Is Metformin Associated With Improved Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer?

BACKGROUND: Efforts to determine whether metformin can increase the effectiveness of neoadjuvant chemoradiotherapy in rectal cancer have increased in recent years. However, retrospective studies have yielded inconclusive results. OBJECTIVES: The aim of this study was to compare oncological outcomes and survival after neoadjuvant chemoradiotherapy in patients with rectal cancer taking metformin versus in those not taking metformin. METHODS: This study analyzed 423 consecutive patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy and curative surgery between January 2010 and May 2020; of these, 59 were taking metformin and 364 were not taking metformin. RESULTS: Patients taking metformin had a lower proportion of tumor regression (6.8% versus 22.0%, P = 0.012) as well as a lower proportion of patients achieving a pathological complete response (6.8% versus 20.6%, P = 0.011). In the multivariate analysis, independent predictors of pathologic complete response were not taking metformin (OR: 5.26, 95% CI: 1.12-24.85, P= 0.035) and cT2 stage (OR: 3.49, 95% CI: 1.10-11.07, P= 0.034); the interval was also an independent predictor of tumor regression (OR: 1.78, 95% CI: 1.06-2.96, P= 0.028). No differences were observed in survival between groups. CONCLUSION: Metformin was not associated with better tumor responses or survival after neoadjuvant treatment.

Risk factors for suboptimal laparoscopic surgery in rectal cancer patients.

PURPOSE: Laparoscopic surgery for rectal cancer is technically complex. This study aimed to identify risk factors for suboptimal laparoscopic surgery (involved margins, incomplete mesorectal excision, and/or conversion to open surgery) in patients with rectal cancer. METHODS: We included patients undergoing laparoscopic anterior resection for rectal cancer between June 2009 and June 2018. We defined the outcome variable suboptimal laparoscopic surgery as conversion to open surgery or inadequate histopathological specimens (margins < 1 mm or involved and/or poor-quality mesorectal excision). To identify independent predictors of suboptimal laparoscopic surgery, we analyzed 15 prospectively recorded demographic, clinical, and anthropometric variables obtained from our rectal cancer unit's database. Subanalyses examined the same variables with respect to conversion and to inadequate histopathological specimens. RESULTS: Of the 323 patients included, 91 (28.2%) had suboptimal laparoscopic surgery. In the multivariate analysis, the independent factors associated with all suboptimal laparoscopic surgery were tumor location ≤ 5 cm from the anal verge (OR = 2.95, 0.95% CI 1.32-6.60; p = 0.008) and the intertuberous distance (OR = 0.79, 0.95% CI 0.65-0.96; p = 0.019). In the subanalyses, the promontorium-retropubic axis was an independent predictor of conversion (OR 0.70, 0.95% CI 0.51-0.96; p = 0.026), and tumor location ≤ 5 cm from the anal verge (OR 3.71, 0.95% 1.51-9.15; p = 0.004) was an independent predictor of inadequate histopathological specimens. CONCLUSIONS: Predictive factors for suboptimal laparoscopic anterior resection for rectal cancer were tumor location and the intertuberous distance. These results could help surgeons decide whether to use other surgical approaches in complex cases. TRIAL REGISTRATION: The study was registered at Clinicaltrials.org (No. NCT03107650).

Comparison of Outcomes between Obese and Nonobese Patients in Laparoscopic Adrenalectomy: A Cohort Study.

