Robotic resection of left renal vein with preservation of left kidney for leiomyosarcoma: Case report and review of the literature.

INTRODUCTION: Radical surgical resection with negative margins is the mainstay of treatment for retroperitoneal vascular leiomyosarcomas. Given the retroperitoneal location of these tumors, open surgery is, historically, the chosen surgical approach, however, it is burdened with high postoperative morbidity. In selected cases, the small dimension of the tumor and a favorable location, allow to perform a minimally invasive treatment. PRESENTATION OF CASE: A 67-year-old female patient with a diagnosis of a leiomyosarcoma arising from the left renal vein underwent a robotic resection of the left renal vein with preservation of the left kidney and a relative outflow trough the gonadal vessels. The patient was discharged on the fourth postoperative day without any complications and there was no tumor recurrence noted during the 24-month follow-up period. DISCUSSION: Vascular retroperitoneal leiomyosarcomas are very rare tumors requiring a complete en bloc gross tumor resection in order to achieving microscopically negative margins on the vein of origin. Thanks to the preoperative histological diagnosis and radiological study of the neoplasm, it was possible to proceed to a highly personalized and minimally invasive treatment with respect of oncological criteria. CONCLUSION: In selected cases, a minimally invasive surgery of vascular leiomyosarcoma could be a feasible and safe treatment option.

Vascular- and nerve-sparing bowel resection for deep endometriosis: A retrospective single-center study.

OBJECTIVE: Surgical management of bowel endometriosis is still controversial. Recently, many authors have pointed out the potential benefits of preserving the superior rectal artery, thus ensuring better perfusion of the anastomosis. The aim of this study was to evaluate the complication rate and functional outcomes of a bowel resection technique for deep endometriosis (DE) involving a nerve- and vascular-sparing approach. METHODS: A single-center retrospective study was conducted by enrolling patients who underwent segmental resection of the rectus sigmoid for DE in our department between September 2019 and April 2022. Intraoperative and postoperative complications were recorded for each woman, and functional outcomes relating to the pelvic organs were assessed using validated questionnaires (Knowles-Eccersley-Scott-Symptom [KESS] questionnaire and Gastro-Intestinal Quality of Life Index [GIQLI] for bowel function, Bristol Female Lower Urinary Tract Symptoms [BFLUTS] for urinary function, and Female Sexual Function Index [FSFI] for sexual function). These were evaluated preoperatively and postoperatively after 6 months from surgery. RESULTS: Sixty-one patients were enrolled. No patients had Clavien-Dindo grade 3 or 4 complications, there were no rectovaginal fistulas or ureteral lesions, and in no cases was it necessary to reoperate. Temporary bladder voiding deficits were reported in 8.2% of patients, which were treated with self-catheterizations, always resolving within 45 days of surgery. Gastrointestinal function evaluated by KESS and GIQLI improved significantly after surgery, whereas sexual function appeared to worsen, although without reaching the level of statistically significant validity. CONCLUSION: Our vascular- and nerve-sparing segmental bowel resection technique for DE had a low intraoperative and postoperative complication rate and produced an improvement in gastrointestinal function after surgery.

Gastric cancer with peritoneal metastases: a single center outline and comparison of different surgical and intraperitoneal treatments.

INTRODUCTION: Gastric cancer with peritoneal metastasis (GCPM) has an unfavourable prognosis. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) are promising treatment options that have been shown to improve survival. The aim of this study was to assess the impact of different treatments such as systemic chemotherapy, systemic chemotherapy + PIPAC, and CRS + HIPEC in patients with GCPM. MATERIAL AND METHODS: This single-centre retrospective study included 82 patients with GCPM treated between January 2016 and June 2021. After first-line chemotherapy, depending on disease response and burden, the patients were divided into three treatment groups: chemotherapy alone, chemotherapy + PIPAC, and CRS + HIPEC. The primary outcome was overall survival (OS) from diagnosis, which was compared among the treatment groups. RESULTS: Thirty-seven (45.1%) patients were administered systemic chemotherapy alone, 25 (30.4%) received chemotherapy + PIPAC, and 20 (24.4%) underwent CRS + HIPEC. The CRS + HIPEC group had better OS (median 24 months) than the PIPAC group (15 months, p = 0.01) and chemotherapy group (5 months, p = 0.0001). Following CRS + HIPEC, the postoperative grade 3-4 complication rate was 25%, and no postoperative in-hospital deaths occurred. The median disease-free survival (DFS) was 12 months. Multivariate analysis identified peritoneal carcinomatosis index (PCI) > 7 as an independent predictor of worse DFS. No independent predictors of OS were identified. CONCLUSION: Among patients with GCPM, we identified a highly selected population with oligometastatic disease. In this group, CRS + HIPEC provided a significant survival advantage with an acceptable major complication rate compared with other available therapies (systemic chemotherapy alone or in combination with PIPAC).

