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PURPOSE The 2-year Russian oncology residency focuses on diagnosis and treatment of malignancies but lacks evidence-based medicine (EBM) and patient communication skills (PCS) training. To overcome these educational disparities, the 5-year national program, the Higher School of Oncology (HSO), involving Russian expatriate physicians trained in the United States was established. METHODS A retrospective study was conducted. Highly motivated oncology residents were enrolled in the program through the three-step selection process. US-trained Russian expatriate physicians acted as mentors. EBM skills were taught through weekly online journal clubs and clinical case presentations. PCS training included live seminars and simulations after journal clubs. EBM knowledge was assessed using Fresno test among newly enrolled and postgraduate year (PGY) 2-5 HSO residents. PCS were evaluated via simulation exam including two clinical scenarios (maximum score 100 each) among 17 PGY2 HSO residents and seven non-HSO trainees. RESULTS Overall, 54 residents were enrolled over 5 years (8-13 annually); four were released from the program. The mean age was 24 ± 1 years, and 56% were females. Median scores of Fresno test were significantly higher among PGY 2-4 HSO residents compared with newly enrolled participants: 111 (IQR, 71-128) versus 68 (IQR, 42-84), P = .042; moreover, performance correlated with year of program participation (rs = 0.5; P < .0001). PCS assessment score was significantly higher among HSO residents than non-HSO trainees: 71 (IQR, 58-84) versus 15 (IQR, 10-30) for scenario number 1 ( P < .0001) and 78 (IQR, 71-85) versus 22 (IQR, 4-58) for scenario number 2 ( P = .005), respectively. CONCLUSION The involvement of Western-trained expatriates in remote education improves EBM and PCS among oncology trainees from their home country. This strategy can be useful in overcoming global medical education disparities in other specialties and in countries facing similar challenges.

Diaphragmatic resection (DR) is often required during cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) to achieve complete cytoreduction (CC). While CC provides the best survival, requiring a DR may indicate unfavorable tumor biology. We assessed how DR during CRS/HIPEC affects outcomes. A retrospective cohort study was conducted using a prospective single-center database from October 1994–May 2020. Peritoneal surface malignancy patients who underwent CRS/HIPEC with CC-0/1/2 were assigned to DR and NoDR groups. Survival was measured using the Kaplan–Meier method. Subgroup analysis was performed for patients with peritoneal cancer index (PCI) ≥ 20 to eliminate confounding of more extensive disease in DR. Of 824 CRS/HIPECs, 774 were included: 134 DR and 640 NoDR. PCI was significantly higher in DR: 29 versus 21, p < 0.001. CC-0/1 rate was 89% in DR and 95% in NoDR (p = 0.003). Neither 100-day morbidity nor mortality differed between the groups (p = 0.355 and p = 1.000). Median follow-up was 64 months. Median overall survival (OS) was significantly lower in DR (32 vs. 96 months, p < 0.001). Subgroup analysis by tumor type in patients with PCI ≥ 20 showed significantly shorter OS in DR than NoDR in appendiceal (40 vs. 196 months, p < 0.001) and colorectal (14 vs. 23 months, p = 0.003), but not in ovarian tumors (32 vs. 42 months, p = 0.893), whereas median PCI did not differ among subgroups. DR during CRS/HIPEC does not increase morbidity and mortality. It is associated with worse survival in appendiceal and colorectal tumors, even after adjusting for tumor burden but does not appear to impact ovarian cancer survival.

Introduction Genital necrosis (GN) is a rare complication of cytoreductive surgery with hyperthermic intraoperative chemotherapy (CRS/HIPEC) which can be confused with necrotizing fasciitis. We present an analysis of GN after CRS/HIPEC to define its natural history. Methods We identified patients with GN after CRS/HIPEC at two peritoneal surface malignancy institutions. Patient demographic, surgical, and postoperative data were extracted from prospective databases. Results Of 1597 CRS/HIPECs performed, 13 patients (0.8%) had GN. The median age was 57 years (IQR: 49–64) and 77% (n = 10) were male. Mitomycin-C was the perfusion agent in all cases of GN (100%). The median time to GN onset after CRS/HIPEC was 64 days (IQR: 60–108) and 2 (15%) patients were receiving systemic chemotherapy at the time of GN onset. Symptoms included severe pain (100%), edema (100%), labial or scrotal skin ulceration (92%), signs of infection (39%), and fever (15%). Seven (54%) patients had thrombocytosis >400 ∗109/L, whereas coagulation tests were within normal reference range in 100% cases. All patients initially underwent conservative treatment, with antibiotic therapy administered in 62% (n = 8). Surgical debridement was performed in 9 (70%) cases with median time after GN onset of 57 (IQR: 8–180). Conclusion GN is a debilitating complication after CRS/HIPEC with delayed onset and a protracted clinical course. Optimal treatment results could be achieved with initial conservative management until complete lesion demarcation followed by surgical debridement. The pathophysiology of GN is unclear, and we call for other researchers attention to better understand the complication and prevention.

