Completion pancreatectomy or a pancreas-preserving procedure during relaparotomy for pancreatic fistula after pancreatoduodenectomy: a multicentre cohort study and meta-analysis.

BACKGROUND: Despite the fact that primary percutaneous catheter drainage has become standard practice, some patients with pancreatic fistula after pancreatoduodenectomy ultimately undergo a relaparotomy. The aim of this study was to compare completion pancreatectomy with a pancreas-preserving procedure in patients undergoing relaparotomy for pancreatic fistula after pancreatoduodenectomy. METHODS: This retrospective cohort study of nine institutions included patients who underwent relaparotomy for pancreatic fistula after pancreatoduodenectomy from 2005-2018. Furthermore, a systematic review and meta-analysis were performed according to the PRISMA guidelines. RESULTS: From 4877 patients undergoing pancreatoduodenectomy, 786 (16 per cent) developed a pancreatic fistula grade B/C and 162 (3 per cent) underwent a relaparotomy for pancreatic fistula. Of these patients, 36 (22 per cent) underwent a completion pancreatectomy and 126 (78 per cent) a pancreas-preserving procedure. Mortality was higher after completion pancreatectomy (20 (56 per cent) versus 40 patients (32 per cent); P = 0.009), which remained after adjusting for sex, age, BMI, ASA score, previous reintervention, and organ failure in the 24 h before relaparotomy (adjusted odds ratio 2.55, 95 per cent c.i. 1.07 to 6.08). The proportion of additional reinterventions was not different between groups (23 (64 per cent) versus 84 patients (67 per cent); P = 0.756). The meta-analysis including 33 studies evaluating 745 patients, confirmed the association between completion pancreatectomy and mortality (Mantel-Haenszel random-effects model: odds ratio 1.99, 95 per cent c.i. 1.03 to 3.84). CONCLUSION: Based on the current data, a pancreas-preserving procedure seems preferable to completion pancreatectomy in patients in whom a relaparotomy is deemed necessary for pancreatic fistula after pancreatoduodenectomy.

Volume-outcome relationship of liver surgery: a nationwide analysis.

BACKGROUND: Evidence for an association between hospital volume and outcomes for liver surgery is abundant. The current Dutch guideline requires a minimum volume of 20 annual procedures per centre. The aim of this study was to investigate the association between hospital volume and postoperative outcomes using data from the nationwide Dutch Hepato Biliary Audit. METHODS: This was a nationwide study in the Netherlands. All liver resections reported in the Dutch Hepato Biliary Audit between 2014 and 2017 were included. Annual centre volume was calculated and classified in categories of 20 procedures per year. Main outcomes were major morbidity (Clavien-Dindo grade IIIA or higher) and 30-day or in-hospital mortality. RESULTS: A total of 5590 liver resections were done across 34 centres with a median annual centre volume of 35 (i.q.r. 20-69) procedures. Overall major morbidity and mortality rates were 11·2 and 2·0 per cent respectively. The mortality rate was 1·9 per cent after resection for colorectal liver metastases (CRLMs), 1·2 per cent for non-CRLMs, 0·4 per cent for benign tumours, 4·9 per cent for hepatocellular carcinoma and 10·3 per cent for biliary tumours. Higher-volume centres performed more major liver resections, and more resections for hepatocellular carcinoma and biliary cancer. There was no association between hospital volume and either major morbidity or mortality in multivariable analysis, after adjustment for known risk factors for adverse events. CONCLUSION: Hospital volume and postoperative outcomes were not associated.

