Highlights • One fifth of operated colorectal cancer patients will develop metachronous metastases. • Colon and rectal cancer patients have different patterns of metastatic spread. • Median time to ...diagnosis depends on site of metastasis. • The risk for metastases is associated with patient and tumour characteristics.
Cancer and pandemics are leading causes of death globally, with severe socioeconomic repercussions. To better understand these repercussions, we investigate similarities between pandemics and cancer ...and describe the limited growth in number of infections or cancer cells, using mathematical models. For a pandemic, the analysis shows that in most cases, the initial fast growth is followed by a slower decay in the recovery phase. The risk of infection increases due to the airborne virus contact crossing a risk-threshold. For cancers caused by carcinogens, the increasing risk with age and absorbed dose of toxins that cross a risk-threshold, may lead to the disease onset. The time scales are different for both causes of death: years for cancer development and days to weeks for contact with airborne viruses. Contamination by viruses is on a time scale of seconds or minutes. The risk-threshold to get ill and the number-threshold in cancer cells or viruses, may explain the large variability in the outcome. The number of infected persons per day is better represented in log-lin plots instead of the conventional lin-lin plots. Differences in therapies are discussed. Our mathematical investigation between cancer and pandemics reveals a multifactorial correlation between both fragilities and brings us one step closer to understand, timely predict and ultimately diminish the socioeconomic hurdle of both cancer and pandemics.
BACKGROUND:Textbook outcome (TO) is a multidimensional measure for quality assurance, reflecting the “ideal” surgical outcome.
METHODS:Post-hoc analysis of patients who underwent ...pancreatoduodenectomy (PD) or distal pancreatectomy (DP) for all indications between 2014 and 2017, queried from the nationwide prospective Dutch Pancreatic Cancer Audit. An international survey was conducted among 24 experts from 10 countries to reach consensus on the requirements for TO in pancreatic surgery. Univariable and multivariable logistic regression was performed to identify TO predictors. Between-hospital variation in TO rates was compared using observed-versus-expected rates.
RESULTS:Based on the survey (92% response rate), TO was defined by the absence of postoperative pancreatic fistula, bile leak, postpancreatectomy hemorrhage (all ISGPS grade B/C), severe complications (Clavien–Dindo ≥III), readmission, and in-hospital mortality. Overall, 3341 patients were included (2633 (79%) PD and 708 (21%) DP) of whom 60.3% achieved TO; 58.3% for PD and 67.4% for DP. On multivariable analysis, ASA class 3 predicted a worse TO rate after PD (ASA 3 OR 0.59 0.44–0.80), whereas a dilated pancreatic duct (>3 mm) and pancreatic ductal adenocarcinoma (PDAC) were associated with a better TO rate (OR 2.22 2.05–3.57 and OR 1.36 1.14–1.63, respectively). For DP, female sex and the absence of neoadjuvant therapy predicted better TO rates (OR 1.38 1.01–1.90 and OR 2.53 1.20–5.31, respectively). When comparing institutions, the observed-versus-expected rate for achieving TO varied from 0.71 to 1.46 per hospital after casemix-adjustment.
CONCLUSIONS:TO is a novel quality measure in pancreatic surgery. TO varies considerably between pancreatic centers, demonstrating the potential benefit of quality assurance programs.
Preoperative biliary drainage is often performed in patients with obstructive jaundice caused by cancer of the pancreatic head, but the benefit of the procedure is unclear. This randomized trial ...compared 4 to 6 weeks of preoperative biliary drainage, followed by surgery, with immediate surgery alone for cancer of the pancreatic head. The drainage procedure increased morbidity and did not decrease the rate of surgical complications.
This randomized trial compared 4 to 6 weeks of preoperative biliary drainage, followed by surgery, with immediate surgery alone for cancer of the pancreatic head. The drainage procedure increased morbidity and did not decrease the rate of surgical complications.
