Assessing morbidity, mortality, and survival in patients with peritoneal carcinomatosis undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy / Avaliação da morbimortalidade e da sobrevida em pacientes portadores de carcinomatose peritoneal submetidos a cirurgia citorretorredutora e quimioterapia hipertérmica intraperitoneal (HIPEC)

ABSTRACT Peritoneal carcinomatosis (PC) indicates advanced stage cancer, which is generally associated with a poor outcome and a 6 to 12 months. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an option for treating patients with primary PC, such as mesothelioma, or secondary PC, such as colorectal cancer (CRC) or pseudomixoma. Until recently, such patients were deemed untreatable. Objective: The purpose of this study was to assess the results of CRS + HIPEC in patients with PC. Postoperative complications, mortality and survival rates were evaluated according to the diagnosis. Results: Fifty-six patients with PC, undergoing full CRS + HIPEC between October 2004 and January 2020, were enrolled. The mortality rate was 3.8% and the morbidity rate was 61.5%. Complications were significantly higher in proportion to the duration of surgery (p<0.001). The overall survival rates, as shown in the Kaplan-Meyer curve, were respectively 81%, 74% and 53% at 12, 24 and 60 months. Survival rates according to each diagnosis for the same periods were 87%, 82% and 47% in patients with pseudomixoma, and 77%, 72% and 57% in patients with CRC (log-rank 0.371, p=0.543). Conclusion: CRS with HIPEC is an option for pacients with primary or secondary PC. Although complication rates are high, a longer survival rate may be attained compared to those seen in previously published results; in some cases, patients may even be cured.

RESUMO O diagnóstico de carcinomatose peritoneal (CP), indica um estágio avançado do câncer e em geral está associado a um mau prognóstico com sobrevida média variando de 6 a 12 meses. A cirurgia citorredutora (CRS) associada à quimioterapia intraperitoneal hipertérmica (HIPEC) tem sido descrita como uma opção de tratamento para os pacientes portadores de CP primária como nos portadores de mesotelioma, ou secundária como em portadores de cancer colorretal ou pseudomixoma, até recentemente considerados sem possibilidade terapêutica. Objetivo: Avaliar os resultados do tratamento de pacientes portadores de CP submetidos a CRS + HIPEC. Foram analisadas as taxas complicações pós-operatórias, mortalidade e a sobrevida desses pacientes. Resultados: Foram incluídos 56 pacientes com CP, submetidos a c CRS + HIPEC, no período de Outubro 2004 a Janeiro 2020. A taxa de mortalidade foi de 3,8% e taxa de morbidade de 61,5%, sendo a ocorrência de complicações significativamente maior quanto maior o tempo cirúrgico (p<0,001). A sobrevida global pela curva de Kaplan-Meyer foi de 81%, 74% e 53% em 12, 24 e 60 meses respectivamente. Já a sobrevida por diagnóstico nos mesmos períodos foi de 87%, 82%, 47% para os pacientes portadores de pseudomixoma e de 77%, 72% e 57% para pacientes portadores de câncer colorretal (Log -RANK 0,371, p=0,543). Conclusão: A CRS + HIPEC é uma opção de tratamento para pacientes portadores de CP primária ou secundária. Embora com taxa de complicações elevadas, pode proporcionar aumento da sobrevida quando comparado com resultados prévios da literatura e em alguns casos até a cura.

Prognosis and influencing factors of platinum sensitive recurrent ovarian cancer treated by secondary cytoreduction surgery in patients with unsatisfactory primary cytoreduction surgery / 国际肿瘤学杂志

