Multicentre study of short-course radiotherapy, systemic therapy and resection/ablation for stage IV rectal cancer.

BACKGROUND: The optimal treatment sequence for patients with rectal cancer and synchronous liver metastases remains unclear. The aim of this study was to evaluate the feasibility and effectiveness of short-course pelvic radiotherapy (5 × 5 Gy) followed by systemic therapy and local treatment of all tumour sites in patients with potentially curable stage IV rectal cancer in daily practice. METHODS: This was a retrospective study performed in eight tertiary referral centres in the Netherlands. Patients aged 18 years or above with rectal cancer and potentially resectable liver ± extrahepatic metastases, treated between 2010 and 2015, were eligible. Main outcomes included full completion of treatment schedule, symptom control and survival. RESULTS: In total, 169 patients were included with a median follow-up of 49·5 (95 pr cent c.i. 43·6 to 55·6) months. The completion rate for the entire treatment schedule was 65·7 per cent. Three-year progression-free survival and overall survival (OS) rates were 24·2 (95 per cent c.i. 16·6 to 31·6) and 48·8 (40·4 to 57·2) per cent respectively. Median OS of patients who responded well and completed the treatment schedule was 51·5 months, compared with 15·1 months for patients who did not complete the treatment (P < 0·001). Adequate symptom control of the primary tumour was achieved in 87·0 per cent of all patients. CONCLUSION: Multimodal treatment leads to relief of symptoms in most patients, and is associated with good survival rates in those able to complete the schedule. [Correction added on 12 February 2020, after first online publication: the Conclusion has been reworded for clarity].

ANTECEDENTES: La secuencia óptima de tratamiento en pacientes con cáncer de recto y metástasis hepáticas sincrónicas sigue sin estar clara. El objetivo de este estudio fue evaluar en la práctica diaria la viabilidad y efectividad de la radioterapia pélvica de ciclo corto (5 x 5 Gy) seguida de tratamiento sistémico y tratamiento local de todas las localizaciones del tumor primario en pacientes con cáncer de recto estadio IV potencialmente curables. MÉTODOS: Estudio retrospectivo realizado en ocho centros terciarios de referencia en Holanda. Se consideró elegibles a los pacientes mayores de 18 años con cáncer de recto y metástasis hepáticas ± extrahepáticas potencialmente resecables, que fueron tratados entre 2010 y 2015. Los criterios de valoración principales incluyeron la finalización completa del programa de tratamiento, el control de los síntomas y la supervivencia. RESULTADOS: En total se incluyeron 169 pacientes con una mediana de seguimiento de 50 meses (rango 2-89 meses). La tasa de finalización del programa de tratamiento completo fue del 65,7%. Las tasas de supervivencia libre de progresión a 3 años y supervivencia global (overall survival, OS) fueron 24,2% (i.c. del 95% 16,6-31,6) y 48,8% (i.c. del 95% 40,4-57,2), respectivamente. La mediana de OS de los pacientes que respondieron bien y completaron el programa de tratamiento fue de 51,5 meses, en comparación con 15,1 meses en pacientes que no completaron el tratamiento (P < 0,001). Se logró un control adecuado de los síntomas del tumor primario en el 87,0% de todos los pacientes. CONCLUSIÓN: El tratamiento multimodal consigue paliar los síntomas en la mayoría de los pacientes y se asocia con buenas tasas de supervivencia en aquellos pacientes que pueden completar el programa.

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.

Tissue diagnosis during colorectal cancer surgery using optical sensing: an in vivo study.

BACKGROUND: In colorectal cancer surgery there is a delicate balance between complete removal of the tumor and sparing as much healthy tissue as possible. Especially in rectal cancer, intraoperative tissue recognition could be of great benefit in preventing positive resection margins and sparing as much healthy tissue as possible. To better guide the surgeon, we evaluated the accuracy of diffuse reflectance spectroscopy (DRS) for tissue characterization during colorectal cancer surgery and determined the added value of DRS when compared to clinical judgement. METHODS: DRS spectra were obtained from fat, healthy colorectal wall and tumor tissue during colorectal cancer surgery and results were compared to histopathology examination of the measurement locations. All spectra were first normalized at 800 nm, thereafter two support vector machines (SVM) were trained using a tenfold cross-validation. With the first SVM fat was separated from healthy colorectal wall and tumor tissue, the second SVM distinguished healthy colorectal wall from tumor tissue. RESULTS: Patients were included based on preoperative imaging, indicating advanced local stage colorectal cancer. Based on the measurement results of 32 patients, the classification resulted in a mean accuracy for fat, healthy colorectal wall and tumor of 0.92, 0.89 and 0.95 respectively. If the classification threshold was adjusted such that no false negatives were allowed, the percentage of false positive measurement locations by DRS was 25% compared to 69% by clinical judgement. CONCLUSION: This study shows the potential of DRS for the use of tissue classification during colorectal cancer surgery. Especially the low false positive rate obtained for a false negative rate of zero shows the added value for the surgeons. Trail registration This trail was performed under approval from the internal review board committee (Dutch Trail Register NTR5315), registered on 04/13/2015, https://www.trialregister.nl/trial/5175 .

