Analysis of outcomes achieved with squamous cell carcinomas of the anus in a single university hospital over the last two decades: Clinical response rate, relapse and survival of 190 patients.

BACKGROUND AND OBJECTIVES: We reviewed our series of anal squamous cell carcinomas (ASCC) treated over the last two decades. METHODS: ASCC patients undergoing treatment at the Leicester Royal Infirmary between 1998 and 2016 were selected. Age, gender, pathological tumor characteristics, treatment adopted, the overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) at 5-year follow-up were recorded and calculated. RESULTS: A total of 190 ASCC were reviewed, of these 64.2% (n = 122) received primary radical chemoradiotherapy. Complete response rate was 92.6% (n = 113) and four patients with residual disease underwent a salvage APER. Twenty-eight patients experienced recurrent disease (23.0%) either systemic (n = 8), local (n = 14), or both (n = 6); six had a salvage APER. Complete follow-up data are available for 63.1% patients (77/122). Overall, the locoregional failure rate of primary chemoradiotherapy (residual + recurrent disease) was present in 29 patients (29/122; 23.8%). OS was 41.6% CSS was 69.2% and DFS 60.0% at 5 years follow-up. CONCLUSIONS: In our series of ASCC primary chemoradiotherapy had achieved significant initial complete response rates, however, long term-follow ups still present systemic and local recurrences. APR is able to treat 30% of the pelvic recurrences (6/20), the others are either associated with systemic disease or locally inoperable masses.

Rectal cancers with microscopic circumferential resection margin involvement (R1 resections): Survivals, patterns of recurrence, and prognostic factors.

BACKGROUND AND OBJECTIVES: We have reviewed our series of rectal cancer patients with circumferential resection margin involvement (R1) with particular regard to survival and prognostic factors. METHODS: R1 rectal cancer patients undergoing surgery at the Leicester Royal Infirmary between 1998 and 2008. Age, gender, radiological, and pathological tumor characteristics, neoadjuvant and adjuvant therapies were examined as prognostic factors on the overall survival (OS) and disease-free survival (DFS) at 5-year follow-up. RESULTS: A total of 885 rectal cancers were reviewed. Six hundred ninety-nine patients underwent a mesorectal excision and 71 of them were R1 resections (12.9%). OS was 43.7% (CI95% 33.5-53.8%; median survival 39 months). DFS was 57.4% (CI95% 43.0-71.8%; median survival 31 months). Pelvic recurrence rate occurred in 16 patients (26.2%, CI95% 16.5-36.0%), systemic recurrence rate in 23 patients (37.7%, CI95% 25.5-49.9%). At Cox-regression LNR and adjuvant chemotherapy were associated with both OS and DFS. No significant association was found between OS or DFS and adjuvant radiotherapy. CONCLUSIONS: In our series of R1 patients, the rates of local recurrence and OS at 5 years were 26.2% and 43.7%, respectively. Factors influencing systemic recurrences (LNR, adjuvant chemotherapy) are more associated with OS and DFS than those potentially affecting locoregional recurrences (adjuvant radiotherapy). J. Surg. Oncol. 2016;114:642-648. © 2016 Wiley Periodicals, Inc.

Circumferential resection margins and perineal complications after neoadjuvant long-course chemoradiotherapy followed by extralevator abdominoperineal excision of the rectum: Five years of activity at a single institution.

BACKGROUND: Prone extralevator abdominoperineal excision of the rectum (ELAPE) has been introduced to improve the circumferential resection margins (CRM) compared with traditional APER. OBJECTIVE: We present short-term results achieved with prone ELAPE preceded by neoadjuvant chemoradiotherapy during the last 5 years of activity. DESIGN: A retrospective review was conducted. SETTINGS AND PATIENTS: Prone ELAPE operations performed between September 2010 and August 2014 at Leicester Royal Infirmary preceded by neoadjuvant chemoradiotherapy. INTERVENTIONS AND MAIN OUTCOME MEASURES: Data regarding demographics, staging, neoadjuvant therapies, intraoperative perforations, and perineal complications were collected. RESULTS: Seventy-two patients were included. Pretreatment radiological T4 were 25.0%, histological T4 2.8%. Intraoperative perforations occurred in 2.8%, CRM was involved in 11.1%. Perineal complications consisted of superficial wound infections (20.8%), full thickness dehiscences (16.7%), hematomas (9.7%), pelvic collections (6.9%), and perineal hernias (5.6%). CONCLUSIONS: In our experience, prone ELAPE preceded by long-course chemoradiotherapy has been successfully used in the last 5 years to resect low rectal tumors. Perineal wound complications rates are similar to those presented in series using direct perineal closures. J. Surg. Oncol. 2016;114:86-90. © 2016 Wiley Periodicals, Inc.

