Is Systemic Chemotherapy Useful in Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Colorectal Peritoneal Metastases? A Propensity-Score Analysis.

PURPOSE: Multimodal treatment of colorectal (CRC) peritoneal metastases (PM) includes systemic chemotherapy (SC) and surgical cytoreduction (CRS), eventually with hyperthermic intraperitoneal chemotherapy (HIPEC), in select patients. Considering lack of clear guidelines, this study was designed to analyze the role of chemotherapy and its timing in patients treated with CRS-HIPEC. METHODS: Data from 13 Italian centers with PM expertise were collected by a collaborative group of the Italian Society of Surgical Oncology (SICO). Clinicopathological variables, SC use, and timing of administration were correlated with overall survival (OS), disease-free survival (DFS), and local (peritoneal) DFS (LDFS) after propensity-score (PS) weighting to reduce confounding factors. RESULTS: A total of 367 patients treated with CRS-HIPEC were included in the propensity-score weighting. Of the total patients, 19.9% did not receive chemotherapy within 6 months of surgery, 32.4% received chemotherapy before surgery (pregroup), 28.9% after (post), and 18.8% received both pre- and post-CRS-HIPEC treatment (peri). SC was preferentially administered to younger (p = 0.02) and node-positive (p = 0.010) patients. Preoperative SC is associated with increased rate of major complications (26.9 vs. 11.3%, p = 0.0009). After PS weighting, there were no differences in OS, DFS, or LDFS (p = 0.56, 0.50, and 0.17) between chemotherapy-treated and untreated patients. Considering SC timing, the post CRS-HIPEC group had a longer DFS and LDFS than the pre-group (median DFS 15.4 vs. 9.8 m, p = 0.003; median LDFS 26.3 vs. 15.8 m, p = 0.026). CONCLUSIONS: In patients with CRC-PM treated with CRS-HIPEC, systemic chemotherapy was not associated with overall survival benefit. The adjuvant schedule was related to prolonged disease-free intervals. Additional, randomized studies are required to clarify the role and timing of systemic chemotherapy in this patient subset.

Microsatellite and RAS/RAF Mutational Status as Prognostic Factors in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) leads to prolonged survival for selected patients with colorectal (CRC) peritoneal metastases (PM). This study aimed to analyze the prognostic role of micro-satellite (MS) status and RAS/RAF mutations for patients treated with CRS. METHODS: Data were collected from 13 Italian centers with PM expertise within a collaborative group of the Italian Society of Surgical Oncology. Clinical and pathologic variables and KRAS/NRAS/BRAF mutational and MS status were correlated with overall survival (OS) and disease-free survival (DFS). RESULTS: The study enrolled 437 patients treated with CRS-HIPEC. The median OS was 42.3 months [95% confidence interval (CI), 33.4-51.2 months], and the median DFS was 13.6 months (95% CI, 12.3-14.9 months). The local (peritoneal) DFS was 20.5 months (95% CI, 16.4-24.6 months). In addition to the known clinical factors, KRAS mutations (p = 0.005), BRAF mutations (p = 0.01), and MS status (p = 0.04) were related to survival. The KRAS- and BRAF-mutated patients had a shorter survival than the wild-type (WT) patients (5-year OS, 29.4% and 26.8% vs 51.5%, respectively). The patients with micro-satellite instability (MSI) had a longer survival than the patients with micro-satellite stability (MSS) (5-year OS, 58.3% vs 36.7%). The MSI/WT patients had the best prognosis. The MSS/WT and MSI/mutated patients had similar survivals, whereas the MSS/mutated patients showed the worst prognosis (5-year OS, 70.6%, 48.1%, 23.4%; p = 0.0001). In the multivariable analysis, OS was related to the Peritoneal Cancer Index [hazard ratio (HR), 1.05 per point], completeness of cytoreduction (CC) score (HR, 2.8), N status (HR, 1.6), signet-ring (HR, 2.4), MSI/WT (HR, 0.5), and MSS/WT-MSI/mutation (HR, 0.4). Similar results were obtained for DFS. CONCLUSION: For patients affected by CRC-PM who are eligible for CRS, clinical and pathologic criteria need to be integrated with molecular features (KRAS/BRAF mutation). Micro-satellite status should be strongly considered because MSI confers a survival advantage over MSS, even for mutated patients.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer with Synchronous Peritoneal Metastases: Multicenter Study of 'Italian Peritoneal Surface Malignancies Oncoteam-S.I.C.O.'

