Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases.

BACKGROUND: There is little evidence on KRAS mutational profiles in colorectal cancer (CRC) peritoneal metastases (PM). This study aims to determine the prevalence of specific KRAS mutations and their prognostic value in a homogeneous cohort of patients with isolated CRC PM treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. MATERIALS AND METHODS: Data were collected from 13 Italian centers, gathered in a collaborative group of the Italian Society of Surgical Oncology. KRAS mutation subtypes have been correlated with clinical and pathological characteristics and survival [overall survival (OS), local (peritoneal) disease-free survival (LDFS) and disease-free survival (DFS)]. RESULTS: KRAS mutations occurred in 172 patients (47.5%) out of the 362 analyzed. Two different prognostic groups of KRAS mutation subtypes were identified: KRASMUT1 (G12R, G13A, G13C, G13V, Q61H, K117N, A146V), median OS > 120 months and KRASMUT2 (G12A, G12C, G12D, G12S, G12V, G13D, A59E, A59V, A146T), OS: 31.2 months. KRASMUT2 mutations mainly occurred in the P-loop region (P < 0.001) with decreased guanosine triphosphate (GTP) hydrolysis activity (P < 0.001) and were more frequently related to size (P < 0.001) and polarity change (P < 0.001) of the substituted amino acid (AA). When KRASMUT1 and KRASMUT2 were combined with other known prognostic factors (peritoneal cancer index, completeness of cytoreduction score, grading, signet ring cell, N status) in multivariate analysis, KRASMUT1 showed a similar survival rate to KRASWT patients, whereas KRASMUT2 was independently associated with poorer prognosis (hazard ratios: OS 2.1, P < 0.001; DFS 1.9, P < 0.001; LDFS 2.5, P < 0.0001). CONCLUSIONS: In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.

Right hemicolectomy with complete mesocolic excision is safe, leads to an increased lymph node yield and to increased survival: results of a systematic review and meta-analysis.

BACKGROUND: The introduction of complete mesocolic excision (CME) for right colon cancer has raised an important discussion in relation to the extent of colic and mesenteric resection, and the impact this may have on lymph node yield. As uncertainty remains regarding the usefulness of and indications for right hemicolectomy with CME and the benefits of CME compared with a traditional approach, the purpose of this meta-analysis is to compare the two procedures in terms of safety, lymph node yield and oncological outcome. METHODS: We performed a systematic review of the literature from 2009 up to March 15th, 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two hundred eighty-one publications were evaluated, and 17 met the inclusion criteria and were included. Primary endpoints analysed were anastomotic leak rate, blood loss, number of harvested lymph nodes, 3- and 5-year oncologic outcomes. Secondary outcomes were operating time, conversion, intraoperative complications, reoperation rate, overall and Clavien-Dindo grade 3-4 postoperative complications. RESULTS: In terms of safety, right hemicolectomy with CME is not inferior to the standard procedure when comparing rates of anastomotic leak (RR 0.82, 95% CI 0.38-1.79), blood loss (MD -32.48, 95% CI -98.54 to -33.58), overall postoperative complications (RR 0.82, 95% CI 0.67-1.00), Clavien-Dindo grade III-IV postoperative complications (RR 1.36, 95% CI 0.82-2.28) and reoperation rate (RR 0.65, 95% CI 0.26-1.75). Traditional surgery is associated with a shorter operating time (MD 16.43, 95% CI 4.27-28.60) and lower conversion from laparoscopic to open approach (RR 1.72, 95% CI 1.00-2.96). In terms of oncologic outcomes, right hemicolectomy with CME leads to a higher lymph node yield than traditional surgery (MD 7.05, 95% CI 4.06-10.04). Results of statistical analysis comparing 3-year overall survival and 5-year disease-free survival were better in the CME group, RR 0.42, 95% CI 0.27-0.66 and RR 0.36, 95% CI 0.17-0.56, respectively. CONCLUSIONS: Right hemicolectomy with CME is not inferior to traditional surgery in terms of safety and has a greater lymph node yield when compared with traditional surgery. Moreover, right-sided CME is associated with better overall and disease-free survival.

