Peritoneal Spread Research Articles

Retrospective study of histopathological and prognostic characteristics of primary fallopian tube carcinomas: twenty-year experience (SOCRATE)

ObjectivePrimary fallopian tube carcinoma represents a rare entity, accounting for about 0.75%–1.2% of all gynecological malignancies. The rationale of our study is to describe the prognosis of primary fallopian tube...

ASO Visual Abstract: Systemic Chemotherapy in High-Grade Mucinous Appendiceal Cancer with Peritoneal Spread after Unsuccessful Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC)

ASO Visual Abstract: Systemic Chemotherapy in High-Grade Mucinous Appendiceal Cancer with Peritoneal Spread after Unsuccessful Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC)

Abstract 4210: Gene therapy approach to suppress metastasis in a mouse melanoma model

Abstract Immune checkpoint inhibitors (ICIs) have been demonstrated to have significant clinical benefits. Effectiveness of ICIs have been limited by both primary and acquired resistance. In addition, absence of T cell infiltration within the tumor site is one of the major obstacles limiting ICIs efficacy against solid tumors. Interleukin-12 (IL-12) is a potent immune stimulator that has been shown to stimulate growth and survival of T cells as well as NK cells. Utilizing a B16.F10 melanoma model in C57Bl/6 mice, we observed a significant reduction in T regulatory cells and myeloid derived suppressor cells while T effector cells were significantly increased within the tumor microenvironment (TME) following intratumor delivery of a plasmid encoding IL-12 using gene electrotransfer. Monotherapy with plasmid IL-12 delivered with gene electrotransfer (pIL-12 GET) resulted in prolonged disease-free survival as well as long term immune memory. To determine the robustness of this therapeutic approach and to evaluate the responsiveness in combination with anti-PD1, we used a two-tumor model consisting of a subcutaneous B16F10 tumor and B16F10 cells expressing luciferase injected via the intraperitoneal route in a C57Bl/6 mouse. Intratumor delivery of pIL-12 GET as a monotherapy resulted in reduction or elimination of the subcutaneous tumor. However, the monotherapy approach was only successful in reducing the peritoneal spread in about 50% of the mice. When pIL-12 GET was combined with anti-PD1 administered via an intraperitoneal injection not only was there an elimination of the subcutaneous tumor, but it resulted in the elimination of intraperitoneal metastatic growth. The elimination of peritoneal spread was confirmed utilizing an In Vivo Imaging System. Observations on day 60 revealed background levels of luminescence in 90% of mice treated with the combination therapy thus confirming long-term disease-free survival of these mice. This level of response was not seen in mice treated with anti-PD-1 alone or with simple injection of pIL-12. In addition, the combination therapy resulted in an enhanced memory response which protected against growth of new tumors following challenge. In addition, exposure of tumor cells to IL-12 resulted in upregulation of MHC class 1 and PDL1 expression. The results have this study suggest that the combination of pIL-12 GET combined with ICIs could be utilized as an effective combination therapy for melanoma. Citation Format: Richard Heller, Megan Scott, Cathryn Mangiamele, Jody Synowiec, Guilan Shi. Gene therapy approach to suppress metastasis in a mouse melanoma model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4210.

Abstract 107: Reciprocal Sox2 regulation by SMAD1 and SMAD3 is critical for anoikis resistance and metastasis in ovarian cancer

