Peritoneal metastases from rare ovarian cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).

Objectives: There are limited treatment options and no consensus on the management of advanced rare ovarian malignancies. Rare ovarian malignancies can present with peritoneal metastases (PM), featuring a similar presentation to more common ovarian subtypes. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an effective treatment for PM of non-gynecologic origin and, recently, epithelial ovarian cancer. We evaluated the feasibility of CRS/HIPEC in the management of PM from rare ovarian malignancies and report postoperative outcomes on these patients. Methods: A retrospective review of a single center, prospective database (1994-2021) was performed to identify patients with rare ovarian malignancies treated with CRS/HIPEC. Clavien-Dindo 90-day morbidity/mortality and Kaplan-Meier overall (OS) and progression-free survival (PFS) were analyzed. Results: Of 44 patients identified, 28 underwent CRS/HIPEC. Six were aborted due to extensive disease. Histologic subtypes included: clear cell (5/28, 17.9 %), endometrioid (5/28, 17.9 %), granulosa cell (3/28, 10.7 %), low-grade serous (6/28, 21.4 %), mesonephric (1/28, 3.6 %), mucinous (6/28, 21.4 %), and small cell (2/28, 7.1 %) carcinomas. Eight (28.6 %) patients had primary and 20 (71.4 %) had recurrent disease. Median peritoneal cancer index (PCI) was 21 (IQR: 6-29). Complete cytoreduction (<2.5 mm residual disease) was achieved in 27/28 (96.4 %). Grade III/IV complications occurred in 9/28 (32.1 %) with one (3.6 %) mortality. After a median follow-up of 65.8 months, 20 patients were alive. Five-year OS and PFS were 68.5 and 52.6 %, respectively. Conclusions: In patients with PM from rare ovarian malignancies, CRS/HIPEC is feasible and has an acceptable safety profile. Longer follow-up and multicenter trials are needed.

Mucinous neoplasm of the appendix: A case report and review of literature.

BACKGROUND: Appendiceal mucinous neoplasms (AMNs), although not classified as rare, are relatively uncommon tumors most often discovered incidentally during colorectal surgery. Accurate identification of AMNs is difficult due to non-specific symptoms, overlapping tumor markers with other conditions, and the potential for misdiagnosis. This underscores the urgent need for precision in diagnosis to prevent severe complications. CASE SUMMARY: This case report describes the unexpected discovery and treatment of a low-grade AMN (LAMN) in a 74-year-old man undergoing laparoscopic hemicolectomy for transverse colon adenocarcinoma (AC). Preoperatively, non-specific gastrointestinal symptoms and elevated tumor markers masked the presence of AMN. The tumor, presumed to be an AMN peritoneal cyst intraoperatively, was confirmed as LAMN through histopathological examination. The neoplasm exhibited mucin accumulation and a distinct immunohistochemical profile: Positive for Homeobox protein CDX-2, Cytokeratin 20, special AT-rich sequence-binding protein 2, and Mucin 2 but negative for cytokeratin 7 and Paired box gene 8. This profile aids in distinguishing appendiceal and ovarian mucinous tumors. Postoperative recovery was uncomplicated, and the patient initiated adjuvant chemotherapy for the colon AC. CONCLUSION: This case highlights the diagnostic complexity of AMNs, emphasizing the need for vigilant identification to avert potential complications, such as pseudomyxoma peritonei.

Data-Driven Surveillance Protocol for Patients at Risk for Peritoneal Recurrence of Primary Colon Cancer: Surveillance for Peritoneal Carcinomatosis.

