Recent studies have shown that CD32/CD8a/CD28/CD3ζ chimeric receptor cells directly kill breast cancer cells, suggesting the existence of cell surface myeloid FcγR alternative ligands (ALs). Here, we investigated the metabolism, ALs, cytotoxicity, and immunoregulatory functions of CD64/CD28/CD3ζ in colorectal cancer (CRC) and squamous cell carcinoma of the head and neck. The CD64/CD28/CD3ζ -SFG retroviral vector was used to produce viruses for T-cell transduction. T-cell expansion and differentiation were monitored via flow cytometry. Gene expression was assessed by RNA-seq. Bioenergetics were documented on a Seahorse extracellular flux analyzer. CD64/CD28/CD3ζ polarization was identified via confocal microscopy. Cytotoxicity was determined by MTT assay and bioluminescent imaging, and flow cytometry. Tridimensional antitumor activity of CD64/CD28/CD3ζ T cells was achieved by utilizing HCT116-GFP 3D spheroids via the IncuCyte S3 Live-Cell Analysis system. The intraperitoneal distribution and antitumor activity of NIR-CD64/CD28/CD3ζ and NIR-nontransduced T cells were investigated in CB17-SCID mice bearing subcutaneous FaDu Luc + cells by bioluminescent and fluorescent imaging. IFNγ was assessed by ELISA. Compared to CD16/CD8a/CD28/CD3ζ T cells, CD32/CD8a/CD28/CD3ζ T cells, and non-transduced T cells, CD64/CD28/CD3ζ T cells exhibited the highest levels of cell expansion and persistence capacity. A total of 235 genes linked to cell division and 52 genes related to glycolysis were overexpressed. The glycolytic phenotype was confirmed by functional in vitro studies accompanied by preferential T-cell effector memory differentiation. Interestingly, oxamic acid was found to inhibit CD64-CR T cell proliferation, indicating the involvement of lactate. Upon CD64/CD28/CD3ζ T-cell conjugation with CRC cells, CD64/CD28/CD3ζ cells polarize at immunological synapses, leading to CRC cell death. CD64/CD28/CD3ζ T cells kill SCCHN cells, and in combination with the anti-B7-H3 mAb (376.96) or anti-EGFR mAb, these cells trigger antibody-dependent cellular cytotoxicity (ADCC) in vitro under 2D and 3D conditions. The 376.96 mAb combined with CD64/CD28/CD3ζ T cells had anti-SCCHN activity in vivo. In addition, they induce the upregulation of PD-L1 and HLA-DR expression in cancer cells via IFNγ. PD-L1 positive SCCHN cells in combination with anti-PD-L1 mAb and CD64-CR T cells were killed by ADCC, which enhanced direct cytotoxicity. These findings indicate that the glycolytic phenotype is involved in CD64-CR T cell proliferation/expansion. These cells mediate long-lasting HLA-independent cytotoxicity and ADCC in CRC and SCCHN cells. CD64/CD28/CD3ζ T cells could significantly impact the rational design of personalized studies to treat CRC and SCCHN and the identification of novel FcγR ALs in cancer and healthy cells.

Background/Objectives: The indirect impact of the pandemic on the diagnosis and treatment of new primary melanoma has been carefully evaluated in recent years. The aim of the present study was to investigate if the indirect impact of the pandemic in Italy could be detectable also in the second year of the pandemic, as suggested by the characteristics of melanoma at diagnosis. Methods: Retrospective analysis of 1640 diagnoses of cutaneous melanoma in pre-pandemic period and 1292 diagnoses in the pandemic period from 10 centers (from 1 March 2019 to 28 February 2022). Results: Our findings confirmed an indirect impact of the pandemic on characteristics of incident melanoma, also in the second year of the pandemic in Italy (Breslow thickness p < 0.0001, tumor stage p = 0.002, ulceration p = 0.04, SNLB p = 0.03), without statistically significant differences between centers. A statistically significant reduction in the time interval from diagnosis to surgical treatment was observed, but only in centers that had to modify their case mix to address the needs of treating COVID-19 patients (p = 0.0002). Conclusions: Our study confirmed the indirect impact of the pandemic on melanoma characteristics at the diagnosis in the second year of the pandemic in Italy. We also found no differences in melanoma characteristics between hospitals with different organization. Diagnostic delays may be related to a delayed access of the patient to the entire diagnostic pathway, and therefore, especially in the case of a pandemic, policies to support early diagnosis are crucial.