Abstract The tumor ascites environment is enriched with cytokines and growth factors especially members of the Transforming Growth Factor-β (TGF-β) family, that play crucial roles in modulating anoikis sensitivity and consequently metastatic progression in ovarian cancer. Here, we demonstrated for the first-time significant broad dichotomy between these TGF-β members: BMPs and TGF-β/activin and their regulated SMADs in this process. We previously reported BMP9/GDF2 to be in low to undetected levels in ovarian cancer patient-derived ascites and promoted anoikis resistance in both breast and ovarian cancer cell lines. We have now identified additional BMPs -BMP2, BMP4 and BMP9 as promoting anoikis sensitivity in a spectrum of ovarian cancer cells. Conversely, we found TGF-βs (1 and 2) to be in much higher expression and demonstrated that TGF-β and activin promoted anoikis resistance in ovarian cancer. Hence, in an attempt to identify genes downstream of BMPs that may provide anoikis resistance, transcriptomics was performed leading to the identification of Sox2, a developmental gene with prior established roles in OVCA, as being significantly downregulated in response to BMP9. We further uncovered Sox2 to be reciprocally regulated by anoikis-promoting BMPs (2, 4 and 9) and anoikis suppressing TGF-β and activin A. Our findings highlight a novel contrasting SMAD dependent regulation of Sox2 as a central node for controlling tumor cell survival in ovarian cancers demonstrating a subset of BMPs as a therapeutic strategy in cancer. The studies presented here begin to elucidate the mechanisms of reciprocal epigenetic regulation of Sox2 by BMP and TGF-β/activin in the context of ovarian cancer, which is the most lethal gynecologic malignancy in women due to peritoneal metastatic spread. Citation Format: Zainab M. Shonibare, Mehri Monavarian, Kathleen O'Connell, Diego Altamore, Abigail Shelton, Shubham Mehta, Renata Jaskula-Sztul, Rebecca Phaeton, Andrew Berchuck, Andrew B. Nixon, Rebecca Arend, Nam Y. Lee, Ryan Miller, Nadine Hempel, Karthikeyan Mythreye. Reciprocal Sox2 regulation by SMAD1 and SMAD3 is critical for anoikis resistance and metastasis in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 107.

Abstract 3474: Molecular subtypes characterize appendiceal adenocarcinoma genomic evolution and disease behavior

Abstract Appendiceal adenocarcinoma (AC) are rare gastrointestinal tumors that exhibit a heterogeneous spectrum of tumor histology and differentiation patterns. Personalized AC treatments are limited by the lack of robust histopathological or genomic predictors of disease behavior. We utilized the MSK IMPACT sequencing panel to profile genomic signature patterns in somatic mutations, copy number alterations, and germline mutations in a large curated dataset of patients with AC. We evaluated co-occurrence and clonality patterns between frequently altered genes in AC (RAS, GNAS, TP53) to establish five molecular subtypes of mucinous appendiceal adenocarcinoma (MAAP): RAS mutated-only, GNAS mutated, TP53 & KRAS mutated, TP53 mutated-only, and none (all wild-type). In multivariable Cox regression models, patients with RAS mutated-only tumors exhibit a nearly non-lethal disease course compared to other molecular subtypes, including TP53 mutated-only tumors (hazard ratio for death: 75.6, p<0.001). Inclusion of tumor molecular subtype in conventional multivariable models improves model prognostic strength. In addition, MAAP-derived molecular subtypes prognosticate patient survival in a separate cohort of 248 patients with right-sided, mismatch-repair-proficient metastatic colorectal cancer. Molecular characterization of AC also reveals differences in tumor biology and behavior. In addition to an improved prognosis, RAS mutated-only MAAP tumors exhibit significantly lower tumor mutational quantity and aneuploidy compared to other subtypes in multivariable models (p<0.001). Together with clonality patterns, this suggests that RAS mutated-only tumors exhibit a relatively younger molecular age. In a subset of patients with MAAP who underwent cytoreductive surgery, patients with RAS-only tumors demonstrate significantly lower intra-operative assessed peritoneal cancer indices (PCI) compared to patients with other molecular subtypes (p=0.049). Microscopic assessment of surgical samples reveals that RAS mutated-only tumors are significantly less likely (p<0.001) to exhibit destructive metastatic stromal invasion compared to GNAS and TP53 mutated subtypes. Molecular subtype is also a significant independent predictor of both radiographic and biochemical response to first line chemotherapy for patients with AC. Overall, through a comprehensive profiling of the AC mutational landscape we introduce a unique disease entity of RAS-only mutated MAAP that exhibits dramatically low lethality, low peritoneal spread, and decreased tissue invasiveness despite high-risk histological characteristics. The behavior of this clinically-metastatic, but molecularly-young subtype introduces a new characterization of metastatic pathogenesis and risk that may apply to other premalignant and malignant diseases. Citation Format: Michael B. Foote, Henry Walch, Walid Chatila, Efsevia Vakiani, Chris Chandler, Felix Steinrucke, Garrett Nash, Zsofia Stadler, Sebastian Chung, Yelena Kemel, Anna Maio, Margaret Sheehan, Nikolaus Shultz, Luis A. Diaz, Andrea Cercek. Molecular subtypes characterize appendiceal adenocarcinoma genomic evolution and disease behavior [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3474.