Women 65 years of age or older with epithelial ovarian cancer (EOC) are thought to have a worse prognosis than younger patients. However, no consensus exists concerning the best treatment for ovarian cancer in this age group. This report presents outcomes for patients treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). A prospective database of EOC patients treated with CRS/HIPEC (1998–2019) was analyzed. Perioperative variables were compared by treatment including upfront CRS/HIPEC, neoadjuvant chemotherapy plus CRS/HIPEC (NACT + CRS/HIPEC), and salvage CRS/HIPEC, and by age at surgery (

Background. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) after neoadjuvant chemotherapy (NACT) showed promise as initial treatment for stage IIIC (SIII) epithelial ovarian cancer (EOC); however, stage IV (SIV) outcomes are rarely reported. We assessed our experience and outcomes treating newly diagnosed SIV EOC with NACT plus CRS/HIPEC compared to SIII patients. Methods. Advanced EOC from 2015–2018 managed with NACT (carboplatin/paclitaxel) due to unresectable disease or poor performance status followed by interval CRS/HIPEC were reviewed. Perioperative factors were assessed. Overall survival (OS) and progression-free survival (PFS) were analyzed by stage. Results. Twenty-seven FIGO stage IIIC (n = 12) and IV (n = 15) patients were reviewed. Median NACT cycles were 3 and 4, respectively. Post-NACT omental caking, ascites, and pleural effusions decreased/resolved in 91%, 91%, and 100% of SIII and 85%, 92%, and 71% of SIV. SIII/SIV median PCI was 21 and 20 obtaining 92% and 100% complete cytoreduction (≤0.25 cm), respectively. Median organ resections were 6 and 7, respectively. Grade III/IV surgical complications were 0% SIII and 23% SIV, without hospital mortality. Median time to adjuvant chemotherapy was 53 and 74 days, respectively ( p = 0.007 ). SIII OS at 1 and 2 years was 100% and 83% and 87% and 76% in SIV ( p = 0.269 ). SIII 1-year PFS was 54%; median PFS: 12 months. SIV 1- and 2- year PFS was 47% and 23%; median PFS: 12 months ( p = 0.944 ). Conclusion. Outcomes in select initially diagnosed and unresectable SIV EOC are similar to SIII after NACT plus CRS/HIPEC. SIV EOC may benefit from CRS/HIPEC, and further studies should explore this treatment approach.

Comparing genetic mutations of first‐degree relatives with appendiceal pseudomyxoma peritonei may explain clinical outcomes and disease pathogenesis. Molecular profiling of mucinous tumors may identify improved treatments to traditional chemotherapy.

Low-grade appendiceal mucinous neoplasms (LAMN) are tumors that frequently present with peritoneal spread of either acellular mucin (AM) or cellular mucin (CM). We aim to determine how mucin types and distribution affect survival. PATIENTS AND METHODS: A retrospective cohort study was conducted using a prospective database. Newly diagnosed LAMN patients with AM versus CM treated with cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) were compared. Postoperative pathology reports were reviewed to assess each involved abdominal zone. Survival was analyzed using the Kaplan-Meier method.Of 121 identified patients, 50 (41%) had peritoneal lesions with AM and 71 (59%) with CM. Peritoneal cancer index was lower in AM versus CM (mean: 19 ± 13 vs 28 ± 10, p = 0.004), but complete cytoreduction (CC) rates were similar (98% vs 96%, p = 0.642). The 5-year progression-free survival (PFS) was higher in AM versus CM (96% vs 69.8%, p = 0.002). CM patients had zones with both types of lesions: with and without cells. The CM subgroup analysis showed significant differences in 5-year progression-free survival (PFS) among patients with 1-3, 4-7, and 8-10 zones with cells (95.2%, 68.4%, and 35.7%, respectively, p 0.001), but PFS was not affected by the number of zones with any lesion type. There was no difference in overall survival (OS) between groups.Despite comparable CC rates after CRS/HIPEC, CM patients have shorter PFS than AM patients. In CM patients, more zones with cells, but not the total number of involved zones, negatively impact PFS. Mucin type does not impact OS. It is important to assess and report mucin cellularity in LAMN specimens.

Background Patient navigation is the logistical and emotional support necessary to achieve diagnostic and treatment compliance. It can improve time to diagnosis, initiation of treatment, and patient satisfaction, as well as reduce the cost of treatment. Colombia has a well-defined Cancer Control Plan, but its implementation is lacking. Aim To implement the first patient navigation initiative in Colombia, as part of a pilot program for the early detection of breast cancer. Methods The process involved assessing and addressing the barriers faced by women to access breast health care by providing training for health personnel, strengthening primary health care providers, and coordinating diverse level institutions for the provision of services. This led to the design and implementation of a navigation strategy focused on the needs of patients in Cali, Colombia and the involvement of the local health system to provide such services. Results Time to diagnosis was significantly reduced; research advanced by the Colombian National Institute of Cancerology shows that the average time between the first medical consultation and diagnosis was 91 days (CI 95%: 82-97 days), while this study carried out the same process in an average of 30 days, but patients still had issues with continuity of treatment due to financial strain between healthcare providers and insurers. Navigation, however, manages to overcome many of these problems by assisting women in the clinical and administrative care processes and seeking well-being for the beneficiaries. In addition, patient navigation helped identify critical failures in care, such as fragmentation of care and excessive bureaucracy. The navigation process improved data collection and established agreements to simplify and make the delivery of care more efficient. In addition, it generated partnerships between service providers and insurers. Conclusion While several barriers and poor understanding of the navigation process still exist, a navigation program can help implement a Cancer Control Plan.

