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.

Diagnostic and Therapeutic Pathway of Advanced Ovarian Cancer with Peritoneal Metastases.

Over two thirds of ovarian cancer patients present with advanced stage disease at the time of diagnosis. In this scenario, standard treatment includes a combination of cytoreductive surgery and carboplatinum-paclitaxel-based chemotherapy. Despite the survival advantage of patients treated with upfront cytoreductive surgery compared to women undergoing neo-adjuvant chemotherapy (NACT) and interval debulking surgery (IDS) due to high tumor load or poor performance status has been demonstrated by multiple studies, this topic is still a matter of debate. As a consequence, selecting the adequate treatment through an appropriate diagnostic pathway represents a crucial step. Aiming to assess the likelihood of leaving no residual disease at the end of surgery, the role of the CT scan as a predictor of cytoreductive outcomes has shown controversial results. Similarly, CA 125 level as an expression of tumor load demonstrated limited applicability. On the contrary, laparoscopic assessment of disease distribution through a validated scoring system was able to identify, with the highest specificity, patients undergoing suboptimal cytoreduction and therefore best suitable for NACT-IDS. Against this background, with this article, we aim to provide a comprehensive review of available evidence on the diagnostic and treatment pathways of advanced ovarian cancer.

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.

Exploring the Effectiveness of Sustainability Measurement: Which ESG Metrics Will Survive COVID-19?

This paper aims to investigate the current state of play on Environmental Social and Governance (ESG) integration and check the validity of the current metrics system by assessing if it will survive the COVID-19 crisis. By adopting a qualitative research approach through semi-structured anonymous interviews with 14 senior managers of six European listed companies we use a framework by assessing the mechanisms of reactivity on the effectiveness of ESG measures in times of COVID-19. By interpreting the practitioners' points of view through the lens of the sociological framework by Espeland and Sauder (Am J Sociol 113:1-40, 2007) our findings show different mechanisms of reactivity by companies on the effectiveness of ESG measures in times of COVID-19, i.e., active and passive conformity and active resistance. We also identified the main Corporate Social Responsibility (CSR) institutional factors that affect managers' reactivity. An extensive re-formulation of the ESG metrics is required in the light of times of crisis, given that accountability and transparency are strongly linked to quantitative measures which can play a critical role in the financial system and investors' engagement. Particularly, the strict distinction between "E", "S" and "G" issues should be abandoned claiming a different holistic re-design of sustainability measures by considering the increasing relevance of the Social dimension in time of COVID-19. This study provides a valuable contribution to the existing literature on the measurement of sustainability within the link of accountability and crisis by highlighting new corporate needs to re-design the ESG metrics system.

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.

Laparoscopic Cytoreduction Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Peritoneal Surface Malignancies (PSM): Italian PSM Oncoteam Evidence and Literature Review.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has gained increasing acceptance in clinical practice. Performing CRS and HIPEC laparoscopically represents a challenging and intriguing technical evolution. However, the experiences are limited, and the evidence is low. This retrospective analysis was performed on patients treated with laparoscopic CRS-HIPEC within the Italian Peritoneal Surface Malignancies Oncoteam. Clinical, perioperative, and follow-up data were extracted and collected on prospectively maintained databases. We added a systematic review according to the PRISMA method for English-language articles through April 2022 using the keywords laparoscopic, hyperthermic, HIPEC, and chemotherapy. From 2016 to 2022, fourteen patients were treated with Lap-CRS-HIPEC with curative intent within the Italian centers. No conversion to open was observed. The median duration of surgery was 487.5 min. The median Peritoneal Cancer Index (PCI) was 3, and complete cytoreduction was achieved in all patients. Two patients (14.3%) had major postoperative complications, one requiring reintervention. After a median follow-up of 16.9 months, eleven patients were alive without disease (78.6%), two patients developed recurrence (14.3%), and one patient died for unrelated causes (7.1%). The literature review confirmed these results. In conclusion, current evidence shows that Lap-CRS-HIPEC is feasible, safe, and associated with a favorable outcome in selected patients. An accurate patient selection will continue to be paramount in choosing this treatment.

Peritoneal carcinomatosis from colorectal cancer in the pediatric population: Cytoreductive surgery and HIPEC. A systematic review.

