Cáncer colorrectal ­ diagnóstico y tratamiento: revisión bibliográfica / Colorectal cancer ­ diagnosis and treatment: literature review

Colorectal cancer (CRC) is the third most prevalent cancer worldwide. Although improvements in detection and treatment have been implemented; CRC incidence, prevalence, and mortality remain high, even in developed countries. The risk of developing this cancer is related to poor eating habits, smoking, inflammatory bowel disease, polyps, genetic factors, and aging. There are several methods for detecting colorectal cancer, including the guaiac test, stool immunochemical test, stool DNA test, sigmoidoscopy, colonoscopy, and barium enema. The stage at which the cancer is detected determines the patient's prognosis, survival, and treatment. Treatments include endoscopic and surgical local excision, preoperative radiation therapy and systemic downstage therapy, extensive surgery for locoregional and metastatic disease, local ablative therapies for metastases, and palliative, targeted chemotherapy and immunotherapy.

El cáncer colorrectal (CCR) es el tercer cáncer más prevalente a nivel mundial. A pesar de que se han implementado mejoras en la detección y el tratamiento; la incidencia, la prevalencia y la mortalidad del CCR siguen siendo altas, incluso en países desarrollados. El riesgo de desarrollar este cáncer está relacionado con malos hábitos alimentarios, tabaquismo, enfermedad inflamatoria intestinal, pólipos, factores genéticos y envejecimiento. Existen varios métodos para detectar el cáncer colorrectal, como la prueba de guayaco, la prueba inmunoquímica de heces, la prueba de ADN en heces, la sigmoidoscopia, la colonoscopia y el enema de bario. El estadio en el que se detecta el cáncer determina el pronóstico, la supervivencia y el tratamiento del paciente. Los tratamientos incluyen escisión local endoscópica y quirúrgica, radioterapia preoperatoria y terapia sistémica de reducción del estadio, cirugía extensa para enfermedad locorregional y metastásica, terapias ablativas locales para metástasis y quimioterapia paliativa, terapia dirigida e inmunoterapia.

A Randomized Controlled Trial of Mindfulness in Recovery from Colorectal Cancer / 中国结合医学杂志

OBJECTIVE@#This study examined whether a 4-week group-based mindfulness intervention would be superior in reducing psychological distress in colorectal cancer (CRC) patients compared to a psychoeducation and cognitive behavioural skills learning support active control group.@*METHODS@#Patients with CRC were randomized via Computerised Permuted Block Randomisation to mindfulness or active control groups (2-h weekly sessions over 4 weeks). Outcomes were measured pre-intervention, and 8 weeks and 6 months post-baseline. The primary outcome was psychological distress measured by the Hospital Anxiety and Depression Scale. Secondary outcomes were generic quality of life (QoL), disease specific QoL, mindfulness, and intervention credibility and acceptability.@*RESULTS@#Sixty-eight participants were randomized to mindfulness (n=35) or active control group (n=33). Uptake of potentially eligible patients consenting was low (28.0%) and the dropout rate was 33.8%. Depression scores were reduced in both groups at week 8 (P=0.020). Control participants had greater improvement in generic mental QoL scores at week 8 than mindfulness (P=0.023). In disease specific QoL, there was reduction in impotence symptom in the mindfulness group (P=0.022) and reduction in faecal incontinence in the control group (P=0.019). The embarrassment symptom had a significantly lower increase in the mindfulness group at week 8 compared to the control group (P=0.009). Both groups rated the treatments as credible and acceptable.@*CONCLUSIONS@#Mindfulness was not superior to the active control group in terms of alleviating psychological distress but both treatments were associated with some improvements in depression. There was low uptake of both interventions. (Trial registration number: ACTRN12616001033437).

Watch and wait, worth It?

Background: The surgery with total mesorectal excision recommended by R. J. Heald in 1982 is the gold standard. Rectal cancer (RC) surgery has a morbidity rate ranging from 6 to 35%, and it can cause functional issues such as sexual, urinary, and bowel dysfunction in the long term. Neoadjuvant chemoradiotherapy (CRT) has been gaining ground in patients with lesions in the middle and lower rectum. The aim of the present study is to present the experience of a reference service in the treatment of RC. Patients and Methods: A retrospective study involving 53 patients diagnosed with RC between January 2017 and December 2019 with follow-up until December 2020. We examined tumor location, disease stage, digital rectal exam findings, carcinoembryonic antigen (CEA), therapeutic modality offered, and follow-up time. Results: A total of 32% of the patients were men and 68% were women, with a mean age of 60 years old. Location: upper rectum in 6 cases, middle rectum in 21 cases, and lower rectum in 26 cases with evolution from 9.8 to 13.5 months. The most frequent complaints were hematochezia and constipation. A total of 36 patients underwent neoadjuvant therapy: 11 complete clinical response (CCR) (30.5%), 20 (55.5%) partial clinical response (PCR), and no response in 5 patients (14%). The follow-up ranged from 12 to 48 months, with a mean of 30.5 months. A total of 25% of the patients had RC that went beyond the mesorectal fascia, and 22.64% had metastases in other parts of the body when they were diagnosed. Conclusion: Neoadjuvant radio and chemotherapy present themselves as an alternative in the treatment of rectal cancer. In 36 patients, 30.5% had a complete clinical response, 55.5% had a partial clinical response, and 14% had no response. It was worth doing the "Watch and Wait" (W&W) to sample. A definitive colostomy was avoided. However, it is necessary to expand the study to a larger follow-up and more patients. Additionally, it is necessary to implement a multicenter study. (AU)