Bounds on Lorentz Invariance Violation from MAGIC Observation of GRB 190114C.

On January 14, 2019, the Major Atmospheric Gamma Imaging Cherenkov telescopes detected GRB 190114C above 0.2 TeV, recording the most energetic photons ever observed from a gamma-ray burst. We use this unique observation to probe an energy dependence of the speed of light in vacuo for photons as predicted by several quantum gravity models. Based on a set of assumptions on the possible intrinsic spectral and temporal evolution, we obtain competitive lower limits on the quadratic leading order of speed of light modification.

Mid-transverse colon cancer and extended versus transverse colectomy: Results of the Italian society of surgical oncology colorectal cancer network (SICO CCN) multicenter collaborative study.

INTRODUCTION: Transverse colon cancer (TCC) is poorly studied, and TCC cases are often excluded from large prospective randomized trials because of their complexity and their potentially high complication rate. The best surgical approach for TCC has yet to be established. The aim of this large retrospective multicenter Italian series is to investigate the advantages and disadvantages of both hemicolectomy and transverse colectomy in order to identify the best surgical approach. MATERIALS AND METHODS: This was a retrospective cohort study of patients with mid-transverse colon cancer treated with a segmental colon resection or an extended hemicolectomy (right or left) between 2006 and 2016 in 28 high-volume (more than 70 procedures/year) Italian referral centers for colorectal surgery. RESULTS: The study included 1529 patients, 388 of whom underwent a segmental resection while 1141 underwent an extended resection. A higher number of complications has been reported in the segmental group than in the extended group (30.1% versus 23.6%; p 0.010). In 42 cases the main complication was the anastomotic leak (4.4% versus 2.2%; p 0.020). Recovery outcomes also showed statistical differences: time to first flatus (p 0.014), time to first mobilization (p 0.040), and overall hospital stay (p < 0.001) were significantly shorter in the extended group. Even if overall survival were similar between the groups (95.1% versus 97%; p 0.384), 3-year disease-free survival worsened after segmental resection (78.1% versus 86.2%; p 0.001). CONCLUSIONS: According to our results, an extended right colon resection for TCC seems to be surgically safer and more oncologically valid.

Survival comparison in gastric cancer patients between 7th and 8th edition of the AJCC TNM staging system: The first western single center experience.

BACKGROUND: The objective of this study was to compare the 7th and the 8th edition of American Joint Committee on Cancer staging system (AJCC TNM) in terms of better stratification in our gastric cancer resected patients. METHODS AND MATERIALS: A retrospective analysis of a single western center series was made. Patients who underwent surgery from January 2004 to December 2016 were enrolled in the study. We compared survival rates across patients classified according to the 7th and the 8th AJCC TNM staging system. RESULTS: Among 295 patients we observed 9.8% stage migration according the 8th edition. Of these 2.1% and 7.9% of patients showed respectively a higher and a lower stage. 5 years Overall Survival (5Y-OS) according to the 8th edition for stage IIIB and IIIC were 32% versus 9% showing a better stratification compared to the 7th edition in which 5Y-OS were respectively 26% versus 22%. CONCLUSION: Restaging system seems to improve survival rate discrimination in particular comparing stage IIIB and stage IIIC; whereas in stage IIIA this is not so clear. More studies are necessary to confirm these data.

