Operative and non-operative management for intestinal emergencies: findings from a single-centre retrospective cohort study.

BACKGROUND: Patients with an intestinal emergency who do not have surgery are poorly characterised. This study used electronic healthcare records to provide a rapid insight into the number of patients admitted with an intestinal emergency and compare short-term outcomes for non-operative and operative management. METHODS: A single-centre retrospective cohort study was conducted at a tertiary NHS hospital (from 1 December 2013 to 31 January 2020). Patients were identified using diagnosis codes for intestinal emergencies, based on the inclusion criteria for the National Emergency Laparotomy Audit. Relevant data were extracted from electronic healthcare records (n=3,997). RESULTS: Nearly half of patients admitted with an intestinal emergency received nonoperative management (43.7%). Of those who underwent surgery, 63.7% were started laparoscopically. The non-operative group had a shorter hospital stay (median: 5.4 days vs 8.2 days [started laparoscopically] or 16.8 days [started open]) and fewer unintended intensive care admissions than the surgical group (2.4% vs 8.7% [started laparoscopically] 21.1% [started open]). However, 30-day mortality for non-operative treatment was double that for surgery (22.4% vs 10.1%). The 30-day mortality rate was found to be even higher for non-operative management (50.3%) compared with surgery (19.5%) in a sub-analysis of patients with admission National Early Warning Score ≥4 (n=683). CONCLUSION: The proportion of patients with intestinal emergencies who do not have surgery is greater than expected, and it appears that many respond well to non-operative treatment. However, 30-day mortality for non-operative management was high, and the low number of admissions to intensive care suggests that major invasive treatment was not appropriate for most in this group.

Novel predictors of mortality in emergency bowel surgery: a single-centre cohort study.

Pre-operative risk stratification is a key part of the care pathway for emergency bowel surgery, as it facilitates the identification of high-risk patients. Several novel risk scores have recently been published that are designed to identify patients who are frail or significantly unwell. They can also be calculated pre-operatively from routinely collected clinical data. This study aimed to investigate the ability of these scores to predict 30-day mortality after emergency bowel surgery. A single centre cohort study was performed using our local data from the National Emergency Laparotomy Audit database. Further data were extracted from electronic hospital records (n = 1508). The National Early Warning Score, Laboratory Decision Tree Early Warning Score and Hospital Frailty Risk Score were then calculated. The most abnormal National or Laboratory Decision Tree Early Warning Score in the 24 or 72 h before surgery was used in analysis. Individual scores were reasonable predictors of mortality (c-statistic 0.699-0.740) but all were poorly calibrated. A National Early Warning Score ≥ 4 was associated with a high overall mortality rate (> 10%). A logistic regression model was developed using age, National Early Warning Score, Laboratory Decision Tree Early Warning Score and Hospital Frailty Risk Score as predictor variables, and its performance compared with other established risk models. The model demonstrated good discrimination and calibration (c-statistic 0.827) but was marginally outperformed by the National Emergency Laparotomy Audit score (c-statistic 0.861). All other models compared performed less well (c-statistics 0.734-0.808). Pre-operative patient vital signs, blood tests and markers of frailty can be used to accurately predict the risk of 30-day mortality after emergency bowel surgery.

Outcomes of posterior component separation with transversus abdominis release (TAR) in large and other complex ventral hernias: a single-surgeon experience.

