Functional outcomes after laparoscopic versus robotic-assisted rectal resection: a systematic review and meta-analysis.

Surgical resection is crucial for curative treatment of rectal cancer. Through multidisciplinary treatment, including radiochemotherapy and total mesorectal excision, survival has improved substantially. Consequently, more patients have to deal with side effects of treatment. The most recently introduced surgical technique is robotic-assisted surgery (RAS) which seems equally effective in terms of oncological control compared to laparoscopy. However, RAS enables further advantages which maximize the precision of surgery, thus providing better functional outcomes such as sexual function or contience without compromising oncological results. This review was done according to the PRISMA and AMSTAR-II guidelines and registered with PROSPERO (CRD42018104519). The search was planned with PICO criteria and conducted on Medline, Web of Science and CENTRAL. All screening steps were performed by two independent reviewers. Inclusion criteria were original, comparative studies for laparoscopy vs. RAS for rectal cancer and reporting of functional outcomes. Quality was assessed with the Newcastle-Ottawa scale. The search retrieved 9703 hits, of which 51 studies with 24,319 patients were included. There was a lower rate of urinary retention (non-RCTs: Odds ratio (OR) [95% Confidence Interval (CI)] 0.65 [0.46, 0.92]; RCTs: OR[CI] 1.29[0.08, 21.47]), ileus (non-RCTs: OR[CI] 0.86[0.75, 0.98]; RCTs: OR[CI] 0.80[0.33, 1.93]), less urinary symptoms (non-RCTs mean difference (MD) [CI] - 0.60 [- 1.17, - 0.03]; RCTs: - 1.37 [- 4.18, 1.44]), and higher quality of life for RAS (only non-RCTs: MD[CI]: 2.99 [2.02, 3.95]). No significant differences were found for sexual function (non-RCTs: standardized MD[CI]: 0.46[- 0.13, 1.04]; RCTs: SMD[CI]: 0.09[- 0.14, 0.31]). The current meta-analysis suggests potential benefits for RAS over laparoscopy in terms of functional outcomes after rectal cancer resection. The current evidence is limited due to non-randomized controlled trials and reporting of functional outcomes as secondary endpoints.

Consensus on definition and severity grading of lymphatic complications after kidney transplantation.

BACKGROUND: The incidence of lymphatic complications after kidney transplantation varies considerably in the literature. This is partly because a universally accepted definition has not been established. This study aimed to propose an acceptable definition and severity grading system for lymphatic complications based on their management strategy. METHODS: Relevant literature published in MEDLINE and Web of Science was searched systematically. A consensus for definition and a severity grading was then sought between 20 high-volume transplant centres. RESULTS: Lymphorrhoea/lymphocele was defined in 32 of 87 included studies. Sixty-three articles explained how lymphatic complications were managed, but none graded their severity. The proposed definition of lymphorrhoea was leakage of more than 50 ml fluid (not urine, blood or pus) per day from the drain, or the drain site after removal of the drain, for more than 1 week after kidney transplantation. The proposed definition of lymphocele was a fluid collection of any size near to the transplanted kidney, after urinoma, haematoma and abscess have been excluded. Grade A lymphatic complications have a minor and/or non-invasive impact on the clinical management of the patient; grade B complications require non-surgical intervention; and grade C complications require invasive surgical intervention. CONCLUSION: A clear definition and severity grading for lymphatic complications after kidney transplantation was agreed. The proposed definitions should allow better comparisons between studies.