Inflammatory Markers as Prognostic Factors of Survival in Patients Affected by Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

INTRODUCTION: Transarterial chemoembolization (TACE) is a good choice for hepatocellular carcinoma (HCC) treatment when surgery and liver transplantation are not feasible. Few studies reported the value of prognostic factors influencing survival after chemoembolization. In this study, we evaluated whether preoperative inflammatory factors such as neutrophil to lymphocyte ratio and platelet to lymphocyte ratio affected our patient survival when affected by hepatocellular carcinoma. METHODS: We retrospectively evaluated a total of 72 patients with hepatocellular carcinoma that underwent TACE. We enrolled patients with different etiopathogeneses of hepatitis and histologically proven HCC not suitable for surgery. The overall study population was dichotomized in two groups according to the median NLR value and was analyzed also according to other prognostic factors. RESULTS: The global median overall survival (OS) was 28 months. The OS in patients with high NLR was statistically significantly shorter than that in patients with low NLR. The following pretreatment variables were significantly associated with the OS in univariate analyses: age, Child-Pugh score, BCLC stage, INR, and NLR. Pretreated high NLR was an independently unfavorable factor for OS. CONCLUSION: NLR could be considered a good prognostic factor of survival useful to stratify patients that could benefit from TACE treatment.

A 5-D Implementation of FGM for the Large Eddy Simulation of a Stratified Swirled Flame with Heat Loss in a Gas Turbine Combustor.

Numerical simulations are foreseen to provide a tremendous increase in gas-turbine burners efficiency in the near future. Modern developments in numerical schemes, turbulence models and the consistent increase of computing power allow Large Eddy Simulation (LES) to be applied to real cold flow industrial applications. However, the detailed simulation of the gas-turbine combustion process remains still prohibited because of its enormous computational cost. Several numerical models have been developed in order to reduce the costs of flame simulations for engineering applications. In this paper, the Flamelet-Generated Manifold (FGM) chemistry reduction technique is implemented and progressively extended for the inclusion of all the combustion features that are typically observed in stationary gas-turbine combustion. These consist of stratification effects, heat loss and turbulence. Three control variables are included for the chemistry representation: the reaction evolution is described by the reaction progress variable, the heat loss is described by the enthalpy and the stratification effect is expressed by the mixture fraction. The interaction between chemistry and turbulence is considered through a presumed beta-shaped probability density function (PDF) approach, which is considered for progress variable and mixture fraction, finally attaining a 5-D manifold. The application of FGM in combination with heat loss, fuel stratification and turbulence has never been studied in literature. To this aim, a highly turbulent and swirling flame in a gas turbine combustor is computed by means of the present 5-D FGM implementation coupled to an LES turbulence model, and the results are compared with experimental data. In general, the model gives a rather good agreement with experimental data. It is shown that the inclusion of heat loss strongly enhances the temperature predictions in the whole burner and leads to greatly improved NO predictions. The use of FGM as a combustion model shows that combustion features at gas turbine conditions can be satisfactorily reproduced with a reasonable computational effort. The implemented combustion model retains most of the physical accuracy of a detailed simulation while drastically reducing its computational time, paving the way for new developments of alternative fuel usage in a cleaner and more efficient combustion.

Extended lymphadenectomy in elderly and/or highly co-morbid gastric cancer patients: A retrospective multicenter study.

BACKGROUND: Gastrectomy with extended lymphadenectomy is considered the gold standard treatment for advanced gastric cancer, with no age- or comorbidity-related limitations. We evaluated the safety and efficacy of curative gastrectomy with extended nodal dissection, verifying survival in elderly and highly co-morbid patients. METHODS: In a retrospective multicenter study, we examined 1322 non-metastatic gastric-cancer patients that underwent curative gastrectomy with D2 versus D1 lymphadenectomy from January 2000 to December 2009. Postoperative complications, overall survival (OS), and disease-specific survival (DSS) according to age and the Charlson Comorbidity Score were analyzed in relation to the extent of lymphadenectomy. RESULTS: Postoperative morbidity was 30.4%. Complications were more frequent in highly co-morbid elderly patients, and, although general morbidity rates after D2 and D1 lymphadenectomy were similar (29.9% and 33.2%, respectively), they increased following D2 in highly co-morbid elderly patients (39.6%). D2-lymphadenectomy significantly improved 5-year OS and DSS (48.0% vs. 37.6% in D1, p < 0.001 and 72.6% vs. 58.1% in D1, p < 0.001, respectively) in all patients. In elderly patients, this benefit was present only in 5-year DSS. D2 nodal dissection induced better 5-year OS and DSS rates in elderly patients with positive nodes (29.7% vs. 21.2% in D1, p = 0.008 and 47.5% vs. 30.6% in D1, p = 0.001, respectively), although it was present only in DSS when highly co-morbid elderly patients were considered. CONCLUSION: Extended lymphadenectomy confirmed better survival rates in gastric cancer patients. Due to high postoperative complication rate and no significant improvement of the OS, D1 lymphadenectomy should be considered in elderly and/or highly co-morbid gastric cancer patients.