BACKGROUND: The development of multimodality treatment, including cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC), has led to promising results in selected patients with peritoneal disease of gastric origin. The aim of this study was to investigate the short- and long-term outcomes of CRS/HIPEC in the treatment of synchronous peritoneal metastasis in gastric cancer. METHODS: The Italian Peritoneal Surface Malignancies Oncoteam-S.I.C.O. retrospective registry included patients with synchronous peritoneal malignancy from gastric cancer submitted to gastrectomy with CRS and HIPEC between 2005 and 2018 from 11 high-volume, specialized centers. RESULTS: A total of 91 patients with a median age of 58 years (range 26-75) were enrolled. The median overall survival (OS) time for the whole group of patients was 20.2 months (95% confidence interval [CI] 11.8-28.5] and the median recurrence-free survival (RFS) was 7.3 months (95% CI 4-10.6). The completeness of cytoreduction score (CCS) of 0 and Peritoneal Cancer Index (PCI) score of ≤ 6 groups showed a significantly better long-term survival (median OS 40.7 and 44.3 months, respectively) compared with the incomplete resected groups (median OS 10.7 months, p = 0.003) and PCI score of > 6 group (median OS 13.4 months, p = 0.005). A significant difference was observed in the survival rate according to neoadjuvant treatment (untreated patients: 10.7 months, 95% CI 5.1-16.2; treated patients: 35.3 months, 95% CI 2.8-67.8; p = 0.022). CONCLUSIONS: In referral centers, CRS and HIPEC after neoadjuvant treatment significantly improved survival in selected patients. Patients with a PCI score ≤ 6, complete cytoreduction, negative nodal involvements, and negative cytology had encouraging results, showing a clinically meaningful survival.

Upfront debulking surgery versus interval debulking surgery for advanced tubo-ovarian high-grade serous carcinoma and diffuse peritoneal metastases treated with peritonectomy procedures plus HIPEC.

BACKGROUND: Whether patients with advanced tubo-ovarian high-grade serous cancer (HGSC) fare better after upfront debulking surgery (UDS) or neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) remains controversial. METHODS: We studied patients with HGSC who underwent UDS or NACT-IDS between July 2000 and December 2015, with peritonectomy procedures combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Clinical reports were included peritoneal cancer index (PCI), NACT responses, surgical complexity score (SCS), completeness of cytoreduction (CC), complete follow-up with timing, site, and treatment of recurrence. Outcome measures were morbidity, progression-free survival (PFS), PFS2, and overall survival during a mean 5-year follow-up. RESULTS: A total of 34 patients (23.6%) underwent UDS and 110 (76.4%) NACT-IDS both combined with HIPEC. At a median 66.3-month follow-up, patients who underwent UDS or NACT-IDS had similar outcomes. NACT subgroup responses correlated with PCI, SCS, morbidity, and CC. Patients who underwent UDS had lower recurrence rates than those who responded partly or poorly to NACT (PFS, P < .04; PFS2, P < .01). Despite HIPEC, the peritoneal disease recurred in 42.5% of the overall patients. CONCLUSION: In patients with primary HGSC who undergo UDS or NACT-IDS, despite similar outcomes, peritonectomy procedures combined with HIPEC seem unable to prevent peritoneal recurrence.

Inflammatory biomarkers, vascular procedures of lower limbs, and wound healing.

Abnormal, persistent inflammation after bypass surgery could prevent healing of an ischaemic foot lesion. In 37 patients with peripheral arterial disease (PAD) (Rutherford Grade III Category 5) who underwent infrapopliteal vein graft and midfoot amputation, plasma levels of fibrinogen, C-reactive protein (CRP), interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), and matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) were determined preoperatively and during the follow up. Nine patients without clinical and Doppler evidence of arterial disease, who underwent post-traumatic midfoot primary amputation, were included in the experiment group, and 15 age-matched healthy volunteers served as control. In patients who had midfoot amputation for trauma, all wounds healed. Seven (19%) wounds in patients with an occluded graft healed, and five (13%) required major amputation because of a non-healing wound. Time required for complete healing of the lesion was similar between trauma and PAD patients (8 ± 2 months vs 11 ± 6, respectively, P = NS). Univariate analysis demonstrated that, in PAD patients, the postoperative high levels of TNF-α, IL-6, and MMP-2 and -9 were predictive for wound healing failure at 3, 6, and 9 months (P < 0.05), respectively. Furthermore, the subgroup of patients who experienced occlusion of the vein graft during follow up had a significant increase of MMP-2, -9, IL-6, and TNF-α at 3, 6, and 9 months (P < 0.05), respectively. Monitoring inflammatory markers allows the determination of patients at risk of healing failure of midfoot amputation after distal revascularisation and might predict the fate of the vein graft.