PURPOSE: Over the last years, great advances in the repair of abdominal wall hernias have dramatically improved patients' outcomes. Especially for large and other complex ventral hernias, the application of component separation techniques has been a landmark in their successful management. The aim of this study is to present our experience with the posterior component separation with transversus abdominis release (TAR) in patients with these demanding ventral hernias. METHODS: A retrospective analysis of prospectively collected data of all patients who underwent elective ventral hernia repair with TAR between January 2016 and December 2019 was performed. Preoperative, intraoperative, and postoperative data were analyzed. RESULTS: A total of 125 patients with large and other complex ventral hernias were included in the final analysis. More than 80% of patients had one or more comorbidities. Of all patients, 116 (92.8%) had a history of previous abdominal surgery, 27 (21.6%) had a history of SSI and nine (7.2%) had active fistulas. Postoperatively, SSOs were presented in 11 patients (8.8%), including three cases of SSI. Neither mesh infection occurred, nor mesh excision required. With a mean follow-up of 2.5 years, only one recurrence was observed. CONCLUSIONS: With a wound complication rate of less than 9% and a recurrence rate of less than 1%, our results show that TAR is a reliable, safe and effective technique for the repair of massive and other complex ventral hernias. The combination of knowledge of the abdominal wall anatomy at a proficient level, proper training, and adoption of a strict prehabilitation program are considered prerequisites for the successful management of such demanding hernias.

The impact of laparoscopy on emergency surgery for adhesional small bowel obstruction: prospective single centre cohort study.

INTRODUCTION: Laparoscopic adhesiolysis is increasingly being used to treat adhesional small bowel obstruction (ASBO) as it has been associated with reduced postoperative length of stay (LOS) and faster recovery. However, concerns regarding limited working space, iatrogenic bowel injury and failure to relieve the obstruction have limited its uptake. This study reports our centre's experience of adopting laparoscopy as the standard operative approach. METHODS: A single-centre prospective cohort study was performed incorporating local data from the National Emergency Laparotomy Audit Database; January 2015 to December 2019. All patients undergoing surgery for ASBO were included. Patient demographic, operative and inhospital outcomes data were compared between different surgical approaches. Linear regression analysis was performed for LOS. RESULTS: A total of 299 cases were identified. Overall, 76.3% of cases were started laparoscopically and 52.2% were completed successfully. Patients treated laparoscopically had lower Portsmouth - Physiological and Operative Severity Score for the enuMeration of Mortality and morbidity (P-POSSUM) predicted mortality (median 2.1 (interquartile range (IQR) 1.3-5.0) vs 5.7 (IQR 2.0-12.4), p=<0.001) and shorter postoperative LOS compared with open (median 4.2 days (IQR 2.5-8.2) vs 11.3 days (IQR 7.3-16.6), p=0.000). Inhospital mortality was lower in the laparoscopic group (2 vs 7 deaths, p=<0.001). In regression analysis, laparoscopic surgery was found to have the strongest association with postoperative LOS (ß -8.51 (-13.87 to -3.16) p=0.002) compared with open surgery. CONCLUSIONS: Laparoscopy is a safe and feasible approach for adhesiolysis in the majority of patients with ASBO. It is associated with reduced LOS with no impact on complications or mortality.

Bio-optical evidence for increasing Phaeocystis dominance in the Barents Sea.

Increasing contributions of prymnesiophytes such as Phaeocystis pouchetii and Emiliania huxleyi to Barents Sea (BS) phytoplankton production have been suggested based on in situ observations of phytoplankton community composition, but the scattered and discontinuous nature of these records confounds simple inference of community change or its relationship to salient environmental variables. However, provided that meaningful assessments of phytoplankton community composition can be inferred based on their optical characteristics, ocean-colour records offer a potential means to develop a synthesis between sporadic in situ observations. Existing remote-sensing algorithms to retrieve phytoplankton functional types based on chlorophyll-a (chl-a) concentration or indices of pigment packaging may, however, fail to distinguish Phaeocystis from other blooms of phytoplankton with high pigment packaging, such as diatoms. We develop a novel algorithm to distinguish major phytoplankton functional types in the BS and apply it to the MODIS-Aqua ocean-colour record, to study changes in the composition of BS phytoplankton blooms in July, between 2002 and 2018, creating time series of the spatial distribution and intensity of coccolithophore, diatom and Phaeocystis blooms. We confirm a north-eastward expansion in coccolithophore bloom distribution, identified in previous studies, and suggest an inferred increase in chl-a concentrations, reported by previous researchers, may be partly explained by increasing frequencies of Phaeocystis blooms. This article is part of the theme issue 'The changing Arctic Ocean: consequences for biological communities, biogeochemical processes and ecosystem functioning'.