Obstructive jaundice is the most common symptom in patients with periampullary cancer (located near the ampulla of Vater) or cancer of the pancreatic head. For patients with a resectable tumor who have no radiologic evidence of metastasis, surgical resection is the only option for cure.
1
–
3
Since surgery in patients with jaundice is thought to increase the risk of postoperative complications, preoperative biliary drainage was introduced to improve the postoperative outcome.
4
In several experimental studies and retrospective case series, preoperative biliary drainage reduced morbidity and mortality after surgery.
4
–
7
However, two meta-analyses of randomized trials and a systematic review of . . .
Local intraperitoneal drug administration is considered a challenging drug delivery route. The therapeutic efficiency is low, mainly due to rapid clearance of drugs. To increase the intraperitoneal ...retention time of specific drugs, a pH‐sensitive supramolecular hydrogel that can act as a drug delivery vehicle is developed. To establish the optimal formulation of the hydrogel and to study its feasibility, safety, and tissue compatibility, in vitro, postmortem, and in vivo experiments are performed. In vitro tests reveal that a hydrogelator formulation with pH ≥ 9 results in a constant viscosity of 0.1 Pa·s. After administration postmortem, the hydrogel covers the parietal and visceral peritoneum with a thin, soft layer. In the subsequent in vivo experiments, 14 healthy rats are subjected to intraperitoneal injection with the hydrogel. Fourteen and 28 days after implantation, the animals are euthanized. Intraperitoneal exposure to the hydrogel is not resulted in significant weight loss or discomfort. Moreover, no macroscopic adverse effects or signs of organ damage are detected. In several intra‐abdominal tissues, vacuolated macrophages are found indicating a physiological degradation of the synthetic hydrogel. This study demonstrates that the supramolecular hydrogel is safe for intraperitoneal application and that the hydrogel shows good tissue compatibility in rats.
Several in vitro and postmortem tests are conducted to establish an optimal hydrogel formulation specifically for the intraperitoneal application. Subsequent in vivo experiments demonstrate the feasibility, safety, and tissue compatibility of the intraperitoneal administration of a pH‐sensitive supramolecular hydrogel in 14 healthy rats. No significant weight loss or discomfort, macroscopic adverse effects, or signs of organ damage are found.
Pseudomyxoma peritonei (PMP) originating from an appendiceal mucinous neoplasm remains a biologically heterogeneous disease. The purpose of our study was to evaluate outcome and long-term survival ...after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) consolidated through an international registry study.
A retrospective multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group International.
Two thousand two hundred ninety-eight patients from 16 specialized units underwent CRS for PMP. Treatment-related mortality was 2% and major operative complications occurred in 24% of patients. The median survival rate was 196 months (16.3 years) and the median progression-free survival rate was 98 months (8.2 years), with 10- and 15-year survival rates of 63% and 59%, respectively. Multivariate analysis identified prior chemotherapy treatment (P < .001), peritoneal mucinous carcinomatosis (PMCA) histopathologic subtype (P < .001), major postoperative complications (P = .008), high peritoneal cancer index (P = .013), debulking surgery (completeness of cytoreduction CCR, 2 or 3; P < .001), and not using HIPEC (P = .030) as independent predictors for a poorer progression-free survival. Older age (P = .006), major postoperative complications (P < .001), debulking surgery (CCR 2 or 3; P < .001), prior chemotherapy treatment (P = .001), and PMCA histopathologic subtype (P < .001) were independent predictors of a poorer overall survival.
The combined modality strategy for PMP may be performed safely with acceptable morbidity and mortality in a specialized unit setting with 63% of patients surviving beyond 10 years. Minimizing nondefinitive operative and systemic chemotherapy treatments before definitive cytoreduction may facilitate the feasibility and improve the outcome of this therapy to achieve long-term survival. Optimal cytoreduction achieves the best outcomes.
Purpose
We explored differences in survival between primary tumor locations, hereby focusing on the role of metastatic sites in synchronous metastatic colorectal cancer (mCRC).