Adjuvant hepatic arterial infusion pump chemotherapy and resection versus resection alone in patients with low-risk resectable colorectal liver metastases - the multicenter randomized controlled PUMP trial.

BACKGROUND: Recurrences are reported in 70% of all patients after resection of colorectal liver metastases (CRLM), in which half are confined to the liver. Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy aims to reduce the risk of intrahepatic recurrence. A large retrospective propensity score analysis demonstrated that HAIP chemotherapy is particularly effective in patients with low-risk oncological features. The aim of this randomized controlled trial (RCT) --the PUMP trial-- is to investigate the efficacy of adjuvant HAIP chemotherapy in low-risk patients with resectable CRLM. METHODS: This is an open label multicenter RCT. A total of 230 patients with resectable CRLM without extrahepatic disease will be included. Only patients with a clinical risk score (CRS) of 0 to 2 are eligible, meaning: patients are allowed to have no more than two out of five poor prognostic factors (disease-free interval less than 12 months, node-positive colorectal cancer, more than 1 CRLM, largest CRLM more than 5 cm in diameter, serum Carcinoembryonic Antigen above 200 µg/L). Patients randomized to arm A undergo complete resection of CRLM without any adjuvant treatment, which is the standard of care in the Netherlands. Patients in arm B receive an implantable pump at the time of CRLM resection and start adjuvant HAIP chemotherapy 4-12 weeks after surgery, with 6 cycles of floxuridine scheduled. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, hepatic PFS, safety, quality of life, and cost-effectiveness. Pharmacokinetics of intra-arterial administration of floxuridine will be investigated as well as predictive biomarkers for the efficacy of HAIP chemotherapy. In a side study, the accuracy of CT angiography will be compared to radionuclide scintigraphy to detect extrahepatic perfusion. We hypothesize that adjuvant HAIP chemotherapy leads to improved survival, improved quality of life, and a reduction of costs, compared to resection alone. DISCUSSION: If this PUMP trial demonstrates that adjuvant HAIP chemotherapy improves survival in low-risk patients, this treatment approach may be implemented in the standard of care of patients with resected CRLM since adjuvant systemic chemotherapy alone has not improved survival. TRIAL REGISTRATION: The PUMP trial is registered in the Netherlands Trial Register (NTR), number: 7493 . Date of registration September 23, 2018.

Differentiation of healthy and malignant tissue in colon cancer patients using optical spectroscopy: A tool for image-guided surgery.

BACKGROUND: Surgery for colorectal cancer aims for complete tumor resection. Optical-based techniques can identify tumor and surrounding tissue through the tissue specific optical properties, absorption and scattering, which are both influenced by the biochemical and morphological composition of the tissue. OBJECTIVE: To evaluate the feasibility of dual-modality Diffuse Reflectance Spectroscopy-Fluorescence Spectroscopy (DRS-FS) for discrimination between healthy and malignant tissue in colorectal surgery. METHODS: Surgical specimens from colorectal cancer patients were measured immediately after resection using a fiber-optic needle capable of dual-modality DRS-FS. Model-based analyses were used to derive scattering and absorption coefficients and intrinsic fluorescence. Volume fractions of chromophores were estimated. Furthermore, optical data were recorded along a trajectory from healthy tissue towards tumor. RESULTS: Spectral characteristics were identified in 1,273 measured spectra from 21 specimens. Combined DRS and FS discriminated tumor from surrounding tissue with a sensitivity of 95% and a specificity of 88%. Significant spectral changes were seen along the trajectory from healthy tissue to tumor. CONCLUSION: This study demonstrates that dual-modality DRS-FS can identify colorectal cancer from surrounding healthy tissue. The quantification of comprehensible parameters allows robust classification and facilitates extrapolation towards the clinical setting. The technique, here demonstrated in a needle like probe, can be incorporated into surgical tools for optically guided surgery in the near future. Lasers Surg. Med. 47:559-565, 2015. © 2015 Wiley Periodicals, Inc.

