Robotic versus laparoscopic distal pancreatectomy: multicentre analysis.

BACKGROUND: The role of minimally invasive distal pancreatectomy is still unclear, and whether robotic distal pancreatectomy (RDP) offers benefits over laparoscopic distal pancreatectomy (LDP) is unknown because large multicentre studies are lacking. This study compared perioperative outcomes between RDP and LDP. METHODS: A multicentre international propensity score-matched study included patients who underwent RDP or LDP for any indication in 21 European centres from six countries that performed at least 15 distal pancreatectomies annually (January 2011 to June 2019). Propensity score matching was based on preoperative characteristics in a 1 : 1 ratio. The primary outcome was the major morbidity rate (Clavien-Dindo grade IIIa or above). RESULTS: A total of 1551 patients (407 RDP and 1144 LDP) were included in the study. Some 402 patients who had RDP were matched with 402 who underwent LDP. After matching, there was no difference between RDP and LDP groups in rates of major morbidity (14.2 versus 16.5 per cent respectively; P = 0.378), postoperative pancreatic fistula grade B/C (24.6 versus 26.5 per cent; P = 0.543) or 90-day mortality (0.5 versus 1.3 per cent; P = 0.268). RDP was associated with a longer duration of surgery than LDP (median 285 (i.q.r. 225-350) versus 240 (195-300) min respectively; P < 0.001), lower conversion rate (6.7 versus 15.2 per cent; P < 0.001), higher spleen preservation rate (81.4 versus 62.9 per cent; P = 0.001), longer hospital stay (median 8.5 (i.q.r. 7-12) versus 7 (6-10) days; P < 0.001) and lower readmission rate (11.0 versus 18.2 per cent; P = 0.004). CONCLUSION: The major morbidity rate was comparable between RDP and LDP. RDP was associated with improved rates of conversion, spleen preservation and readmission, to the detriment of longer duration of surgery and hospital stay.

Laparoscopic versus open extended radical left pancreatectomy for pancreatic ductal adenocarcinoma: an international propensity-score matched study.

BACKGROUND: A radical left pancreatectomy in patients with pancreatic ductal adenocarcinoma (PDAC) may require extended, multivisceral resections. The role of a laparoscopic approach in extended radical left pancreatectomy (ERLP) is unclear since comparative studies are lacking. The aim of this study was to compare outcomes after laparoscopic vs open ERLP in patients with PDAC. METHODS: An international multicenter propensity-score matched study including patients who underwent either laparoscopic or open ERLP (L-ERLP; O-ERLP) for PDAC was performed (2007-2015). The ISGPS definition for extended resection was used. Primary outcomes were overall survival, margin negative rate (R0), and lymph node retrieval. RESULTS: Between 2007 and 2015, 320 patients underwent ERLP in 34 centers from 12 countries (65 L-ERLP vs. 255 O-ERLP). After propensity-score matching, 44 L-ERLP could be matched to 44 O-ERLP. In the matched cohort, the conversion rate in L-ERLP group was 35%. The L-ERLP R0 resection rate (matched cohort) was comparable to O-ERLP (67% vs 48%; P = 0.063) but the lymph node yield was lower for L-ERLP than O-ERLP (median 11 vs 19, P = 0.023). L-ERLP was associated with less delayed gastric emptying (0% vs 16%, P = 0.006) and shorter hospital stay (median 9 vs 13 days, P = 0.005), as compared to O-ERLP. Outcomes were comparable for additional organ resections, vascular resections (besides splenic vessels), Clavien-Dindo grade ≥ III complications, or 90-day mortality (2% vs 2%, P = 0.973). The median overall survival was comparable between both groups (19 vs 20 months, P = 0.571). Conversion did not worsen outcomes in L-ERLP. CONCLUSION: The laparoscopic approach may be used safely in selected patients requiring ERLP for PDAC, since morbidity, mortality, and overall survival seem comparable, as compared to O-ERLP. L-ERLP is associated with a high conversion rate and reduced lymph node yield but also with less delayed gastric emptying and a shorter hospital stay, as compared to O-ERLP.