Colorectal cancer (CRC) is a rare condition in the pediatric population, but it is usually associated with worse prognosis compared to the adult population. Surgical resection is the gold standard and most effective treatment for CRC. Cytoreductive surgery (CRS) and Heated Intra-Peritoneal Chemotherapy (HIPEC) is a feasible option in resectable primary tumour with carcinomatosis and non-evidence of extra-abdominal disease. Although it is very uncommon in children when performed, CRS-HIPEC is based on the description by Sugarbaker et al. and the two most common administrated drugs are Cisplatin and Mitomycin-C. We present a review of the cases found in the literature of peritoneal carcinomatosis from CRC treated with CRS and HIPEC in children. A systematic search was performed in the major databases up to February 2020. We included all the reviews and studies reporting clinical data on pediatric patients with peritoneal colorectal carcinomatosis. Nine cases were extracted from the literature. Patient age was between 11 and 16 years old. All patients underwent neoadjuvant chemotherapy. All patients were treated with HIPEC and the majority of them received a complete cytoreduction (CC-0). At follow-up, three patients were found free from disease with an average time of follow up of 74 weeks (40-100). In 33% of cases, recurrence was described. No postoperative death within 30 days from surgery was observed. CRS and HIPEC can be a feasible option for CRC peritoneal carcinomatosis in children. Because CRC is unusual among the pediatric population, multi-institutional studies should be done to achieve larger cohorts and a more reliable analysis.

A new anterior approach to parastomal hernia repair (PHR) with linear stapler suture: A case report.

INTRODUCTION: Parastomal hernia is a type of incisional hernia occurring in abdominal integuments in the vicinity of a stoma. The best surgical approach for PSH remains controversial. Most studies report short follow-up time after surgery and a low number of cases to allow conclusions. Actually, we don't have a relevant recommendation about an optimal surgical technique or the most effective mesh for PSH repair. PRESENTATION OF THE CASE: Once packaged the latero-lateral mechanical anastomosis to restore the continuity of the intestinal tract of the patient, an adequate disinfection of trough of the stoma was done. The lateral and medial margins of the defect are then transposed towards each other and kept side by side with a gripper; a 60 mm tristaple linear stapler was placed, incorporating both edges and the charge is fired to obtain a perfect synthesis of the retromuscular plane. DISCUSSION: In the literature has been described several surgical techniques for its repair: suture repair, relocation, mesh-based technique with open or laparoscopic approach. Both, the simple corrective surgery of Thorlakson in 1965 and the use of the peritoneomuscular flap for closing the defect, suggested by Bewes, led to high incidence of recurrence. An important reduction in the rate of parastomal hernia derives also from the mesh reinforcement of the stoma trephine. CONCLUSION: The authors suggest that this technique should be help the surgeons to repair parastomal hernia in patients with multiple risk factors to develop a recurrence of parastomal hernia.

A novel surgical approach with peritonectomy to extranodal multisystemic histiocytic sarcoma: A case report and literature review.

INTRODUCTION: Histiocytic sarcoma (HS) is a very rare malignant histiocytic derivation cancer. The extranodal multisystemic HS has an aggressive clinical course and poor Disease-Free Survival (DFS) and Overall Survival (OS). There are no shared and effective therapeutic protocols; our approach aims to improve the prognosis for advanced diseases. PRESENTATION OF THE CASE: 53-year-old female patient admitted to hospital for intestinal obstruction in April 2016 with evidence of an ileal mass in the right iliac fossa and peritoneal metastases, undergoing urgent surgery of ileal resection, ileostomy and nodular peritoneal mass biopsy. Histological examination diagnosed HS. Staging exams excluded the involvement of other gastro-intestinal districts in the absence of concomitant lymphoproliferative disorders, and PET-CT revealed multiple abdominal and mediastinal nodes hyperplasia. The patient performed chemotherapy and, seeing the partial abdominal extranodal response, was performed cytoreductive surgery (CRS). Histological examination confirmed the diagnosis of HS with multiple peritoneal, ileal, colic and omental localisation. Adjuvant second-line chemotherapy treatment (4 DHAP cycles) was performed. Disease Free Survival at ten months from cytoreductive surgery, Overall Survival at 21 months from diagnosis. DISCUSSION: Despite a multimodal therapy with surgery and chemotherapy, extranodal multisystemic HS has a poor prognosis. Up to now the role of surgery is limited to biopsies or complications treatment. Our results of DFS and OS show that cytoreductive surgery may be a valid therapeutic choice. CONCLUSION: The surgical approach with major cytoreductive purposes could improve the prognosis in cases with prevalent abdominal extranodal localisation.

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.

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.