Objective:To investigate the prognosis and influencing factors of secondary cytoreduction surgery (SCS) in patients with platinum-sensitive recurrent ovarian cancer whose tumor reduction with unsatisfactory primary cytoreduction surgery.Methods:The clinical and follow-up data of 116 patients with platinum-sensitive recurrent ovarian cancer whose tumor reduction with unsatisfactory primary cytoreduction surgery and received the first diagnosis and operation in Shanxi Provincial Cancer Hospital from January 2005 to December 2018 were retrospectively analyzed. Among them, 33 patients received SCS+chemotherapy and 83 patients received chemotherapy alone. In order to eliminate the component differences in general clinical data between the two groups, 28 pairs total 56 patients were selected from each group to form a matching cohort by propensity score matching, and their data were analyzed. The main outcome measures were progression-free survival (PFS) and overall survival (OS). Kaplan-Meier method was used to draw the survival curve accompanied with log-rank test. Cox regression model was used to analyze the prognostic factors of patients with platinum-sensitive recurrent ovarian cancer whose tumor reduction with unsatisfactory primary cytoreduction surgery.Results:The median PFS of 56 matched patients with platinum-sensitive recurrent ovarian cancer whose tumor reduction with unsatisfactory primary cytoreduction surgery was 9.0 months. The 0.5- and 1-year PFS rates were 67.9% and 25.0% respectively. The median OS of 56 patients was 57.5 months. The 3- and 5-year OS rates were 60.7% and 39.3% respectively. The median PFS was 10.5 months in the SCS+chemotherapy patients and 7.5 months in the chemotherapy alone patients, and the 0.5- and 1-year PFS rates were 82.1% vs. 57.1% and 32.1% vs. 21.4% respectively, with a statistically significant difference ( χ2=3.88, P=0.049). The median OS was 70.0 months in the SCS+chemotherapy patients, and 60.0 months in the chemotherapy alone patients, and the 3- and 5-year OS rates of the SCS+chemotherapy patients and chemotherapy alone patients were 88.5% vs. 64.3% and 70.0% vs. 53.0%, with no statistically significant difference ( χ2=3.63, P=0.057). Univariate analysis showed that International Federation of Gynecology and Obstetrics (FIGO) staging ( HR=3.17, 95% CI: 1.32-7.59, P=0.010) and treatment-free interval from the last platinum (TFIp) ( HR=0.35, 95% CI: 0.18-0.68, P=0.002) were independent influencing factors of PFS in patients with platinum-sensitive recurrent ovarian cancer whose tumor reduction with unsatisfactory primary cytoreduction surgery. Carbohydrate antigen 125 ( HR=2.46, 95% CI: 1.21-5.00, P=0.013) was an independent influencing factor of OS in patients with platinum-sensitive recurrent ovarian cancer whose tumor reduction with unsatisfactory primary cytoreduction surgery. Multivariate analysis showed that FIGO staging ( HR=2.95, 95% CI: 1.18-7.36, P=0.020) and TFIp ( HR=0.33, 95% CI: 0.16-0.66, P=0.002) were independent prognostic factors of PFS. Conclusion:For platinum-sensitive recurrent ovarian cancer patients who do not achieve satisfactory tumor reduction after primary cytoreduction surgery, but achieve clinical complete response after postoperative chemotherapy, SCS may prolong their PFS after treatment, and OS also shows a beneficial trend after treatment, but with no statistically significant difference. FIGO staging at initial treatment and TFIp before the first relapse are independent prognostic factors of PFS in patients with platinum-sensitive recurrent ovarian cancer whose tumor reduction with unsatisfactory primary cytoreduction surgery.

Research progress of hyperthermic intraperitoneal chemotherapy in the treatment of colorectal cancer / 国际外科学杂志

Colorectal cancer is a common digestive system malignant tumor in the world, its incidence and mortality rate is in the forefront, with the social progress and the change of diet structure, the incidence of colorectal cancer is gradually increasing, and there is a trend of younger age. Among them, peritoneal metastasis is the main cause of death in patients with colorectal cancer. Non-surgical treatment has been used in the past, but the prognosis is poor. How to treat and prevent peritoneal metastasis in colorectal cancer patients and improve the prognosis of such patients as much as possible is a question worth our in-depth study. The hyperthermic intraperitoneal chemotherapy provides a new direction for the treatment of colorectal cancer patients, usually combined with surgical treatment, and co-applied in the clinic as a new treatment model. This article reviews the treatment mode of hyperthermic intraperitoneal chemotherapy, the choice of drugs, and the progress of research in the treatment and prevention of peritoneal metastasis in colorectal cancer.

The expression and significance of protease activated receptor 2 in ovarian epithelial carcinoma / 中华肿瘤杂志

Objective: To investigate the expression and significance of protease activated receptor 2 (PAR2) in ovarian epithelial carcinoma. Methods: PAR2 mRNA expression levels in 410 cases of epithelial ovarian carcinoma and 88 cases of human normal ovary were analyzed from cancer Genome Atlas (TCGA) database and tissue genotypic expression database (GTEx). Immunohistochemical (IHC) staining of PAR2 protein was performed in 149 patients with ovarian cancer who underwent primary surgical treatment at Cancer Hospital of Chinese Academy of Medical Sciences. Then the relationship between mRNA/protein expression of PAR2 and clinicopathological features and prognosis was analyzed. Gene functions and related signaling pathways involved in PAR2 were studied by enrichment analysis. Results: The mRNA expression of PAR2 in epithelial ovarian carcinoma was significantly higher than that in normal ovarian tissue (3.05±0.72 vs. 0.33±0.16, P=0.004). There were 77 cases showing positive and 19 showing strong positive of PAR2 IHC staining among the 149 patients, accounting for 64.4% in total. PAR2 mRNA/protein expression was closely correlated with tumor reduction effect and initial therapeutic effect (P<0.05). Survival analysis showed that the progression free survival time (P=0.033) and overall survival time (P=0.011) in the group with high PAR2 mRNA expression was significantly lower than that in the low PAR2 mRNA group. Multivariate analysis showed tumor reduction effect, initial therapeutic effect were independent prognostic factors on both progression-free survival and overall survival (P<0.05). The progression-free survival (P=0.016) and overall survival (P=0.038) of the PAR2 protein high expression group was significantly lower than that of the low group. Multivariate analysis showed PAR2 expression, initial treatment effect and chemotherapy resistance were independent prognostic factors on both progression-free survival and overall survival (P<0.05). Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), PAR2 target genes were mainly enriched in function related to intercellular connection, accounting for 40%. Gene enrichment analysis (GSEA) showed that the Wnt/β-catenin signaling pathway (P=0.023), the MAPK signaling pathway (P=0.029) and glycolysis related pathway (P=0.018) were enriched in ovarian cancer patients with high PAR2 mRNA expression. Conclusions: PAR2 expression is closely related to tumor reduction effect, initial treatment effect and survival of ovarian cancer patients. PAR2 may be involved in Wnt/β-catenin signaling pathway and intercellular connection promoting ovarian cancer invasion and metastasis.