Gemcitabine-based adjuvant chemotherapy in subtypes of ampullary adenocarcinoma: international propensity score-matched cohort study.

BACKGROUND: Whether patients who undergo resection of ampullary adenocarcinoma have a survival benefit from adjuvant chemotherapy is currently unknown. The aim of this study was to compare survival between patients with and without adjuvant chemotherapy after resection of ampullary adenocarcinoma in a propensity score-matched analysis. METHODS: An international multicentre cohort study was conducted, including patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma between 2006 and 2017, in 13 centres in six countries. Propensity scores were used to match patients who received adjuvant chemotherapy with those who did not, in the entire cohort and in two subgroups (pancreatobiliary/mixed and intestinal subtypes). Survival was assessed using the Kaplan-Meier method and Cox regression analyses. RESULTS: Overall, 1163 patients underwent pancreatoduodenectomy for ampullary adenocarcinoma. After excluding 187 patients, median survival in the remaining 976 patients was 67 (95 per cent c.i. 56 to 78) months. A total of 520 patients (53·3 per cent) received adjuvant chemotherapy. In a propensity score-matched cohort (194 patients in each group), survival was better among patients who received adjuvant chemotherapy than in those who did not (median survival not reached versus 60 months respectively; P = 0·051). A survival benefit was seen in patients with the pancreatobiliary/mixed subtype; median survival was not reached in patients receiving adjuvant chemotherapy and 32 months in the group without chemotherapy (P = 0·020). Patients with the intestinal subtype did not show any survival benefit from adjuvant chemotherapy. CONCLUSION: Patients with resected ampullary adenocarcinoma may benefit from gemcitabine-based adjuvant chemotherapy, but this effect may be reserved for those with the pancreatobiliary and/or mixed subtype.

ANTECEDENTES: Actualmente se desconoce si la quimioterapia adyuvante ofrece un beneficio en la supervivencia de los pacientes que se someten a resección de un adenocarcinoma ampular. El objetivo de este estudio fue comparar la supervivencia mediante la concordancia estimada por emparejamiento por puntaje de propensión, entre pacientes con y sin quimioterapia adyuvante después de la resección de un adenocarcinoma ampular. MÉTODOS: Se realizó un estudio internacional de cohortes multicéntrico, que incluyó a los pacientes que se sometieron a una duodenopancreatectomía por adenocarcinoma ampular (2006-2017) en 13 centros de seis países. Los puntajes de propensión se usaron para emparejar a los pacientes que recibieron quimioterapia adyuvante con los que no; tanto en la cohorte completa como en dos subgrupos (subtipo pancreaticobiliar / mixto e intestinal). La supervivencia se evaluó utilizando el método de Kaplan-Meier y las regresiones de Cox. RESULTADOS: En total, 1.163 pacientes fueron sometidos a una duodenopancreatectomía por adenocarcinoma ampular. Después de excluir a 179 pacientes, la mediana de supervivencia de los 976 pacientes restantes fue de 67 meses (i.c. del 95%, 56-78), de los cuales un total de 520 pacientes (53%) recibieron quimioterapia adyuvante. En una cohorte de emparejamiento por puntaje de propensión (194 versus 194 pacientes), la mediana de supervivencia fue mejor en los pacientes tratados con quimioterapia adyuvante en comparación con aquellos sin quimioterapia adyuvante (no se alcanzó la mediana de supervivencia versus 60 meses, respectivamente; P = 0,051). En el subtipo pancreaticobiliar/mixto se observó un beneficio en la supervivencia; no se alcanzó la mediana de supervivencia en pacientes que recibieron quimioterapia adyuvante versus 32 meses en el grupo sin quimioterapia, P = 0,020. El subtipo intestinal no mostró beneficio en la supervivencia de la quimioterapia adyuvante. CONCLUSIÓN: Los pacientes con adenocarcinoma ampular resecado pueden beneficiarse de la quimioterapia adyuvante basada en gemcitabina, pero este efecto podría reservarse para aquellos pacientes con subtipo de tumor pancreaticobiliar y/o mixto.