Peritoneal carcinomatosis (PC) is rarely discovered early due to low sensitivity of screening imaging and tumor markers, however, earlier identification may improve outcomes. This study assesses risk factors and time to recurrence of PC and implementation of a surveillance system. Patients with stage II-III colon adenocarcinoma undergoing curative colectomy between 2005-2022 were retrospectively reviewed at a single tertiary care institution. Patients were divided into three cohorts: no recurrence (NR), PC, and other types of recurrence (OTR). Baseline characteristics between cohorts were compared with univariate analysis. Overall survival and PC risk were assessed using multivariate analysis with Cox's proportional-hazard modelling. 412 patients were included; 78.4% had NR, 7.8% had PC, and 13.8% had OTR. Patient demographics, comorbidities, tumor side, and histologic features were similar between cohorts. Patients with PC were more likely to have microscopic tumor perforation (25% vs. 8.8% vs. 6.8%, p = 0.002), margin involvement (25% vs. 8.8% vs. 4.6%, p < 0.001), lymphovascular invasion (56.2% vs. 33.3%, vs. 24.5%, p < 0.001), perineural invasion (28.1% vs. 15.8% vs. 11.5%, p = 0.026) compared to OTR or NR. Median time to PC after colectomy was 11 months. Tumor characteristics of stage II-III colon cancer define a high-risk profile for PC. An early surveillance program sensitive for peritoneal disease should be adopted for these patients.

Staging laparoscopy with peritoneal lavage to identify peritoneal metastases and free intraperitoneal cancer cells in the management of locally advanced gastric cancer.

INTRODUCTION: Gastric cancer often presents in advanced stage with a significant risk for peritoneal dissemination. Staging laparoscopy can be used to detect peritoneal carcinomatosis (PC+) and free cancer cells in peritoneal lavage cytology (CY+). The current study aimed to present the outcomes of staging laparoscopy and the prognosis of PC+ and CY+ in a Swedish high-volume center. MATERIALS AND METHODS: A cohort study including all consecutive patients with locally advanced gastric cancer who underwent staging laparoscopy between February 2008 and October 2022. The laparoscopy findings were categorized as PC+, PC-CY+ (positive cytology without peritoneal carcinomatosis) or negative laparoscopy (PC-CY-). The primary endpoint was overall survival (OS) stratified by laparoscopy findings. The secondary endpoint was OS within each laparoscopy finding group stratified by subsequent treatment. RESULTS: Among 168 patients who underwent staging laparoscopy, 78 patients (46%) had PC-CY-, 29 patients (17%) had PC-CY+ and 61 patients (36%) had PC+. Decreased OS was observed for both PC-CY+ patients (aHR 2.14, 95% CI 1.13-4.06) and PC+ patients (aHR 5.36, 95% CI 3.21-8.93), compared to PC-CY-. Patients with PC-CY+ who converted to PC-CY- after chemotherapy and underwent tumor resection seemed to have a better prognosis compared to patients with persisting PC-CY+. CONCLUSIONS: Staging laparoscopy is an important tool in the staging of locally advanced gastric cancer. Tumor resection for patients with PC-CY+ who convert to PC-CY- may lead to improved survival for these patients.

Role of endometrial sampling to differentiate between advanced endometrial versus ovarian malignancy: retrospective cohort study.

OBJECTIVE: Distinguishing between advanced stage endometrial and ovarian cancer at diagnosis can be challenging, especially when patients do not present with abnormal uterine bleeding. Given emerging systemic therapies specific for ovarian versus endometrial cancers, it has become increasingly critical to establish the correct diagnosis at presentation to ensure appropriate treatment. This study evaluates the frequency with which advanced endometrial cancer is mistakenly presumed to be ovarian cancer. METHODS: A retrospective analysis was performed of patients with a final diagnosis of advanced endometrial cancer treated consecutively at a single academic institution between 2013 and 2022. Variables abstracted included abnormal uterine bleeding, endometrial sampling, and timing of endometrial cancer diagnosis. We quantified incorrect diagnoses made after 2018, when frontline targeted treatments differentiating advanced endometrial from advanced ovarian cancer became available. RESULTS: We identified 270 patients with an ultimate diagnosis of stage III or IV endometrial cancer. The most common presenting symptom was abnormal uterine bleeding (219/270, 81%), followed by abdominal or pelvic pain (48/270, 18%) and bloating (27/270, 10%). Forty-eight patients (18%) received neoadjuvant chemotherapy, of whom 11 (23%) had an incorrect diagnosis of ovarian cancer. Since 2018, six patients have received neoadjuvant chemotherapy for presumed ovarian cancer, three of whom received a systemic regimen specific for ovarian cancer when they, in fact, had endometrial cancer. CONCLUSION: In patients with presumed advanced ovarian cancer dispositioned to neoadjuvant chemotherapy, endometrial sampling can identify some cases that are actually primary endometrial cancers. Correct diagnosis guides the use of appropriate antineoplastic therapies, optimizing response and survival outcomes while minimizing toxicity and cost of unindicated therapies.