Estadificación laparoscópica en pacientes con carcinomatosis peritoneal. Un enfoque desde la cirugía citorreductiva / Laparoscopic staging in patients with peritoneal carcinomatosis. An approach from cytoreductive surgery

Introducción. Las metástasis peritoneales representan un estado avanzado de muchos cánceres intraabdominales y suelen dar un pronóstico ominoso a los pacientes que las desarrollan. Hasta hace poco la única opción terapéutica para este escenario era la quimioterapia paliativa. Sin embargo, la mayoría de los tumores metastásicos al peritoneo continúan siendo relativamente resistentes a las drogas citotóxicas y citostáticas administradas por vía endovenosa y, en general, a las terapias individuales. Métodos. Se realizó una búsqueda de la literatura en las bases de datos de PubMed, SciELO y Google Scholar utilizando las palabras claves: laparoscopia, carcinomatosis peritoneal, estadificación, citorreducción. Se incluyeron para la revisión los artículos con mayor relevancia publicados en inglés y español. Discusión. La cirugía citorreductiva asociada a técnicas de quimioterapia hipertérmica intraperitoneal se ofrece actualmente a pacientes con indicaciones precisas según el primario subyacente. Es aquí donde la laparoscopia de estadificación realizada de manera correcta y completa juega un papel determinante, puesto que ha demostrado ser un método fiable para realizar una aproximación del compromiso peritoneal. Conclusión. Todos los especialistas quirúrgicos, en especial los cirujanos generales, deben estar familiarizados en cómo realizar de forma completa una laparoscopia de estadificación, de manera que se pueda hacer una mejor aproximación al grado de compromiso peritoneal, contribuyendo en el manejo integral oncológico del paciente.

Introduction. Peritoneal metastases represent an advanced stage of many intra-abdominal neoplasms and often give an ominous prognosis. Recently, the only therapeutic option for this setting was palliative chemotherapy. However, most tumors metastatic to the peritoneum remain relatively resistant to intravenously administered cytotoxic and cytostatic drugs and, in general, to individual therapies. Methods. A literature search was performed in PubMed, SciELO and Google Scholar databases using the keywords: laparoscopy, peritoneal carcinomatosis, staging, cytoreduction. The most relevant articles published in English and Spanish were included in the review. Discussion. Cytoreductive surgery associated with intraperitoneal hyperthermic chemotherapy techniques is currently offered to patients with precise indications according to the underlying primary. It is here where staging laparoscopy performed in a complete and correct manner plays a determining role, since it has proven to be a reliable method for approximating peritoneal involvement. Conclusion. All surgical specialists, especially general surgeons, should be familiar with how to perform a complete staging laparoscopy, leading to a correct approach of the degree of peritoneal involvement and contributing to the integral oncologic management of the patient.

Impact of proper surgical treatment on the survival of patients with epithelial ovary cancer / Impacto do tratamento cirúrgico adequado na sobrevida de mulheres com carcinoma epitelial ovariano

ABSTRACT Objective: to evaluate the quality of surgical treatment of ovarian cancer patients and assess the impact of adequate surgical oncological treatment on disease-free survival and overall survival of patients with advanced epithelial ovarian cancer. Methods: this is an observational, retrospective study with quantitative analysis, with the collection of data in medical records of a temporal convenience sample of patients diagnosed with ovarian cancer admitted to a High Complexity Oncology Unit, in Belo Horizonte, from the period of 2014 to 2020. Results: a total of 91 patients diagnosed with ovarian cancer were evaluated, with the epithelial histopathological type being the most frequent (85%). Of this total, 68 patients (74.7%) had advanced-stage ovarian cancer. Appropriate surgical treatment was performed in 30.9% of patients with advanced epithelial ovarian cancer and the type of performed surgery was statistically significant for overall survival. This low proportion of appropriate surgical oncological treatment was not related to surgical specially or surgeon competence, but mainly to advanced disease related to patient flow at UNACON. It was not possible to confirm if the advanced-stage disease was related to tumor biology or losing time from diagnosis to oncological surgery. Conclusion: overall survival of advanced-stage epithelial ovarian cancer patients is directly influenced by appropriate surgical treatment, however, in this study, the percentage of advanced ovarian cancer receiving adequate surgical treatment was much lower than the rates reported in the literature. To improve these outcomes, we believe that surgeons should keep following patients during neoadjuvant chemotherapy to point to a better time for surgery, and clinical oncologists should better consider adequate oncological surgery as one of the pillars of ovarian cancer treatment and get more involved in facilitating surgeries.