ANTECEDENTES: La asociación entre el volumen hospitalario y los resultados de la cirugía hepática no está clara. Según la recomendación actual de las guías holandesas se requiere un volumen mínimo de 20 procedimientos anuales por centro. El objetivo de este estudio fue analizar la asociación entre el volumen hospitalario con los resultados postoperatorios en la auditoría hepatobiliar obligatoria holandesa a nivel nacional. MÉTODOS: Se realizó un estudio a nivel nacional en los Países Bajos. Se incluyeron todas las resecciones hepáticas registradas en la auditoría hepatobiliar holandesa entre 2014 y 2017. El volumen anual del centro se calculó y se clasificó en categorías de 20 procedimientos por año. Los objetivos principales fueron la morbilidad de mayor grado (Clavien-Dindo grado IIIA o superior) y la mortalidad hospitalaria o la mortalidad a los 30 días. RESULTADOS: Se realizaron un total de 5.590 resecciones en 34 centros con una mediana (rango intercuartílico) de volumen anual de 35 procedimientos (20-69). La tasa global de morbilidad mayor fue del 11% y la mortalidad del 2%. La mortalidad fue de 1,9% después de la resección por metástasis hepáticas colorrectales (colorectal liver metastases, CRLM), 1,2% para no CRLM, 0,4% para tumores benignos, 4,9% para carcinoma hepatocelular, y 10,3% para tumores biliares. Los centros de mayor volumen realizaron más resecciones hepáticas mayores y más resecciones por carcinoma hepatocelular y cáncer biliar. En el análisis multivariable después de ajustar por factores de riesgo conocidos de eventos adversos, no se observó ninguna asociación entre el volumen hospitalario y la morbilidad o mortalidad mayor. CONCLUSIÓN: No hubo asociación entre el volumen hospitalario y los resultados postoperatorios de la cirugía hepática en los Países Bajos.

Multicentre study of multidisciplinary team assessment of pancreatic cancer resectability and treatment allocation.

BACKGROUND: Multidisciplinary team (MDT) meetings have been adopted widely to ensure optimal treatment for patients with cancer. Agreements in tumour staging, resectability assessments and treatment allocation between different MDTs were assessed. METHODS: Of all patients referred to one hospital, 19 patients considered to have non-metastatic pancreatic cancer for evaluation were selected randomly for a multicentre study of MDT decisions in seven units across Northern Europe. Anonymized clinical information and radiological images were disseminated to the MDTs. All patients were reviewed by the MDTs for radiological T, N and M category, resectability assessment and treatment allocation. Each MDT was blinded to the decisions of other teams. Agreements were expressed as raw percentages and Krippendorff's α values, both with 95 per cent confidence intervals. RESULTS: A total of 132 evaluations in 19 patients were carried out by the seven MDTs (1 evaluation was excluded owing to technical problems). The level of agreement for T, N and M categories ranged from moderate to near perfect (46·8, 61·1 and 82·8 per cent respectively), but there was substantial variation in assessment of resectability; seven patients were considered to be resectable by one MDT but unresectable by another. The MDTs all agreed on either a curative or palliative strategy in less than half of the patients (9 of 19). Only fair agreement in treatment allocation was observed (Krippendorff's α 0·31, 95 per cent c.i. 0·16 to 0·45). There was a high level of agreement in treatment allocation where resectability assessments were concordant. CONCLUSION: Considerable disparities in MDT evaluations of patients with pancreatic cancer exist, including substantial variation in resectability assessments.

The DULK (Dutch leakage) and modified DULK score compared: actively seek the leak.

AIM: A standardized postoperative score, the DULK (Dutch leakage) score, has been demonstrated to be a useful clinical tool in the diagnosis of anastomotic leakage. It is complicated, however, and a simplification (the modified DULK score) based on fewer parameters derived from multiple logistic regression analyses has been developed. These include clinical condition, abdominal pain not localized at the wound, C-reactive protein level and respiratory rate. The accuracy of each was compared. METHOD: Data of all patients from five Dutch centres operated on between 16 October 2007 and 1 November 2009 with an anastomosis in the colon or rectum were entered into a prospectively maintained database. RESULTS: In total, 782 patients were included of whom 81 (10.4%) had a clinically relevant anastomotic leakage. The DULK score gave an overall sensitivity of 97% for anastomotic leakage, overall specificity of 53%, a positive predictive value (PPV) of 16% and a negative predictive value (NPV) of 99%. The modified DULK score used clinical condition, abdominal pain not localized at the wound, C-reactive protein level and respiratory rate. With at least one parameter present, overall sensitivity was 97%, overall specificity 57%, PPV 17% and NPV 99.5%. With at least two points PPV was 41% and with three points 57%. CONCLUSION: Both the original and modified DULK scores are useful for the early diagnosis of clinically relevant anastomotic leakage. The modified DULK score offers the benefit of fewer parameters and so can easily be used in a clinical environment to estimate the likelihood of anastomotic leakage. However, the early diagnosis of anastomotic leakage remains difficult.

Clinical relevant pancreatic fistula after pancreatoduodenectomy: when negative amylase levels tell the truth.