Development of a bio-optical model for the Barents Sea to quantitatively link glider and satellite observations.

A bio-optical model for the Barents Sea is determined from a set of in situ observations of inherent optical properties (IOPs) and associated biogeochemical analyses. The bio-optical model provides a pathway to convert commonly measured parameters from glider-borne sensors (CTD, optical triplet sensor-chlorophyll and CDOM fluorescence, backscattering coefficients) to bulk spectral IOPs (absorption, attenuation and backscattering). IOPs derived from glider observations are subsequently used to estimate remote sensing reflectance spectra that compare well with coincident satellite observations, providing independent validation of the general applicability of the bio-optical model. Various challenges in the generation of a robust bio-optical model involving dealing with partial and limited quantity datasets and the interpretation of data from the optical triplet sensor are discussed. Establishing this quantitative link between glider-borne and satellite-borne data sources is an important step in integrating these data streams and has wide applicability for current and future integrated autonomous observation systems. This article is part of the theme issue 'The changing Arctic Ocean: consequences for biological communities, biogeochemical processes and ecosystem functioning'.

Ovarian inguinal hernia.

INTRODUCTION: Gynaecological structures such as the ovaries, fallopian tubes, ligaments and uterus are rarely encountered inside a hernial sac. The prevalence of groin hernias containing parts of female genitalia remains unknown. The aim of this review was to summarise the existing evidence on inguinal hernias containing ovaries with or without the other female adnexa. METHODS: A systematic search was conducted for literature published up to February 2018 using the MEDLINE®, Scopus® and Google Scholar™ databases along with the references of the full-text articles retrieved. Papers on observational studies and case reports concerning women who were diagnosed with an ovarian inguinal hernia (pre or intraoperatively) were considered eligible for inclusion in the review. RESULTS: Fifteen papers (13 case reports, 2 case series) comprising seventeen patients (mean age 47.9 years) were evaluated. A left-sided hernia was noted in 13 cases (77%) whereas 4 patients had a right-sided hernia. Eight patients underwent preoperative imaging with computed tomography, ultrasonography or both. This was diagnostic in five cases. In 11 patients, hernia contents were repositioned, 2 had a salpingo-oophorectomy and 2 an oophorectomy. Eight patients underwent hernia repair with mesh placement while three had a herniorrhaphy. CONCLUSIONS: Ovarian inguinal hernias should be considered among the differential diagnoses of a groin mass or swelling. In women of reproductive age, repair of the hernia with the intent to preserve fertility is of critical importance.

Contamination of the Preservation Solution in Solid Organ Transplantation.

INTRODUCTION: Preservation solutions (PS), in which grafts for patients undergoing liver transplantation are stored, represent a medium suitable for microorganism growth and a potential source for transmission of pathogenic germs to the transplant recipients. The aim of the present study was to review the relevant literature for the incidence and predictors of positive microbiological findings in the PS. PATIENTS AND METHODS: We performed a literature review of publications on bacterial and fungal contamination of PS during cold organ storage focusing on its impact on bacteremia and/or nosocomial infection of the recipient. RESULTS: Overall 19 studies were reviewed, published between the years 2000 and 2016, that encompassed a total of 5647 patients. Positive cultures were identified in 1428 patients (25%). The documentation of bacteremia showed a wide deviation with documented ranges between 0% and 69%. Data on the identification of same species or of related nosocomial infections were only sparsely available; same species were found in a rate of 0% to 8%, and nosocomial infections were attributed to them in an incidence of 0% to 19%. CONCLUSIONS: Our study underlines both the limited published data and the contradictory available information on contamination of preservation solution in solid organ transplantation, not allowing for any recommendations. The necessity for prospective, multicentric studies on this topic is mandatory.