Preoperative predictors for non-resectability in perihilar cholangiocarcinoma.

INTRODUCTION: Explorative laparotomy without subsequent curative-intent liver resection remains a major clinical problem in the treatment of perihilar cholangiocarcinoma (pCCA). Thus, we aimed to identify preoperative risk factors for non-resectability of pCCA patients. MATERIAL AND METHODS: Patients undergoing surgical exploration between 2010 and 2022 were eligible for the analysis. Separate binary logistic regressions analyses were used to determine risk factors for non-resectability after explorative laparotomy due to technical (tumor extent, vessel infiltration) and oncological (peritoneal carcinomatosis, distant nodal or liver metastases)/liver function reasons. RESULTS: This monocentric cohort comprised 318 patients with 209 (65.7%) being surgically resected and 109 (34.3%) being surgically explored [explorative laparotomy: 87 (27.4%), laparoscopic exploration: 22 (6.9%)]. The median age in the cohort was 69 years (range 60-75) and a majority had significant comorbidities with ASA-Score ≥ 3 (202/318, 63.5%). Statistically significant (p < 0.05) risk factors for non-resectability were age above 70 years (HR = 3.76, p = 0.003), portal vein embolization (PVE, HR = 5.73, p = 0.007), and arterial infiltration > 180° (HR = 8.05 p < 0.001) for technical non-resectability and PVE (HR = 4.67, p = 0.018), arterial infiltration > 180° (HR = 3.24, p = 0.015), and elevated CA 19-9 (HR = 3.2, p = 0.009) for oncological/liver-functional non-resectability. CONCLUSION: Advanced age, PVE, arterial infiltration, and elevated CA19-9 are major risk factors for non-resectability in pCCA. Preoperative assessment of those factors is crucial for better therapeutical pathways. Diagnostic laparoscopy, especially in high-risk situations, should be used to reduce the amount of explorative laparotomies without subsequent liver resection.

Imaging Evaluation of Peritoneal Metastasis: Current and Promising Techniques.

Early diagnosis, accurate assessment, and localization of peritoneal metastasis (PM) are essential for the selection of appropriate treatments and surgical guidance. However, available imaging modalities (computed tomography [CT], conventional magnetic resonance imaging [MRI], and 18fluorodeoxyglucose positron emission tomography [PET]/CT) have limitations. The advent of new imaging techniques and novel molecular imaging agents have revealed molecular processes in the tumor microenvironment as an application for the early diagnosis and assessment of PM as well as real-time guided surgical resection, which has changed clinical management. In contrast to clinical imaging, which is purely qualitative and subjective for interpreting macroscopic structures, radiomics and artificial intelligence (AI) capitalize on high-dimensional numerical data from images that may reflect tumor pathophysiology. A predictive model can be used to predict the occurrence, recurrence, and prognosis of PM, thereby avoiding unnecessary exploratory surgeries. This review summarizes the role and status of different imaging techniques, especially new imaging strategies such as spectral photon-counting CT, fibroblast activation protein inhibitor (FAPI) PET/CT, near-infrared fluorescence imaging, and PET/MRI, for early diagnosis, assessment of surgical indications, and recurrence monitoring in patients with PM. The clinical applications, limitations, and solutions for fluorescence imaging, radiomics, and AI are also discussed.

Experiences of patients with peritoneal carcinomatosis-related complex care needs and their caregivers.