Organoids From Mucinous Appendiceal Adenocarcinomas as High-Fidelity Models for Individual Therapy.

BackgroundMucinous appendiceal adenocarcinoma (MAA) is a rare, heterogeneous disease. Patients with unrespectable mucinous appendiceal adenocarcinoma presenting with peritoneal spread are treated by intraperitoneal chemotherapy, hyperthermic intraperitoneal chemotherapy, systemic chemotherapy, or targeted therapy. However, there are no guidelines for efficacious drugs against mucinous appendiceal adenocarcinoma. Therefore, relevant high-fidelity models should be investigated to identify effective drugs for individual therapy.MethodsSurgical tumor specimens were obtained from a mucinous appendiceal adenocarcinoma patient. The tissue was digested and organoid culture was established. H&E and immunohistochemistry staining as well as DNA sequencing was performed on tissue and organoid. The pathological characteristics and gene mutations of the organoid were compared to those of the original tumor. Drug sensitivity tests were performed on organoid and the patient clinical responds to chemotherapy and targeted therapy was compared.ResultsOrganoids were successfully established and stably passaged. Pathological characteristics of organoids including H&E staining and expression of protein markers (CK20, CDX-2, STAB2, CD7, PAX8) were consistent to those of the original tumor. Moreover, the organoids carried the same gene mutations as the primary tumor. Sensitivity of the organoids to chemotherapeutic drugs and tyrosine kinase inhibitors included: 5-FU (IC50 43.95 μM), Oxaliplatin (IC50 23.49 μM), SN38 (IC50 1.02 μM), Apatinib (IC50 0.10 μM), Dasatinib (IC50 2.27 μM), Docetaxel (IC50 5.26 μM), Regorafenib (IC50 18.90 μM), and Everolimus (IC50 9.20 μM). The sensitivities of organoid to these drugs were comparable to those of the patient's clinical responses.ConclusionThe mucinous appendiceal adenocarcinoma organoid model which retained the characteristics of the primary tumor was successfully established. Combined organoid-based drug screening and high throughput sequencing provided a promising way for mucinous appendiceal adenocarcinoma treatment.

Sex and gender disparities in patients with advanced gastroesophageal adenocarcinoma: data from the AGAMENON-SEOM registry

BackgroundRecommendations for research articles include the use of the term sex when reporting biological factors and gender for identities or psychosocial or cultural factors. There is an increasing awareness of incorporating the effect of sex and gender on cancer outcomes. Thus, these types of analyses for advanced gastroesophageal adenocarcinoma are relevant.Patients and methodsPatients with advanced gastroesophageal adenocarcinoma from the Spanish AGAMENON-SEOM registry treated with first-line combination chemotherapy were selected. Epidemiology, characteristics of the disease, treatment selection, and results were examined according to sex.ResultsThis analysis included 3274 advanced gastroesophageal adenocarcinoma patients treated with combination chemotherapy between 2008 and 2021: 2313 (70.7%) men and 961 (29.3%) women. Tumors in females were more frequently HER2-negative (67.8% versus 60.8%; P < 0.0001), grade 3 (45.4% versus 36.8%; P < 0.001), diffuse (43.3% versus 26.5%; P < 0.0001), and signet ring cell histology (40.5 versus 23.9%; P < 0.0001). Peritoneal spread was more common in women (58.6% versus 38.9%; P < 0.0001), while liver burden was lower (58.9% versus 71.1%; P < 0.0001). There were no significant differences in treatment recommendation. Treatment doses, density, and duration were comparable between sexes. Women experienced more diarrhea (46% versus 37%; P < 0.0001), neutropenia (51% versus 43%; P < 0.0001), and anemia (62% versus 57%; P < 0.0001). After a median 59.6-month follow-up [95% confidence interval (CI) 54.5-70.8], there were no statistically significant differences between the sexes in progression-free survival [6.21 months (95% CI 5.8-6.5 months) versus 6.08 months (95% CI 5.8-6.3 months); log-rank test, χ2 = 0.1, 1 df, P = 0.8] or in overall survival [10.6 months (95% CI 9.8-11.1 months) versus 10.9 months (95% CI 10.4-11.4 months); log-rank test: χ2 = 0.6, 1 df, P = 0.5].ConclusionThis sex analysis of patients with advanced gastroesophageal adenocarcinoma from the AGAMENON-SEOM registry receiving first-line polychemotherapy found no differences in survival. Although women had worse prognostic histopathology, metastatic disease pattern, and greater toxicity, treatment allocation and compliance were equivalent.

