Extended Resections for Advanced Gallbladder Cancer: Results from a Nationwide Cohort Study.

BACKGROUND: Extended resections (i.e., major hepatectomy and/or pancreatoduodenectomy) are rarely performed for gallbladder cancer (GBC) because outcomes remain inconclusive. Data regarding extended resections from Western centers are sparse. This Dutch, multicenter cohort study analyzed the outcomes of patients who underwent extended resections for locally advanced GBC. METHODS: Patients with GBC who underwent extended resection with curative intent between January 2000 and September 2018 were identified from the Netherlands Cancer Registry. Extended resection was defined as a major hepatectomy (resection of ≥ 3 liver segments), a pancreatoduodenectomy, or both. Treatment and survival data were obtained. Postoperative morbidity, mortality, survival, and characteristics of short- and long-term survivors were assessed. RESULTS: The study included 33 patients. For 16 of the patients, R0 resection margins were achieved. Major postoperative complications (Clavien Dindo ≥ 3A) occurred for 19 patients, and 4 patients experienced postoperative mortality within 90 days. Recurrence occurred for 24 patients. The median overall survival (OS) was 12.8 months (95% confidence interval, 6.5-19.0 months). A 2-year survival period was achieved for 10 patients (30%) and a 5-year survival period for 5 patients (15%). Common bile duct, liver, perineural and perivascular invasion and jaundice were associated with reduced survival. All three recurrence-free patients had R0 resection margins and no liver invasion. CONCLUSION: The median OS after extended resections for advanced GBC was 12.8 months in this cohort. Although postoperative morbidity and mortality were significant, long-term survival (≥ 2 years) was achieved in a subset of patients. Therefore, GBC requiring major surgery does not preclude long-term survival, and a subgroup of patients benefit from surgery.

Comparing practice and outcome of laparoscopic liver resection between high-volume expert centres and nationwide low-to-medium volume centres.

BACKGROUND: Based on excellent outcomes from high-volume centres, laparoscopic liver resection is increasingly being adopted into nationwide practice which typically includes low-medium volume centres. It is unknown how the use and outcome of laparoscopic liver resection compare between high-volume centres and low-medium volume centres. This study aimed to compare use and outcome of laparoscopic liver resection in three leading European high-volume centres and nationwide practice in the Netherlands. METHOD: An international, retrospective multicentre cohort study including data from three European high-volume centres (Oslo, Southampton and Milan) and all 20 centres in the Netherlands performing laparoscopic liver resection (low-medium volume practice) from January 2011 to December 2016. A high-volume centre is defined as a centre performing >50 laparoscopic liver resections per year. Patients were retrospectively stratified into low, moderate- and high-risk Southampton difficulty score groups. RESULTS: A total of 2425 patients were included (1540 high-volume; 885 low-medium volume). The median annual proportion of laparoscopic liver resection was 42.9 per cent in high-volume centres and 7.2 per cent in low-medium volume centres. Patients in the high-volume centres had a lower conversion rate (7.4 versus 13.1 per cent; P < 0.001) with less intraoperative incidents (9.3 versus 14.6 per cent; P = 0.002) as compared to low-medium volume centres. Whereas postoperative morbidity and mortality rates were similar in the two groups, a lower reintervention rate (5.1 versus 7.2 per cent; P = 0.034) and a shorter postoperative hospital stay (3 versus 5 days; P < 0.001) were observed in the high-volume centres as compared to the low-medium volume centres. In each Southampton difficulty score group, the conversion rate was lower and hospital stay shorter in high-volume centres. The rate of intraoperative incidents did not differ in the low-risk group, whilst in the moderate-risk and high-risk groups this rate was lower in high-volume centres (absolute difference 6.7 and 14.2 per cent; all P < 0.004). CONCLUSION: High-volume expert centres had a sixfold higher use of laparoscopic liver resection, less conversions, and shorter hospital stay, as compared to a nationwide low-medium volume practice. Stratification into Southampton difficulty score risk groups identified some differences but largely outcomes appeared better for high-volume centres in each risk group.

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.

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.

Health-related quality of life after pancreatic resection for malignancy.