Different inflammatory cytokines release after open and endovascular reconstructions influences wound healing.

Prodromal signs of a non-healing wound after revascularisation, which might be strictly linked with impending failure of vascular reconstructions, are associated with an inflammatory response mediated by several circulating adhesion molecules, extracellular endopeptidases, and cytokines. The aim of our study was to investigate the role of selected plasma biomarkers in the prediction of both wound healing and failure of infrapopliteal vein graft or percutaneous trans-luminal angioplasty (PTA) with selective stent positioning of the superficial femoral artery (SFA) in a population affected with critical limb ischaemia. A total of 68 patients who underwent either surgical or endovascular revascularisation of the inferior limb with autologous saphenous vein infrapopliteal bypass or PTA and selective stenting of the SFA were enrolled in our study. Patients were divided into two groups according to treatment: 41 patients were included in Group 1 (open surgery) and 27 in Group 2 (endovascular procedure). Plasma and blood samples were collected on the morning of surgery and every 6 months thereafter for up to 2 years of follow-up or until an occlusion occurred of either the vein bypass graft or the vessel treated endovascularly. Fifteen age-matched healthy male volunteers were considered a reference for biological parameters. Vascular cell adhesion molecule 1 [VCAM-1]/CD106, inter-cellular adhesion molecule-1 [ICAM-1]/CD54), interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), and metalloproteinases (MMP)-2 and -9 plasma levels were measured with enzyme-linked immunosorbent assay (ELISA) kits. The mean observed time to heal of 54 wounds was 13 ± 4 months, with no statistically significant differences among the groups. The healing failure of the remaining wounds was strictly related to an unsuccessful open (n = 12) or endovascular (n = 8) treatment. The 2-year primary patency rate was 65% (SE = .09) in Group 1 and 52% (SE = .1) in Group 2. When compared with mean concentration values of Group 1, VCAM-1 and ICAM-1 were always significantly higher during follow-up in patients of Group 2 (P < .05). Furthermore, in the same group, IL-6 and tumour necrosis factor alpha (TNF-α) were found to be significantly higher at 6- and 12-month (P < .05) when compared with surgically treated patients. Cox regression analysis showed that elevated plasma levels of VCAM-1, ICAM-1, IL-6, and TNF-α during follow up were strongly related to impaired wound healing and/or revascularisation failure (P < .05). Elevated plasma levels of inflammatory markers VCAM-1, ICAM-1, IL-6, and TNF-α may be related to the failure of wound healing and revascularisation procedures. Interestingly, we have observed that endovascular treatments cause a higher level of these inflammation biomarkers when compared with a vein graft, although wound-healing and patency and limb salvage rates are not influenced.

Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy for Patients with Peritoneal Metastases from Endometrial Cancer.

BACKGROUND: More information is needed for selection of patients with peritoneal metastases from endometrial cancer (EC) to undergo cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: This study analyzed clinical, pathologic, and treatment data for patients with peritoneal metastases from EC who underwent CRS plus HIPEC at two tertiary centers. The outcome measures were morbidity, overall survival (OS), and progression-free survival (PFS) during a median 5 year follow-up period. Uni- and multivariate analyses were performed to identify significant factors related to outcome. RESULTS: A total of 33 patients met the inclusion criteria and completed the follow-up period. At laparotomy, the median peritoneal cancer index (PCI) was 15 (range 3-35). The CRS procedure required a mean 8.3 surgical procedures per patient, and for 22 patients (66.6%), a complete cytoreduction was achieved. The mean hospital stay was 18 days, and major morbidity developed in 21% of the patients. The operative mortality was 3%. When surgery ended, HIPEC was administered with cisplatin 75 mg/m2 for 60 min at 43 °C. During a median follow-up period of 73 months, Kaplan-Meier analysis indicated a 5 year OS of 30% (median 33.1 months) and a PFS of 15.5% (median 18 months). Multivariate analysis identified the completeness of cytoreduction (CC) score as the only significant factor independently influencing OS. Logistic regression for the clinicopathologic variables associated with complete cytoreduction (CC0) for patients with metachronous peritoneal spread from EC who underwent secondary CRS plus HIPEC identified the PCI as the only outcome predictor. CONCLUSIONS: For selected patients with peritoneal metastases from EC, when CRS leaves no residual disease, CRS plus HIPEC achieves outcomes approaching those for other indications such as colon and ovarian carcinoma.

