High mortality rate of oesophageal perforation is associated with delayed hospital admission : a prospective observational case series study.

BACKGROUND: To assess mortality rate of oesophageal perforation cases and study their etiology, diagnosis and management in a single specialized UK centre. PATIENTS AND METHODS: A prospective observational study was performed between January 2012 and January 2015. All consecutive patients admitted with acute iatrogenic or spontaneous esophageal perforation were included. Anastomotic leak patients were excluded. Patients were managed conservatively, endoscopically, surgically or with a combination of the above. Primary outcome was mortality rate and its association with time to hospital admission. Secondary outcomes were nature of perforation, anatomic location, type of management as well as length of hospital stay and surgical complication rate. RESULTS: There were 13 cases included. Mean patients' age was 58.3 years. Overall 90-day mortality rate was 38.4% (n=5), while 30-day mortality rate 30.8% (n=4). Admission within 24 hours of perforation was recorded in 69.2% of patients (n=9). The main anatomic location of perforation was the lower third of the esophagus in 53.8% (n=7). Operative management was adopted in 53.8% of cases (n=7). Mean hospital stay was 58.3 days. Mean follow-up was 3.1 years, while no patient developed any complication from the perforation or surgery. CONCLUSIONS: Mortality following esophageal perforation is at approximately 40%, while there is a significant impact of time of presentation on prognosis.

Epidemiology, diagnosis, and management of esophageal perforations: systematic review.

We performed a systematic review of epidemiological, diagnostic, and therapeutic outcomes of esophageal perforations. A systematic review was performed in PubMed database using the key-phrase 'esophageal perforation'. All studies regarding acute esophageal perforations were reviewed and parameters of epidemiology, diagnosis, and management published in the literature from 2005 up to 2015 were included in the study. Studies of postoperative esophageal leaks were excluded. Two researchers performed individually the research, while quality assessment was performed according to GRADE classification. Main outcomes and exposure were overall mortality, perforation-to-admission interval, anatomical position, cause, prevalent symptom at admission, diagnostic tests used, type of initial management (conservative or surgery), healing rate, and fistula complication. There were 1319 articles retrieved, of which 52 studies including 2,830 cases finally met inclusion criteria. Mean duration of study period was 15.2 years. Mean patient age was 58.4 years. Out of 52 studies included, there were 43 studies of very low or low quality included. The overall mortality rate according to extracted data was 13.3% (n = 214, 1,644 patients, 39 studies). Admission before 24 hours was reported in 58.1% of patients (n = 514). Position was thoracic in 72.6% of patients (n = 813, 1,120 patients, 20 studies). Mean cause of perforation was iatrogenic in 46.5% of patients (n = 899, 1,933 patients, 40 studies). Initial management was conservative in 51.3% of cases (n = 904, 1,762 patients, 41 studies) CT confirmed diagnosis in 38.7% of overall cases in which it was used as imaging diagnostic procedure (n = 266), X-ray in 36.6% (n = 231), and endoscopy in 37.4% (n = 343). Sepsis on admission was observed in 23.3% of cases (209 out of 898 patients, 16 studies). The present systematic review highlighted the significant proportion of cases diagnosed with delay over 24 hours, mortality rates ranging over 10% and no consensus regarding optimal therapeutic approach and optimal diagnostic management. As esophageal perforation represents a high-risk clinical condition without consensus regarding optimal management, there should be large multicenter prospective studies or Randomized Controlled Trial (RCT)s performed in order to advance diagnostic and therapeutic approach of such challenging pathology.

Pneumomediastinum Secondary to Barotrauma after Recreational Nitrous Oxide Inhalation.

We present a case of a seventeen-year-old patient, admitted in the care of the surgical team following inhalation of nitrous oxide at high pressure, leading to extensive pneumomediastinum and surgical emphysema. We discuss the subsequent investigations and management for this patient. In the absence of history of airway injury and respiratory problems including asthma and with no oesophageal perforation on investigations, the diagnostic and management challenges encountered have been discussed which will help in future management of similar cases.

Annual computed tomography scans do not improve outcomes following esophagectomy for cancer: a 10-year UK experience.

