Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) are increasingly utilised in the management of colorectal peritoneal metastases (CPM). This combined modality is ...associated with a significant learning curve (LC) and is often criticised for its associated morbidity. This study aims to inspect the LC of this procedure in our institute.
A retrospective review of the institution's prospectively maintained database of CRS-HIPEC cases was performed. Patients treated for CPM were stratified into two groups: Group 1 consists of patients in our initial 100 cases of CRS-HIPEC and Group 2 comprises patients treated subsequently. Perioperative prognostic factors and oncological outcomes were analysed.
Between 2001 and 2016, 77 patients with CPM underwent CRS-HIPEC, of which 31 patients (40.3%) were in Group 1 and 46 patients (59.7%) in Group 2. Median follow-up duration was 96 months in Group 1 and 25 months in Group 2. There were no differences in OS (35 months vs 46 months, p = 0.054) and DFS (13 months vs 14 months, p = 0.676) between the groups. There were more patients with higher PCI (≥12) (57.1% vs 22.2%, p = 0.006) and high-grade complications (25.8% vs 8.7%, p = 0.045) in Group 1. Group 2 patients had a shorter hospitalisation (14 days vs 11 days, p = 0.015) and SICU stay (1 day vs 0 days, p < 0.001).
An improvement in the perioperative outcomes after CRS-HIPEC for CPM may be partly attributed to overcoming the LC and incorporation of better patient selection methods.
Background
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly used in peritoneal carcinomatosis (PC) management. This modality is criticized for its ...high morbidity and mortality. We evaluate the morbidity and mortality of patients undergoing this procedure in our institution.
Methods
A review of our institution’s database was performed. All patients who underwent CRS/HIPEC between July 2011 and March 2018 were divided into three groups: no, low-grade, and high-grade complications. Prognostic factors were determined with Cox regression, while morbidity risk factors were analyzed using multinomial logistic regression.
Results
225 consecutive patients underwent CRS/HIPEC. The most common primary cancer types were colorectal (35.1%), appendiceal (25.8%), and ovarian (22.2%). Median age was 55 years old (range 14–77), and patients were typically female (68.0%). 38.7% developed low-grade complications and 14.7% had high-grade complications. No 30-day mortality was observed. Different tumor origins are associated with significant differences in overall survival (
p
< 0.001). Patients without complications had significantly better survival than those with high-grade complications (HR 0.35, 95% CI 0.15–0.81,
p
< 0.001). Males were more likely to develop low-grade complications (OR 3.30, 95% CI 1.31–8.30,
p
= 0.011). Intra-operative blood loss was associated with greater odds of developing any post-operative complications (OR 1.001, 95% CI 1.0003–1.002,
p
= 0.007; and OR 1.002, 95% CI 1.001–1.002,
p
< 0.001, for low and high grade, respectively).
Conclusion
Presence of high-grade complication was associated with poorer survival in patients after CRS/HIPEC. Pre-operative careful assessment of patients is pivotal to ensure favorable patient outcome following this complex procedure.
Retroperitoneal liposarcomas (RPLPSs) are a rare tumor group for which current guidelines recommend aggressive
en bloc
resection to attain microscopically negative (R0) margins. To ensure R0 margins, ...resection of adherent or adjacent organs is often required. However, it is still unclear if R0 margins confer any additional benefit to patients over a grossly negative but microscopically positive (R1) margin. We performed a systematic search of PubMed and Embase databases for studies including patients receiving R0 or R1 resection for RPLPS. Nine retrospective cohort studies, one prospective cohort study, and 49 case reports/case series were included. A total of 552 patients with RPLPS were evaluated: 346 underwent R0 resection and 206 underwent R1 resection. In the R0 group, 5-year overall survival (OS) ranged from 58.3% to 85.7%; local recurrence (LR) ranged from 45.5% to 52.3%. In the R1 group, 5-year OS ranged from 35% to 55.3%; LR ranged from 66.7% to 91.7%. Among cohort studies, OS, disease-free survival (DFS), LR rate, and LR-free survival (LRFS) were significantly associated with R0 resections. Assessment of case series and reports suggested that the R0 margin led to a slightly higher morbidity than that of R1. In conclusion, this review found the R0 margin to be associated with reductions in LR rates and improved OS when compared with the R1 margins, though accompanied by slight increases in morbidity. The roles of tumor histotype and perioperative chemotherapy or radiotherapy were not well-elucidated in this review.