ANTECEDENTES: La incidencia de complicaciones linfáticas tras el trasplante renal (post-kidney-transplantation lymphatic, PKTL) varía considerablemente en la literatura. Esto se debe en parte a que no se ha establecido una definición universalmente aceptada. Este estudio tuvo como objetivo proponer una definición aceptable para las complicaciones PKTL y un sistema de clasificación de la gravedad basado en la estrategia de tratamiento. MÉTODOS: Se realizó una búsqueda sistemática de la literatura relevante en MEDLINE y Web of Science. Se logró un consenso para la definición y la clasificación de gravedad de las PKTL entre veinte centros de trasplante de alto volumen. RESULTADOS: En 32 de los 87 estudios incluidos se definía la linforrea/linfocele. Sesenta y tres artículos describían como se trataban las PKTL, pero ninguno calificó la gravedad de las mismas. La definición propuesta para la linforrea fue la de un débito diario superior a 50 ml de líquido (no orina, sangre o pus) a través del drenaje o del orificio cutáneo tras su retirada, más allá del 7º día postoperatorio del trasplante renal. La definición propuesta para linfocele fue la de una colección de líquido de tamaño variable adyacente al riñón trasplantado, tras haber descartado un urinoma, hematoma o absceso. Las PKTL de grado A fueron aquellas con escaso impacto o que no requirieron tratamiento invasivo; las PKTL de grado B fueron aquellas que precisaron intervención no quirúrgica y las PKTL de grado C aquellas en que fue necesaria la reintervención quirúrgica. CONCLUSIÓN: Se propone una definición clara y una clasificación de gravedad basada en la estrategia de tratamiento de las PKTLs. La definición propuesta y el sistema de calificación en 3 grados son razonables, sencillos y fáciles de comprender, y servirán para estandarizar los resultados de las PKTL y facilitar las comparaciones entre los diferentes estudios.

Outcome after liver resection for primary and recurrent intrahepatic cholangiocarcinoma.

Background: Liver resection is the only curative therapeutic option for intrahepatic cholangiocarcinoma (ICC), but the approach to recurrent ICC is controversial. This study analysed the outcome of liver resection in patients with recurrent ICC. Methods: Demographic, radiological, clinical, operative, surgical pathological and follow-up data for all patients with a final surgical pathological diagnosis of ICC treated in a tertiary referral centre between 2001 and 2015 were collected retrospectively and analysed. Results: A total of 190 patients had liver resection for primary ICC. The 1-, 3- and 5-year overall survival (OS) rates were 74·8, 56·6 and 37·9 per cent respectively. Independent determinants of OS were age 65 years or above (hazard ratio (HR) 2·18, 95 per cent c.i. 1·18 to 4·0; P = 0·012), median tumour diameter 5 cm or greater (HR 2·87, 1·37 to 6·00; P = 0·005), preoperative biliary drainage (HR 2·65, 1·13 to 6·20; P = 0·025) and local R1-2 status (HR 1·90, 1·02 to 3·53; P = 0·043). Recurrence was documented in 87 patients (45·8 per cent). The mean(s.d.) survival time after recurrence was 16(17) months. Independent determinants of recurrence were median tumour diameter 5 cm or more (HR 1·71, 1·09 to 2·68; P = 0·020), high-grade (G3-4) tumour (HR 1·63, 1·04 to 2·55; P = 0·034) and local R1 status (HR 1·70, 1·09 to 2·65; P = 0·020). Repeat resection with curative intent was performed in 25 patients for recurrent ICC, achieving a mean survival of 25 (95 per cent c.i. 16 to 34) months after the diagnosis of recurrence. Patients deemed to have unresectable disease after recurrence received chemotherapy or chemoradiotherapy alone, and had significantly poorer survival. Conclusion: Patients with recurrent ICC may benefit from repeat surgical resection.

Antecedentes: La resección hepática es la única opción terapéutica curativa para el colangiocarcinoma intrahepático (intrahepatic colangiocarcinoma, iCCA), pero el enfoque terapéutico de la recidiva del iCCA es controvertido. En este estudio se analizaron los resultados de la resección hepática en pacientes con recidiva de un iCCA. Métodos: Se recopilaron de forma retrospectiva y se analizaron los datos demográficos, radiológicos, clínicos, quirúrgicos, de anatomía patológica y de seguimiento de todos los pacientes con diagnóstico anatomopatológico definitivo de iCCA en un centro de referencia terciario entre 2001 y 2015. Resultados: En total, 190 pacientes se sometieron a resección hepática por iCCA primario. La supervivencia global (overall survival, OS) a 1, 3 y 5 años fue del 75%, 57% y 38%, respectivamente. La edad de ≥ 65 años (cociente de riesgos instantáneos, hazard ratio, HR 2,2, i.c. del 95% 1,2­4,0, P = 0,012), la mediana del diámetro del tumor ≥ 5 cm (HR 2,9, i.c. del 95% 1,4­6,0, P = 0,005), el drenaje biliar preoperatorio (HR 2,6, i.c. del 95% 1,3­6,2, P = 0.025) y el estado local R1/2 (HR 1,9, i.c. del 95% 1,0­3,5, P = 0,043) fueron factores pronósticos independientes de la OS. La recidiva se documentó en 87 (45,8%) pacientes. El tiempo medio de supervivencia después de la recidiva fue de 16 ± 2 meses. Los factores pronósticos independientes de recidiva fueron la mediana del diámetro del tumor ≥ 5 cm (HR 1,7, i.c. del 95% 1,1­2,7, P = 0,020), el tumor de alto grado (G3­G4) (HR 1,6, i.c. del 95% 1,0­2,5, P = 0,034) y el estado local R1 (HR 1,7, i.c. del 95% 1,1­2,6, P = 0,020). La resección repetida con intención curativa se realizó en 25 pacientes con iCCA recidivado, con una supervivencia media de 25 meses (i.c. del 95% 16­34 meses) tras el diagnóstico de recidiva. Los pacientes que se consideraron no resecables después de la recidiva se sometieron a quimioterapia o quimiorradioterapia y presentaron una supervivencia significativamente peor. Conclusión: Los pacientes con recidiva de un iCCA pueden beneficiarse de la resección quirúrgica repetida.

