Índice de irresecabilidad asociado a citorreducción óptima en pacientes con cáncer de ovario: Estudio observacional de centro único / Unresectability index associated with optimal cy-toreduction in patients with ovarian cancer: A single-center observational study

Introducción: El índice de irresecabilidad valora la presencia de cuatro variables (masa abdominal palpable, tumor en fondo de saco de Douglas, presencia de líquido ascítico, valor preoperatorio de Ca 125 mayor a 1000 U/ml); previo a la realización de una cirugía citorreductora primaria en pacientes con cáncer de ovario. El objetivo del presente estudio fue realizar una prueba diagnóstica del índice de irresecabilidad con la decisión de realizar citorreducción óptima en pacientes con cáncer de ovario que fueron operadas en un hospital público de referencia nacional en Ecuador en 3 años de estudio. Metodología: En el presente estudio de pruebas diagnósticas, se estudiaron mujeres operadas con cáncer de ovario, en el Hospital de Especialidades Eugenio Espejo (Ecuador) de septiembre del 2016 a septiembre del 2018. Se incluyeron pacientes con citorreducción óptima y subóptima. Se presenta un análisis descriptivo con frecuencias, porcentajes y promedios. Se evaluó la sensibilidad, especificidad, valor predictivo negativo (VPN) y valor predictivo positivo (VPP) del índice de irresecabilidad comparado con la citorreducción. Resultados: Fueron 148 casos analizados. La especificidad del índice fue de 81 %, con un valor predictivo (VP) positivo del 77 % y VP negativo de 68 %. La sensibilidad de la ascitis 85 % y la masa abdominal palpable del 79 %. En las pacientes que presentaron valores de antígeno CA-125 menor a 1000 U/ml, el riesgo de obtener una citorreducción óptima fue OR: 0.15 (IC95% 0.069 ­ 0.307; P: 0.0001); las pacientes que presentaron valores del índice de irresecabilidad entre 1 y 2 puntos versus 3 y 4 fue de OR: 7.04 (IC95% 3.33 -14.87, P: 0.0001). Conclusiones: El Índice de irresecabilidad presentó una capacidad estadísticamente significativa para predecir citorreducción óptima en las pacientes con cáncer ovario operadas en el Hospital de Especialidades Eugenio Espejo.

Introduction: The unresectability index assesses the presence of four variables (palpable abdominal mass, tumor in the fornix of Douglas, presence of ascitic fluid, preoperative Ca 125 value greater than 1000 U/ml); before performing primary cytoreductive surgery in patients with ovarian cancer. The objective of this study was to carry out a diagnostic test of the unresectability index with the decision to perform optimal cytoreduction in patients with ovarian cancer who underwent surgery in a public hospital of national reference in Ecuador in 3 years of study. Methodology: In the present study of diagnostic tests, women operated on for ovarian cancer were studied at the Eugenio Espejo Specialties Hospital (Ecuador) from September 2016 to September 2018. Patients with optimal and suboptimal cytoreduction were included. A descriptive analysis with frequencies, percentages, and averages is presented. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the unresectable index compared with cytoreduction were evaluated. Results: 148 cases were analyzed. The specificity of the index was 81%, with a positive predictive value (PV) of 77% and a negative PV of 68%. The sensitivity of ascites is 85%, and the palpable abdominal mass of 79%. In patients who presented CA-125 antigen values less than 1000 U/ml, the risk of obtaining optimal cytoreduction was OR: 0.15 (95% CI 0.069 - 0.307; P: 0.0001); The patients who presented unresectability index values between 1 and 2 points versus 3 and 4 were OR: 7.04 (95% CI 3.33 -14.87, P: 0.0001). Conclusions: The unresectability index presented a statistically significant capacity to predict optimal cytoreduction in patients with ovarian cancer operated on at the Eugenio Espejo Specialties Hospital.

Effects of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy treatment in patients with untreated gastric cancer with peritoneal metastasis / 中华胃肠外科杂志

