Background
Colorectal cancer leads to peritoneal metastases (CRPM) in 10% of cases. Cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC) improves survival. Primary tumor ...location and abnormalities in
RAS
,
BRAF
, and mismatch repair/microsatellite stability (MMR/MSI) may affect post-CRS-HIPEC survival, but studies have not been consistent. We estimated the effects of primary tumor site and genomic alterations on post-CRS-HIPEC survival.
Methods
This retrospective cohort study included CRS-HIPEC cases for CRPM at a high-volume center from 2001 to 2020. Next-generation sequencing and microsatellite testing defined the
RAS
,
BRAF
, and MMR/MSI genotypes. Adjusted effects of tumor sidedness and genomics on survival were evaluated using a multivariable Cox proportional hazards model. We analyzed these variables’ effects on progression-free survival and the effects of immune checkpoint-inhibitors.
Results
A total of 250 patients underwent CRS-HIPEC with testing for
RAS
,
BRAF
, and MMR/MSI; 50.8% of patients were
RAS
-mutated, 12.4% were
BRAF
-mutated, and 6.8% were deficient-MMR/MSI-high (dMMR/MSI-H). Genomic alterations predominated in right-sided cancers. After adjustment for comorbidities and oncological and perioperative variables, rectal origin hazard ratio (HR) 1.9,
p
= 0.01,
RAS
mutation (HR 1.6,
p
= 0.01), and
BRAF
mutation (HR 1.7,
p
= 0.05) were associated with worse survival.
RAS
mutation was also associated with shorter progression-free survival (HR 1.6,
p
= 0.01 at 6 months post-operatively), and dMMR/MSI-H status was associated with superior survival (HR 0.3,
p
= 0.01 at 2 years). dMMR/MSI-H patients receiving immune checkpoint-inhibitors trended toward superior survival.
Conclusions
Rectal origin,
RAS
mutations, and
BRAF
mutations are each associated with poorer survival after CRS-HIPEC for CRPM. Patients with CRPM and dMMR/MSI-H status have superior survival. Further research should evaluate benefits of immune checkpoint-inhibitors in this subgroup.
Context: Selective intraarterial calcium injection of the major pancreatic arteries with hepatic venous sampling calcium arterial stimulation (CaStim) has been used as a localizing tool for ...insulinomas at the National Institutes of Health (NIH) since 1989. The accuracy of this technique for localizing insulinomas was reported for all cases until 1996.
Objectives: The aim of the study was to assess the accuracy and track record of the CaStim over time and in the context of evolving technology and to review issues related to result interpretation and procedure complications. CaStim was the only invasive preoperative localization modality used at our center. Endoscopic ultrasound (US) was not studied.
Design and Setting: We conducted a retrospective case review at a referral center.
Patients: Twenty-nine women and 16 men (mean age, 47 yr; range, 13–78) were diagnosed with an insulinoma from 1996–2008.
Intervention: A supervised fast was conducted to confirm the diagnosis of insulinoma. US, computed tomography (CT), magnetic resonance imaging (MRI), and CaStim were used as preoperative localization studies. Localization predicted by each preoperative test was compared to surgical localization for accuracy.
Main Outcome: We measured the accuracy of US, CT, MRI, and CaStim for localization of insulinomas preoperatively.
Results: All 45 patients had surgically proven insulinomas. Thirty-eight of 45 (84%) localized to the correct anatomical region by CaStim. In five of 45 (11%) patients, the CaStim was falsely negative. Two of 45 (4%) had false-positive localizations.
Conclusion: The CaStim has remained vastly superior to abdominal US, CT, or MRI over time as a preoperative localizing tool for insulinomas. The utility of the CaStim for this purpose and in this setting is thus validated.
The CaStim is vastly superior to abdominal ultrasound, CT or MRI as a preoperative localizing tool for insulinomas.
Background
Appendiceal goblet cell adenocarcinomas (GCC) are rare tumors with clinical behavior between classic carcinoids and adenocarcinomas. Current guidelines recommend right hemicolectomy for ...all GCCs.
Patients and Methods
The National Cancer Database was retrospectively queried for appendiceal GCCs undergoing appendectomy or right hemicolectomy between 2004 and 2016. Demographics, tumor characteristics, and post-operative outcomes were collected. The primary outcome was overall survival, which was examined by surgical type and tumor T stage. Multivariate logistic regression was utilized to identify predictors of survival.