Despite meticulous preoperative diagnostics, aborted hyperthermic intraperitoneal chemotherapy (AHIPEC) is a common, unsuccessful outcome of curative cytoreductive surgery (CRS)/HIPEC. The aim of this study was to evaluate the association between AHIPEC and preoperative risk factors of patients with mucinous appendiceal cancer (AC). A single-institute, case–control study was conducted using a prospective database. Potentially resectable patients with peritoneal carcinomatosis of mucinous AC origin with AHIPEC between October 1994 and February 2019 were identified. Preoperative risk factors were reviewed. Analysis was conducted by tumor grade: low-grade, high-grade, and signet ring cell carcinoma (high-S). All available tumor-type-matched successful CRS/HIPEC controls were obtained from the same database. Univariable and multivariable analyses were performed. Overall, 21, 44, and 15 AHIPEC cases and 153, 133, and 53 tumor-matched controls were identified for low-grade, high-grade, and high-S populations, respectively. Multivariable analysis revealed preoperative cancer antigen (CA) 19-9 > 1 upper limit of normal (ULN) [odds ratio (OR) 6.32; p = 0.014], CA125 > 2 ULN (OR 7.02; p = 0.039), C-reactive protein (CRP) > 2.5 mg/L (OR 13.7; p = 0.001), and previous HIPEC (OR 7.5; p = 0.031) were significantly associated with AHIPEC in the low-grade population. Preoperative CRP > 2.5 mg/L (OR 7.77; p

Soft-tissue myoepithelioma (STM) is an extremely rare benign tumor with predominant occurrence in head, neck, pelvic girdle and limbs. These tumors lack specific clinical and morphological features and can easily be confused with more common neoplasms. It may lead to incorrect diagnosis and management. Here, we present a clinical case of a young man with retroperitoneal STM which simulated a pancreatic tumor and required a distal pancreatectomy. Performed literature review highlights current data about clinical, morphologic, immunohistochemical and genetic evaluation, treatment and prognosis of STM. J Med Cases. 2020;11(1):16-21 doi: https://doi.org/10.14740/jmc3407

Neuroendocrine neoplasms (NENs) represent a diverse group of tumors arising from neuroendocrine cells. Current World Health Organization (WHO) classification is based on tumor differentiation and grade defined by mitotic rate and/or Ki-67 index to determine prognosis and treatment options. However, some NENs do not meet WHO pathology criteria due to morphologic heterogeneity and this leads to management challenges. WHO defines poorly differentiated NENs of the gastrointestinal tract as having morphologically large or small cell features with marked elevation of Ki-67. We present a unique clinical case that does not fit either growth pattern and also has heterogeneity with a well-differentiated component. This case report and literature review highlights the current limitations of the WHO classification of small bowel NENs and the subsequent challenges in management decisions for the patients. J Med Cases. 2020;11(1):6-11 doi: https://doi.org/10.14740/jmc3401

Pseudomyxoma peritonei (PMP) is a subtype of peritoneal carcinomatosis that is traditionally treated by cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC). A growing body of evidence suggests that microbes are associated with various tumor types and have been found in organs and cavities that were once considered sterile. Prior and ongoing research from our consortium of PMP researchers strongly suggests that bacteria are associated with PMP tumors. While the significance of this association is unclear, in our opinion, further research is warranted to understand whether these bacteria contribute to the development, maintenance and/or progression of PMP. Elucidation of a possible causal role for bacteria in PMP could suggest a benefit for supplementation of antibiotics to current treatment protocols.

IntroductionDespite optimal patient selection and surgical effort, recurrence is seen in over 70% of patients undergoing cytoreductive surgery (CRS) for peritoneal metastases (PM). Apart from the Peritoneal Cancer Index (PCI), completeness of cytoreduction and tumour grade, there are other factors like disease distribution in the peritoneal cavity, pathological response to systemic chemotherapy (SC), lymph node metastases and morphology of PM which may have prognostic value. One reason for the underutilisation of these factors is that they are known only after surgery. Identifying clinical predictors, specifically radiological predictors, could lead to better utilisation of these factors in clinical decision making and the extent of peritoneal resection performed for different tumours. This study aims to study these factors, their impact on survival and identify clinical and radiological predictors.Methods and analysisThere is no therapeutic intervention in the study. All patients with biopsy-proven PM from colorectal, appendiceal, gastric and ovarian cancer and peritoneal mesothelioma undergoing CRS will be included. The demographic, clinical, radiological, surgical and pathological details will be collected according to a prespecified format that includes details regarding distribution of disease, morphology of PM, regional node involvement and pathological response to SC. In addition to the absolute value of PCI, the structures bearing the largest tumour nodules and a description of the morphology in each region will be recorded. A correlation between the surgical, radiological and pathological findings will be performed and the impact of these potential prognostic factors on progression-free and overall survival determined. The practices pertaining to radiological and pathological reporting at different centres will be studied.Ethics and disseminationThe study protocol has been approved by the Zydus Hospital ethics committee (27 July, 2020) and Lyon-Sud ethics committee (A15-128).Trial registration numberCTRI/2020/09/027709; Pre-results.