Drain Amylase level are routinely determined to diagnose pancreatic fistula after Pancreatocoduodenectomy. Consensus is lacking regarding the cut-off value of amylase to diagnosis clinically relevant postoperative pancreatic fistulae (POPF). The present study proposes a model based on Amylase Value in the Drain (AVD) measured in the first three postoperative days to predict a POPF. Amylase cut-offs were selected from a previous published systematic review and the accuracy were validated in a multicentre database from 12 centres in 2 countries. The present study defined POPF the 2016 ISGPS criteria (3 times the upper limit of normal serum amylase). A learning machine method was used to correlate AVD with the diagnosis of POPF. Overall, 454 (27%) of 1638 patients developed POPF. Machine learning excluded a clinically relevant postoperative pancreatic fistulae with an AUC of 0.962 (95% CI 0.940-0.984) in the first five postoperative days. An AVD at a cut-off of 270 U/L in 2 days in the first three postoperative days excluded a POPF with an AUC of 0.869 (CI 0.81-0.90, p < 0.0001). A single AVD in the first three postoperative days may not exclude POPF after pancreatoduodenectomy. The levels should be monitored until day 3 and have two negative values before removing the drain. In the group with a positive level, the drain should be kept in and AVD monitored until postoperative day five.

Dual origin of mouse spleen macrophages.

The present study concerns the isolation, characterization, origin, and kinetics of spleen macrophages. The spleen was first perfused in situ to remove monocytes from the vascular bed and then dissected and treated with collagenase. The macrophages in the cell suspension thus obtained were characterized morphologically and cytochemically and then quantitated. The spleen cell suspension was incubated for 24 h in Leighton tubes to obtain an enriched glass-adherent population of macrophages for characterization and [3H]thymidine-labeling studies. Almost all of the adhering macrophages were esterase positive, had Fc and C3b receptors, and ingested EIgG and opsonized bacteria. In vitro labeling with [3H]thymidine showed that approximately 5% of the mononuclear phagocytes in the spleen synthesize DNA and must be considered to be dividing cells. The course of the number of labeled monocytes and macrophages after a single injection of [3H]thymidine indicates migration of monocytes into the spleen, where they become macrophages. Calculation of the influx of monocytes into the spleen and of the local production of macrophages by DNA-synthesizing mononuclear phagocytes showed that under steady-state conditions, 55% of the population of spleen macrophages is supplied by monocyte influx and 45% by local production. This means that there is a dual origin of spleen macrophages. The mean turnover time calculated with the value for the efflux of spleen macrophages is 6.0 d.

The kinetics of promonocytes and monocytes in the bone marrow.

The mononuclear phagocytes of the bone marrow can be classified into two cell types, promonocytes and monocytes. The present study was performed to establish whether the promonocytes are the progenitors of the monocytes and to determine the kinetic characteristics of the promonocytes and monocytes in the bone marrow compartment. Both in vitro labeling studies with thymidine-(3)H and determination of the relative amount of DNA in the nuclei of individual cells showed that under normal steady-state conditions the promonocytes are proliferating cells and the monocytes, nondividing cells. In vivo labeling studies provided further evidence that the promonocytes are the progenitor cells of the monocytes. During the first 24 hr after labeling, the promonocytes showed a constant high level of labeling (about 70%). The mean grain count of these cells decreased with time. The labeling index of the monocytes of the bone marrow increased during the first 24 hr after in vivo labeling, but during the same period the mean grain counts remained almost constant, with values amounting to about half those of the promonocytes during the first 6 hr of the experiment. The data concerning the labeling indices and the percentage distribution ratio of the promonocytes and monocytes in the bone marrow, and the labeling indices of the peripheral blood monocytes are used to construct a model population. The results lead to the conclusions that the promonocytes are multiplicative cells and that both daughter cells arising from the division of a promonocyte are monocytes. The DNA-synthesis time found for the promonocytes is 13.6 hr. From this value, the average generation time was computed to be 19.5 hr.

The origin, kinetics, and characteristics of the Kupffer cells in the normal steady state.

