Epithelial-to-Mesenchymal Transition Gene Signature in Circulating Melanoma Cells: Biological and Clinical Relevance.

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.

Feasibility and outcomes of ERAS protocol in elective cT4 colorectal cancer patients: results from a single-center retrospective cohort study.

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.

MCAM/MUC18/CD146 as a Multifaceted Warning Marker of Melanoma Progression in Liquid Biopsy.

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.

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.

Breast Cancer Is Associated with Increased HLA-DRB1*11:01 and HLA-DRB1*10:01 Allele Frequency in a Population of Patients from Central Italy.

The relationship between HLA-DRB1 allele polymorphism and breast cancer (BC) development is still unclear and needs further investigation. To address this issue, we analyzed HLA-DRB1 allele frequency (AF) by sequence-based typing (SBT) in 47 patients from central Italy with BC and 156 sex and age-matched healthy controls. Two hundred ninety-seven individuals from the same region were utilized as historical controls. Pearson's chi-square analysis with Yate's correction or Fisher's Exact test with Bonferroni's correction, as appropriate, were used to compare HLA-DRB1 AF differences in patients and controls. A total of 36 HLA-DRB1 alleles were identified. A detailed study showed that HLA-DRB1*11:01 and HLA-DRB1*10:01 alleles are significantly associated with increased BC risk. In particular, HLA-DRB1*11:01 AF was significantly higher in patients with BC than in healthy females and historical controls, even following Bonferroni's correction (stage I-II BC patients vs historical controls p<0.00; stage III-IV BC patients vs female healthy controls p=0.025 and historical controls p<0.00). The HLA-DRB1*10:01 allele was also positively associated with BC as evidenced by a significantly higher AF in patients with BC than in healthy controls (BC patients stage I-II vs historical controls corrected p =0.01). These results suggest that both HLA-DRB1*11:01 and HLA-DRB1*10:01 AF could represent interesting markers in patients at risk of developing BC.

Partial renal resection by LaparoNewPro: in vivo open and laparoscopic study in an animal model.

INTRODUCTION: The aim of this research project was to test an incremental bipolar radiofrequency generator with open and laparoscopic inline electrode probe for partial renal resection without vascular clamping. MATERIAL AND METHODS: Sixteen polar resections with clamping and six without were performed in four pigs in the acute phase. Three pigs underwent laparoscopic polar resection and were live housed for ten days and reoperated to verify the presence of hematic and urinary collection and the condition of the renal edge. Five pigs underwent laparoscopic polar resection without clamping, and two of these were live housed and reoperated after ten days. RESULTS: Polar renal resection by our system (LaparoNewPro) turned out to be effective and safe, without cardio-respiratory complications or damage to the remaining parenchyma. Coagulation of the renal parenchyma before resection is effective and safe; at the reoperation, no complications were observed. The laparoscopic version of the probe is ergonomic and safe, with effective coagulation and a small amount of smoke produced. No complications occurred in the housed animals. No damage, local or to residual parenchyma, or thrombosis of the renal vessels were found. CONCLUSIONS: LaparoNewPro is able to deliver coagulation of the resection line effectively and independently of clamping of the vessels both in the open and laparoscopic approaches. Coagulation times are short, the automatism of the generator is reliable, and the open and laparoscopic probes are ergonomic.

Role of KIR and CD16A genotypes in colorectal carcinoma genetic risk and clinical stage.

BACKGROUND: NK cell cytotoxicity is regulated by the types of the interaction between killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands on target cells and the different binding affinity of the Fcγ receptor IIIA (CD16A) for IgG-coated tumor cells. Thus, it is conceivable that KIR and CD16A gene contents may contribute to the function of NK cells by modulating an immune response in the colorectal carcinoma (CRC) microenvironment. This hypothesis is supported by recent evidence suggesting that NK cells improve the clinical course of CRC patients by enhancing the anti-CRC effect of CD8 + T cells. This information provides the rationale to test the hypothesis whether the independent KIR segregation and specificity, as well as CD16A gene polymorphisms, have an impact on CRC. METHODS: Using polymerase chain reaction-sequence-specific primers (PCR-SSP) and sequence-based typing (SBT), we investigated KIR/HLA-C complex and CD16A (48H/R/L,158V/F) gene polymorphisms in 52 CRC patients and 61 local healthy controls (LCTRs). RESULTS: The allele frequency (AF) of at least five activating KIR (aKIRs) of the B haplotype (p = 0.036, OR 0.204), KIR2DL2 (p = 0.047, OR 0.2616), and KIR2DS2 genes (5.8 vs LCTR 13.8 % and vs. Fasano's CTR 16.3 %, p = 0.05, OR 0.3145), in the absence of their cognate HLA-C1 ligands, were significantly associated with a reduced genetic risk of CRC. In contrast, CD16A-48H polymorphism was positively associated with an increased genetic risk of CRC (p = 0.05, OR 2.761). The latter was also found to be correlated with advanced stages of disease [III and IV (p = 0.03, OR 3.625)]. CONCLUSIONS: Our data suggest that the analysis of aKIRs and KIR2DL2 gene and CD16A-48H may be of interest for the identification of individuals at reduced and increased genetic risk of CRC, respectively.