RESUMO Objetivo: avaliar a qualidade do tratamento cirúrgico de pacientes com câncer de ovário e o impacto do tratamento oncológico cirúrgico adequado na sobrevida livre de doença e sobrevida global de pacientes com câncer de ovário epitelial avançado. Métodos: Trata-se de um estudo observacional, retrospectivo, de análise quantitativo, com coleta de dados em prontuários de uma amostra de conveniência temporal de pacientes com diagnóstico de câncer de ovário internadas em uma Unidade de Oncologia de Alta Complexidade (UNACON), em Belo Horizonte, no período de 2014 a 2020. Resultados: foram avaliadas 91 pacientes diagnosticadas com câncer de ovário, sendo o tipo histopatológico epitelial o mais frequente (85%). Desse total, 68 pacientes (74,7%) apresentavam câncer de ovário em estágio avançado. O tratamento cirúrgico adequado foi realizado em 30,9% das pacientes com câncer de ovário epitelial avançado e o tipo de cirurgia realizada foi estatisticamente significativo para a sobrevida global. Essa baixa proporção de tratamento cirúrgico oncológico adequado não esteve relacionada à especialidade cirúrgica ou competência do cirurgião, mas principalmente à doença avançada relacionada ao fluxo de pacientes na UNACON. Não foi possível confirmar se a doença em estágio avançado estava relacionada à biologia tumoral ou à perda de tempo do diagnóstico para a cirurgia oncológica. Conclusão: A sobrevida global de pacientes com câncer de ovário epitelial em estágio avançado é diretamente influenciada pelo tratamento cirúrgico adequado. Porém, o percentual de câncer de ovário avançado recebendo tratamento cirúrgico adequado foi muito inferior aos índices relatados na literatura. Para melhorar esses resultados, acreditamos que os cirurgiões devem continuar acompanhando as pacientes durante a quimioterapia neoadjuvante para apontar um melhor momento para a cirurgia, e os oncologistas clínicos devem considerar melhor a cirurgia oncológica adequada como um dos pilares do tratamento do câncer de ovário e se envolver mais na facilitação das cirurgias.

Tratamiento de tumores malignos epiteliales de ovario en estadios avanzados. Experiencia del Hospital Italiano de Buenos Aires / Treatment of advanced epithelial ovarian tumor. Hospital Italiano de Buenos Aires experience

Resumen El cáncer de ovario ocupa el tercer lugar en frecuencia entre los cánceres ginecológicos en Argentina. Existe un déficit de información de esta enfermedad en nuestro país respecto al tratamiento y evolución oncológica de las pacientes. El objetivo de nuestro trabajo fue evaluar los resultados perioperatorios y oncológicos, en pacientes con tumor epitelial de ovario con estadios avanzados. Presentamos una cohorte retrospectiva en la que se evaluó la supervivencia libre de enfermedad y la supervivencia global en pacientes con tumores epiteliales de ovario tratadas en el Hospital Italiano de Buenos Aires entre junio del 2009 a junio del 2017. De 170 pacientes incluidas en el estudio, 72 (42.4%) fueron tratadas con una cirugía de citorreducción primaria (CCP), mientras que 98 (57.6%) recibieron neoadyuvancia y luego cirugía del intervalo (CI). La tasa de citorreducción óptima fue de 75% y de 79% respectivamente. No se encontraron diferencias en los resultados perioperatorios, ni en las complicaciones graves entre ambos grupos. La mediana de SLE en el grupo de CCP fue de 2.5 años (IC 95% 1.6-3.1) mientras que en el grupo de CI fue de 1.4 (IC 95% 1.2-1.7) p < 0.001. La mediana de supervivencia global fue de 5.8 años en CCP, y de 3.5 años en CI. En pacientes adecuadamente seleccionadas la CCP presenta mejores resultados oncológicos a la neoadyuvancia y CI. La selección correcta de las pacientes para tratamiento primario es fundamental para definir la conducta terapéutica.

Abstract Ovarian cancer represents the third gynecological cancer in frequency in Argentina. There is a lack of information on this pathology in our country regarding the treatment and evolution of patients who suffer it. The aim of this study was to evaluate the perioperative and oncological results in patients with advanced epithelial ovarian tumor. We present a retrospective cohort in which we evaluated disease-free survival and overall survival in patients with epithelial ovarian tumor treated at the Hospital Italiano de Buenos Aires between June 2009 and June 2017. Of 170 patients included in the study, 72 (42.4%) received primary debulking surgery (CCP), while 98 (57.6%) received neoadjuvant therapy and interval surgery (CI). The optimal cyto-reduction rate was 75% and 79% respectively. No differences were found in perioperative outcomes, or in severe complications between the two groups. The median disease-free survival in the CCP group was 2.5 years (95% CI 1.6-3.1) while in the CI group it was 1.4 (95% CI 1.2-1.7) p < 0.001. The median overall survival was 5.8 years in CPP, and 3.5 years in CI. Faced with a meticulous selection by a group of experts, patients with advanced ovarian cancer treated with CCP present better oncological results than those who received neoadjuvant therapy and CI.

