Enhanced recovery after surgery (ERAS) implementation in cytoreductive surgery (CRS) and hyperthermic IntraPEritoneal chemotherapy (HIPEC): Insights from Italian peritoneal surface malignancies expert centers.

BACKGROUND: Cytoreductive surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a complex procedure that involves extensive peritoneal and visceral resections followed by intraperitoneal chemotherapy. The Enhanced Recovery After Surgery (ERAS) program aims to achieve faster recovery by maintaining pre-operative organ function and reducing the stress response following surgery. A recent publication introduced dedicated ERAS guidelines for CRS and HIPEC with the aim of extending the benefits to patients with peritoneal surface malignancies. METHODS: A survey was conducted among 21 Italian centers specializing in peritoneal surface malignancies (PSM) treatment to assess adherence to ERAS guidelines. The survey covered pre/intraoperative and postoperative ERAS items and explored attitudes towards ERAS implementation. RESULTS: All centers completed the survey, demonstrating expertise in PSM treatment. However, less than 30 % of centers adopted ERAS protocols despite being aware of dedicated guidelines. Preoperative optimization was common, with variations in bowel preparation methods and fasting periods. Intraoperative normothermia control was consistent, but fluid management practices varied. Postoperative practices, including routine abdominal drain placement and NGT management, varied greatly among centers. The majority of respondents expressed an intention to implement ERAS, citing concerns about feasibility and organizational challenges. CONCLUSIONS: The study concludes that Italian centers specialized in PSM treatment have limited adoption of ERAS protocols for CRS ± HIPEC, despite being aware of guidelines. The variability in practice highlights the need for standardized approaches and further evaluation of ERAS applicability in this complex surgical setting to optimize patient care.

Diagnostic and Therapeutic Pathway of Advanced Ovarian Cancer with Peritoneal Metastases.

Over two thirds of ovarian cancer patients present with advanced stage disease at the time of diagnosis. In this scenario, standard treatment includes a combination of cytoreductive surgery and carboplatinum-paclitaxel-based chemotherapy. Despite the survival advantage of patients treated with upfront cytoreductive surgery compared to women undergoing neo-adjuvant chemotherapy (NACT) and interval debulking surgery (IDS) due to high tumor load or poor performance status has been demonstrated by multiple studies, this topic is still a matter of debate. As a consequence, selecting the adequate treatment through an appropriate diagnostic pathway represents a crucial step. Aiming to assess the likelihood of leaving no residual disease at the end of surgery, the role of the CT scan as a predictor of cytoreductive outcomes has shown controversial results. Similarly, CA 125 level as an expression of tumor load demonstrated limited applicability. On the contrary, laparoscopic assessment of disease distribution through a validated scoring system was able to identify, with the highest specificity, patients undergoing suboptimal cytoreduction and therefore best suitable for NACT-IDS. Against this background, with this article, we aim to provide a comprehensive review of available evidence on the diagnostic and treatment pathways of advanced ovarian cancer.

Repeated Cytoreduction Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Selected Patients Affected by Peritoneal Metastases: Italian PSM Oncoteam Evidence.

The reiteration of surgical cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients affected by recurrent peritoneal metastases is still questioned regarding safety and effectiveness. This study evaluates the safety, efficacy, and associated factors of iterative CRS combined with HIPEC. This multicentric retrospective study collected data from four surgical oncology centers, on iterative HIPEC. We gathered data on patient and cancer characteristics, the peritoneal cancer index (PCI), completeness of cytoreduction (CC), postoperative complications, and overall survival (OS). In the study period, 141 CRS-plus-HIPECs were performed on 65 patients. Nine patients underwent three iterative procedures, and one underwent five. No increased incidence of complications after the second or third procedure was observed. Furthermore, operative time and hospitalization stay were significantly shorter after the second than after the first procedure (p < 0.05). Optimal cytoreduction was achieved in more than 90% of cases in each procedure, whether first, second, or third. A five-year (5 y) OS represented 100% of the cases of diffuse malignant-peritoneal-mesotheliomas, 81.39% of pseudomyxoma peritonei, 34.67% of colorectal cancer (CRC), and 52.50% of ovarian cancer. During the second CRS combined with HIPEC, we observed a lower rate of complete cytoreduction and a non-significantly better survival in cases with complete cytoreduction (5 y-OS CC-0 56.51% vs. 37.82%, p = 0.061). Concomitant hepatic-CRC-metastasis did not compromise the CRS-plus-HIPEC safety and efficacy. This multicentric experience encourages repeated CRS-plus-HIPEC, showing promising results.