Surgical outcomes after pediatric kidney transplantation at the University of Heidelberg.

BACKGROUND: Kidney transplantation (KTx) is the treatment of choice for children with end-stage renal disease (ESRD). OBJECTIVE: An update of 48 years of surgical experience with pediatric KTx (PKTx) is presented, and the results between recipients of organs from deceased donors (DDs) and living donors (LDs) are compared. STUDY DESIGN: All patients younger than 18 years who underwent KTx between 1967 and 2015 were evaluated. Data from 540 PKTx operations (409 DD and 131 LD) were obtained from the transplant center database. Peri-operative data and graft and patient survival were analyzed in the DD and LD groups. RESULTS: Fewer recipients in the LD group underwent dialysis before PKTx than those in the DD group (50.8% in LD vs. 94.9% in DD, P < 0.001). The mean duration of dialysis (DD: 798 ± 525 days vs. LD: 625 ± 650 days, P = 0.03), time on the waiting list (DD: 472 ± 435 days vs. LD: 120 ± 243 days, P < 0.001), cold ischemia time (CIT) (DD: 1206 ± 368 min vs. LD: 140 ± 63 min, P < 0.001), operation time, and hospital stay were lower in the LD group. Except for arterial stenosis, the rates of postoperative vascular and urological complications were not different between the two groups. The cumulative 25-year graft and patient survival rates were 46.4% and 84.1% in the DD group and 76.5% and 96.1% in the LD group, respectively. DISCUSSION: PKTx is the treatment of choice for children with ESRD. Graft quality has a direct impact on KTx outcome and rate of graft failure. Better HLA compatibility and shorter CIT reduce the impairment of graft function after LD PKTx. In addition, Establishment of an interdisciplinary approach using an individualized risk assessment and prevention model can improve PKTx outcomes. CONCLUSION: Compared with DD PKTx, LD PKTx has better graft survival associated with a shorter duration of preceding dialysis, waiting time, and CIT and seems to be more beneficial for children.

[Role of neoadjuvant radiotherapy for rectal cancer : Is MRI-based selection a future model?]. / Rolle der neoadjuvanten Strahlentherapie beim Rektumkarzinom : Ist die MRT-basierte Selektion ein Zukunftsmodell?

Following the introduction of total mesorectal excision (TME) in the curative treatment of rectal cancer, the role of neoadjuvant therapy has evolved. By improving the surgical technique the local recurrence rate could be reduced by TME surgery alone to below 8 %. Even if local control was further improved by additional preoperative irradiation this did not lead to a general survival benefit. Guidelines advocate that all patients in UICC stage II and III should be pretreated; however, the stage-based indications for neoadjuvant therapy have limitations. This is mainly attributable to the facts that patients with T3 tumors comprise a very heterogeneous prognostic group and preoperative lymph node diagnostics lack accuracy. In contrast, in recent years the circumferential resection margin (CRM) has become an important prognostic parameter. Patients with tumors that are very close to or infiltrate the pelvic fascia (positive CRM) have a higher rate of local recurrence and poorer survival. With high-resolution pelvic magnetic resonance imaging (MRI) examination in patients with rectal cancer, the preoperative CRM can be determined with a high sensitivity and specificity. Improved T staging and better prediction of the resection margins by pelvic MRI potentially facilitate the selection of patients for study-based treatment strategies omitting neoadjuvant radiotherapy.

