Gastric Cancer (GC) with Peritoneal Metastases (PMs): An Overview of Italian PSM Oncoteam Evidence and Study Purposes.

Gastric cancer (GC) continues to be one of the leading types of malignancies worldwide, despite an ongoing decrease in incidence. It is the fifth most frequent type of cancer in the world and the fourth leading cause of cancer death. Peritoneal metastases (PMs) occur in 20-30% of cases during the natural history of the disease. Systemic chemotherapy (SC) is undoubtedly the standard of care for patients with GC and PMs. However, with the development of highly effective regimens (SC combined with intraperitoneal chemotherapy), significant tumor shrinkage has been observed in many patients with synchronous GC and PMs, allowing some to undergo curative resection "conversion surgery" with long-term survival. In recent years, there has been growing interest in intraperitoneal chemotherapy for PMs, because the reduced drug clearance associated with the peritoneal/plasma barrier allows for direct and prolonged drug exposure with less systemic toxicity. These procedures, along with other methods used for peritoneal surface malignancies (PSMs), can be used in GCs with PMs as neoadjuvant chemotherapy or adjuvant treatments after radical surgery or as palliative treatments delivered either laparoscopically or-more recently-as pressurized intraperitoneal aerosol chemotherapy. The great heterogeneity of patients with stage IV gastric cancer did not allow us to carry out a systemic review; therefore, we limited ourselves to providing readers with an overview to clarify the indications and outcomes of integrated treatments for GCs with PMs by analyzing reports from the international clinical literature and the specific experiences of our oncoteam.

Effects of oral immunonutrition on histological changes of inflammatory infiltration of the tumor microenvironment among patients with a new diagnosis of gastric cancer.

OBJECTIVES: We assessed the effects of oral immunonutrition (OI) on the inflammatory infiltration of the tumor microenvironment (TME) of patients undergoing surgery for gastric cancer. METHODS: We analyzed patients at the time of their first gastric cancer diagnosis. We collected surgical tissue specimens (stomach), and performed an immunohistochemical analysis to evaluate the inflammatory infiltration of the TME. Patients receiving OI were compared with patients receiving standard oral nutritional supplements and no nutritional support. RESULTS: We enrolled 12 patients with gastric cancer in the study. The median body weight loss was 5.6%. Four patients received OI, five patients received standard nutritional supplement, and three patients received no nutritional supplementation. No difference in age, body mass index (BMI), and body weight loss was observed between the three groups. The OI group showed a tendency of increased number of T-lymphocyte cluster of differentiation (CD) 8+ compared with the other groups, as well as the number of CD83+ and CD68+. The absence of F4/80+ cells was documented only in the TME of the OI group, where a linear positive correlation was present between lymphocytes CD4+ and CD8+ (R = 0.48), and between CD4+ and CD83+ (R = 0.89), although not statistically significant. In the OI group, we observed a positive correlation (not significant) between the number of lymphocytes CD8+ and macrophages CD68+ (R = 0.70; P = 0.30). A strong significant correlation was documented between CD68+ and CD40+ (R = 0.99; P = 0.01), but this correlation did not reach the significance among the patients of the other two groups (R = 0.60; P = 0.116). CONCLUSIONS: The administration of OI in patients with gastric cancer might determine changes in inflammatory patterns of the TME.

Selected Patients With Peritoneal Metastases From Breast Cancer May Benefit From Cytoreductive Surgery: The Results of a Multicenter Survey.