Objective: To investigate the efficacy of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy (HIPEC-IP-IV) in the treatment of peritoneal metastases from gastric cancer (GCPM). Methods: This was a descriptive case series study. Indications for HIPEC-IP-IV treatment include: (1) pathologically confirmed gastric or esophagogastric junction adenocarcinoma; (2) age 20-85 years; (3) peritoneal metastases as the sole form of Stage IV disease, confirmed by computed tomography, laparoscopic exploration, ascites or peritoneal lavage fluid cytology; and (4) Eastern Cooperative Oncology Group performance status 0-1. Contraindications include: (1) routine blood tests, liver and renal function, and electrocardiogram showing no contraindications to chemotherapy; (2) no serious cardiopulmonary dysfunction; and (3) no intestinal obstruction or peritoneal adhesions. According to the above criteria, data of patients with GCPM who had undergone laparoscopic exploration and HIPEC from June 2015 to March 2021 in the Peking University Cancer Hospital Gastrointestinal Center were analyzed, after excluding those who had received antitumor medical or surgical treatment. Two weeks after laparoscopic exploration and HIPEC, the patients received intraperitoneal and systemic chemotherapy. They were evaluated every two to four cycles. Surgery was considered if the treatment was effective, as shown by achieving stable disease or a partial or complete response and negative cytology. The primary outcomes were surgical conversion rate, R0 resection rate, and overall survival. Results: Sixty-nine previously untreated patients with GCPM had undergone HIPEC-IP-IV, including 43 men and 26 women; with a median age of 59 (24-83) years. The median PCI was 10 (1-39). Thirteen patients (18.8%) underwent surgery after HIPEC-IP-IV, R0 being achieved in nine of them (13.0%). The median overall survival (OS) was 16.1 months. The median OS of patients with massive or moderate ascites and little or no ascites were 6.6 and 17.9 months, respectively (P<0.001). The median OS of patients who had undergone R0 surgery, non-R0 surgery, and no surgery were 32.8, 8.0, and 14.9 months, respectively (P=0.007). Conclusions: HIPEC-IP-IV is a feasible treatment protocol for GCPM. Patients with massive or moderate ascites have a poor prognosis. Candidates for surgery should be selected carefully from those in whom treatment has been effective and R0 should be aimed for.

Construction and evaluation of a nomogram for predicting the prognosis of patients with colorectal cancer with peritoneal carcinomatosis treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy / 中华胃肠外科杂志

Objectives: To construct a nomogram incorporating important prognostic factors for predicting the overall survival of patients with colorectal cancer with peritoneal metastases treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), the aim being to accurately predict such patients' survival rates. Methods: This was a retrospective observational study. Relevant clinical and follow-up data of patients with colorectal cancer with peritoneal metastases treated by CRS + HIPEC in the Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University from 2007 January to 2020 December were collected and subjected to Cox proportional regression analysis. All included patients had been diagnosed with peritoneal metastases from colorectal cancer and had no detectable distant metastases to other sites. Patients who had undergone emergency surgery because of obstruction or bleeding, or had other malignant diseases, or could not tolerate treatment because of severe comorbidities of the heart, lungs, liver or kidneys, or had been lost to follow-up, were excluded. Factors studied included: (1) basic clinicopathological characteristics; (2) details of CRS+HIPEC procedures; (3) overall survival rates; and (4) independent factors that influenced overall survival; the aim being to identify independent prognostic factors and use them to construct and validate a nomogram. The evaluation criteria used in this study were as follows. (1) Karnofsky Performance Scale (KPS) scores were used to quantitatively assess the quality of life of the study patients. The lower the score, the worse the patient's condition. (2) A peritoneal cancer index (PCI) was calculated by dividing the abdominal cavity into 13 regions, the highest score for each region being three points. The lower the score, the greater is the value of treatment. (3) Completeness of cytoreduction score (CC), where CC-0 and CC-1 denote complete eradication of tumor cells and CC-2 and CC-3 incomplete reduction of tumor cells. (4) To validate and evaluate the nomogram model, the internal validation cohort was bootstrapped 1000 times from the original data. The accuracy of prediction of the nomogram was evaluated with the consistency coefficient (C-index), and a C-index of 0.70-0.90 suggest that prediction by the model was accurate. Calibration curves were constructed to assess the conformity of predictions: the closer the predicted risk to the standard curve, the better the conformity. Results: The study cohort comprised 240 patients with peritoneal metastases from colorectal cancer who had undergone CRS+HIPEC. There were 104 women and 136 men of median age 52 years (10-79 years) and with a median preoperative KPS score of 90 points. There were 116 patients (48.3%) with PCI≤20 and 124 (51.7%) with PCI>20. Preoperative tumor markers were abnormal in 175 patients (72.9%) and normal in 38 (15.8%). HIPEC lasted 30 minutes in seven patients (2.9%), 60 minutes in 190 (79.2%), 90 minutes in 37 (15.4%), and 120 minutes in six (2.5%). There were 142 patients (59.2%) with CC scores 0-1 and 98 (40.8%) with CC scores 2-3. The incidence of Grade III to V adverse events was 21.7% (52/240). The median follow-up time is 15.3 (0.4-128.7) months. The median overall survival was 18.7 months, and the 1-, 3- and 5-year overall survival rates were 65.8%, 37.2% and 25.7%, respectively. Multivariate analysis showed that KPS score, preoperative tumor markers, CC score, and duration of HIPEC were independent prognostic factors. In the nomogram constructed with the above four variables, the predicted and actual values in the calibration curves for 1, 2 and 3-year survival rates were in good agreement, the C-index being 0.70 (95% CI: 0.65-0.75). Conclusions: Our nomogram, which was constructed with KPS score, preoperative tumor markers, CC score, and duration of HIPEC, accurately predicts the survival probability of patients with peritoneal metastases from colorectal cancer treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.