INTRODUCTION: Obesity is usually considered a risk factor for surgical complications. Laparoscopic adrenalectomy has replaced open adrenalectomy as the standard operation for adrenal tumors. OBJECTIVE: To compare the safety of laparoscopic adrenalectomy to treat adrenal tumors in obese versus nonobese patients. METHODS: This observational cohort study analyzed consecutive patients who underwent laparoscopic adrenalectomy with a lateral transperitoneal approach at a single center (2003-2020). Data and outcomes of obese (body mass index ≥30 kg/m2) and nonobese patients were compared. To analyze the association between operative time and other variables, we used simple and multivariate linear regression. RESULTS: N = 160 (90 obese/70 nonobese) patients underwent laparoscopic adrenalectomy. Cushing syndrome and pheochromocytoma were the most frequent indications. Obese patients were older (58 vs. 52 years, p < 0.001). A greater proportion of obese patients were ASA grade III + IV (71.1 vs. 48.6%, p = 0.004). Obesity was associated with a longer operative time (72.5 vs. 60 min, p < 0.001) and greater blood loss (40 vs. 20 mL, p = 0.022). There were no differences in conversion, morbidity, or hospital stay. After adjustment for confounding factors, operative time was positively correlated with BMI ≥30 kg/m2, learning curve, estimated blood loss, 2D laparoscopy, and specimen size. CONCLUSION: Lateral transperitoneal laparoscopic adrenalectomy is safe in patients with a BMI 30-35 kg/m2, so these patients also benefit from this minimally invasive surgery.

[Impact of SARS-COV-2 pandemic on elective and emergency surgery in a university hospital]. / Estudio del impacto de la pandemia por SARS-CoV-2 en la práctica quirúrgica urgente y electiva en un hospital de tercer nivel.

Introduction: SARS-CoV-2 pandemic has caused an important impact in our country and elective surgery has been postponed in most cases. There's not known information about the decreasing and impact on surgery. Mortality of surgical patients with SARS-CoV-2 infection is estimated to be around 20%. Methods: We conducted prospective data recruitment of people inpatient in our Digestive and General Surgery section of Girona's University Hospital Dr. Josep Trueta from 03/14 to 05/11. Our objective is to analyze the impact that SARS-CoV-2 pandemic over elective and urgent surgery. Results: During the peak occupation of our center Intensive Care Unit (303.8%) there was a reduction on elective (93.8%) and urgent (72.7%) surgery. Mortality of patients with SARS-CoV-2 infection who underwent surgery (n = 10) is estimated to be a 10%. An 80% of these patients suffer complications (sever complications in 30%). Conclusions: The actual study shows a global reduction of the surgical activity (elective and urgent) during de SARS-CoV-2 pandemic. Global mortality of patients with SARS-CoV-2 infection are low, but the severe complications have been over the usual.

Three-dimensional (3D) system versus two-dimensional (2D) system for laparoscopic resection of adrenal tumors: a case-control study.

PURPOSE: Laparoscopy is the standard technique for resecting adrenal tumors worldwide. The main drawbacks of conventional 2D laparoscopy are limited depth perception and tactile feedback. Currently available high-quality 3D laparoscopy systems might improve surgical outcomes for adrenalectomy. We compare the safety and efficacy of 3D versus 2D laparoscopy in the treatment of adrenal tumors. METHODS: This case-control study analyzed prospectively collected data from patients with benign or malignant adrenal tumors treated laparoscopically at a single academic medical center between April 2003 and March 2020. We collected demographic, diagnostic, preoperative, and operative variables, and used multiple linear and logistic regression to analyze differences in various short-term outcomes between the two approaches while adjusting for potential confounders. RESULTS: We included 150 patients: 128 with benign tumors and 22 with malignant tumors; 95 treated with 3D laparoscopy (case group); and 55 with 2D laparoscopy (control group). After adjustment for patient, surgical, and tumor characteristics, a 2D vision was associated with a longer operative time (ß = 0.26, p = 0.002) and greater blood loss (ß = 0.20, p = 0.047). There was no significant difference in rates of conversion to open surgery (odds ratio [OR] = 1.47 (95% CI 0.90-22.31); p = 0.549) or complications (3.6% vs. 2.1%; p = 0.624). CONCLUSIONS: With experienced surgeons, laparoscopic adrenalectomy was safer and more feasible with the 3D system than with the 2D system, resulting in less operative blood loss and shorter operative time with no differences in rates of conversion to open surgery or postoperative complications. For adrenal tumors, 3D laparoscopy offers advantages over 2D laparoscopy.

Challenges and Learning Curves in Adopting TaTME and Robotic Surgery for Rectal Cancer: A Cusum Analysis.