BACKGROUND: Health-related quality of life (QoL) is of major importance in pancreatic cancer, owing to the limited life expectation. The aim of this prospective longitudinal study was to describe QoL in patients undergoing resection for pancreatic or periampullary malignancy. METHODS: QoL was measured on a scale of 0-100 in patients who underwent pancreatic resection for malignancy or premalignancy at the University Medical Centre Utrecht before resection, and 1, 3, 6 and 12 months after surgery. Measures consisted of the RAND-36, the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ-C30) and the EORTC pancreatic cancer-specific module (QLQ-PAN26). RESULTS: Between March 2012 and November 2013, 68 consecutive patients with a malignancy (59 patients) or premalignancy (9) were included. Physical role restriction, social and emotional domains showed a significant and clinically relevant deterioration directly after operation in 53 per cent (RAND-36, P < 0.001), 63 and 78 per cent (QLQ-C30 and RAND-36 respectively, P < 0.001) and 37 per cent (RAND-36, P < 0.001) of patients respectively. Most domains demonstrated recovery to preoperative values or better at 3 months, except for physical functioning. Emotional functioning at 3, 6 and 12 months was better than at baseline (P < 0.001). Symptom scores revealed a deterioration in vitality, pain (P = 0.002), fatigue (P < 0.001), appetite loss (P < 0.001), altered bowel habit (P = 0.001) and side-effects (P < 0.001) after 1 month. After 3 months, only side-effects were worse than preoperative values (P < 0.001). CONCLUSION: QoL after pancreatic resection for malignant and premalignant tumours decreased considerably in the early postoperative phase. Full recovery of QoL took up to 6 months after the operation.

Totally laparoscopic right hemicolectomy with intracorporeal anastomosis is a technically and oncologically safe procedure.

BACKGROUND: During laparoscopic right hemicolectomy, most surgeons perform an extracorporeal anastomosis. A totally laparoscopic procedure with intracorporeal anastomosis may improve cosmesis because midline- or paraumbilical incisions can be avoided. Here, we investigate the safety of an intracorporeal anastomosis from a technical and oncological perspective. METHODS: All patients who underwent right hemicolectomy with intracorporeal anastomosis between 2003-2011 were retrospectively analyzed. Parameters were duration of surgery, intraoperative blood loss, mortality and morbidity. Adequacy of oncologic resections was scored by resectional margins and number of harvested lymph nodes. RESULTS: A total of 162 patients were included with a median age of 69 years (IQR60-76). The duration of surgery was 100 minutes (80-120) and intraoperative blood loss was 30 mL (10-100). Hundred-twenty patients (74%) underwent an oncologic resection. Number of harvested lymph nodes was 12 (9-18). RO-resection was achieved in 100%. Four patients died (2.5%). Postoperative complications were: anastomotic leakage (3.1%; n = 5), ileus (4.9%; n = 8), abscesses (2.5% ; n = 4), wound infection (3.1% ; n = 5) and cardiopulmonary complications (10.5% ; n = 17). Duration of oncological follow-up was 2.5 years (1.3-4.6). Local recurrence and overall survival rates at two years were 0.8% and 85.4%, respectively. CONCLUSION: Right hemicolectomy with intracorporeal anastomosis is a technically and oncologically safe procedure with acceptable operating time and low mortality.

Treatment dilemmas in patients with synchronous colorectal liver metastases.

Approximately 20 % of patients with colorectal cancer have synchronous liver metastases at the time of diagnosis. In some instances it is difficult to determine the best treatment strategy in these patients. For example, should the primary tumor be removed in those patients with unresectable liver metastases and who do not have any symptoms of the primary tumor? Or which operation should be performed first in patients with rectal cancer and synchronous resectable liver metastases? Unfortunately, there are no clear answers to these questions from prospective randomized trials. In the present article retrospective studies are analyzed in order to define the best possible treatment strategy for patients with synchronous colorectal liver metastases.

Advances in adjuvant therapy of biliary tract cancer: an overview of current clinical evidence based on phase II and III trials.