BACKGROUND: Patients with peritoneal carcinomatosis (PC) frequently undergo palliative procedures, yet these patients and their caregivers report being unprepared to manage ostomies, drains, and other complex care needs at home. The purpose of this study was to characterize the unique needs of these patients and their caregivers during care transitions. METHODS: Patients completed measures of health status and advance care planning, caregivers completed measures of preparedness and burden, and all participants completed measures of depression and anxiety. Participants detailed their experiences in individual, semi-structured interviews. We analyzed data using descriptive statistics and conventional content analysis. RESULTS: Sixty-one patients and 39 caregivers completed baseline measures. Twenty-four (39.3%) patients acknowledged their terminal illness and seven (11.5%) had discussed end-of-life care preferences with clinicians. Most (26/39, 66.7%) caregivers provided daily care. Among caregivers who managed symptoms, few were taught how to do so (6/20, 30%). Seven patients (11.5%) and seven caregivers (17.9%) met case criteria for anxiety, while 15 patients (24.6%) and two caregivers (5.1%) met case criteria for depression. Interview participants described a diagnosis of PC as a turning point for which there is no road map and identified the need for health systems change to minimize suffering. CONCLUSION: Patients with PC and their caregivers are highly burdened by symptoms and care needs. Patients' prognostic understanding and advance care planning are suboptimal. Interventions that train patients with PC and their caregivers to perform clinical care tasks, facilitate serious illness conversations, and provide psychosocial support are needed.

A rare presentation of mesenteric cyst as persistent ascites: A case report.

BACKGROUND: Mesenteric cysts have been typically described as cystic lesions of mesentery or omentum occurring either intra-abdominally or in the retroperitoneum. With no typical symptoms, the preoperative diagnosis of mesenteric cyst becomes challenging to establish. PATIENT AND METHODS: In this case report, we describe the case of a 29-year-old female who presented with abdominal distension for seven years associated with intermittent constipation. Following complete history, a meticulous physical examination was performed. Laboratory investigations and radiological imaging techniques were used to facilitate the diagnosis which was confirmed on laparotomy. RESULTS: Physical examination revealed abdominal ascites. Laboratory investigations were unremarkable. Abdominal ultrasound revealed multiloculated massive ascites. A well-defined cystic area 27 × 18cm displacing abdominal viscera was observed on computed tomography (abdomen and pelvis) with contrast medium. Exploratory laparotomy revealed a massive cyst involving almost the entire peritoneal cavity. On histopathology, no signs of malignancy were reported. The post-operative course was excellent, and the patient was discharged following surgery. CONCLUSION: As this lesion is rarely considered preoperatively, and the clinical manifestations can be non-specific, we report this case of mesenteric cyst mimicking ascites in order to inform improved decision making among healthcare professionals regarding the timely diagnosis and appropriate management.

Developing a hyperthermic intraperitoneal chemotherapy (HIPEC) gynecologic oncology program: a Canadian experience.

Hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for epithelial ovarian cancer following cytoreductive surgery. The intraperitoneal spread of the disease makes the peritoneal cavity an ideal target for drug delivery. HIPEC has shown promising results in improving overall survival in epithelial ovarian cancer patients when performed during interval cytoreductive surgery. Recent studies have provided level 1 evidence supporting increased overall survival in stage III ovarian cancer patients treated with HIPEC during interval cytoreduction. Meta-analyses have further confirmed the survival improvement in women receiving HIPEC. Despite its inclusion in guidelines, many centers have been hesitant to implement HIPEC programs due to perceived obstacles, such as increased morbidity, cost, and resource requirements. Studies have shown that morbidity rates are acceptable in selected patients, and the addition of HIPEC to cytoreductive surgery is cost effective. Therefore, the main barrier to implementing HIPEC programs is related to resource requirements and logistics, but with proper preparation, these challenges can be overcome. Establishing a successful HIPEC program requires institutional support, a knowledgeable and dedicated team, adequate resources and equipment, and proper training and audit. This review aims to provide evidence based information to guide the development of successful HIPEC programs, including preoperative, anesthetic, and surgical considerations. It also reviews the different equipment and protocols for the perfusion and common postoperative events.

A global analysis of nutrition support practices in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancy.

