Search Results (14)

Background: The outcomes of patients with peritoneal metastases from gastric cancer (GCPMs) remain dismal, with an overall survival (OS) of less than 1 year. Approaches reported from East Asia include normothermic intraperitoneal systemic chemotherapy, aimed at downstaging the disease, allowing an R0 resection. This is the first Western study evaluating a bidirectional regimen in a neoadjuvant setting of GCPMs. This phase II study evaluates the tolerability, efficacy and conversion surgery rate. Methods: Patients with PCI < 13 without ascites or HER2 overexpression and no extraperitoneal spread were enrolled starting in January 2018. After staging laparoscopy combined with PIPAC (cisplatin + doxorubicin), NIPS began following Yonemura’s schedule: cisplatin (30 mg/m²) + docetaxel (30 mg/m²), intraperitoneally (day 1); capecitabine 1000 mg/m², orally (days 2–15); and cisplatin (30 mg/m²) + docetaxel (30 mg/m²), intravenous (day 8). After three cycles, patients with no progressive disease and negative peritoneal cytology underwent cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Three additional NIPS cycles were reserved for patients who underwent surgery. Results: Among the 25 treated patients with 17.3-month (95%CI: 10.4; NA) OS, no adverse events (CTCAE) ≥ G3 arose. With a 52% conversion surgery rate, 13 patients underwent CRS combined with HIPEC (cisplatin 100 mg/m²), 10 with CC0 status 3 with CC experienced no operative mortality, and major complications rated Clavien–Dindo IIIB occurred in 2 patients (15.4%). The median OS for patients undergoing surgery was 26 (95%CI: 23.1; NA) months, with progression-free survival of 20 (95%CI: 16.7–NA) months. Conclusions: NIPS is safe and effective. The conversion rate in our Western patients is comparable to that reported in Eastern Asian countries. Full article

Background: Peritoneal metastases from gastric cancer (GCPM) represent a significant clinical challenge in terms of therapeutic options and prognosis. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has demonstrated promising survival benefits within a multimodal approach, particularly in carefully selected patients. Methods: This retrospective single-center study evaluated outcomes in patients with synchronous GCPM treated with CRS + HIPEC following neoadjuvant chemotherapy. The primary endpoints included overall survival (OS), disease-free survival (DFS), and identification of prognostic factors associated with poor outcomes. Additionally, we sought to characterize patients achieving long-term survival (OS ≥ 24 months). Results: The median OS and DFS were 18 and 13 months, respectively. A peritoneal cancer index (PCI) ≥ 7 and major postoperative complications were independently associated with reduced survival. Recurrence was significantly linked to PCI ≥ 7 and signet ring cell histology. Stratification by survival outcome identified PCI ≥ 7 as the only statistically significant variable differentiating average- and long-survival groups. Moreover, elevated PCI was independently associated with a higher incidence of major postoperative complications. Conclusions: CRS + HIPEC may offer a survival advantage over the use of systemic therapy exclusively in appropriately selected patients, particularly those with limited peritoneal disease burden. These results underscore the importance of accurate patient selection to balance surgical risks and maximize oncological benefits in the treatment of GCPM. Full article

Local excision is gaining acceptance as standard treatment for T1 colon cancer (CC); however, not all patients are eligible for endoscopic resection. Colonoscopy-assisted laparoscopic wedge resection (CAL-WR) is a relatively new technique that could fill the gap between endoscopic resection and major surgery. The aim of this study was to analyze the oncological safety of CAL-WR for CC. Methods: A retrospective cohort study was performed, including patients that underwent CAL-WR for CC. Exclusion criteria were double tumors, <1 year follow-up, previous other colorectal malignancy, inflammatory bowel disease or synchronous metastases. The primary outcome was disease recurrence and the secondary outcome was overall survival. Results: Fifty-three patients were included; 35 patients were diagnosed with T1 CC. CAL-WR was radical (R0) for all T1 CC in 94.3% and 94.7% for tumors with deep submucosal invasion (sm2-3 Kikuchi). The mean follow-up was 3.3 years (Q1: 2.0; Q3: 4.3) for disease recurrence and 4.2 years (Q1: 2.8; Q3: 5.2) for overall survival. None of the patients with T1 CC had disease recurrence or died due to their malignancy. There were 14 patients with a T2 and 4 patients with a T3 CC, 17/18 patients underwent completion surgery. Three patients with T2 and one with T3 CC developed a locoregional recurrence (peritoneal). One patient with T3 CC developed lung metastases. Two patients with T3 and one with T2 CC died due to their malignancy. Conclusions: This study suggests that CAL-WR is oncologically safe as treatment for T1 CC. The safety of incidental CAL-WR for >T1 CC, followed by completion surgery, remains unclear. Prospective studies are needed to evaluate these results. Full article

