Adoption of minimally invasive surgery after neoadjuvant chemotherapy in women with metastatic uterine cancer.

OBJECTIVE: Utilization of neoadjuvant chemotherapy (NACT) for advanced stage uterine cancer is increasing. We analyzed the use and outcomes of open versus minimally invasive surgery (MIS) for women with stage IV uterine cancer who received NACT and underwent IDS. METHODS: The National Cancer Database was used to identify women with stage IV uterine cancer diagnosed from 2010 to 2017 and treated with NACT. Among women who underwent IDS, overall survival (OS) was compared between those who underwent laparotomy vs a minimally invasive approach. To account for imbalances in confounders, a propensity score analysis using inverse probability of treatment weighting (IPTW) was performed. RESULTS: A total of 1618 women were identified. Minimally invasive IDS was performed in 31.1% and increased from 16.2% in 2010 to 40.4% in 2017 (P < 0.001). More recent year of diagnosis and performance of surgery at a comprehensive cancer center were associated with increased use of MIS (P < 0.05). Women with serous and clear cell tumors, and carcinosarcomas (compared to endometrioid tumors), as well as Medicaid coverage (compared to commercial insurance) were less likely to undergo an MIS approach (P < 0.05). The median OS was 28 months (95% CI 23.7-30.7) and 24.3 months (95% CI 22.3-26.1) for MIS and laparotomy, respectively. After propensity score balancing, there was no association between the use of MIS and survival (HR = 0.90, 95% CI 0.71-1.14). CONCLUSIONS: Among women with stage IV uterine cancer treated with NACT performance of minimally invasive debulking surgery is increasing. Compared to laparotomy, MIS does not appear to negatively impact survival.

Integration of proteomics with CT-based qualitative and radiomic features in high-grade serous ovarian cancer patients: an exploratory analysis.

OBJECTIVES: To investigate the association between CT imaging traits and texture metrics with proteomic data in patients with high-grade serous ovarian cancer (HGSOC). METHODS: This retrospective, hypothesis-generating study included 20 patients with HGSOC prior to primary cytoreductive surgery. Two readers independently assessed the contrast-enhanced computed tomography (CT) images and extracted 33 imaging traits, with a third reader adjudicating in the event of a disagreement. In addition, all sites of suspected HGSOC were manually segmented texture features which were computed from each tumor site. Three texture features that represented intra- and inter-site tumor heterogeneity were used for analysis. An integrated analysis of transcriptomic and proteomic data identified proteins with conserved expression between primary tumor sites and metastasis. Correlations between protein abundance and various CT imaging traits and texture features were assessed using the Kendall tau rank correlation coefficient and the Mann-Whitney U test, whereas the area under the receiver operating characteristic curve (AUC) was reported as a metric of the strength and the direction of the association. P values < 0.05 were considered significant. RESULTS: Four proteins were associated with CT-based imaging traits, with the strongest correlation observed between the CRIP2 protein and disease in the mesentery (p < 0.001, AUC = 0.05). The abundance of three proteins was associated with texture features that represented intra-and inter-site tumor heterogeneity, with the strongest negative correlation between the CKB protein and cluster dissimilarity (p = 0.047, τ = 0.326). CONCLUSION: This study provides the first insights into the potential associations between standard-of-care CT imaging traits and texture measures of intra- and inter-site heterogeneity, and the abundance of several proteins. KEY POINTS: • CT-based texture features of intra- and inter-site tumor heterogeneity correlate with the abundance of several proteins in patients with HGSOC. • CT imaging traits correlate with protein abundance in patients with HGSOC.

An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor.