BACKGROUND: Perioperative nutritional care has been identified as an important factor in the management of patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Nevertheless, there is no published consensus on best practice for nutritional management specific to this patient group. The purpose of this study was to identify the current nutrition care practices among international centres performing CRS and HIPEC for patients with peritoneal malignancy. METHODS: An online survey was developed and sent to experienced CRS and HIPEC centres. The survey questions covered clinician and institution demographics, formal nutrition care pathways, pre-operative nutrition care, post-operative nutrition support and post-discharge nutritional follow-up. RESULTS: Eighty-two centres were contacted, and 42 responses were received. Respondents were from 20 different countries and were mostly dietitians (71%). Nutrition assessments were frequently completed (52% pre-operatively and 86% post-operatively) and most centres used a validated nutrition screening or assessment tool (79%). Perioperative nutrition support with respect to the use of enteral nutrition, parenteral nutrition and enhanced recovery after surgery varied widely between centres. The use of routine parenteral and enteral nutrition was significantly higher in Europe compared with other locations (p = 0.028). CONCLUSIONS: Nutrition care is pivotal and has been positively integrated into the complex management of patients undergoing CRS and HIPEC globally, however variation in practice is evident. The findings highlight a unique opportunity to collaboratively investigate the role nutrition plays in determining outcomes and to identify the most appropriate nutrition support methods to achieve improved clinical outcomes for these high-risk patients.

Is the measurement of sarcopenia associated with oncological disease in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy?

BACKGROUND: Peritoneal malignancies are challenging cancers to manage. While cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC), may offer a cure, it is a radical procedure associated with significant morbidity. Pre-emptive identification of deconditioned patients for optimization may mitigate surgical risk. However, the difficulty lies in identifying a cost-effective predictive tool. Recently, there has been interest in sarcopenia, which may occur due to malignancy. The purpose of this study was to assess the utility of sarcopenia at predicting post-operative outcomes. METHODS: A quaternary-centre retrospective study of CRS and HIPEC patients (2017-2020), were conducted to determine the association between pre-operative sarcopenia on oncological (peritoneal carcinomatosis index (PCI)) and surgical outcomes (complications). Sarcopenia from lumbar CT-images were measured using Slice-o-matic™. Statistical differences were analysed using Mann-Whitney U and Chi-squared test. RESULTS: Cohort analysis (n = 94) found 40% had sarcopenia, majority were female (53.2%), and average age of 55 years. The major pathologies was colorectal cancer (n = 39, 41.5%), appendix adenocarcinoma (n = 21, 22.3%), and pseudomyxoma peritonei (PMP) (n = 19, 20.2%). Sarcopenia was associated with decreased weight, 72.7 versus 82.2 kg (P = 0.014) and shorter survival, 1.4 versus 2.1 years (95% CI, 1.09-3.05, P = 0.032). Median PCI (excluding PMP) was 11 (6-18) and median PCI (only PMP) was 25 (11-32). Post-operatively, sarcopenia patients experienced more complications (72.5% vs. 64.8%, P = 0.001). CONCLUSION: Pre-emptive identification of sarcopenia may be a useful prognostic indicator and predictor of post-operative outcomes in CRS and HIPEC. For oncological patients, sarcopenia may be an indicator of patients requiring targeted pre-operative rehabilitation, or advanced disease requiring further treatment.

Design and Implementation of a Learner-Centered Self-Paced Peritoneal Oncology Education Program.

BACKGROUND: Current educational programs for peritoneal surface malignancies (PSM) are unstructured and often target advanced learners. The authors describe the design and implementation of a structured, self-paced course at a high-volume PSM center. METHODS: In 2020, a learner-centered course was designed using the Canvas educational platform in consultation with the Center for Teaching at the University of Chicago. The course consisted of disease-site-specific modules, perioperative care pathways, in-built voluntary quizzes, and multimedia supplements for advanced learners. Trainees were provided access during the PSM service rotation, and engagement was compared across training levels by measuring the time spent online. RESULTS: Course design and management required 71 h between 2020 and 2022, with the majority of time spent in the design phase. During 3 years, 62 personnel (21 [34%] medical students, 28 [45%] residents, 8 [13%] staff, and 5 [8%] fellows) were assigned the course. The overall engagement rate was 83.9% (86% of medical students, 75% of residents, 100% of staff and fellows), and the median time spent online was 12.4 min/week (interquartile range [IQR], 2.1-53.0 min/week). Fourth-year medical students and clinical fellows spent more time online than other learners (73 min/week [IQR, 24.5-100 min/week] vs 13.3 min/week [IQR, 7.3-26.5 min/week]) (p = 0.001). CONCLUSIONS: The design and implementation of a PSM-specific course was feasible and sustainable using an online learning platform. Higher engagement was noted among invested learners. Non-technical factors for reduced engagement need to be ascertained further to improve the next iteration of this course.