Results
In total, 1083 GCCs were included, and 81.8% underwent right hemicolectomy. Mean age was 57 years, and 89% were White. Patients undergoing hemicolectomy had higher T-stage tumors (66.6%/14.4% T3/T4 vs. 55.8%/8.1%,
p
< 0.001). Lymph node positivity increased with T stage (1.1%, 2.1%, 9.9%, and 29.1% for T1–T4). GCCs undergoing colectomy were more frequently moderately or poorly differentiated (16.7%/9.0% vs. 12.2%/6.6%,
p
=
0.011). Appendectomy surgical margins were positive in 17.3% (3.4% hemicolectomy,
p
< 0.001). In T3/T4 tumors, a significant survival benefit at 5 years was observed in patients undergoing colectomy as compared with appendectomy (85.4% vs. 82.0%,
p
= 0.028). On multivariate analysis, lymph node positivity markedly decreased survival overall for the entire cohort (HR 7.58,
p
< 0.001) and for T3/T4 tumors (HR 7.63,
p
< 0.001). In patients with T3/T4 tumors, there was a trend towards improved survival with right hemicolectomy (HR 0.42,
p
= 0.068).
Conclusion
Omitting right hemicolectomy can be considered for select T1/T2 appendiceal GCCs with negative appendectomy margins, given low rates of lymph node metastases and lack of survival benefit with right hemicolectomy.
Background
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a treatment option in patients with carcinomatosis from high-grade appendiceal (HGA) primaries. It is ...unknown if there is a Peritoneal Carcinomatosis Index (PCI) upper limit above which a complete CRS/HIPEC does not assure long-term survival.
Methods
Retrospective analysis from three centers was performed. The PCI was used to grade volume of of disease. Survival in relation to PCI was studied on patients with complete cytoreduction.
Results
Overall, 521 HGA patients underwent CRS/HIPEC from 1993 to 2015, with complete CRS being achieved in 50% (260/622). Mean PCI was 14.8 (standard deviation 8.7, range 0–36). Median survival for the complete CRS cohort was 6.1 years, while 5- and 10-year survival was 51.7% (standard error SE 4.6) and 36.1% (SE 6.3), respectively. Arbitrary cut-off PCI limits with 5-point splits (
p
= 0.63) were not predictive of a detrimental effect on survival as long as a complete CRS was achieved. A linear effect of the PCI on survival (
p
= 0.62) was not observed, and single-point PCI cohort splits within a PCI range of < 5 to > 10 were not predictive of survival for complete CRS patients. The PCI correlated with the ability to achieve a complete CRS, with a mean PCI of 14.7 (8.7) for completeness of cytoreduction (CC)0, 22.3 (7.8) for CC1 and 26.1 (9.5) for CC2/3 resections (
p
= 0.0001, hazard ratio 1.12, 95% confidence interval 1.09), with an HR of 1.15 for each 1-unit increase in the PCI score. Only 21% of the cohort achieved a complete CRS with a PCI ≥ 21.
Conclusions
The PCI correlates with the ability to achieve a complete CRS in carcinomatosis from HGA. PCI is not associated with survival as long as a complete CRS can be achieved.
To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-alpha) to a melphalan-based hyperthermic isolated limb perfusion (HILP) ...treatment would improve the complete response rate for locally advanced extremity melanoma.
Patients with locally advanced extremity melanoma were randomly assigned to receive melphalan or melphalan plus TNF-alpha during standard HILP. Patient randomization was stratified according to disease/treatment status and regional nodal disease status.
The intervention was completed in 124 patients of the 133 enrolled. Grade 4 adverse events were observed in 14 (12%) of 129 patients, with three (4%) of 64 in the melphalan-alone arm and 11 (16%) of 65 in the melphalan-plus-TNF-alpha arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-alpha arm, and one disease progression-related upper extremity amputation in the melphalan-alone arm. There was no treatment-related mortality in either arm of the study. One hundred sixteen patients were assessable at 3 months postoperatively. Sixty-four percent of patients (36 of 58) in the melphalan-alone arm and 69% of patients (40 of 58) in the melphalan-plus-TNF-alpha arm showed a response to treatment at 3 months, with a complete response rate of 25% (14 of 58 patients) in the melphalan-alone arm and 26% (15 of 58 patients) in the melphalan-plus-TNF-alpha arm (P = .435 and P = .890, respectively).
In locally advanced extremity melanoma treated with HILP, the addition of TNF-alpha to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-alpha plus melphalan was associated with a higher complication rate.
Background
Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (CRS HIPEC) can offer significant survival advantage for select patients with colorectal peritoneal metastases (CRPM). ...Low socioeconomic status (SES) is implicated in disparities in access to care. We analyze the impact of SES on postoperative outcomes and survival at a high-volume tertiary CRS HIPEC center.