Establishment of treatment center for peritoneal metastasis in colorectal cancer / 中华胃肠外科杂志

The prognosis of patients with peritoneal metastasis from colorectal cancer is poor. At present, the comprehensive treatment system based on cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has significantly improved the survival of these patients. However, CRS and HIPEC have strict indications, high procedural difficulty, and high morbidity and mortality. If CRS+HIPEC is performed in an inexperienced center, overall survival and quality of life of patients may bo compromised. The establishment of specialized diagnosis and treatment centers can provide a guarantee for standardized clinical diagnosis and treatment. In this review, we first introduced the necessity of establishing a colorectal cancer peritoneal metastasis treatment center and the construction situation of the diagnosis and treatment center for peritoneal surface malignancies at home and abroad. Then we focused on introducing our construction experience of the colorectal peritoneal metastasis treatment center, and emphasized that the construction of the center must be done well in two aspects: firstly, the clinical optimization should be realized and the specialization of the whole workflow should be strengthened; secondly, we should ensure the quality of patient care and the rights, well-being and health of every patient.

Molecular mechanism and treatment strategy of colorectal cancer peritoneal metastasis / 中华胃肠外科杂志

Peritoneal metastatic colorectal cancer (pmCRC) is common and has been considered as the terminal stage. The theory of "seed and soil" and "oligometastasis" are the acknowledged hypotheses of pathogenesis of pmCRC. In recent years, the molecular mechanism related to pmCRC has been deeply researched. We realize that the formation of peritoneal metastasis, from detachment of cells from primary tumor to mesothelial adhesion and invasion, depends on the interplay of multiple molecules. Various components of tumor microenvironment also work as regulators in this process. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been widely used in clinical practice as an established treatment for pmCRC. Besides systemic chemotherapy, targeted and immunotherapeutic drugs are also increasingly used to improve prognosis. This article reviews the molecular mechanisms and treatment strategies related to pmCRC.

Recent progress and future prospects of treatment for peritoneal metastasis in gastric cancer / 中华胃肠外科杂志

Peritoneal metastasis is one of the most frequent patterns of metastasis in gastric cancer, and remains a major unmet clinical problem. Thus, systemic chemotherapy remains the mainstay of treatment for gastric cancer with peritoneal metastasis. In well-selected patients, the reasonable combination of cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and neoadjuvant intraperitoneal chemotherapy with systemic chemotherapy will bring significant survival benefits to patients with gastric cancer peritoneal metastasis. In patients with high-risk factors, prophylactic therapy may reduce the risk of peritoneal recurrence, and improves survival after radical gastrectomy. However, high-quality randomized controlled trials will be needed to determine which modality is better. The safety and efficacy of intraoperative extensive intraperitoneal lavage as a preventive measure has not been proven. The safety of HIPEC also requires further evaluation. HIPEC and neoadjuvant intraperitoneal and systemic chemotherapy have achieved good results in conversion therapy, and it is necessary to find more efficient and low-toxicity therapeutic modalities and screen out the potential benefit population. The efficacy of CRS combined with HIPEC on peritoneal metastasis in gastric cancer has been preliminarily validated, and with the completion of clinical studies such as PERISCOPE II, more evidence will be available.

Progress in diagnosis and treatment of ovarian metastases in rectal cancer / 中华胃肠外科杂志

Rectal cancer is the most common tumor of digestive tract. For female patients, ovarian metastasis ranks the second place in intraperitoneal organ metastasis. Its symptoms are occult, easily missed and insensitive to systemic treatment, so the prognosis is poor. Surgery is the treatment of choice for patients with rectal ovarian metastases, whether R0 resection is possible or not, and reducing tumor load is associated with better prognosis. With the continuous development of hyperthermic intraperitoneal chemotherapy (HIPEC), tumor reduction can reach the cellular level, which can significantly improve survival. Prophylactic ovariectomy remains a controversial issue in patients at high risk of ovarian metastasis. In this review, we summarize the diagnosis, treatment and prevention strategies of rectal cancer ovarian metastases, hoping to provide some reference for clinical practice.

China Anti-Cancer Association (CACA) guidelines for holistic integrative management of cancer-peritoneal tumours from gastrointestinal tract / 中华胃肠外科杂志

Peritoneal tumours have a large population and a poor prognosis with limited therapeutic options available, and are common originated from gastric, colorectal, appendix and other cancers. Traditionally, peritoneal tumours have long been considered to be a terminal condition with a median survival of 3-6 months, and the palliative symptomatic treatment is recommended. Recently, the multimodal therapeutic strategy of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has resulted in more effective on the prevention and treatment of peritoneal metastasis, which can significantly improve the survival and quality of life. Under the guidance of the China Anti-Cancer Association (CACA), the "CACA Guidelines for Holistic Integrative Management of Cancer-Peritoneal Tumours" was jointly completed by experts in related fields organized by the Chinese Society of Peritoneal Oncology. This guideline is guided by the concept of integrative medicine and focuses on the domestic epidemiology, genetic background and original studies. It emphasizes the multidisciplinary team to holistic integrative medicine (MDT to HIM), and pays attention to the whole-course management of "prevention, screening, diagnosis, treatment, and rehabilitation". This guideline mainly focuses on peritoneal metastasis from gastrointestinal tumours, aiming to standardize the clinical diagnosis and treatment process, and jointly promote the management of peritoneal metastasis in China.