OBJECTIVES: We evaluated four different treatment regimens for advanced-stage mucinous epithelial ovarian cancer. METHODS: We conducted a multicenter randomized factorial trial (UK and US). Patients were diagnosed with primary mEOC: FIGO stage II-IV or recurrence after stage I disease. Treatment arms were paclitaxel-carboplatin, oxaliplatin-capecitabine, paclitaxel-carboplatin-bevacizumab, or oxaliplatin-capecitabine-bevacizumab. Chemotherapy was given 3-weekly for 6 cycles, and bevacizumab (3-weekly) was continued as maintenance (for 12 cycles). Endpoints included overall-survival (OS), progression-free survival (PFS), toxicity and quality of life (QoL). RESULTS: The trial stopped after 50 patients were recruited due to slow accrual. Median follow-up was 59 months. OS hazard ratios (HR) for the two main comparisons were: 0.78 (p = 0.48) for Oxal-Cape vs. Pac-Carbo (each with/without bevacizumab), and 1.04 (p = 0.92) for bevacizumab vs. no bevacizumab. Corresponding PFS HRs were: 0.84 and 0.80. Retrospective central pathology review revealed only 45% (18/40) cases with available material had confirmed primary mEOC. Among these, OS HR for Oxal-Cape vs. Pac-Carbo was 0.36 (p = 0.14); PFS HR = 0.62 (p = 0.40). Grade 3-4 toxicity was seen in 61% Pac-Carbo, 61% Oxal-Cape, 54% Pac-Carbo-Bev, and 85% Oxal-Cape-Bev. QoL was similar between the four arms. CONCLUSION: mEOC/GOG0241 represents an example of a randomized rare tumor trial. Logistical challenges led to early termination, including difficulties in local histopathological diagnosis and accessing drugs outside their labelled indication. There was misalignment between central funders who support clinical trials in rare cancers and the deprioritisation of such work by those managing and funding research at a local level. Rare cancer trials should include centralised pathology review before treatment. Clinical trial registry number: ISRCTN83438782.

SOX2 and SOX9 are markers of clinically aggressive disease in metastatic high-grade serous carcinoma.

OBJECTIVE: The aim of this study was to analyze the expression, biological role and clinical relevance of cancer stem cell markers in high-grade serous carcinoma (HGSC). METHODS: mRNA expression by qRT-PCR of NANOG, OCT4, SOX2, SOX4, SOX9, LIN28A and LIN28B was analyzed in 134 HGSC specimens (84 effusions, 50 surgical specimens). Nanog, OCT3/4, SOX2 and SOX9 protein expression by immunohistochemistry was analyzed in 52 HGSC effusions. Nanog protein expression in exosomes from 80 HGSC effusions was studied by Western Blotting. OVCAR3 cells underwent CRISPR/Cas9 Nanog knockout (KO), and the effect of Nanog KO on migration, invasion, proliferation and proteolytic activity was analyzed in OVCAR3 and OVCAR8 cells. RESULTS: OCT4 mRNA was overexpressed in effusions compared to solid specimens (p = 0.046), whereas SOX9 was overexpressed in the ovarian tumors compared to effusions and solid metastases (p = 0.003). Higher SOX2 and SOX9 expression was associated with primary (intrinsic) chemoresistance (p = 0.009 and p = 0.02, respectively). Higher SOX9 levels were associated with shorter overall survival in univariate (p = 0.04) and multivariate (p = 0.049) analysis. OCT3/4, SOX2 and SOX9 proteins were found in HGSC cells, whereas Nanog was detected only in exosomes. Higher SOX2 protein expression was associated with shorter overall survival in univariate analysis (p = 0.049). OVCAR cells exposed to OVCAR3 NANOG KO exosomes had reduced migration, invasion and MMP9 activity. CONCLUSIONS: SOX2 and SOX9 mRNA levels in HGSC effusions may be markers of clinically aggressive disease. Nanog is secreted in HGSC exosomes in effusions and modulates tumor-promoting cellular processes in vitro.

Evidence for lineage continuity between early serous proliferations (ESPs) in the Fallopian tube and disseminated high-grade serous carcinomas.