A Systematic Review of Surgical Management Strategies in the Treatment of Peritoneal Carcinomatosis of Neuroendocrine Origin.

Cytoreductive surgery (CRS) represents the cornerstone of surgical management for peritoneal carcinomatosis (PC) and involves peritonectomy procedures aimed at complete peritoneal tumour resection. Frequently, CRS is combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The combination of CRS + HIPEC is now considered the standard of care in patients with colorectal and ovarian PC. However, the role of this multi-modality treatment approach in patients with PC of neuroendocrine tumour origin (NET-PC) is less well understood. This systematic review provides a summary of available evidence on management strategies for patients with NET-PC. A systematic literature search was performed using Ovid Medline, EMBASE and Cochrane Library databases to identify studies reporting outcomes for patients with NET-PC undergoing surgical treatment. Eligible studies were assessed for methodological quality and design and evaluated for a method of surgical treatment, method of HIPEC delivery, oncological outcomes, and treatment-related morbidity. Eight studies, including a total of 1240 patients with NET-PC, met predefined inclusion criteria and have been included in this review. In three of the included studies, CRS alone was performed for patients with NET-PC, while five studies reported outcomes with combined treatment using CRS plus HIPEC. All studies were performed at tertiary peritoneal malignancy centres. Only one study directly compared outcomes in patients with NET-PC undergoing CRS plus HIPEC compared with CRS in isolation, with no significant difference in overall survival reported. Carefully selected patients with NET-PC may benefit from aggressive surgical treatment in the form of CRS +/- HIPEC. These procedures are best undertaken at centres with expertise in the management of both neuroendocrine tumours and peritoneal malignancy, as both are conditions that require tertiary-level care. The additional benefit of the HIPEC component in this group of patients remains unclear and warrants further investigation in clinical trials. Overall, the quality of data on this subject is restricted by the low number of studies and the variability in treatment methods employed. A multi-national data registry for patients with NET-PC may offer the opportunity to better define treatment algorithms. Translational research efforts in parallel should focus on developing a better biological understanding of NET-PC, with a view to identifying more effective intraperitoneal cytocidal agents.

Achieving Intraperitoneal Disease Control Using Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Two Cases of Metastatic Breast Cancer.

Peritoneal metastases from breast cancer (PMBC) tend to occur late in the disease course and are challenging to manage. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) provide peritoneal disease control in other malignancies and may achieve similar results in PMBC. We assessed intraperitoneal disease control and outcomes in two PMBC patients after CRS/HIPEC. Patient 1, diagnosed at age 64, had hormone-positive/human epidermal growth factor receptor 2 (HER2)-negative lobular carcinoma treated with mastectomy. Prior to salvage CRS/HIPEC at age 72, five cycles of intraperitoneal chemotherapy via an indwelling catheter failed to control recurrent peritoneal disease. Patient 2, diagnosed at age 52, had hormone-positive/HER2-negative ductal-lobular carcinoma and received lumpectomy, hormonal therapy, and target therapy. Prior to salvage CRS/HIPEC at age 59, she had recurring ascites that was resistant to hormonal therapy and required multiple paracenteses. Both underwent complete CRS/HIPEC with melphalan. The only major complication was anemia, which required a transfusion in both patients. They were discharged on postoperative days 8 and 13, respectively. Patient 1 had peritoneal recurrence 26 months post-CRS/HIPEC and died of disease at 49 months. Patient 2 never had peritoneal recurrence and died of extraperitoneal progression at 38 months. In conclusion, CRS/HIPEC is safe and can provide intraperitoneal disease and symptom control in select patients with PMBC. Thus, CRS/HIPEC can be offered to these rare patients who have failed standard treatments.