Enzymatic digestion with pronase and DNAase was used to isolate Kupffer cells from mouse liver. The characteristics of these cells were found to be similar to those of peritoneal macrophages, except that in the initial suspension the percentage of Kupffer cells with Fc receptors was low, C receptors were absent and the ingestion of opsenized bacteria was very poor, because of the effect of pronase on the cell membrane. After 24 h incubation in vitro all these characteristics return. The in vitro and 1 h-pulse [(3)H]thymidine labeling of the Kupffer cells is low (0.8 and 1 percent, respectively) indicating that in essence these cells do not divide. It was also shown that the small percentage of in vitro labeled Kupffer cells was recently derived from the circulation. After an intravenous injection of zymosan the in vitro labeling index of the Kupffer cells increased 16-fold, but it was proven that these dividing cells were immature mononuclear phagocytes very recently recruited from the bone marrow. The labeling of Kupffer cells aider one or four injections of [(3)H]thymidine reached a peak of 10.4 percent at 48 h or 24.1 percent at 60 h, respectively, indicating that these cells are derived from labeled monocytes. Further evidence for this conclusion was obtained by the absence of an increase of labeled Kupffer cells during treatment with hydrocortisone, which causes a monocytopenia during which no circulating monocytes are available to migrate to the tissues. Labeling studies in animals X-irradiated with hind-limb shielding gave a Kupffer cell labeling index of 5-10 percent of the normal values, which confirms their bone marrow origin. A quantitative study on the production of labeled monocytes in the bone marrow and their transit through the circulation showed that in the normal steady state at least 56.4 percent of the monocytes leaving the circulation become Kupffer cells. Considering the Kupffer cells as kinetically homogeneous this gives a mean turnover time of the total population of Kupffer cells of 21 days.

The effect of azathioprine (Imuran) on the cell cycle of promonocytes and the production of monocytes in the bone marrow.

The present communication concerns the effect of azathioprine on the mitotic activity of promonocytes and the production of monocytes. In vitro and in vivo labeling with [3H]thymidine showed that during azathioprine treatment the promonocytes synthesize DNA and that, contrary to expectation, the labeling index increases. Cytospectrophotometric determination of the Feulgen-DNA content of the promonocytes during azathioprine treatment showed an increase in the percentage of tetraploid promonocytes, and determination of the various phases of the cell cycle showed significantly increased DNA synthesis and cell cycle times as compared with the normal steady state. On the basis of these results it can be concluded that azathioprine arrests the cell cycle of the promonocytes late in the DNA synthesis phase or in the postsynthesis (G2) phase and mitosis does not occur. This timing of the effect of azathioprine had not been previously observed. The diminished mitotic activity of the promonocytes during azathioprine treatment depressed monocyte production. During treatment with 3 mg/kg azathioprine the cell cycle time of the promonocytes was on the average 5.5 h longer than in the normal steady state and the rate of monocyte production was reduced by 70%. During an acute inflammatory reaction too, monocyte production is affected by azathioprine. In animals not treated with azathioprine but with an acute inflammation the cell cycle time becomes shorter and the monocyte production increases, but animals treated with (3 mg/kg) azathioprine do not show this effect. The kinetics of the monocyte also changes under the low dosage of azathioprine. As consequence of the diminished production of monocytes, far fewer (about 50%) monocytes enter and leave the circulation than during the normal steady state. During an acute inflammatory reaction the numbers in transit through the circulation are slightly augmented but remain considerably lower than in nonazathioprine-trehat of animals not treated with azathioprine.

Quantitative study on the production and kinetics of mononuclear phagocytes during an acute inflammatory reaction.