Factors affecting long-term survival of advanced high-grade serous ovarian cancer / 中华妇产科杂志

Objective:To identify the factors associated with long-term survival and guide the decision for primary surgery in patients with advanced high-grade serous ovarian cancer(HGSOC).Methods:In this case-control study, clinical parameters, including surgical and non-surgical associated factors, were collected and compared between the patients with short-term (<2 years) and long-term (>5 years) survival who all underwent primary debulking surgery (PDS) followed by carboplatin and paclitaxel chemotherapy from January 2004 to December 2016. Univariate analysis was examined by chi-square test and multivariate analysis was performed by logistic regression analysis.Results:There were 95 cases long-term survival (LTS group) and 77 cases short-term survival (STS group) in 698 newly diagnosed HGSOC patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ⅲc and Ⅳ who met include and exclude criteria. (1) Univariate analysis showed that the proportion of complete cytoreduction with no visible residual disease (R0) at PDS and platinum sensitivity in LTS group were significantly higher than those in STS group ( P<0.01). The surgical complexity score (SCS), the preoperative serum CA 125 level and the ascites volume in the LTS group were significantly lower than those of the STS group (all P<0.05). In the LTS group, the preoperative incidence of lesions in retrograde peritoneum of the bladder, serosal and mesangial membrane of the small intestine, upper abdominal peritoneum and liver parenchyma were significantly lower than those in the STS group (all P<0.05). Multivariate logistic regression analysis showed that platinum sensitivity ( OR=0.016, 95% CI: 0.004-0.063, P<0.01), ascites volume >500 ml ( OR=3.193, 95% CI: 1.285-7.930, P=0.012), and SCS ≥8 ( OR=17.433, 95% CI: 2.281-133.25, P=0.003) were independent factors affecting long-term survival ( P>0.05). (2) Totally 37 of 95 in long-term survival and 16 of 77 in short-term survival achieved R0 cytoreduction at PDS. Univariate analysis showed that preoperative serum CA 125 level, preoperative lesion score, preoperative lesion (DS) score, ascites volume, platinum sensitivity,and SCS were significantly correlated with the R0 PDS (all P<0.05). Multivariate analysis showed that ascites volume >500 ml ( OR=5.199, 95% CI: 2.015-13.409, P=0.001), DS >2 ( OR=15.264, 95% CI: 5.843-39.874, P<0.01) and SCS ≥4 ( OR=4.176, 95% CI: 1.618-10.777, P=0.003) were independent factors associated with R0 cytoreduction. In patients with DS ≤2 or SCS <4, but not those with DS >2 or SCS ≥4, R0 cytoreduction was significantly associated with long-term survival. Conclusion:The intrinsic biology of tumor is the factor influencing long-term survival of advanced HGSOC patients, and those who present with wide intraperitoneal metastases and need to remove multiple organs may not benefit from R0 cytoreduction.

Analysis of factors related to the prognostic benefit of neoadjuvant chemotherapy followed by interval debulking surgery in patients with advanced ovarian cancer / 中华妇产科杂志

Objective:To explore the prognostic factors of patients with advanced epithelial ovarian cancer (EOC) who received neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS).Methods:The clinical and pathological data of patients with stage Ⅲc-Ⅳ EOC underwent surgical treatment in Sichuan Cancer Center from January 1st, 2014 to December 31th, 2018 were retrospectively analyzed, and the prognosis was followed up.Results:(1) A total of 216 EOC patients were included in the study, whose age was (52.1±8.7) years old, the median follow-up time was 44.6 months (17.2-80.1 months), the median progression free survival (PFS) was 11.1 months (8.5-13.8 months), and the median overall survival (OS) was 40.0 months (32.7-47.3 months). (2) Among 216 patients with advanced EOC, there were 75 cases in the primary debulking surgery (PDS) group and 141 cases in the NACT+IDS group. Compared with the PDS group, the serum CA 125 level before treatment (median: 859.4 vs 1 371.0 kU/L), proportion of stage Ⅳ patients [5.3% (4/75) vs 23.4% (33/144)] and no visible residual disease (R0) cytoreduction rate in the NACT+IDS group were significantly higher [(41.3% (31/75) vs 61.7% (87/144); all P<0.05]. The median PFS in the NACT+IDS group was significantly shorter than that of the PDS group (9.1 vs 15.2 months; χ2=7.014, P=0.008), but there was no significant difference in the median OS between the two groups (42.6 vs 38.0 months; χ2=1.325, P=0.250). (3) Univariate analysis showed that body mass index (BMI), preoperative serum CA 125 level, surgical-pathological stage, NACT effect, postoperative residual tumor size, time to initiation of postoperative chemotherapy and chemotherapy regimen were significantly correlated with PFS in the NACT+IDS group (all P<0.05); preoperative serum CA 125 level, surgical-pathological stage, NACT effect, postoperative residual tumor size, postoperative chemotherapy regimen were significantly related with OS in the NACT+IDS group (all P<0.05). Multivariate analysis showed that BMI, postoperative residual tumor size, time to initiation of postoperative chemotherapy were independent factors of PFS in the NACT+IDS group (all P<0.05); preoperative serum CA 125 level, surgical-pathological stage, postoperative residual tumor size were independent factors of OS in the NACT+IDS group (all P<0.05). The results showed that the PFS of patients with normal preoperative serum CA 125 level and (or) chemotherapy ≤7 days after IDS was longer, while no significant difference comparable with those in the PDS group ( P>0.05), and OS was also showing an prolonged trend, but the difference was also not statistically significant ( P>0.05). Conclusions:Normal CA 125 before IDS and time received chemotherapy no longer than 7 days after IDS are two related factors of prognosis benefit in advance EOC patients treated with NACT+IDS. Therefore, timely adjustment of the dose and regimen of NACT to reduce CA 125 level to normal range in about three cycles before IDS, and strengthen IDS perioperative management to promote postoperative recovery and perform chemotherapy as soon as possible might help to improve the prognosis of patients.