New techniques are being developed to improve the results of laparoscopic surgery for rectal cancer. This paper analyzes the learning curves for transanal total mesorectal excision (taTME) and robot-assisted surgery in our colorectal surgery department. We analyzed retrospectively data from patients undergoing curative and elective surgery for rectal cancer ≤12 cm from the anal verge. We excluded extended surgeries. We used cumulative sum (CUSUM) curve analysis to identify inflection points. Between 2015 and 2021, 588 patients underwent surgery for rectal cancer at our center: 67 taTME and 79 robot-assisted surgeries. To overcome the operative time learning curve, 14 cases were needed for taTME and 53 for robot-assisted surgery. The morbidity rate started to decrease after the 17th case in taTME and after the 49th case in robot-assisted surgery, but it is much less abrupt in robot-assisted group. During the initial learning phase, the rate of anastomotic leakage was higher in taTME (35.7% vs. 5.7%). Two Urological lesions occurred in taTME but not in robot-assisted surgery. The conversion rate was higher in robot-assisted surgery (1.5% vs. 10.1%). Incorporating new techniques is complex and entails a transition period. In our experience, taTME involved a higher rate of serious complications than robot-assisted surgery during initial learning period but required a shorter learning curve.

Impact of SARS-COV-2 pandemic on elective and emergency surgery in a university hospital. / Estudio del impacto de la pandemia por SARS-CoV-2 en la práctica quirúrgica urgente y electiva en un hospital de tercer nivel.

INTRODUCTION: SARS-CoV-2 pandemic has caused an important impact in our country and elective surgery has been postponed in most cases. There's not known information about the decreasing and impact on surgery. Mortality of surgical patients with SARS-CoV-2 infection is estimated to be around 20%. METHODS: We conducted prospective data recruitment of people inpatient in our Digestive and General Surgery section of Girona's University Hospital Dr. Josep Trueta from 03/14 to 05/11. Our objective is to analyze the impact that SARS-CoV-2 pandemic over elective and urgent surgery. RESULTS: During the peak occupation of our center Intensive Care Unit (303.8%) there was a reduction on elective (93.8%) and urgent (72.7%) surgery. Mortality of patients with SARS-CoV-2 infection who underwent surgery (n=10) is estimated to be a 10%. An 80% of these patients suffer complications (sever complications in 30%). CONCLUSIONS: The actual study shows a global reduction of the surgical activity (elective and urgent) during de SARS-CoV-2 pandemic. Global mortality of patients with SARS-CoV-2 infection are low, but the severe complications have been over the usual.

Factors associated with prolonged hospital stay after laparoscopic adrenalectomy.

Laparoscopy is the standard technique for resecting adrenal tumors, but short-term outcomes such as length of stay (LOS) vary widely between centers. We aimed to identify factors associated with LOS after lateral transperitoneal laparoscopic adrenalectomy (LTLA). We analyzed consecutive patients undergoing unilateral LTLA between April 2003 and April 2020. Prolonged LOS was defined as a stay longer than the 75th percentile of the overall cohort. To identify potential factors associated with prolonged LOS, we compared collected data from patients with LOS ≤ 2 days versus LOS > 2 days and elaborated multivariate logistic regression models. We included 150 patients (73 men and 77 women, median age 54 years), with benign (n = 128) and malignant tumors (n = 22). The median LOS after LTLA was 2 days; 64 (42.7%) patients had prolonged hospitalization. Variables significantly associated with prolonged LOS in the univariate analysis included ASA III + IV (p = 0.016), pheochromocytoma (p < 0.001), learning curve (p = 0.032), surgery on Thursday or Friday (p < 0.001), 2D laparoscopy (p = 0.003), operative time (p < 0.001), estimated blood loss (p < 0.001), drainage (p < 0.001), specimen size (p = 0.011), conversions (p = 0.002), complications (p = 0.019), and hospital stay (p < 0.001). After adjustment for patient, surgical, and tumor characteristics, risk factors associated with prolonged LOS in the multivariate analysis were specimen size > 9 cm (OR:13.03, p = 0.005), surgery on Thursday or Friday (OR:6.92, p = 0.001), estimated blood loss ≥ 60 ml (OR:6.22, p = 0.021), and drainage (OR:5.29, p = 0.005). Prolonged length of stay after LTLA was associated with specimen size > 9 cm, operating on Thursday or Friday, estimated blood loss ≥ 60 mL, and drainage.