Presentation patterns and outcomes in patients with colorectal cancer seeking the emergency department for consultation

Background: Patients with colorectal cancer may seek the emergency department for symptoms related to chemotherapy and radiotherapy side effects as well as those from the disease itself and from surgery complications. Objectives: To establish the epidemiological and clinical profile of colorectal cancer patients that look for consultations in the emergency department. Methods: Retrospective study of emergency room charts from colorectal cancer patients that consulted in a single oncological hospital for the period of 1 year. Results: Four hundred and forty-six consultations were identified (49.5% males and 50.5% females) with a mean age of 63 years and with advanced disease (most with tumor, node, metastases [TNM] stages III and IV). The most common complaint was abdominal pain (27.5%), followed by nausea (4.7%; more commonly seen in females with p =0.03) and bladder symptoms (4.7%; more commonly seen in males, with p =0.003). Infections (10.3%) and acute abdominal pain (9.1%) were the most frequent diagnoses. About 18% of them were admitted to the hospital and 80% were discharged home. Conclusion: The profile of patients with colorectal cancer seeking the emergency department comprises patients with advanced disease and a similar proportion of males and females. Symptom-driven complaints were the most frequent reason for consultations. (AU)

Surgical roles in the management of metachronus para-aortic lymph node recurrence and synchronous para-aortic lymph node metastasis in colorectal cancer patients

Background: The relative rarity of synchronous para-aortic lymph node (PALN) metastasis (SPM) and metachronous PALN recurrence (MPR) in colorectal carcinoma (CRC) patients leads to a limited number of studies on patient management, and no treatment guidelines have been established to date. Objective: To assess the prognostic, predictive roles, and long-term outcomes of different management strategies for isolated MPR and SPM in CRC patients to establish the best one. Materials and Methods: We included 35 CRC patients with isolated MPR and 25 patients with isolated SPM who underwent curative R0 resection. We performed PALN dissection (PALND) in 15 cases in MPR group and in 10 cases in the SPM group; all remaining patients in both groups underwent chemoradiotherapy (CRT) without further surgical intervention. During the study period of about 5 years, we compared the patients who underwent PALND and those who underwent CRT. Results: The overall survival and recurrence-free survival rates were significantly longer in patients who underwent PALND (p = 0.049 and 0.036 respectively). (AU)

The possibility of early diagnosis of colorectal cancer through expression of Lncrna UCA1, Lncrna LINC00970, and Wnt genes; an in-vitro study

Colorectal cancer is the 4thcause of cancer death; with considering the growth process of this cancer and the necessity of early diagnosis, the purpose of the research is to state the LncRNA 00970, LncRNA UCAI,and the Wntgene before and after the treatment by 5-Azacytidine epigenetic medicine, to reach the biomarker in the very first steps of colorectal cancer. In this experiment, the human colon cancer cell line (HT29) treated with different concentrations of 5-aza-2'-deoxycytidine (5-aza-dC) was utilized to induce DNA demethylation; Quantitative PCR (qPCR) was used to measure LncRNA UCA1and LncRNA LINC00970 and Wntexpression. There was a significant relationship between the expression of LncRNA 00970, LncRNA UCAI,and the Wntgene and its effects on colorectal (p < 0.05). The Wntgene was treated by 1 and 10 of 5-Azacytidine epigenetic medicine, which then experienced decreases. In LncRNA UCAI and LncRNA00970 in dose 1 micromolar of 5-Azacytidine had decrement and increment of expressionrespectively that explains their efficiency but in treatment by dose 10 mM of this medicine, no significant LncRNA expression difference was detected, 5-azacitidine has a direct impact on its target genes and LncRNAs.Therefore, it can be used in the early diagnosis of colorectal cancer.