Fluid administration in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: neither too much nor too little

Abstract Introduction Intraoperative fluid therapy in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy plays an important role in postoperative morbidity. Studies have found an association between overload fluid therapy and increased postoperative complications, advising restrictive intraoperative fluid therapy. Our objective in this study was to compare the morbidity associated with restrictive versus non-restrictive intraoperative fluid therapy. Methods Retrospective analysis of a database collected prospectively in the Anesthesiology Service of Virgen del Rocío Hospital, from December 2016 to April 2019. One hundred and six patients who underwent complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were divided into two cohorts according to Fluid Therapy received 1. Restrictive ≤ 9 mL.kg-1.h-1 (34 patients), 2. Non-restrictive ≥ 9 mL.kg-1.h-1 (72 patients). Percentage of major complications (Clavien-Dindo grade III-IV) and length hospital stay were the main outcomes variables. Results Of the 106 enrolled patients, 68.9% were women; 46.2% had ovarian cancer, 35.84% colorectal cancer, and 7.5% peritoneal cancer. The average fluid administration rate was 11 ± 3.58 mL.kg-1.h-1. The restrictive group suffered a significantly higher percentage of Clavien-Dindo grade III-IV complications (35.29%) compared with the non-restrictive group (15.27%) (p= 0.02). The relative risk associated with restrictive therapy was 1.968 (95% confidence interval: 1.158-3.346). We also found a significant difference for hospital length of stay, 20.91 days in the restrictive group vs 16.19 days in the non-restrictive group (p= 0.038). Conclusions Intraoperative fluid therapy restriction below 9 mL.kg-1.h-1 in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy was associated with a higher percentage of major postoperative complications.

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.

Predictors of recurrence of peritoneal carcinomatosis among patients with colorectal cancer following cytoreductive surgery alone versus cytoreductive surgery plus HIPEC

Background: Peritoneal carcinomatosis (PC) is a lethal regional progression in patients with colorectal cancer (CRC). Treatment with complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) achieves better local control than systemic palliative chemotherapy. Objectives: To assess the efficacy on the prognosis of CRS and HIPEC compared with CRS only and to identify possible clinicopathological factors associated with the recurrence of PC. Methods: The present retrospective study included all colorectal carcinoma cases with PC subjected to CRS with or without HIPC from January 2009 to June 2018 at the National Cancer Institute (NCI), Cairo University, Cairo, Egypt. The outcome is evaluated in terms of recurrence-free survival (RFS) and its predictors. Results: Out of the 61 patients, 45 patients (73.8%) underwent CRS plus HIPEC, and 16 (26.2%) underwent CRS alone. The 1-year RFS was 55.7%, with a median of 12 months. The risk factors for recurrence identified in the univariate analysis were T4 primary tumor, high-grade, positive lymphovascular invasion (LVI), positive extracapsular nodal spread, and patients treated with CRS only, without HIPEC. In the multivariate analysis, the independent risk factors for recurrence were high grade and patients treated with CRS only. Conclusion: T4 primary tumor, high grade, positive LVI, and positive extracapsular nodal spread seemed to be important predictors of recurrence following the treatment of PC. Our study also demonstrated that the addition of HIPEC to CRS improved the RFS. (AU)

Analysis of perioperative efficacy and safety of cytoreductive surgery in the treatment of colorectal cancer peritoneal metastases / 中华胃肠外科杂志

Objective: To analyzed perioperative safety of cytoreductive surgery (CRS) for patients with colorectal cancer peritoneal metastasis (CRPM) and to construct a predictive model for serious advese events (SAE). Methods: A descriptive case-series study was conducted to retrospectively collect the clinicopathological data and treatment status (operation time, number of organ resection, number of peritoneal resection, and blood loss, etc.) of 100 patients with peritoneal metastases from colorectal cancer or appendix mucinous adenocarcinoma who underwent CRS at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to August 2021. There were 53 males and 47 females. The median age was 52.0 (39.0-61.8) years old. Fifty-two patients had synchronous peritoneal metastasis and 48 had metachronous peritoneal metastasis. Fifty-two patients received preoperative neoadjuvant therapy. Primary tumor was located in the left colon, the right colon and the rectum in 43, 28 and 14 cases, respectively. Fifteen patients had appendix mucinous adenocarcinoma. Measures of skewed distribution are expressed as M (range). Perioperative safety was analyzed, perioperative grade III or higher was defined as SAE. Risk factors associated with the occurrence of SAEs were analyzed using multivariate logistic regression. A nomogram was plotted by R software to predict SAE, the efficacy of which was evaluated using the area under the ROC curve (AUC) and correction curves. Results: The median peritoneal cancer index (PCI) score was 16 (1-39). Sixty-eight (68.0%) patients achieved complete tumor reduction (tumor reduction score: 0-1). Sixty-two patients were treated with intraperitoneal hyperthermic perfusion chemotherapy (HIPEC). Twenty-one (21.0%) patients developed 37 SAEs of grade III-IV, including 2 cases of ureteral injury, 6 cases of perioperative massive hemorrhage or anemia, 7 cases of digestive system, 15 cases of respiratory system, 4 cases of cardiovascular system, 1 case of skin incision dehiscence, and 2 cases of abdominal infection. No grade V SAE was found. Multivariate logistic regression analysis showed that CEA (OR: 8.980, 95%CI: 1.428-56.457, P=0.019), PCI score (OR: 7.924, 95%CI: 1.486-42.259, P=0.015), intraoperative albumin infusion (OR: 48.959, 95%CI: 2.115-1133.289, P=0.015) and total volume of infusion (OR: 24.729, 95%CI: 3.956-154.562, P=0.001) were independent risk factors for perioperative SAE in CRS (all P<0.05). Based on the result of multivariate regression models, a predictive nomogram was constructed. Internal verification showed that the AUC of the nomogram was 0.926 (95%CI: 0.872-0.980), indicating good prediction accuracy and consistency. Conclusions: CRS is a safe and effective method to treat CRPM. Strict screening of patients and perioperative fluid management are important guarantees for reducing the morbidity of SAE.