IntroductionDespite optimal patient selection and surgical effort, recurrence is seen in over 70% of patients undergoing cytoreductive surgery(CRS) for peritoneal metastases (PM). Apart from the peritoneal cancer index(PCI), completeness of cytoreduction and tumor grade, there are other factors like disease distribution in the peritoneal cavity, pathological response to systemic chemotherapy(SC), lymph node metastases and morphology of PM which may have prognostic value. One reason for the underutilization of these factors is that they are known only after surgery. Identifying clinical predictors, specifically radiological predictors, could lead to better utilization of these factors in clinical decision making and the extent of peritoneal resection performed for different tumors. This study aims to study these factors, their impact on survival and identify clinical and radiological predictors. Methods and analysisThere is no therapeutic intervention in the study. All patients with biopsy proven PM from colorectal, appendiceal, gastric and ovarian cancer and peritoneal mesothelioma undergoing CRS will be included. The demographic, clinical, radiological, surgical and pathological details will be collected according to a pre-specified format that includes details regarding distribution of disease, morphology of PM, regional node involvement and pathological response to SC. In addition to the absolute value of PCI, the structures bearing the largest tumor nodules and a description of the morphology in each region will be recorded. A correlation between the surgical, radiological and pathological findings will be performed and the impact of these potential prognostic factors on progression-free and overall survival determined. The practices pertaining to radiological and pathological reporting at different centers will be studied. Ethics and disseminationThe study protocol has been approved by the Zydus Hospital ethics committee (27th July, 2020) and Lyon-sud ethics committee (A15-128). It is registered with the clinical trials registry of India (CTRI/2020/09/027709).The results will be published in peer-reviewed scientific journals.Strength and limitationsA prospective correlation between the radiological, surgical and pathological findings in patients undergoing CRS will be performed which has not been done before.Being prospective in nature it will also enable us to evaluate the impact of the current treatment practices on the clinical end-pointsThere is fixed protocol for radiological and pathological evaluation for which there are no specific guidelinesThe data collection format will capture all the relevant data but this may affect compliance.Despite the large sample size planned for each primary site, the heterogeneity of treatment protocols may be a limiting factor while evaluating the impact on survival.

We present the first case of isolated peritoneal carcinomatosis (PC) from prostate cancer carrying a previously unreported pathogenic BRCA2 mutation without other organ involvement. CT showed PC with no extra-peritoneal metastases. Treatment included neoadjuvant chemotherapy, cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), and adjuvant chemotherapy. Patient is disease-free after 30-months. Germline genetic testing showed BRCA2 c.1813dupA (p.I605Nfs*11) mutation, reported in breast and ovarian cancers. Tumor genomic testing also revealed TMPRSS2, TBX3, and TP53 mutations. Given the comparable presentation and BRCA-mutation profile to ovarian cancer, BRCA2 mutations may contribute to disease phenotypes. CRS/HIPEC may provide long-term outcomes for this unique metastatic pattern.

The authors have requested that this preprint be removed from Research Square.

Key Clinical Message Peritoneal sarcomatosis from uterine sarcoma is a rare disease with no effective treatment and poor prognosis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has successful results in peritoneal carcinomatosis from gastrointestinal/gynecological origins. We show that CRS/HIPEC is safe, feasible, and may benefit selected patients with peritoneal sarcomatosis from uterine sarcoma.

MD Anderson Cancer Center developed a computed tomography (CT)-based preoperative assessment tool simplified preoperative assessment for appendix tumor (SPAAT) for predicting incomplete cytoreduction (IC) in low-grade mucinous adenocarcinoma (LGMA) of the appendix, based on preoperative CT scans. This study independently evaluates the tool’s performance. Seventy-six preoperative CT scans of LGMA patients were evaluated by two surgeons unfamiliar with the patients’ medical history. Scores were assigned based on SPAAT criteria, with a SPAAT ≥3 predictive of IC. Binary regression analyses and area under the receiver operating characteristic (AUROC) curve analyses were performed. Patients with splenic resection were excluded due to the structure of the SPAAT assessment tool. Seventy-six LGMA patients underwent attempted cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Of 68 patients, 58 had complete cytoreduction and 10 had IC; 8 patients were ineligible due to prior splenectomy. The mean SPAAT score was 0.8, with six patients having SPAAT scores ≥3. SPAAT scores ≥3 were predictive of IC, with a hazard ratio (HR) of 19 (95% confidence interval 2.8–124.1) (p = 0.002). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were 40, 97, 50, and 90%, respectively. A SPAAT score ≥3 was not associated with worse survival prognosis. Median follow-up was 2.4 years and AUROC curve was 71%. SPAAT components with respective HR and p-values were foreshortening of the bowel mesentery (29.5; p = 0.004), and scalloping of the pancreas (9; p = 0.008), spleen (4.3; p = 0.04), portal vein (3.1; p = 0.4), and liver (2.1; p = 0.3). A SPAAT score ≥3 predicted IC based on a binary regression model. The clinical value of this score is controversial due to low sensitivity and PPV.

Survival in peritoneal dissemination from appendiceal cancer after complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) varies within each histopathologic subtype. Analyzing patients with unique responses may uncover the mechanisms behind their extreme outcomes. We proposed a method to identify retrospectively and to characterize patients who responded exceptionally well or very poorly within each histopathologic subtype. Retrospective review of patients with low-grade mucinous carcinoma peritonei (LGMCP), high-grade MCP (HGMCP), and HGMCP with signet ring cells (HGMCP-S) with complete CRS/HIPEC (CC-0/1) was performed. Patients were divided by recurrence status. Median follow-up was calculated for each. Exceptional responders (ExR) were defined as alive without recurrence after median follow-up of the nonrecurrent group. Poor responders (PoR) were defined as disease recurrence before median follow-up of the recurrent group. Perioperative characteristics were analyzed. LGMCP, HGMCP, and HGMCP-S had 48 (41%), 19 (23%), and 7 (14%) ExR and 11 (10%), 20 (24%), and 20 (39%) PoR, respectively. All ExR had lower median PCI (26 vs. 36 [p = 0.004]; 13 vs. 33.5 [p