Immunotherapy for microsatellite-instability-high advanced colorectal cancer / 中华胃肠外科杂志

Microsatellite instability-high (MSI-H) colorectal cancer accounts for approximately 10%-15% of all colorectal cancer patients, while in metastatic diseases the MSI-H population accounts for only 5% of patients. Previous studies have shown that early-stage MSI-H colorectal cancer patients have a good prognosis, but those with advanced disease have a poor prognosis and are not sensitive to chemotherapy. The advent of PD-1 antibodies has significantly improved the prognosis and changed treatment landscape in this population, not only achieving good outcomes in late-line therapy, but also significantly outperforming traditional chemotherapy combined with targeted therapy in first-line therapy. How to overcome primary and secondary drug resistance is a key issue in improving the outcome of MSI-H metastatic colorectal cancer, and commonly used approaches include changing chemotherapy regimens, combining with other immunotherapies, combining with anti-angiogenesis, and local treatments (surgery, radiotherapy, or interventional therapy). It is worth noting that immunotherapy has certain lifelong or even lethal toxicity, and the indications for neoadjuvant immunotherapy must be evaluated with caution. Neoadjuvant immunotherapy in MSI-H advantaged population can achieve high rates of pathological complete remission (pCR) and clinical complete remission (cCR). Therefore, for MSI-H patients with a strong intention to preserve anal sphincter and a strict evaluation of cCR after neoadjuvant immunotherapy, the Watch-and-Wait strategy offers an opportunity to preserve sphincter function and improve long-term survival quality in a subset of mid-to-low rectal cancers. Research on adjuvant immunotherapy in the field of colorectal cancer is also in full swing, and the results are worth waiting for.

Neoadjuvant immunotherapy in microsatellite stability or mismatch repair proficient colorectal cancer / 中华胃肠外科杂志

Immunotherapy has become an important treatment option for microsatellite instability-high (MSI-H) and mismatch repair deficient (dMMR) colorectal cancer. From late-line to first-line treatment, and even in neoadjuvant setting for early stage colorectal cancer, promising efficacy was observed with immunotherapy. In microsatellite stability (MSS) or mismatch repair proficient (pMMR) colorectal cancer, the researches of neoadjuvant immunotherapy have been conducted constantly. This paper focuses on the recent researches and progress of neoadjuvant immunotherapy for MSS or pMMR colorectal cancer. Neoadjuvant immunotherapy alone led to a good pathological response in a subset of patients. Studies of induction or consolidation immunotherapy before or after neoadjuvant chemoradiotherapy or concurrent immunotherapy during radiotherapy showed higher pathological complete remission (pCR) rates as compared to standard chemoradiotherapy. Studies on sequential dual immunotherapy after radiochemotherapy and targeted therapy combined with neoadjuvant immunotherapy are ongoing. At present, most of these are pilot studies with small sample size. More researches and long-term follow-up are needed to prove the efficacy of neoadjuvant immunotherapy in MSS or pMMR colorectal cancer.

Prognostic value of inflammation-based prognostic scores in patients with colorectal cancer

Background: Anatomopathological staging is the primary method to determine the prognosis of patients with colorectal carcinoma (CRC). However, new tools have been developed that can complement it, such as the analysis of the elevation of systemic inflammatory markers. Objective: To evaluate the impact of the elevation of scores based on inflammatory markers (the neutrophil-to-lymphocyte ratio [NLR], the Glasgow Prognostic Score [GPS], and isolated C-reactive protein [CRP]) in the prognosis of patients diagnosed with CRC and submitted to potentially curative surgery in Hospital de Braga, Portugal, between January 1st, 2005, and December 31st, 2010. Methods: A retrospective analysis of the data of 426 patients was performed, with a collection of several clinico-pathological variables, as well as the levels of lymphocytes, neutrophils, albumin and CRP, in the pre- and postoperative periods, to apply the different scores to the sample. Results: From the analysis of the survival curves, we concluded that patients with increased NLR in the pre- and postoperative periods present a lower cancer-related survival than patients with normal NLR (preoperative period: 93.7 versus 122 months; p<0.001; postoperative period: 112 versus 131 months; p=0.002). Patients with increased NLR in the pre- and postoperative periods also had a lower disease-free survival (preoperative period: 88.0 versus 122 months; p<0.001; postoperative period: 111 versus 132 months; p=0.002). In addition, increased pre- and postoperative NLR was associatedwith a higher risk of death due to CRC (preoperatively: hazard ratio [HR]=2.25; p<0.001; postoperatively: HR=2.18; p=0.003). However, the multivariate analysis shows that only postoperative NLR (ajusted HR =2.66; p=0.002) does so independently of the remaining variables. Conclusion: Regarding the scores applied to the sample, the NLR was the one that most consistently related to the prognosis of the patients. However, it would be useful to develop a prospective study that could confirm this relationship. (AU)