The distal Fallopian tube is a site of origin for many 'ovarian' high-grade serous carcinomas (HGSCs) with intraepithelial carcinomas (STICs) that share identical TP53 mutations with metastatic tumors. TP53 mutation-positive early serous proliferations (ESPs) comprise a spectrum including p53 signatures and serous tubal intraepithelial lesions (STILs) and are not considered malignant; however, ESPs are often the only abnormality found in Fallopian tubes of women with metastatic HGSC. The purpose of this study was to determine if a relationship exists between isolated ESPs and concurrent metastatic HGSCs in the absence of STIC. Fallopian tubes from 32 HGSCs without a co-existing STIC/HGSC in the endosalpinx were exhaustively sectioned. The presence of either STIC/HGSC or ESP in the endosalpinx was documented and DNA from tissues containing ESPs, concurrent HGSC, and control epithelia were interrogated for TP53 mutations by targeted amplicon-based sequencing with average coverage reads >4000 across DNA replicate samples. Serial sectioning revealed a previously unrecognized STIC/HGSC in 3 of 32 (9.3%) and ESPs in 13 (40.6%). Twelve contained TP53 mutations. Nine (75%) shared identical TP53 mutations with concurrent HGSCs, four at high (≥ 5%) and five at low (< 5%) allele frequency. All control epithelia were TP53 mutation-negative. This study, for the first time, indicates lineage identity between ESPs in the distal tube and some metastatic HGSCs via a shared site-specific TP53 mutation. It supports a novel serous carcinogenic sequence in which an ESP could eventually culminate in a metastatic serous cancer via 'precursor escape' and would explain the apparent sudden onset of cancers without co-existing STICs. This paradigm for serous cancer development underscores the likelihood that multiple precursor types in the Fallopian tube contribute to serous cancer development with implications for the evolution, pathologic classification, and prevention of this lethal malignancy. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Peritoneal Carcinomatosis of Rare Ovarian Origin Treated by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Multi-Institutional Cohort from PSOGI and BIG-RENAPE.

PURPOSE: Ovarian cancer is the most common deadly cancer of gynecologic origin. Patients often are diagnosed at advanced stage with peritoneal metastasis. There are many rare histologies of ovarian cancer; some have outcomes worse than serous ovarian cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can be considered for patients with recurrence. This study was designed to assess the impact of CRS and HIPEC on survival of patient with peritoneal metastasis from rare ovarian malignancy. METHODS: A prospective, multicentric, international database was retrospectively searched to identify all patients with rare ovarian tumor (mucinous, clear cells, endometrioid, small cell hypercalcemic, and other) and peritoneal metastasis who underwent CRS and HIPEC through the Peritoneal Surface Oncology Group International (PSOGI) and BIG-RENAPE working group. The postoperative complications, long-term results, and principal prognostic factors were analyzed. RESULTS: The analysis included 210 patients with a median follow-up of 43.5 months. Median overall survival (OS) was 69.3 months, and the 5-year OS was 57.7%. For mucinous tumors, median OS and DFS were not reached at 5 years. For granulosa tumors, median overall survival was not reached at 5 years, and median DFS was 34.6 months. Teratoma or germinal tumor showed median overall survival and DFS that were not reached at 5 years. Differences in OS were not statistically significant between histologies (p = 0.383), whereas differences in DFS were (p < 0.001). CONCLUSIONS: CRS and HIPEC may increases long-term survival in selected patients with peritoneal metastasis from rare ovarian tumors especially in mucinous, granulosa, or teratoma histological subtypes.

Expression and clinical role of long non-coding RNA in high-grade serous carcinoma.

OBJECTIVE: To profile long non-coding RNA (lncRNA) expression at the various anatomic sites of high-grades serous carcinoma (HGSC) and in effusion-derived exosomes. METHODS: LncRNA profiling was performed on 60 HGSC specimens, including 10 ovarian tumors, 10 solid metastases and 10 malignant effusions, as well as exosomes from 30 effusion supernatants. Anatomic site-related expression of ESRG, Link-A, GAS5, MEG3, GATS, PVT1 H19, Linc-RoR, HOTAIR and MALAT1 was validated by quantitative PCR and assessed for clinical relevance in a series of 77 HGSC effusions, 40 ovarian carcinomas, 21 solid metastases and 42 supernatant exosomes. RESULTS: Significantly different (p<0.05) expression of 241, 406 and 3634 lncRNAs was found in comparative analysis of the ovarian tumors to solid metastases, effusions and exosomes, respectively. Cut-off at two-fold change in lncRNA expression identified 54 lncRNAs present at the 3 anatomic sites and in exosomes. Validation analysis showed significantly different expression of 5 of 10 lncRNAs in the 4 specimen groups (ESRG, Link-A, MEG3, GATS and PVT1, all p<0.001). Higher ESRG levels in HGSC effusions were associated with longer overall survival in the entire effusion cohort (p=0.023) and in patients with pre-chemotherapy effusions tapped at diagnosis (p=0.048). Higher Link-A levels were associated with better overall (p=0.015) and progression-free (p=0.023) survival for patients with post-chemotherapy effusions. Link-A was an independent prognostic marker in Cox multivariate analysis in the latter group (p=0.045). CONCLUSIONS: We present the first evidence of differential LncRNA expression as function of anatomic site in HGSC. LncRNA levels in HGSC effusions are candidate prognostic markers.