Cytoreduction (Peritonectomy Procedures) Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Advanced Ovarian Cancer: Retrospective Italian Multicenter Observational Study of 511 Cases.

PURPOSE: The aim of this study was to help with the process of selecting patients with advanced ovarian cancer to undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) by analyzing outcome data at distinct clinical time points reflecting the natural history of the disease. METHODS: In a retrospective Italian multicenter study investigating patients with advanced ovarian cancer who underwent CRS plus HIPEC between 1998 and 2014, we analyzed data for consecutive patients at eight treatment time points: primary debulking surgery (PDS); interval debulking surgery after partial response, after no response, and after a pathologic complete response to neoadjuvant chemotherapy; first recurrence with a progression-free interval >12, <12 months, or >12 months in patients who underwent further chemotherapy before CRS and HIPEC; and patients who underwent two or more CRS procedures and chemotherapy lines before CRS and HIPEC. RESULTS: The 511 enrolled patients underwent 3373 procedures; 72.6% achieved complete cytoreduction, with an overall major morbidity of 17.4%. At a median follow-up of 53.8 months, overall survival (OS) was 54.2 months (95% confidence interval [CI] 44-58.4) and progression-free (PFS) survival was 16.6 months (95% CI 14.7-19.1). Outcome analysis in patients in whom CRS plus HIPEC was used for primary advanced cancer or recurrent ovarian cancer showed significant differences in OS and PFS according to the time points analyzed. Multivariate analysis identified completeness of CRS, Peritoneal Cancer Index, and the times when patients underwent CRS plus HIPEC as independent prognostic factors. CONCLUSIONS: This selective information on survival should help in interpreting the findings from ongoing randomized studies focusing on CRS plus HIPEC in patients with advanced ovarian cancer.

Diagnostic performance of computed tomography and magnetic resonance imaging for detecting peritoneal metastases: systematic review and meta-analysis.

PURPOSE: Primary end point was to assess diagnostic accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) in detecting peritoneal metastases (PM). Secondary end points were determining the diagnostic sensitivity and specificity of CT in detecting PM according to the peritoneal cancer index (PCI), investigating correlations between radiological and surgical PCI, and comparing diagnostic yield of CT versus positron emission tomography (PET)/CT. MATERIALS AND METHODS: We searched MEDLINE, Cochrane Library, Embase and Web of Science databases. Analytic methods were based on PRISMA. Pooled estimates for sensitivity, specificity, positive and negative likelihood ratios were calculated using fixed and random effect models. I 2 was used to evaluate heterogeneity. RESULTS: Of the 529 articles initially identified, 22 were selected for inclusion (934 patients). Cumulative data for per patient CT diagnostic accuracy were sensitivity 83 % (95 % CI 79-86 %), specificity 86 % (95 % CI 82-89 %), pooled positive LR 4.37 (2.58-7.41), and pooled negative LR 0.20 (0.11-0.35). On a per region basis CT performed best in epigastrium and pelvis. Correlation analysis showed a high correlation between CT-PCI and surgical-PCI scores, ranging from 0.49 to 0.96. MRI and PET/CT achieved similar per patient diagnostic accuracy. CONCLUSIONS: CT should be the preferred diagnostic imaging modality for detecting peritoneal metastases because of the robustness of the data. MRI and PET/CT should be considered second choices, until more consistent information on their diagnostic yield in detecting PM are obtained.

Computerized System for Staging Peritoneal Surface Malignancies.