Background: T4 colorectal cancer (CRC) is associated with an increased risk of peritoneal metastases (PM), but it is currently not possible to accurately predict which patients with T4 CRC develop PM. We investigated the occurrence and risk factors for PM in these patients. Methods: A mono-institutional prospective database of 352 patients undergoing T4 primary CRC resection from 2012 to 2021 was reviewed. Clinico-pathological variables potentially associated with synchronous or metachronous PM were tested by univariate and multivariate analyses. Results: The prevalence of synchronous PM was 73/352 (20.7%) and was significantly associated with age (p = 0.037), primary site (p = 0.002), positive nodes (p = 0.005), elevated CA19.9 (p = 0.001), and non-intestinal histology (p = 0.001). After a median follow-up of 35.9 months (95% confidence interval [CI] = 29.5–44.9), metachronous CRC-PM occurred in 36/164 patients (22.0%) with available data, accounting for a three-year cumulative incidence of 21.5% (95% CI = 14.3–28.1). Metachronous CRC-PM occurred in 3/48 patients (6.2%) with negative nodes and normal CEA, as compared with 33/116 patients (28.4%) with positive nodes and/or elevated CEA (p < 0.001). Combined nodal and CEA status (hazard ratio [HR] = 1.27; 95% CI = 1.02–1.59; p = 0.033), postoperative chemotherapy (HR= 0.51; 95% CI = 0.33–0.77; p = 0.001), and positive resection margins (HR = 2.01; 95% CI = 1.20–3.39; p = 0.008) were significantly associated with PM. Conclusions: The peritoneum is a major site for treatment failure in T4 CRC. Patients with normal CEA and negative lymph nodes are associated with a significantly lower risk for metachronous CRC-PM. These findings may help in refining patient selection for integrated approaches aiming at the prevention or early treatment of CRC-PM, which are pending validation in prospective studies. Full article

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved the 5-year survival for colorectal cancer (CRC) patients with peritoneal metastases (PM). Little is known about recurrence patterns and recurrence rates between synchronous (S) and metachronous (M) PM following CRS+HIPEC. We aimed to describe the recurrence patterns, overall survival (OS) and disease-free survival (DFS) in S-PM and M-PM patients after complete CRS+HIPEC. From June 2006 to December 2020, a prospective cohort study included 310 CRC patients, where 181 patients had S-PM (58.4%) and 129 patients had M-PM (41.6%). After a median 10.3-month follow-up, 247/310 (79.7%) patients experienced recurrence, and recurrence sites included isolated peritoneal (32.4%), multifocal (peritoneal and liver and/or lung(s)) (22.7%), isolated liver (17.8%), isolated lung (10.5%) and other (16.6%) sites. Recurrence patterns did not differ between S-PM and M-PM. M-PM patients had an impaired DFS compared to S-PM patients (9.4 months (95% CI: 7.3–12.1) vs. 12.5 months (95% CI: 11.2–13.9), p = 0.01). The median OS was similar for S-PM and M-PM (38.4 months (95% CI: 31.2–46.8) vs. 40.8 months (95% CI: 28.8–46.8), p = 0.86). Despite frequent recurrence at extraperitoneal locations, long-term survival was achievable after CRS+HIPEC in CRC patients with PM. The recurrence patterns and OS did not differ between groups, yet M-PM patients had a shorter DFS. Full article