Prophylactic surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC CO2) versus standard surgery in colorectal carcinoma at high risk of peritoneal carcinomatosis: short-term and long-term outcomes from the CHECK study - protocol for a randomised, multicentre, phase 3 trial.

INTRODUCTION: Up to one-fifth of patients with colorectal cancer will develop peritoneal metastases, frequently without other districts' involvement. Despite the recent unsuccesses of hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer peritoneal metastases treatment, the rationale in the prophylactic setting remains strong. Several clinical and pharmacokinetic data suggest that the efficacy of intraperitoneal chemotherapy is highest when the disease is microscopic. However, robust evidence demonstrating whether the addition of HIPEC for high-risk colorectal cancers offers better control of local recurrence is lacking. METHODS AND ANALYSIS: This is a multicentre randomised phase 3 trial comparing prophylactic surgery plus HIPEC CO2 with mitomycin, over standard surgical excision in patients with colorectal cancer at high risk of peritoneal carcinomatosis; 388 patients will be included in this study. The primary objective is to compare the efficacy of prophylactic surgery (radical colorectal resection, omentectomy, appendectomy, round ligament of the liver resection and bilateral adnexectomy) plus HIPEC CO2 with mitomycin and standard surgery in terms of local recurrence-free survival. The main secondary endpoints are disease-free survival (DFS), overall survival (OS) and safety. The primary endpoint will be described with a cumulative incidence function and will be analysed with Grey test to take account of the competing risks. DFS and OS will be described with the Kaplan-Meier method. ETHICS AND DISSEMINATION: This trial has been evaluated by the Italian Medicines Agency, local ethics committees and will be submitted to the Ministry of Health to notify the start of the trial according to the regulation of trials on devices with CE mark/certification.The results will be submitted for presentation at academic meetings and for publication in a peer-reviewed journal, whatever the findings. TRIAL REGISTRATION NUMBER: NCT03914820.

The Road to Technical Proficiency in Cytoreductive Surgery for Peritoneal Carcinomatosis: Risk-Adjusted Cumulative Summation Analysis.

Background: Cytoreductive surgery (CRS) is a technically demanding procedure, and there is considerable debate about its safe application. This study investigated the learning curve for CRS and the clinical outcomes of consecutive patients treated by a single surgeon at a single institution. Methods: We collected 251 consecutive patients who underwent CRS for peritoneal metastases by a single surgeon at Fondazione Policlinico Universitario A. Gemelli IRCCS, between January 2016 and December 2020. The learning curve was estimated using the cumulative summation analysis (CUSUM) for operative time (OT). Risk-adjusted CUSUM (RA-CUSUM) charts were developed using a composite variable (surgical failure), defined as the occurrence of at least one of the following events: major postoperative complications (Clavien-Dindo grade ≥3), blood loss ≥500 mL, incomplete cytoreduction. Three learning phases were thus derived from the RA-CUSUM analysis, and were compared in terms of perioperative outcomes. Results: CUSUM-OT showed that the operation time improved significantly after the 161th case. RA-CUSUM analysis allowed to break the CRS learning curve into three different phases: phase 1, "the learning phase" (cases 1-99), phase 2 "the experienced phase" (cases 100-188), and phase 3, "the mastership phase" (cases 189-251). The rate of major postoperative complications decreased significantly over the three phases (p = 0.019). Operative time decreased significantly as well (p = 0.031) and was significantly shorter in phase 3 with respect to the other two phases (phase 3 vs phase 2: 420 min vs 500 min, p = 0.017; phase 3 vs phase 1: 420 min vs 503 min, p = 0.021). Blood loss consistently decreased throughout the three phases (p = 0.001). The rate of incomplete cytoreduction was significantly lower in phase 3 than in phase 2 (4.8% vs 14.6%, p = 0.043). Conclusion: The CRS failure rate stabilized after the first 99 cases, and the complete surgical proficiency was achieved after 189 cases. A standardised and mentored learning model is a safer strategy to shorten the learning process, to reduce morbidity and mortality, to improve oncologic outcomes.