PO2 21% oxygenated hypothermic machine perfusion in kidney transplantation: Any clinical benefit?

BACKGROUND: In deceased donor kidney transplantation (KT), the use of hypothermic machine perfusion (HMP) has been acquiring the status of best practice in the pre-transplant management of kidney grafts. Two types of HMP are currently available, oxygenated HMP and non-oxygenated HMP. However, data on the real clinical impact of oxygenation on KT outcome are still heterogeneous. METHODS: Retrospective study on a cohort of 103 patients transplanted with a single kidney graft that was managed either with end-ischemic oxygenated (O2 group, Waves Machine, n = 51, 49.5%) or non-oxygenated HMP (no-O2 group, Life Port Kidney Transporter Machine, n = 52, 50.5%), during the period January 2016-December 2020. Oxygenation was performed at pO2 21%. RESULTS: The median cold ischemia time was 29 h:40 min [IQR 26 h:55 min-31 h:10 min] and the prevalence of grafts from extended criteria donors (ECD) was 46.7%, with a median kidney donor profile index (KDPI) of 72 [41-94]. The study groups were homogeneous in terms of recipient characteristics, ischemia times and donor characteristics. O2 and no-O2 groups showed comparable outcomes in terms of delayed graft function (O2 vs no-O2, 21.5% vs 25%, p = 0.58), vascular (0.2% vs 0.2%, p > 0.99) and urologic (13.7% vs 11.5%, p = 0.77) complications, and episodes of graft rejection (11.7% vs 7.7%, p = 0.52). At 1 year follow up, even creatinine serum levels were comparable between the groups (1.27 mg/dL [1.09 and 1.67] vs 1.4 mg/dL [1.9-1.78], p = 0.319), with similar post-transplant trend (p = 0.870). No significant benefit was either observed in ECD or KDPI > 60 subgroups, respectively. CONCLUSIONS: Oxygenation at pO2 21% during HMP seems not to significantly enhance the KT outcomes in terms of postoperative complications or graft function.

Laparoscopic Cytoreduction Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Peritoneal Surface Malignancies (PSM): Italian PSM Oncoteam Evidence and Literature Review.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has gained increasing acceptance in clinical practice. Performing CRS and HIPEC laparoscopically represents a challenging and intriguing technical evolution. However, the experiences are limited, and the evidence is low. This retrospective analysis was performed on patients treated with laparoscopic CRS-HIPEC within the Italian Peritoneal Surface Malignancies Oncoteam. Clinical, perioperative, and follow-up data were extracted and collected on prospectively maintained databases. We added a systematic review according to the PRISMA method for English-language articles through April 2022 using the keywords laparoscopic, hyperthermic, HIPEC, and chemotherapy. From 2016 to 2022, fourteen patients were treated with Lap-CRS-HIPEC with curative intent within the Italian centers. No conversion to open was observed. The median duration of surgery was 487.5 min. The median Peritoneal Cancer Index (PCI) was 3, and complete cytoreduction was achieved in all patients. Two patients (14.3%) had major postoperative complications, one requiring reintervention. After a median follow-up of 16.9 months, eleven patients were alive without disease (78.6%), two patients developed recurrence (14.3%), and one patient died for unrelated causes (7.1%). The literature review confirmed these results. In conclusion, current evidence shows that Lap-CRS-HIPEC is feasible, safe, and associated with a favorable outcome in selected patients. An accurate patient selection will continue to be paramount in choosing this treatment.

Extraskeletal myxoid chondrosarcoma: a case report with adjuvant intraoperative treatment.