Inflammation, well-known as one of the hallmarks of cancer, has been demonstrated to have a key role in the incidence and growth of different tumors. However, its role as a prognostic factor for melanoma has not yet been clarified. Our study aimed to evaluate the correlation of neutrophil to lymphocyte ratio (NLR), platelet to monocyte ratio (PMR), systemic inflammation index (SII), and aggregate index of systemic inflammation (AISI) with clinical stages of disease, to define whether higher values of these markers correlate with a more aggressive disease. We retrospectively analyzed NLR, PMR, SII, and AISI in a total of 129 newly diagnosed melanoma patients. All values were calculated using the complete blood count data. Higher NLR was associated with advanced stages ( P < 0.001). Mean NLR among patients with early stage disease (IB and IIA) was 2.01, while the mean NLR for patients with advanced stage disease (from stage IIB to IV) was 3.22. Mean PMR among patients with early stage disease (IB and IIA) was 520, while the mean PMR for patients with advanced stage disease was 479 ( P = 0.049). Mean AISI in the early stage was 247 and 482 in advanced stages ( P < 0.001). Mean SII was 480 in the early stage and 747 in advanced stages ( P = 0.004). Our data confirmed the association between NLR and newly reported the association of PMR, AISI, and SII with high-risk and aggressive melanoma. Further investigations are required to define a meaningful prognostic system for patients with advanced melanoma. This could help classify patients with advanced stages of disease, demanding a short follow-up.

BACKGROUND:The identification in breast cancer (BC) of novel genetic biomarkers regulating natural killer (NK) cell function, including the HLA, KIR, and CD16A (FCGR3A), may be still a challenge. OBJECTIVE:We aimed to evaluate whether the combined effect of these polymorphisms has an impact on BC susceptibility and progression. METHODS:47 BC Italian patients and healthy individuals (39 females and 66 males/ females) were genotyped by Sanger sequencing (HLA-C exon 2-4 and FCGR3A- 158V/F, 48L/R/H) and PCR-SSP typing (KIR genes). RESULTS:HLA-C gene allele analysis showed the group C1, with HLA-C*07:02:01 allele, to be significantly associated with tumor progression (16.7% vs. 4.0%, p=0.04, OR=4.867), and instead, group C2, with HLA-C*05:01:01, was protective against disease susceptibility (0.0% vs. 7.2%, p=0.019, OR=0.087). In addition, we highlighted a significant reduction of the KIR2DS4ins in BC patients (pcorr.=0.022) and an increased combined presence of KIR2DL1 and KIR2DS1 genes in advanced BC patients compared to earlier stages (66.7% vs. 19.2%, p=0.002). The concurrent lack of KIR2DL2 and KIR2DS4 genes in the presence of HLA-C2 alleles was significantly associated with increased susceptibility to BC (p=0.012, OR=5.020) or with lymph node involvement (p=0.008, OR=6.375). Lastly, we identified different combinations of the FCGR3A-48/158 variants and KIR genes in BC patients compared to controls. CONCLUSION:Our findings suggest that in the development of BC probably exists a disorder of the NK innate immunity influenced by KIR/HLA-C gene content and FCGR3A-158 polymorphisms and that the combined analysis of these biomarkers might help predict genetic risk scores for tailored screening of BC patients in therapy.