The long-term clinical efficacy of tumor cytoreduction surgery with hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal cancer / 解放军医学杂志

Objective: To study the long-term efficacy of cytoreduction surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis from colorectal cancer. Methods: The clinical data were collected of 103 patients with peritoneal carcinomatosis (PC) from colorectal cancer undergoing CRS with HIPEC in the Department of General Surgery of the First Medical Center of Chinese PLA General Hospital from January 1, 2012 to May 31, 2013, and divided into colonic group (n=60) and rectal group (n=43) according to the origin position of peritoneal cancer. The surgical status of patients (whether combined with other organ resection, number of stoma, peritoneal carcinomatosis index (PCI), completeness of cytoreduction (CC) score, transfusion, etc.) and the short-term complications and long-term survival after operation in the both groups were compared. Kaplan-meier method was used to draw the survival curve of patients, and log-rank method was employed to compare the survival differences between the two groups. Results: There was no significant difference in the surgical data between the two groups (PCI, CC score, hepatectomy, number of anastomosed stoma, transfusion, etc., P>0.05). The follow-up time of the 103 patients was (28.43±15.65) months, median survival time (OS) was 26.3 months, median disease free survival time (DFS) was 17.7 months, median recurrence to time of death (TTD) was 18.3 months. The 3-year and 5-year survival rate were 35.9% and 8.7%, respectively. The patients' survival was better in colonic group than in rectal group (OS: 28.5 months vs. 19.7 months; DFS: 21.1 months vs. 13.6 months; TTD: 22.3 months vs. 12.1months; 3-year survival rate: 48.3% vs. 18.6%; 5-year survival rate: 15.0% vs. 0, P<0.05). Conclusion: When CRS with HIPEC is implemented, the incidence of short-term complications in patients with PC originated from colon may match to those with PC originated from rectum, while the long-term efficacy is better in the former than in the latter.

Factors associated with surgical morbidity of primary debulking in epithelial ovarian cancer

Well-trained gynecologic oncologists can perform bowel resection and upper abdominal surgery safely / 부인종양

Characteristics and survival of ovarian cancer patients treated with neoadjuvant chemotherapy but not undergoing interval debulking surgery / 부인종양

Predictive value of changes in the serum CA-125 levels in patients undergoing interval debulking surgery after neoadjuvant chemotherapy in advanced epithelial ovarian carcinoma

Background: The objective of this study is to evaluate the predictive value of serum CA-125 changes in the management of patients undergoing neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in advanced epithelial ovarian carcinoma (EOC).Methods: A retrospective hospital-based study of patients with advanced epithelial ovarian cancers (stage III and IV) was conducted at Department of Obstetrics and Gynecology in Gujarat Cancer and Research Institute, Ahmedabad, for two years. Total 50 patients were treated with NACT followed by surgical cytoreduction and followed up till August 2010. Response to NACT, optimal cytoreduction rate and overall response rate were analyzed.CA 125 levels before (baseline) and after NACT were analyzed.Results: Out of 50, there were 43 patients (86%) with stage III disease and 7 (14%) with stage IV disease. Maximum 37(74%) patients had CA 125 levels >500 on presentation while none of the patients had baseline CA125 levels in the normal range (<35). Range of baseline CA 125 was 164-5394.All patients were given NACT and after NACT, out of 50 patients, 22(44%) patients had CA 125 values within the normal range (<35) while 23(46%) had values between 35 and 100. Thus, statistically significant difference (Z = 6.154, P<0.0001) was found between CA 125 level before and after NACT. Out of 45 patients with CA 125 <100, 35(77.8%) underwent optimal cytoreduction.Conclusions: Baseline (prechemotherapy) serum CA-125 levels are powerful indicators of the presence and extent of spread of disease while CA-125 level particularly <100U/ml after NACT strongly predicts optimal cytoreduction in advanced epithelial ovarian cancers.