Lymph node retrieval for colorectal cancer: Estimation of the minimum resection length to achieve at least 12 lymph nodes for the pathological analysis.

INTRODUCTION: Adequate lymph node retrieval is important in colorectal cancer staging for the selection of patients that necessitate adjuvant treatments. The minimum number of 12 lymph nodes is one of the premises and is dependent, among the other factors, from the length of bowel resected. We have reviewed our specimens to identify the high-risk operations for inadequate nodal sampling and estimate the minimum length of bowel needed to resect to achieve this purpose. MATERIALS AND METHODS: A retrospective review of colorectal specimens over 10 years of activity looking at data including location of the tumor, type of operation performed, length of bowel resected and number of lymph nodes retrieved. RESULTS: Abdominoperineal and Hartmann's resections produced significant lower adequate retrievals compared to other colorectal operations, corresponding to 45.4% and 59.1% of cases respectively. The measured average length of bowel was 30 cm and 25 cm respectively, increasing the length to 36 cm and 42 cm would increase the adequacy rate to 90%. CONCLUSIONS: Abdominoperineal and Hartmann's resections are, in our series, high-risk operations that frequently do not produce the minimum number of lymph nodes necessary. These operations may require additional maneuvers such as mobilization of the splenic flexure to achieve the minimum length of bowel to resect.

The "kidney-liver" multiorgan ex vivo perfused model improves the circuit's biochemical milieu during perfusion compared to the "liver-kidney" counterpart.

The multiorgan ex vivo perfused liver-kidney model allows studying the hepatic pathophysiology and purifying waste products. We tested if the addition of the kidney first followed by the liver (KL circuit) produces better results compared to the classic liver-first approach (LK). Intact livers and kidneys were obtained post mortem from ten female domestic white pigs, five experiments were conducted with the KL circuit and five with the LK. Bile, urine production, arterial blood gases, glucose, renal and liver tests were collected hourly during the perfusions. The KL circuit had values more close to physiological ranges, more stable over time and showed less variability compared to the LK circuit for urine production, glucose, PH, anion gap, lactate, urea, sodium, potassium and Alanine Transaminase (ANOVA test for repeated measures p < 0.05). The KL circuit produced a more physiological and reliable biochemical milieu.

Subtotal cholecystectomy for "difficult gallbladders": systematic review and meta-analysis.