The present communication concerns a quantitative study on the production and kinetics of mononuclear phagocytes during an acute inflammatory response as compared with the steady-state condition. During an acute inflammation induced by an intraperitoneal injection of NBCS, the peritoneal macrophages increase 2.5 times and there is a concomitant threefold increase of the monocytes in the peripheral blood. This increase of the peritoneal macrophages could be caused by a local proliferation of these cells or by the recruitment of monocytes from the circulation. The results of the in vitro and pulse-labeling studies demonstrate that the mitotic activity of the peritoneal macrophages is not increased during the inflammatory response, which indicates that the increase in the number of these cells is not due to local proliferation. Evidence is also presented that the small proportion (maximally 4%) of peritoneal macrophages that synthesize DNA are very recently arrived from the circulation. In agreement with this is the finding that a small number (less than 3%) of the peripheral blood monocytes are capable of synthesizing DNA. Since proof was obtained that the macrophages in the inflammatory peritoneal exudate originate from peripheral blood monocytes and the number of these cells in the circulation was also augmented, an increased formation of monocytes in the bone marrow was expected. Because increased monocyte production could be brought about by an increased number of promonocytes and/or an acceleration of the mitotic activity of the promonocytes, the various parameters of the cell cycle of these cells were determined. In normal mice the DNA-synthesis time of the promonocytes was 11.8 h, the cell cycle time 16.2 h, and the G(1) + G(2) + M phases 4.4 h. During the first 12 h of the inflammatory response a significantly shorter DNA-synthesis time (7.6 h) and cell cycle time (10.8 h) was found. At 24 h, these values approximated those found in normal mice. Next, both the total production and the rate of production of the monocytes were calculated and compared for both conditions. This computation showed that the total production of labeled monocytes during the first 48 h of an acute inflammation was 64% greater than in normal mice. The rate of production, calculated in two ways (i.e., from the data of the total production and also from the data of the cell cycle time together with the total number of promonocytes) complemented each other very well. During the first 12 h of the inflammatory response the production rate was increased 1.5 times and then leveled off, reaching almost the normal rate after 24 h. Furthermore, the excellent agreement between the results of the two methods of calculation for the normal steady state confirmed once more that the promonocyte is the direct precursor cell of the monocyte, giving rise to the two monocytes after each division. The kinetics of the monocytes in the peripheral blood was also altered during the inflammatory response. During the first 48 h, twice the normal number of labeled monocytes went from the bone marrow to the peripheral blood and twice the normal number also left the circulation. Furthermore, at least 70% of this increased number of labeled monocytes leaving the circulation migrated into the inflammatory exudate of the peritoneal cavity, leading to a roughly 11-fold increase of labeled peritoneal macrophages.

Preoperative imaging for colorectal liver metastases: a nationwide population-based study.

BACKGROUND: In patients with colorectal liver metastases (CRLM) preoperative imaging may include contrast-enhanced (ce) MRI and [18 F]fluorodeoxyglucose (18 F-FDG) PET-CT. This study assessed trends and variation between hospitals and oncological networks in the use of preoperative imaging in the Netherlands. METHODS: Data for all patients who underwent liver resection for CRLM in the Netherlands between 2014 and 2018 were retrieved from a nationwide auditing database. Multivariable logistic regression analysis was used to assess use of ceMRI, 18 F-FDG PET-CT and combined ceMRI and 18 F-FDG PET-CT, and trends in preoperative imaging and hospital and oncological network variation. RESULTS: A total of 4510 patients were included, of whom 1562 had ceMRI, 872 had 18 F-FDG PET-CT, and 1293 had combined ceMRI and 18 F-FDG PET-CT. Use of ceMRI increased over time (from 9·6 to 26·2 per cent; P < 0·001), use of 18 F-FDG PET-CT decreased (from 28·6 to 6·0 per cent; P < 0·001), and use of both ceMRI and 18 F-FDG PET-CT 16·9 per cent) remained stable. Unadjusted variation in the use of ceMRI, 18 F-FDG PET-CT, and combined ceMRI and 18 F-FDG PET-CT ranged from 5·6 to 100 per cent between hospitals. After case-mix correction, hospital and oncological network variation was found for all imaging modalities. DISCUSSION: Significant variation exists concerning the use of preoperative imaging for CRLM between hospitals and oncological networks in the Netherlands. The use of MRI is increasing, whereas that of 18 F-FDG PET-CT is decreasing.

