optimal outcomes. The Madrid modification contributes to facilitating a complete retromuscular preperitoneal repair without incision of the transversus abdominis. The extensive abdominal wall retromuscular dissection obtained enables the placement of very large meshes with minimal fixation.

Laparoscopic adrenalectomy for giant pheochromocytoma. What is the size limit ?

AIM: This case report describes a giant pheochromocytoma in a young female, experienced cardiac symptoms, treated by a transperitoneal laparoscopic right adrenalectomy. MATERIAL AND METHODS: A 29 years old female with Taki-tsubo syndrome, consequent to the chronic release of catecholamines, with a palpable abdominal mass and vague abdominal symptoms was referred to our department. Abdominal CT scan has demonstrated a solid mass of 13 cm in the right adrenal space so, after pre-operative management with alpha-adrenergic receptor and beta blockade and a 3D CT scan reconstruction a right adrenalectomy laparoscopic approach was performed. RESULTS: Our result underlines that 13 cm in size for a giant pheochromocytoma is not an absolute contraindication to perform a minimally invasive approach in expert hands, with optimal surgical, oncological and cosmetic results. DISCUSSION: The only curative option for non-metastatic pheochromocytomas disease is surgical resection. Laparoscopic adrenalectomy is the treatment of choice but the limit size for a safe and feasible minimally invasive approach is not yet defined. CONCLUSIONS: This case report could help to better define more solid recommendations in the next future and also provide landmarks and key steps for laparoscopic surgeons. KEY WORDS: Giant Pheochromocytoma, Laparoscopic Adrenalectomy, Pheochromocytoma Management.

TRPM8 indicates poor prognosis in colorectal cancer patients and its pharmacological targeting reduces tumour growth in mice by inhibiting Wnt/ß-catenin signalling.

BACKGROUND AND PURPOSE: Transient receptor potential melastatin type-8 (TRPM8) is a cold-sensitive cation channel protein belonging to the TRP superfamily of ion channels. Here, we reveal the molecular mechanism of TRPM8 and its clinical relevance in colorectal cancer (CRC). EXPERIMENTAL APPROACH: TRPM8 expression and its correlation with the survival rate of CRC patients was analysed. To identify the key pathways and genes related to TRPM8 high expression, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted in CRC patients. TRPM8 functional role was assessed by using Trpm8-/- mice in models of sporadic and colitis-associated colon cancer. TRPM8 pharmacological targeting by WS12 was evaluated in murine models of CRC. KEY RESULTS: TRPM8 is overexpressed in colon primary tumours and in CD326+ tumour cell fraction. TRPM8 high expression was related to lower survival rate of CRC patients, Wnt-Frizzled signalling hyperactivation and adenomatous polyposis coli down-regulation. In sporadic and colitis-associated models of colon cancer, either absence or pharmacological desensitization of TRPM8 reduced tumour development via inhibition of the oncogenic Wnt/ß-catenin signalling. TRPM8 pharmacological blockade reduced tumour growth in CRC xenograft mice by reducing the transcription of Wnt signalling regulators and the activation of ß-catenin and its target oncogenes such as C-Myc and Cyclin D1. CONCLUSION AND IMPLICATIONS: Human data provide valuable insights to propose TRPM8 as a prognostic marker with a negative predictive value for CRC patient survival. Animal experiments demonstrate TRPM8 involvement in colon cancer pathophysiology and its potential as a drug target for CRC.

Clinics and pathology of Krukenberg tumor: a systematic review and meta-analysis.

INTRODUCTION: Krukenberg tumor (KT) is defined as a secondary neoplasm of the ovary. While ovarian metastases account for about 30% of ovarian tumors, KTs are rare, accounting for about 1-2% of the total. The rarity of KT is at least in part responsible for the lack of a precise clinic-pathological characterization of these tumors. Clinically, KT may have a subtle clinical presentation, with few symptomatic manifestations and nonspecific clinical signs, even though in literature there is disagreement about the clinical presentation of these patients; such difficulties in the diagnostic framework often leads to a delayed diagnosis with serious consequences on the patient outcome. We aimed to provide a clinico-pathological characterization of Krukenberg Tumor (KT) through a systematic review and meta-analysis to improve the diagnosis and management of KT. EVIDENCE ACQUISITION: Electronic databases were searched for all studies assessing clinico-pathological features of KT series. Pooled prevalence of each clinical or pathological factor was calculated according to the random-effect model. EVIDENCE SYNTHESIS: Forty-eight studies with 3025 KT patients were included; 39.7% of patients were ≥50 and 39.8% were postmenopausal. The most common primary tumor sites were stomach (42.5%), colon-rectum (26.1%), breast (9.3%), and appendix (5%); 48.7% of KTs were synchronous with the primary tumor, 64.3% were bilateral, 40.5% had a diameter ≥10 cm; 55.3% showed extraovarian extent and 49% showed peritoneal involvement. The most common presenting symptoms were ascites (51.7%), palpable mass (31.3%), pain (29.3%), abdominal distention (28.7%), irregular bleeding (9.1%), asymptomatic (11.2%). CONCLUSIONS: KT shows a highly variable presentation. Understanding the prevalence of clinico-pathological factors may be helpful to improve the diagnosis and management of KT.