Impact of the Covid-19 pandemic on colorectal cancer surgery in Madrid

Introduction: The Covid-19 pandemic has had an important impact on colorectal cancer surgery, for hospital resources had to be redistributed in favour of Covid-19 patients. The aim of the present study is to analyze our results in colorectal oncologic surgery during the Covid-19 pandemic in patients with and without perioperative SARSCoV- 2 infection. Methods: In total, 32 patients (19 male and 13 female patients), with a mean age of 64 years (range: 57.2 to 69.5 years) with colorectal cancer underwent surgery under the recommendations of surgical societies included in a protocol. Data collection included clinical characteristics (gender, age, body mass index, American Society of Anesthesiologists score, tumor location, preoperative staging, lymphopenia), data related to SARS-CoV-2 infection (postoperative symptoms, diagnostic tests), operative details (surgical procedure, approach, duration, stoma), pathological outcomes (tumor stage, number of lymph nodes harvested, distal and circumferential radial margins, quality of the total mesorectal excision), and surgical outcomes (morbidity, mortality, hospital stay, and the rates of reoperation and readmission). Results: A total of 3 (9.4%) patients who underwent colorectal surgery during the Covid-19 pandemic were infected by SARS-CoV-2 in the postoperative period. Chronic obstructive pulmonary disease was associated with Covid-19 (6.2% versus 33.3%; p=0.042), and surgical morbidity was higher among Covid-19 patients (100% versus 37.9%; p=0.039). There were not significant differences between COVID-19 patients and non-COVID-19 patients in relation to the rest of the analyzed outcomes. Conclusion: During the Covid-19 pandemic, colorectal cancer surgery should be performed according to the recommendations of surgical societies. However, Covid- 19 patients could present a higher morbidity rate. (AU)

Proteinemia as a Prognostic Factor in Colorectal Cancers beyond Surgery and Chemotherapy

Background: Globally, 1,096,601, 704,376, and 48,541 new colon, rectum, and anus cancer cases were recorded in 2018, respectively. Besides, 551,269, 310,394 and 19,129 cases of colon, rectum, and anus cancer deaths occurred in the same year. As a result, these cancers ranked in the third level of cancer incidence, and in the second level of cancer mortality. As it is known, all cancer patients are subjected to cancerinduced and therapy-induced nutritional deficiencies (mainly of proteins and calories). The present study aimed to assess proteins level in colorectal cancer (CRC) patients who underwent surgery and chemotherapy. Methods: A combined retrospective and prospective study was performed. The present study enrolled 100 CRC patients with their data on surgical procedures and chemotherapy management. Assessments of the studied samples were conducted as a baseline before receiving chemotherapy and preoperatively as P0, while the period after that was termed as P1. The serum samples were collected to measure protein concentration. Total Protein Kit, Micro was used. Results: The mean age of the patients was 50.7±12.88 years old. Only 8% had a positive CRC family history. Rectosigmoid cancer represented the most frequent site, figured in 41% of the cases, followed by rectum cancer. Multiple sites of CRC metastasis were recorded in 15% of the patients. All patients received chemoradiation. Folinic acid (leucovorin), 5-FU, and oxaliplatin (FOLFOX) was the most used regimen, administered in 40% of the patients. Oxaliplatin and capecitabine (also called Xeloda) (XELOX) were administered in 14% of the patients. Folinic acid (leucovorin), 5-FU, oxaliplatin, and irinotecan (FOLFOXIRI) were administered in 16% of the patients. Single-agent oxaliplatin or carboplatin were administered in 6% of the patients, each. 5-FU plus leucovorin was administered to 12% of the patients. Three patients received irinotecan, and oxaliplatin (IROX). One patient received folinic acid (leucovorin), 5-FU and irinotecan (FOLFIRI). Also, Gemzar was administered to two patients only. A total of 80% of the patients underwent several surgical procedures. Anterior perineal resection (APR) and total mesorectal excision (TME) were the most common two surgeries, performed in 20 and in 30% of the patients, respectively. In P0 status, 44% of the patients suffered from low protein levels, and 13% of the patients were within the normal level. These findings were statistically different (p=0.03). After CRC management (i.e., P1 status), 70% of the patients had protein deficiency. These results have strong significant differences (p=0.000). The mean of protein concentration declined gradually after management, from 8.82±0.9 μg/L to 6.210.78 μg/L, with a strong association between a reduction in proteins levels towards deficiency and surgical procedures and chemotherapy protocols (p=0.000). Conclusion: The incidence of CRC is increasing annually, and the chance of being diagnosed with this type of cancer has risen in recent years. In the present study, the male to female ratio was 1:1.5, and the 5th decade of life was themost common age for the diagnosis of CRC. A negative family history and bowel inflammatory diseases (IBD) history did not exclude people from exposure to the incidence of CRC. Colorectal cancer with localized and moderately differentiated adenocarcinoma were the most common types in the present work. Tumor distance from the anal verge seems to be very important and plays a significant role in the choosing of surgical intervention types and chemoradiation protocols. Colorectal cancer acts as a complex condition and, in addition to its management, nutritional state influences it in different mechanisms. Most patients suffered from hypoproteinemia after surgery and chemoradiation. As a result, alteration in the treatment outcomes, delaying in wound healing, and an increase in postoperative complications may occur. (AU)