A phase 2 trial of short-course Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) at interval cytoreductive surgery (iCRS) for advanced ovarian cancer / Quimioterapia Intraperitoneal Hipertérmica (HIPEC) de curta duração ao tempo da cirurgia citorredutora de intervalo (iCRS) para câncer de ovário avançado: ensaio clínico de fase 2

ABSTRACT Objective: to report the final analysis of a phase 2 trial assessing the efficacy and safety of short-course hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with advanced epithelial ovarian cancer (EOC). Methods: this was an open-label, multicenter, single-arm trial of HIPEC in patients with advanced EOC who underwent interval cytoreductive surgery (iCRS) after neoadjuvant chemotherapy (NACT). HIPEC was performed as a concentration-based regimen of platinum-based chemotherapy for 30 minutes. Primary endpoint was the rate of disease progression occurring at nine months following iCRS plus HIPEC (PD9). Secondary endpoints were postoperative complications, time to start adjuvant chemotherapy, length of hospital and ICU stay, quality of life (QoL) over treatment, and ultimately 2-year progression-free survival (PFS) and overall survival (OS). Analysis was by intention-to-treat with final database lock for survival outcomes on February 23, 2021. Results: fifteen patients with stage III EOC were enrolled between February 2015 and July 2019, in four centers. The intention to treat PD9 was 6.7%. With a median follow-up of 33 months (IQR, 24.3-46.5), the median PFS was 18.1 months and corresponding 2-year rates of PFS and OS was 33.3% and 93.3%, respectively. Three patients (20%) experienced graded III complications. Median length of hospital and ICU stay was 5 (IQR, 4-6.5) and 1 (IQR, 1-1) days, respectively. Time to restart systemic chemotherapy was 39 (IQR, 35-49.3) days and no significant difference over time in QoL was observed. Conclusions: we demonstrate preliminary efficacy and safety of short-course HIPEC in patient with advanced EOC.

RESUMO Objetivo: apresentar a análise final de ensaio clínico de fase 2 que avaliou a eficácia e a segurança da quimioterapia intraperitoneal hipertérmica (HIPEC) de curta duração em pacientes com câncer epitelial de ovário avançado (EOC). Métodos: estudo aberto, multicêntrico, de braço único avaliando a HIPEC em pacientes com EOC avançado submetidos a cirurgia citorredutora de intervalo (iCRS) após quimioterapia neoadjuvante (NACT). A HIPEC foi realizada como regime baseado na concentração de cisplatina, perfundida por 30 minutos. O desfecho primário foi a taxa de progressão da doença 9 meses após a iCRS com HIPEC (PD9). Os desfechos secundários foram complicações pós-operatórias, tempo para iniciar a quimioterapia adjuvante, tempo de internação e permanência em UTI, qualidade de vida (QoL) ao longo do tratamento e, finalmente, sobrevida cumulativa livre de progressão (PSF) e global (OS) em 2 anos. As análises foram em intenção de tratar (ITT) com fechamento dos dados para análise da sobrevida em 23 de fevereiro de 2021. Resultados: quinze pacientes com EOC em estágio III foram incluídos no estudo entre fevereiro de 2015 e julho de 2019 em quatro centros recrutadores. A PD9 por ITT foi de 6,7%. Com acompanhamento mediano de 33 meses (IQR, 24,3-46,5), a PFS mediana foi de 18,1 meses e as taxas correspondentes de PFS e OS em 2 anos foram 33,3% e 93,3%, respectivamente. Três pacientes (20%) apresentaram complicações grau III. O tempo mediano de internamento hospitalar e em UTI foi de 5 (IQR, 4-6,5) e 1 (IQR, 1-1) dias, respectivamente. O tempo para reinício da quimioterapia sistêmica foi de 39 dias (IQR, 35-49,3) e não foi observada diferença significativa na QoL ao longo do tratamento. Conclusões: demonstrou-se eficácia e segurança preliminares da HIPEC de curta duração em pacientes com EOC avançado.