Peritoneal metastases (PM) are observed in approximately 8% of patients diagnosed with colorectal cancer, either synchronously or metachronously during follow-up. PM often manifests as the sole site of metastasis. PM is associated with a poor prognosis and typically shows resistance to systemic chemotherapy. Consequently, there has been a search for alternative treatment strategies. This review focuses on the global evolution of the combined approach involving cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for the management of PM. It encompasses accepted clinical guidelines, principles for patient selection, surgical and physiological considerations, biomarkers, pharmacological protocols, and treatment outcomes. Additionally, it integrates the relevant literature and findings from previous studies. The role of CRS and HIPEC, in conjunction with other therapies such as neoadjuvant and adjuvant chemotherapy, is discussed, along with the management of patients presenting with oligometastatic disease. Furthermore, potential avenues for future development in this field are explored. Full article

Metastatic colorectal cancer (CRC) is a common cause of cancer-related mortality, of which peritoneal metastases (PMs) have the worse outcome. Metastasis-specific markers may help predict the spread of tumor cells and select patients for preventive strategies. This exploratory pilot study aimed to gain more insight into genetic alterations in primary CRC tumors, which might be a predictive factor for the development of PM. Forty patients with T3 stage CRC were retrospectively divided in three groups: without metachronous metastases during 5-year follow-up (M0, n = 20), with metachronous liver metastases (LM, n = 10) and with metachronous PM (PM, n = 10). Patients with synchronous metastases were excluded. Primary formalin-fixed paraffin-embedded tumor samples were analyzed via comprehensive genome sequencing (TSO500 analysis) to identify DNA alterations and RNA fusion transcripts in 523 genes and 55 genes, respectively. Thirty-eight samples were included for final analysis. Four M0 tumors and one PM tumor were microsatellite instable. BRAF mutations were uniquely identified in three microsatellite-stable (MSS) PM tumors (37.5%, p = 0.010). RNA analysis showed an additional FAM198A-RAF1 fusion in one PM sample. BRAF p.V600E mutations were only present in PM patients with MSS tumors. Greater attention should be paid to BRAF-mutated tumors in relation to the development of metachronous PM. Full article

Gastric cancer (GC) continues to be one of the leading types of malignancies worldwide, despite an ongoing decrease in incidence. It is the fifth most frequent type of cancer in the world and the fourth leading cause of cancer death. Peritoneal metastases (PMs) occur in 20–30% of cases during the natural history of the disease. Systemic chemotherapy (SC) is undoubtedly the standard of care for patients with GC and PMs. However, with the development of highly effective regimens (SC combined with intraperitoneal chemotherapy), significant tumor shrinkage has been observed in many patients with synchronous GC and PMs, allowing some to undergo curative resection “conversion surgery” with long-term survival. In recent years, there has been growing interest in intraperitoneal chemotherapy for PMs, because the reduced drug clearance associated with the peritoneal/plasma barrier allows for direct and prolonged drug exposure with less systemic toxicity. These procedures, along with other methods used for peritoneal surface malignancies (PSMs), can be used in GCs with PMs as neoadjuvant chemotherapy or adjuvant treatments after radical surgery or as palliative treatments delivered either laparoscopically or—more recently—as pressurized intraperitoneal aerosol chemotherapy. The great heterogeneity of patients with stage IV gastric cancer did not allow us to carry out a systemic review; therefore, we limited ourselves to providing readers with an overview to clarify the indications and outcomes of integrated treatments for GCs with PMs by analyzing reports from the international clinical literature and the specific experiences of our oncoteam. Full article