Evidence for the best approach to follow-up patients after esophagectomy for cancer is scant and conflicting, and has led to a wide variety in practice. The aim of this study was to evaluate whether our annual routine computed tomography (aCT) scan program changes outcomes. A retrospective review of 169 patients who underwent esophagectomy for cancer in our unit between 2001 and 2010 was performed. aCT scan was part of follow-up in all patients to 5 years. Minimum follow-up was 37 months. The primary outcome measure was survival. Recurrence was detected in 61 cases (36%). aCT scan diagnosed recurrence in only a minority of cases (17 cases, 28%). In the majority of patients, clinical evidence prompted an unplanned CT scan (uCT; 44 cases, 72%). There was no difference in unadjusted survival between the two groups (hazard ratio = 0.61, 95% confidence interval 0.34-1.08, P = 0.090), nor was one more likely to receive secondary oncological treatment (aCT 41% vs. uCT 44%, P = 1.000). When we adjusted survival patterns for confounding covariates, the uCT cohort showed a protective effect (hazard ratio = 0.54, 95% confidence interval 0.28-0.98, P = 0.042). These data suggest that aCT scans do not influence management or survival after esophagectomy. A consensus follow-up protocol for patients treated for esophageal cancer remains to be established.

Multidisciplinary care of gastrointestinal stromal tumour: a review and a proposal for a pre-treatment classification.

The introduction of receptor tyrosine kinase inhibitors (TKIs) has revolutionized the management of gastrointestinal stromal tumour (GIST). Strong evidence supports the use of imatinib as first-line treatment in metastatic or unresectable tumours and its efficacy in the post-operative adjuvant setting has been confirmed by phase III trials. There are a number of reports concerning the administration of imatinib in the pre-operative setting, however, the heterogeneity of the terminology used and the indications for pre-operative treatment make it difficult to determine the true value of pre-operative imatinib. Larger studies, or a phase III trial could be helpful but patient accrual and standardization of care could be difficult. We propose a pre-treatment classification of GIST in order to facilitate the comparison and collection of data from different institutions, and overcome the difficulties related to accrual. Moreover, in the current era of multidisciplinary treatment of GIST, an appropriate classification is mandatory to properly design clinical trials and plan stage-adapted treatment.

Treatment of experimental esophagogastric myotomy with bone marrow mesenchymal stem cells in a rat model.

BACKGROUND: Over the last 15 years, many studies demonstrated the myogenic regenerative potential of bone marrow mesenchymal stem cells (BM-MSC), making them an attractive tool for the regeneration of damaged tissues. In this study, we have developed an animal model of esophagogastric myotomy (MY) aimed at determining the role of autologous MSC in the regeneration of the lower esophageal sphincter (LES) after surgery. METHODS: Syngeneic BM-MSC were locally injected at the site of MY. Histological and functional analysis were performed to evaluate muscle regeneration, contractive capacity, and the presence of green fluorescent protein-positive BM-MSC (BM-MSC-GFP(+) ) in the damaged area at different time points from implantation. KEY RESULTS: Treatment with syngeneic BM-MSC improved muscle regeneration and increased contractile function of damaged LES. Transplanted BM-MSC-GFP(+) remained on site up to 30 days post injection. Immunohistochemical analysis demonstrated that MSC maintain their phenotype and no differentiation toward smooth or striated muscle was shown at any time point. CONCLUSIONS & INFERENCES: Our data support the use of autologous BM-MSC to both improve sphincter regeneration of LES and to control the gastro-esophageal reflux after MY.

Assessment of response to chemoradiation therapy in rectal cancer using MR volumetry based on diffusion-weighted data sets: a preliminary report.

PURPOSE: This study evaluated the feasibility of magnetic resonance (MR) volumetry using a diffusion-weighted data set (V(DWI)) and compared it with conventional T2-weighted volumetry (V(C)) in patients affected by rectal cancer treated with chemoradiation therapy (CHRT). MATERIALS AND METHODS: Fourteen patients with a biopsy diagnosis of rectal cancer underwent MR examination before and after CHRT. T2-weighted images were used to extrapolate V(C). A diffusion-weighted (DW) sequence was acquired [spin-echo diffusion-weighted echo-planar imaging (SE-DW-EPI)] with a b-value of 800 s/mm(2) and volume (V(DWI)) was calculated by semiautomatic segmentation of tumour hyperintensity. Two radiologists independently assessed volumes and analysed data in order to establish interobserver agreement and compare and correlate volumes to tumour regression grade (TRG), as evaluable at pathological examination of the surgical specimen. RESULTS: Interobserver agreement was 0.977 [(95% confidence interval (CI) 0.954-0.989) and 0.956 (95% CI 0.905-0.980) for V(C) and V(DWI) and 0.964 (95% CI 0.896-0.988) and 0.271 (95% CI-0.267 to 0.686) between V(C) and V(DWI) before and after CHRT. The correlation between TRG and V(C) and V(DWI) was, respectively, rho = 0.597 (p<0.05) and r(2)=0.156 (p=0.162) and rho=0.847 (p<0.001). CONCLUSIONS: V(DWI) seems to be a promising tool for assessing response to CHRT in rectal cancer. Further studies on large series of patients are needed to refine the technique and evaluate its potential predictive value.