Background. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is debated. Melphalan as a perfusion agent has also demonstrated survival benefit in other recurrent and chemoresistant malignancies. Thus, we hypothesize that melphalan as a HIPEC agent may improve overall survival (OS) and progression-free survival (PFS) in patients with PC from CRC. Methods. A retrospective review of a prospective database of 48 patients who underwent optimal CRS (CC-0/1) and HIPEC from 2001-2016 was performed. Nineteen had CRS/HIPEC with melphalan (group I) and 29 with mitomycin-C (group II). Survival was estimated using the Kaplan-Meier method. Cox regression was used for multivariate analysis. Perioperative variables were compared. Results. Mean age at CRS/HIPEC was 53±10 years. Median peritoneal cancer index (PCI) was 17 vs 13 in groups I and II, respectively (p=0.86). PCI≥20 occurred in 9 (47%) and 13 (45%) patients in groups I and II, respectively. Positive lymph nodes were identified in 8/19 (42%) vs 12/29 (41%) in groups I and II, respectively (p=0.73). Multivariate analysis identified PCI≥20 as a predictive factor of survival (HR: 7.5). Median OS in groups I and II was 36 and 28 months, respectively (p=0.54). Median PFS in groups I and II was 10 and 20 months, respectively (p=0.05). Conclusions. CRS/HIPEC with MMC had longer median PFS in PC from CRC. PCI≥20 was the only independent predictive factor for survival. Until longer follow-up is available, we recommend using MMC in CRS/HIPEC for PC from CRC. Further prospective randomized studies are necessary.

Objective Uterine sarcomas (USs) are characterized by poor response to systemic chemotherapy and high recurrence rates. This study evaluates whether the use of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) confers survival benefit in comparison with conventional treatment modalities in patients with recurrent US. Methods/Materials A retrospective analysis of patients with recurrent US at a single institution for an 11-year study period was performed. All women with a pathologic diagnosis of leiomyosarcoma, adenosarcoma, endometrial stromal sarcoma, or undifferentiated US were identified. Overall and disease-free survival was estimated using Kaplan-Meier method. Comparisons between the study groups were performed with the log-rank test and Cox regression. Results A total of 26 patients were identified. Five patients received chemotherapy and/or radiotherapy without surgical intervention, 14 patients underwent surgery alone or a combination of surgery and adjuvant systemic chemotherapy, and 7 patients received cytoreductive surgery with HIPEC. There was no treatment-related mortality in any group, and only 1 patient had grade III–IV surgical complications. Median disease-free survival was 2.4 months for patients with nonsurgical treatments, 5.3 months for patients treated with conventional surgery, and 11.3 months for patients treated with HIPEC. Median overall survival was 35.9 months for patients treated with conventional surgery and 43.8 months for patients treated with HIPEC. Conclusions Our study is the first to compare survival outcomes of HIPEC versus conventional therapies for recurrent US and is suggestive of treatment benefit. Further studies with more patients and longer follow-up to evaluate the role of HIPEC in management of this disease are warranted.

We evaluated the 7th edition of the American Joint Committee on Cancer (AJCC) staging classification in terms of overall survival (OS) in patients with PMP treated with cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC). A total of 208 PMP patients treated with CRS/HIPEC were identified from a prospective database. Patients with peritoneal mucinous carcinomatosis (PMCA) were retrospectively staged at time of diagnosis according to AJCC staging classification. Patients with disseminated peritoneal adenomucinosis (DPAM) were evaluated in a separate group. Median follow-up was 5.2 years. Of 208 patients, 124 had PMCA and 84 patients had DPAM. According to the AJCC staging classification 47 lymph node (LN) negative patients with well-differentiated PMCA, were classified as a stage IVA. 77 patients with either moderately or poorly differentiated PMCA irrespective of LN status, or well-differentiated PMCA with positive LN were classified as stage IVB. 84 patients with DPAM, constituted a separate group. OS of stage IVA and IVB patients was 100, 90, 67, and 91, 50, and 27 for 1, 3, and 5 years, respectively (p

Background Patients with PMCA commonly undergo surgery before CRS/HIPEC. We evaluated the role of extensive surgical treatment before CRS/HIPEC in terms of overall survival (OS). Methods 105 patients with PMCA who underwent a CRS/HIPEC procedure were identified from a prospective database. Patients were divided into two groups based on Prior Surgery Score (PSS): PSS ≤1 limited surgery group (LSG), PSS >1 extensive surgery group (ESG). Survival of lymph node (LN) negative and positive patients was analyzed separately. Results 40 patients were in LSG and 65 in ESG. Mean time from diagnosis to CRS/HIPEC was 6 and 17 months for LSG and ESG, respectively (p = 0.004). Groups were well balanced in peritoneal cancer index, complete cytoreduction rate, and LN status. One, 3, and 5-year OS among LN negative patients was 95, 83, and 75% for the LSG (n = 22) group and 87, 55, and 32% for the ESG (n = 35), group respectively (p = 0.026). One, 3, and 5-year OS among LN positive patients was 69, 50, and 17% for the LSG (n = 18) group and 80, 21, and 14% for the ESG (n = 30), group respectively (p = 0.613). For all patients 1, 3, and 5-year OS was 84, 65, and 54% for the LSG (n = 40) group and 86, 43, and 26% for the ESG (n = 65) group, respectively (p = 0.029). Conclusion Extensive surgical treatment before CRS/HIPEC is associated with delay of CRS/HIPEC and poorer OS overall, especially among LN negative patients. We recommend early referral of PMCA patients to a peritoneal surface malignancy center.