Mixed Hepatocellular Cholangiocarcinoma: A Review of Long-Term Outcomes Following Liver Transplantation.

INTRODUCTION: Mixed hepatocellular cholangiocarcinoma (HCC-CC) represents a rare hepatic tumor, which demonstrates histological features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). HCC-CC can be an unexpected finding in patients undergoing liver transplantation (LT) for HCC. The objective of our review was to review and evaluate long-term outcomes in patients undergoing LT for mixed HCC-CC. METHODS: A meticulous MEDLINE search was performed for articles referring to long-term results in patients who underwent LT and whose final pathology revealed HCC-CC. RESULTS: A total of 7 studies, which comprised 93 patients who underwent LT and whose resected specimen revealed mixed HCC-CC, were included in our review. One-year overall survival (OS) rates ranged from 64% to 93%, 3-year OS ranged from 38% to 78%, and 5-year OS rates range from 14% to 78%. Disease-free-survival (DFS) rates at 1-year from LT ranged from 60-% to 64%, whereas both 3- and 5-year DFS rates ranged from 30% to 53.3%. CONCLUSIONS: Long-term results of LT in the setting of mixed HCC-CC are associated with fairly unfavorable overall outcomes compared to LT for other indications including HCC yet are improved compared to others such as intrahepatic CC. A stricter preoperative evaluation could potentially help identify the patients with mixed HCC-CC who are at high-risk after LT, reduce the risks of recurrence, and improve OS.

Liver Transplantation for Giant Hepatic Hemangioma: A Systematic Review.

INTRODUCTION: Despite their benign nature, liver hemangiomas (LH) are lesions that can cause major complications requiring intervention. Liver transplantation (LT) has been suggested as an effective treatment option in selected patients with giant LHs causing severe symptoms and cannot be treated otherwise. The aim of our study was to investigate the indications, aspects and post-operative outcomes of patients with a LH who underwent LT. MATERIALS AND METHODS: A meticulous search of the literature was performed. Studies presenting cases of LT due to LH were evaluated. Studies presenting patients characteristics and symptoms, aspects of the disease, transplantation indications and details were selected. RESULTS: Fifteen studies were included in the present review that involved 16 patients. Among them, 4 were male while the remaining 12 were female with a mean age of 39.9 ± 8.7 years. The main indications for LT included respiratory distress, massive hemorrhage, Kasabach-Merritt syndrome, and unsuccessful previous treatment strategies. Four patients were transplanted from living donors and the remaining 12 from cadaveric donors. No post-operative deaths were reported and all patients returned to normal activity. No deaths during the long-term follow-up were reported. CONCLUSIONS: LH is an extremely rare indication for LT. Nevertheless, the currently available data suggest that LT is a safe and efficient treatment in the management of symptomatic or complicated LH in selected patients.

Comparison Between Salvage Liver Transplantation and Repeat Liver Resection for Recurrent Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

INTRODUCTION: Repeat liver resection (RLR) has been adopted by surgeons as the first-line treatment in the case of intrahepatic recurrence of hepatocellular carcinoma (HCC), whereas salvage liver transplantation (SLT) is considered a second-line option. The aim of our study was to evaluate the results of SLT and RLR for HCC. METHODS: We searched for articles published up to December 1, 2017, in the PubMed database that compared SLT with RLR for HCC. We extracted data about patient and tumor characteristics, operative and postoperative outcomes, and survival and performed a meta-analysis. RESULTS: Patients who underwent SLT had somewhat larger liver lesions (mean difference: 0.73 cm, 95% confidence interval [CI]: 0.29-1.18, P = .001; I2: 0%, P = .82). Moreover, salvage liver transplantation resulted in higher blood loss, longer operating time, longer hospital stay, and higher postoperative morbidity (risk ratio [RR]: 2.45, 95% CI: 1.6-3.75, P < .0001; I2: 0%, P = .58) than RLR, whereas there was no significant difference in terms of postoperative mortality (RR: 6.48, 95% CI: 0.51-82.54, P = .15; I2: 61%, P = .08). On the other hand, SLT led to longer disease-free survival (DFS) than RLR (HR: 0.42, 95% CI: 0.25-0.7, P = .0009; I2: 63%, P = .03), but there was no significant difference in regard to overall survival (OS) (HR: 0.82, 95% CI: 0.55-1.23, P = .34; I2: 0%, P = .62). CONCLUSIONS: SLT seems to be inferior to RLR regarding operative and postoperative results but presents a significant advantage in terms of DFS over RLR.