Background: Even though breast cancer is the most frequent extra-abdominal tumor causing peritoneal metastases, clear clinical guidelines are lacking. Our aim is to establish whether cytoreductive surgery (CRS) could be considered in selected patients with peritoneal metastases from breast cancer (PMBC) to manage abdominal spread and allow patients to resume or complete other medical treatments. Methods: We considered patients with PMBC treated in 10 referral centers from January 2002 to May 2019. Clinical data included primary cancer characteristics (age, histology, and TNM) and data on metastatic disease (interval between primary BC and PM, molecular subtype, other metastases, and peritoneal spread). Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate and multivariable data for OS were analyzed using the Cox proportional hazards model. Results: Of the 49 women with PMBC, 20 were treated with curative aim (CRS with or without HIPEC) and 29 were treated with non-curative procedures. The 10-year OS rate was 27%. Patients treated with curative intent had a better OS than patients treated with non-curative procedures (89.2% vs. 6% at 36 months, p < 0.001). Risk factors significantly influencing survival were age at primary BC, interval between BC and PM diagnosis, extra-peritoneal metastases, and molecular subtype. Conclusions: The improved outcome in selected cases after a multidisciplinary approach including surgery should lead researchers to regard PMBC patients with greater attention despite their scarce epidemiological impact. Our collective efforts give new information, suggest room for improvement, and point to further research for a hitherto poorly studied aspect of metastatic BC.

Prehospital Hemorrhage Assessment Criteria: A Concise Review.

OBJECTIVE: Early assessment of the clinical status of trauma patients is crucial for guiding the treatment strategy, and it requires a rapid and systematic approach. The aim of this report is to critically review the assessment parameters currently used in the prehospital setting to quantify blood loss in trauma. DATA SOURCES: Studies regarding hemorrhagic shock in trauma were pooled from PubMed, EMBASE, and Cochrane databases using key words such as "hemorrhagic shock," "vital signs evaluation," "trauma," "blood loss," and "emergency medical service," alone or combined. STUDY SELECTION: Articles published since 2009 in English and Italian were considered eligible if containing data on assessment parameters in blood loss in adults. DATA EXTRACTION: Sixteen articles matching the inclusion criteria were considered in our study. DATA SYNTHESIS: Current prehospital assessment measures lack precise correlation with blood loss. CONCLUSIONS: Traditional assessment parameters such as heart rate, systolic blood pressure, shock index, and Glasgow Coma Scale score often lag in providing accurate blood loss assessment. The current literature supports the need for a noninvasive, continuously monitored assessment parameter to identify early shock in the prehospital setting.

WSES-AAST guidelines: management of inflammatory bowel disease in the emergency setting.

BACKGROUND: Despite the current therapeutic options for the treatment of inflammatory bowel disease, surgery is still frequently required in the emergency setting, although the number of cases performed seems to have decreased in recent years. The World Society of Emergency Surgery decided to debate in a consensus conference of experts, the main pertinent issues around the management of inflammatory bowel disease in the emergent situation, with the need to provide focused guidelines for acute care and emergency surgeons. METHOD: A group of experienced surgeons and gastroenterologists were nominated to develop the topics assigned and answer the questions addressed by the Steering Committee of the project. Each expert followed a precise analysis and grading of the studies selected for review. Statements and recommendations were discussed and voted at the Consensus Conference of the 6th World Society of Emergency Surgery held in Nijmegen (The Netherlands) in June 2019. CONCLUSIONS: Complicated inflammatory bowel disease requires a multidisciplinary approach because of the complexity of this patient group and disease spectrum in the emergency setting, with the aim of obtaining safe surgery with good functional outcomes and a decreasing stoma rate where appropriate.

The role of procalcitonin in reducing antibiotics across the surgical pathway.

Procalcitonin (PCT) is widely considered as a highly sensitive biomarker of bacterial infection, offering general and emergency surgeons a key tool in the management of surgical infections. A multidisciplinary task force of experts met in Bologna, Italy, on April 4, 2019, to clarify the key issues in the use of PCT across the surgical pathway. The panelists presented the statements developed for each of the main questions regarding the use of PCT across the surgical pathway. An agreement on the statements was reached by the Delphi method, and this document reports the executive summary of the final recommendations approved by the expert panel.

Will the COVID-19 pandemic transform infection prevention and control in surgery? Seeking leverage points for organizational learning.