[Peritoneal carcinomatosis secondary to CUP syndrome : Diagnosis and indications for multimodal treatment]. / Peritonealkarzinose beim CUP­Syndrom : Diagnostik und Indikationsstellung für die multimodale Therapie.

CLINICAL PROBLEM: Peritoneal carcinomatosis secondary to cancer of unknown primary (CUP) syndrome is a rare entity for which there are no uniform treatment recommendations or guidelines. The median survival time is 3 months. DIAGNOSIS: Computed tomography (CT), magnetic resonance imaging (MRI), and 18F­FDG positron emission tomography (PET)/CT are valid imaging modalities for the detection of peritoneal carcinomatosis. The sensitivity of all techniques is highest for large, macronodular peritoneal carcinomatosis manifestations. A limitation of all imaging techniques is limited and small-nodular peritoneal carcinomatosis. Also, peritoneal metastasis in the small bowel mesentery or diaphragmatic domes can only be visualized with low sensitivity. Therefore, exploratory laparoscopy should be considered as the next diagnostic step. In half of these cases an unnecessary laparotomy can be avoided, because the laparoscopy revealed diffuse, small-nodule involvement of the small bowel wall and thus an irresectable situation. TREATMENT: In selected patients, performing complete cytoreduction followed by hyperthermic intra-abdominal chemotherapy (HIPEC) is a good therapeutic option. Therefore, the identification of the extent of peritoneal tumor manifestation as accurately as possible is important for the definition of the increasingly complex oncological therapy strategies.

Peripheral PD-1 and Tim-3 percentages are associated with primary sites and pathological types of peritoneal neoplasms.

PURPOSE: Programmed death-1 (PD-1) and T cell immunoglobulin and mucin-domain-containing molecule 3(Tim-3) may be used as the biomarkers for the therapy in patients with peritoneal neoplasms. In the current study, the differential percentages of peripheral PD-1 and Tim-3 are explored to investigate whether to associate with primary sites and pathological types of patients with peritoneal neoplasms or not. We also investigated the frequencies of PD-1 and Tim-3 on circulating Lymphocytes, CD3 + T cells, CD3 + CD4 + T cells and CD3 + CD8 + T cells if would correlate with the progression-free survival of peritoneal neoplasms patients. METHODS: 115 patients with peritoneal neoplasms were recruited, subjected to multicolor flow cytometric analyses of the percentages of PD-1 and Tim-3 receptors of circulating Lymphocytes, CD3 + T cells, CD3 + CD4 + T cells and CD3 + CD8 + T cells. The peritoneal neoplasms patients were divided into primary group and secondary group depending on whether the tumor had primary focus and limited to peritoneal tumor or not. Then all the patients were regrouped by the pathological types of neoplasms (adenocarcinoma, mesothelioma, and pseudomyxoma). The secondary peritoneal neoplasms group was divided into the different primary site groups (colon, gastric, gynecology). This study also enrolled 38 cases of normal volunteers. The above markers were explored by flow cytometer, to find the differential levels in peritoneal neoplasms patients compared with normal group in peripheral blood. RESULTS: Higher levels of CD4 + T lymphocytes, CD8 + T lymphocytes, CD45 + PD-1 + lymphocytes, CD3 + PD-1 + T cells, CD3 + CD4 + PD-1 + T cells, CD3 + CD8 + PD-1 + T cells and CD45 + Tim-3 + lymphocytes were found in peritoneal neoplasms group than normal control (the p value was respectively 0.004, 0.047, 0.046, 0.044, 0.014, 0.038 and 0.017). Compared with primary peritoneal neoplasms group, the percentages of CD45 + PD-1 + lymphocytes, CD3 + PD-1 + T cells, and CD3 + CD4 + PD-1 + T cells were increased in the secondary peritoneal neoplasms group (the p value was respectively 0.010, 0.044, and 0.040), while PD-1 did not correlate with the primary sites in secondary group (P > 0.05). Tim-3 had no statistical differences in primary peritoneal neoplasms group compared with secondary group (p > 0.05), but CD45 + Tim-3+% lymphocytes, CD3 + Tim-3+%T cells, and CD3 + CD4 + Tim-3 + T cells were associated with different secondary sites of peritoneal neoplasms (p < 0.05). In the different pathological type groups, the percentages of CD45 + PD-1 + lymphocytes, CD3 + PD-1 + T cells presented the higher levels in adenocarcinoma group compared with mesothelioma group (p = 0.048, p = 0.045). The frequencies of CD45 + PD-1 + lymphocytes and CD3 + PD-1 + T cells in peripheral blood were associated with progression-free survival (PFS). CONCLUSIONS: Our work uncovers peripheral PD-1 and Tim-3 percentages are associated with primary sites and pathological types of peritoneal neoplasms. Those findings might provide important assessment to predict peritoneal neoplasms patients' immunotherapy responses.

