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.

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.

Statins increase pathological response in locally advanced rectal cancer treated with chemoradiation: a multicenter experience.

Aims: To investigate the influence of various concomitant medications on outcomes in patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation. Materials & methods: The authors retrospectively identified 246 patients from 2003 to 2018, collecting demographic and clinicopathological data of interest. Odds ratio (OR) was used to assess the association between concomitant drugs and outcomes. Results: The authors found an association between statins and a Dworak regression grade of 3-4 (OR = 8.78; p = 0.01). Furthermore, statins were significantly associated with more frequent chemoradiation-related toxicity (OR = 2.39; p = 0.0098) and chemotherapy dose reduction or discontinuation (OR = 2.26; p = 0.03). Conclusion: Despite higher frequency of radiotherapy and chemotherapy interruption or dose reduction, the concomitant use of statins during neoadjuvant chemoradiation proved to be associated with better tumor regression.

Handling and Processing of Blood Specimens from Patients with COVID-19 for Safe Studies on Cell Phenotype and Cytokine Storm.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 heavily involves all those working in a laboratory. Samples from known infected patients or donors who are considered healthy can arrive, and a colleague might be asymptomatic but able to transmit the virus. Working in a clinical laboratory is posing several safety challenges. Few years ago, International Society for Advancement of Cytometry published guidelines to safely analyze and sort human samples that were revised in these days. We describe the procedures that we have been following since the first patient appeared in Italy, which have only slightly modified our standard one, being all human samples associated with risks. © 2020 International Society for Advancement of Cytometry.

Chronic and recurrent benign lymphadenopathy without constitutional symptoms associated with human herpesvirus-6B reactivation.

Chronic/recurrent behaviour may be encountered in some distinct atypical or malignant lymphoproliferations, while recurrences are not generally observed in reactive/benign lymphadenopathies. We retrospectively analysed a consecutive series of 486 human immunodeficiency virus-negative adults, who underwent lymphadenectomy. Neoplastic and benign/reactive histopathological pictures were documented in 299 (61·5%) and 187 (38·5%) cases, respectively. Of note, seven of the 111 (6·3%) patients with benign lymphadenopathy without well-defined aetiology, showed chronic/recurrent behaviour, without constitutional symptoms. Enlarged lymph nodes were round in shape and hypoechoic, mimicking lymphoma. Reactive follicular hyperplasia and paracortical expansion were observed. Human herpesvirus (HHV)-6B positive staining in follicular dendritic cells (FDCs) was documented in all seven patients. Serological, molecular and immunological examinations suggested HHV-6B reactivation. Among the remaining 104 cases with reactive lymphoid hyperplasia in the absence of well-known aetiology and without recurrences, positivity for HHV-6B on FDCs was found in three cases, whereas in seven further patients, a scanty positivity was documented in rare, scattered cells in inter-follicular regions. Immunohistochemistry for HHV-6A and HHV-6B was invariably negative on 134 lymph nodes, with either benign pictures with known aetiology or malignant lymphoproliferative disorders, tested as further controls. Future studies are warranted to investigate a potential association between HHV-6B reactivation and chronic/recurrent benign lymphadenopathy.

Enhanced recovery after surgery (ERAS) implementation in cytoreductive surgery (CRS) and hyperthermic IntraPEritoneal chemotherapy (HIPEC): Insights from Italian peritoneal surface malignancies expert centers.

BACKGROUND: Cytoreductive surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a complex procedure that involves extensive peritoneal and visceral resections followed by intraperitoneal chemotherapy. The Enhanced Recovery After Surgery (ERAS) program aims to achieve faster recovery by maintaining pre-operative organ function and reducing the stress response following surgery. A recent publication introduced dedicated ERAS guidelines for CRS and HIPEC with the aim of extending the benefits to patients with peritoneal surface malignancies. METHODS: A survey was conducted among 21 Italian centers specializing in peritoneal surface malignancies (PSM) treatment to assess adherence to ERAS guidelines. The survey covered pre/intraoperative and postoperative ERAS items and explored attitudes towards ERAS implementation. RESULTS: All centers completed the survey, demonstrating expertise in PSM treatment. However, less than 30 % of centers adopted ERAS protocols despite being aware of dedicated guidelines. Preoperative optimization was common, with variations in bowel preparation methods and fasting periods. Intraoperative normothermia control was consistent, but fluid management practices varied. Postoperative practices, including routine abdominal drain placement and NGT management, varied greatly among centers. The majority of respondents expressed an intention to implement ERAS, citing concerns about feasibility and organizational challenges. CONCLUSIONS: The study concludes that Italian centers specialized in PSM treatment have limited adoption of ERAS protocols for CRS ± HIPEC, despite being aware of guidelines. The variability in practice highlights the need for standardized approaches and further evaluation of ERAS applicability in this complex surgical setting to optimize patient care.