Cirurgia Citorredutora com Quimioterapia Intraperitoneal Hipertérmica em Pacientes com Adenocarcinoma Mucinoso de Apêndice: Série de 43 Casos / Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy in Patients with Appendix Mucinous Adenocarcinoma: Series of 43 Casess / Cirugía Citorreductiva con Quimioterapia Intraperitoneal Hipertermal en Pacientes con Adenocarcinoma Mucinoso de Apéndice: Serie de 43 Caso

Introdução: O carcinoma primário de apêndice é uma condição rara. Muitas revisões retrospectivas internacionais delineiam a experiência de diferentes centros em neoplasias apendiculares. Por sua vez, o tratamento do câncer nessa localização é complexo e depende do subtipo histológico e da extensão da doença. Um dos tratamentos mais promissores é a cirurgia citorredutora (CCR) associada à quimioterapia intraperitoneal hipertérmica (HIPEC). No Brasil, não há descrição de séries de casos que tiveram essa abordagem terapêutica. O objetivo desta série de casos é analisar as características sociodemográficas e o tipo de intervenção terapêutica em pacientes com doenças malignas de apêndice em um Centro de Assistência de Alta Complexidade em Oncologia III (Cacon III). Relato dos casos: Foram incluídos 43 casos de tumores primários de apêndice. O adenocarcinoma do apêndice do tipo mucinoso de baixo grau foi a neoplasia mais diagnosticada. O principal protocolo utilizado foi de uma a duas cirurgias e aplicação de mitomicina C em temperatura média de 40 graus. Os casos apresentaram grande heterogeneidade quanto ao uso do protocolo. Conclusão: O presente relato de 43 casos é importante por se tratar de um tumor raro nessa localização. A modalidade terapêutica descrita é promissora, mas não há protocolo definido para essa finalidade. É necessário atualizar as diretrizes terapêuticas para normatizar a conduta internamente, especialmente em se tratando de uma unidade de referência nacional

Introduction: Primary appendix carcinoma is a rare condition. Many international retrospective reviews outline the experience of different centers in appendicular neoplasms. The cancer treatment in this location is complex and depends on the histological subtype and the extent of the disease. One of the most promising treatments is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In Brazil, there is no description of series of cases with this therapeutic approach. The purpose of this case series is to analyze the sociodemographic characteristics and the type of therapeutic intervention in patients with malignant diseases of the appendix in a High Complexity Care Center in Oncology III (Cacon III). Case reports: 43 cases of primary appendix tumors were included. Low-grade mucinous adenocarcinoma was the most diagnosed neoplasm. The main protocol used was 1 to 2 surgeries and application of mitomycin C at an average temperature of 40 degrees. There was great heterogeneity regarding the use of the protocol. Conclusion: The present report of 43 cases is important because it is a rare tumor with this location. The therapeutic modality described is promising, but there is no defined protocol for this purpose. It is necessary to update the therapeutic guidelines to standardize the conduct internally, especially in the case of a national reference unit

Introducción: El carcinoma primario de apéndice es una entidad poco frecuente. Numerosas revisiones retrospectivas internacionales describen la experiencia de diferentes centros en neoplasias apendiculares. A su vez, el tratamiento de esta localización del cáncer es complejo y depende del subtipo histológico y la extensión de la enfermedad. Uno de los tratamientos más prometedores es la cirugía citorreductora (CCR) asociada a quimioterapia intraperitoneal hipertérmica (HIPEC). En Brasil, no hay descripción de series de casos que tuvieran este abordaje terapéutico. El propósito de esta serie de casos es analizar las características sociodemográficas y el tipo de intervención terapéutica en pacientes con enfermedades malignas del apéndice en un Centro Asistencial de Alta Complejidad en Oncología III (Cacón III). Reporte de los casos: Se incluyeron 43 casos de tumores primarios de apéndice. El adenocarcinoma mucinoso de bajo grado tuvo la mayor incidencia. El protocolo principal utilizado fue de una a dos cirugías y aplicación de mitomicina C a una temperatura promedio de 40 grados. Los casos mostraron gran heterogeneidad en cuanto al uso del protocolo. Conclusión: El presente informe es importante porque es un tumor raro. La modalidad terapéutica descrita es prometedora, pero no existe un protocolo definido para tal fin. Es necesario actualizar las pautas terapéuticas para normalizar la conducta internamente, especialmente en el caso de una unidad de referencia nacional

Comparación histopatológica entre biopsia preoperatoria y debulking luego de la cirugía micrográfica de Mohs en carcinomas cutáneos / Histopathological comparison between preoperative biopsy and debulking after Mohs micrographic surgery in cutaneous carcinomas / Comparação histopatológica entre biópsia pré-operatória e citorredução após cirurgia micrográfica de Mohs em carcinomas cutâneos