Objectives: The aim of this study was to analyze the prognostic factors of survival in patients with peritoneal metastasis (PM) from colorectal cancer (CRC). The type of relationship between survival and the PM time of detection was used to determine whether it was synchronous with the primary tumor or metachronous. Patients and Methods: Retrospective observational study. It included patients treated for colorectal adenocarcinoma diagnosed between January 2005 and December 2019 who presented PM at the time of diagnosis or during follow-up. Variables, such as sex, age, differentiation grade, positive adenopathy (pN+), tumor size (pT), tumor location, mucinous component, peritoneal carcinomatosis index (PCI), and KRAS mutational status, were analyzed. Results: During the study period, 1882 patients were surgically treated for CRC in our hospital. Of these, 240 patients (12.8%) were included in the study after evidence of PM. The mean age was 67 ± 12 years (range: 32–92 years), and 114 patients were female (47.5%). The mean follow-up was 20 ± 13 months (median 12 months). The Kaplan–Meier survival at 36 months was higher in patients with metachronous PM (24% vs. 8%; p = 0.002), WT-KRAS tumors (31% vs. 15%; p < 0.001), N0 stage (30% vs. 19%; p < 0.001), T3 stage tumors (18% vs. 19% in T4A and 3% in T4B; p > 0.001), and tumors with classic adenocarcinoma histology (18% vs. 8%; p = 0.011). Patients with a PCI of 1–10 showed a likelihood of survival at 36 months of 56%, which was longer than that found in patients with a PCI of 11–20 (8%) or a PCI of >20 (0%) (p < 0.001). In the multiple regression analysis, the factors with an independent prognostic value were: poor grade of differentiation (HR 1.995; 95% CI: 1.294–3.077), KRAS mutation (HR 1.751; 95% CI: 1.188–2.581), PCI 11–20 (HR: 9.935; 95% CI: 5.204–18.966) and PCI > 20 (HR: 4.011; 95% CI: 2.291–7.023). Conclusions: PCI should continue as the as the most useful prognostic indicator in order to assess prognostic estimations as well as therapeutic and surgical decisions, but tumor grade and KRAS mutational status may help in the treatment decision process by providing complementary information. The time of PM detection did not achieve statistical significance in the multiple regression analysis. Full article

Background: Mucinous adenocarcinoma is a frequent subtype in colorectal cancer (CRC). A higher initial T-stage, poorer differentiation, worse response to anti-tumor therapies, and shorter survival are characteristic of mucinous CRC. Moreover, the therapeutic benefit of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) in mucinous CRC has not been significantly investigated. Methods: A retrospective analysis of 218 CRC patients with synchronous or metachronous peritoneal metastases was conducted. Results: 129 and 89 patients had synchronous and metachronous metastases, and 36 (27.8%) and 22 (24.8%) of these were mucinous CRC, respectively. Mucinous CRC was more frequent in the proximal colon, with a higher T-stage and N-stage and with an average peritoneal carcinomatosis index that was 2 values higher. Disease-specific survival was significantly worse in the synchronous mucinous group (median survival: 22.4 months vs. 36.3 months, p = 0.0229). In contrast, no such difference was observed in the metachronous cohort (32.6 months vs. 34.4 months, p = 0.6490). Conclusions: In the case of synchronous peritoneal metastases originating from mucinous CRC, the positive effect of CRS+HIPEC cannot be verified, and the added value of this highly invasive treatment is therefore somewhat questioned. However, CRS + HIPEC is recommended for metachronous metastases, since no difference between the two CRC-subtypes could be verified. Full article

Small intestinal neuroendocrine tumors (SI-NETs) may rarely metastasize to the left supraclavicular lymph nodes, also known as Virchow’s node metastasis (VM). Data on prevalence, prognostic significance, and clinical course of disease for SI-NET patients with VM is limited. In this retrospective analysis of 230 SI-NET patients treated at two tertiary referral centers, we found nine patients with VM (prevalence 3.9%). Among those, there were 5 females and median age at SI-NET and VM diagnosis was 61 and 65 years, respectively. Two patients had G1 tumors and five G2, while two tumors were of unspecified grade (median Ki67: 7%, range 2–15%). Four patients presented with synchronous VM, whereas five developed metachronous VM after a median of twenty-four months (range: 4.8–117.6 months). Hepatic metastases were present in seven patients, extrahepatic metastases (EM) in eight (six para-aortic distant lymph node metastases, one lung and one pancreatic metastasis), whereas peritoneal carcinomatosis (PC) in two patients. We used a control group of 18 age- and sex-matched SI-NET patients from the same cohort with stage IV disease but no extra-abdominal metastases. There was no difference in best-recorded response to first line treatment according to RECIST 1.1 as well as progression-free survival (PFS) between patients with VM and those in the control group (Chi-square test p = 0.516; PFS 71.7 vs. 106.9 months [95% CI 38.1–175.8]; log-rank p = 0.855). In addition, median overall survival (OS) of SI-NET patients with VM did not differ from those in the control group (138.6 [95% CI 17.2–260] vs. 109.9 [95% CI 91.7–128] months; log-rank p = 0.533). In conclusion, VM, although relatively rare in patients with SI-NETs, is more often encountered in patients with G2 tumors and established distant para-aortic lymph node metastases. The presence of VM in SI-NET patients does not seem to impact patients’ survival outcomes and treatment responses, when compared to age- and sex-matched SI-NET patients with stage IV disease confined in the abdomen. Full article