The detrimental effect of adopting interval debulking surgery in advanced stage low-grade serous ovarian cancer / 부인종양

OBJECTIVE: To examine outcomes of patients having treatments for newly diagnosed advanced stage low-grade serous ovarian cancer (LGSC). METHODS: We conducted a retrospective case series of women affected by advanced stage (stage IIIB or more) LGSC undergoing surgery in a single oncologic center between January 2000 and December 2017. Survival outcomes were assessed using Kaplan-Meier and Cox models. RESULTS: Data of 72 patients were retrieved. Primary cytoreductive surgery was attempted in 68 (94.4%) patients: 19 (27.9%) had residual disease (RD) >1 cm after primary surgery. Interval debulking surgery (IDS) was attempted in 15 of these 19 (78.9%) patients and the remaining 4 patients having not primary debulking surgery. Twelve out of 19 (63.1%) patients having IDS had RD. After a mean (±standard deviation) follow-up was 61.6 (±37.2) months, 50 (69.4%) and 22 (30.5%) patients recurred and died of disease, respectively. Via multivariate analysis, non-optimal cytoreduction (hazard ratio [HR]=2.79; 95% confidence interval [CI]=1.16–6.70; p=0.021) and International Federation of Obstetrics and Gynecologists (FIGO) stage IV (HR=3.15; 95% CI=1.29–7.66; p=0.011) were associated with worse disease-free survival. Via multivariate analysis, absence of significant comorbidities (HR=0.56; 95% CI=0.29–1.10; p=0.093) and primary instead of IDS (HR=2.95; 95% CI=1.12–7.74; p=0.027) were independently associated with an improved overall survival. CONCLUSION: LGSC is at high risk of early recurrence. However, owing to the indolent nature of the disease, the majority of patients are long-term survivors. Further prospective studies and innovative treatment modalities are warranted to improve patients care.

The efficacy of secondary cytoreductive surgery for recurrent ovarian, tubal, or peritoneal cancer in Tian-model low-risk patients / 부인종양

OBJECTIVE: In patients with recurrent ovarian cancer (ROC) in whom surgery is likely to render them disease-free, it is unclear whether secondary cytoreductive surgery (SCS) combined with chemotherapy is superior to chemotherapy alone. The aim of this study was to evaluate the 2 treatment options in Tian-model low-risk patients. METHODS: We retrospectively reviewed 118 ROC cases treated in our hospital between 2004 and 2016. Of these, 52 platinum-sensitive cases were classified as low-risk (complete resection anticipated) using the Tian model. Prognostic factors were assessed with univariate and multivariate analysis using Cox's regression model. Progression-free survival (PFS) and overall survival (OS) were compared in patients treated with SCS plus chemotherapy (SCS group) and those treated with chemotherapy alone (chemotherapy group), using a propensity-score-based matching method. RESULTS: By multivariate analysis, the only factor associated with better OS was SCS. PFS and OS were significantly longer in the SCS group compared to the chemotherapy group in the matched cohort (median PFS: 21.7 vs. 15.1 months, p=0.027 and median OS: 91.4 vs. 33.4 months, p=0.008, respectively). In cases with multiple-site recurrence, the SCS group also showed significantly longer OS than the chemotherapy group (median 91.4 vs. 34.8 months, p=0.022). In almost all SCS cases, cooperation was required from other departments, and operation time was lengthy (median 323 minutes); however, no serious complications occurred. CONCLUSION: SCS combined with chemotherapy results in better PFS and OS than chemotherapy alone in first platinum-sensitive ROC patients categorized as low-risk by Tian's model.

Treatment strategies for patients with advanced ovarian cancer undergoing neoadjuvant chemotherapy: interval debulking surgery or additional chemotherapy? / 부인종양

OBJECTIVE: To treat advanced ovarian cancer, interval debulking surgery (IDS) is performed after 3 cycles each of neoadjuvant chemotherapy (NAC) and postoperative chemotherapy (IDS group). If we expect that complete resection cannot be achieved by IDS, debulking surgery is performed after administering additional 3 cycles of chemotherapy without postoperative chemotherapy (Add-C group). We evaluated the survival outcomes of the Add-C group and determined their serum cancer antigen 125 (CA125) levels to predict complete surgery. METHODS: A retrospective chart review of all stage III and IV ovarian, fallopian tube, and peritoneal cancer patients treated with NAC in 2007–2016 was conducted. RESULTS: About 117 patients comprised the IDS group and 26 comprised the Add-C group. Univariate and multivariate analyses revealed that Add-C group had an equivalent effect on progression-free survival (PFS; p=0.09) and overall survival (OS; p=0.94) compared with the IDS group. Multivariate analysis revealed that patients who developed residual disease after surgery had worse PFS (hazard ratio [HR]=2.18; 95% confidence interval [CI]=1.45–3.28) and OS (HR=2.33; 95% CI=1.43–3.79), and those who received <6 cycles of chemotherapy had worse PFS (HR=5.30; 95% CI=2.56–10.99) and OS (HR=3.05; 95% CI=1.46–6.38). The preoperative serum CA125 cutoff level was 30 U/mL based on Youden index method. CONCLUSIONS: Administering 3 additional cycles of chemotherapy followed by debulking surgery exhibited equivalent effects on survival as IDS followed by 3 cycles of postoperative chemotherapy. Preoperative serum CA125 levels of ≤30 U/mL may be a useful predictor of achieving complete surgery.