Resumen: Introducción: el subtipo histopatológico es uno de los determinantes fundamentales en la clasificación de riesgo de los carcinomas cutáneos. Surge de una biopsia incisional que representa solo un porcentaje de la masa tumoral, siendo la principal preocupación la no detección de un subtipo agresivo. De ahí nace el interés de comparar la similitud entre ésta y la pieza de escisión quirúrgica (debulking) de la cirugía micrográfica de Mohs (CMM). Objetivos: comparar los resultados histopatológicos entre la biopsia incisional y el debulking en los carcinomas cutáneos tratados con CMM en el Servicio de Dermatología del Hospital de Clínicas en el período de noviembre de 2013 a marzo de 2019. Metodología: estudio retrospectivo descriptivo, se analizaron 202 pacientes con carcinomas de piel no melanoma (CPNM) sometidos a CMM en el servicio de Cirugía Dermatológica del Hospital de Clínicas "Dr. Manuel Quintela" entre noviembre de 2013 y marzo de 2019. Resultados: únicamente se consideran los casos donde en el debulking se halló tumor. Del total, la biopsia coincidió con el debulking en 61,39% de los casos. El debulking mostró un subtipo agresivo que no fue detectado en la biopsia en 8,41% de los casos. Conclusiones: el estudio histopatológico del debulking ha demostrado ser relevante, siendo la biopsia incisional parcialmente representativa para determinar el subtipo histopatológico de un CPNM, ya que aproximadamente 1 de cada 10 carcinomas podrían ser subdiagnosticados y tratados de manera insuficiente.

Abstract: Introduction: histological subtype is a vital element in determining the risk of skin cancer. It may be determined by an incisional biopsy which represents just a percentage of the tumor mass, the main concern lying in its potential failure to detect an agressive subtype. Therefore, comparing the results of biopsies with the surgically obtained piece with Mohs micrographic surgery is significantly relevant. Objective: to compare histopathologic evaluation results of incisional biospy and debulking in skin cancer treated with Mohs micrographic surgery at the Dermatology Service of the Clinicas University Hospital, between November, 2013 and March, 2019. Methodology: retrospective, descriptive study analysing 202 non-melanoma carcinomas which were treated with Mohs micrographic surgery the Dermatology Service of the "Dr. Manuel Quintela" Clinicas Hospital, between November, 2013 and March, 2019. Results: the study only considered the cases where bulking identified the tumor. Biopsy matched debulking in 61.39% of cases. Debulking detected an agressive subtype that was not detected in the biopsy in 8.41% of the cases. Conclusions: the hystopathological study of debulking has proved to be relevant, and the incisional biopsy was found to be partially representative in determining the histopathological subtype of non-melanoma carcinomas, since approximately 1 out of 10 carcinomas could be underdiagnosed and not appropriately treated.

Resumo: Introdução: o subtipo histopatológico é um dos determinantes fundamentais na classificação de risco dos carcinomas cutâneos. Identifica-se na biópsia incisional que representa apenas uma porcentagem da massa tumoral, sendo a principal preocupação a não detecção de um subtipo agressivo. Daí o interesse de comparar a semelhança entre esta e o material de excisão cirúrgica (citorreduçao - debulking) da Cirurgia Micrográfica de Mohs (CMM). Objetivos: comparar os resultados histopatológicos entre biópsia incisional e citorredução em carcinomas de pele tratados com CTM no serviço de Dermatologia do Hospital de Clínicas de novembro de 2013 a março de 2019. Metodologia: estudo descritivo retrospectivo onde foram analisados 202 carcinomas de pele não melanoma (NSCLC) submetidos a CCM no serviço de Cirurgia Dermatológica do Hospital de Clínicas "Dr. Manuel Quintela" entre novembro de 2013 e março de 2019. Resultados: foram considerados somente os casos em que um tumor foi encontrado em citorredução. Do total, a biópsia coincidiu com a cirurgia citorredutora em 61,39% dos casos. A citorredução mostrou um subtipo agressivo que não foi detectado na biópsia em 8,41% dos casos.

Application and prospect of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal metastasis from colorectal cancer / 中华肿瘤杂志

Colorectal cancer is one of the common malignant tumors in China, and its incidence is increasing with years. As the second most common metastatic site of colorectal cancer, peritoneum is difficult to diagnose early and with a poor prognosis. Systemic intravenous chemotherapy was used as the main treatment strategy for peritoneal metastasis in the past, but its systemic toxic and side effects were obvious, and it could not effectively control tumor progression. In recent years, the continuous development of surgical techniques, concepts, and equipment, as well as the introduction of new chemotherapy drugs and targeted drugs have significantly improved the quality of life and prognosis of patients with peritoneal metastasis of colorectal cancer. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) can effectively eradicated the intraperitoneal free cancer cells and subclinical lesions, while reducing systemic side effects of chemotherapy drugs, and achieve the radical cure of the tumor at the macro and micro levels to the greatest extent. It has been used as the first-line treatment program for peritoneal metastasis of colorectal cancer at home and abroad. This article focuses on the analysis and summary of the survival efficacy, prognostic factor analysis, and chemotherapy safety of CRS+ HIPEC in the treatment of colorectal cancer peritoneal metastasis. The existing problems and controversies of HIPEC therapy are discussed simultaneously.