Fatores sociodemográficos e clínicos associados ao tempo para o início do tratamento de câncer de cólon e reto no Brasil, 2006-2015 / Sociodemographic and clinical factors associated with time to treatment for colorectal cancer in Brazil, 2006-2015 / Factores sociodemográficos y clínicos relacionados con el tiempo para el inicio del tratamiento de cáncer de colon y recto en Brasil, 2006-2015

O câncer de cólon e reto apresenta alta incidência mundialmente, porém a letalidade da doença é maior em países em desenvolvimento. O objetivo deste estudo é analisar fatores sociodemográficos e clínicos associados ao atraso para o início de tratamento de câncer de cólon e reto em hospitais no Brasil. Trata-se de estudo retrospectivo com dados dos registros hospitalares de câncer no Brasil de 2006 a 2015. O desfecho analisado é o tempo para início do tratamento de câncer de cólon e reto e possíveis associações entre variáveis sociodemográficas e referentes a fatores clínicos. Observaram-se disparidades no tempo para início do tratamento de acordo com estratos sociodemográficos e regiões geográficas. Há maior chance de atraso para o início do tratamento de câncer de cólon em pacientes com idade acima de 50 anos, de raça/cor de pele preta (OR = 1,50; IC95%: 1,21-1,84) e parda (OR = 1,28; IC95%: 1,17-1,42), analfabetos (OR = 1.50; IC95%: 1,19-1,90) ou com baixa escolaridade e cujo tratamento ocorreu em um município distinto de sua residência (OR = 1,25; IC95%: 1,14-1,38). Em pacientes com câncer de reto, há maior chance de atraso para o início do tratamento entre os casos com idade acima de 50 anos, de raça/cor de pele preta (OR = 1,44; IC95%: 1,20-1,72) e parda (OR = 1,29; IC95%: 1,19-1,39), analfabetos (OR = 1,71; IC95%: 1,40-2,09) ou com baixa escolaridade e cujo tratamento ocorreu em um município distinto de sua residência (OR = 1,35; IC95%: 1,25-1,47). Como conclusão, maior atenção deve ser destinada a reduzir o tempo para iniciar o tratamento nas regiões desfavorecidas e nos estratos identificados com barreiras de acesso ao tratamento em tempo oportuno.

Colorectal cancer presents high incidence worldwide, but case-fatality is higher in developing countries. The study's objective was to analyze sociodemographic and clinical factors associated with delay in the initiation of treatment for colorectal cancer in hospitals in Brazil. This is a retrospective study of data from hospital cancer registries in Brazil from 2006 to 2015. The target variable is time to initiation of treatment for colorectal cancer and possible associations between sociodemographic variables and clinical factors. The analysis revealed disparities in time to treatment according to sociodemographic strata and geographic regions. Higher odds of treatment delay were associated with age over 50 years, black race/color (OR = 1.50; 95%CI: 1.21-1.84) and brown race/color (OR = 1.28; 95%CI: 1.17-1.42), illiteracy or low schooling (OR = 1.50; 95%CI: 1.19-1.90), and treatment in a city far from the patient's residence (OR = 1.25; 95%CI: 1.14-1.38). For rectal cancer, higher odds of treatment delay were associated with age over 50 years, black (OR = 1.44; 95%CI: 1.20-1.72) or brown race/color (OR = 1.29; 95%CI: 1.19-1.39), illiteracy or low schooling (OR = 1.71; 95%CI: 1.40-2.09), and treatment in a city far from the patient's residence (OR = 1.35; 95%CI: 1.25-1.47). In conclusion, greater attention should be given to reducing the time to initiation of treatment in underprivileged regions and in social strata identified with barriers to timely treatment access.