Is it necessary to perform routine appendectomy for mucinous ovarian neoplasms? A retrospective study and meta-analysis.

OBJECTIVES: To evaluate whether routine appendectomy is necessary in all patients with mucinous borderline ovarian tumor (mBOT) or mucinous ovarian cancer (MOC) who undergo gynecologic surgery. METHODS: The database of Qilu Hospital was searched for women who underwent appendectomy in a primary surgery for an ovarian tumor between June 2005 and June 2015 and whose final diagnosis was mBOT, MOC or primary appendiceal tumor. A retrospective review was performed, as well as a meta-analysis of the literature to further validate the findings. RESULTS: Seventy-one patients, 29 with mBOT and 42 with malignant mucinous tumors (including 40 with primary MOC and 2 with appendiceal mucinous adenocarcinoma), underwent appendectomy at the time of primary surgery. Among those with mBOT, two (6.9%) appendices were grossly abnormal and pathologically diagnosed with appendiceal implantation by mBOT. In the 42 patients with malignant disease, five (12%) appendices had a grossly abnormal appearance, one (2.4%) was diagnosed with an appendiceal metastasis from MOC and two (4.7%) were primary appendiceal adenocarcinoma. For grossly normal appendices, only one (2.4%) was confirmed to have microscopic metastasis from MOC. The meta-analysis included a total of 914 mBOT and MOC cases with appendectomies, including our current cases. The estimated rate of overall appendiceal pathology is 4.97%, and the pooled odds ratio (OR) showed statistical differences between MOC and mBOT (MOC vs. mBOT, OR=2.15, P<0.05). The estimated malignant pathology rate in macroscopically normal vs. abnormal appendices is 1.4% and 59%, respectively, with an estimated OR up to 97.5 (95% CI 28.1-338.5, P<0.05). CONCLUSION: There is not sufficient evidence to support a routine appendectomy for patients with a grossly normal appendix in mBOT and MOC. A careful intra-operative exploration of the appendix is crucial, but appendectomy is only warranted when the appendix is abnormal.

Subtypes of stage IV ovarian cancer; response to treatment and patterns of disease recurrence.

BACKGROUND: To compare three different patterns of stage IV epithelial ovarian cancer; pleural effusion, parenchymal metastases and extra-abdominal lymph node metastases with treatment response and pattern of disease recurrence, and correlate treatment modality with outcome. METHODS: Retrospective analysis of FIGO stage IV epithelial ovarian cancer diagnosed between 2008 and 2012 in three gynaecologic oncology centres in New Zealand. RESULTS: 124 patients were analysed, 58 had pleural effusions, 38 parenchymal metastases, and 28 extra-abdominal lymph nodes. There was no significant difference in overall survival between these three groups. The most common site of first or any recurrence in all three groups was the abdomen with only a small number of recurrences arising in extra-abdominal sites. When looking at treatment modality, 13% had primary debulking surgery, 47% had neoadjuvant chemotherapy with interval debulking surgery, and 40% never had surgery. Overall survival was highest in patients with no residual abdominal disease after surgery. CONCLUSION: The site of extra-abdominal disease did not alter prognosis or pattern of disease recurrence in stage IV epithelial ovarian cancer, with most recurrences in the abdomen suggesting controlling abdominal disease with surgery may be important in all stage IV disease.