HLA-DRB1*13:01 allele in the genetic susceptibility to colorectal carcinoma.

Increasing evidence suggests that HLA-DRB1 alleles reduce or increase the risk of developing ulcerative colitis-associated colorectal carcinoma (CRC) tumors. However, the role of HLA-DRB1 locus on the susceptibility to develop CRC tumor, in the absence of a history of inflammatory bowel diseases (IBDs), is unclear. The aim of our study was to determine whether HLA-DRB1 alleles are associated with IBD-independent CRC tumor. HLA-DRB1 allele polymorphisms were identified by sequence-based typing method in 53 CRC patients and 57 sex- and age-matched healthy Caucasian controls. Pearson's chi-squared analysis with Yate's correction or Fisher's exact test with Bonferroni's correction, as appropriate, were used to compare the allele frequency (AF) differences of HLA-DRB1 in patients and controls. A total of 29 HLA-DRB1 alleles were recognized. A detailed study of these alleles allowed to identify DRB1*13:01 and DRB1*11:01 alleles that were significantly associated with an increased and reduced risk to develop CRC tumor, respectively. AF of DRB1*13:01, in CRC patients, was significantly higher than that of healthy controls, even following Bonferroni's correction (p = 0.029). In contrast, the presence of the DRB1*11:01 allele was negatively associated with CRC tumor as evidenced by the significantly lower AF in CRC patients than that of healthy controls (p = 0.005). However, following Bonferroni's correction, the AF of DRB*11:01 lost its statistical significance. These results suggest that HLA-DRB1*13:01 allele could be a potential marker for predicting genetic susceptibility to CRC tumor. In contrast, the protective role of DRB1*11:01 remains unclear.

Natural humoral immune response to ribosomal P0 protein in colorectal cancer patients.

BACKGROUND: Tumor associated antigens are useful in colorectal cancer (CRC) management. The ribosomal P proteins (P0, P1, P2) play an important role in protein synthesis and tumor formation. The immunogenicity of the ribosomal P0 protein in head and neck, in breast and prostate cancer patients and the overexpression of the carboxyl-terminal P0 epitope (C-22 P0) in some tumors were reported. METHODS: Sera from 72 colorectal tumor patients (67 malignant and 5 benign tumors) were compared with 73 healthy donor sera for the presence of antibodies to CEA, EGFR, ErbB2 and ribosomal P proteins by western blotting or ELISA. Expression of the C-22 P0 epitope on tissues and colon cancer cells was determined by immunoperoxidase staining and indirect immunofluorescence/western blotting, respectively, employing MAb 2B2. Biological effects of MAb 2B2 on colon cancer cells were assessed by the Sulforhodamine B cell proliferation assay, trypan blue exclusion test and cleaved caspase-3 detection. Fisher's exact test was used to compare the number of auto-antibodies positive patients with healthy donors. Variation in the C-22 P0 expression, and in the number of apoptotic cells was evaluated by Student's t-test. Variation in cell survival and cell death was evaluated by Newman-Keuls test. RESULTS: No significant humoral response was observed to CEA, EGFR and ErbB2 in CRC patients. Conversely, 7 out of 67 CRC patient sera reacted to ribosomal P proteins. The prevalence of P proteins auto-antibodies in CRC patients was significant. Five patients showed restricted P0 immunoreactivity, while two patients reacted simultaneously to all P proteins. The C-22 P0 epitope was homogenously expressed both in malignant tumors and the adjacent mucosa, but the intensity of expression was higher in the tumor. Starved colon cancer cells showed a higher C-22 P0 epitope plasma membrane expression compared to control cells. MAb 2B2 inhibited colon cancer cell growth and induced cell death in a dose dependent manner. CONCLUSIONS: Our study shows a spontaneous humoral immune response to ribosomal P0 protein in CRC patients and the inhibition of in vitro cancer cell growth after C-22 P0 epitope targeting. The ribosomal P0 protein might be a useful immunological target in CRC patients.