Delayed Gastric Emptying After Multivisceral Resection for Retroperitoneal Sarcoma.

INTRODUCTION: Delayed gastric emptying (DGE) is a common complication in surgery, but incidence and relevance following multivisceral resection are unknown. METHODS: Data from 100 consecutive patients treated for primary retroperitoneal sarcoma (RPS) were analyzed from our institutional prospectively maintained database from January 2019 to April 2020. DGE severity was graded according to the International Study Group of Pancreatic Surgery and classified as primary or secondary to other complications. The primary outcome was incidence and grade of clinically relevant DGE (grades B-C). Secondary outcomes were correlation with patient, tumor, and treatment characteristics, and non-DGE morbidity [Clavien-Dindo (CD) grade ≥ 3]. RESULTS: Forty-two patients developed DGE and 28 had clinically relevant DGE. DGE was primary in 10 patients and secondary in 18 patients; the most common associated complications were: infections (11/18, 61.1%), pancreatic leak (7/18, 38.9%), bleeding (6/18, 33.3%), and bowel leak (6/18, 33.3%). DGE was related to longer length of hospital stay (P < 0.001), ICU admission (P = 0.004), ICU length of stay (P = 0.001), postoperative complications (CD [Formula: see text] 3 in 14/28 in DGE patients vs 11/72 in no-DGE; P = 0.04), and re-operation (P = 0.03). With multivariate analysis, the independent risk factors for DGE were patient comorbidities (OR 1.05; 95% CI 1.01-1.1; P = 0.04) and tumor size (OR 1.05; 95% CI 1.0-1.1; P = 0.02). DISCUSSION: Following multivisceral resection, DGE is a clinically relevant event that can be caused by an underlying complication. Prompt diagnosis and treatment of both DGE and any underlying complications led to full recovery in all cases.

Prognostic Factors for Surgical Failure in Malignant Bowel Obstruction and Peritoneal Carcinomatosis.

Introduction: Patients with peritoneal metastasis frequently develop malignant bowel obstruction (MBO). Medical palliative management is preferred but often fails. Conversely, the role of palliative surgery remains unclear and debated. This study aims to identify patients who could benefit from invasive surgical interventions and factors associated with successful surgical palliation. Materials and Methods: In this retrospective study, 98 consecutive patients who underwent palliative surgery for MBO over 5 years were reviewed. We evaluate as the primary outcome surgical failure to select patients who could benefit from palliative surgery, avoiding unnecessary surgery. A prognostic score was developed based on a logistic regression model to identify patients at risk of surgical failure. The score was evaluated for overall accuracy by receiver operating characteristic curve analysis. Results: Palliative surgery was achieved in 76 (77.5%) patients. The variables that were found to be significant factors for surgical failure are recurrent disease (P = 0.015), absence of bowel obstruction (P < 0.001), absence of bowel distension (P < 0.001), and mesenteric involvement (P = 0.001) and retraction (P < 0.001). The absence of bowel distension (P = 0.046) and bowel obstruction (P = 0.012) emerged as independent predictors of surgical failure. Carcinomatosis level assessment for peritoneum score, based on these factors, was built to evaluate the risk of surgical failure. Conclusion: Our proposed scoring system might help select patients most likely to benefit from palliative surgery.

Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei of Appendiceal Origin: A Single Center Experience.

Background: Pseudomyxoma peritonei (PMP) originating from appendiceal mucinous neoplasm is a rare peritoneal malignancy characterized by the progressive intraperitoneal accumulation of mucus leading to death if left untreated. In recent years, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) offered increased survival rates. This study aims to identify the clinical, pathological, and surgical features influencing safety and survival outcomes of patients undergoing CRS and HIPEC for PMP of appendiceal origin. Methods: A retrospective analysis of all patients undergoing CRS and HIPEC for PMP of appendiceal origin from January 2015 to May 2019 was conducted at our institution. Results: Study population included 50 patients (74% female, 26% male). The median age at CRS was 60 (38-84). The median peritoneal cancer index (PCI) was 17. Complete cytoreductive surgery (CC 0-1) was achieved in 47 patients (94%). HIPEC chemotherapeutic regimen was based on oxaliplatin for 13 (28%) patients and mitomycin for 34 (72%) patients. We experienced a total of 19 (38%) postoperative complications, of which 14 (74%) of grade I-II and 5 (26%) of grade III-IV, according to the Clavien-Dindo classification. The median follow-up period was 27 months (12-107) from the date of cytoreductive surgery. The mean survival rate was 100 months, with a 5-year OS of 91%. The mean progression-free survival rate was 77 months (0-107), with a 5-year PFS of 63%. Multivariate analysis identified adenocarcinoma histotype and incomplete cytoreduction to significantly worsen progression-free survival, while incomplete cytoreduction was the only independent predictor of poorer overall survival. Conclusion: Complete cytoreduction and appendiceal neoplasm histotype play a crucial role in the survival of patients affected by PMP of appendiceal origin. The rates of morbidity associated with CRS and HIPEC for PMP are acceptable.