Coalition of Oct4A and ß1 integrins in facilitating metastasis in ovarian cancer.

BACKGROUND: Ovarian cancer is a metastatic disease and one of the leading causes of gynaecology malignancy-related deaths in women. Cancer stem cells (CSCs) are key contributors of cancer metastasis and relapse. Integrins are a family of cell surface receptors which allow interactions between cells and their surrounding microenvironment and play a fundamental role in promoting metastasis. This study investigates the molecular mechanism which associates CSCs and integrins in ovarian cancer metastasis. METHODS: The expression of Oct4A in high-grade serous ovarian tumors and normal ovaries was determined by immunofluorescence analysis. The functional role of Oct4A was evaluated by generating stable knockdown (KD) of Oct4A clones in an established ovarian cancer cell line HEY using shRNA-mediated silencing. The expression of integrins in cell lines was evaluated by flow cytometry. Spheroid forming ability, adhesion and the activities of matrix metalloproteinases 9/2 (MMP-9/2) was measured by in vitro functional assays and gelatin zymography. These observations were further validated in in vivo mouse models using Balb/c nu/nu mice. RESULTS: We report significantly elevated expression of Oct4A in high-grade serous ovarian tumors compared to normal ovarian tissues. The expression of Oct4A in ovarian cancer cell lines correlated with their CSC-related sphere forming abilities. The suppression of Oct4A in HEY cells resulted in a significant diminution of integrin ß1 expression and associated α5 and α2 subunits compared to vector control cells. This was associated with a reduced adhesive ability on collagen and fibronectin and decreased secretion of pro-MMP2 in Oct4A KD cells compared to vector control cells. In vivo, Oct4A knock down (KD) cells produced tumors which were significantly smaller in size and weight compared to tumors derived from vector control cells. Immunohistochemical analyses of Oct4A KD tumor xenografts demonstrated a significant loss of cytokeratin 7 (CK7), Glut-1 as well as CD34 and CD31 compared to vector control cell-derived xenografts. CONCLUSION: The expression of Oct4A may be crucial to promote and sustain integrin-mediated extracellular matrix (ECM) remodeling requisite for tumor metastasis in ovarian cancer patients.

Brain metastases in patients with EOC: Clinico-pathological and prognostic factors. A multicentric retrospective analysis from the MITO group (MITO 19).

BACKGROUND: Brain metastases (BM) from epithelial ovarian cancer (EOC) are considered a rare and unfavourable event. There is no consensus regarding the best management of these patients. METHODS: A multicenter retrospective analysis of patients with BM from EOC treated between 1997 and 2014 in 18 institutions of the MITO (Multicenter Italian Trials in Ovarian cancer) group was conducted. Univariate and multivariate analysis were performed. RESULTS: A total of 174 women were identified as having BM from EOC. The median time interval between primary diagnosis of EOC and occurrence of BM was 26months (range 2-129months). The median overall survival from primary EOC diagnosis was 48months (95% CI 39.5-56.4months) and from diagnosis of BM was 12months (95% CI 9.6-14.3months). The majority of enrolled women (81.7%) were classified as sensitive to platinum-based chemotherapy. Four variables were significantly associated with poor overall survival in multivariate analysis: multiple BM [HR: 1.86 (95% CI: 1.22-2.84)], presence of extracranial disease [HR: 1.77 (95% CI: 1.11-2.83)] age [HR: 1.74 (95% CI: 1.17-2.59)], and monotherapy [HR: 2.57 (95% CI: 1.64-3.86)]. On the contrary, residual tumor at primary surgery, FIGO stage at primary diagnosis and platinum sensitivity were found to have no significant impact on survival from diagnosis of brain lesions. CONCLUSIONS: Our results suggest that BM is a rare and late manifestation of EOC, with a 12-month life-span expectation. Multiple approach is a positive independent prognostic factor and should be proposed to carefully selected patients.

Widespread cutaneous metastasis from ovarian serous adenocarcinoma.