The role of primary inguinal surgical debulking for locally advanced penile cancer followed by reconstruction with myocutaneous flap

ABSTRACT Purpose: To evaluate surgical complications and oncological outcomes of patients submitted to primary radical inguinal surgical debulking (PRISD) and myocutaneous pediculate flap reconstruction (MPFR) for locally advanced penile cancer (PC). Materials and Methods: Forty-two patients with ulcerated and/or fixed bulky inguinal masses underwent unilateral or bilateral PRISD with MPFR. Tensor fascia lata flap (TFL) was the standard of care for all patients. Additional use of the gracilis flap (GF) was carried out when necessary. Contra-lateral radical inguinal lymphadenectomy (RIL) was conduced when PRISD was performed unilaterally. Surgical complications were analyzed and stratified into minor and major according to the Bevan-Thomas classification. Adjunctive treatments were assessed and oncological outcomes analyzed. Results: Of the 42 patients evaluated, 10 (23.8%) underwent bilateral PRISD and 32 (76.2%) unilateral PRISD with contra-lateral RIL, totaling 84 lymphadenectomies. A total of 62 MPFRs were performed, 52 with TFL and 10 with GF. A total of 53 complications were identified, 49 related to PRISD with MPFR and 4 to RIL. Adjuvant chemotherapy was carried out in 16 patients. Median follow-up was 10.8 months with a median overall survival (OS) of 14.0 months against 6.0 months (p=0.006) for patients submitted to PRISD with adjuvant chemotherapy in relation to surgery alone. Conclusions: PRISD alone for advanced loco-regional PC is unlikely to promote long-term survival, although it can lead to temporary local control of the disease. Despite the feasibility of the procedure, it is related to high incidence of complications. Surgical treatment with adjuvant chemotherapy is associated with improved OS.

Ovarian metastasis from colorectal adenocarcinoma / Metástase ovariana de adenocarcinoma colorretal

Introduction: Ovarian metastases of gastrointestinal origin, also called Krukenberg tumors, have a guarded prognosis. Physicians need to look for alternatives in diagnosis and treatment for this clinical condition in order to improve the outcome of the patients. Objectives: To report the experience of the authors in the treatment of these patients, and to perform a review of the literature on the epidemiology, clinical presentation, diagnosis, treatment, and prognosis for ovarian metastases from colorectal cancer. Methods: We collected clinical information regarding the patients treated for ovarian metastasis from colorectal adenocarcinoma at our coloproctology service, and performed a search on the PubMed database using the terms colorectal cancer, ovarian metastasis, Krukenberg tumor and surgery. Conclusion: Large abdominal tumors are the most frequent presentation of ovarian metastasis from colorectal cancer. The diagnosis is based on a histopathological analysis, levels of carcinoembryonic antigen (CEA) and cancer antigen 125 (CA-125), and immunohistochemical studies for the cytokeratin 20 (CK20), caudal-type homeobox 2 (CDX2) and vilina markers. Citoreductive surgical procedures are the most promising approach to treatment, with the highest impact on overall survival. The prognosis is negatively influenced by the extent of the metastasis, by citoreductive surgical procedures with persistence of macro- or microscopic foci of the disease, and by low scores on the general well-being index of the patient. (AU)

Introdução: As metástases ovarianas de tumores gastrointestinais, também chamadas de tumores de Krukenberg, são neoplasias de prognóstico reservado. Exigem conhecimento de alternativas diagnósticas e terapêuticas para garantir melhora da sobrevida das pacientes. Objetivos: Relatar a experiência dos autores no tratamento dessas pacientes, e fazer uma revisão da literatura sobre a epidemiologia, apresentação clínica, diagnóstico, tratamento e prognóstico das metástases ovarianas do câncer colorretal. Métodos: Foi realizada uma coleta de informações clínicas de pacientes tratados por metástases ovarianas de adenocarcinoma colorretal em nosso serviço de coloproctologia, em conjunto com uma pesquisa na base de dados PubMed com os termos colorectal cancer, ovarian metastasis, Krukenberg tumor, e surgery. Conclusão: Volumosas massas abdominais constituem a principal apresentação clínica da doença. As alternativas diagnósticas incluem a avaliação histopatológica, a identificação dos níveis de antígeno cárcino-embriônico (ACE) e de antígeno de câncer 125 (CA-125), e exame imunoistoquímico de espécimes cirúrgicos para os marcadores citoqueratina 20 (CK20), homeobox 2 do tipo caudal (CDX2), e vilina. O tratamento citorredutor completo demonstrou o maior impacto na sobrevida dos pacientes. O prognóstico é influenciado negativamente pela extensão da doença metastática, por cirurgia citorredutiva com persistência focos microscópicos ou macroscópicos da doença, e baixo escore de índice de bem-estar geral do paciente. (AU)