Systemic Chemotherapy for High-Grade Mucinous Appendiceal Cancer with Peritoneal Spread After Unsuccessful CRS/HIPEC.

The best management of patients who have unresectable mucinous appendiceal cancer (MAC) with peritoneal spread after a failed attempt at cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is unclear. This study aimed to assess outcomes after systemic chemotherapy (SCT) for patients with unresectable peritoneal metastases from high-grade MAC. A single-center retrospective cohort study was conducted using a prospective CRS/HIPEC database. The study included high-grade MAC patients with peritoneal carcinomatosis who were deemed surgical candidates, but had an aborted CRS/HIPEC or only palliative HIPEC due to unresectable disease. Overall survival (OS) was compared. Of 72 identified patients, 20 received SCT and 52 did not (NoCT). The groups were balanced by age (p = 0.299), sex (p = 0.930), histopathologic subtype (p = 0.096), preoperative chemotherapy (p = 0.981), and postoperative major complication rates (p = 0.338). Both groups had extensive disease (median peritoneal cancer index at exploration, 39 vs 39). The median number of cycles was 12 (interquartile range [IQR], 6-15), and the median time between the procedure and SCT was 7 weeks (IQR, 5-10 weeks). The median follow-up period was 65 months. The median OS was significantly higher for the SCT group (26 months; 95 % confidence interval [CI], 10.8-41.5 months) than for the NoCT group (12 months; 95 % CI, 9.6-14.4 months) (p < 0.001), with hazard ratio (HR) of 0.22 (95 % CI, 0.08-0.66; p = 0.007) after adjustment for other factors. Systemic chemotherapy is associated with improved OS for high-grade MAC patients with unresectable peritoneal metastases who are deemed surgical candidates but underwent an unsuccessful CRS/HIPEC attempt. Further prospective studies with a larger sample are required to identify patient subgroups who benefit the most from SCT.

Fine needle aspiration cytology of a gastric mass-A riddle wrapped up in an enigma.

Malignant mesothelioma (MM) is a recognised neoplasm which can be diffuse or can rarely present as a localised mass. Cytological diagnosis is a challenge and three morphological subtypes—epithelioid, sarcomatoid, and biphasic—are recognised. Rarely MM can present as a gastric mass with diffuse peritoneal spread and ascites, posing a diagnostic dilemma. Cell block and immunohistochemical stains are critical for establishing the diagnosis by fine needle aspiration cytology (FNAC).

Selected Patients With Peritoneal Metastases From Breast Cancer May Benefit From Cytoreductive Surgery: The Results of a Multicenter Survey.

BackgroundEven though breast cancer is the most frequent extra-abdominal tumor causing peritoneal metastases, clear clinical guidelines are lacking. Our aim is to establish whether cytoreductive surgery (CRS) could be considered in selected patients with peritoneal metastases from breast cancer (PMBC) to manage abdominal spread and allow patients to resume or complete other medical treatments.MethodsWe considered patients with PMBC treated in 10 referral centers from January 2002 to May 2019. Clinical data included primary cancer characteristics (age, histology, and TNM) and data on metastatic disease (interval between primary BC and PM, molecular subtype, other metastases, and peritoneal spread). Overall survival (OS) was estimated using the Kaplan–Meier method. Univariate and multivariable data for OS were analyzed using the Cox proportional hazards model.ResultsOf the 49 women with PMBC, 20 were treated with curative aim (CRS with or without HIPEC) and 29 were treated with non-curative procedures. The 10-year OS rate was 27%. Patients treated with curative intent had a better OS than patients treated with non-curative procedures (89.2% vs. 6% at 36 months, p < 0.001). Risk factors significantly influencing survival were age at primary BC, interval between BC and PM diagnosis, extra-peritoneal metastases, and molecular subtype.ConclusionsThe improved outcome in selected cases after a multidisciplinary approach including surgery should lead researchers to regard PMBC patients with greater attention despite their scarce epidemiological impact. Our collective efforts give new information, suggest room for improvement, and point to further research for a hitherto poorly studied aspect of metastatic BC.