[Wearing surgical masks in the operation theatre: yes or no?] / Wel of geen mondmaskers dragen op de OK?

OBJECTIVE: In the Netherlands, the surgical mask is part of the standard surgical attire even for the non-sterile personnel in the operation theatre. Solid evidence on the effect on postoperative infection rates is missing. Due to a national scarcity in surgical masks during the first wave of the COVID-19 crisis the usage of these masks was decreased. In our tertiary referral centre for Surgical Oncology, this led to the decision that, for a period of ten weeks, the surgical masks were only being used by the sterile surgical team and not by non-sterile operation theatre personnel. This retrospective study evaluates the influence of this intervention in terms of postoperative wound infection rates. DESIGN: Retrospective cohort study. METHOD: Consecutive patients undergoing surgery during the first COVID-19 wave (2-3-2020 until 11-05-2020) were compared with patients undergoing surgery in the same period a year earlier. Patients undergoing surgery for soft-tissue malignancies were included. Intra-abdominal surgery was excluded. Primary outcome measurement was wound infection rate within 30 days following surgery. Secondary, a cost reduction analysis was made. RESULTS: In the COVID-19 wave, a total of 219 patients underwent surgery for soft-tissue malignancies, compared to 241 a year earlier. The incidence of postoperative wound infection was 58/460 (12.6%) for the total cohort. There was no difference in infection rate between the COVID-19 period and the same period in 2019; 25/219 (11,4%; 95% CI: 7,8-16,4)) vs. 33/241 (13,7%; 95% CI: 9,8-18,6), p = 0,46) respectively. During the COVID-19 wave, a total of 6.400 of surgical masks were used by the personnel in the operation theatre complex, compared to a total of 11.000 in the same period in 2019. This resulted in a reduction of 42% in usage of surgical masks. CONCLUSION: Based on this mono-centric, explorative retrospective cohort study, it seems that omitting the surgical mask for the non-sterile operation theatre personnel does not influence the postoperative wound infection rate. Despite the fact that our sample size is small, the impressive reduction in usage of 42% demands further research initiatives on a larger scale.

Predictive Factors for Hypertrophy of the Future Liver Remnant After Portal Vein Embolization: A Systematic Review.

This systematic review was conducted to determine factors that are associated with the degree of hypertrophy of the future liver remnant following portal vein embolization. An extensive search on September 15, 2020, and subsequent literature screening resulted in the inclusion of forty-eight articles with 3368 patients in qualitative analysis, of which 18 studies were included in quantitative synthesis. Meta-analyses based on a limited number of studies showed an increase in hypertrophy response when additional embolization of segment 4 was performed (pooled difference of medians = - 3.47, 95% CI - 5.51 to - 1.43) and the use of N-butyl cyanoacrylate for portal vein embolization induced more hypertrophy than polyvinyl alcohol (pooled standardized mean difference (SMD) = 0.60, 95% CI 0.30 to 0.91). There was no indication of a difference in degree of hypertrophy between patients who received neo-adjuvant chemotherapy and those who did not receive pre-procedural systemic therapy(pooled SMD = - 0.37, 95% CI - 1.35 to 0.61), or between male and female patients (pooled SMD = 0.19, 95% CI - 0.12 to 0.50).The study was registered in the International Prospective Register of Systematic Reviews on April 28, 2020 (CRD42020175708).

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.

Initial and long-term outcome after palliative surgical drainage of 269 patients with malignant biliary obstruction.

AIMS: This study aimed to analyse the current outcome after palliative surgical drainage of malignant biliary obstruction. METHOD: From 1992 to 2003, perioperative parameters and the incidence and indications of readmissions were analysed in 269 patients who underwent a palliative biliary bypass for periampullary carcinoma. RESULTS: Hospital mortality occurred in seven patients and median postoperative stay was 10 days. Anastomotic leakage occurred in three patients and intraabdominal haemorrhage in eight patients. Overall 75 patients experienced a complication. Nine patients underwent a relaparotomy during initial hospital admission. Overall, 142 patients were readmitted, 13 for indications related to the biliary bypass, 11 for surgery-related indications. Twenty-five patients were readmitted for radiochemotherapy, 112 for progressive disease and 23 for indications not related to the disease. Median survival was 7.5 months and the 3-year survival 3%. Survival was significantly lower in patients with metastases and in those who underwent elective bypass for gastric outlet obstruction. CONCLUSION: Current hospital mortality after palliative biliary bypass as well as readmission rates for complications related to the biliary bypass or surgical procedure are low. Surgical biliary bypass is a safe and effective palliative treatment for patients with malignant biliary obstruction.