El cáncer de colon y recto presenta una alta incidencia mundialmente, pese a que la letalidad de la enfermedad es mayor en países en desarrollo. El objetivo de este estudio fue analizar los factores sociodemográficos y clínicos, asociados al retraso para el inicio del tratamiento de cáncer de colon y recto en hospitales en Brasil. Se trata de un estudio retrospectivo con datos de registros hospitalarios de cáncer en Brasil de 2006 a 2015. El resultado analizado es el tiempo para el inicio del tratamiento de cáncer de colon y recto, así como las posibles asociaciones entre variables sociodemográficas y las relacionadas con factores clínicos. Se observó disparidades en el tiempo para el inicio del tratamiento, según estratos sociodemográficas y regiones geográficas. Existe una mayor oportunidad de retraso para el inicio del tratamiento de cáncer de colon en pacientes con una edad por encima de 50 años, de raza/afrodescendiente (OR = 1,50; IC95%: 1,21-1,84) y mulata/mestiza (OR = 1,28; IC95%: 1,17-1,42), analfabetos (OR = 1,50; IC95%: 1,19-1,90) o con baja escolaridad, y cuyo tratamiento se produjo en un municipio distinto al de su residencia (OR = 1,25; IC95%: 1,14-1,38). En pacientes con cáncer de recto existe una mayor oportunidad de atraso para el inicio del tratamiento entre los casos con una edad por encima de 50 años, de raza/afrodescendiente (OR = 1,44; IC95%: 1,20-1,72) y mulata/mestiza (OR = 1,29; IC95%: 1,19-1,39), analfabetos (OR = 1,71; IC95%: 1,40-2,09) o con baja escolaridad, y cuyo tratamiento se produjo en un municipio distinto al de su residencia (OR = 1,35; IC95%: 1,25-1,47). Como conclusión, se debe prestar mayor atención a la reducción del tiempo para comenzar el tratamiento en las regiones desfavorecidas y en estratos identificados con barreras de acceso al tratamiento en el tiempo adecuado.

China guideline for diagnosis and comprehensive treatment of colorectal liver metastases (version 2020) / 中华胃肠外科杂志

The liver is the most common anatomical site for hematogenous metastases of colorectal cancer, and colorectal liver metastasis is one of the most difficult and challenging situations in the treatment of colorectal cancer. In order to improve the diagnosis and comprehensive treatment in China, the Guidelines have been edited and revised for several times since 2008, including the overall evaluation, personalized treatment goals and comprehensive treatments, to prevent the occurrence of liver metastases, improve the resection rate of liver metastases and survival. The revised Guideline version 2020 includes the diagnosis and follow-up, prevention, multidisciplinary team (MDT), surgery and local ablative treatment, neoadjuvant and adjuvant therapy, and comprehensive treatment, with state-of-the-art experience and findings, detailed content, and strong operability.

Microbe-based management for colorectal cancer / 中华医学杂志(英文版)

Colorectal cancer (CRC) is one of the most prevalent, most lethal cancers in the world. Increasing evidence suggests that the intestinal microbiota is closely related to the pathogenesis and prognosis of CRC. The normal microbiota plays an essential role in maintaining gut barrier function and the immune microenvironment. Recent studies have identified carcinogenic bacteria such as enterotoxigenic Bacteroides fragilis (ETBF) and Streptococcus gallolyticus (S. gallolyticus), as well as protective bacterial such as Akkermansia muciniphila (A. muciniphila), as potential targets of CRC treatment. Gut microbiota modulation aims to restore gut dysbiosis, regulate the intestinal immune system and prevent from pathogen invasion, all of which are beneficial for CRC prevention and prognosis. The utility of probiotics, prebiotics, postbiotics, fecal microbiota transplantation and dietary inventions to treat CRC makes them novel microbe-based management tools. In this review, we describe the mechanisms involved in bacteria-derived colorectal carcinogenesis and summarized novel bacteria-related therapies for CRC. In summary, we hope to facilitate clinical applications of intestinal bacteria for preventing and treating CRC.

Meta analysis of whether cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy can improve survival in patients with colorectal cancer peritoneal metastasis / 中华胃肠外科杂志