Randomized clinical trial comparing side to end vs end to end techniques for colorectal anastomosis.

BACKGROUND: Low anterior resection syndrome affects 60%-90% of patients with anastomoses after colorectal resection. Consensus regarding the best anastomosis is lacking. OBJECTIVE: To compare outcomes after end-to-end versus side-to-end anastomoses. DESIGN: Randomized clinical trial. SETTINGS: University hospital (April 2016-October 2017). PATIENTS: Patients aged ≥18 years with rectal or sigmoid adenocarcinoma. INTERVENTIONS: Patients were randomized to undergo mechanical end-to-end or side-to-end (n = 33) anastomosis after laparoscopic resection. MAIN OUTCOME MEASURES: Primary outcome was to assess intestinal function (COREFO and LARS questionnaires) 12 months after surgery or ileostomy closure. Secondary outcomes were postoperative complications and intestinal function and quality of life (SF-36® questionnaire) at different time points after surgery or ileostomy closure. RESULTS: No significant differences in intestinal function were observed between the two groups 12 months after surgery. Subanalysis of low-mid rectum tumors with end-to-end anastomosis yielded better function at 12 months. Postoperative complications did not differ between the two groups (p = 0.070), but reinterventions were more common in the side-to-end group (p = 0.040). Multivariate analysis found neoadjuvant treatment was independently associated with intestinal dysfunction at 12 months (ß = 0.41, p = 0.033, COREFO; ß = 0.41, p = 0.024, LARS). CONCLUSIONS: End-to-end anastomosis yielded low rates of severe complications and reintervention, as well as better intestinal function at 12 months in the subgroup with tumors in the low-mid rectum. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02746224.

Delaying surgery by more than 10 weeks after long-course neoadjuvant radiotherapy in locally advanced rectal cancer patients improves pathologic complete response.

BACKGROUND: We currently do not know the optimal time interval between the end of chemoradiotherapy and surgery. Longer intervals have been associated with a higher pathological response rate, worse pathological outcomes and more morbidity. The aim of this study was to evaluate the effect and safety of the current trend of increasing time interval between the end of chemoradiotherapy and surgery (< 10 weeks vs. ≥ 10 weeks) on postoperative morbidity and pathological outcomes. This study analyzed 232 consecutive patients with locally advanced rectal cancer treated with long-course neoadjuvant chemoradiotherapy from January 2012 to August 2018. 125 patients underwent surgery before 10 weeks from the end of chemoradiotherapy (Group 1) and 107 patients underwent surgery after 10 or more weeks after the end of chemoradiotherapy (Group 2). Results have shown that wait for ≥ 10 weeks did not compromise surgical safety. Pathological complete response and tumor stage was statistically significant among groups. The effect of wait for ≥ 10 weeks before surgery shown higher tumor regression than the first group (Group 1, 12.8% vs Group 2, 31.8%; p < 0.001). On multivariate analysis, wait for ≥ 10 weeks was associated with pathological compete response. Patients from the second group were four time more likely to achieve pathologic complete response than patients from the first group (OR, 4.27 95%CI 1.60-11.40; p = 0.004). Patients who undergo surgery after ≥ 10 weeks of the end of chemoradiotherapy are four time more likely to achieve complete tumor remission without compromise surgical safety or postoperative morbidity.

Lethal intestinal perforation after foreign body ingestion in a superobese patient.

Accidental ingestion of foreign bodies is common in the general population. Most foreign bodies pass through the entire digestive tract without incidents. However, in some cases, the ingested foreign body can cause complications such as acute abdomen due to intestinal perforation and even death. Bowel perforation may not be more common in the massively obese than in the normal-weight population but may be more problematic. We describe a super-obese female (body mass index, 52.3 kg/m2) who underwent emergency surgery for small-bowel perforation caused by an ingested foreign body (fish bone); the patient died despite segmental intestinal resection and intensive care.