[Centralisation of pancreatic resection: a systematic review and evaluation in the Netherlands]. / Centralisatie van pancreasoperaties: een systematische review en evaluatie in Nederland.

OBJECTIVE: To analyse the volume-outcome effect of pancreatic surgery by means of a systematic review, and to determine the effect of the ongoing plea for centralisation of pylorus-preserving pancreaticoduodenectomy in the Netherlands. DESIGN: Systematic review and retrospective evaluation. METHOD: A systematic search for studies comparing hospital mortality rates after pancreatic resection in high- and low-volume hospitals was conducted. The studies were independently assessed regarding design, inclusion criteria, threshold value for high and low volume and primary hospital mortality outcome. Data were obtained from the Dutch nation-wide registry on the mortality outcome of pancreaticoduodenectomy in 1994-2003. Hospitals were divided into 4 categories based on the number of pancreaticoduodenectomies performed. The effect of the ongoing plea for centralisation was analysed. RESULTS: Twelve observational studies comprising a total of 19,688 patients were included. Because the studies were too heterogeneous to allow a meta-analysis, a qualitative analysis was performed. The relative risk of dying in a high-volume hospital compared with a low-volume hospital was between 0.07 and 0.76 and was inversely proportional to the arbitrarily defined volume cut-off values. Various analyses conducted over a to-year period in the Netherlands reported mortality rates of 14-17% in hospitals that performed fewer than 5 pancreaticoduodenectomies per year, compared with rates of 0.0-3.50 degrees h in hospitals that performed more than 24 pancreaticoduodenectomies per year. The percentage of patients undergoing surgery in hospitals with a volume less than ro pancreaticoduodenectomies per year was 57% in 2000-2003 (454/792), compared with 65% (280/428) in 1994-1995. CONCLUSION: This systematic review provided evidence of an inverse relationship between hospital volume and mortality after pancreaticoduodenectomy and confirmed the value of centralisation of this procedure in high-volume hospitals. The 10-year-long plea of the Dutch surgical community for quality assessment and, if necessary, centralisation has not resulted in a reduction in mortality rates after pancreatic resection or a change in referral patterns in The Netherlands.

Surgical treatment of pancreatic adenocarcinoma; actual survival and prognostic factors in 343 patients.

Survival data of patients with pancreatic carcinoma are often overestimated because of incomplete follow-up. Therefore, the aim of this study was to approach complete follow-up and to analyse survival and prognostic factors of patients who underwent surgical treatment for pancreatic adenocarcinoma. Between 1992 and 2002, 343 patients underwent surgical treatment for pancreatic adenocarcinoma. One hundred and sixty patients underwent a resection with a curative intention and 183 patients underwent bypass surgery for palliation. Follow-up was complete for 93% of patients. Median survival after resection and bypass was 17.0 and 7.5 months, and 5-year survival was 8% and 0, respectively. In multivariate analysis, tumour-positive lymph nodes, non-radical surgery, poor tumour differentiation, and tumour size were independent prognostic factors for survival after resection. For patients treated with bypass surgery, metastatic disease and tumour size independently predicted survival. In conclusion, actual survival of patients with pancreatic adenocarcinoma is disappointing compared with the actuarial survival rates reported in the literature. The independent prognostic factors for survival of patients who underwent surgical treatment for pancreatic adenocarcinoma are tumour-related.

Surgical management of neoplasms of the ampulla of Vater: local resection or pancreatoduodenectomy and prognostic factors for survival.

