Colorectal peritoneal metastases are a devastating consequence of colorectal cancer (CRC) with extremely poor prognosis. Patients that can undergo complete cytoreduction by cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) have a markedly improved overall survival. Traditionally, patients with extremely high peritoneal cancer index (PCI), PCI >20, are not offered CRS/HIPEC.
We performed a retrospective analysis of our prospectively maintained CRS/HIPEC database and evaluated all patients with CRC peritoneal metastases between 2012 and 2022. We divided the cohorts between those with low operative PCI (PCI<20) and high operative PCI (PCI =>20). We examined demographic, clinicopathologic data, perioperative, and oncological outcomes between the cohorts.
Of the 691 patients who underwent CRS/HIPEC, 289 were evaluable with CRC metastases, 234 with PCI <20 and 43 with PCI => 20. Median radiologic preoperative and operative PCI was 4 and 10 versus 7 and 24.5 in the low and high PCI cohorts, respectively. Operative time was longer (6 vs. 4 h) and blood loss higher (500 vs. 400 mL) in the high PCI cohort. All other demographic, clinicopathological, and operative characteristics were similar. Median disease free survival (DFS) was longer in the low PCI cohort (11.5 vs. 7 months) but overall survival (OS) showed benefit (41.3 vs. 31.8 months), (p = 0.001 and p = 0.189, respectively), comparatively with an only chemotherapy strategy.
Appropriately selected patients with CRC metastases and extremely high PCI demonstrate similar perioperative safety outcomes in experienced tertiary referral centers. Despite a shorter median DFS, these carefully selected patients demonstrated similar median OS.

BACKGROUND: The treatment of peritoneal malignancies has evolved and select patients can undergo effective surgical therapies. Access to innovative oncology procedures can be improved if programs are developed within and outside of academic cancer centers. We report the creation of a high volume, comprehensive peritoneal malignancy program developed in a community center.
METHODS: A retrospective single-site study was conducted using registry data comprising all patients who underwent Cytoreductive Surgery (CRS) and Heated Intraperitoneal Chemotherapy (HIPEC) between October 2011-December 2021.
RESULTS: 353 patients underwent CRS and HIPEC. 208 patients experienced in-hospital morbidity (58.9 ​%). Group comparison by disease site, PCI, and the completeness of cytoreduction demonstrated survival differences in mean overall survival and disease-free survival in 1-, 3- and 5-year ranges.
CONCLUSIONS: This study demonstrates that with a standardized protocol and a surgeon-led multidisciplinary team it is possible to offer safe outcome driven, complex oncologic surgery in a community-based cancer program.

OBJECTIVE: Despite advances in systemic therapy, outcomes of patients with gastric cancer (GC) peritoneal carcinomatosis (PC) remain poor, in part because of poor penetrance of systemic therapy into peritoneal metastasis due to the plasma-peritoneal barrier and anarchic intra-tumoral circulation. Hence, regional treatment approach with administration of chemotherapy directly into the peritoneal cavity (intraperitoneal, IP) under various conditions, combined with or without cytoreductive surgery (CRS) has remained an area of significant research interest. The purpose of this review is to provide high-level evidence for regional treatment approaches in the management of GCPC with limited peritoneal disease.
METHODS: A review of the current literature and ongoing clinical trials for regional IP therapies for GCPC was performed. Studies included in this review comprise of phase III randomized controlled trials, non-randomized phase II studies, high-impact retrospective studies, and active ongoing clinical trials for each available IP modality.
RESULTS: The three common IP approaches are heated intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal chemotherapy (NIPEC) and more recently introduced, pressurized intraperitoneal aerosolized chemotherapy (PIPAC). These IP approaches have been combined with systemic therapy and/or CRS with varying degrees of promising results, demonstrating evidence of improvements in survival rates and peritoneal disease control. Patient selection, optimization of systemic therapy, and completeness of cytoreduction have emerged as major factors influencing the design of contemporary and ongoing trials.
CONCLUSIONS: IP chemotherapy has a clear role in the management of patients with GCPC, and when combined with CRS in appropriately selected patients has the potential to significantly improve survival. Ongoing and upcoming IP therapy clinical trials hold great promise to shape the treatment paradigm for GCPC.