BACKGROUND: Peritoneal surface malignancies (PSMs) are usually staged using Sugarbaker's Peritoneal Cancer Index (PCI) and completeness of cytoreduction score (CC-s). Although these staging tools are essential for selecting patients and evaluating outcome after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), both scoring models lack some anatomic information, thus making staging laborious and unreliable. Maintaining Sugarbaker's original concepts, we therefore developed a computerized digital tool, including a new anatomic scheme for calculating PCI and CC-s corresponding closely to patients' real anatomy. Our new anatomic model belongs in a web-based application known as the PSM Staging System, which contains essential clinical and pathological data for the various PSMs currently treated. METHODS: The new digital tool for staging PSM runs on a personal computer or tablet and comprises male and female colored anatomic models for the 13 endoabdominal regions, with borders defined according to real anatomic landmarks. A drag-and-drop tool allows users to compute the PCI and CC-s, making it easier to localize and quantify disease at diagnosis and throughout treatment, and residual disease after CRS. CONCLUSIONS: Once tested online by registered users, our computerized application should provide a modern, shareable, comprehensive, user-friendly PSM staging system. Its anatomic features, along with the drag-and-drop tool, promise to make it easier to compare preoperative and postoperative PCIs, thus improving the criteria for selecting patients to undergo CRS plus HIPEC. By specifying the size, site, and number of residual lesions after CRS plus HIPEC, our digital tool should help stratify patients into outcome classes.

Ultrasound-Guided Placement of Central Venous Port Systems via the Right Internal Jugular Vein: Are Chest X-Ray and/or Fluoroscopy Needed to Confirm the Correct Placement of the Device?

BACKGROUND: Percutaneous central venous port (CVP) placement using ultrasound-guidance (USG) via right internal jugular vein is described as a safe and effective procedure. The aim of this study is to determine whether intraoperative fluoroscopy (IF) and/or postoperative chest X-ray (CXR) are required to confirm the correct position of the catheter. METHODS: Between January 2012 and December 2014, 302 adult patients underwent elective CVP system placement under USG. The standard venous access site was the right internal jugular vein. The length of catheter was calculated based on the height of the patient. IF was always performed to confirm US findings. RESULTS: 176 patients were men and 126 were women and average height was 176.2 cm (range 154-193 cm). The average length of the catheter was 16.4 cm (range 14-18). Catheter malposition and pneumothorax were observed in 4 (1.3 %) and 3 (1 %) patients, respectively. IF confirmed the correct position of the catheter in all cases. Catheter misplacement (4 cases) was previously identified and corrected on USG. Our rates of pneumothorax are in accordance with those of the literature (0.5-3 %). CONCLUSION: Ultrasonography has resulted in improved safety and effectiveness of port system implantation. The routine use of CXR and IF should be considered unnecessary.

Does the Implantation Technique for Totally Implantable Venous Access Ports (TIVAPs) Influence Long-Term Outcome?

BACKGROUND: Totally implantable venous access ports (TIVAP) are eventually explanted for various reasons, related or unrelated to the implantation technique used. Having more information on long-term explantation would help improve placement techniques. METHODS: From a series of 1572 cancer patients who had TIVAPs implanted in our center with the cutdown technique or Seldinger technique, we studied the 542 patients who returned to us to have their TIVAP explanted after 70 days or more. As outcome measures we distinguished between TIVAPs explanted for long-term complications (infection, catheter-, reservoir-, and patient-related complications) and TIVAPs no longer needed. Univariate and multivariate analyses were run to investigate the reasons for explantation and their possible correlation with implantation techniques. RESULTS: The most common reason for explantation was infection (47.6 %), followed by catheter-related (20.8 %), patient-related (14.7 %), and reservoir-related complications (4.7 %). In the remaining 12.2 % of cases, the TIVAP was explanted complication free after the planned treatments ended. Infection correlated closely with longer TIVAP use. Univariate and multivariate analyses identified the Seldinger technique as a major risk factor for venous thrombosis and catheter dislocation. CONCLUSIONS: The need for long-term TIVAP explantation in about one-third of cancer patients is related to the implantation techniques used.

Cytoreduction and HIPEC in the treatment of "unconventional" secondary peritoneal carcinomatosis.

