Nationwide Use and Outcome of Surgery for Locally Advanced Pancreatic Cancer Following Induction Chemotherapy.

BACKGROUND: Several international high-volume centers have reported good outcomes after resection of locally advanced pancreatic cancer (LAPC) following chemo(radio)therapy, but it is unclear how this translates to nationwide clinical practice and outcome. This study aims to assess the nationwide use and outcome of resection of LAPC following induction chemo(radio)therapy. PATIENTS AND METHODS: A multicenter retrospective study including all patients who underwent resection for LAPC following chemo(radio)therapy in all 16 Dutch pancreatic surgery centers (2014-2020), registered in the mandatory Dutch Pancreatic Cancer Audit. LAPC is defined as arterial involvement > 90° and/or portomesenteric venous > 270° involvement or occlusion. RESULTS: Overall, 142 patients underwent resection for LAPC, of whom 34.5% met the 2022 National Comprehensive Cancer Network criteria. FOLFIRINOX was the most commonly (93.7%) used chemotherapy [median 5 cycles (IQR 4-8)]. Venous and arterial resections were performed in 51.4% and 14.8% of patients. Most resections (73.9%) were performed in high-volume centers (i.e., ≥ 60 pancreatoduodenectomies/year). Overall median volume of LAPC resections/center was 4 (IQR 1-7). In-hospital/30-day major morbidity was 37.3% and 90-day mortality was 4.2%. Median OS from diagnosis was 26 months (95% CI 23-28) and 5-year OS 18%. Surgery in high-volume centers [HR = 0.542 (95% CI 0.318-0.923)], ypN1-2 [HR = 3.141 (95% CI 1.886-5.234)], and major morbidity [HR = 2.031 (95% CI 1.272-3.244)] were associated with OS. CONCLUSIONS: Resection of LAPC following chemo(radio)therapy is infrequently performed in the Netherlands, albeit with acceptable morbidity, mortality, and OS. Given these findings, a structured nationwide approach involving international centers of excellence would be needed to improve selection of patients with LAPC for surgical resection following induction therapy.

Prophylactic Intra-Uterine ß-Cyclodextrin Administration during Intra-Uterine Ureaplasma parvum Infection Partly Prevents Liver Inflammation without Interfering with the Enterohepatic Circulation of the Fetal Sheep.

Chorioamnionitis can lead to inflammation and injury of the liver and gut, thereby predisposing patients to adverse outcomes such as necrotizing enterocolitis (NEC). In addition, intestinal bile acids (BAs) accumulation is causally linked to NEC development. Plant sterols are a promising intervention to prevent NEC development, considering their anti-inflammatory properties in the liver. Therefore, we investigated whether an intra-amniotic (IA) Ureaplasma parvum (UP) infection affected the liver and enterohepatic circulation (EHC) and evaluated whether an IA administered plant sterol mixture dissolved in ß-cyclodextrin exerted prophylactic effects. An ovine chorioamnionitis model was used in which liver inflammation and the EHC were assessed following IA UP exposure in the presence or absence of IA prophylactic plant sterols (a mixture of ß-sitosterol and campesterol dissolved in ß-cyclodextrin (carrier)) or carrier alone. IA UP exposure caused an inflammatory reaction in the liver, histologically seen as clustered and conflated hepatic erythropoiesis in the parenchyma, which was partially prevented by IA administration of sterol + ß-cyclodextrin, or ß-cyclodextrin alone. In addition, IA administration of ß-cyclodextrin prior to UP caused changes in the expression of several hepatic BAs transporters, without causing alterations in other aspects of the EHC. Thereby, the addition of plant sterols to the carrier ß-cyclodextrin did not have additional effects.

Improved overall survival for patients with rectal cancer since 1990: the effects of TME surgery and pre-operative radiotherapy.