BACKGROUND: Peritoneal metastases of colorectal carcinoma origin (PM-CRC) are treated by cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC). However, the majority of patients recur, calling for novel treatments. We explored the immunogenic changes induced by HIPEC and the possibility to use thymosin α1 (Tα1) as an immune-stimulatory agent.
METHODS: We used an experimental murine model of PM-CRC combined with mitomycin (MMC)-based HIPEC. We determined immune cell infiltration into tumor metastases after HIPEC administration by means of immunohistochemistry, and determined immunogenic cell death signals in tumor cells by real-time polymerase chain reaction.
RESULTS: Mice with PM-CRC treated by HIPEC had increased overall survival (OS) compared to sham-treated mice (median OS 22.8 vs 18.9 days, respectively; P < 0.001). HIPEC induced increased infiltration of CD4+, CD8+, CD68 + and CD20 + cells into omental and visceral metastases at a magnitude of 40-100 %. We searched for potential immune signals induced by HIPEC by determining its effects on known immunogenic cell death proteins (heat-shock protein [HSP]-70, HSP-90 and calreticulin). HIPEC significantly increased HSP-90 mRNA expression (2.37 ± 1.5 vs 1-fold change, P < 0.05). The OS of Tα1 treated mice significantly improved compared to HIPEC-treated mice (16.3 ± 0.8 vs 14.1 ± 0.6 days, respectively, P = 0.02) and vs sham (11.8 ± 0.8 days, P = 0.007).
CONCLUSIONS: HIPEC induced immunogenic changes that led to increased immune cell infiltration. These changes were further augmented by Tα1 treatment. Future studies aimed at optimizing Tα1 treatment should focus upon the immune response it evokes.

Patients treated surgically for local non-invasive mucinous appendiceal neoplasm (NI-MAN) may recur with the development of peritoneal dissemination (PD). The risk of recurrence and predictive factors are not well studied. Patients with NI-MAN, with or without peritoneal dissemination at presentation, were included. Patients with limited disease underwent surgical resection only. Patients with peritoneal dissemination underwent cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC). Patients without PD (nPD) were compared to those who presented with PD. Thirty-nine patients were included, 25 in nPD and 14 in PD. LAMN was diagnosed in 96% and 93% of patients in nPD and PD, respectively. Acellular mucin on the peritoneal surface was seen in 16% of nPD patients vs. 50% of PD patients (p = 0.019). Two (8%) patients in the nPD group who had LAMN without wall rupture recurred, at 57 and 68 months, with a PCI of 9 and 22. The recurrence rate in the PD group was 36%. All recurred patients underwent CRS+HIPEC. A peritoneal recurrence is possible in NI-MANs confined to the appendix even with an intact wall at initial diagnosis. The peritoneal disease may occur with significant delay, which is longer than a conventional follow-up.

OBJECTIVE: Up to a third of patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC) of appendiceal or colorectal origin receive a stoma during primary surgery. Stoma reversal provides an opportunity for second-look surgery.
METHODS: We performed a retrospective analysis of prospectively collected data of patients with colorectal cancer (CRC) or high-grade appendiceal cancer (AC) from 2006 to 2021 from our database. A total of 34 consecutive stoma closure patients with no evidence of preoperative disease recurrence (tumor markers and CT scans) were compared with 141 consecutive re-do CRS/HIPEC patients with known recurrence.
RESULTS: Eleven patients (32.4%) were identified to have peritoneal recurrence at stoma closure. Time between first and second CRS was 12 months (4 to 64.2) in the stoma closure group vs. 24.6 months (5.8 to 119.8) in the re-do group, while median peritoneal cancer index (PCI) was 4 (3 to 6) vs. 8 (1 to 39), respectively (p=0.0143).
CONCLUSIONS: Second-look laparotomy during stoma closure identified unexpected PC in 32.4% of our patients with significantly lower PCI than planned re-do operations.

UNASSIGNED: Malignant peritoneal mesothelioma (MPM) is an insidious neoplasm that arises from the mesothelial lining of the abdominal cavity. Historically, outcomes of MPM were dismal, as MPM is relatively resistant to cytotoxic chemotherapy. However, with advances in technology and improved understanding of tumor pathophysiology, treatments for MPM have produced encouraging 5-year survival. The standard of care for patients with resectable disease remains cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Patients with inoperable MPM can be offered several systemic treatments, including chemotherapy, immune checkpoint inhibitors, or investigational treatments. Our objective is to provide an overview of our current knowledge concerning MPM and latest advances in treatment.
UNASSIGNED: Narrative overview of the literature published in English from database origin until January 31, 2022 relating to MPM was searched in PubMed database, Google Scholar, and ClinicalTrials.gov.
UNASSIGNED: CRS-HIPEC has offered improved survival for surgical candidates, however outcomes for inoperable MPM remains dismal. With advancements in technology and better understanding of underlying MPM biology, new treatment approaches are arising and imperative.
UNASSIGNED: MPM is a rare and lethal disease of the peritoneum. CRS-HIPEC remains the standard of care for resectable disease. In 2022, several clinical trials are available for patients with MPM offering future advances in therapy and further understanding of this rare disease process.