Cancer of the sigmoid colon and antibodies. A puzzle.

UNLABELLED: In this work we describe the case report of a woman affected by cancer of the sigmoid colon and with a positive direct antiglobulin test (DAT) and indirect antiglobulin test (IAT). Case report with results: A meticulous medical history showed that the woman had been suffering from recurrent fetal loss. Then she had cardiac and coagulative problems. These data suggested a phospholipid syndrome. CONCLUSION: The patient had a medical history positive for a phospholipid syndrome and we think that this disease could explain the onset of the autoantibody.

Chronically sun-damaged melanomas express low levels of nuclear glutathione-S-transferase-π: an epidemiological and clinicopathological study in Italy.

The detoxifying enzyme glutathione-s-transferase pi (GST-π) is present in keratinocytes and melanocytes and exerts a protective role against tumour progression. Melanomas close to melanocytic naevus remnants occur less frequently on sun-exposed areas, whereas solar dermal elastosis, hallmark of chronic sun-damage, characterise melanomas on sun-exposed skin. We evaluated the expression of GST-π in 113 melanomas associated to melanocytic naevus remnants or to solar dermal elastosis, classified according to clinical characteristics, history of sun exposure, histological subtypes and AJCC staging. Chronically sun-damaged melanomas, identified by moderate-severe solar dermal elastosis, showed a lower nuclear GST-π expression and a higher thickness than those related to melanocytic naevus remnants (p < 0.03). Multivariate logistic regression analysis demonstrated that male gender and chronic sun-exposure are independent risk factors significantly associated to melanomas localised on the trunk (OR = 3.36, 95% CI: 1.31-8.65; OR = 5.97, 95% CI: 1.71-20.87). If confirmed on a larger series, lower expression of nuclear GST-π in melanoma cells could represent a possible marker of chronically sun-damaged melanoma pathogenesis.

Partial nephrectomy using radiofrequency incremental bipolar generator with multi electrode probe: experimental study in bench pig kidneys.

BACKGROUND: The aim of this research project was the realization of an incremental bipolar radiofrequency generator with inline 4-electrode probe for partial renal resection without clamping of the vessels. METHODS: The experimentation was carried out across two phases: the preliminary realization of a specific generator and an inline multielectrode probe for open surgery (Phase 1); system testing on 27 bench kidneys for a total of 47 partial resection (Phase 2). The parameters evaluated were: power level, generator automatisms, parenchymal coagulation times, needle caliber, thickness of the coagulated tissue "slice", charring, ergonomy, feasibility of the application of "bolster" stitches. RESULTS: The analysis of the results referred to the homogeneity and thickness of coagulation, energy supply times with reference to the power level and caliber of the needles. The optimal results were obtained by using needles of 1.5 mm caliber at power level 5, and with coagulation times of 54 seconds for the first insertion and 30 seconds for the second. CONCLUSIONS: The experimentation demonstrated that the apparatus, consisting of a generator named "LaparoNewPro" and fitted with a dedicated probe for open surgery, is able to carry out a coagulation of the line of resection of the renal parenchyma in a homogeneous manner, in short times, without tissue charring, and with the possibility of stitching both on coagulated tissue and the caliceal system. The generator automatism based on the flow of the current supplied by each electrode is reliable, and the cessation of energy supply coincides with optimal coagulation.

Impact of HLA Class I Antigen, Killer Inhibitory Receptor, and FCGR3A Genotypes on Breast Cancer Susceptibility and Tumor Stage.

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.

From In Silico Simulation between TGF-ß Receptors and Quercetin to Clinical Insight of a Medical Device Containing Allium cepa: Its Efficacy and Tolerability on Post-Surgical Scars.

(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-ß/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-ß/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-ß/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-ß/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.

Use of intraoperative endoscopy to localize bleeding in the small intestine.