Background The role of SC before CRS/HIPEC for patients with PMCA is unclear. This study explores the effect of SC prior to CRS/HIPEC on overall survival (OS) in patients with PMCA. Methods 72 patients with recently diagnosed PMCA who underwent CRS/HIPEC were identified from a prospective database. Thirty patients had SC before CRS/HIPEC (Group 1) and 42 did not (Group 2). Patients who were referred to our center after multiple lines of SC were excluded from this analysis. OS was estimated. Results Median follow-up was 3.2 years. Groups were similar regarding lymph node positivity, postoperative SC and rate of complete cytoreduction. Twenty-four (80%) patients in Group 1 and 21 (50%) in Group 2 had high grade histology (HG) (p = 0.01). OS from CRS/HIPEC at 1, 2, and 3 years was 93, 68, 51% in Group 1 and 82, 64, 60% in Group 2, respectively (p = 0.74). Among HG patients 3-year survival was 36% in the SC group vs. 35% in the group without SC (p = 0.67). The 3-year OS for patients with low grade (LG) tumors was 100% in the SC group vs. 79% in the group with no prior SC (p = 0.26). Among patients with signet ring cell (SRC) histology, 1, 2 and 3-year survival was 94, 67 and 22% in the SC group vs. 43, 14, 14% in the group with no SC, respectively (p = 0.028). There were only 6 patients with LG PMCA who received prior SC. Conclusions Preoperative SC could improve the prognosis of patients with high-grade PMCA with SRC histology.

Port-site metastases (PSMs) have been reported after laparoscopy in patients with peritoneal carcinomatosis (PC). We hypothesize that PSM is an independent negative predicting factor of survival in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). A retrospective review of a prospective database was conducted to search patients who underwent laparoscopy prior to CRS/HIPEC. Most of the tumors were of appendiceal origin. All previous laparoscopy port sites were excised regardless of macroscopic tumor involvement. Patients were divided into two groups: patients with PSM [PSM (+)] and patients without PSM [PSM (−)]. Overall survival (OS) was estimated by Kaplan–Meier curves and the log-rank test. Cox regression [hazard ratios (HRs) and 95 % confidence intervals (CIs)] was used to test for independent effects of the PSM (+) and the associated clinicopathological variables. Sixty-five patients had laparoscopy before CRS/HIPEC. One hundred and forty-four port-sites were resected; 41 (29 %) ports were positive for malignancy in a total of 22 (34 %) patients. Mean OS at 1, 3, and 5 years was 88, 66, and 63 %, respectively. Survival in patients with PSM was 73, 35, and 23 %, respectively, compared with 95, 82, and 82 %, respectively, in patients without PSM (p ≤ 0.001). Positive lymph nodes (LNs) were detected in 13/22 patients with PSM and 11/43 patients without PSM. Independent effects on survival shows an HR of 3.136, 95 % CI 1.150–8.549 (p = 0.026) for LN metastases, and an HR of 3.462, 95 % CI 1.198–10.006 (p = 0.022) in patients with positive PSM. PSMs are common in patients with PC undergoing CRS/HIPEC and are independently associated with a worse prognosis. Resection of previous laparoscopy port sites is advocated in patients with PC to ensure complete cytoreduction.

CRS/HIPEC has evolved as a therapeutic option for selected patients with peritoneal surface malignancies. To achieve complete cytoreduction (CC), some patients require extensive abdominal-wall resection (AWR) and subsequent complex reconstructions, which may be associated with wound complications (WC) and delay of postoperative cancer therapy. Review of a prospective database of 350 patients revealed 213 patients with peritoneal carcinomatosis who underwent AWR due to suspected or proven wound/port site metastases during CRS/HIPEC. Tumor origin included: appendix, colon, ovarian, peritoneal mesothelioma, primary peritoneal, and others. WC were related to peritoneal carcinomatosis index (PCI), CC score, length of surgery, type of AWR and closure, blood transfusion, and albumin levels using binary logistic regression (odds ratios (OR) and 95 % CIs) analysis. PCI ≥ 20 was found in 151 (71 %), CC was achieved in 178 (84 %). Mean length of surgery was 613 min. Postoperative WC were detected in 49 of 213 (23 %) patients, 13 (6 %) had Grade III (according to Clavien–Dindo’s classification) WC, and led to delay of postoperative chemotherapy. WC occurred in 21 of 64 (32.8 %) patients with excision of port sites (odds ratio [OR] = 2.11, confidence interval [CI] = 1.09–4.10, p = 0.026). Primary fascial closure was performed in 191 of 213 (89.7 %) patients, 40 (21 %) of whom had WC. Mesh-assisted abdominal wall reconstruction was required in 22 of 213 (10.3 %) patients, of whom 9 (40.9 %) had WC (OR = 2.61, CI = 1.04–6.55, p = 0.035). Port-site excision and mesh-assisted abdominal wall reconstruction were associated with higher incidence of postoperative WC following CRS/HIPEC. The implications of these preliminary findings may need to be considered during surgical planning for these patients.