Epigenomic Profiling of Epithelial Ovarian Cancer Stem-Cell Differentiation Reveals GPD1 Associated Immune Suppressive Microenvironment and Poor Prognosis.

Intraperitoneal metastasis is a challenging clinical scenario in epithelial ovarian cancer (EOC). As they are distinct from hematogenous metastasizing tumors, epithelial ovarian cancer cells primarily disseminate within the peritoneal cavity to form superficially invasive carcinomas. Unfavorable pharmacokinetics for peritoneal tumors and gut toxicity collectively lead to a narrow therapeutic window and therefore limit the opportunities for a favorable clinical outcome. New insights into tumor metastasis in the peritoneal microenvironment are keenly awaited to develop new therapeutic strategies. Epithelial ovarian cancer stem cell (OCSC) seeding is considered to be a critical component of the peritoneal spread. Using a unique and stepwise process of the OCSC differentiation model may provide insight into the intraperitoneal metastasis. The transcriptome and epigenome of OCSC differentiation were characterized by expression array and MethylCap-Seq. The TCGA, AOCS, and KM-Plotter databases were used to evaluate the association between survival outcomes and the methylation/expression levels of candidate genes in the EOC datasets. The STRING database was used to investigate the protein–protein interaction (PPI) for candidates and their associated genes. The infiltration level of immune cells in EOC patients and the association between clinical outcome and OCSCs differentiation genes were estimated using the TIDE and TIME2.0 algorithms. We established an EOC differentiation model using OCSCs. After an integrated transcriptomics and methylomics analysis of OCSCs differentiation, we revealed that the genes associated with earlier OCSC differentiation were better able to reflect the patient’s outcome. The OCSC differentiation genes were involved in regulating metabolism shift and the suppressive immune microenvironment. High GPD1 expression with high pro-tumorigenic immune cells (M2 macrophage, and cancer associated fibroblast) had worst survival. Moreover, we developed a methylation signature, constituted by GNPDA1, GPD1, GRASP, HOXC11, and MSLN, that may be useful for prognostic prediction in EOC. Our results revealed a novel role of epigenetic plasticity OCSC differentiation and suggested metabolic and immune intervention as a new therapeutic strategy.

Ultrasound-guided Percutaneous Core-needle Biopsy of Focal Pancreatic Lesions - Practical Aspectss.

Ultrasound-guided percutaneous core-needle biopsy is an excellent diagnostic tool for solid pancreatic lesions. It allows for identifying neoplastic pancreatic tumors with nearly 100% sensitivity, specificity and accuracy. Unresectable tumor assessment prior to planned palliative treatment is the primary indication for percutaneous pancreatic tumor biopsy. In the case of potential tumors eligible for radical surgery, endosonography-guided biopsy is used, if clinically necessary, to avoid the peritoneal spread of tumor cells during puncture. The possibility of obtaining a specimen for a detailed microscopic assessment during an easily accessible and simple procedure is the main advantage of core-needle biopsy over the low, yet higher when compared to other biopsy techniques, risk of complications. Obtaining tissue samples for molecular analysis is essential for palliative targeted therapy in pancreatic cancer and may become the main indication for the common core-needle biopsy of inoperable pancreatic tumors in the near future. The present paper describes the indications and the technique for core-needle biopsy in pancreatic tumors. Based on the studies published to date, the safety of the procedure, significant complications, including bleeding in particular, and the diagnostic sensitivity and specificity, also compared to other biopsy techniques, have been summarized. The present paper may contribute to the introduction of core-needle biopsy of pancreatic masses into clinical practice.

Current Medical Care Situation of Patients in Germany Undergoing Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC).