Multicentre observational cohort study of implementation and outcomes of laparoscopic distal pancreatectomy.

BACKGROUND: Laparoscopic distal pancreatectomy (LDP) is increasingly being performed as an alternative to open surgery. Whether the implementation and corresponding learning curve of LDP have an impact on patient outcome is unknown. The aim was to investigate the temporal trends in practice across UK centres. METHODS: This was a retrospective multicentre observational cohort study of LDP in 11 tertiary referral centres in the UK between 2006 and 2016. The learning curve was analysed by pooling data for the first 15 consecutive patients who had LDP and examining trends in surgical outcomes in subsequent patients. RESULTS: In total, 570 patients underwent LDP, whereas 888 underwent open resection. For LDP the median duration of operation was 240 min, with 200 ml blood loss. The conversion rate was 12·1 per cent. Neuroendocrine tumours (26·7 per cent) and mucinous cystic neoplasms (19·7 per cent) were commonest indications. The proportion of LDPs increased from 24·4 per cent in 2006-2009 (P1) to 46·0 per cent in 2014-2016 (P3) (P < 0·001). LDP was increasingly performed for patients aged 70 years or more (16 per cent in P1 versus 34·4 per cent in P3; P = 0·002), pancreatic ductal adenocarcinoma (6 versus 19·1 per cent; P = 0·005) and advanced malignant tumours (27 versus 52 per cent; P = 0·016). With increasing experience, there was a trend for a decrease in blood transfusion rate (14·1 per cent for procedures 1-15 to 3·5 per cent for procedures 46-75; P = 0·008), ICU admissions (32·7 to 19·2 per cent; P = 0·021) and median duration of hospital stay (7 (i.q.r. 5-9) to 6 (4-7) days; P = 0·002). After 30 procedures, a decrease was noted in rates of both overall morbidity (57·7 versus 42·2 per cent for procedures 16-30 versus 46-75 respectively; P = 0·009) and severe morbidity (18·8 versus 9·7 per cent; P = 0·031). CONCLUSION: LDP has increased as a treatment option for lesions of the distal pancreas as indications for the procedure have expanded. Perioperative outcomes improved with the number of procedures performed.

ANTECEDENTES: Cada día se utiliza más la pancreatectomía distal laparoscópica (laparoscopic distal pancreatectomy, LDP) como una alternativa a la cirugía abierta. Se desconoce si la implementación y la correspondiente curva de aprendizaje de la LDP tienen impacto en los resultados. El objetivo fue investigar las tendencias relacionadas con su implementación en los centros del Reino Unido a los largo del tiempo. MÉTODOS: Se realizó el estudio observacional retrospectivo y multicéntrico de una cohorte de LDP en once centros de referencia terciarios del Reino Unido entre 2006-2016. Se analizó la curva de aprendizaje agrupando los 15 primeros pacientes consecutivos de LDP y se compararon los resultados quirúrgicos con los obtenidos en los pacientes subsiguientes. RESULTADOS: En total, se incluyeron 570 pacientes con LDP y 888 con resección abierta. Para el LDP, la mediana de tiempo operatorio fue de 240 minutos con 200 ml de pérdida de sangre. La tasa de conversión fue del 12,2%. Las indicaciones más frecuentes fueron los tumores neuroendocrinos (26,7%) y las neoplasias quísticas mucinosas (19,7%). La proporción de LDP aumentó del 24% al 46% (de 2006-2009 a 2014-2016; P < 0,001). La LDP se realizó cada vez con mayor frecuencia en pacientes de ≥ 70 años (15,8% versus 34,4%, P = 0,002), en pacientes con adenocarcinoma ductal pancreático (6,5% versus 19,1%, P = 0,005) y en pacientes con tumores malignos avanzados (27,3% versus 51,85%, P = 0,016). Con el aumento de la experiencia, disminuyeron las tendencias de la tasa de transfusión sanguínea (14,1% al 3,5%, P = 0,008), los ingresos en la UCI (32,7% a 19,2%, P = 0.021) y la mediana de la duración de la estancia hospitalaria (7 (rango intercuartílico 5-9) a 6 (rango intercuartilico 4-7) días, P = 0,002). Tras 30 procedimientos, disminuyeron tanto la morbilidad global (57,7% versus 42,2%, P = 0,009) como las tasas de morbilidad grave (21,5% versus 14,6%, P = 0,022). CONCLUSIÓN: La pancreatectomía distal laparoscópica se ha incrementado como una opción de tratamiento para las lesiones del páncreas distal a medida que se han ido ampliando las indicaciones del procedimiento. Los resultados perioperatorios mejoran con el número de procedimientos realizados.