Pharmacokinetics of cisplatin during open and minimally-invasive secondary cytoreductive surgery plus HIPEC in women with platinum-sensitive recurrent ovarian cancer: a prospective study / 부인종양

OBJECTIVE: Evidences from animal models seem to suggest that minimally invasive surgery may enhance cisplatin diffusion when the drug is administered in the context of post-operative hyperthermic intraperitoneal chemotherapy (HIPEC). The present study evaluates the cisplatin pharmacokinetic profile in a prospective series of women with platinum sensitive recurrent epithelial ovarian cancer treated with open secondary cytoreductive surgery (O-SCS) or minimally-invasive secondary cytoreductive surgery (MI-SCS). METHODS: Cisplatin levels were assessed at 0, 20, 40, 60, and 120 minutes in: 1) blood samples, 2) peritoneal perfusate, and 3) peritoneal biopsies at the end of HIPEC. Median Cmax has been used to identify women with high and low drug levels. Progression-free survival (PFS) was calculated as the time elapsed between SCS+HIPEC and secondary recurrence or last follow-up visit. RESULTS: Nine (45.0%) women received MI-SCS, and 11 (55.0%) O-SCS. At 60 minutes, median cisplatin Cmax in peritoneal tissue was higher in patients treated with MI-SCS compared to O-SCS (Cmax=8.262 µg/mL vs. Cmax=4.057 µg/mL). Furthermore, median cisplatin plasma Cmax was higher in patients treated with MI-SCS compared to O-SCS (Cmax=0.511 vs. Cmax=0.254 µg/mL; p-value=0.012) at 120 minutes. With a median follow-up time of 24 months, women with higher cisplatin peritoneal Cmax showed a longer PFS compared to women with low cisplatin peritoneal levels (2-years PFS=70% vs. 35%; p-value=0.054). CONCLUSIONS: We demonstrate for the first time that minimally invasive route enhances cisplatin peritoneal tissue uptake during HIPEC, further evaluations are needed to confirm the correlation between peritoneal cisplatin levels after HIPEC and survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01539785

Diagnosis and treatment of pseudomyxoma peritonei of extra-appendiceal origin:analysis of 34 cases / 中国肿瘤临床

Objective: To investigate the clinicopathological features and treatment strategy of pseudomyxoma peritonei (PMP) of ex-tra-appendiceal origin. Methods: Clinical data of 34 patients diagnosed with PMP of extra-appendiceal origin who were treated by cy-toreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the Aerospace Center Hospital from September 2011 to February 2019 were retrospectively analyzed. Clinical and imaging features were summarized and the Log-rank test was used for survival analysis. Results: The clinical manifestations of the 34 patients with PMP of extra-appendiceal origin were mainly abdomi-nal distension (58.8%) and abdominal pelvic mass (52.9%), which are very similar to those of appendiceal PMP. The incidence of main complications after CRS and HIPEC was 14.7%. During the follow-up period of a median of 12 months (range 1-46 months), 9 patients died, and the 1-and 3-year overall survival rates were 69.6% and 53.5%, respectively. In the univariate analysis, peritoneal cancer in-dex (PCI)>20, no HIPEC, and non-radical surgery were significant risk factors for poor prognosis, while gender, age, origin, and patho-logical type did not show significant correlations. Conclusions: The clinical features of PMP of extra-appendiceal origin are not differ-ent to those of PMP originating from the appendix. It is difficult to ascertain the primary lesion before the operation; however, regard-less of the origin, CRS combined with HIPEC is always a safe and effective treatment choice.

Manejo del mesotelioma peritoneal maligno con citorreducción quirúrgica más quimioterapia hipertérmica intraperitoneal en el Instituto Nacional de Cancerología, Colombia: reporte de un caso y revisión bibliográfica / Peritoneal malignant mesothelioma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy at the National Cancer Institute, Colombia: case report and literature review

El mesotelioma peritoneal es una neoplasia que se origina en las células mesoteliales del peritoneo. Histórica-mente, la supervivencia de los pacientes con mesotelioma peritoneal maligno sin tratamiento, es menor de 12 meses y se considera una neoplasia resistente a la quimioterapia. La citorreducción quirúrgica y la quimioterapia regional administrada como quimioterapia hipertérmica intraperitoneal (Hyperthermic Intraperitoneal Chemothe-rapy, HIPEC) se asocia con mejor supervivencia a largo plazo.Se presenta el caso de un paciente con antecedentes de exposición al asbesto y con diagnóstico de mesotelioma peritoneal maligno de tipo epitelioide, que fue tratado con cirugía citorreductora más quimioterapia hipertérmica intraperitoneal en el Instituto Nacional de Cancerología con una supervivencia de un año libre de enfermedad

Peritoneal mesothelioma is originated at the mesothelial cells of the peritoneum. Historically the survival of patients with this disease is less than 12 months without treatment and it is considered a neoplasm resistant to chemotherapy. Citorreductive surgery with hiperthermic intraperitoneal chemotherapy (HIPEC) is associated with an increased long-term survival. Here we present the case of a patient who had a past history of asbestos exposure and who was diagnosed with peritoneal mesothelioma of the epithelioid subtype. The patient was treated with cytoreductive surgery and HIPEC at the Instituto Nacional de Cancerología (Bogotá, Colombia) and has had a 12 month disease free survival