(1) Objective: Keloid and hypertrophic scars are a challenge in clinical management, causing functional and psychological discomfort. These pathological scars are caused by a proliferation of dermal tissue following skin injury. The TGF-β/Smad signal pathway in the fibroblasts and myofibroblasts is involved in the scarring process of skin fibrosis. Today, multiple therapeutic strategies that target the TGF-β/Smad signal pathway are evaluated to attenuate aberrant skin scars that are sometimes difficult to manage. We performed a head-to-head, randomized controlled trial evaluating the appearance of the post-surgical scars of 64 subjects after two times daily topical application to compare the effect of a class I pullulan-based medical device containing Allium cepa extract 5% and hyaluronic acid 5% gel versus a class I medical device silicone gel on new post-surgical wounds. (2) Methods: Objective scar assessment using the Vancouver Scar Scale (VSS), POSAS, and other scales were performed after 4, 8, and 12 weeks of treatment and statistical analyses were performed. The trial was registered in clinicalTrials.gov ( NCT05412745). In parallel, molecular docking simulations have been performed to investigate the role of Allium cepa in TGF-β/Smad signal pathway. (3) Results: We showed that VSS, POSAS scale, itching, and redness reduced significantly at week 4 and 8 in the subjects using devices containing Allium cepa and HA. No statistically significant differences in evaluated scores were noted at 12 weeks of treatment. Safety was also evaluated by gathering adverse events related to the application of the gel. Subject compliance and safety with the assigned gel were similar between the two study groups. Molecular docking simulations have shown how Allium cepa could inhibit fibroblasts proliferation and contraction via TGF-β/Smad signal pathway. (4) Conclusions: The topical application of a pullulan-based medical device containing Allium cepa and HA showed a clear reduction in the local inflammation, which might lead to a reduced probability of developing hypertrophic scars or keloids.

The most promising method for monitoring patients with minimal morbidity is the detection of circulating melanoma cells (CMCs). We have shown that CD45−CD146+ABCB5+ CMCs identify a rare primitive stem/mesenchymal CMCs population associated with disease progression. The epithelial-to-mesenchymal transition (EMT) confers cancer cells a hybrid epithelial/mesenchymal phenotype promoting metastatization. Thus, we investigated the potential clinical value of the EMT gene signature of these primitive CMCs. A reliable quantitative real-time polymerase chain reaction (qRT-PCR) protocol was settled up using tumor cell lines RNA dilutions. Afterwards, immune-magnetically isolated CMCs from advanced melanoma patients, at onset and at the first checkpoint (following immune or targeted therapy), were tested for the level of EMT hallmarks and EMT transcription factor genes. Despite the small cohort of patients, we obtained promising results. Indeed, we observed a deep gene rewiring of the EMT investigated genes: in particular we found that the EMT gene signature of isolated CMCs correlated with patients’ clinical outcomes. In conclusion, We established a reliable qRT-PCR protocol with high sensitivity and specificity to characterize the gene expression of isolated CMCs. To our knowledge, this is the first evidence demonstrating the impact of immune or targeted therapies on EMT hallmark gene expressions in CMCs from advanced melanoma patients.

Colorectal carcinoma is the second leading cause of cancer-related deaths, and indeed, rectal cancer accounting for approximately one third of newly diagnosed patients. Gold standard in the treatment of rectal cancer is a multimodality approach, aiming at a good control of the local disease. Distant recurrences are the major cause of mortality. Currently, Locally Advanced Rectal Cancer (LARC) patients undergo a combined treatment of chemotherapy and radiotherapy, followed by surgery. Eventually, more chemotherapy, namely adjuvant chemotherapy (aCT), may be necessary. Total Neoadjuvant Therapy (TNT) is an emerging approach aimed to reduce distant metastases and improve local control. Several ongoing studies are analyzing whether this new approach could improve oncological outcomes. Published results were encouraging, but the heterogeneity of protocols in use, makes the comparison and interpretation of data rather complex. One of the major concerns regarding TNT administration is related to its effect on larger and more advanced cancers that might not undergo similar down-staging as smaller, early-stage tumors. This minireview, based on a systematic literature search of randomized clinical trials and meta-analysis, summarizes current knowledge on TNT. The aim was to confirm or refute whether or not current practice of TNT is based on relevant evidence, to establish the quality of that evidence, and to address any uncertainty or variation in practice that may be occurring. A tentative grouping of general study characteristics, clinical features and treatments characteristics has been undertaken to evaluate if the reported studies are sufficiently homogeneous in terms of subjects involved, interventions, and outcomes to provide a meaningful idea of which patients are more likely to gain from this treatment.