10512 Background: Disparities in current global oncology care are a major concern for many societies. Two-year oncological training in Russia is deficient in evidence-based medicine (EBM) and effective patient communication skills, despite the fact that these dictate the ability to provide optimal cancer care. We report a 3.5-year sustained program aimed at implementing Western-oriented education among young Russian oncologists to combat these educational deficiencies. Methods: The Higher School of Oncology (HSO) is a 5-year national competitive program established to supplement the traditional 2-year Russian oncology curriculum with an emphasis on patient communication, critical appraisal of oncologic articles, multidisciplinary cancer care, and program development. A total of 35 PGY1-4 residents (8-9 residents annually) have enrolled in the program. Expatriate Russian physicians practicing in the US led 140 online educational seminars with journal clubs and clinical case presentations. Communication skills were evaluated by an independent private educational group. Results: Significant improvement of EBM knowledge was marked among HSO residents, from inability to explain basic concepts to practicing and teaching EBM. Beginning in the 3rd year of the program, residents organized educational courses and conducted journal clubs for HSO and non-HSO colleagues. Residents of the program had higher patient communication scores compared to that of residents of standard Russian programs. HSO residents promoted the spread and popularization of EBM and a patient-centered approach among attending physicians, improving the quality of cancer care. The HSO also triggered imitation of similar projects in other residency programs. Conclusions: The HSO project has pioneered EBM training and led to systemic changes in cancer patient care for Russian oncologists. This model has shown success and may be useful in overcoming global medical educational disparities in other specialties and in other countries facing similar challenges.

Background Vascular endothelial growth factor (VEGF) is a prognostic factor and target treatment for metastatic colorectal and ovarian cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival on peritoneal carcinomatosis (PC) from appendiceal cancer. We hypothesize that tumoral high expression of VEGF receptor 2 (VEGFR-2) is a negative prognostic factor for survival in patients with PC from appendiceal cancer. Methods A retrospective study of a prospective database revealed 89 patients with PC from appendiceal cancer who underwent 127 CRS/HIPECs. Surgical specimens from 59 patients were tested to identify high vs. low VEGFR-2 expression. Patient outcomes and survival were analyzed. Results There were 26 males and 33 females. Mean age was 51 years. Forty-seven VEGFR-2 high expressers and 15 low expressers were identified. Mean follow-up of high and low expressers was 25.1 and 26.6 months, respectively (p = 0.806). At follow-up, 33 (70%) high expressers were alive and 14 (30%) deceased, while 11 (92%) low expressers were alive and 1 (8%) deceased. Recurrence, use of bevacizumab, CC score, PCI, and LN status showed no differences between high and low expressers. OS for high expressers was 90.5%, 59.8%, and 47.1% at 1-, 3-, and 5-years, respectively, while OS for low expressers remained stable at 91.7% at 1-, 3-, and 5-years (p = 0.133). Conclusion There is a trend towards better outcomes and survival in patients with PC from appendiceal cancer who have low expression of VEGFR-2 compared to high expression. More studies are encouraged to confirm this trend.

Background Cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC) is the procedure of choice in patients with peritoneal dissemination from appendiceal cancer. Although recurrence rates are 26%–44% after first CRS/HIPEC, the role of repeated CRS/HIPEC has not been well defined. We hypothesize that patients undergoing multiple CRS/HIPEC's have meaningful long term survival. Methods A retrospective study of a prospective database of 294 patients with peritoneal carcinomatosis (PC) was conducted, of these 162 had PC of appendiceal origin. Twenty-six of these patients underwent 56 CRS/HIPEC. Survival and outcomes was analyzed. Results The percentage of patients with pre-surgical PCI scores ≥20 for the first, second, and third CRS/HIPEC was 65, 65, and 25%, respectively. Complete cytoreduction (CC 0-1) at first, second, and, third surgeries was 96, 65 and 75%, respectively. The mean operating time was 10.1 h. There was no 30-day peri-operative mortality. Following the first, second, and third CRS/HIPEC 27, 42, and 50% experienced grade III complications, respectively. Mean follow up was 51, 28, and 16 months from the first, second, and third CRS/HIPEC, respectively. Overall survival rate for the first CRS/HIPEC was 100, 83, 54, and 46% at years 1, 3, 5 and 10, respectively; from the second CRS/HIPEC 91, 53, and 34% at 1, 3, and 5 years, respectively; and from the third CRS/HIPEC was 75% at one year. Conclusion Repeat CRS/HIPEC can lead to meaningful long term survival rates in patients with appendiceal peritoneal carcinomatosis with morbidity and mortality similar to those of the initial CRS/HIPEC.

Diffuse malignant peritoneal mesothelioma (DMPM) is an uncommon malignancy, which can be difficult to treat. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have evolved as the treatment of choice when complete cytoreduction is to be achieved. This study reports the outcomes of CRS/HIPEC for peritoneal mesothelioma performed in a center for peritoneal surface malignancy. A retrospective analysis of a prospective database of 389 CRS/ HIPEC procedures identified 23 patients who underwent CRS/HIPEC for DMPM from 1999 to 2014. Gender, age at diagnosis, age at surgery, previous surgeries, follow-up time, peritoneal cancer index (PCI) score, completeness of cytoreduction (CC), pathology, and overall survival (OS) were analyzed. The univariate analysis was used to determine the prognostic value of age, gender, neoadjuvant chemotherapy, histopathology of the tumor, PCI, CC, and lymph node status on survival. Mean follow-up time from surgery was 31 months (range = 0.5–124). The median PCI score was 28, and 77 per cent had PCI ≥20. CC 0–1 was achieved in 65 per cent of cases. One- and 5-year actuarial OS rates from diagnosis were 86 per cent and 60 per cent, respectively. One- and 5-year actuarial OS from HIPEC was 70 per cent and 64 per cent, respectively. The univariate analysis showed that the CC was the only significant prognostic factor. Patients with DMPM may achieve long-term survival when treated with CRS/HIPEC. The CC is the most significant prognostic factor for long-term survival.