Predictive Factors for Anastomotic Leakage after Laparoscopic and Open Total Gastrectomy: A Systematic Review.

The aim of this systematic review is to identify patient-related, perioperative and technical risk factors for esophago-jejunal anastomotic leakage (EJAL) in patients undergoing total gastrectomy for gastric cancer (GC). A comprehensive literature search of PubMed/MEDLINE, Embase and Scopus databases was performed. Studies providing factors predictive of EJAL by uni- and multivariate analysis or an estimate of association between EJAL and related risk factors were included. All studies were assessed for methodological quality, and a narrative synthesis of the results was performed. A total of 16 studies were included in the systematic review, with a total of 42,489 patients who underwent gastrectomy with esophago-jejunal anastomosis. Age, BMI, impaired respiratory function, prognostic nutritional index (PNI), alcohol consumption, chronic renal failure, diabetes and mixed-type histology were identified as patient-related risk factors for EJAL at multivariate analysis. Likewise, among operative factors, laparoscopic approach, anastomosis type, additional organ resection, blood loss, intraoperative time and surgeon experience were found to be predictive factors for the development of EJAL. In clinical setting, we are able to identify several risk factors for EJAL. This can improve the recognition of higher-risk patients and their outcomes.

N-Acylethanolamine acid amidase (NAAA) is dysregulated in colorectal cancer patients and its inhibition reduces experimental cancer growth.

BACKGROUND AND PURPOSE: N-Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme accountable for the breakdown of N-acylethanolamines (NAEs) and its pharmacological inhibition has beneficial effects in inflammatory conditions. The knowledge of NAAA in cancer is fragmentary with an unclarified mechanism, whereas its contribution to colorectal cancer (CRC) is unknown to date. EXPERIMENTAL APPROACH: CRC xenograft and azoxymethane models were used to assess the in vivo effect of NAAA inhibition. Further, the tumour secretome was evaluated by an oncogenic array, CRC cell lines were used for in vitro studies, cell cycle was analysed by cytofluorimetry, NAAA was knocked down with siRNA, human biopsies were obtained from surgically resected CRC patients, gene expression was measured by RT-PCR and NAEs were measured by LC-MS. KEY RESULTS: The NAAA inhibitor AM9053 reduced CRC xenograft tumour growth and counteracted tumour development in the azoxymethane model. NAAA inhibition affected the composition of the tumour secretome inhibiting the expression of EGF family members. In CRC cells, AM9053 reduced proliferation with a mechanism mediated by PPAR-α and TRPV1. AM9053 induced cell cycle arrest in the S phase associated with cyclin A2/CDK2 down-regulation. NAAA knock-down mirrored the effects of NAAA inhibition with AM9053. NAAA expression was down-regulated in human CRC tissues, with a consequential augmentation of NAE levels and dysregulation of some of their targets. CONCLUSION AND IMPLICATIONS: Our results show novel data on the functional importance of NAAA in CRC progression and the mechanism involved. We propose that this enzyme is a valid drug target for the treatment of CRC growth and development.

Ki67 as a prognostic marker in uterine leiomyosarcoma: A quantitative systematic review.

Ki67 labeling index (LI) has been proposed as a prognostic factor in uterine leiomyosarcoma (uLMS), although the evidence in this field is still unclear. We aimed to assess the prognostic value of ki67 LI in uLMS. A systematic review was performed by searching electronic databases from their inception to August 2020 for all studies assessing the prognostic value of ki67 LI in uLMS. Ki67 LI was assessed to the nearest 10% to define the most prognostically accurate threshold. Cox regression survival analysis with calculation of hazard ratio (HR) of death was performed; a p-value < 0.05 was considered significant. Ten studies were included in the qualitative review, out of which 6 were suitable for quantitative review. The absolute risk of death was 0.29 for a ki67 LI < 10%, remained stable at 0.49 in the 10%-39% LI range and increased to 0.65 for a LI ≥ 40%. On univariate analysis, both 10% and 40% thresholds were significantly associated with the hazard of death, with HRs of 3.349 (p = 0.007) and 3.172 (p = 0.001), respectively. On multivariate analysis, only the 10% threshold was significantly associated with the hazard of death (HR = 2.712; p = 0.028). In conclusion, a Ki67 LI ≥ 10% is a significant prognostic factor in uLMS.