BACKGROUND: In response to the coronavirus disease of 2019 (COVID-19) pandemic, healthcare systems worldwide have stepped up their infection prevention and control efforts in order to reduce the spread of the infection. Behaviours, such as hand hygiene, screening and cohorting of patients, and the appropriate use of antibiotics have long been recommended in surgery, but their implementation has often been patchy. METHODS: The current crisis presents an opportunity to learn about how to improve infection prevention and control and surveillance (IPCS) behaviours. The improvements made were mainly informal, quick and stemming from the frontline rather than originating from formal organizational structures. The adaptations made and the expertise acquired have the potential for triggering deeper learning and to create enduring improvements in the routine identification and management of infections relating to surgery. RESULTS: This paper aims to illustrate how adopting a human factors and ergonomics perspective can provide insights into how clinical work systems have been adapted and reconfigured in order to keep patients and staff safe. CONCLUSION: For achieving sustainable change in IPCS practices in surgery during COVID-19 and beyond we need to enhance organizational learning potentials.

Perforated gastric cancer: a critical appraisal.

Gastric cancer perforation is a life-threatening condition that accounts for less than 5% of all gastric cancer patients and typically requires emergency surgery. However, preoperative diagnosis is difficult and management has a dual purpose: to treat peritonitis and to achieve a curative resection. The optimal surgical strategy is still unclear and prognosis remains poor. A search of the literature was performed using MEDLINE databases (Pubmed, EMBASE, Web of Science and Cochrane) using terms such as "perforated gastric cancer", "perforated gastric cancer and surgery", "perforated gastric tumour" and "gastric cancer perforated". Case reports, other reviews, non-english written papers and papers written before 2010 were excluded. Eight articles published between 2010 and 2020 matched the inclusion criteria for this review. Perforated gastric cancer was more prevalent in elderly males. Distal stomach was most frequently involved. Preoperative diagnosis was uncommon. Mortality rates ranged from 2 to 46%. Patients able to receive an R0 resection demonstrated better long-term survival compared with patients who had simple closure procedures. Laparoscopic procedure was mentioned only in one study. In an emergency situation, curative RO resection should always be offered in patients without multiple adverse factors. A surgical strategy using laparoscopic local repair as first step of surgery to resolve the peritonitis followed by a radical open or laparoscopic gastrectomy with lymphadenectomy could be considered. A balance between emergency and oncological needs should drive the surgical choice on a case by case basis.

SARS-CoV-2 pandemic: implications in the management of patients with colorectal cancer.

The SARS-CoV-2 pandemic has already reached 3,207,248 patients with more than 225,000 deaths all over the world. Colorectal cancer is the third most diagnosed cancer worldwide, and the healthcare system is struggling to manage daily activities for elective cancer surgery. This review integrates clinical, microbiological, architectural and surgical aspects to develop indications on strategies to manage colorectal cancer patients and ensure safety during the pandemic. Telephone or virtual clinics must be encouraged and phone follow-up should be implemented. Indications for surgery must be rigorous, balancing the advantage of early surgical treatment and risks of treatment delay. To decrease the occupancy rate of intensive care unit beds, elective surgical treatment should be delayed until local endemic control, according to stage of disease. Patients with SARS-CoV-2 infection should be treated only after clinical recovery, two consecutive negative oropharyngeal swabs and, if available, a negative stool sample. Before any elective oncologic procedure, a multidisciplinary oncologic team including an anaesthesiologist and an infectious disease specialist must assess every patient to evaluate the risk of infection and its impact on perioperative morbidity, mortality and oncologic prognosis. The hospital should organise to manage all elective oncologic patients in an 'infection-free' area or refer them to a non-SARS-CoV-2 hospital.

Role of Leptin in Neoplastic and Biliary Tree Disease.