AIM: The aim was to study the effects of the introduction of TME surgery and pre-operative radiotherapy on overall survival (OS) by comparing patients treated in the period before (1990-1995), during (1996-1999) and after (2000-2002) the TME trial. PATIENTS AND METHODS: Patients diagnosed with rectal carcinoma in the region of Comprehensive Cancer Centres South and West were used (n=3179). RESULTS: Five-year OS was, respectively, 56%, 62% and 65% in the pre-trial, trial and post-trial periods (p<0.001). Pre-operative RT was increasingly used over time and significantly related to OS in the post-trial period (p=0.002), but not in the pre-trial and trial periods. CONCLUSIONS: Population-based OS improved markedly since the introduction of TME surgery. With standardised TME surgery, pre-operative RT improved OS, whereas withholding pre-operative RT was associated with a poorer prognosis. The present study supports that pre-operative RT was correctly introduced as a standard treatment before TME surgery in our national guideline.

Patients with curative resection of cT3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group.

PURPOSE: European Organisation for Research and Treatment of Cancer (EORTC) trial 22921 compared adjuvant fluorouracil-based chemotherapy (CT) to no adjuvant treatment in a 2 x 2 factorial trial with randomization for preoperative (chemo)radiotherapy in patients with resectable T3-4 rectal cancer. The results showed no significant impact of adjuvant CT on progression-free or overall survival, although a difference seemed to emerge at approximately, respectively, 2 and 5 years after the start of preoperative treatment. We further explored the data with the aim of refining our understanding of the long-term results. PATIENTS AND METHODS: Data of 785 of the 1,011 randomly assigned patients who whose disease was M0 at curative surgery were used. Using meta-analytic methods, we investigated the homogeneity of the effect of adjuvant CT on the time to relapse or death after surgery (disease-free survival [DFS]) and survival in patient subgroups. RESULTS: Although there was no statistically significant impact of adjuvant CT on DFS for the whole group (P > .5), the treatment effect differed significantly between the ypT0-2 and the ypT3-4 patients (heterogeneity P = .009): only the ypT0-2 patients seemed to benefit from adjuvant CT (P = .011). The same pattern was observed for overall survival. CONCLUSION: Exploratory analyses suggest that only good-prognosis patients (ypT0-2) benefit from adjuvant CT. This could explain why, in the whole group, the progression-free and overall survival diverged only after the poor-prognosis patients (ypT3-4) had experienced treatment failure. Patients in whom no downstaging was achieved did not benefit. This also suggests that the same prognostic factors may drive both tumor sensitivity for the primary treatment and long-term clinical benefit from further adjuvant CT.

Survival of elderly rectal cancer patients not improved: analysis of population based data on the impact of TME surgery.

INTRODUCTION: The incidence of rectal cancer is highest in elderly patients. However, these patients are often underrepresented in randomised studies. Therefore, it is not clear whether results of rectal cancer studies are equally applicable to both elderly and younger patients. In this paper, the Dutch Total Mesorectal Excision (TME) study is revisited, focused on patients aged 75 years and above. The rectal cancer databases of the Comprehensive Cancer Centres (CCC) South and West were combined to analyse the effect of the TME-study in three different periods: before (1990-1995), during (1996-1999) and after (2000-2002) the trial. RESULTS: Implementation of preoperative radiotherapy, as investigated in the TME trial, and the introduction of TME surgery resulted in improved 5 year survival during the subsequent periods, in patients younger than 75 years, of 60% (1990-1995) to 67% (1996-1999) and 70% (2000-2002) (log rank p<0.0001). The older patients did not improve and remained at 41%, 40% and 43% at 5 years in the respective periods. Furthermore, mortality during the first 6-month period after treatment is significantly raised compared to younger patients: 14% in the elderly, compared to 3.9% in the younger TME-study patient (p<0.0001 X2). In the CCC database these figures were confirmed at 16% and 3.9% (p<0.0001 X2). CONCLUSION: Overall survival was not improved in the elderly rectal cancer patient after introduction of preoperative radiotherapy and TME-surgery. Non-cancer related mortality is a significant problem in the first 6 months after surgery.