Meta-analysis of reconstruction techniques after low anterior resection for rectal cancer.

BACKGROUND: Options for reconstruction after low anterior resection (LAR) for rectal cancer include straight or side-to-end coloanal anastomosis (CAA), colonic J pouch and transverse coloplasty. This systematic review compared these techniques in terms of function, surgical outcomes and quality of life. METHODS: A systematic literature search (MEDLINE, Embase and the Cochrane Library, from inception of the databases until November 2014) was conducted to identify randomized clinical trials comparing reconstructive techniques after LAR. Random-effects meta-analyses were carried out, and results presented as weighted odds ratios or mean differences with corresponding 95 per cent c.i. A network meta-analysis was conducted for the outcome anastomotic leakage. RESULTS: The search yielded 965 results; 21 trials comprising data from 1636 patients were included. Colonic J pouch was associated with lower stool frequency and antidiarrhoeal medication use for up to 1 year after surgery compared with straight CAA. Transverse coloplasty and side-to-end CAA had similar functional outcomes to the colonic J pouch. No superiority was found for any of the techniques in terms of anastomotic leak rate. CONCLUSION: Colonic J pouch and side-to-end CAA or transverse coloplasty lead to a better functional outcome than straight CAA for the first year after surgery.

[Perioperative complications of the lower gastrointestinal tract : Prevention, recognition and treatment]. / Perioperative Komplikationen des unteren Gastrointestinaltraktes : Prävention, Erkennung, Therapie.

Perioperative complications following surgical procedures of the lower gastrointestinal tract still represent a relevant problem. The perioperative morbidity may negatively affect short and long-term outcomes of treatment of individual patients. The additional diagnostics and treatment required also lead to additional costs that burden the healthcare system. Ideally, complications should be avoided by preventive measures. In the event of a complication, early detection is essential for appropriate treatment.Surgical site infections (SSI) have been described as the most common complication in the postoperative period and may occur in up to 30% of cases. Through various perioperative measures up to 40-60% of SSI are preventable. Depending on the location, the reported anastomotic leakage rate ranges from 1% to 23%. The therapeutic strategy ranges from conservative measures through interventional methods up to surgical revision. An early postoperative burst abdomen occurs in about 3% of cases. A midline closure with small stitches and small suture distances (suture length to wound length ratio of 4) seems to be superior to large stitches with long distance intervals. A rare but potentially fatal complication is bleeding. The identification of patients with relevant risk factors is of great importance. This article summarizes the prevention, recognition and treatment of perioperative complications after surgery of the lower gastrointestinal tract.

[Radiotherapy-associated morbidity and mortality in rectal surgery]. / Strahlentherapieassoziierte Morbidität und Mortalität in der Rektumchirurgie.

The treatment of rectal cancer has evolved significantly in recent decades. Both modern radiotherapy treatment concepts and surgical techniques have been able to improve oncological as well as functional outcomes for rectal cancer patients. Large-scale, multicenter, randomized trials have been able to demonstrate the benefits of neoadjuvant treatment over adjuvant radiotherapy. In addition, local tumor control is improved by neoadjuvant irradiation. Conversely, patients receiving a total mesorectal excision showed no survival advantage following irradiation vs. only surgically resected patients. In addition, radiation therapy is associated with a certain morbidity and mortality. This paper summarizes the available evidence regarding postoperative morbidity, mortality, and long-term chronic effects of neoadjuvant radiotherapy.

Concurrent chemotherapy inhibits herpes simplex virus-1 replication and oncolysis.