Clinical and Molecular Features in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinosis from Colorectal Cancer.

PURPOSE: Careful patient selection plays a crucial role in avoiding overtreatment and further increases survival rates in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer (CRC) with peritoneal metastases (PM). METHODS: The clinical and molecular factors influencing survival in patients who had undergone CRS with HIPEC between January 2015 and December 2018 were analyzed. RESULTS: Sixty-six patients underwent CRS with HIPEC during the study period. The median overall survival (OS) was 36 months, with a 3-year OS of 43%. Multivariate analysis revealed increased PCI (HR: 1.21; 95% CI: 1.02-1.41; p = 0.020), right-sided primary tumor (HR: 3.01; 95% CI: 1.27-7.13; p = 0.017), and BRAF V600E mutation (HR: 4.55; 95% CI: 1.21-17.21; p = 0.025) as independent predictors for worse OS. CONCLUSION: In addition to confirming the prognostic role of PCI, our study extends the role of BRAF mutation and right primary tumor location as markers for worse prognosis.

Cytoreductive surgery and mitomycin C hyperthermic intraperitoneal chemotherapy with CO2 recirculation (HIPEC-CO2) for colorectal cancer peritoneal metastases: analysis of short-term outcomes.

Peritoneal dissemination from colorectal cancer (CRC) has long been associated with unfavorable prognosis. However, in the last decades, the combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) was able to obtain up to 30% 5-year survival rate in selected centers. Despite the wide diffusion of CRS and HIPEC, until now, there are no clear recommendations on the drug of choice for HIPEC nor its technique, and safety and efficacy data of HIPEC regimens and techniques are lacking. We performed a retrospective analysis of a prospectively maintained database of 26 CRS and mitomycin C HIPEC with CO2 recirculation (HIPEC-CO2) for CRC peritoneal metastasis (PM) performed at our center. The main endpoints were morbidity, mortality, the temperature of perfusate during HIPEC and metabolic changes throughout the procedure. Morbidity was assessed by analysis of postoperative adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.0). Continuous variables of Arterial Blood Gas (ABG) analysis at three time-points were compared by the Student t test. There were no postoperative deaths. The overall grade 3-4 CTCAE complications rate at 30 days was 38.4%, with ten severe adverse events occurring to six (23.0%) patients. The temperature within HIPEC perfusion maintained between 41 and 42 °C in all cases and we experienced no HIPEC-related intraoperative complications. We observed a significant difference between all baseline and pre-HIPEC ABG parameters evaluated but no statistically significant differences between pre- and post-HIPEC ABG outcomes. This study shows that mitomycin C HIPEC-CO2 is feasible and has a safety profile comparable to that of other HIPEC techniques reported in the literature. Further research is needed to validate prospectively the safety and efficacy of this technique.

Systemic chemotherapy and pressurized intraperitoneal aerosol chemotherapy (PIPAC): A case report of a multimodal treatment for peritoneal metastases of pancreatic origin.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) with peritoneal metastases (PM) has a dismal prognosis and palliative systemic chemotherapy, which represents the standard treatment option, has significant pharmacokinetics limitations and low efficacy. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new method of drug delivery that is expected to maximize exposure of peritoneal nodules to antiblastic agents. A combination of systemic chemotherapy and PIPAC may be valuable. PRESENTATION OF CASE: A 55 years old male affected by PDAC with synchronous PM underwent a multimodal treatment comprising systemic chemotherapy and PIPAC without any procedural-related adverse events. Tumor genomic profiling evaluation from peritoneal biopsies addressed further tailored systemic chemotherapy. DISCUSSION: The presented case illustrates the possibility of adding PIPAC to systemic chemotherapy with a fair tolerance profile and good quality of life while allowing monitoring of therapy-response and tailoring of the antiblastic treatment.