IMPORTANCE: Subtotal cholecystectomy (SC) is a procedure that removes portions of the gallbladder when structures of the Calot triangle cannot be safely identified in "difficult gallbladders." OBJECTIVE: To conduct a systematic review and meta-analysis to evaluate current studies and present an evidence-based assessment of the outcomes for the techniques available for SC. DATA SOURCES: A literature search of the PubMed/MEDLINE (1954 to November 2013) and EMBASE (1974 to November 2013) databases was conducted. Search criteria included the words subtotal, partial, insufficient or incomplete, and cholecystectomy. STUDY SELECTION: Inclusion criteria were all randomized, nonrandomized, and retrospective studies with data on SC techniques and outcomes. Exclusion criteria were studies that reported data on SC along with other interventions (eg, cholecystostomy) without the possibility to discriminate results specific to SC. DATA EXTRACTION AND SYNTHESIS: This systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. MAIN OUTCOMES AND MEASURES: The primary outcome of the study was the occurrence of common bild duct injury. Secondary outcomes included the occurrence of other SC-related morbidities, such as hemorrhage, subhepatic collection, bile leak, retained stones, postoperative endoscopic retrograde cholangiopancreatography, wound infection, reoperation, and mortality. RESULTS: Thirty articles were included. Subtotal cholecystectomy was typically performed using the laparoscopic technique (72.9%), followed by the open (19.0%) and laparoscopic converted to open (8.0%) techniques. The most common indications were severe cholecystitis (72.1%), followed by cholelithiasis in liver cirrhosis and portal hypertension (18.2%) and empyema or perforated gallbladder (6.1%). Morbidity rates were relatively low (postoperative hemorrhage, 0.3%; subhepatic collections, 2.9%; bile duct injury, 0.08%; and retained stones, 3.1%); the rate for bile leaks was higher (18.0%). Reoperations were necessary in 1.8% of the cases; the 30-day mortality rate was 0.4%. The laparoscopic approach produced less risk of subhepatic collection (odds ratio [OR], 0.4; 95% CI, 0.2-0.9), retained stones (OR, 0.5; 95% CI, 0.3-0.9), wound infection (OR, 0.07; 95% CI, 0.04-0.2), reoperation (OR, 0.5; 95% CI, 0.3-0.9), and mortality (OR, 0.2; 95% CI, 0.05-0.9) but more bile leaks (OR, 5.3; 95% CI, 3.9-7.2) compared with the open approach. CONCLUSIONS AND RELEVANCE: Subtotal cholecystectomy is an important tool for use in difficult gallbladders and achieves morbidity rates comparable to those reported for total cholecystectomy in simple cases. The various technical differences appear to influence outcomes only for the laparoscopic approach.

Case report of mannose-binding lectin (MBL) deficiency and postoperative sepsis and coagulopathy in a patient following total pancreatectomy for chronic pancreatitis.

CONTEXT: Complement plays a central role against infection and coordinates the activity of coagulation and fibrinolysis. In this report we present a patient that underwent total pancreatectomy experienced sepsis, coagulopathy and bleeding that endangered the postoperative course. CASE REPORT: A sixty-five-year-old woman underwent total pancreatectomy for intractable pain without islet transplant, this patient was diagnosed as AP and MBL deficient from a blood test performed preoperatively. On the postoperative course she experienced severe haemorrhages and sepsis for 3 weeks postoperatively. An analysis of serial perioperative serum samples conducted which showed further depletion of the alternate and MBL complement pathway without restoration to baseline levels. CONCLUSION: This is the first reported case of alternative and mannose-binding lectin pathways depletion associated with major postoperative bleeding and sepsis following pancreatic surgery. Future research should examine the relationship between complement pathways activity and postoperative complications in order to possibly introduce it as a preoperative screening and possible replacement therapy prior to any major surgical intervention.

Routine versus selective histologic analysis of gallbladder specimens for the detection of incidental gallbladder cancers. A retrospective review over 9 years of activity with a special focus on patients' age.

BACKGROUND: Incidental gallbladder cancer (IGC) is an infrequent possibility in patients undergoing cholecystectomies. Routine histologic examination of all gallbladder specimens is the current approach to detect this disease. Our study presents the influence of age to perform a selective histologic analysis. METHODS: A retrospective review was conducted of all gallbladder specimens during the last 9 years in our hospital. The medical notes were retrieved for cases of IGC or dysplasia and perioperative data were collected. RESULTS: A total of 3,330 cholecystectomies were conducted over the study period, 3,041 for gallstone disease. Twelve patients were found with dysplasia and 13 patients with IGC, all of them occurred in gallbladders removed for gallstone diseases. There were 18 men with a median age of 65 years (range 18 to 85). Median age for cancer patients was 70 years (range 51 to 85) and 54 years for dysplasia (range 18 to 75). No patient below the age of 51 years (n = 1,464) experienced IGCs. CONCLUSION: Age should be considered as an additional factor for a selective approach to the histologic analysis of all gallbladder specimens following cholecystectomies.

A case of recurrent mesocolon myxoid liposarcoma and review of the literature.