The Impact of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) versus Conventional Surgery on Patient-Reported Outcomes: A Comparative Cohort Study between the CAIRO6 Trial and the PROCORE Study.

Purpose-To compare patient-reported outcomes (PROs) of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for colorectal peritoneal metastases to PROs of colorectal cancer (CRC) patients undergoing conventional surgery. Methods-Data were extracted from the CAIRO6 trial (CRS-HIPEC group) and the PROCORE study (conventional surgery group). Nine predefined PROs (derived from the EORTC QLQ-C30 questionnaire) were compared at baseline, in the early postoperative period and one year postoperatively, with correction for treatment with systemic therapy using linear mixed modeling. Results-In total, 331 patients were included: 71 in the CRS-HIPEC group and 260 in the conventional surgery group. All predefined PROs (fatigue, diarrhea, C30 summary score, Global Health Status, physical, role, emotional, cognitive, and social functioning) did not differ significantly between the groups at all three timepoints, and differential effects over time for all PROs did not differ significantly between the groups. Significant worsening of fatigue, C30 summary score, physical and role functioning (both groups), and cognitive and social functioning (conventional surgery group only) was present in the early postoperative period. All scores returned to baseline at one year postoperatively, except for physical and cognitive functioning in the conventional surgery group. Emotional functioning improved postoperatively in both groups compared to baseline. Conclusion-Despite a more extensive procedure with greater risk of morbidity, CRS-HIPEC in patients with colorectal peritoneal metastases did not have a greater negative impact on PROs than conventional surgery in patients with CRC. Further, systemic therapy did not affect these PROs. These findings may facilitate future patient counseling and shared decision making in clinical practice.

Peritoneal metastases from primary appendiceal and colorectal carcinomas demonstrate distinct molecular identities on comprehensive tumor analysis.

BACKGROUND AND OBJECTIVES: Published data comparing peritoneal metastases from appendiceal cancers (pAC) and colorectal cancers (pCRC) remain sparse. We compared pAC and pCRC using comprehensive tumor profiling (CTP). METHODS: CTP was performed, including next-generation sequencing and analysis of copy number variation (CNV), microsatellite instability (MSI) and tumor mutational burden (TMB). RESULTS: One hundred thirty-six pAC and 348 pCRC samples underwent CTP. The cohorts' age and gender were similar. pCRC demonstrated increased pathogenic variants (PATHs) in APC (48% vs. 3%, p < 0.01), ARID1A (12% vs. 2%, p < 0.01), BRAF (12% vs. 2%, p < 0.01), FBXW7 (7% vs. 2%, p < 0.01), KRAS (52% vs. 41%, p < 0.05), PIK3CA (15% vs. 2%, p < 0.01), and TP53 (53% vs. 23%, p < 0.01), and decreased PATHs in GNAS (8% vs. 31%, p < 0.01). There was no difference in CNV, fusion rate, or MSI. Median TMB was higher in pCRC (5.8 vs. 5.0 mutations per megabase, p = 0.0007). Rates of TMB-high tumors were similar (pAC 2.1% vs. pCRC 9.0%, p = 0.1957). pCRC had significantly more TMB-high tumors at lower thresholds. CONCLUSIONS: Despite a reduced overall TMB, pAC demonstrated mutations distinct from those seen in pCRC. These may serve as discrete biomarkers for future study.