Extraskeletal myxoid chondrosarcoma is a rare form of malignant mesenchymal neoplasm mainly localized into the limbs, particularly in the thigh and popliteal fossa. It has been classified as a low-grade sarcoma so far, but it shows a tendency to relapse and metastasize. In the early stage of disease, surgery represents the only chance of cure. In case of diffuse metastatic disease, systemic chemotherapy with anthracyclines is the standard of care. In this paper, we present a case of a patient affected by this rare disease and the analysis of radiological, surgical and histopathological aspects.

Microscopic peritoneal carcinomatosis in gastric cancer: Prevalence, prognosis and predictive factors.

Peritoneal carcinomatosis (PC) is typically identified in advanced stage gastric cancer and is frequently considered to be an incurable disease. Along with macroscopic PC, microscopic PC may be diagnosed through pathological examination of tissue specimens and is not detectable during surgical intervention. The present study aimed to analyse the prevalence, prognostic value and predictive factors for microscopic PC. In the present retrospective study, data from patients with epithelial gastric cancer that were treated with curative intent surgery were examined. Patients with macroscopic PC were excluded. Additionally, the study population was divided into two groups based on the presence or absence of microscopic PC. The prevalence of microscopic PC was 5.5%. Microscopic PC exhibited a significant negative effect on overall survival. In addition, multivariate analyses revealed that the significant predictive factors for the presence of microscopic PC were adenocarcinoma of a diffuse type, lymphatic and vascular invasion, cancer location at the site of previous gastric surgery and a tumour extent >T2. In particular, the presence of lymphatic and vascular invasion was the most significant predictive factor. These results indicate that ≥5.5% of patients with gastric cancer who undergo surgery with a curative intent may benefit from more aggressive loco-regional treatment against microscopic PC at the time of surgery.

Embolisation of arteriovenous intrahepatic fistulas associated with diffuse haemangiomatosis of the liver. Report of a case in an adult and review of the literature.

Diffuse hepatic haemangiomatosis is rare in adults. Association with high output intrahepatic arteriovenous fistulas has been described. To avoid heart failure complications, treatment is essential. The second case in the literature, treated with repeated transcatheter arterial embolizations (TAE) but complicated by infection of multiple haemangiomas and by Kasabach-Merritt syndrome, is presented. Complications were due to the persistent presence of haemangiomas within the liver, where an impressive collection of platelets and a superinfection were observed. Therefore, to treat arteriovenous fistula-related problems and to prevent possible complications due to persistence of the haemangiomas, surgical removal should be preferred over embolisation.

Potential advantages of loco-regional intra-arterial chemotherapy.

Arterial infusion or perfusion are currently used to treat hepatic tumours, head and neck malignancy, melanomas and sarcomas of the limbs. An experimental study with epirubicin and cis-platinum infused into the hepatic artery was performed. Epirubicin was injected via the systemic vein or the hepatic artery in 27 rats. Cis-platinum was injected via a systemic route or the hepatic artery in 29 rats. Drug concentrations were evaluated in liver and tumour tissues. In the rats the tumour tissue drug concentration after hepatic artery infusion was 6- and 4-fold higher than with systemic infusion for epirubicin and cis-platinum, respectively. Arterial administration appeared to be better than systemic in terms of drug concentration within the tumours and systemic toxicity.

Long term results of hepatic resection or orthotopic liver transplantation in patients with liver metastases from gastrointestinal neuroendocrine tumors.