BACKGROUND: Peritoneal metastasis (PM) is considered a terminal and incurable disease. In the last 30 years, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) radically changed the therapeutic approach for these patients and is regarded as the standard of care for pseudomyxoma peritonei from appendiceal cancer and peritoneal mesotheliomas. Improved survival has also been reported in treating PM from ovarian, gastric, and colorectal cancers. However, PM often seriously complicates the clinical course of patients with other primary digestive and non-digestive cancers. There is increasing literature evidence that helped to identify not only the primary tumors for which CRS and HIPEC showed a survival advantage but also the patients who may benefit form this treatment modality for the potential lethal complications. Our goal is to report our experience with cytoreduction and HIPEC in patients with PM from rare or unusual primary tumors, discussing possible "unconventional" indications, outcome, and the peculiar issues related to each tumor. METHODS: From a series of 253 consecutive patients with a diagnosis of peritoneal carcinomatosis and treated by CRS and HIPEC, we selected only those with secondary peritoneal carcinomatosis from rare or unusual primary tumors, excluding pseudomyxoma peritonei, peritoneal mesotheliomas, ovarian, gastric, and colorectal cancers. Complications and adverse effects were graded from 0 to 5 according to the WHO Common Toxicity Criteria for Adverse Events (CTCAE). Survival was expressed as mean and median. RESULTS: We admitted and treated by CRS and HIPEC 28 patients with secondary peritoneal carcinomatosis from rare or unusual primary tumors. Morbidity and mortality rates were in line with those reported for similar procedures. Median survival for the study group was 56 months, and 5-year overall survival reached 40.3 %, with a difference between patients with no (CC0) and minimal (CC1) residual disease (52.3 vs. 25.7), not reaching statistical significance. Ten patients are alive disease-free, and eight are alive with disease. CONCLUSIONS: Cytoreduction and HIPEC should not be excluded "a priori" for the treatment of peritoneal metastases from unconventional primary tumors. This combined therapeutic approach, performed in an experienced center, is safe and can provide a survival benefit over conventional palliative treatments.

Depth of colorectal-wall invasion and lymph-node involvement as major outcome factors influencing surgical strategy in patients with advanced and recurrent ovarian cancer with diffuse peritoneal metastases.

BACKGROUND: More information is needed on the anatomopathological outcome variables indicating the appropriate surgical strategy for the colorectal resections often needed during cytoreduction for ovarian cancer. METHODS: From a phase-II study cohort including 70 patients with primary advanced or recurrent ovarian cancer with diffuse peritoneal metastases treated from November 2000 to April 2009, we selected for this study the 52 consecutive patients who needed colorectal resection. Data collected included type of colorectal resection, peritoneal cancer index (PCI), histopathology (depth of bowel-wall invasion and lymph-node spread), cytoreduction rate and outcome. Correlations were tested between possible prognostic factors and Kaplan-Meier five-year overall and disease-free survival. A Cox multivariate regression model was used to identify independent variables associated with outcome. RESULTS: In the 52 patients, the optimal cytoreduction rate was 86.5% (CC0/1). In all patients, implants infiltrated deeply into the bowel wall, in 75% of the cases up to the muscular and mucosal layer. Lymph-node metastases were detected in 50% of the cases; mesenteric nodes were involved in 42.3%. Most patients (52%) had an uneventful postoperative course. Operative mortality was 3.8%. The five-year survival rate was 49.9% and five-year disease-free survival was 36.7%. Cox regression analysis identified as the main prognostic factors completeness of cytoreduction and depth of bowel wall invasion. CONCLUSIONS: Our findings suggest that the major independent prognostic factors in patients with advanced ovarian cancer needing colorectal resections are completeness of cytoreduction and depth of bowel wall invasion. Surgical management and pathological assessment should be aware of and deal with dual locoregional and mesenteric lymphatic spread.