Liver Transplantation for Wilson's Disease in Non-adult Patients: A Systematic Review.

INTRODUCTION: Wilson's disease (WD) is a rare autosomal recessive disorder transmitted through a gene located on chromosome 13. Liver transplantation (LT) provides a therapeutic option for patients with WD presenting fulminant liver failure or drug resistance. LT in patients with WD has a twofold aim: to save the patient's life when the disorder has progressed to hepatic (or other organ) failure and to cure the underlying metabolic defect. The aim of our study was to investigate the indications, aspects and post-operative outcomes in pediatric patients (< 18 years old) with WD who underwent LT. METHODS: A meticulous search of the literature since 1971 was performed. A retrospective analysis of all the studies, presenting cases of LT in children due to WD, was conducted. Studies that did not report patients' characteristics, transplantation indications, post-operative outcomes, and complications, as well as those with small study populations (< 10 patients), were excluded. RESULTS: Six studies were included in the present review, which involved 290 children. The main indications for LT included chronic liver failure and fulminant liver failure. The average 1-year survival rate was 91.9%, while the average 5-year survival rate was 88.2%. Retransplantation was performed in 16 patients due to transplant rejection. In general, patients transplanted for WD displayed an excellent quality of life after LT. CONCLUSION: LT is a safe and efficient procedure in selected pediatric patients with WD, demonstrating excellent long-term outcomes and quality of life.

Pregnancy Outcomes After Liver Transplantation: A Systematic Review.

PURPOSE: Liver transplantation (LT) constitutes a major therapeutic option for a number of patients suffering from liver pathologies. Pregnancy outcomes in patients who have undergone LT are assessed by a number of studies. The aim of our systematic review was to present the currently available evidence concerning the results of pregnancy in patients with LT. MATERIALS AND METHODS: A meticulous systematic search of the literature published before September 2017 for studies relevant in this field was conducted. All studies, which presented obstetric and maternal outcomes of patients with prior LT, were included. RESULTS: Nineteen studies, which comprised 1290 pregnancies in 885 female LT recipients, were reviewed. A total of 1014 live births were recorded, and the incidence of spontaneous abortions ranged from 0.5% to 33.3%. Concerning live births, a proportion of 32% of pregnancies resulted in preterm births (345 preterm births in 1079 pregnancies, range 0%-39%), and in 16% of pregnancies preeclampsia was reported (188 cases from 1173 pregnancies, range 2%-33.3%). The most commonly administered immunosuppressive drugs were cyclosporine and tacrolimus alone or with steroids. Cesarean section rates ranged from 20% to 67.9% among the included studies, concerning live birth. Moreover, approximately one-third of them resulted in preterm birth. Spontaneous abortions were reported in 176 cases (range: 0.5%-33.3%), and preeclampsia occurred in 188 patients (range: 2%-33.3%). CONCLUSION: Pregnancy outcomes from the included studies are encouraging, nonetheless pregnant patients who have undergone LT are at high risk and therefore require close monitoring by a multidisciplinary team.

Mucinous breast carcinoma with tall columnar cells.