Objective: To explore whether the cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) can improve the survival rate of colorectal cancer patients with peritoneal metastasis. Methods: The relevant studies were systematically retrieved from PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP database, and the study of French Elias' team on peritoneal metastasis was retrieved manually. Inclusion criteria: (1) The patients were colorectal cancer peritoneal metastasis. (2) There were CRS+HIPEC treatments (treatment group) and other treatments (control group). (3) Survival analysis data of treatment group and control group were available. (4) Types of studies were randomized controlled trials, cohort studies, or case-control studies. (5) The literature was in Chinese or English. Exclusion criteria: (1) studies without full-text; (2) studies without complete data. The literature screening and data extraction were carried out by two people independently, and the third person decided on the literature with differences. The extracted data included authors, year of publication, number of patients, time of enrollment, time of follow-up, studies design, treatment regimen, hazard ratio (HR) and 95% CI of treatment group and control groups. If the HR and 95% CI of the treatment group and control group were not provided in the literature, Engauge Digitizer 11.1 software was used to extract the time of follow-up and the survival rate at the corresponding time point from the survival curves of both groups, and the HR and 95% CI of both groups were calculated by combining the number of both groups. The quality of study was evaluated by Newcastle-Ottawa scale (NOS) or Cochrane collaboration's tool for assessing risk bias. STATA 15.1 software was used for statistical analysis. HR and 95% CI of both groups were pooled and analyzed. Inter-trial heterogeneity was assessed by Q test and I(2) statistics. When there was no significant heterogeneity (Q test: P≥0.10), fixed-effect model was used for pooled analysis. When significant heterogeneity existed (Q test: P<0.10), random effect model was used for pooled analysis, and subgroup analysis was used to find out the source of heterogeneity. Sensitivity analysis was used to evaluate the stability of the pooled results. Publication bias was assessed by Egger's test and Begg's test (P<0.05 indicated publication bias) and it is reflected by the visual symmetry of Begg's funnel plot on the natural logarithm of HR. Results: A total of 10 studies were enrolled in the meta-analysis, including 1 randomized controlled trial and 9 cohort studies. The risk of bias in 1 randomized controlled trial was uncertain, and 9 cohort studies were all higher than 7 points, indicating high quality literatures. There were 781 patients in treatment group receiving CRS+HIPEC and 2452 patients in control group receiving other treatment, including tumor cytoreductive surgery (CRS), palliative chemotherapy (PC) and intraperitoneal chemotherapy (IPC). The results of pooled analysis by random effect model showed that the OS rate in treatment group was significantly higher than that in control group (HR=0.43, 95% CI: 0.34-0.54), but the heterogeneity of the study was high (P=0.024, I(2)=52.9%). The subgroup analysis of different control treatments showed that the OS rate in treatment group was significantly higher than that in CRS control group (HR=0.63, 95% CI: 0.44-0.90), in PC control group (HR=0.37, 95% CI: 0.32-0.43), in CRS+ IPC control group (HR=0.60, 95% CI: 0.37-0.96), and the heterogeneity of each subgroup was low (CRS control group: P=0.255, I(2)=22.9%; PC control group: P=0.222, I(2)=29.9%; CRS+IPC control group: P=0.947, I(2)=0). Due to the low heterogeneity of subgroups, fixed-effect models were used to pool and analysis. The results of sensitivity analysis revealed that there was little difference between the pooled analysis results after each study was deleted, suggesting that the pooled analysis results were more reliable. Publication bias detection of each study showed Begg's test (P=0.088) >0.05 and Egger's test (P=0.138)>0.05. According to the Begg's funnel plot, the scatter point distribution was basically symmetric, indicating that there was no publication bias in the included study. Conclusion: CRS+HIPEC can improve the OS of patients with colorectal cancer peritoneal metastasis.

Complete cytoreductive surgery is the key to improving survival of colorectal cancer patients with peritoneal metastases: comment on PROPHYLOCHIP and PRODIGE 7 / 中华胃肠外科杂志

Peritoneal carcinomatosis (PC) is one of the difficult problems in the treatment of colorectal cancer (CRC). Based on several retrospective analyses of large samples and prospective randomized controlled studies (RCTs), NCCN and PSOGI recommend cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for selected CRC patients with mild to moderate PC. There are two important controversial issues in this field: the survival benefit of second-look surgery plus HIPEC for the patients with high risk of PC, and the specific benefit of HIPEC added to CRS for patients with PC. PROPHYLOCHIP found that second-look surgery plus HIPEC in patients at high risk of PC does not result in increased survival. PRODIGE 7 showed that overall survival (OS, 41.7 months vs. 41.2 months, P=0.99) and recurrence-free survival (RFS, 13.1 months vs. 11.1 months, P=0.43) were similar between the HIPEC group and non-HIPEC group, and suggested that HIPEC is not necessary for patients who underwent complete CRS. However, due to a series of problems in the design and implementation of this trial, the conclusion has caused great controversy and has not been widely recognized. Through detailed analysis and in-depth discussion, we believe that the benefit of HIPEC could not be denied according to PRODIGE 7. CRS + HIPEC is the embodiment and model of the concept of "Solid tumor treatment is surgery-based integrated treatment". CRS is the cornerstone of therapeutic strategies with curative intent for CRC PC and complete CRS is the key to improve the prognosis. Furthermore, HIPEC is an effective supplement to CRS.