Validation of the EORTC QLQ-BIL21 questionnaire for measuring quality of life in patients with cholangiocarcinoma and cancer of the gallbladder.

BACKGROUND: There is no specific quality of life (QoL) measurement tool to quantify QoL in patients with biliary tract cancer. Quality of life measurement is an increasingly crucial trial end point and is now being incorporated into clinical practice. METHODS: This International Multicentre Phase IV Validation Study assessed the QLQ-BIL21 module in 172 patients with cholangiocarcinoma and 91 patients with cancer of the gallbladder. Patients completed the questionnaire at baseline pretherapy and subsequently at 2 months. Following this, the psychometric properties of reliability, validity, scale structure and responsiveness to change were analysed. RESULTS: Analysis of the QLQ-BIL21 scales showed appropriate reliability with Cronbach's α-coefficients >0.70 for all scales overall. Intraclass correlations exceeded 0.80 for all scales. Convergent validity >0.40 was demonstrated for all items within scales, and discriminant validity was confirmed with values <0.70 for all scales compared with each other. Scale scores changed in accordance with Karnofsky performance status and in response to clinical change. CONCLUSIONS: The QLQ-BIL21 is a valid tool for the assessment of QoL in patients with cholangiocarcinoma and cancer of the gallbladder.

Complications and follow-up after pancreas-preserving total duodenectomy for duodenal polyps.

BACKGROUND: Patients with duodenal polyps are at risk of duodenal cancer. Pancreas-preserving total duodenectomy (PPTD) is an alternative to partial pancreatoduodenectomy. METHODS: Twelve patients (seven men and five women) with a median age of 59 (interquartile range (i.q.r.) 50-67) years underwent PPTD for large (over 20 mm) solitary polyps or multiple (more than three) duodenal polyps confined to the muscularis propria on endoscopic ultrasonography. RESULTS: Median hospital stay was 21 (i.q.r. 10-36) days with no deaths and no blood transfusion. Six patients developed postoperative complications, one requiring reoperation. Histology demonstrated gastrointestinal stromal tumour in three patients, low-grade dysplasia in one, moderate-grade dysplasia in eight and duodenal intramucosal adenocarcinoma in one. During a median follow-up of 20 (i.q.r. 8-41) months one patient experienced recurrent acute pancreatitis (due to hypertriglyceridaemia) and one developed a jejunal adenocarcinoma in the neoduodenum. CONCLUSION: The morbidity of PPTD is similar to that of partial pancreatoduodenectomy, but PPTD preserves the whole pancreas and reduces the number of anastomoses.

Tumour-associated macrophages (TAMS): disordered function, immune suppression and progressive tumour growth.

Evidence currently available suggests that in established, progressively growing solid tumours, tumour associated macrophages (TAMs) are reprogrammed to induce immune suppression of host defenses in situ, through release of specific cytokines, prostanoids and other humoral mediators. This disordered response, results in the inhibition of effective anti-cancer cell-mediated immune mechanisms. Concurrently, TAMs produce tumour growth promoting factors. The summation of this complex interplay of biological factors results in progressive tumour growth and tumour cell dissemination. A better understanding of these complex inter-relationships should form the basis of novel strategies designed to eradicate tumour cells in man and animals. These various biological aspects and processes are discussed in detail and critically evaluated in this review article.