Hepatic metastases are one of the most important prognostic factors for survival among patients affected by gastrointestinal neuroendocrine tumors (NETs). The present study aims to evaluate the impact of surgery, including hepatic resection or orthotopic liver transplantation (OLT), on the outcome of patients affected by hepatic metastases from NETs, in terms of overall survival (OS). In this multicentric retrospective study, data was collected on 26 patients, who underwent surgery for hepatic metastases from NETs in two Italian University Clinics between January 1990 and December 2012; of which, 22 patients underwent hepatic resective surgery and 4 patients OLT. Hepatic metastases were synchronous in the 53.8% of cases and metachronous in the 46.2% of cases. The median number of resected hepatic metastases was 3. Surgical radicalness (R0) was reached in the 84.6% of cases. In total, 57.7% of patients had a recurrence, 66.7% of which were intra- and 33.3% extra-hepatic. The OS of patients that underwent hepatic resections and OLT was 44.9% [95% confidence interval (CI95), 26.0-77.7%] and 50% (CI95, 12.5-100.0%) at 5 years, respectively. Although the data regarding the survival of patients receiving surgery for hepatic metastases from NETs are encouraging, randomized clinical trials are necessary to more adequately evaluate the effect of surgery on survival of this group of patients.

Prevalence, risk factors, and prognosis of peritoneal metastasis from breast cancer.

Peritoneal metastasis from breast cancer is a serious and deadly condition only limited considered in the literature. Our aim was to study prevalence, risk factors, and prognosis of breast cancer peritoneal metastasis. We retrospectively analyzed 3096 women with a diagnosis of invasive breast cancer. We took into consideration presence and localization of breast cancer distant metastasis as well as the possible risk factors and survival from the diagnosis of the breast cancer metastasis. The prevalence of breast cancer peritoneal metastases was 0.7 % (22/3096), representing the 7.6 % (22/289) of women affected by distant metastases. Moreover, independent risk factors for breast cancer peritoneal metastases resulted high grading, lobular invasive histology, and advanced T and N stage at diagnosis. Overall survival after metastasis diagnosis was shorter in women affected by peritoneal metastases or brain metastases in comparison to other metastatic women. Breast cancer peritoneal metastases were uncommon but not rare events with a poor prognosis after standard treatments.

Adrenal incidentalomas: indications for surgery.

Adrenalectomy represents the gold standard treatment for hyperfunctioning adrenal incidentaloma. In cases of silent adrenal masses, on the other hand, the surgical removal of an adrenocortical cancer entails the sacrifice of a large number of safe benign masses, and in most cases surgery is therefore unjustified. The aim of this paper was to clarify the surgical indications for adrenal incidentaloma by reviewing our experience in comparison with the main reference literature. Over the period from 1995 to 2001 we managed 40 cases of incidentaloma. US and CT abdominal scans, adrenal scintigraphy and biochemical tests were performed on an outpatient basis. Seven pre-Cushing syndromes were removed. Ten incidentalomas measured 4 cm or more in diameter: 5 of these were operated on and in 5 cases surgery was not feasible or was refused. Only one malignant mass was detected (an angiosarcoma). Four postoperative minimal complications (18.7%) were observed. The follow-up (median: 48 months) was uneventful. The surgical approach was traditional in 11 cases and laparoscopic in 1 case. Surgery should be considered mandatory in cases of hyperfunctioning adrenal masses in the presence of suspect radiological evidence, in cases of discordant CT and scintigraphy findings and when the maximum diameter is 4 cm or more.

Curative versus palliative surgical resection of liver metastases in patients with neuroendocrine tumors: a meta-analysis of observational studies.

BACKGROUND: The role of surgical therapy in patients with liver metastases from neuroendocrine tumors (NETs) is unclear. In this study, the results obtained with curative or palliative resection, by reviewing recent literature and performing a meta-analysis, were examined. MATERIALS AND METHODS: A systematic review and meta-analysis of observational studies published between January 1990 and October 2013 were performed. Studies that evaluated the different survival between patients treated by curative or palliative surgical resection of hepatic metastases from NETs were considered. The collected studies were evaluated for heterogeneity, publication bias, and quality. To calculate the pooled hazard ratio (HR) estimate and the 95% confidence interval (95% CI), a fixed-effects model was applied. RESULTS: After the literature search, 2,546 studies were found and, among 38 potentially eligible studies, 3 were considered. We did not find a significant longer survival in patients treated with curative surgical resection of hepatic metastases when compared to palliative hepatic resection HR 0.40 (95% CI: 0.14-1.11). In one study, palliative resection of hepatic metastases significantly increased survival when compared to embolization. CONCLUSIONS: Curative and also palliative surgery of NETs liver metastases may improve survival outcome. However, further randomized clinical trials are needed to elucidate this argument.