Factors influencing survival after hepatectomy for metastases from gastric cancer.

PURPOSE: To investigate clinical factors influencing the prognosis of patients submitted to hepatectomy for metastases from gastric cancer and their clinical role. METHODS: Retrospective multi-center chart review. We evaluated how survival from surgery was influenced by patient-related, gastric cancer-related, metastasis-related and treatment-related candidate prognostic factors. RESULTS: One hundred and five patients submitted to hepatectomy for metastases from gastric cancer, in the synchronous and metachronous setting of the disease. In 89 cases a R0 resection was achieved, while in 16 a R+ hepatic resection was performed. Adjuvant chemotherapy was administered to 29 patients. Surgical mortality was 1% and morbidity 13.3%. Median disease-free survival was 10 months, median overall survival was 14.6 months. Overall 1, 3, and 5-year survival rates were 58.2%, 20.3%, and 13.1%, respectively. Survival was influenced independently by the factor T of the gastric primary (p < 0.001), by the curativity of surgical procedure (p = 0.001), by the timing of hepatic involvement (p < 0.001) and by adjuvant chemotherapy (p < 0.001). T4 gastric cancer, R+ resection, synchronous metastases, and abstention from adjuvant chemotherapy were associated with a worse prognosis; T4 gastric cancer and R+ resections displayed a cumulative effect (p < 0.001). CONCLUSIONS: Our data show that R0 resection must be pursued whenever possible. Furthermore, in the synchronous setting, the coexistence of T4 gastric primaries and R+ resections suggests prudence and probably abstention from hepatectomy. Finally, a multimodal treatment associating surgery and chemotherapy offers the best survival results.

Survival prognostic factors in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy treatment: analysis from a single oncological center.

BACKGROUND: The aim of our study is to analyze survival, treatment-related morbidity, and safety in our experience of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. METHODS: Sixty-four patients were treated. Survival curves were calculated according to the Kaplan-Meier method. Univariate and multivariate analyses were done, and Cox's proportional hazard model was used to identify significant factors. RESULTS: Global 5-year overall survival was 55%. Overall survival was also evaluated according to neutrophils to lymphocytes ratio and neutrophils to platelets ratio. Overall survival according to pre-operative serum albumin level shows a difference in the two groups (P < 0.05). We observed minor or no adverse events in 53 cases (89.8%), while 3 patients (5.1%) showed a grade III-IV complication and 3 post-operative deaths (5.1%). Post-operative complication also influenced overall survival; patients in whom a minor complication occurred had a 3-year overall survival (OS) of 62% vs. a 3-year OS of 28% in patients who underwent a major complication (P < 0.1). CONCLUSIONS: Hyperthermic intraperitoneal chemotherapy (HIPEC) could be a valid and feasible option for selected patients affected by gastrointestinal malignancies' peritoneal carcinomatosis. Pre-operative parameters could be evaluated to choose patient who could benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Emergency transanal haemorrhoidal Doppler guided dearterialization for acute and persistent haemorrhoidal bleeding.