Incarcerated umbilical hernia in a super-super-obese patient.

Abdominal wall hernias are more prevalent in the morbidly obese. Incarceration of external hernias is a relatively common process in adults and is associated to a high rate of complications and mortality. We present the case of a morbidly super-super-obese patient (body mass index, 80 kg/m(2)) who underwent emergency surgery for an incarcerated umbilical hernia; the patient died despite segmental intestinal resection, hernia repair using mesh, and intensive care.

Hepatic evisceration after cholecystectomy in a super obese patient.

Gallbladder pathology in general and cholelithiasis in particular are more common in the morbidly obese. Obesity is a risk factor for conversion to open surgery in laparoscopic cholecystectomy. Obesity is also a risk factor for evisceration after laparotomy in adults. Hepatic evisceration after cholecystectomy is rare. We describe a case of right liver lobe evisceration diagnosed by abdominal computed tomography (CT) in a super obese patient (BMI 57 kg/m2) after emergency laparoscopic surgery for acute calculous cholecystitis converted to open surgery.

Hepatic evisceration after cholecystectomy in a superobese patient.

Gallbladder pathology, in general, and cholelithiasis, in particular, are more common in the morbidly obese. Obesity is a risk factor for conversion to open surgery in laparoscopic cholecystectomy. Obesity is also a risk factor for evisceration after laparotomy in adults. Hepatic evisceration after cholecystectomy is rare. We describe a case of right liver lobe evisceration diagnosed by abdominal computed tomography in a superobese patient (body mass index 57 kg/m(2)) after emergency laparoscopic surgery for acute calculous cholecystitis converted to open surgery.

Gastric perforations from abdominal trauma.

BACKGROUND: Gastric rupture due to abdominal trauma is rare (0.02-1.7%); it is usually caused by traffic accidents. Delayed diagnosis, abdominal contamination and associated lesions cause morbidity and mortality. PATIENTS AND METHODS: Retrospective review of 2,083 patients with abdominal traumatism treated at our center over 20 years. We reviewed recent ingestion of a meal, etiology, time to surgery, site, Stomach Injury Scale, abdominal contamination, treatment, associated injuries, complications and mortality. RESULTS: Gastric perforation occurred in 25 patients (1.2%), median age 35 years. Stomachs were distended from recent meals in 16 (64%). The commonest causes were traffic accidents (n = 13) and blunt weapon injury (n = 7). The median time to surgery was 1 h. Gastric lesions occurred predominantly in the anterior wall (n = 12) followed by the greater curvature (n = 7). Type II lesions repaired with simple suturing were the most usual. Abdominal contamination occurred in all cases. Associated lesions were present in 22 patients; the most commonly affected intra-abdominal organ was the liver, and the lungs were the most affected extra-abdominal organ. The morbidity rate was 60% (n = 15) and the mortality rate 4% (n = 1). CONCLUSION: Early diagnosis and surgical treatment are important for reducing the morbidity and mortality in these patients.

Estudio del impacto de la pandemia por SARS-CoV-2 en la práctica quirúrgica urgente y electiva en un hospital de tercer nivel / Impact of SARS-COV-2 pandemic on elective and emergency surgery in a university hospital

INTRODUCCIÓN: La pandemia por SARS-CoV-2 ha causado un importante impacto en nuestro medio, con la necesidad de demorar la cirugía programada y urgente. Las cifras referentes a la disminución de la actividad quirúrgica y el impacto del periodo aún no se conocen con exactitud. Se estima una mortalidad de hasta un 20% en los pacientes operados con infección peroperatoria por SARS-CoV-2 MÉTODOS: Del 14/03 al 11/05 del 2020 se han recogido los datos de los pacientes ingresados en el servicio de Cirugía General y Digestiva del Hospital Universitari Dr. Josep Trueta de Girona, para analizar el impacto de la pandemia sobre la cirugía electiva y urgente. RESULTADOS: Durante el periodo de ocupación pico de la Unidad de Medicina Intensiva de nuestro centro (con un máximo de 303,8%), la cirugía electiva y la urgente se redujeron un 93,8% y un 72,7%, respectivamente. La mortalidad de los pacientes operados con infección por SARS-CoV-2 en nuestro estudio (n = 10) fue del 10%; las complicaciones fueron del 80% (siendo graves un 30%). CONCLUSIONES: El presente estudio muestra una reducción global de la actividad quirúrgica tanto electiva como urgente durante la pandemia. La mortalidad global de los pacientes operados con infección por SARS-CoV-2 ha sido baja, pero la tasa de complicaciones graves ha sido superior a la global