Preoperative assessment of peritoneal carcinomatosis in patients undergoing hyperthermic intraperitoneal chemotherapy following cytoreductive surgery.

The present study evaluates the accuracy of computed tomographic (CT) scan and positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET)/CT for the quantification of peritoneal carcinomatosis (PC) in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Data were retrospectively collected for 58 patients, who were considered for CRS and HIPEC. The predictability, sensitivity, specificity and accuracy values of FDG-PET/CT and CT were tested. Preoperative CT and FDG-PET/CT failed to detect PC in 9% and 17% of cases, respectively, with a sensitivity of 91% and 82%, a specificity of 33% and 67%, an area under the curve (AUC) of 62% and 74% and a negative likelihood ratio of 0.27 (CI.95 0.07-1.09) and 0.27 (CI.95 0.11-0.62), respectively (p=0.469). Both techniques showed a high prevalence of PC extent underestimation (CT 47% and FDG-PET/CT 43% of cases). Small bowel involvement and optimal CRS had a prevalence of 60% and 76%, respectively, and both the CT and FDG-PET/CT imaging techniques were inaccurate at predicting them (AUC 53% and 52% for small bowel involvement, and 63% and 58% for optimal CRS, respectively). In conclusion both CT and FDG-PET/CT had low preoperative staging reliability for PC, and this can strongly influence the ability to implement the correct treatment strategy for patients with PC.

Surgical treatment and survival in patients with liver metastases from neuroendocrine tumors: a meta-analysis of observational studies.

Introduction. The role of hepatic resection in patients with liver metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is still poorly defined. Therefore, we examined the results obtained with surgical resection and other locoregional or systemic therapies by reviewing the recent literature on this topic. We performed the meta-analysis for comparing surgical resection of hepatic metastases with other treatments. Materials and Methods. In this systematic review and meta-analysis of observational studies, the literature search was undertaken between 1990 and 2012 looking for studies evaluating the different survivals between patients treated with surgical resection of hepatic metastases and with other surgical or nonsurgical therapies. The studies were evaluated for quality, publication bias, and heterogeneity. Pooled hazard ratio (HR) estimates and 95% confidence intervals (CI.95) were calculated using fixed-effects model. Results. We selected six studies in the review, five of which were suitable for meta-analysis. We found a significant longer survival in patients treated with hepatic resection than embolisation HR 0.34 (CI.95 0.21-0.55) or all other nonsurgical treatments HR 0.45 (CI.95 0.34-0.60). Only one study compared surgical resection with liver transplantation and meta-analysis was not feasible. Conclusions. Our meta-analysis provides evidence supporting the hypothesis that hepatic resection increases overall survival in patients with liver metastases from GEP-NETs. Further randomized clinical trials are needed to confirm these findings and it would be desirable to identify new markers to properly select patients for surgical treatment.

The length of peritoneal surgical manipulation correlates with serum CA 125 levels.

BACKGROUND: Peritoneal recovery after uncomplicated serum manipulation usually lasts 7 days and high values of serical CA 125 are measured following abdominal surgery. The aim of this study was to assess a possible correlation between peritoneal manipulation and serical CA 125 levels following abdominal surgery for benign diseases. PATIENTS AND METHODS: Twenty-eight patients with abdominal benign disease were operated on. They were pooled into three groups of low, intermediate and high peritoneal manipulation, according to the extent of laparotomy and length of surgical peritoneal manipulation. Venous blood samples (5 ml) were taken from each patient 24-48 hours before surgery, 12-24 hours after surgery and on the 4th and 7th postoperative day. CA 125 levels were quantified by microparticle enzyme immunoassay. RESULTS: After surgery, patients having high peritoneal manipulation showed significantly higher levels of CA 125 compared to the preoperative levels. In particular, the length of peritoneal manipulation was correlated with increasing levels of the marker (p<0.0001). CONCLUSION: Peritoneal manipulation was significantly correlated to serum CA 125 levels; therefore its role as marker of peritoneal surgical injury should be considered.