Abstract The identification of clinical pathological role of genes regulating NK cell function, including HLA, KIR and FCGR3A, in breast cancer (BC) may be a challenge. The objective of this study was to determine whether these genes have an impact on the BC susceptibility and progression. In this study, 47 BC Italian patientswere genotyped by PCR-SSP typing (KIR) and PCR-SBT method (HLA-C and FCGR3A). HLA-C allele analysis showed that the HLA-C*07:02:01 (p = 0.04, OR = 4.867) and HLA-C*04:01:01 alleles (p = 0.04 OR = 2.364) were predisposing to tumor progression, and instead the HLA-C*05:01:01 allele was protective against disease (p = 0.019 OR = 0.087). In addition, we highlighted a significant reduction of the KIR2DS4ins in BC patients (p = 0.022) and an increased coexistence of KIR2DL1 and KIR2DS1 genes in advanced BC patients compared to early stages (p = 0.002). The concurrent lack of KIR2DL2 and KIR2DS4 genes in the presence of HLA-C2 alleles was significantly associated with increased susceptibility to BC (p = 0.012 OR = 5.020) or with lymph node involvement (p = 0.008 OR = 6.375). We identified different combinations of the FCGR3A-48/158 haplotypes and KIR genes in BC patients compared to controls. Our study provides evidence that the combined analysis of these biomarkers might help predict genetic risk scores for tailored screening of BC patients.

BackgroundTraditionally, synchronous liver resection (LR), cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy for colorectal liver and peritoneal metastases have been contraindicated. Nowadays, clinical practice has promoted this aggressive treatment in selected cases. This study aimed to review surgical and survival results of an extensive surgical approach including CRS with hyperthermic intraperitoneal chemotherapy (HIPEC) and LR.MethodsPubMed, EMBASE, and Web of Science databases were matched to find the available literature on this topic. The search period was limited to 10 years (January 2010–January 2021). A threshold of case series of 10 patients or more was applied.ResultsIn the search period, out of 114 studies found about liver and peritoneal metastases from colorectal cancer, we found 18 papers matching the inclusion criteria. Higher morbidity and mortality were reported for patients who underwent such an extensive surgical approach when compared with patients who underwent only cytoreductive surgery and HIPEC. Also, survival rates seem worse in the former than in the latter.ConclusionThe role of combined surgical strategy in patients with synchronous liver and peritoneal metastases from colorectal cancer remains controversial. Survival rates and morbidity and mortality seem not in favor of this option. A more accurate selection of patients and more restrictive surgical indications could perhaps help improve results in this subgroup of patients with limited curative options.

Human malignant melanoma shows a high rate of mortality after metastasization, and its incidence is continuously rising worldwide. Several studies have suggested that MCAM/MUC18/CD146 plays an important role in the progression of this malignant disease. MCAM/MUC18/CD146 is a typical single-spanning transmembrane glycoprotein, existing as two membrane isoforms, long and short, and an additional soluble form, sCD146. We previously documented that molecular MCAM/MUC18/CD146 expression is strongly associated with disease progression. Recently, we showed that MCAM/MUC18/CD146 and ABCB5 can serve as melanoma-specific-targets in the selection of highly primitive circulating melanoma cells, and constitute putative proteins associated with disease spreading progression. Here, we analyzed CD146 molecular expression at onset or at disease recurrence in an enlarged melanoma case series. For some patients, we also performed the time courses of molecular monitoring. Moreover, we explored the role of soluble CD146 in different cohorts of melanoma patients at onset or disease progression, rather than in clinical remission, undergoing immune therapy or free from any clinical treatment. We showed that MCAM/MUC18/CD146 can be considered as: (1) a membrane antigen suitable for identification and enrichment in melanoma liquid biopsy; (2) a highly effective molecular “warning” marker for minimal residual disease monitoring; and (3) a soluble protein index of inflammation and putative response to therapeutic treatments.