INTRODUCTION: SARS-CoV-2 pandemic has caused an important impact in our country and elective surgery has been postponed in most cases. There's not known information about the decreasing and impact on surgery. Mortality of surgical patients with SARS-CoV-2 infection is estimated to be around 20%. METHODS: We conducted prospective data recruitment of people inpatient in our Digestive and General Surgery section of Girona's University Hospital Dr. Josep Trueta from 03/14 to 05/11. Our objective is to analyze the impact that SARS-CoV-2 pandemic over elective and urgent surgery. RESULTS: During the peak occupation of our center Intensive Care Unit (303.8%) there was a reduction on elective (93.8%) and urgent (72.7%) surgery. Mortality of patients with SARS-CoV-2 infection who underwent surgery (n=10) is estimated to be a 10%. An 80% of these patients suffer complications (sever complications in 30%). CONCLUSIONS: The actual study shows a global reduction of the surgical activity (elective and urgent) during de SARS-CoV-2 pandemic. Global mortality of patients with SARS-CoV-2 infection are low, but the severe complications have been over the usual

Transducin-like enhancer of split 3 (TLE3) in adipose tissue is increased in situations characterized by decreased PPARγ gene expression.

UNLABELLED: Transgenic overexpression of adipose tissue (AT) transducin-like enhancer of split 3 (TLE3) mimicked peroxisome proliferator-activated receptor gamma (PPARγ) agonists, improving insulin resistance in mice. This study aimed to investigate TLE3 gene expression (qRT-PCR) and protein (Western blot) in subjects with a wide spectrum of obesity and insulin sensitivity and in an independent cohort of obese subjects following surgery-induced weight loss. TLE3 was analyzed in human adipocytes and after treatment with rosiglitazone. Given the findings in humans, TLE3 was also investigated in mice after a high-fat diet (HFD) and in PPARγ knockout mice. Subcutaneous (SC) AT TLE3 was increased in subjects with type 2 diabetes (T2D). In fact, SC TLE3 was associated with increased fasting glucose (r = 0.25, p = 0.015) and S6K1 activity (r = 0.671, p = 0.003), and with decreased Glut4 (r = -0.426, p = 0.006) and IRS-1 expression (-31 %, p = 0.007) and activation (P-IRS-1/IRS-1, -17 %, p = 0.024). TLE3 was preferentially expressed in mature adipocytes and increased during in vitro differentiation in parallel to PPARγ. Weight loss led to improved insulin sensitivity, increased AT PPARγ and decreased TLE3 (-24 %, p = 0.0002), while rosiglitazone administration downregulated TLE3 gene expression in fully differentiated adipocytes (-45 %, p < 0.0001). The concept that TLE3 may act as a homeostatic linchpin in AT was also supported by its increased expression in HFD-fed mice (39 %, p = 0.013) and PPARγ knockout (74 %, p = 0.001). In summary, increased AT TLE3 in subjects with T2D and in AT from HFD-fed and PPARγ knockout mice suggest that TLE3 may play an adaptive regulatory role that improves AT function under decreased PPARγ expression. KEY MESSAGE: TLE3 is expressed in mature adipocytes concomitantly with PPARγ. Subcutaneous adipose TLE3 is increased in T2D patients. Adipose TLE3 is upregulated in genetically ablated PPARγ and HFD-fed mice. TLE3 may be a homeostatic linchpin in insulin resistance and defective PPARγ.