Background. Liposarcoma is the second most common soft tissue sarcoma affecting predominantly the retroperitoneal space and extremities. Mesenteric liposarcoma is uncommon and occurs in the small bowel mesentery. In this paper we report the case of a recurrent mesocolon myxoid liposarcoma manifesting 6 years from the initial right hemicolectomy for the primary tumour. Case Report. A 41-year-old female presented with a 4-day history of signs and symptoms indicative of small bowel obstruction, subsequently confirmed on plain abdominal X-ray. In 2006 she underwent a right hemicolectomy for a myxoid liposarcoma of the mesentery. The patient was initially managed conservatively; however she showed no signs of improvement and was taken to theatre for an exploratory laparotomy and division of adhesional bands. During this procedure an incidental finding of a dark purple, smooth pelvic mass was identified with similar macroscopic appearance to that of splenic tissue. Histological examination revealed a recurrent mesocolon myxoid liposarcoma. Conclusion. Mesocolon myxoid liposarcoma is a rare soft tissue neoplastic pathology and carries a high risk of recurrence. Therefore, a symptomatic patient with a previous history of primary liposarcoma excision should be treated with a high index of suspicion and a longer period of followup should be considered.

Medical influences, surgical outcomes: role of common medications on the risk of perforation from untreated diverticular disease.

Numerous drugs, largely used in the wards or at home, have a significant influence on patients with untreated diverticular disease. The consequences can be disastrous, may require an emergency operation, postoperative intensive care, and overall influence the patient's length of stay and the final outcomes. Bearing these considerations in mind the routine or chronic administration of pain-killers, steroids and non-steroidal anti-inflammatory should be balanced in patients with known diverticular disease as it normally happens with other conditions potentially affected by these drugs (i.e., peptic ulcer disease or chronic obstructive pulmonary disease). This is even more important in the old and frail patient where an eventual surgical treatment may not always be possible.

Contrast-enhanced ultrasound detects perfusion defects in an ex vivo porcine liver model: a useful tool for the study of hepatic reperfusion.

Following transplantation, areas of hypoperfusion can be associated with metabolic changes and poor organ recovery. Our study evaluated contrast-enhanced ultrasound (CEUS) agents for the detection of such areas. Livers were collected from ten pigs, connected to extracorporeal circuits and perfused using autologous blood. After 1 and 4 h livers were scanned with an ultrasound machine following the administration of CEUS agents. Biopsies from perfused and non-perfused areas were collected. The entire parenchyma enhanced strongly on non-contrast ultrasound at 1 h with no perfusion defects. Four hours later multiple perfusion defects manifested not evident with non-contrast ultrasound. Histology confirmed non-perfused areas corresponded to ischemic zones. In our model the addition of CEUS revealed perfusion defects after 4 h. This might facilitate detection and characterization of perfusion defects in transplanted livers.

Contrast-enhanced ultrasound in the preoperative, intraoperative and postoperative assessment of liver lesions.

The use of contrast agents (CA) with liver ultrasound (US) has gained recently an established role for the diagnosis of various hepatic diseases due to their safety, high versatility and low costs (contrast-enhanced ultrasound: CEUS). The purpose of this review is to provide a state-of-the-art summary of the available evidence for their use in the characterization of focal liver lesions. A published work search was conducted for all preclinical and clinical studies involving CA on hepatic US imaging. CEUS increases the sensitivity for lesion detection and the specificity to differentiate between benign and malignant diseases due to the enhanced visualization of the tumor microcirculation. Results achieved seem at least equivalent to those of spiral computed tomography or magnetic resonance imaging. The association of CA with intraoperative ultrasound has changed the surgical approach in 25% of patients and guarantees complete ablations by a single session in most of them. CEUS provides detailed information about tumor vasculature, improves the preoperative characterization and therefore the therapeutic strategy, and can evaluate the intraoperative completeness of the ablation.

A systematic review on low-cost box models to achieve basic and advanced laparoscopic skills during modern surgical training.