BACKGROUND: Neoplasms of the ampulla of Vater have a better 5-year survival than pancreatic and bile duct neoplasms after resection. This study was performed to analyze the outcome after local resection and pancreatoduodenectomy (PD) and to identify predictive factors for survival. METHODS: We used a prospective database to evaluate 145 patients (1992-2002) with a neoplasm of the ampulla of Vater. RESULTS: The median age of the entire cohort was 66 years. Agreement between preoperative biopsies and definite resection specimen was 58% for invasive adenocarcinoma. Local resection was performed in 25 patients, but the operation was adequate therapy in only 16 patients (64%). Subsequent PD (n=9) was performed in the remaining patients because of an R1 resection. Other patients (n=120) underwent an elective PD. Hospital mortality was 4.0% (1/25) after local resection and 5.0% (6/120) after PD. Multivariate analysis revealed that advanced invasion and nodal status were independent predictive factors for survival. The overall 5-year actuarial survival of patients with adenocarcinoma after PD was 37%. CONCLUSIONS: Preoperative biopsies have a poor diagnostic accuracy. Local resection is an adequate surgical treatment for adenomas. In experienced hands, PD is the preferred treatment for patients with adenocarcinoma.

Surgical palliation in pancreatic cancer.

The prognosis of patients with pancreatic carcinoma is poor. At the time of diagnosis, approximately 80% of patients are found to have an unresectable tumour, because of local spread or metastatic disease. Therefore, most patients will undergo palliative treatment, which is aimed at the improvement of the quality of life and the prevention of symptoms. The most important symptoms which are associated with advanced pancreatic cancer are pain, obstructive jaundice and gastric outlet obstruction. Controversy remains on the question whether these symptoms should be treated surgically or non-surgically. This review describes the best evidence (if possible randomised controlled trials) in recent literature on the palliation of most important symptoms and focuses on surgical palliative treatment options.

Fiber-chimeric adenoviruses expressing fibers from serotype 16 and 50 improve gene transfer to human pancreatic adenocarcinoma.

Survival of patients with pancreatic cancer is poor. Adenoviral (Ad) gene therapy employing the commonly used serotype 5 reveals limited transduction efficiency due to the low amount of coxsackie-adenovirus receptor on pancreatic cancer cells. To identify fiber-chimeric adenoviruses with improved gene transfer, a library of Ad vectors based on Ad5 and carrying fiber molecules consisting of 16 other serotypes were transduced to human pancreatic carcinoma cell lines. Adenoviruses containing fibers from serotype 16 and 50 showed increased gene transfer and were further analyzed. In a gene-directed prodrug activation system using cytosine deaminase, these adenoviruses proved to be effective in eradicating primary pancreatic tumor cells. Fiber-chimeric Ad5 containing fiber 16 and wild-type Ad5 were also transduced ex vivo to slices of normal human pancreatic tissue and pancreatic carcinoma tissue obtained during surgery. It was shown that fiber-chimeric Ad5 with fiber 16 revealed an improved gene delivery to primary pancreatic tumor tissue compared to Ad5. In conclusion, fiber-chimeric adenoviruses carrying fiber 16 and 50 reveal a significantly enhanced gene transfer and an increased specificity to human pancreatic adenocarcinoma compared to Ad5, whereas transduction to normal pancreatic tissue was decreased. These findings expand the therapeutic window of Ad gene therapy for pancreatic cancer.

Quality of life after curative or palliative surgical treatment of pancreatic and periampullary carcinoma.

BACKGROUND: Quality of life (QOL) is an important outcome measure after treatment of pancreatic and periampullary carcinoma. The aim of this prospective longitudinal study was to analyse QOL after surgery for resectable pancreatic or periampullary carcinoma. METHODS: Patients with potentially resectable tumours underwent pancreaticoduodenectomy (n = 72) or a double-bypass procedure (n = 42). They were asked to complete a questionnaire before laparotomy and at 2 weeks, 6 weeks, and 3, 6, 9 and 12 months after surgery. Fifty-nine patients completed a shortened questionnaire on a weekly basis. RESULTS: There was a temporary decrease in physical and gastrointestinal functioning after pancreaticoduodenectomy. A similar decrease in QOL was observed after double bypass, as well as decreases in mental functioning and overall QOL. Almost all QOL scores returned to preoperative values by about 3 months after surgery, although only briefly so in patients who had a double-bypass procedure. There were no differences between groups in the terminal stages of disease. A rapid decrease on all QOL scales was observed in the last 8 weeks before death. CONCLUSION: Surgery for pancreatic and periampullary carcinoma was not associated with irreversible impairment or protracted recovery of QOL. The relatively long plateau phase after recovery supports the argument for surgical treatment, including surgical palliation in selected patients.