Simple SummaryThe treatment of peritoneal surface malignancies has evolved differently from other fields in surgical oncology in the past decades and modern approaches were introduced into daily-routine. Curative as well as palliative surgical treatment options redefined the fate of patients with this aggressive disease. Nowadays, patients with a limited peritoneal tumor spread of colonic origin have comparable survival rates compared with colorectal liver and pulmonary metastases. After the failure of systemic chemotherapy, the application of PIPAC revolutionized the palliative treatment for these patients and recent results show a high histological response rates, an improvement in quality-of-life and, furthermore, a cost-reduction compared to systemic chemotherapy. The application of PIPAC in other disease-settings (neoadjuvant/adjuvant) needs to be defined in further clinical trials.Objective: Tailored approaches in gastrointestinal oncology have been more frequently introduced in past years and for patients with peritoneal metastases. This article attempts to overview the current strategies in surgical gastrointestinal oncology, with a focus on gastrointestinal peritoneal metastases. Methods: In 2019, all patients undergoing PIPAC therapy in Germany were retrospectively analyzed regarding morbidity and in-hospital mortality rates. Furthermore, patients with chemotherapy-refractory peritoneal metastases from gastric cancer undergoing PIPAC-therapy at our institution were analyzed. Results: In 2019, 534 patients received PIPAC treatment in german hospitals. The in-hospital mortality rate was 0%. In total, 36 patients suffered from postoperative complications (8%). From April 2016 to September 2021, a total of 44 patients underwent 93 PIPAC applications at our institution. The non-access-rate was 0%. The median PRGS was two (range, 1–4). Eleven patients (44%) showed histologically stable disease, whereas six patients (24%) showed histological regression. Median survival, calculated from the date of the first PIPAC application, was 181 days (range, 43–636 days). Conclusions: PIPAC is a safe and feasible procedure with a low in-hospital morbidity and mortality. Furthermore, PIPAC in the palliative and chemorefractory setting and is an appealing approach for patient management in the future.

First experiences with PET-MRI/CT in radiotherapy planning for cervical cancer

PurposePET-CT has recently been included in the NCCN staging recommendations for cervical cancer stages II–IV and is already routinely applied to radiotherapy planning for other malignancies, as it is expected to provide higher accuracy for the detection of areas with tumor cell spread. In this study, we report on our first experiences of PET-based radiotherapy planning for cervical cancer.Methods19 patients with cervical cancer that underwent pre-therapeutic PET imaging treated at our institution between January 2016 and April 2019 were included in the study. Information on the primary tumor, lymph node involvement, metastatic spread and changes in the radiotherapy procedure based on the PET findings are described.ResultsA previously unknown primary tumor extension that was detected by PET imaging in one patient. In patients who underwent a PET before the systematic pelvic and paraaortic lymphonodectomy (n = 2), PET was false negative for pelvic lymph node metastases in 50%. In patients who underwent a PET after the systematic LNE (n = 13), additional lymph node metastases were detected in seven patients (53.80%). Distant metastases were suspected in three patients (15.7%) based on PET imaging. The suspicion was confirmed in one patient (peritoneal spread) and excluded in two patients (supra-diaphragmatic lymph nodes). In 13 patients (68.4%), RT procedures were altered due to findings in PET imaging.ConclusionPET-based radiochemotherapy planning may improve control rates by identifying areas of tumor cell spread eligible for dose escalation. False positivity, however, should be excluded in patients with findings that lead to major modifications of the therapeutic strategy.

Plasmacytoid urothelial carcinoma of the bladder: MRI features and their association with survival.

Plasmacytoid urothelial carcinomas (PUC) of the bladder are rare variants known for diffuse and infiltrative spread, however their magnetic resonance imaging (MRI) features are not well established. We aimed to evaluate MRI features of PUC of the bladder and their association with survival. This retrospective single-center study included 41 patients with pathologically-proven bladder PUC of the bladder that underwent pre-treatment MRI between January 2000 and March 2020. Two radiologists reviewed MRIs independently followed by consensus with a third radiologist. On MRI, tumor extent, size, Vesical Imaging-Reporting and Data System (VI-RADS) scores (≥4, muscle-invasive; 5, extravesical extension [EVE]), pelvic peritoneal spread (PPS), hydronephrosis, pelvic adenopathy and clinicopathological factors of age, gender, pathological stage, and treatment type were extracted. Kaplan-Meier curves and Cox proportional-hazards models were used to evaluate association with survival. Thirty-two men and 9 women (median age 70 years, IQR 64-76) were included. Most were muscle-invasive (n = 30 [73.2%]). On MRI, most tumors were diffuse (n = 28 [68.3%]), >5 cm (n = 30 [73.2%]), VI-RADS 4 to 5 (n = 36 [87.8%]) with features of EVE and (n = 31 [75.6%]) and PPS (n = 25 [61.0%]). Variables associated with survival were: Larger tumors (>5 cm; hazard ratio [HR] = 5.0; 95% confidence interval [CI] 1.6-15.5; P < 0.01), diffuse extent (HR = 4.0; 95% CI 1.4-11.2; P = 0.01), EVE (HR = 4.5; 95% CI 1.5-13.6; P < 0.01), PPS (HR = 3.0; 95% CI 1.2-7.4; P = 0.01), hydronephrosis (HR = 13.7; 95% CI 3.1-60.9; P < 0.01), pathologic stage (≥pT3 vs. pT1; HR = 5.6; 95% CI 1.3-22.0; P = 0.02), and margin positivity (HR = 4.4 [95% CI 1.2-16.4], P = 0.03). PUCs of the bladder are commonly large, diffuse VI-RADS score 4 to 5 tumors with MRI features of EVE and PPS. These features and pathological stage were associated with survival.