Patients and Methods
We conducted a retrospective cohort study examining patients who underwent CRS HIPEC for CRPM from 2000 to 2018. Patients were grouped according to SES. Baseline characteristics, perioperative outcomes, and survival were examined between groups.
Results
A total of 226 patients were analyzed, 107 (47%) low-SES and 119 (53%) high-SES patients. High-SES patients were younger (52 vs. 58 years,
p
= 0.01) and more likely to be White (95.0% vs. 91.6%,
p
= 0.06) and privately insured (83% vs. 57%,
p
< 0.001). They traveled significantly further for treatment and had lower burden of comorbidities and frailty (
p
= 0.01). Low-SES patients more often presented with synchronous peritoneal metastases (48% vs. 35%,
p
= 0.05). Following CRS HIPEC, low-SES patients had longer length of stay and higher burden of postoperative complications, 90-day readmission, and 30-day mortality. Median overall survival following CRS HIPEC was worse for low-SES patients (17.8 vs. 32.4 months,
p
= 0.02). This disparity persisted on multivariate survival analysis (low SES: HR = 1.46,
p
= 0.03).
Conclusions
Despite improving therapies for CRPM, low-SES patients remain at a significant disadvantage. Even patients who overcome barriers to care experience worse short- and long-term outcomes. Improving access and addressing these disparities is crucial to ensure equitable outcomes and improve patient care.
Background
Normal carcinoembryonic antigen (CEA) levels (≤ 2.5 ng/ml) after resection of localized colorectal cancer or liver metastases are associated with improved survival, however, these trends ...are understudied for colorectal peritoneal metastases (CRPM).
Patients and Methods
We conducted a retrospective single-institution study of patients with CRPM undergoing cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) with and without neoadjuvant chemotherapy (NACT). CEA was measured before and after NACT and within 3 months after CRS/HIPEC.
Results
A total of 253 patients (mean age 55.3 years) with CRPM undergoing CRS/HIPEC had complete CEA data and 191 also underwent NACT with complete data. The median peritoneal carcinomatosis index score (PCI) of the overall cohort was 12 and 82.7% of patients had complete cytoreduction (CC0). In total, 64 (33.5%) patients had normal CEA levels after NACT with a median overall survival (OS) of 45.2 months compared with those with an elevated CEA (26.4 months,
p
= 0.004). Patients with normal CEA after NACT had a lower PCI found at the time of surgery than those with elevated CEA (10 versus 14,
p
< 0.001), 68 (26.9%) patients with an elevated preoperative CEA level experienced normalization after CRS/HIPEC, and 118 (46.6%) patients had elevated CEA after CRS/HIPEC. Patients who experienced normalization demonstrated similar OS to patients that had normal CEA levels pre- and post-surgery and improved OS compared with those with elevated postop CEA (median 41.9 versus 47 months versus 17.1 months, respectively,
p
< 0.001).
Conclusions
Normal CEA levels after NACT and/or CRS/HIPEC are associated with improved survival for patients with CRPM. Patients that normalize CEA levels after surgery have similar survival to those with normal preoperative levels.
Background
CRS-HIPEC provides oncologic benefit in well-selected patients with peritoneal carcinomatosis; however, it is a morbid procedure. Decision tools for preoperative patient selection are ...limited. We developed a risk score to predict severity of 90 day complications for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).
Patients and Methods
Adults who underwent CRS-HIPEC at the University of Pittsburgh Medical Center (March 2001–April 2020) were analyzed as part of this study. Primary endpoint was severe complications within 90 days following CRS-HIPEC, defined using Comprehensive Complication Index (CCI) scores as a dichotomous (determined using restricted cubic splines) and continuous variable. Data were divided into training and test sets. Several machine learning and traditional algorithms were considered.
Results
For the 1959 CRS-HIPEC procedures included, CCI ranged from 0 to 100 (median 32.0). Adjusted restricted cubic splines model defined severe complications as CCI > 61. A minimum of 20 variables achieved optimal performance of any of the models. Linear regression achieved the highest area under the receiving operator characteristic curve (AUC, 0.74) and outperformed the NSQIP Surgical Risk calculator (AUC 0.80 vs. 0.66). Factors most positively associated with severe complications included peritoneal carcinomatosis index score, symptomatic status, and undergoing pancreatectomy, while American Society of Anesthesiologists 2 class, appendiceal diagnosis, and preoperative albumin were most negatively associated with severe complications.
Conclusions
This study refines our ability to predict severe complications within 90 days of discharge from a hospitalization in which CRS-HIPEC was performed. This advancement is timely and relevant given the growing interest in this procedure and may have implications for patient selection, patient and referring provider comfort, and survival.
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