ANTECEDENTES: En pacientes con metástasis hepáticas colorrectales (colorrectal liver metastases, CRLM), los estudios de imagen preoperatorios pueden incluir resonancia magnética con contraste (ce)MRI y 18 F-FDG-PET-CT. Este estudio evaluó las tendencias y la variación entre los hospitales y las redes oncológicas en el uso de estudios de imagen preoperatorios en los Países Bajos. MÉTODOS: Todos los pacientes que se sometieron a una resección hepática por CRLM en los Países Bajos entre 2014 y 2018 fueron seleccionados a partir de una base de datos a nivel nacional auditada. El análisis de regresión logística multivariable se utilizó para evaluar el uso de ceMRI, de 18 F-FDG-PET-CT y de ceMRI combinado con 18 F-FDG-PET-CT, así como para determinar las tendencias en los estudios de imagen preoperatorios y las variaciones hospitalarias y de la red oncológica. RESULTADOS: En total, se incluyeron 4.510 pacientes, de los cuales 1.562 se sometieron a ceMRI, 872 a 18 F-FDG-PET-CT y 1.293 a ceMRI combinado con 18 F-FDG-PET-CT. El uso de ceMRI aumentó con el tiempo del 9,6% al 26,2% (P < 0,001), el uso de 18 F-FDG-PET-CT disminuyó (25% a 6,0%, P < 0,001) y el uso de ceMRI y 18 F-FDG-PET- CT (17%) se mantuvo estable. La variación no ajustada entre hospitales en el uso de ceMRI, 18 F-FDG-PET-CT y la combinación de ceMRI y 18 F-FDG-PET-CT oscilaba del 5% al 10%. Después de la corrección por case-mix, la variación hospitalaria y de la red oncológica persistía en todas las pruebas de imagen. CONCLUSIÓN: En los Países Bajos existe una variación significativa entre hospitales y redes oncológicas respecto al uso de pruebas de imagen preoperatorias para el CRLM. El uso de MRI está aumentando, mientras que el uso de 18 F-FDG-PET-CT está disminuyendo.

Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1): a multicenter stepped-wedge cluster randomized controlled trial.

BACKGROUND: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. METHODS/DESIGN: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. DISCUSSION: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018.

Multicentre analysis of oncological and survival outcomes following anastomotic leakage after rectal cancer surgery.

BACKGROUND: The association between diverting stomas and symptomatic anastomotic leakage after rectal cancer surgery was studied, as well as the impact of leakage on local recurrence, distant metastasis, and disease-free, overall and cancer-specific survival. METHODS: Data from the Swedish Rectal Cancer Trial, Dutch TME trial, CAO/ARO/AIO-94 trial, EORTC 22921 trial and Polish Rectal Cancer Trial were pooled (n = 5187). All eligible patients without distant metastases at the time of low anterior resection were selected (n = 2726); overall survival was studied in patients aged 75 years or less (n = 2480). Multivariable models were used to study the association between diverting stomas and anastomotic leakage, and between leakage and recurrence or survival. RESULTS: Some 9.7 per cent of patients were diagnosed with a symptomatic anastomotic leak; diverting stomas were negatively associated with leakage (11.6 per cent without and 7.8 per cent with a stoma; P = 0.002). Anastomotic leakage was negatively associated with overall survival in the multivariable analysis (hazard ratio (HR) 1.29 (95 per cent confidence interval 1.02 to 1.63); P = 0.034), but not with cancer-specific survival (HR 1.12 (0.83 to 1.52); P = 0.466). CONCLUSION: Diverting stomas were associated with less symptomatic anastomotic leakage. Oncological outcome was not significantly influenced by leakage, but overall survival was reduced.

Risk factors for faecal incontinence after rectal cancer treatment.

BACKGROUND: Low anterior resection (LAR) may result in faecal incontinence. This study aimed to identify risk factors for long-term faecal incontinence after total mesorectal excision (TME) with or without preoperative radiotherapy (PRT). METHODS: Between 1996 and 1999, patients with operable rectal cancer were randomized to TME with or without PRT. Eligible patients who underwent LAR were studied retrospectively at 2 years (399 patients) and 5 years (339) after TME. RESULTS: At 5 years after surgery faecal incontinence was reported by 61.5 per cent of patients who had PRT and 38.8 per cent of those who did not (P < 0.001). Excessive blood loss and height of the tumour were associated with long-term faecal incontinence, but only in patients treated with PRT. CONCLUSION: Faecal incontinence is likely to occur after PRT and TME, especially when the perineum is irradiated.

The essentials of locoregional control in the treatment of gastric cancer.