Computer-extracted features of nuclear morphology in hematoxylin and eosin images distinguish stage II and IV colon tumors.

We assessed the utility of quantitative features of colon cancer nuclei, extracted from digitized hematoxylin and eosin‐stained whole slide images (WSIs), to distinguish between stage II and stage IV colon cancers. Our discovery cohort comprised 100 stage II and stage IV colon cancer cases sourced from the University Hospitals Cleveland Medical Center (UHCMC). We performed initial (independent) model validation on 51 (143) stage II and 79 (54) stage IV colon cancer cases from UHCMC (The Cancer Genome Atlas's Colon Adenocarcinoma, TCGA‐COAD, cohort). Our approach comprised the following steps: (1) a fully convolutional deep neural network with VGG‐18 architecture was trained to locate cancer on WSIs; (2) another deep‐learning model based on Mask‐RCNN with Resnet‐50 architecture was used to segment all nuclei from within the identified cancer region; (3) a total of 26 641 quantitative morphometric features pertaining to nuclear shape, size, and texture were extracted from within and outside tumor nuclei; (4) a random forest classifier was trained to distinguish between stage II and stage IV colon cancers using the five most discriminatory features selected by the Wilcoxon rank‐sum test. Our trained classifier using these top five features yielded an AUC of 0.81 and 0.78, respectively, on the held‐out cases in the UHCMC and TCGA validation sets. For 197 TCGA‐COAD cases, the Cox proportional hazards model yielded a hazard ratio of 2.20 (95% CI 1.24–3.88) with a concordance index of 0.71, using only the top five features for risk stratification of overall survival. The Kaplan–Meier estimate also showed statistically significant separation between the low‐risk and high‐risk patients, with a log‐rank P value of 0.0097. Finally, unsupervised clustering of the top five features revealed that stage IV colon cancers with peritoneal spread were morphologically more similar to stage II colon cancers with no long‐term metastases than to stage IV colon cancers with hematogenous spread. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

New Frontiers in Management of Early and Advanced Rectal Cancer.

Simple SummaryRectal cancer has the capacity to present in a variety of forms. Depending on subtle differences in the characteristics of the tumor, it is possible for the treatment protocol to vary drastically. There are many tools available to optimize patients’ outcomes when treating rectal cancer of these various stages. Advances in early-stage, local presentation of rectal cancer focus on minimally invasive endoluminal surgery. Lesions completely responding to neoadjuvant chemoradiation non-operative surveillance have been explored. For rectal cancers patients with problematic pelvic anatomy, new platforms for resection, such as transanal total mesorectal excision and robotic total mesorectal excision, have been introduced. Late solid organ and peritoneal metastasis, originally thought to be a terminal disease, have undergone recent advances in hepatic and pulmonary metastasectomy, cytoreductive surgery, and intraperitoneal chemotherapy. Understanding these various therapeutic interventions will pave the way for improved patient outcomes.It is important to understand advances in treatment options for rectal cancer. We attempt to highlight advances in rectal cancer treatment in the form of a systematic review. Early-stage rectal cancer focuses on minimally invasive endoluminal surgery, with importance placed on patient selection as the driving factor for improved outcomes. To achieve a complete pathologic response, various neoadjuvant chemoradiation regimens have been employed. Short-course radiation therapy, total neoadjuvant chemotherapy, and others provide unique advantages with select patient populations best suited for each. With a clinical complete response, a “watch and wait” non-operative surveillance has been introduced with preliminary equivalency to radical resection. Various modalities for total mesorectal excision, such as robotic or transanal, have advantages and can be utilized in select patient populations. Tumors demonstrating solid organ or peritoneal spread, traditionally defined as unresectable lesions conveying a terminal diagnosis, have recently undergone advances in hepatic and pulmonary metastasectomy. Hepatic and pulmonary metastasectomy has demonstrated clear advantages in 5-year survival over standard chemotherapy. With the peritoneal spread of colorectal cancer, HIPEC with cytoreductive therapy has emerged as the preferred treatment. Understanding the various therapeutic interventions will pave the way for improved patient outcomes.