PEG-Asparaginase Single-Agent Rescue in an Advanced Case of Monomorphic Epitheliotropic Intestinal T Cell Lymphoma.

PURPOSE: MEITL is a very rare and highly aggressive peripheral T cell lymphoma with poor prognosis and for which there is no standard treatment. Treatment options for patients patients with relapsed/refractory disease are scarce and the choice of an appropriate rescue still represents an unmet need. METHODS: Here, we report the case of a 65-year-old woman affected by MEITL, progressing after initial treatment with an anthracycline-based chemotherapy and surgery, who received single-agent PEG-asparaginase salvage therapy at our institution. RESULTS: PEG-asparaginase single-agent rescue proved to be rapidly effective in controlling the disease and its associated paraneoplastic features. Nevertheless, toxicity was high and the patient died due to a treatment-related complication. CONCLUSION: The case we described brings new evidences on the effectiveness of PEG-asparaginase therapy in MEITL patients. Whether PEG-asparaginase should be included in the treatment course of MEITL patients could be the subject of future studies.

Enhanced Recovery after Surgery (ERAS) Program for Patients with Peritoneal Surface Malignancies Undergoing Cytoreductive Surgery with or without HIPEC: A Systematic Review and a Meta-Analysis.

Enhanced recovery after surgery (ERAS) program refers to a multimodal intervention to reduce the length of stay and postoperative complications; it has been effective in different kinds of major surgery including colorectal, gynaecologic and gastric cancer surgery. Its impact in terms of safety and efficacy in the treatment of peritoneal surface malignancies is still unclear. A systematic review and a meta-analysis were conducted to evaluate the effect of ERAS after cytoreductive surgery with or without HIPEC for peritoneal metastases. MEDLINE, PubMed, EMBASE, Google Scholar and Cochrane Database were searched from January 2010 and December 2021. Single and double-cohort studies about ERAS application in the treatment of peritoneal cancer were considered. Outcomes included the postoperative length of stay (LOS), postoperative morbidity and mortality rates and the early readmission rate. Twenty-four studies involving 5131 patients were considered, 7 about ERAS in cytoreductive surgery (CRS) + HIPEC and 17 about cytoreductive alone; the case histories of two Italian referral centers in the management of peritoneal cancer were included. ERAS adoption reduced the LOS (-3.17, 95% CrI -4.68 to -1.69 in CRS + HIPEC and -1.65, 95% CrI -2.32 to -1.06 in CRS alone in the meta-analysis including 6 and 17 studies respectively. Non negligible lower postoperative morbidity was also in the meta-analysis including the case histories of two Italian referral centers. Implementation of an ERAS protocol may reduce LOS, postoperative complications after CRS with or without HIPEC compared to conventional recovery.

Clinical outcomes of patients with complicated post-operative course after gastrectomy for cancer: a GIRCG study using the GASTRODATA registry.

Gastrectomy for gastric cancer is still performed in Western countries with high morbidity and mortality. Post-operative complications are frequent, and effective diagnosis and treatment of complications is crucial to lower the mortality rates. In 2015, a project was launched by the EGCA with the aim of building an agreement on list and definitions of post-operative complications specific for gastrectomy. In 2018, the platform www.gastrodata.org was launched for collecting cases by utilizing this new complication list. In the present paper, the Italian Research Group for Gastric Cancer endorsed a collection of complicated cases in the period 2015-2019, with the aim of investigating the clinical pictures, diagnostic modalities, and treatment approaches, as well as outcome measures of patients experiencing almost one post-operative complication. Fifteen centers across Italy provided 386 cases with a total of 538 complications (mean 1.4 complication/patient). The most frequent complications were non-surgical infections (gastrointestinal, pulmonary, and urinary) and anastomotic leaks, accounting for 29.2% and 17.3% of complicated patients, with a median Clavien-Dindo score of II and IIIB, respectively. Overall mortality of this series was 12.4%, while mortality of patients with anastomotic leak was 25.4%. The clinical presentation with systemic septic signs, the timing of diagnosis, and the hospital volume were the most relevant factors influencing outcome.

External validation of COMPASS and BIOSCOPE prognostic scores in colorectal peritoneal metastases treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).