Mucinous carcinoma of the breast represents 1%-4% of all breast cancers. The World Health Organization classification divides this type of tumour into three different subtypes: mucinous carcinoma, mucinous carcinoma with tall columnar cells (mucinous cystadenocarcinoma and columnar cell mucinous carcinoma) and signet ring cell carcinoma. A 74-year-old woman presented a tumour with inflammatory features in the upper outer quadrant of her left breast, 7 cm in diameter. The core biopsy showed infiltrating ductal carcinoma of no specific type. The tumour-node-metastasis clinical staging was T4cN3M0 (Stage IIIC). She received neoadjuvant chemotherapy, underwent left mastectomy with radical axillary resection and subsequently received radiotherapy and chemotherapy. The histological examination of the surgical specimen revealed two solid tumors in the tail of Spence, which corresponded to adenocarcinoma with high columnar cells. The patient died 16 months after the diagnosis, suffering from pulmonary metastases and anterior chest wall infiltration. A review of the literature revealed only 21 reports of mucinous carcinoma of the breast with tall columnar cells, including our case. This is only the third time that the specific histological type of columnar cell mucinous carcinoma has been reported in the literature.

Comparison Between Minimally Invasive and Open Gastrectomy for Gastric Cancer in Europe: A Systematic Review and Meta-analysis.

AIMS: We compared laparoscopic and robotic gastrectomies with open gastrectomies and with each other that were held for gastric cancer in Europe. METHODS: We searched for studies conducted in Europe and published up to 20 February 2015 in the PubMed database that compared laparoscopic or robotic with open gastrectomies for gastric cancer and with each other. RESULTS: We found 18 original studies (laparoscopic vs open: 13; robotic vs open: 3; laparoscopic vs robotic: 2). Of these, 17 were non-randomized trials and only 1 was a randomized controlled trial. Only four studies had more than 50 patients in each arm. No significant differences were detected between minimally invasive and open approaches regarding the number of retrieved lymph nodes, anastomotic leakage, duodenal stump leakage, anastomotic stenosis, postoperative bleeding, reoperation rates, and intraoperative/postoperative mortality. Nevertheless, laparoscopic procedures provided higher overall morbidity rates when compared with open ones, but robotic approaches did not differ from open ones. On the contrary, blood loss was less and hospital stay was shorter in minimally invasive than in open approaches. However, the results were controversial concerning the duration of operations when comparing minimally invasive with open gastrectomies. Additionally, laparoscopic and robotic procedures provided equivalent results regarding resection margins, duodenal stump leakage, postoperative bleeding, intraoperative/postoperative mortality, and length of hospital stay. On the contrary, robotic operations had less blood loss, but lasted longer than laparoscopic ones. Finally, there were relatively low conversion rates in laparoscopic (0%-6.7%) and robotic gastrectomies (0%-5.6%) in most studies. CONCLUSION: Laparoscopic and robotic gastrectomies may be considered alternative approaches to open gastrectomies for treating gastric cancer. Minimally invasive operations are characterized by less blood loss and shorter hospital stay than open ones. In addition, robotic procedures have less blood loss, but last longer than laparoscopic ones.

Platelet indices and netrophil to lymphocyte ratio in adults with acute appendicitis.

BACKGROUND: A study was performed in adults with acute appendicitis and matched controls to assess the utility of the platelet indices and neutrophil to lymphocyte ratio, as a diagnostic adjunct. METHOD: Data were retrospectively collected from a complete blood count test of 155 adult patients (72 men and 83 women) with histologically proven acute appendicitis upon admission, and of 50 healthy adults (20 men and 30 women). The parameters for white blood cells and platelets were compared between the two groups, and for each gender separately. RESULTS: A higher white blood cell count, neutrophil count, neutrophil percentage, neutrophil to lymphocyte ratio and lower lymphocyte percentage was reported in patients with acute appendicitis than that in the healthy controls, with high areas under the curve (AUC), sensitivities, specifi cities, positive predictive values (PPVs) and moderate negative predictive values (NPVs). The lymphocyte count was lower in patients than it was in the healthy controls. The platletcrit was lower in the female patients than that in the female controls, whereas a difference was not detected in the male participants. Differences were not detected with regard to platelet count, mean platelet volume and platelet distribution width for both genders. CONCLUSION: The neutrophil to lymphocyte ratio increases and lymphocyte percentage decreases in acute appendicitis, and can be used as an additional diagnostic marker. Plateletcrit, and therefore total platelet mass, is reduced in women with acute appendicitis, indicating the involvement of platelets in its pathophysiology. However, it is neither a reliable predictor or excluder of the disease.