Cutaneous metastasis can be rarely first manifestation of internal cancers; these usually develop with advanced stage malignancies. Cutaneous metastasis of ovarian cancer is rare and the majority of are seen around the pelvic region compatible with the localization of the primary ovarian tumor. Herein, we report a patient with ovarian cancer with widespread and distant cutaneous metastases showing multiple nodules and ulcers.

Late recurrence of ovarian cancer: a literature review and description of two cases.

Ovarian cancer is not the most frequent malignancy of female reproductive system, but it causes many deaths in women with this diagnosis. Mostly of the patients with ovarian cancer will have recurrence after first-line standard treatment containing surgery and chemotherapy. This article presents two cases with late recurrence in women with ovarian cancer; both were nine years after the first diagnosis and both were operated and received second-line chemotherapy. The authors reviewed medical literature with late recurrence of ovarian cancer.

Evaluation of residual tumor locations in advanced ovarian cancer patients after incomplete primary cytoreduction.

BACKGROUND: Nowadays complete primary cytoreduction can be achieved in a large number of patients suffering from advanced ovarian cancer. However, there is a group of patients in whom complete tumor resection remains impossible. The authors analyzed the intraoperative limiting factors in patients with residual tumor after primary surgery treated in the present institution. MATERIALS AND METHODS: Patients with advanced epithelial ovarian cancer (FIGO Stage IIIB-IV), who underwent primary incomplete surgery in the present institution between 2006 and 2008 were included in this study. Patients' records were evaluated regarding to intraoperative findings and final surgical results. RESULTS: The authors identified 39 eligible patients in their registry. Twenty-six (66.7%) patients underwent surgery with residual tumor < 1 cm and 13 (33.3%) ≥ 1 cm. The most frequent location of residual tumor limiting complete surgery was disseminated bowel carcinomatosis in 34 (87.2%) patients. Moreover significant differences in tumor residuals locations and operative time between patients with residuals < 1 cm and ≥ 1 cm were reported (p < 0.05). CONCLUSIONS: The most frequent reason for incomplete primary cytoreduction remains disseminated carcinomatosis. However, in patients with residuals under one cm, its frequency is significantly higher. The complication rate is comparable in patients independently of residual tumor < 1 cm and ≥ 1 cm. Therefore the cytoreductive efforts should be made even in primarily not completely operated patients in order to achieve residuals under one cm.

Expression of CD133 and CD117 in 64 Serous Ovarian Cancer Cases.

The cancer stem cells (CSCs) represent a minority of tumor cells that are able to proliferate and self-renew and might be responsible for tumor initiation and maintenance. The CD133 and CD117 are the most commonly used markers for the putative CSCs, especially for the ovarian CSCs, but its clinical significance remains uncertain. The aim of this study was to compare the immunohistochemical expression of CD133 and CD117 in 64 primary ovarian high grade serous carcinoma and peritoneal metastasis, and to examine their potential clinical role. CD133 expression was mainly seen in the apical/endoluminal cell surface of tumor cells and was found in 61% of the carcinoma samples and 41% of the metastasis. The median of CD133 positive cells in tumors was 1 (0.1-7)%, and in metastases was 0.6 (0.1-6)%. CD117 expression appeared as a cytoplasmic and/or membranous stain and was found in 81% of the carcinoma samples and 77% of the metastasis. The median of CD117 positive cells in tumors was 1 (0.1-8)%, and in metastases was 0.1 (0.1-7)%. Multivariate analysis has shown that patients with high CD133 expression in tumor cells have significantly shorter disease free survival and overall survival (p=0.025 and p=0.014, respectively). Patients with high CD117 expression in tumor cells have significantly shorter disease free survival (p=0.031). Cox's proportional hazards model identified expression of CD133 protein in tumor as an independent prognostic factor. Our study indicates that the immunohistochemical assessment of CD133 and CD117 expression may have potential clinical value in predicting disease progression and prognosis in the high grade serous ovarian cancer. CD133 proved to be an independent prognostic factor in the high grade serous ovarian cancer patients.

Multiple MAGE-A genes as surveillance marker for the detection of circulating tumor cells in patients with ovarian cancer.