Intra-arterial hepatic chemotherapy for unresectable colorectal liver metastases: a review of medical devices complications in 3172 patients.

BACKGROUND: Hepatic artery infusion (HAI) is indicated to treat unresectable colorectal hepatic metastases, with recent applications as a neoadjuvant or adjuvant treatment. Traditionally performed with the infusion of fluoropyrimidine-based chemotherapy, it has been now tested with oxaliplatin or irinotecan and associated with systemic chemotherapy. METHODS: To evaluate the impact of medical devices complications we carried out a search of the published studies on HAI in unresectable colorectal liver metastases. Complications were pooled according to the applied medical system: 1) surgical catheter, 2) radiological catheter, and 3) fully implantable pump. The surgical catheter is inserted into the hepatic artery from the gastro-duodenal artery. The radiological catheter is inserted into the hepatic artery through a percutaneous transfemoral or transaxillar access. The fully implantable pump is a totally internal medical device connected to the arterial hepatic catheter during laparotomy. RESULTS: The selection criteria were met in 47/319 studies. The complications of surgical and radiological medical devices connected to a port were found in 16 and 14 studies respectively. Meanwhile, complications with a fully implantable pump were reported in 17 studies. The total number of complications reported in studies evaluating patients with surgical or radiological catheter were 322 (322/948, 34%) and 261 (261/722, 36.1%) respectively. In studies evaluating patients with a fully implantable pump, the total number of complications was 237 (237/1502, 15.8%). In 18/319 studies the number of cycles was reported. The median number of cycles with surgically and radiologically implanted catheters was 8 and 6 respectively. The fully implantable pump allows a median number of 12 cycles. CONCLUSIONS: The fully implantable pump, maintaining a continuous infusion through the system, allows the lowest risk for thrombosis and infection and the best median number of cycles of loco-regional chemotherapy in HAI.

Tamoxifen and its main metabolites serum and tissue concentrations in breast cancer women.

Because of a possible relationship between tamoxifen (T) concentrations and clinical effects, we initiated a preliminary investigation on serum and tissue concentrations of T and its main active metabolites, and 4-hydroxytamoxifen, in women with positive breast cancer estrogen receptor. One hundred forty-eight patients were studied: 80 were admitted for monitoring of therapeutic serum drug concentrations, 22 had tissue concentrations taken at surgery, and 46 patients had uterine mucosa levels measured at diagnostic hysteroscopy. Steady-state serum concentrations were reached after 1 month of continuous treatment, with desmethyltamoxifen being the highest represented derivative from the third week onward. There was no relationship between dose (in mg/kg body weight) and steady-state serum concentrations during therapeutic drug monitoring of patients. The highest tissue concentrations were observed in breast lymph-nodes, cancer tissue, and uterine mucosa. On the basis of these data, we speculate that T and its active metabolites may exert both a defensive role (ie, an obstacle to the diffusion of malignant cells through the local lymphatic system) and a harmful one (induction of uterine malignancies).

Adrenal angiosarcoma: report of a case.

Adrenal epithelioid angiosarcoma is an extremely rare tumor. Even if such tumors are very aggressive, a long survival may occasionally be observed after an adrenal ectomy. A 70-year-old woman suffering from persistent right flank pain showed a 5-cm right adrenal mass plus a 2-cm liver mass at the radiologic workup, and both were suspected of being malignant. No adrenal hypersecretion was demonstrated. During an explorative median laparotomy the right adrenal gland with the whole periadrenal tissue and locoregional lymph nodes was removed. A histological examination revealed an adrenal angiosarcoma. The resection margin was tumor-free with no lymph node infiltration. The liver mass turned out to be a cistobiliary adenoma. Since no distant metastases were observed, no adjuvant chemotherapy was performed. After an 18-month follow-up the patient is still well with no sign of a relapse. When this rare adrenal tumor is encountered and curative treatment is attempted initially extensive surgical procedures are essential.