Since the 19th century, appropriate lymphadenectomy has been considered a cornerstone of oncologic surgery and one of the most important prognostic factors. This approach can be applied to any surgery for gastrointestinal cancer. During surgery for colon and rectal cancer, an adequate portion of the mesentery is removed together with the segment of bowel affected by the disease. The adequate number of lymph nodes to be removed is standardized and reported by several guidelines. It is mandatory to determine the appropriate extent of lymphadenectomy and to balance its oncological benefits with the increased morbidity associated with its execution in cancer patients. Our review focuses on the concept of "complete mesenteric excision (CME) with central vascular ligation (CVL)," a radical lymphadenectomy for colorectal cancer that has gained increasing interest in recent years. The aim of this study was to evaluate the evolution of this approach over the years, its potential oncologic benefits and potential risks, and the improvements offered by laparoscopic techniques. Theoretical advantages of CME are improved local-relapse rates due to complete removal of the intact mesocolic fascia and improved distance recurrence rates due to ligation of vessels at their origin (CVL) which guarantees removal of a larger number of lymph nodes. The development and worldwide diffusion of laparoscopic techniques minimized postoperative trauma in oncologic surgery, providing the same oncologic results as open surgery. This has been widely applied to colorectal cancer surgery; however, CME entails a technical complexity that can limit its wide minimally-invasive application. This review analyzes results of these procedures in terms of oncological outcomes, technical feasibility and complexity, especially within the context of minimally invasive surgery.

In the nineteenth century the idea of a correct surgical approach in oncologic surgery moved towards a good lymphadenectomy. In colon cancer the segment is removed with adjacent mesentery, in gastric cancer or pancreatic cancer a good oncologic resection is obtained with adequate lymphadenectomy. Many guidelines propose a minimal lymph node count that the surgeon must obtain. Therefore, it is essential to understand the adequate extent of lymphadenectomy to be performed in cancer surgery. In this review of the current literature, the focus is on “central vascular ligation”, understood as radical lymphadenectomy in upper and lower gastrointestinal cancer, the evolution of this approach during the years and the improvement of laparoscopic techniques. For what concerns laparoscopic surgery, the main goal is to minimize post-operative trauma introducing the “less is more” concept whilst preserving attention for oncological outcomes. This review will demonstrate the importance of a scientifically based standardization of oncologic gastrointestinal surgery, especially in relation to the expansion of minimally invasive surgery and underlines the importance to further investigate through new randomized trials the role of extended lymphadenectomy in the new era of a multimodal approach, and most importantly, an era where minimally invasive techniques and the idea of “less is more” are becoming the standard thought for the surgical approach.

Purpose: We investigate the vaporization of phase-change ultrasound contrast agents using photon radiation for dosimetry perspectives in radiotherapy. Methods: We studied superheated perfluorobutane nanodroplets with a crosslinked poly(vinylalcohol) shell. The nanodroplets' physico-chemical properties, and their acoustic transition have been assessed firstly. Then, poly (vinylalcohol)-perfluorobutane nanodroplets were dispersed in poly(acrylamide) hydrogel phantoms and exposed to a photon beam. We addressed the effect of several parameters influencing the nanodroplets radiation sensitivity (energy/delivered dose/dose rate/temperature). The nanodroplets-vaporization post-photon exposure was evaluated using ultrasound imaging at a low mechanical index. Results: Poly(vinylalcohol)-perfluorobutane nanodroplets show a good colloidal stability over four weeks and remain highly stable at temperatures up to 78 degrees C. Nanodroplets acoustically-triggered phase transition leads to microbubbles with diameters <10 mu m and an activation threshold of mechanical index = 0.4, at 7.5 MHz. A small number of vaporization events occur post-photon exposure (6MV/15MV), at doses between 2 and 10 Gy, leading to ultrasound contrast increase up to 60% at RT. The nanodroplets become efficiently sensitive to photons when heated to a temperature of 65 degrees C (while remaining below the superheat limit temperature) during irradiation. Conclusions: Nanodroplets' core is linked to the degree of superheat in the metastable state and plays a critical role in determining nanodroplet' stability and sensitivity to ionizing radiation, requiring higher or lower linear energy transfer vaporization thresholds. While poly(vinylalcohol)-perfluorobutane nanodroplets could be slightly activated by photons at ambient conditions, a good balance between the degree of superheat and stability will aim at optimizing the design of nanodroplets to reach high sensitivity to photons at physiological conditions.