A Novel Multi-Port Containment System for Laparoscopic Power Morcellation to Prevent Tumoral Spread: A Retrospective Cohort Study.

ObjectiveTo report a novel multi-port containment (NMC) system for laparoscopic power morcellation to prevent tumoral spread and to evaluate its safety, validity, and feasibility.MethodsThis retrospective study included women who underwent laparoscopic myomectomy (LM) between January 2014 and August 2020 at a single academic institution. The NMC system was used in the study group (n = 193); the control group underwent unprotected LM (n = 1753).ResultsAfter 1:1 propensity score matching, no significant differences in the baseline characteristics were observed between 193 matched pairs. Bag damages were detected in two cases in the study group before morcellation, and the NMC systems were replaced. There were no significant differences between the two groups in terms of the complications, total operative time, estimated blood loss, or postoperative hospitalization duration. In the study group, all operations were completed and no system rupture or leakage was observed. The median follow-up times were 21 and 54 months in the study and control groups, respectively. There was no peritoneal tissue spread in the study group. However, three (3/5, 0.6%) and six (6/1,753, 0.3%) patients in the control group experienced malignant and benign peritoneal tissue spread, respectively.ConclusionThe NMC system for laparoscopic power morcellation is valid, safe, and feasible for preventing a tumor spread.

Correlation of circulating tumor DNA (ctDNA) with clinical outcomes in appendiceal cancers (AC).

29 Background: Appendiceal Cancers are a heterogenous group of rare tumors with distinct histopathologic and genomic alterations. These often have peritoneal spread that might not be easily detected on current imaging modalities, and conventional tumor markers may not lend diagnostic support. Hence, novel diagnostic techniques are needed. Measurement of ctDNA for recurrence risk prediction, response to therapy and and early diagnosis is a promising technique. However, limited published data exist in AC to validate the role and utility of ctDNA in clinical practice. Here we present a single institution experience of ctDNA analysis in patients with AC. Methods: ctDNA measurements of 37 pts with stage II-IV AC treated between 1/1/2019 and 9/15/2021 were reviewed retrospectively. ctDNA analysis was done using Signatera bespoke mPCR NGS assay. ctDNA results were compared to crossectional imaging, CEA levels, and clinical evaluation. Results: 19/37 patients (51%) had at least one positive ctDNA test result. Of those, 8 had testing done during the surveillance setting (two with grade 3, one with grade 2, two with grade 1, and three with unknown grade). Of those, 5 pts (62.5%) had positive ctDNA detected, while 33.33% had elevated CEA level, 25% had radiographic and 42.9% had clinical evidence of recurrence (Table). 7/14 (50%) pts had high-grade pathology and positive ct-DNA, 3/6 (50%) patients had low-grade (grade 1) pathology and positive ct-DNA findings. 4 patients had longitudinal ct-DNA measurements available which correlated well with their disease course. Median duration to recurrence (radiographic or laparoscopic) was 376 days. Median duration to the first positive ctDNA test was 370 days. Median duration to positive CEA after initial treatment was 475 days. Conclusions: Measurement of ctDNA can be a useful tool to follow disease course and to guide management decision-making in patients with AC. Prospective studies with serial measurements of ctDNA are planned. [Table: see text]

Intratumoral Bromelain and Acetylcysteine for Recurrent and Unresectable Pseudomyxoma Peritonei. A Phase I/II, unicentric study.

Background: Mucinous neoplasms with peritoneal spread constitute an infrequent entity known as Pseudomyxoma Peritonei. The massive intraabdominal affectation contrast with the optimistic prognosis owing to its histological low grade. Cytoreductive surgery and HIPEC are the standard treatment. Locoregional recurrence occurs in 20-30% of the cases. The scarce success of intravenous chemotherapy compel to iterative surgeries as the best treatment for recurrences. Hence, patients with several surgeries have an inadmissible morbidity risk for another cytoreduction in case of new relapses, being the supportive care the only available treatment.