Ovarian cancer is a leading cause of death among gynecologic malignancies. In this study, we reported the expression of melanoma-associated antigens A (MAGE-A) genes in peripheral blood from 80 patients with ovarian cancer and 30 healthy donors. MAGE-As expression was associated with the factors indicating poor prognosis. The expressions of MAGE-As and each individual MAGE-A genes were also associated with low overall survival of patients with ovarian cancer. Our results suggested MAGE-A genes may have the potential to be surveillance markers for the detection of circulating tumor cells and represent a poor prognosis for patients with ovarian cancer.

The differences in clinicopathological features and prognosis among the subtypes of signet ring cell, mucinous, papillary, and lymphoepithelioma-like carcinoma in advanced gastric cancer.

BACKGROUND/AIMS: There are differing histologic subtypes of gastric cancer. We investigated the clinicopathological features and prognosis of: signet ring cell (SRC), mucinous (MGC), papillary (PGC), and lymphoepithelioma-like (LELC) carcinoma in advanced gastric cancer. METHODOLOGY: One hundred thirty six advanced gastric cancer patients, including 62 SRCs, 43 MGCs, 9 PGCs, and 22 LELCs, who underwent R0 gastrectomy between 2002 and 2013, were retrospectively evaluated. RESULTS: There were significant differences in several clinicopathological features. There were found to be statistical differences in postoperative outcomes in the type of gastrectomy and type of anastomosis (p<0.001 and p<0.001, respectively). In terms of overall survival analysis, there was no statistical survival difference among the subtypes of advanced gastric cancer (p=0.088). However, LELC had a better prognosis than the other groups. CONCLUSIONS: There were some differences in several of the clinicopathological features of the subtypes advanced gastric cancer. Although there were no statistical differences in survival, those with LELC showed a better prognosis than did the other groups. Therefore, the treatment of advanced gastric cancer should be individualized, and prognosis considered, according to the subtype.

Glisson's capsule blistering after hyperthermic intraperitoneal chemotherapy.

Hypertermic intraperitoneal chemotherapy is a treatment option after cytorreduction of certain types of malignancies with peritoneal spread. Blistering of the Glisson's capsule has not been previously reported as a consequence of this treatment modality. Patient do not experiment any associated morbidity.

Total parietal peritonectomy performed during interval cytoreductive surgery for advanced epithelial serous ovarian cancer results in a low incidence of platinum resistant recurrence- results of a prospective multi-centre study.

BACKGROUND: The reported incidence of platinum resistant recurrence (PRR) (recurrence within 6 months of the last dose of platinum therapy) after interval debulking/cytoreductive surgery (CRS) is high compared to that after primary CRS. The goal was to study PRR following a total parietal peritonectomy (TPP), that addresses occult disease more completely. METHODS: This is a prospective multi-center study (CTRI/2018/08/015350). A TPP was performed during interval CRS following a fixed surgical protocol. Patients with a follow-up of 6 months(M) or more were included in this analysis. The incidence and patterns of PRR and factors affecting recurrence were analyzed. RESULTS: From July 2018 to October 2019, 70 patients with serous carcinoma were included. The median surgical PCI was 15 [range 5-37]. A CC-0 resection was obtained in 55 (78.5%); CC-1 in 10 (14.2%). Occult residual disease was seen in 40%. At a median follow-up of 13 months, 17 (24.2%) had developed recurrence/progression. PRR was seen in 5 (7.1%) patients. The sites of progression (>1 in 2 patients) were pleura (n = 1), visceral peritoneum (n = 2), retroperitoneal nodes (n = 2), mediastinal nodes (n = 1) and small bowel mesentery (n = 2). Overall, though the most common site of recurrence was the visceral peritoneum (N = 9), seven (>40%) patients did not develop recurrence in the visceral peritoneum. Patients with high PCI and grade 3-4 complications had a higher probability of developing recurrence. CONCLUSIONS: TPP performed during interval CRS resulted in a very low incidence of PRR. These findings need confirmation in a larger series. The benefit of TPP over conventional surgery should be evaluated in a randomized trial.