10 Years of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC): A Systematic Review and Meta-Analysis.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel intraperitoneal drug delivery method of low-dose chemotherapy as a pressurized aerosol in patients affected by peritoneal cancer of primary or secondary origin. We performed a systematic review and meta-analysis with the aim of assessing the feasibility, safety, and efficacy of PIPAC. METHODS: A systematic literature search was performed using Medline and Web of Science databases from 1 January 2011, to inception, to 31 December 2021. Data were independently extracted by two authors. The Newcastle-Ottawa Scale was used to assess the quality and risk of bias of studies. Meta-analysis was performed for pathological response, radiological response, PCI variation along treatment, and for patients undergoing three or more PIPAC. Pooled analyses were performed using the Freeman-Tukey double arcsine transformation, and 95% CIs were calculated using Clopper-Pearson exact CIs in all instances. RESULTS: A total of 414 papers on PIPAC were identified, and 53 studies considering 4719 PIPAC procedure in 1990 patients were included for analysis. The non-access rate or inability to perform PIPAC pooled rate was 4% of the procedures performed. The overall proportion of patients who completed 3 or more cycles of PIPAC was 39%. Severe toxicities considering CTCAE 3-4 were 4% (0% to 38.5%). In total, 50 studies evaluated deaths within the first 30 postoperative days. In the included 1936 patients were registered 26 deaths (1.3%). The pooled analysis of all the studies reporting a pathological response was 68% (95% CI 0.61-0.73), with an acceptable heterogeneity (I2 28.41%, p = 0.09). In total, 10 papers reported data regarding the radiological response, with high heterogeneity and a weighted means of 15% (0% to 77.8%). PCI variation along PIPAC cycles were reported in 14 studies. PCI diminished, increased, or remained stable in eight, one and five studies, respectively, with high heterogeneity at pooled analysis. Regarding survival, there was high heterogeneity. The 12-month estimated survival from first PIPAC for colorectal cancer, gastric cancer, gynecological cancer and hepatobiliary/pancreatic cancer were, respectively, 53%, 25%, 59% and 37%. CONCLUSIONS: PIPAC may be a useful treatment option for selected patients with PM, with acceptable grade 3 and 4 toxicity and promising survival benefit. Meta-analysis showed high heterogeneity of data among up-to-date available studies. In a subset analysis per primary tumor origin, pathological tumor regression was documented in 68% of the studies with acceptable heterogeneity. Pathological regression seems, therefore, a reliable outcome for PIPAC activity and a potential surrogate endpoint of treatment response. We recommend uniform selection criteria for patients entering a PIPAC program and highlight the urgent need to standardize items for PIPAC reports and datasets.

Diagnostic and Therapeutic Pathway in Diffuse Malignant Peritoneal Mesothelioma.

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare form of mesothelioma that carries a very poor prognosis. The 5-year overall survival is about 20% (±5.9). Survival is optimal for patients suitable for cytoreductive surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC), with a median OS ranging from 34 to 92 months. However, selecting patients for surgery remains a complex task and requires a careful preoperative workup, rational analysis of prognostic profiles, and risk prediction models. Systemic chemotherapy could be offered: (1) in the adjuvant setting for high-risk patients; (2) for patients not eligible for CRS; and (3) for those with recurrent disease. It mainly includes the combination of Platin compound with Pemetrexed or immunotherapy. The biology of DMPM is still largely unknown. However, progress has been made on some fronts, such as telomere maintenance mechanisms, deregulation of apoptosis, tyrosine kinase pathways, and mutation of BRCA1-associated protein 1 (BAP1). Future perspectives should include translational research to improve our understanding of the disease biology to identify druggable targets. We should also clear the role of immune checkpoint inhibitors and investigate new locoregional technologies, such as pressurized intraperitoneal aerosol chemotherapy (PIPAC) or normothermic intraperitoneal chemotherapy (NIPEC).

Gastric Cancer (GC) with Peritoneal Metastases (PMs): An Overview of Italian PSM Oncoteam Evidence and Study Purposes.

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.

Case report: The use of PRP in the treatment of diabetic foot: case series and a review of the literature.

Background: Diabetes mellitus is a prevalent chronic condition that significantly impacts global health. Diabetic foot complications, such as foot ulcers, pose a substantial burden on individuals with diabetes and can lead to serious consequences, including amputation. Platelet-rich plasma (PRP) has emerged as a promising therapeutic approach for enhancing the healing of diabetic foot ulcers. Methods: In our study, we treated 12 patients with chronic diabetic ulcers using PRP injections administered at three-week intervals. Our objective was to assess the reduction in wound size and the rate of complete healing at 6 months after the start of the treatment. Additionally, we conducted a comprehensive literature review to contextualize our findings. Results: Out of the 12 patients, 8 achieved complete healing of their diabetic foot ulcers, while the remaining four showed significant improvement with more than 50% reduction in the initial lesion size. 3 patients developed mild irritation at the inoculation site. These outcomes, combined with the evidence from published studies, highlight the effectiveness of PRP in promoting the healing of diabetic foot ulcers. Conclusion: In conclusion, our study demonstrates the potential of platelet-rich plasma (PRP) as a successful therapeutic option for enhancing the healing process of chronic diabetic foot ulcers. The favorable outcomes observed, including a high rate of complete healing and significant wound size reduction, underscore the value of PRP treatment in managing this challenging complication. Further research and larger studies may provide additional insights into the mechanisms and long-term benefits of PRP in diabetic wound healing.