Methods
Data for ...patients diagnosed with synchronous mCRC between 1989 and 2014 were retrieved from the Netherlands Cancer registry. Relative survival and relative excess risks (RER) were analyzed by primary tumor location (right colon (RCC), left colon (LCC), and rectum). Metastatic sites were reported per primary tumor location. Survival was analyzed for metastatic sites combined and for single metastatic sites.
Results
In total, 36,297 patients were included in this study. Metastatic sites differed significantly between primary tumor locations, with liver-only metastases in 43%, 54%, and 52% of RCC, LCC, and rectal cancer patients respectively (
p
< 0.001). Peritoneal metastases were most prevalent in RCC patients (33%), and lung metastases were most prevalent in rectal cancer patients (28%). Regardless of the location of metastases, patients with RCC had a worse survival compared with LCC (RER 0.81, 95% CI 0.78–0.83) and rectal cancer (RER 0.73, 95% CI 0.71–0.76). The survival disadvantage for RCC remained present, even in cases with metastasectomy for liver-only disease (LCC: RER 0.66, 95% CI 0.57–0.76; rectal cancer: RER 0.84, 95% CI 0.66–1.06).
Conclusions
This study showed significant differences in relative survival between primary tumor locations in synchronous mCRC, which can only be partially explained by distinct metastatic sites. Our findings support the concept that RCC, LCC and rectal cancer should be considered distinct entities in synchronous mCRC.
The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin to interval cytoreductive surgery improves recurrence‐free (RFS) and overall survival (OS) in patients with stage III ...ovarian cancer. Homologous recombination deficient (HRD) ovarian tumors are usually more platinum sensitive. Since hyperthermia impairs BRCA1/2 protein function, we hypothesized that HRD tumors respond best to treatment with HIPEC. We analyzed the effect of HIPEC in patients in the OVHIPEC trial, stratified by HRD status and BRCAm status. Clinical data and tissue samples were collected from patients included in the randomized, phase III OVHIPEC‐1 trial. DNA copy number variation (CNV) profiles, HRD‐related pathogenic mutations and BRCA1 promotor hypermethylation were determined. CNV‐profiles were categorized as HRD or non‐HRD, based on a previously validated algorithm‐based BRCA1‐like classifier. Hazard ratios (HR) and corresponding 99% confidence intervals (CI) for the effect of RFS and OS of HIPEC in the BRCAm, the HRD/BRCAwt and the non‐HRD group were estimated using Cox proportional hazard models. Tumor DNA was available from 200/245 (82%) patients. Seventeen (9%) tumors carried a pathogenic mutation in BRCA1 and 14 (7%) in BRCA2. Ninety‐one (46%) tumors classified as BRCA1‐like. The effect of HIPEC on RFS and OS was absent in BRCAm tumors (HR 1.25; 99%CI 0.48‐3.29), and most present in HRD/BRCAwt (HR 0.44; 99%CI 0.21‐0.91), and non‐HRD/BRCAwt tumors (HR 0.82; 99%CI 0.48‐1.42), interaction P value: 0.024. Patients with HRD tumors without pathogenic BRCA1/2 mutation appear to benefit most from treatment with HIPEC, while benefit in patients with BRCA1/2 pathogenic mutations and patients without HRD seems less evident.
What's new?
Serous ovarian cancers that are homologous recombination deficient (HRD) often are sensitive to platinum‐containing chemotherapy. Whether hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin benefits patients with HRD tumors, however, remains unclear. In this study, an algorithm‐based HRD classifier was validated using data and tissue derived from the randomized, phase III OVHIPEC‐1 trial. Interval cytoreductive surgery and HIPEC was found to prolong recurrence‐free and overall survival moin patients with HRD/BRCA1 wild‐type ovarian cancers. Responses of BRCA1/2‐mutated and HR‐proficient ovarian cancers to HIPEC were less pronounced. The HRD classifier is a promising tool for identifying ovarian cancer patients who may benefit from HRD relying treatment modalities.