AIM: The effectiveness of Doppler guided transanal haemorrhoidal dearterialization (THD) for arresting persistent haemorrhoidal bleeding in patients admitted as an emergency was studied. METHOD: Eleven patients with severe anal bleeding underwent emergency THD as definitive treatment for haemorrhoids. In the majority of patients antiplatelet or anticoagulant therapy was ongoing and severe anaemia was present in six patients. RESULTS: The mean operative time was 39.7 min. Six to nine feeding arteries were ligated. Intra-operative blood loss was nil. Bleeding was well controlled in all patients. No blood transfusion was required. Mean pain score per verbal numeric scale was 3.6 and 1.4 on day 1 and day 3 respectively. The mean time to resumption of normal activities was 8 days. No major complications were experienced. Six months follow-up demonstrated good control of haemorrhoidal disease. CONCLUSION: THD is effective in controlling acute haemorrhoidal bleeding with a low incidence of postoperative complications.

Small bowel mesentery solitary fibrous tumor. A rare neoplasia in a young male.

Extrapleural Solitary Fibrous Tumors (SFT), in particular small bowel mesentery SFTs, are extremely rare neoplasms. We describe the case of a young male hospitalized for unspecific abdominal symptoms and evidence of a well-circumscribed mass arising from the small bowel mesentery. Histopathological and immunohistochemical analysis on the surgical specimen confirmed the diagnosis of SFT. A Pubmed search revealed only another case of small bowel mesentery SFT, confirming the extremely rarity of this tumor.

Sequential versus contemporaneous portal and arterial reperfusion during liver transplantation.

Although sequential portal and arterial revascularization (SPAr) is the most common method of graft reperfusion at liver transplantation (OLT), contemporaneous portal and hepatic artery revascularization (CPAr) has been used to reduce arterial ischemia to the bile ducts. The aim of this study was to prospectively compare SPAr (group 1; n=19) versus CPAr (group 2; n=21) among 40 consecutive OLT from heart-beating donors. There were no differences in the demographics characteristics, Model for End-stage Liver Disease scores, indication for OLT and donor parameters between the groups. OLT was performed using the piggyback technique. The biliary anastomosis was performed in all cases by a duct-to-duct technique with a T-tube in 32% versus 29% of cases without a T tube (P=.83). In the CPAr group, the liver was reperfused simultaneously via the portal vein and hepatic artery. CPAr showed a longer warm ischemia (66 ± 8 vs 37 ± 7 minutes; P<.001), while SPAr had a longer arterial ischemia 103 ± 42 vs 66 ± 8 minutes (P=.0004). Recovery of graft function was similar. There was no primary nonfunction and delayed graft function occurred among 10% versus 9%. Liver function tests were similar between the two groups up to 90 days case of follow-up- One-year graft and patient survivals were, respectively, 89% and 95% versus 94% and 100% (P=.29). At a median follow-up of 13 ± 6 versus 14 ± 7 months, biliary complications included anastomotic stenoses in 15% versus 19% (P=.78) and intrahepatic non-anastomotic biliary strictures in 26% versus none (P=.01) for SPAr and CPAr, respectively. CPAr was safe and feasible, reducing the incidence of intrahepatic biliary strictures by decreasing the duration of arterial ischemia to the intrahepatic bile ducts.

Long-term outcomes of orthotopic liver transplantation in human immunodeficiency virus-infected patients and comparison with human immunodeficiency virus-negative cases.

Human immunodeficiency virus (HIV) positivity is no longer a contraindication for orthotopic liver transplantation (OLT) due to the efficacy of antiretroviral therapy. The aim of this study was to compare OLT among HIV-positive and HIV-negative cohorts; the results were also stratified for hepatitis C virus (HCV) coinfection. Between 2004 and 2009, all HIV-infected patients undergoing OLT from heart-beating deceased donors (n=27) were compared with an HIV-negative cohort (n = 27). The pure HCV infection rate was similar between HIV-positive and HIV-negative subjects (63% each). HIV-positive recipients were younger (P=.013). The CD4 count for HIV-positive subjects was 376 ± 156 at transplantation. The mean model for end-stage liver disease (MELD) score at transplantation was 15 ± 7 in both groups (P=.92). No differences were observed for donor age (P=.72) or time on the waiting list (P=.56). The median follow-up was 26 (range, 1-64) and 27 months (range, 1-48) for HIV and non-HIV recipients, respectively (P=.85). The estimated 1-, 3-, and 5-year patient and graft survival rates were 88%, 83%, and 83% versus 100%, 73%, and 73% (P=.95), and 92%, 87%, and 87% versus 95%, 88%, and 88% (P=.59) for HIV and non-HIV cases, respectively. HIV/HCV-coinfected patients were younger, namely 47 (range, 40-53) versus 52 years (range, 37-68; P=.003), and displayed lower MELD scores at transplantation compared with HCV-mono-infected patients 10 (range, 7-19) versus 17 (range, 8-30) (P=.008). For HIV/HCV-coinfected and HCV-mono-infected cases the estimated 1-, 3-, and 5-year patients and graft survival rates were respectively 93%, 76%, and 76% versus 100%, 70%, and 60% (P=.99) and 93%, 84%, and 84% versus 100%, 70%, and 60% (P=.64), respectively. No difference was observed in the histological severity of HCV recurrence. In conclusion, under specific, well-determined conditions, OLT can be a safe, efficacious procedure in HIV patients.