The peritoneum is a common metastatic site in gastric cancer. This systematic review provides an overview of the incidence, risk factors and survival of synchronous peritoneal metastases from gastric cancer. A systematic search was performed to identify studies wherein the incidence, risk factors and survival of gastric cancer with peritoneal metastases were investigated. Of all 38 potentially eligible studies, 17 studies were included based on the eligibility criteria. The incidence of synchronous gastric peritoneal metastases was reviewed for population-based studies (10–21%), for observational cohort studies (2–15%) and for surgical cohort studies (13–40%). Potential risk factors for synchronous gastric peritoneal metastases were younger age, non-cardia gastric cancer, female sex, signet ring cell carcinoma, diffuse type histology or linitis plastica, T4 stage, Hispanic ethnicity and more than one metastatic location. Synchronous peritoneal metastases are commonly diagnosed in patients with gastric cancer with an incidence up to 21% in recent population-based studies. Furthermore, prognosis of patients with gastric peritoneal metastases is poor with median overall survival ranging from 2 to 9 months. The high incidence and poor prognosis require intensive research on diagnostic features and effective treatment options to improve survival. Full article

This article summarizes the histories of six patients with different solid tumors treated with a new strategy based on tumor burden reduction and immune evasion as potential targets. All six patients were at a high risk of relapse and were likely to have a minimal residual disease following conventional therapy: biochemical recurrence (BCR) following radical prostatectomy (RP) (two prostate cancers patients), removal of distant metastases (one colorectal and one breast cancer), and complete response (CR) of distant metastases to conventional therapy (one breast cancer and one esophageal–gastric junction cancer). Four of the patients, two after RP and BCR, one after removal of a single pulmonary metastasis from breast cancer, and one after CR to chemotherapy of peritoneal metastases and ascites from an esophageal–gastric junction primary cancer, regularly received cycles of a new drug schedule with the aim of inhibiting immune suppression (IT). In these four patients, preliminary laboratory tests of peripheral blood suggested an interleukin (IL)-2/IL-12 mediated stimulation of cellular immune response with a concomitant decrease in vascular endothelial growth factor (VEGF) immune suppression. The fifth case was a breast cancer patient with distant metastases in CR, while receiving beta-interferon and interleukin-2 in addition to conventional hormone therapy. To date, all five patients are alive and doing well and they have been unexpectedly disease-free for 201 and 78 months following BCR, 28 months following the removal of a single pulmonary metastases, 32 months following CR to chemotherapy of peritoneal metastases and ascites, and 140 months following diagnosis of multiple bone metastases, respectively. The sixth patient, who had colorectal cancer and multiple synchronous liver metastases and underwent nine surgical interventions for metastatic disease, although not disease-free, is doing well 98 months after primary surgery. Our six cases reports can be interpreted with the hypothesis that immune manipulation and/or a concomitant low tumor burden favored their clinical outcome. Full article

In the event of multiple synchronous gynecological lesions, a fundamental piece of information to determine patient management, prognosis, and therapeutic regimen choice is whether the simultaneous malignancies arise independently or as a result of metastatic dissemination. An example of synchronous primary tumors of the female genital tract most frequently described are ovarian and endometrial cancers. Surgical findings and histopathological examination aimed at resolving this conundrum may be aided by molecular analyses, although they are too often inconclusive. High mitochondrial DNA (mtDNA) variability and its propensity to accumulate mutations has been proposed by our group as a tool to define clonality. We showed mtDNA sequencing to be informative in synchronous primary ovarian and endometrial cancer, detecting tumor-specific mutations in both lesions, ruling out independence of the two neoplasms, and indicating clonality. Furthermore, we tested this method in another frequent simultaneously detected gynecological lesion type, borderline ovarian cancer and their peritoneal implants, which may be monoclonal extra-ovarian metastases or polyclonal independent masses. The purpose of this review is to provide an update on the potential use of mtDNA sequencing in distinguishing independent and metastatic lesions in gynecological cancers, and to compare the efficiency of molecular analyses currently in use with this novel method. Full article