BACKGROUND: Heated intraperitoneal chemotherapy (HIPEC) is currently implemented in the treatment of peritoneal metastases from colorectal carcinoma (PM-CRC) origin. However, recurrence is common and the effectiveness of HIPEC has been questioned. The aim of this study was to evaluate the use of thymosin alpha 1 (Tα1), an immunomodulatory molecule, as an adjuvant to HIPEC treatment.
METHODS: We developed an experimental model of HIPEC by the induction of PM-CRC in C57BL mice and intra-abdominal perfusion of mitomycin C (MMC). Mice were treated with Tα1 at 0.6 mg/kg for 5 days after HIPEC. Clinical and immunological parameters were compared between HIPEC and HIPEC + Tα1 groups.
RESULTS: Treatment with Tα1 increased overall survival of mice compared to HIPEC treatment alone and sham-treated animals (16.1 ± 0.8 vs. 14.1 ± 0.6 and 11.8 ± 0.8, respectively, p = 0.02). Tα1 had no direct anti-tumor effect, as seen by lack of inhibition of tumor cell proliferation. Tα1 treatment induced a T helper (Th) 1 immune response in tumor metastases as evidenced by a significant increase of the Th1-specific markers IFN-γ and T-bet (1.21 ± 0.3 vs. 0.52 ± 0.08, p < 0.05; 0.88 ± 0.04 vs. 0.64 ± 0.14, p < 0.05, respectively). This Th1 skew was accompanied by increased CD8+ infiltration into omental and visceral metastases by Tα1 treatment compared to sham and HIPEC-treated animals (21.24 ± 2.16 vs. 10.45 ± 0.89 and 7.7 ± 1.3, p < 0.001; 14.12 ± 1.54 vs. 12.12 ± 0.01 and 6.64 ± 0.87, p < 0.01, respectively).
CONCLUSIONS: Tα1 augments the effect of HIPEC by the induction of a Th1 anti-tumor immune response. Further experiments should evaluate Tα1 and other novel immunomodulators in order to exploit the immunological opportunities created by HIPEC.

OBJECTIVE: Sociodemographic factors have been shown to impact surgical outcomes. However, the effects of these factors on patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) are not well known. This study aims to evaluate the impact of sociodemographic factors on patients undergoing CRS/HIPEC.
METHODS: Adult patients at a tertiary center who underwent CRS/HIPEC were evaluated. Perioperative variables were collected and analyzed. A national database was also used to evaluate patients undergoing CRS/HIPEC.
RESULTS: There were 90 patients who underwent CRS/HIPEC (32% non-White). There was no statistically significant difference in postoperative complications, length of stay, or discharge disposition based upon race (white vs. non-White patients), socioeconomic status (SES), or insurance type. Nationally, we found that Black and Hispanic patients were less likely to undergo CRS/HIPEC than Non-Hispanic white patients (Black: odds ratio [OR]: 0.60, [confidence interval {CI}: 0.39-0.94]; Hispanic: OR: 0.52, [CI: 0.28-0.98]). However, there were no significant differences in postoperative complications based upon race/ethnicity.
CONCLUSIONS: Sociodemographic factors including race, SES, and insurance status did not impact postoperative outcomes in patients undergoing CRS/HIPEC at our single institution. On a national level, Black and Hispanic patients underwent CRS/HIPEC at lower rates compared to white patients.

OBJECTIVE: Formation of stoma during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC) is often performed to reduce the risk of anastomotic leak. Subsequent stoma reversal provides a unique opportunity for second-look surgery to detect early peritoneal recurrence. Current surveillance methods often fail to detect disease early, including imaging and biochemical markers. In our study, we examined the safety and efficacy of second-look surgery for detection and treatment of disease recurrence.
METHODS: We performed a retrospective analysis of prospectively collected data from 35 patients undergoing stoma reversal from 2015 to 2019 with negative pre-operative imaging.
RESULTS: A total of 37% of cases had disease recurrence, with a median peritoneal cancer index of 4. Complete cytoreduction was achieved in all patients. The majority of patients (77%) suffered minor complications only. Median length of hospital stay was 12 days.
CONCLUSIONS: Second-look surgery detects early disease recurrence and is a safe alternative to conventional screening methods post primary CRS/HIPEC for PC. Long-term, routine second-look surgery can improve survival.