Patients with biliary tract cancer (BTC) have a high recurrence rate after complete surgical resection. To reduce the risk of recurrence and to improve survival, several chemotherapeutic agents that have shown to be active in locally advanced and metastatic BTC have been investigated in the adjuvant setting in prospective clinical trials. Based on the results of the BILCAP phase III trial, capecitabine was adapted as the standard of care by the ASCO clinical practice guideline. Ongoing randomized controlled trials mainly compare capecitabine with gemcitabine-based chemotherapy or chemoradiotherapy. This review provides an update of adjuvant therapy in BTC based on published data of phase II and III trials and ongoing randomized controlled trials (RCTs).

[Diagnostic image (392). A woman with redness and swelling of the breast]. / Diagnose in beeld (392). Een vrouw met roodheid en zwelling van de mamma.

A 40-year-old woman presented with progressive swelling and red to purple discoloration of the left mamma. A mammary carcinoma had been radically removed two years before. Skin biopsy showed diffuse intralymphatic malignant cells consistent with inflammatory breast cancer.

Portal vein ligation versus portal vein embolization for induction of hypertrophy of the future liver remnant: A systematic review and meta-analysis.

An important risk of major hepatic resection is postoperative liver failure, which is directly related to insufficient future liver remnant (FLR). Portal vein embolization (PVE) and portal vein ligation (PVL) can minimize this risk by inducing hypertrophy of the FLR. The aim of this systematic review and meta-analysis was to compare the efficacy and safety of PVE and PVL for FLR hypertrophy. A systematic search was conducted on the17th of January 2017. The methodological quality of the studies was assessed using the Oxford Critical Appraisal Skills Program for cohort studies. The primary endpoint was the relative rate of hypertrophy of the FLR. Number of cancelled hepatic resection and postoperative morbidity and mortality were secondary endpoints. For meta-analysis, the pooled hypertrophy rate was calculated for each intervention. The literature search identified 21 eligible studies with 1953 PVE and 123 PVL patients. All studies were included in the meta-analysis. No significant differences were found regarding the rate of FLR hypertrophy (PVE 43.2%, PVL 38.5%, p = 0.39). The number of cancelled hepatic resections due to inadequate hypertrophy was significantly lower after PVL (p = 0.002). No differences were found in post-intervention mortality and morbidity. This meta-analysis demonstrated no significant differences in safety and rate of FLR hypertrophy between PVE and PVL. PVE should be considered as the preferred strategy, since it is a minimally invasive procedure. However, during a two-stage procedure, PVL can be performed with expected comparable outcome as PVE.

Partial monosomy 8p and partial trisomy 8p with moderate mental retardation.

A female patient with mosaicism for partial monosomy 8p and partial trisomy 8p is presented. Her karyotype is 46,XX, del(8)(p21)/46,XX, dup(8)(p21----pter). She showed minimal dysmorphic features, agenesis of the corpus callosum and moderate developmental delay. There is no previous report of mosaicism for partial monosomy and partial trisomy 8p. The clinical findings in the presently described patient are less severe than those reported in cases with only monosomy or trisomy of the distal part of chromosome 8.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal and gastrointestinal origin shows acceptable morbidity and high survival.

BACKGROUND: Peritoneal carcinomatosis from colorectal origin carries a poor prognosis. Recent clinical studies show that cytoreductive surgery (CS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival of selected patients with a colorectal carcinoma and isolated peritoneal carcinomatosis in the absence of extra-abdominal metastases. Here, we report the clinical outcomes and survival after cytoreductive surgery and HIPEC of the first cohort of patients treated in our institution. METHODS: Sixty-seven patients underwent a laparotomy. Complete cytoreduction could be performed in 49 patients, who underwent a total of 53 CS-HIPEC procedures. All had peritoneal carcinomatosis originating from primary colorectal, cecal, appendiceal, and gastric tumors. RESULTS: In patients who underwent CS-HIPEC, an R0 resection could be achieved in 4%, R1 in 88%, and R2 in 8%. The 30-day mortality was 0; one patient died in-hospital after 10 weeks. The median hospital stay was 12 days (range 4-56). The overall morbidity was 43%, including extended gastroparesis (11%), anastomotic failure (11%) and intra-abdominal abscess (9%). Mean time to clinical recurrence was 12 months (range 4-22). The actuarial 1-year survival was 88% and 2-year survival was 75%. CONCLUSION: In well-selected patients referred to a specialized institution, CS-HIPEC has an acceptable morbidity and high survival rate.