INTRODUCTION: The selection of patients undergoing cytoreductive- surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is crucial. BIOSCOPE and COMPASS are prognostic scores designed to stratify survival into four classes according to clinical and pathological features. The purpose of this study is to analyze the prognostic role of these scores using a large cohort of patients as an external reference. METHODS: Overall survival analysis was performed using Log-Rank and Kaplan-Meier curves for each score. The probability of survival at 12, 36, and 60 months was tested using receiver operating characteristic (ROC) curves to determine sensitivity and specificity. RESULTS: From the validation cohort of 437 patients, the analysis included 410 patients in the COMPASS group and 364 patients in the BIOSCOPE group (100% data completeness). We observed a different patient distribution between classes (high-risk for BIOSCOPE compared to COMPASS, p = 0.0001). Nevertheless, both COMPASS and BIOSCOPE effectively stratified overall survival (Log-Rank, p = 0.0001 in both cases), with a lack of discrimination between COMPASS classes II and III (p = n.s.). COMPASS at 12 m and BIOSCOPE at 60 m showed the best performance in terms of survival prediction (AUC of 0.82 and 0.81). The specificity of the two tests is good (median 81.3%), whereas sensibility is quite low (median 64.2%). CONCLUSION: Following external validation in a large population of patients with CRC-PM who are eligible for surgery, the COMPASS and BIOSCOPE scores exhibit high inter-test variability but effectively stratify cancer-related mortality risk. While the quality of the scores is similar, BIOSCOPE shows better inter-tier differentiation, suggesting that tumor molecular classification could improve test discrimination capability. More powerful stratification scores with the inclusion of novel predictors are needed.

A national survey on the current status of minimally invasive gastric practice on behalf of GIRCG.

Italian Research Group for Gastric Cancer (GIRCG), during the 2013 annual Consensus Conference to gastric cancer, stated that laparoscopic or robotic approach should be limited only to early gastric cancer (EGC) and no further guidelines were currently available. However, accumulated evidences, mainly from eastern experiences, have supported the application of minimally invasive surgery also for locally advanced gastric cancer (AGC). The aim of our study is to give a snapshot of current surgical propensity of expert Italian upper gastrointestinal surgeons in performing minimally invasive techniques for the treatment of gastric cancer in order to answer to the question if clinical practice overcome the recommendation. Experts in the field among the Italian Research Group for Gastric Cancer (GIRCG) were invited to join a web 30-item survey through a formal e-mail from January 1st, 2020, to June 31st, 2020. Responses were collected from 46 participants out of 100 upper gastrointestinal surgeons. Percentage of surgeons choosing a minimally invasive approach to treat early and advanced gastric cancer was similar. Additionally analyzing data from the centers involved, we obtained that the percentage of minimally invasive total and partial gastrectomies in advanced cases augmented with the increase of surgical procedures performed per year (p = 0.02 and p = 0.04 respectively). It is reasonable to assume that there is a widening of indications given by the current national guideline into clinical practice. Propensity of expert Italian upper gastrointestinal surgeons was to perform minimally invasive surgery not only for early but also for advanced gastric cancer. Of interest volume activity correlated with the propensity of surgeons to select a minimally invasive approach.

Vaginal Evisceration of Small Bowel With Extraperitoneal Ileal Resection of the Herniated Loops: A Case Report.

Introduction: Vaginal evisceration is an extremely rare surgical emergency that can be described as the extrusion of abdominal viscera through a defect or a rupture of the vaginal wall. We reported the case of an acute abdomen due to small bowel evisceration secondary to vaginal vault dehiscence that required combined vaginal-abdominal approach. Case: We discuss the case of a 72-year-old female who presented to the emergency department for a large prolapse with visible extrusion of the small bowel per vagina. The eviscerated bowel was resected by external vaginal approach due to excessive swelling of the loops which made it impossible to reduce them through the vagina defect. A midline laparotomy was undertaken for further assessment, and the vault defect was closed by transabdominal repair. Conclusion: From its first description in 1864, just a few cases of vaginal evisceration had been described in the medical literature; the most common organ to eviscerate is the distal ileum, although cases of omentum, colon, fallopian tube, and appendix evisceration have also been reported. We described a rare case of transvaginal evisceration of the small bowel in our emergency department; it is a rare surgical emergency that must be managed to prevent serious consequences, such as bowel ischemia and necrosis, sepsis, and death. We suggest that a multidisciplinary approach to prompt examination and management by gynecologists and general surgeons is recommended to reduce the risk of morbidity and mortality. With this paper the authors would like to share the surgical manage of this rare emergency with other surgeons all around the world.

Polyphenols, Olive oil and Colonrectal cancer: the effect of Mediterranean Diet in the prevention.

In recent years, scientific research has shown that the incidence of various diseases, including some cancers, is relatively low in the Mediterranean Countries compared to that of other European countries or North America. This support the hypothesis that the Mediterranean diet, rich in bioactive food components, including methyl group donors, polyphenols, and fatty acids has efficacy in terms of prevention. Few studies evaluated the efficacy of Med Diet on colon cancer however they all support the beneficial effects of this Diet in preventing cancer.