Open-access colonoscopy (OAC), whereby the colonoscopy is performed without a prior office visit with a gastroenterologist, is affected by inappropriateness which leads to overprescription and reduced availability of the procedure in case of alarming symptoms. The clinical care pathway (CCP) is a healthcare management tool promoted by national health systems to organize work-up of various morbidities. Recently, we started a CCP dedicated to colorectal cancer (CRC), including a colonoscopy session for CRC diagnosis and prevention. We aimed to evaluate the appropriateness, the quality, and the efficiency in the delivery of colonoscopy with the open-access system and a CCP program in the CRC. Quality indicators for colonoscopy in subjects in the CCP were compared to referrals by general practitioners (OAC) or by non-gastroenterologist physicians (non-gastroenterologist physician colonoscopy, NGPC). Attendance rate to colonoscopy was greater in the CCP group and NGPC group than in the OAC group (99%, 99%, and 86%, respectively). Waiting time in the CCP group was shorter than in the OAC group (3.88 ± 2.27 vs. 32 ± 22.31 weeks, respectively). Appropriateness of colonoscopy prescription was better in the CCP group than in the OAC group (92 vs. 50%, respectively). OAC is affected by the lack of timeliness and low appropriateness of prescription. A CCP reduces the number of inappropriate colonoscopies, especially for post-polypectomy surveillance, and improves the delivery of colonoscopy in patients requiring a fast-track examination. The high rate of inappropriate OAC suggests that this modality of healthcare should be widely reviewed.

article: Long-term efficacy and safety of adalimumab on a severe case of hidradenitis suppurativa - Italian Journal of Dermatology and Venereology 2021 February;156(1):101-2 - Minerva Medica - Journals

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.

Background Programs of Enhanced Recovery After Surgery reduces morbidity and shorten recovery in patients undergoing colorectal resections for cancer. Patients presenting with more advanced disease such as T4 cancers are frequently excluded from undergoing ERAS programs due to the difficulty in applying established protocols. The primary aim of this investigation was to evaluate the possibility of applying a validated ERAS protocol in patients undergoing colorectal resection for T4 colon and rectal cancer and to evaluate the short-term outcome. Methods Single-center, retrospective cohort study. All patients with a clinical diagnosis of stage T4 colorectal cancer undergoing surgery between November 2016 and January 2020 were treated following the institutional fast track protocol without exclusion. Short-term postoperative outcomes were compared to those of a control group treated with conventional care and that underwent surgical resection for T4 colorectal cancer at the same institution from January 2010 to October 2016. Data from both groups were collected retrospectively from a prospectively maintained database. Results Eighty-two patients were diagnosed with T4 cancer, 49 patients were included in the ERAS cohort and 33 in the historical conventional care cohort. Both, the mean time of tolerance to solid food diet and postoperative length of stay were significantly shorter in the ERAS group than in the control group (3.14 ± 1.76 vs 4.8 ± 1.52; p < 0.0001 and 6.93 ± 3.76 vs 9.50 ± 4.83; p = 0.0084 respectively). No differences in perioperative complications were observed. Conclusions Results from this cohort study from a single-center registry support the thesis that the adoption of the ERAS protocol is effective and applicable in patients with colorectal cancer clinically staged T4, reducing significantly their length of stay and time of tolerance to solid food diet, without affecting surgical postoperative outcomes.

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.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

BACKGROUND Completely isolated enteric duplication cysts (CIDCs) are rare malformations that can occur at any site in the gastrointestinal system. This report describes a woman with a CIDC and an incidental appendiceal neuroendocrine tumor (ANET). CASE REPORT A 26-year-old woman who presented with dysmenorrhea was assessed by ultrasound (US), which revealed a pelvic mass. Other imaging modalities, including magnetic resonance imaging (MRI), failed to clarify the origin of the mass. Intraoperative findings during diagnostic laparoscopy revealed an isolated, ovaloid mass with autonomous peristalsis and a short pedicle towards the root of the ileal mesentery. In addition, the appendix appeared enlarged with a hardened consistency. The mass was resected and an appendectomy performed laparoscopically. The pelvic mass was diagnosed as a CIDC and the appendix was incidentally found to contain a pT3Nx carcinoid tumor. Based on histological examination and guidelines of the European Neuroendocrine Tumor Network (ENET), the patient later underwent a laparoscopic right hemicolectomy. CONCLUSIONS CIDC in adulthood is very rare, especially when combined with an incidentally discovered pT3Nx appendiceal carcinoid tumor. Neither US nor MRI was able to provide a precise preoperative diagnosis. Diagnostic laparoscopy clarified the nature of the mass and revealed a lesion missed during the preoperative workup. Because of the diagnosis of ANET, the patient subsequently underwent a laparoscopic right hemicolectomy.