4098 Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) have become standard of care for patients with peritoneal carcinomatosis (PC) from appendiceal cancer (AC). We reviewed our experience and outcomes. Methods: A retrospective review of 614 CRS/HIPEC procedures from 1998-2016 was performed. Patient characteristics, surgical variables, and postoperative outcomes of first CRS/HIPEC were analyzed. Results: Two hundred ninety patients with PC from AC underwent 334 CRS/HIPEC’s. Median age at diagnosis and surgery was 52 (22-79) and 53 (23-81) years, respectively; 65% (187) were female. Prior surgical score was 0, 1, 2, and 3 in 20%, 38%, 37%, and 5%, respectively. Prior systemic chemotherapy was reported in 30% of patients. Median time from diagnosis to CRS/HIPEC was 4 months (0-182). Pre-operative tumor markers (CEA, CA-125, CA-19-9) were positive in 48% with one, two, and three positive markers in 21%, 15%, and 13% patients, respectively. Median Peritoneal Cancer Index was 29. Mitomycin-C was the HIPEC agent of choice. Mean operative time was 10 hours (R: 4-19) and median length of stay was 10 days (R: 4-93). Histology included 59% (171) peritoneal mucinous carcinomatosis (PMCA), 41% (119) disseminated peritoneal adenomucinosis (DPAM). Lymph nodes were positive in 47% PMCA. Complete cytoreduction rate was 87% (84% PMCA, 92% DPAM [p = 0.048]). Grade III-V complications occurred in 21%, with one 30-day mortality (0.3%). Overall, median progression-free survival (PFS) was 84 months with 5-year PFS of 56%. Median PFS was 43 months in PMCA and not reached in DPAM. Five year PFS was 40% PMCA and 82% DPAM (p < 0.001). Median overall survival (MOS) was 139 months with 61% 5-year OS. MOS was 53 months in PMCA and not reached in DPAM. Five year OS was 47% PMCA and 85% DPAM (p < 0.001). At 42-month median follow-up, 68% were alive (92 PMCA/103 DPAM) with 84% disease free (72 PMCA/92 DPAM), 28% died of disease (73 PMCA/7 DPAM). Conclusions: CRS/HIPEC is an effective treatment for patients with PC from AC providing meaningful long term survival in low and high grade tumors and should be considered the standard of care.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has survival benefit in the treatment of selected patients with peritoneal carcinomatosis (PC) from appendiceal cancer (AC). We evaluated factors affecting the survival of patients with PC from AC after CRS/HIPEC. A retrospective analysis of 387 CRS/HIPEC procedures performed between February 1998 and February 2013 identified 202 patients with PC from AC. Tumor histopathology, complete cytoreduction (CC 0–1), Peritoneal Cancer Index (PCI), and lymph node (LN) status were related to overall survival (OS) and progression-free survival (PFS) using the Kaplan–Meier method. Overall, 129 women (64 %) and 73 men (36 %), mean age 54 years (range 25–81), with a mean follow-up of 36 months were included in the study. Seventy-seven low-grade tumors (disseminated peritoneal adenomucinosis [DPAM]; 38 %) and 125 high-grade tumors (peritoneal mucinous carcinomatosis [PMCA]; 62 %) were identified. Five- and 10-year OS was 56 % and 47 %, respectively, with PFS of 44 % at 5 and 10 years. Five-year OS in DPAM patients was 83 %, with a 5-year OS significant difference related to CC 0–1 versus CC 2–3 (incomplete cytoreduction) [p = 0.021]. Five-year OS in PMCA patients was 41 %, with a 5-year OS significant difference related to CC 0–1 versus CC 2–3 (p

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has become an option for peritoneal carcinomatosis (PC). Frequently, these patients have failed systemic chemotherapies and surgeries, including CRS/HIPEC with traditional regimens (mitomycin-C or platinum based). An alternative agent for failed or repeated CRS/HIPEC is unknown. We hypothesize that melphalan is an alternative agent in patients with PC from aggressive primaries, including recurrences following failed regional therapies.A retrospective review of a prospective database of 247 patients revealed 25 patients (9 male and 16 female) who received intraperitoneal melphalan (50 mg/m(2)) in 31 CRS/HIPEC procedures, of which 19 were repeated. Primary malignancies included 17 appendiceal, one colorectal, two ovarian, two uterine sarcomas, two primary peritoneal and one mesentery sarcoma.PC index (PCI) was ≥20 in 76 % of patients (19/25). 88 % of patients (22/25) had complete cytoreduction. Seventeen patients were alive, with mean survival of 63.6 months, and eight patients are deceased. Overall survival (OS) for the entire group since diagnosis was 95.8, 84.5, 50.9, and 38.2 % at 1, 3, 5, and 10 years, respectively; OS since melphalan HIPEC was 89.4, 45, and 30 % at 1, 3, and 5 years, respectively; and OS in patients with appendiceal malignancies was 91.7, 48.1 and 32.1 % at 1, 3 and 5 years, respectively. There was no postoperative mortality. Grade III-IV morbidity was 23 % (7/31). Nine patents had neutropenia, controlled with filgrastim.Melphalan is an efficacious alternative agent in patients undergoing CRS/HIPEC for aggressive and recurrent peritoneal surface malignancies. Its postoperative significant myelosuppression effect should be addressed.