Accuracy of transrectal ultrasound after preoperative radiochemotherapy compared to computed tomography and magnetic resonance in locally advanced rectal cancer.

INTRODUCTION: The aim of the present study was to compare the restaging results obtained by transrectal ultrasound (TRUS), computed tomography (CT), and magnetic resonance imaging (MRI) performed after preoperative chemoradiation with pathologic staging of the operative specimen. METHODS: From January 2008 to December 2009, all the consecutive patients with locally advanced rectal cancer that underwent neoadjuvant therapy at our department were evaluated. The results of diagnostic examinations and the definitive pathological examination were considered and compared. RESULTS: Thirty-seven patients were included in the study (27 males, 73%), mean age was 65.5 years (range 45­82 years). In all the patients TRUS and CT and in 20 patients MRI were performed before and after the treatment. Concerning the depth of invasion after treatment TRUS agreed with histopathology in 25/37 patients (67.5%), CT agreed in 22/ 37 cases (59.5%), and MRI in 12/20 cases (60%). Considering only neoplasia with stage T3, TRUS agreed in 23/24 cases (96%), CT in 19 cases (79%), and MRI in 10/12 cases (83.5%). Considering the tumors that did not exceed the rectal wall (T0, T1, and T2), TRUS agreed with histology in 2/13 cases (15.5%),CTin 3/13 cases (23%), andMRI 2/8 cases (25%). Concerning the presence of positive lymph nodes TRUS agreed with histology in 28/37 cases (75.5%), while CT agreed in 21/37 cases (56.5%) and MRI in 11/20 cases (55%). The concordance between the techniques was found to be low. CONCLUSIONS: Transrectal ultrasonography resulted as the most accurate method to determine neoplastic wall infiltration and lymph node involvement even after radiochemotherapy. In most cases, considering the poor correlation between the diagnostic procedures and the disagreement of the results, a restaging performed only with TRUS could be proposed, limiting the use of the other imaging methods to selected cases.

Immunohistochemical expression of p53 and Ki67 in colorectal adenomas and prediction of malignancy and development of new polyps.

The aim of this study was to investigate the immunohistochemical expression of p53 and Ki67 in colorectal adenomas in order to clarify their significance as indicators of malignancy and development of new polyps. Seventy-eight polyps were removed from 51 patients and examined. Twenty-nine patients (56.9%) had adenomas with low-grade atypia (13 of them developed new polyps at 3-year follow-up) and 22 (43.1%) had adenomas with high-grade atypia (6 of them developed new polyps at 3-year follow-up). We tested the association between p53 and Ki67 expression and various clinicopathological variables, and regression analysis was performed to identify the risk factors for malignancy and development of new adenomas. A significant correlation between the grade of atypia and p53 immunoreactivity was observed. Ki67 expression was not related to atypia and no correlation was found between p53 and Ki67 immunoreactivity. Regression analysis showed that size (p=0.0002) and p53 staining (p=0.0111) were the selected factors related to malignant transformation, whereas the number of synchronous primary polyps emerged as the only predictive factor of development of new adenomas, although without statistical significance. The expression of biological markers may be in future added to the currently examined features of polyps; however, further studies are needed to better define their predictive value.

Coagulation factor levels in non-metastatic colorectal cancer patients.