INTRODUCTION: Bleeding within the small intestine is difficult to diagnose and localize because it typically occurs at a slow rate. These patients may undergo multiple transfusions and repeated endoscopy, contrast studies, bleeding scans, and angiography before the bleeding source is identified. CASE REPORT: We report a case of 64-year-old woman, where both endoscopic and angiographic techniques were used to localize protracted bleeding. During endoscopic treatment, the arteriovenous malformations continued bleeding. However, highly selective angiography and intraoperative endoscopy outlined the segments of small intestine for resection. This case reviews the evaluation, localization and treatment of small intestine bleeding. DISCUSSION: Localizing the site of protracted bleeding in the small intestine beyond the duodenum bulb can be problematic. For some patients, the course of examinations and transfusions can take years. The small intestine is an uncommon site for gastrointestinal hemorrhage, and only 3%-5% of gastrointestinal bleeding occurs between the ligament of Treitz and the ileocecal valve. The length and location of the small intestine, along with other anatomical factors, make this area difficult to assess with endoscopy or radiology. In this case of protracted bleeding, highly selective angiography and intraoperative endoscopy were used to locate the source of the bleeding.

Inflammatory fibroid polyp. A case report and review of the literature.

INTRODUCTION: The Inflammatory fibroid polyp (IFP) is a mesenchymal polypoid lesion of the gastrointestinal tract that follows a benign course. Incidence is extremely low: from 0,1% to 2 %. Histologically, it consists of a sub mucous proliferation of vascolarized fibromuscolar tissue with a high eosinophils inflammatory infiltration. IFP can arise everywhere in the gastrointestinal tract but is described more frequently in the gastric antrum (70%). CASE REPORT: We report a case of a 71-year-old woman presented to our department with a worsening history of lack's appetite, nausea and early satiety. We performed a review of the literature from 1949 to 2011. 196 cases of IFPs were found. CONCLUSION: Clinical symptoms are heterogeneous and endoscopy's examination revealed only presence of a sub-mucosal lesion, and their biopsies often gave not diagnostic localization. In the differential diagnosis, it's important to discern between eosinophilic gastroenteritis, gastrointestinal stromal tumor, inflammatory pseudotumor, hemangioendothelioma, and hemangiopericytoma. Eco-endoscopic appearance and biopsies associated may provide useful informations, that can steer to the diagnostic suspect of IFP. Despite this is a benign lesion, this one often needs a surgical excision on healthy margin. In literature is also described high local recurrence, specially when incomplete excision proceeded. KEYWORDS: Gastric sub-mucosal tumor, Inflammatory fibroid polyp, Stomach, Vanek's Tumor.

Total neoadjuvant therapy for the treatment of locally advanced rectal cancer: a systematic minireview.

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.

Synchronous liver and peritoneal metastases from colorectal cancer: Is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy combined with liver resection a feasible option?

Background: Traditionally, 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. Methods: PubMed, 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. Results: In 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. Conclusion: The 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.

Spontaneous intraperitoneal rupture of pyonephrosis in a patient with unknown kidney carcinosarcoma: a case report.

Seventeen cases of peritonitis due to rupture of a pyonephrosis have been reported. The majority of these cases occur secondary to renal stones. Only two cases of ruptured pyonephrosis with concurrent kidney neoplasm have been described and only one of these presented as an acute peritonitis. In this presentation we discuss an unusual case of a 68 year old man with a chronic history of bilateral nephrolithiasis and recent pyonephrosis. He presented acutely with peritonitis and was later found to have a carcinosarcoma of the kidney. The case highlights the importance of recognizing the possibility of underling renal carcinoma in patients presenting with a ruptured pyonephrosis and discuss steps to avoid this serious complication.

[Bodypackers syndrome. A case report and review of the literature]. / La sindrome "body packers". Caso clinico e revisione della letteratura.

INTRODUCTION: With the term Body packers we identify people who carry drugs hidden in their bodies especially on international flights. These event are constantly increasing all over the world. The accidental spontaneous opening of the drug packers is the major risk for patient's life, because the release cocaine inside the bowel can stir up the Body packers Syndrome. This eventuality is a medical surgical emergency that needs a wel timed diagnosis and a sudden treatment. CASE REPORT: We report a case of a 31 years old Caucasian woman, admitted from Rome International Airport to the nearest Emergency Unit and then moved to our Department because of suspected epilepsy hiding a diagnosis of Body packers Syndrome in acute phase. When the diagnosis was made, the woman was submitted to a colonoscopy and ciecotomy, and fifty-three packets were removed. In intensive care any complication occurred after surgery. CONCLUSION: The Body packing of drugs it's constantly a going problem. In Italy currently there aren't shared guide lines about the management of these patients. The international experience reports that in asymptomatic patients is enough a conservative treatment to help the spontaneous evacuation of packets but if the Body packers Syndrome is already present the best treatment is the surgical one. Quickness, accuracy and right use of radiology are the main factors to reach a correct diagnosis and to obtain a good result.