Pneumocystis jirovecii pneumonia in liver transplant recipients: a systematic review.

BACKGROUND: Pneumocystis jirovecii is a fungus that causes pneumonia in immunocompromised patients, such as liver transplant recipients. METHODS: We searched the Medline database in September 2013 for articles referring to infections from P. jirovecii in liver transplant recipients, using the terms "liver transplantation" and "pneumocystis." Our search yielded 60 articles, 35 of which were used for our review. RESULTS: P. jirovecii pneumonia (PJP) has an incidence of 1%-11% in liver transplant recipients without prophylaxis and mortality rates of 7%-88%. Most cases occur within the first 7 months after transplantation. When prophylactic treatment with oral trimethoprim-sulfamethoxazole is used, its incidence is only 0%-3%. The duration of its use varies from 3 months to 1 year after the liver transplantation. CONCLUSIONS: PJP has relatively high incidence and high mortality rates in liver transplant recipients without prophylactic treatment, which diminishes or even eliminates its occurrence. Therefore, oral trimethoprim-sulfamethoxazole should be used as prophylaxis for 1 year after the liver transplantation in this population.

Meta-analysis of the predictive value of KRAS mutations in treatment response using cetuximab in colorectal cancer.

PURPOSE: The monoclonal antibody cetuximab that targets epidermal growth factor receptor (EGFR) has been found effective in the treatment of colorectal cancer. However, mutations in exons 12 and 13 of KRAS oncogene have been reported as negative predictive factors for the treatment response using cetuximab. The purpose of this study was to conduct a meta-analysis of the published studies investigating the predictive value of KRAS mutations in the efficacy of cetuximab in patients suffering from colorectal cancer. METHODS: A systematic search of the literature was performed in PubMed, Medline, and Cochrane databases. Sensitivities, specificities and predictive values (negative and positive) of KRAS mutations as regards treatment response were calculated. RESULTS: Twenty-six studies were initially found during the literature search. After thorough evaluation, 13 papers were excluded for various reasons. Therefore, 13 studies were included in the present meta-analysis. In these studies, specificities were found much higher than sensitivities. Combining the data from the 13 studies, it was found that KRAS mutations comprise a negative predictive biomarker for response to cetuximab with very high specificity (0.96; 95% CI 0.84-0.99), and low sensitivity (0.47; 95% CI 0.43-0.50). Finally, the publication bias was found statistically significant. CONCLUSION: The results of the present meta-analysis suggest that cetuximab should be administered only to patients with colorectal cancer who have the wild type (KRASw) oncogene. Mutations in the KRAS gene are a negative predictive factor for response to cetuximab with very high specificity and low sensitivity. The latter may very well be attributed to additional mechanisms of resistance to anti-EGFR therapies such as mutations in BRAF.

Synthesis, cytotoxic activity, NMR study and stereochemical effects of some new pyrano[3,2-b]thioxanthen-6-ones and pyrano[2,3-c]thioxanthen-7-ones.

Some new substituted pyrano[3,2-b]thioxanthen-6-ones and pyrano[2,3-c]thioxanthen-7-ones were prepared and their cytotoxic activity was evaluated using acronycine as the reference compound. The conformation of the molecules was also investigated in an effort to correlate this parameter with the biological activity.