BACKGROUND/AIM: Leptin is a small hormone of protein nature, it is strongly involved in the regulation of lipid metabolism and its functioning mechanism is not yet well known or whether or not it is actually secreted by cholangiocytes, nor if the biliary tree expresses its receptors. In the past, various studies have tried to correlate leptin levels with certain neoplasms. The aim of this study was to demonstrate that serum leptin values can become a new sensitive and specific serum marker for cholangiocarcinoma. MATERIALS AND METHODS: Seventy-two patients with gallbladder stones, hepatolithiasis with benign biliary stenosis, cholangiocarcinoma, and a group of patients without hepato-biliary diseases were enrolled in the study. In all cases blood and bile samples were collected for evaluation of leptin levels and liver biopsies were performed to confirm diagnosis. In all patients, both ultrasound and cholangio-magnetic resonance imaging (MRI) were performed to complete the diagnostic procedure. RESULTS: Twenty-two patients were affected by cholangiocarcinoma, 50 by benign biliary disease (35 cholelithiasis and 6 hepatolithiasis and 9 by inflammatory biliary stenosis). The mean values of serum leptin in patients with cholangiocarcinoma were 19.28±8.76 ng/ml, significantly higher than those observed in non-neoplastic biliary diseases. CONCLUSION: Serum leptin levels might be a useful marker to differentiate patients with cholangiocarcinoma from those with biliary lithiasis and inflammatory stenosis.

Minimal Open Access Ileocolic Resection in Complicated Crohn's Disease of the Terminal Ileum.

The objective of this study was to evaluate the possibility to undertake an ileocolic resection in complex Crohn's disease using a minimal open abdominal access using standard laparoscopic instruments. The incision was carried out over the previous McBurney scar, with a mean length of 6 cm. Seventy-two patients with complicated Crohn's disease underwent IC resection in the considered period; 12 patients had a McBurney scar due to a previous appendectomy and represented the group of study. Feasibility and safety of the procedure were evaluated. Clinical data and outcome were compared with a control arm of 15 patients who had a standard laparoscopic IC resection, pooled out from our database among those who had a McBurney incision as service incision. Mean operative time and postoperative stay were significantly shorter in the study group. Blood loss and operative costs were also lower in the study group but did not reach statistical significance. Minimal open access ileocolic resection (MOAIR) through a small McBurney incision seems safe and feasible in complex Crohn's disease. Some advantages over standard laparoscopic surgery could be found in surgical outcomes and costs.

Injury patterns and causes of death in 953 patients with penetrating abdominal war wounds in a civilian independent non-governmental organization hospital in Lashkargah, Afghanistan.

Background: Management of penetrating abdominal war injuries centers upon triage, echeloned care, and damage control. A civilian hospital based in a war zone can rarely rely upon these principles because it normally has limited resources and lacks rapid medical evacuation. We designed this study to describe organ injury patterns and factors related to mortality in patients with penetrating abdominal war injuries in a civilian hospital in an active war zone in Afghanistan, examine how these findings differ from those in a typical military setting, and evaluate how they might improve patients' care. Methods: We reviewed the records of all patients admitted at the Lashkargah "Emergency" hospital with penetrating abdominal injuries treated from January 2006 to December 2016. Demographic and clinical data were recorded; univariate and multivariate analyses were used to identify variables significantly associated with death. Results: We treated 953 patients for penetrating abdominal injury. The population was mainly civilian (12.1% women and 21% under 14). Mean age was 23 years, and patients with blast injuries were younger than in the other groups. The mechanism of injury was bullet injury in 589 patients, shell injury in 246, stab wound in 97, and mine injury in 21. The most frequent abdominal lesion was small bowel injury (46.3%). Small and large bowel injuries were the most frequent in the blast groups, stomach injury in stab wounds. Overall mortality was 12.8%. Variables significantly associated with death were age > 34 years, mine and bullet injury, length of stay, time since injury > 5 h, injury severity score > 17, and associated injuries. Conclusions: Epidemiology and patterns of injury in a civilian hospital differ from those reported in a typical military setting. Our population is mainly civilian with a significant number of women and patients under 14 years. BI are more frequent than blast injuries, and gastrointestinal injuries are more common than injuries to solid organs. In this austere setting, surgeons need to acquire a wide range of skills from multiple surgical specialties. These findings might guide trauma and general surgeons treating penetrating abdominal war wounds to achieve better care and outcome.

Surgical treatment of intraperitoneal metastases from lung cancer: two case reports and a review of the literature.