UNLABELLED: There is evidence that high plasma levels of factor (F) VIII, FIX, FXI and fibrinogen are independent risk factors for venous thromboembolism. AIM: To determine the plasma concentrations of several coagulation factors and C4b-binding protein (C4BP) in a group of patients with non-metastatic colorectal cancer in order to investigate some aspects of cancer-acquired thrombophilia. METHODS: Plasma fibrinogen, FII, FV, FVII, FVIII, FIX, FX, FXI and FXII activity levels and C4BP concentrations were determined in 73 patients with non-metastatic colorectal cancer (48 colon and 25 rectum) and in 67 matched control subjects. No one in either group had had previous thrombotic events. RESULTS: Mean plasma concentrations of fibrinogen (functional and antigen), FVIII, FIX, FV and C4BP were significantly higher in colorectal cancer patients than in control subjects, while FVII and FXII levels were significantly decreased. Several correlations were found between the increased coagulation factors and C4BP concentrations, while FVII was highly correlated with FXII. CONCLUSIONS: In colorectal cancer patients high plasma fibrinogen, FVIII and FIX levels might represent further risk factors for venous thrombotic complications in the immediate post-surgery period, while decreased FVII and FXII concentrations may be an index of intravascular coagulation activation, still in a subclinical phase.

Coagulation factor levels in non-metastatic colorectal cancer patients.

There is evidence that high plasma levels of factor (F) VIII, FIX, FXI and fibrinogen are independent risk factors for venous thromboembolism. AIM: To determine the plasma concentrations of several coagulation factors and C4b-binding protein (C4BP) in a group of patients with non-metastatic colorectal cancer in order to investigate some aspects of cancer-acquired thrombophilia. METHODS: Plasma fibrinogen, FII, FV, FVII, FVIII, FIX, FX, FXI and FXII activity levels and C4BP concentrations were determined in 73 patients with non-metastatic colorectal cancer (48 colon and 25 rectum) and in 67 matched control subjects. No one in either group had had previous thrombotic events. RESULTS: Mean plasma concentrations of fibrinogen (functional and antigen), FVIII, FIX, FV and C4BP were significantly higher in colorectal cancer patients than in control subjects, while FVII and FXII levels were significantly decreased. Several correlations were found between the increased coagulation factors and C4BP concentrations, while FVII was highly correlated with FXII. CONCLUSIONS: In colorectal cancer patients high plasma fibrinogen, FVIII and FIX levels might represent further risk factors for venous thrombotic complications in the immediate post-surgery period, while decreased FVII and FXII concentrations may be an index of intravascular coagulation activation, still in a subclinical phase.

Serum ferritin in colorectal cancer patients and its prognostic evaluation.

The aim of this study was to investigate the relationship between preoperative serum ferritin levels, clinico-pathological parameters and survival analysis of patients with colorectal cancer. Ninety-four patients (57 males) with a mean age of 65 years (39-87 years) underwent 63 curative and 31 palliative operations. Follow-up was at least 5 years. Patients were categorized with normal (30-215 ng/mL in men and 11-148 ng/mL in women), low, or high serum ferritin levels. Prognostic evaluation was undertaken with stratified survival analysis and Cox's regression model. Twenty-nine of the patients (30.9%) had raised ferritin levels and 14 (14.9%) had low values. Comparisons of the survival curves showed significant differences in stage C disease; specifically, patients with either low or high ferritin levels had a shorter survival than patients with normal levels. Patients who underwent palliative surgery and had high ferritin serum values also had a shorter survival. In multivariate analysis, the variables with a negative effect on survival were stage, serum ferritin levels and age. Our data suggest that patients with advanced colorectal cancer having normal preoperative serum ferritin levels may have a better prognosis, although the prognostic value related to this association requires further investigation.

Experimental internal anal sphincter replacement with demucosated colonic plication.

BACKGROUND: Selective re-creation of a new internal anal sphincter could be indicated when the natural one is irreversibly damaged or excised. METHODS: In this preliminary experimental work, surgical techniques of internal anal sphincter replacement in pigs were investigated. After preoperative anorectal manometry, surgical procedure was done in two phases: abdominal, mobilization of the colon-rectum to the pelvic floor; and perianal, dissection of the anal canal from the external anal sphincter through the intersphincteric space. The fully mobilized anorectal segment, including the internal anal sphincter, was pulled down through the anus and resected. The distal colonic stump was then demucosated and two types of plications of the demucosated segment were accomplished, each type in three animals. The plicated segment was then returned into the anal canal, inside the external sphincter. Short-term follow-up with clinical and manometric evaluations was performed and, subsequently, histological analysis of the plicated segment, after the animals were sacrificed. RESULTS: None of the animals became incontinent. Anal manometry identified a high-pressure zone and relaxation reflex in the new anal canal. Histologic studies showed hypertrophy of smooth muscle layers without degenerative changes. CONCLUSION: This study indicates that a plication of colonic smooth muscle wall can re-create a high-pressure zone in the anal canal after the internal anal sphincter has been excised.