The reported incidence of synchronous and metachronous ovarian metastases (OM) from colorectal cancer (CRC) is ~3.4%. OM from CRC are often considered sanctuary sites due to their lower sensitivity ...to systemic treatment. It has thus been hypothesized that the presence of OM decreases overall survival. Therefore, the purpose of our study was to evaluate the impact of synchronous OM on overall survival in female patients with stage IV CRC treated with systemic therapy alone with palliative intent. The present study used data from the Netherlands Cancer Registry and included female CRC patients with synchronous systemic metastases who were treated with systemic therapy between 2008 and 2018. A subsample was created using propensity score matching to create comparable groups. Propensity scores were determined using a logistic regression model in which the dependent variable was the presence of OM and the independent variables were the variables that differed significantly between both groups. Our study included 5253 patients with stage IV CRC that received systemic therapy. Among these patients, 161 (3%) had OM while 5092 (97%) had extra‐ovarian metastases only. Three‐year overall survival rates did not show a significant difference between patients with OM compared to patients without ovarian metastases. Moreover, the propensity score‐matched analysis showed that the presence of OM in patients treated with systemic therapy for stage IV CRC disease was not associated with decreased 3‐year overall survival. However, the results of the present study should be interpreted with caution, due to its observational character and used selection criteria.
What's new?
The ovaries are a refuge for metastatic colorectal cancer (CRC) cells, and thus ovarian metastases from CRC exhibit reduced sensitivity to systemic therapy. Evidence suggests that, because of this sanctuary site, ovarian metastasis is a negative prognostic factor for patients with advanced CRC. Here, using data from the Netherlands Cancer Registry, the authors evaluated the impact of synchronous ovarian metastases on survival among female stage IV CRC patients that were treated with systemic therapy alone. Analyses show that just 3% of patients in the study group had ovarian metastases. Moreover, the presence of synchronous ovarian metastases was not associated with reduced 3‐year overall survival.
The aims of this study were to investigate incidence, risk factors and treatment of synchronous or metachronous peritoneal metastases (PM) from gastric cancer and to estimate survival of these ...patients using population‐based data. Patients diagnosed with gastric cancer in 2015 to 2016 were selected from the Netherlands Cancer Registry. The incidence of synchronous and metachronous PM were calculated. Multivariable regression analyses were performed to identify factors associated with the occurrence of PM. Treatment and survival were compared between patients with synchronous and metachronous PM. Of 2206 patients with gastric cancer, 741 (34%) were diagnosed with PM. Of these, 498 (23%) had synchronous PM. The cumulative incidence of metachronous PM in patients who underwent potentially curative treatment (n = 675) was 22.8% at 3 years. A factor associated with synchronous and metachronous PM was diffuse type histology. Patients diagnosed with synchronous PM more often received systemic treatment than patients with metachronous PM (35% vs 18%, respectively, P < .001). Median overall survival was comparable between synchronous and metachronous PM (3.2 vs 2.3 months, respectively, P = .731). Approximately one third of all patients with gastric cancer are diagnosed with PM, either at primary diagnosis or during 3‐year follow‐up after potentially curative treatment. Patients with metachronous PM less often received systemic treatment than those with synchronous PM but survival was comparable between both groups. Future trials are warranted to detect gastric cancer at an earlier stage and to examine strategies that lower the risk of peritoneal dissemination. Also, specific treatment options for patients with gastric PM should be further investigated.
What's new?
The overall burden of peritoneal metastases in patients with gastric cancer and a better understanding of peritoneal recurrence are still to be established. In this population‐based study, approximately one third of patients with gastric cancer were diagnosed with peritoneal metastases, either at primary diagnosis or within 3 years after potentially curative treatment. Patients with metachronous peritoneal metastases less often received systemic treatment than patients with synchronous peritoneal metastases, but survival was comparable between the two groups. Future trials are warranted to detect gastric cancer at an earlier stage and examine strategies for lowering the risk of peritoneal dissemination.
PDF