INTRODUCTION: Low-cost box models (BMs) are a valuable tool alternative to virtual-reality simulators. We aim to provide surgical trainees with a description of most common BMs and to present their validity to achieve basic and advanced laparoscopic skills. MATERIALS AND METHODS: A literature search was undertaken for all studies focusing on BMs, excluded were those presenting data on virtual-reality simulators only. Databases were screened up to December 2011. RESULTS: Numerous studies focused on various BMs to improve generic tasks (ie, instrument navigation, coordination, and cutting). Only fewer articles described models specific for peculiar operations. All studies showed a significant improvement of basic laparoscopic skills after training with BMs. Furthermore, their low costs make them easily available to most surgical trainees. CONCLUSIONS: BMs should be developed by all surgical trainees during their training. Fields for future improvement regard endoscopy and complex laparoscopic operations for which ad hoc BMs are not available.

The development of a multiorgan ex vivo perfused model: results with the porcine liver-kidney circuit over 24 hours.

We already developed an ex vivo liver-kidney model perfused for 6 h in which the kidney acted as a homeostatic organ to improve the circuit milieu compared to liver alone. In the current study, we extended the multiorgan perfusions to 24 h to evaluate the results and eventual pitfalls manifesting with longer durations. Five livers and kidneys were harvested from female pigs and perfused over 24 h. The extracorporeal circuit included a centrifugal pump, heat exchanger, and oxygenator. The primary end point of the study was the evaluation of the organ functions as gathered from biochemical and acid-base parameters. In the combined liver-kidney circuit, the organs survived and maintained an acceptable homeostasis for different lengths of time, longer for the liver (up to 19-23 h of perfusions) than the kidney (9-13 h of perfusions). Furthermore, glucose and creatinine values decreased significantly over time (from the 5th and 9th hour of perfusion onward). The addition of a kidney to the perfusion circuit improved the biochemical environment by removing excess products from ongoing metabolic processes. The consequence is a more physiological milieu that could improve results from future experimental studies. However, it is likely that long perfusions require some nutritional support over the hours to maintain the organ's vitality and functionality throughout the experiments.

History, ethics, advantages and limitations of experimental models for hepatic ablation.

Numerous techniques developed in medicine require careful evaluation to determine their indications, limitations and potential side effects prior to their clinical use. At present this generally involves the use of animal models which is undesirable from an ethical standpoint, requires complex and time-consuming authorization, and is very expensive. This process is exemplified in the development of hepatic ablation techniques, starting experiments on explanted livers and progressing to safety and efficacy studies in living animals prior to clinical studies. The two main approaches used are ex vivo isolated non-perfused liver models and in vivo animal models. Ex vivo non perfused models are less expensive, easier to obtain but not suitable to study the heat sink effect or experiments requiring several hours. In vivo animal models closely resemble clinical subjects but often are expensive and have small sample sizes due to ethical guidelines. Isolated perfused ex vivo liver models have been used to study drug toxicity, liver failure, organ transplantation and hepatic ablation and combine advantages of both previous models.

Histological changes during extracorporeal perfusions of the porcine liver: implications for temporary support during acute liver failures.

Ex vivo perfused porcine livers have been used for temporary support during acute liver failure. The aim of this study was to assess both the histological changes and temporal pattern of the changes that occur during extracorporeal liver perfusions and to correlate these with factors that may influence them. Five porcine livers were harvested, preserved in cold ice and reperfused for 6 h in an extracorporeal circuit using autologous normothermic blood. Tissue biopsies were collected hourly. The Ishak score was used to quantify hepatic necrosis, and immunohistochemistry was used to evaluate apoptosis and regeneration. Liver weight, perfusion parameters, arterial blood gases and blood samples were also collected. The Ishak score peaked immediately before and 4 h after the start of reperfusion. Scattered necrosis, microvesicular steatotic vacuolization, sinusoidal dilatation and red cell extravasation were present. Anion gap acidosis was associated with the Ishak score. An inverse correlation was present between liver regeneration and necrosis, and between liver weight and regeneration. No changes were observed for apoptosis. Among the inflammatory cytokines evaluated, interleukin-6 and -8 levels increased significantly during the perfusions. Hepatic necrosis was always present during the extracorporeal perfusions, followed a definite pattern and was inversely correlated with regeneration. Apoptosis did not increase over baseline levels. The meaning of these findings and their correlation with clinical outcomes during acute hepatic failures deserve further investigation.