Herpes simplex virus-1 (HSV-1) replication in cancer cells leads to their destruction (viral oncolysis) and has been under investigation as an experimental cancer therapy in clinical trials as single agents, and as combinations with chemotherapy. Cellular responses to chemotherapy modulate viral replication, but these interactions are poorly understood. To investigate the effect of chemotherapy on HSV-1 oncolysis, viral replication in cells exposed to 5-fluorouracil (5-FU), irinotecan (CPT-11), methotrexate (MTX) or a cytokine (tumor necrosis factor-α (TNF-α)) was examined. Exposure of colon and pancreatic cancer cells to 5-FU, CPT-11 or MTX in vitro significantly antagonizes both HSV-1 replication and lytic oncolysis. Nuclear factor-κB (NF-κB) activation is required for efficient viral replication, and experimental inhibition of this response with an IκBα dominant-negative repressor significantly antagonizes HSV-1 replication. Nonetheless, cells exposed to 5-FU, CPT-11, TNF-α or HSV-1 activate NF-κB. Cells exposed to MTX do not activate NF-κB, suggesting a possible role for NF-κB inhibition in the decreased viral replication observed following exposure to MTX. The role of eukaryotic initiation factor 2α (eIF-2α) dephosphorylation was examined; HSV-1-mediated eIF-2α dephosphorylation proceeds normally in HT29 cells exposed to 5-FU, CPT-11 or MTX. This report demonstrates that cellular responses to chemotherapeutic agents provide an unfavorable environment for HSV-1-mediated oncolysis, and these observations are relevant to the design of both preclinical and clinical studies of HSV-1 oncolysis.

Comparison of intravenous versus intraperitoneal administration of oncolytic herpes simplex virus 1 for peritoneal carcinomatosis in mice.

hrR3 is an oncolytic herpes simplex virus 1 (HSV-1) mutant that replicates preferentially in tumors compared with normal tissues. Portal venous administration of hrR3 in mice bearing diffuse colorectal carcinoma liver metastases significantly reduces tumor burden and prolongs animal survival. In this study, we compared survival benefit and biodistribution of hrR3 following intravenous (i.v.) administration versus intraperitoneal (i.p.) administration in immunocompetent mice bearing colon carcinoma peritoneal metastases. Mice bearing peritoneal metastases received 1 x 10(8) plaque-forming units hrR3 or mock-infected media every other day for three doses and were randomized to have the viruses administered by either an i.p. or i.v. route. Biodistribution was assessed by PCR amplification of HSV-1-specific sequences from tumor and normal tissues including the small bowel, liver, spleen, kidney, lung, heart and brain. LD(50) for i.p. administration was compared with the LD(50) for i.v. administration. In subsequent experiments, animals were monitored for survival. The frequency of HSV-1 detection in peritoneal tumors was similar in mice randomized to either i.p. or i.v. administration. However, i.p. administration resulted in a more restricted systemic biodistribution, with a reduced frequency of virus detected in the kidney, lung and heart. The LD(50) associated with i.p. administration was higher than that with i.v. administration. Tumor burden was more effectively reduced with i.p. compared with i.v. administration. Median survival following i.p. administration was approximately twice that observed with i.v. administration. I.p. administration of an HSV-1 oncolytic mutant is associated with a more restricted biodistribution, less toxicity and greater efficacy against peritoneal metastases compared with i.v. administration.

Intravenous glycine after cecal ligation and puncture has no effect on impaired hepatic microperfusion, leukocyte adhesion, and mortality in septic rats.

Recent studies indicated that prefeeding of a glycine supplemented diet reduces the hepatic inflammatory response and liver damage in sepsis. We investigated the effect of a glycine-enriched infusion on hepatic microcirculatory disturbances and mortality in a rat model of sepsis after the onset of the disease. Male Wistar rats (240 +/- 13 g) underwent cecal ligation and puncture (CLP) or laparotomy (LAP). A glycine (CLP + Gly, n = 24), valine (CLP + Val, n = 24), or sodium chlorid (CLP + Sc, n = 24) infusion was started 2 h after CLP. The LAP group received sodium chloride intravenously (LAP + Sc, n = 18 ). Five hours, 10 h, and 20 h after CLP or LAP intravital microscopy (IVM) was performed to investigate leukocyte-endothelial interaction (LEI) and mean erythrocyte velocity in liver sinusoids (sMEV) and postsinosoidal venules (vMEV). The portal blood flow (PBF), hepatic enzyme liberation, and glycine values in blood were measured. Immunohistochemical staining for ICAM-1 in liver tissue was performed and survival was observed. Glycine values were significantly elevated in the CLP + Gly vs. the CLP + Val and the CLP + Sc group at every timepoint of investigation. Glycine infusion had no beneficial effects on sMEV, vMEV, LEI, hepatic enzyme liberation, and survival. Heart rate and mean arterial pressure remained stable but PBF decreased significantly in all groups 20 h after CLP. Although glycine reduces the hepatic inflammatory response and liver damage in pretreatment of septic rats, there was no effect of intravenous glycine after the onset of sepsis in our experiments. Our animal model does not support the use of glycine in patients.