Small bowel metastasis from lung cancer: a possible cause of acute abdomen. Case report and literature review.

OBJECTIVE: Lung cancer represents the leading cause of tumor death in the world with 50% of patients presenting metastatic disease at the time of diagnosis. Gastrointestinal (GI) lung cancer metastasis were thought to be extremely rare, but a much higher incidence has been noted in several autoptic reports. Clinical relevance of GI metastasis is low, but can increase with the higher number of newly diagnosed patients and with the efficacy of systemic chemotherapy in advanced stages. Prognosis of complicated GI lung cancer metastasis seems to be worse than the natural course of the disease and acute bleeding or perforation of metastatic site can be accelerated by chemotherapy. CASE REPORT: We describe the clinical case of a patient presenting with acute abdomen due to small bowel perforation from GI lung cancer metastasis. A review of the most recent published literature on GI lung cancer metastasis was performed. DISCUSSION: GI metastasis from lung cancer may occur within the clinical course of the disease and require surgical treatment followed by a poor outcome. Percentage of lung cancer patients with GI metastasis can reach level of 14%. Large cells carcinomas causing kidney and adrenal metastasis are more likely associated with GI localization of the disease. CONCLUSIONS: Complications of GI metastases, although rare, must be considered as possible cause of acute abdomen in patients with lung cancer. Identification of clinical indicators of GI metastasis may help in the therapeutic strategy.

Simultaneous surgery for obstructive coronary artery disease and ulcerated gastric cancer.

A patient with ulcerated gastric cancer causing mild anaemia and simultaneous three-vessel coronary artery disease (CAD) underwent "off pump" coronary artery bypass grafting (OP-CABG) and total D2 gastrectomy.

[Metastatic gastric cancer successfully treated with surgery and chemotherapy. Case report]. / Un caso di neoplasia gastrica metastatica trattato con successo con chirurgia e chemioterapia.

A case of long-term survivor 50-year-old man treated for advanced gastric cancer with two liver metastases is described. Patient underwent a total gastrectomy with D2 lymphadenectomy and atipic liver resection. After surgery, chemotherapy with PELF achieved a complete clinical response; six month from the fourth cycle, Ca19.9 levels slowly increased until 185 U/mL and a retro-peritoneal lymphadenopathy was detected by US. Three different chemotherapeutic combinations (FOLFOX, FOLFIRI, FOLFOX4) was administrated but two new liver recurrences spread out. From November 2007 until now, patient received 8 CDF cycles and he obtained a complete clinical response supported by persistent negativity of TC-PET scans. The radiological investigations performed after last admission in our Department for jaundice, revealed multiple liver lesions with Ca 19.9 levels of 6.766 U/mL. The patient required placement of metallic biliary endoprosthesis. He is still alive 41 month after primary surgery. We consider this case a successful example of survival increasing by integrated surgery-chemotherapy treatment but also an expression of the failure of current available therapy in the definitive cure for gastric cancer. Metastatic gastric cancer should be considered a disease treatable but not curable.