Systemic chemotherapy and pressurized intraperitoneal aerosol chemotherapy (PIPAC): A bidirectional approach for gastric cancer peritoneal metastasis.

BACKGROUND: Few patients affected by gastric cancer peritoneal metastasis (GCPM) are offered locoregional treatment, despite several proof-of-efficacy trials. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged in recent years as a promising tool to control peritoneal carcinomatosis. The combination of PIPAC with systemic chemotherapy may offer a greater clinical benefit than standard treatment alone. METHODS: A single-center cohort of 28 consecutive patients affected by GCPM was scheduled for bidirectional treatment, comprising PIPAC and systemic chemotherapy, from September 2017 to September 2019. Data recorded included safety, efficacy and survival outcomes. Ascite volumes, the Peritoneal Cancer Index (PCI) and pathological response through the Peritoneal Regression Grading Score (PRGS) were compared in those patients who underwent more than one PIPAC procedure. RESULTS: Forty-six PIPAC procedures were administered, with a mean of 1.7 PIPAC procedures per patient. The median time to resume systemic chemotherapy after PIPAC was 6 days (range 4-7). Concerning safety, two grade 3-4 CTCAE (Common Terminology Criteria for Adverse Events v4.0) toxicity events and one intraoperative complication were recorded. Thirteen patients repeated PIPAC. A pathological response was recorded in 61.5% of patients (one with complete and seven with partial regression). The median overall survival was 12.3 months in the overall population and 15.0 months in patients undergoing more than one PIPAC procedure. CONCLUSIONS: A bidirectional approach for GCPM was feasible and safe, as the PIPAC procedure integrates well with several systemic chemotherapy regimens. The pathological response demonstrated the antitumoral efficacy of PIPAC. The proposed bidirectional approach may be further investigated in the first-line treatment of metastatic gastric cancer.

From palliation to cure: PIPAC for peritoneal malignancies.

INTRODUCTION: Systemic chemotherapy offers poor control over peritoneal disease, maybe as a consequence of restricted drug availability within the abdominal cavity. Locoregional chemotherapy may overcome these shortcomings but its administration is limited to a few patients with confined peritoneal spread. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) emerged in the last years as a novel method of intraperitoneal drug administration. EVIDENCE ACQUISITION: We report a meta-analysis of published studies on PIPAC safety and pathological anti-tumoral efficacy on PC from various tumor entities, with the aim of providing more evidence to support further research. This systematic review and meta-analysis were designed, conducted and reported according to the PRISMA statement. EVIDENCE SYNTHESIS: An overall pathological response rate of 43.7% was calculated on a total of 668 patients who underwent 1480 PIPAC cycles across the 20 studies. Pooled severe adverse events rate (CTCAE grade 3-4) was 10% and seven deaths across all studies were reported, of which only four were related to PIPAC. CONCLUSIONS: PIPAC is a safe procedure which has a relevant anti-tumoral activity on peritoneal carcinomatosis. Further studies, even in the early stage of disease, are awaited to assess the clinical benefit of PIPAC. This review may serve as a reliable basis for future research.

Hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancies using new hybrid CO2 system: preliminary experience in referral center.

The most frequent peritoneal surface malignancies originate principally by gastric cancer, colorectal cancer and ovarian cancer. Apart from the origin, peritoneal carcinosis (PC) is considered a negative prognostic factor. The hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal malignancies is considered an attractive method to deliver chemotherapy with enhanced effect directly at the tumor site. The use of such loco-regional approach has proved to improve prognosis of peritoneal carcinomatosis from different origins. Recently, new devices are suitable for loco-regional intraperitoneal chemotherapy as Peritoneal Recirculation System (PRS-1.0 Combat) with CO2 technology. This is a retrospective study with the aim to assess the perioperative outcomes using PRS. Seventeen patients were enrolled affected by colorectal or ovarian cancer. Complete cytoreduction (RT = 0) was achieved for all cases. Median operative time was 420 min (range: 335-665) and median drugs dose used for HIPEC was 137 mg/m2 (115-756). Median EBL was 200 ml (range 50-1000). Median post-operative hospital stay was 9 days (range: 4-24). Treatment-related early complications were recorded in 8 (47.0%) cases and were G1-G2 Major complications occurred in two (11.7%) cases. Considering our aim to test the PRS in different cases and in different pathologies, the results confirmed that the technique is feasible with good perioperative outcomes.