The success of personalised therapy depends on identification and inhibition of the oncogene(s) on which that tumour is dependent. We aimed to determine whether a receptor tyrosine kinase (RTK) array ...could be used to select the most effective therapeutic strategies in molecularly heterogeneous oesophago-gastric adenocarcinomas.
Gene expression profiling from oesophago-gastric tumours (n=75) and preinvasive stages (n=57) identified the active signalling pathways, which was confirmed using immunohistochemistry (n=434). RTK arrays on a cell line panel (n=14) determined therapeutic targets for in vitro cytotoxic testing. Feasibility of this personalised approach was tested in tumour samples (n=46).
MAPK was the most frequently activated pathway (32/75 samples (42.7%)) with progressive enrichment in preinvasive disease stages (p<0.05) and ERK phosphorylation in 148/434 (34.3%) independent samples. Cell lines displayed a range of RTK activation profiles. When no RTKs were activated, tyrosine kinase inhibitors (TKIs) and a Mek inhibitor were not useful (MKN1). In lines with a dominant phosphorylated RTK (OE19, MKN45 and KATOIII), selection of this TKI or Mek in nM concentrations induced cytotoxicity and inhibited Erk and Akt phosphorylation. In cells lines with complex activation profiles (HSC39 and OE33), a combination of TKIs or Mek inhibition (in nM concentrations) was necessary for cytotoxicity and inhibition of Erk and Akt phosphorylation. Human tumours demonstrated diverse activation profiles and 65% of cases had two or more active RTKs.
The MAPK pathway is commonly activated in oesophago-gastric cancer following activation of a variety of RTKs. Molecular phenotyping can inform a rational choice of targeted therapy.
Peritoneal surface malignancies (PSM) present insidiously and often pose diagnostic challenges. There is a paucity of literature quantifying the frequency and extent of therapeutic delays in PSM and ...its impact on oncological outcomes.
A review of a prospectively maintained registry of PSM patients undergoing Cytoreductive Surgery and Hyperthermic Intra-peritoneal Chemotherapy (CRS-HIPEC) was conducted. Causes for treatment delays were identified. We evaluate the impact of delayed presentation and treatment delays on oncological outcomes using Cox proportional hazards models.
319 patients underwent CRS-HIPEC over a 6-years duration. 58 patients were eventually included in this study. Mean duration between symptom onset and CRS-HIPEC was 186.0 ± 37.1 days (range 18-1494 days) and mean duration of between patient-reported symptom onset and initial presentation was 56.7 ± 16.8 days. Delayed presentation (> 60 days between symptom onset and presentation) was seen in 20.7% (n=12) of patients and 50.0% (n=29) experienced a significant treatment delay of > 90 days between 1
presentation and CRS-HIPEC. Common causes for treatment delays were healthcare provider-related i.e. delayed or inappropriate referrals (43.1%) and delayed presentation to care (31.0%). Delayed presentation was a significantly associated with poorer disease free survival (DFS) (HR 4.67, 95% CI 1.11-19.69, p=0.036).
Delayed presentation and treatment delays are common and may have an impact on oncological outcomes. There is an urgent need to improve patient education and streamline healthcare delivery processes in the management of PSM.
Introduction Field cancerization is suggested to arise from imbalanced differentiation in individual basal progenitor cells leading to clonal expansion of mutant cells that eventually replace the ...epithelium, although without evidence. Methods We performed deep sequencing analyses to characterize the genomic and transcriptomic landscapes of field change in two patients with synchronous aerodigestive tract tumors. Results Our data support the emergence of numerous genetic alterations in cancer-associated genes but refutes the hypothesis that founder mutation(s) underpin this phenomenon. Mutational signature analysis identified defective homologous recombination as a common underlying mutational process unique to synchronous tumors. Discussion Our analyses suggest a common etiologic factor defined by mutational signatures and/or transcriptomic convergence, which could provide a therapeutic opportunity.
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