BACKGROUND: Peritoneal metastases are often reported in several abdominal tumors. Peritoneal diffusion from extra-abdominal tumors is thought to be rare. Lung cancer is one of the most common cancers in the world with early metastases and it is associated with poor prognosis in advanced stages. Peritoneal metastases from lung cancer are uncommon and the real mechanism of its diffusion to the peritoneum is unknown. However, its clinical behavior is similar to any other peritoneal metastasis from abdominal tumors. CASE PRESENTATION: We present two Caucasian patients (a 44-year-old man and a 59-year-old man) with bowel obstruction from peritoneal metastases from non-small cell lung cancer who successfully underwent emergency cytoreductive surgery and had a good prognosis and survival. CONCLUSIONS: In our patients with isolated peritoneal metastases from lung cancer, cytoreduction showed good prognosis with acceptable morbidity. This treatment option might be considered in highly selected cases to improve survival. Strict follow-up is mandatory to allow early diagnosis of peritoneal diffusion.

Prognostic Factors Influencing Infectious Complications after Cytoreductive Surgery and HIPEC: Results from a Tertiary Referral Center.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) showed promising results in selected patients. High morbidity restrains its wide application. The aim of this study was to report postoperative infectious complications and investigate possible correlations with the preoperative nutritional status and other prognostic factors in patients with peritoneal metastases treated with CRS and HIPEC. METHODS: For the study, we reviewed the clinical records of all patients with peritoneal metastases from different primary cancers treated with CRS and HIPEC in our Institution from November 2000 to December 2017. Patients were divided according to their nutritional status (SGA) into groups A (well-nourished) and B/C (mild or severely malnourished, respectively). Possible statistical correlations between risk factors and postoperative complication rates have been investigated by univariate and multivariate analysis. RESULTS: Two hundred patients were selected and underwent CRS and HIPEC during the study period. Postoperative complications occurred in 44% of the patients, 35.3% in SGA-A patients, and 53% in SGA-B/C patients. Cause of complications was infective in 42, noninfective in 37, and HIPEC related in 9 patients. Infectious complications occurred more frequently in SGA-B/C patients (32.6% vs. 9.8% of SGA-A patients). The most frequent sites of infection were surgical site infections (SSI, 35.7%) and central line-associated bloodstream infections (CLABSI, 26.2%). The most frequent isolated species was Candida (22.8%). ASA score, blood loss, performance status, PCI, large bowel resection, postoperative serum albumin levels, and nutritional status correlated with higher risk for postoperative infectious complications. CONCLUSIONS: Malnourished patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are more prone to postoperative infectious complications, and adequate perioperative nutritional support should be considered, including immune-enhancing nutrition. Sequential monitoring of common sites of infection, antifungal prevention of candidiasis, and careful patient selection should be implemented to reduce the complication rate.

Proactive Management for Gastric, Colorectal and Appendiceal Malignancies: Preventing Peritoneal Metastases with Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

An integrated treatment strategy using peritonectomy procedures plus hyperthermic intraperitoneal chemotherapy (HIPEC) is now a clinical standard of care in selected patients with peritoneal metastases and primary peritoneal tumors. This comprehensive approach can offer many patients, who hitherto had no hope of cure, a good quality of life and survival despite limited morbidity. The increasingly successful results and chance of interfering in the natural history of disease has prompted research to develop for some clinical conditions a therapeutic strategy designed to prevent malignant peritoneal dissemination before it becomes clinically evident and treat it microscopically (tertiary prevention). The main factor governing successful cytoreductive surgery and predicting outcome is the extent of peritoneal spread assessed with the peritoneal cancer index (PCI). In peritoneal metastases from colorectal and gastric cancer the PCI score acquires a specific role acting as the cut-off between patients who can undergo curative surgery or palliation. Long-term results show that the only group enjoying favorable results are patients with limited disease (a statistical minority). By applying to appropriately selected patients with primary malignancies a proactive management strategy including HIPEC we can treat patients with microscopic peritoneal dissemination and therefore at PCI 0. Among treated conditions pseudomyxoma peritonei enjoys the best results. But a major future advance comes from identifying among lesions at major risk of pseudomyxoma.

Does the Implantation Technique for Totally Implantable Venous Access Ports (TIVAPs) Influence Long-Term Outcome?