Gastric cancer is the fourth most frequent cancer in the world. For curative treatment and local control of gastric cancer, surgery is essential. The extent of the lymph node dissection is still under debate. Only one available trial showed significantly increased overall survival, whereas in all other randomised trials no significant difference could be found. As surgery alone often is not sufficient in the curative treatment in gastric cancer, different (neo)adjuvant treatment strategies have extensively been studied. The recently published MAGIC trial showed downstaging, downsizing and an improved overall survival for patients treated with perioperative chemotherapy, compared to surgery alone (difference 13%, p = 0.009). The INT 0116 trial on the other hand, demonstrated the benefit of postoperative chemoradiotherapy compared to surgery alone for patients with a curative resection of gastric cancer. However, the quality of resections in this trial was poor, illustrating the importance of standardisation by quality control. This could be done by the Maruyama index, which quantifies the likelihood of unresected disease. In the Netherlands, the CRITICS trial has recently been launched, which will be a quality controlled trial comparing postoperative chemoradiotherapy and chemotherapy on survival and/or locoregional control in patients who receive neoadjuvant chemotherapy followed by a D1+ gastric resection.

The European Organization for Research and Treatment for Cancer (EORTC) strategy for quality assurance in surgical clinical research: Assessment of the past and moving towards the future.

AIMS: Quality assurance (QA) in a surgical trial must be planned and implemented from study development to completion. Elements of quality must be consistently described in a protocols, case report forms (CRFs) and reported in publications. The purpose of this review was to evaluate the most common surgical parameters and how consistently they were described in EORTC study documents where surgery was included. This was the preliminary step in mapping out the challenges of developing a surgical QA strategy in EORTC. METHODS: A systematic review of EORTC surgical protocols from 1980 to 2013 was performed. Two independent reviewers selected and reviewed the protocols. Data extraction was done using a questionnaire developed by EORTC QA committee. The results were compared across the time period. RESULTS: The most common quality parameters described in protocols were surgical technique, definition of resectability, surgical margins and methods of assessing adverse events using the Common Terminology Criteria for Adverse Event (CTCAE). However, these were not consistently reported in publications. A general improvement in the method of protocol development was observed since year 2000 after standardization measures by EORTC. A new surgical chapter template has been proposed. CONCLUSION: There is a need to consistently define and report surgical parameters from protocol development to publication as a first step to QA. A standard surgical chapter in the EORTC protocol template can help address this need. A framework to consistently implement QA for future surgical trials is needed and the rationale for this is described in this review.

[Diagnostic image (221). A female multitrauma patient]. / Diagnose in beeld (221). Een vrouwelijke multitraumapatiënt.

A 39-year-old woman who was involved in a high-energy trauma suffered a haematopneumothorax, subcutaneous emphysema, multiple fractures including a fracture of corpus Tx, and air in the epidural space.

Cell kinetic analysis of a murine macrophage cell line.

For the present study, which was performed to find a reliable method suitable for determination of the cell kinetic parameters of a continuous cell line, use was made of the macrophage cell line J774.1. The doubling time of the cell population was approximately 27 h. The continuous labeling curve showed that all the cells divide and almost no quiescent cells occur. The cell-cycle time as determined from the curve of the labeled cells in mitosis, the course of the stathmokinetic index, and time-lapse videorecordings, was about 19 h. The discrepancy between the population doubling time and the cell-cycle time must be due to death and disintegration of cells during culture in vitro. The results indicate that the doubling time of a cell population is not a reliable parameter to determine the kinetics of a population of continuously proliferating cells and that determination of the course of the stathmokinetic index offers a rapid and simple method to establish the cell-cycle time reliably.

The characterization, origin, and kinetics of skin macrophages during inflammation.

This report deals with the characterization, origin, and kinetics of exudate skin macrophages. The inflammatory stimulus used was a subcutaneously inserted glass coverslip. The macrophages adhering to the glass surface have many characteristics in common with circulating monocytes. During this kind of inflammation there is little differentiation into a more mature or activated type of mononuclear phagocyte. The kinetic studies with [3H]thymidine as cell marker and calculation of local production at the site of inflammation as well as the influx of cells to that site led to the conclusion that greater than or equal to 99% of the exudate skin macrophages were monocyte derived and less than or equal to 1% originated by local division of macrophages.

Micro-CO2-incubator for use on a microscope.

A simple micro-CO2-incubator designed for use on the stage of an inverted microscope is described. This micro-incubator is easy to use, offers a handy tool for the culture of cells under the microscope and its performance compares well with that of a conventional CO2-incubator. A standard disposable culture dish can be placed in the micro-incubator. The culture medium is covered by a gas-permeable layer of mineral oil, this protects the culture from the environment without affecting the culture conditions and allows easy cell manipulation under microscopical control.