BACKGROUND: Totally implantable venous access ports (TIVAP) are eventually explanted for various reasons, related or unrelated to the implantation technique used. Having more information on long-term explantation would help improve placement techniques. METHODS: From a series of 1572 cancer patients who had TIVAPs implanted in our center with the cutdown technique or Seldinger technique, we studied the 542 patients who returned to us to have their TIVAP explanted after 70 days or more. As outcome measures we distinguished between TIVAPs explanted for long-term complications (infection, catheter-, reservoir-, and patient-related complications) and TIVAPs no longer needed. Univariate and multivariate analyses were run to investigate the reasons for explantation and their possible correlation with implantation techniques. RESULTS: The most common reason for explantation was infection (47.6 %), followed by catheter-related (20.8 %), patient-related (14.7 %), and reservoir-related complications (4.7 %). In the remaining 12.2 % of cases, the TIVAP was explanted complication free after the planned treatments ended. Infection correlated closely with longer TIVAP use. Univariate and multivariate analyses identified the Seldinger technique as a major risk factor for venous thrombosis and catheter dislocation. CONCLUSIONS: The need for long-term TIVAP explantation in about one-third of cancer patients is related to the implantation techniques used.

Cytoreduction and HIPEC in the treatment of "unconventional" secondary peritoneal carcinomatosis.

BACKGROUND: Peritoneal metastasis (PM) is considered a terminal and incurable disease. In the last 30 years, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) radically changed the therapeutic approach for these patients and is regarded as the standard of care for pseudomyxoma peritonei from appendiceal cancer and peritoneal mesotheliomas. Improved survival has also been reported in treating PM from ovarian, gastric, and colorectal cancers. However, PM often seriously complicates the clinical course of patients with other primary digestive and non-digestive cancers. There is increasing literature evidence that helped to identify not only the primary tumors for which CRS and HIPEC showed a survival advantage but also the patients who may benefit form this treatment modality for the potential lethal complications. Our goal is to report our experience with cytoreduction and HIPEC in patients with PM from rare or unusual primary tumors, discussing possible "unconventional" indications, outcome, and the peculiar issues related to each tumor. METHODS: From a series of 253 consecutive patients with a diagnosis of peritoneal carcinomatosis and treated by CRS and HIPEC, we selected only those with secondary peritoneal carcinomatosis from rare or unusual primary tumors, excluding pseudomyxoma peritonei, peritoneal mesotheliomas, ovarian, gastric, and colorectal cancers. Complications and adverse effects were graded from 0 to 5 according to the WHO Common Toxicity Criteria for Adverse Events (CTCAE). Survival was expressed as mean and median. RESULTS: We admitted and treated by CRS and HIPEC 28 patients with secondary peritoneal carcinomatosis from rare or unusual primary tumors. Morbidity and mortality rates were in line with those reported for similar procedures. Median survival for the study group was 56 months, and 5-year overall survival reached 40.3 %, with a difference between patients with no (CC0) and minimal (CC1) residual disease (52.3 vs. 25.7), not reaching statistical significance. Ten patients are alive disease-free, and eight are alive with disease. CONCLUSIONS: Cytoreduction and HIPEC should not be excluded "a priori" for the treatment of peritoneal metastases from unconventional primary tumors. This combined therapeutic approach, performed in an experienced center, is safe and can provide a survival benefit over conventional palliative treatments.

Ebola：a review on the state of the art on prevention and treatment

The aim of this paper is to highlight the current development in the research field for helping people just exposed to Ebola virus survive (treatment) and to prevent the disease when given at various times after exposure (vaccine). Concerning the treatment, recombinant anti-Ebola monoclonal antibodies and small interfering RNAs that block the expression of essential viral proteins, are the most promising way in stopping the disease when it has already reached the humans. As far as concerns the prevention field, two candidate vaccines have clinical-grade vials available for phase 1 pre-licensure clinical trials, and demonstrated to have a 100%efficacy in studies on non human primates. Well-informed communities can reduce the main ways of spread the infection, by avoiding unprotected home-based care of people who are infected and also by completely modifying traditional burial practices that are way of diffusion of the contagion.