Strategies and challenges in the diagnosis and treatment of colorectal cancer peritoneal metastasis / 中华胃肠外科杂志

Peritoneum is a common metastatic site of colorectal cancer and has worse prognosis compared with other metastatic sites. Peritoneal metastasis was previously considered as a terminal state of the disease, and palliative treatment with systemic chemotherapy was the main treatment method. With the gradual acceptance of the cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) treatment model by surgeons and the application of targeted and immunotherapeutic drugs, the prognosis of patients with colorectal cancer peritoneal metastasis has been greatly improved. However, the diagnosis and treatment of peritoneal metastasis still face many challenges and controversies. Based on the evolution of the understanding of colorectal cancer peritoneal metastasis, the possible mechanisms of peritoneal metastasis are discussed, including the theory of "oligometastases" and the theory of "seed and soil". Besides, we further investigate the diagnosis and treatment strategies of colorectal cancer peritoneal metastasis and the facing challenges, including the limitations of imaging examination, the controversy of laparoscopic exploration, the difficulty in assessing peritoneal metastatic load, the limited means of postoperative recurrence monitoring and efficacy evaluation, and the significant variation in the diagnosis and treatment level among different regions of China. Meanwhile, we emphasize the importance of multidisciplinary perioperative management of CRS+HIPEC, and propose that the basic and clinical transformation research of peritoneal metastasis should be strengthened, and the promotion of standardized diagnosis and treatment of peritoneal metastasis is the key to improve the prognosis of patients with colorectal cancer peritoneal metastasis.

A challenge for colorectal surgeons: pathogenesis, progression and management of the secondary tumors of the ovary / 中华胃肠外科杂志

A common clinical problem encountered by colorectal surgeons is the secondary tumors of the ovary (STO), particularly in young female patients. Most STO are from the digestive tract, and the known possible metastatic mechanisms include lymphatic, hematogenous, and intraperitoneal spreading. The molecular and histopathological characteristics of STO from different sites are diverse. It is particularly important to correctly identify the origin and feature of STO, which should be clarified by combining medical history, histopathology, immunohistochemistry, molecular biology, imaging and other means. The prognosis of patients with STO is poor in general. Comprehensive therapies based on surgical resection can benefit some patients. There is no specific treatment for STO at present, but not giving up easily on these patients is the right choice that every surgeon should understand.

Research progress of conversion therapy in colorectal cancer liver metastases / 中华胃肠外科杂志

The probability of developing liver metastases in patients with colorectal cancer is 40%-50%. Liver metastases remain an important adverse factor affecting long-term prognosis of colorectal cancer patients. Surgical resection of liver metastases is the only potentially curative treatment option. After comprehensive treatment, initially unresectable liver metastases might be converted to resectable tumors. This concept is known as conversion therapy. In this review, research status of conversion therapy in colorectal cancer liver metastases was summarized, providing updated concept of resectability, discussions on the assessment of tumor response and timing of operation, debates on the influence on tumor sidedness, and latest advancement in the treatment strategy of conversion therapy. Through analyzing existing problems, we hope to offer insights into possible progress in the future and provide references for the development of clinical practice.

Repermeabilización portal intrahepática luego de ligadura de rama derecha de vena porta: reporte de un caso / Intrahepathic portal revascularization following right portal vein ligation: a case report / Repermeabilização portal intra-hepática após ligadura do ramo direito da veia porta: relato de caso

Resumen: La ligadura de una rama de la vena porta constituye un procedimiento con buenos resultados para evitar la falla hepática posoperatoria en caso de hepatectomías extremas al provocar la hipertrofia del hígado contralateral. Sin embargo, la repermeabilización de ésta ha sido demostrada por la presencia de anastomosis porto portales intrahepáticas, pudiendo determinar una disminución de la hipertrofia esperada o necesaria. Como objetivo documentamos un caso clínico de repermeabilización intrahepática de la vena porta, evento no deseado de la hepatectomía en dos tiempos para el tratamiento de metástasis hepáticas bilobares de origen colorrectal y describimos alternativas para evitar o tratar dicha repermeabilización.

Summary: Left or right portal vein ligation to prevent post-operative liver failure in the case of extreme hepatectomy constitutes a procedure with a good prognosis, as it causes contralateral liver hypertrophy. However, its revascularization has been proved by intrahepatic porto-portal anastomoses, which could result in a reduction of the expected or required hypertrophy. The study aims to record a clinical case of intrahepatic revascularization of the portal vein, an unwanted event of the two-stage hepatectomy to treat bilobar hepatic metastasis of colorectal origin, and describe alternatives to avoid or treat such revascularization.

Resumo: A ligadura de um ramo da veia porta é um procedimento com bons resultados para evitar a insuficiência hepática pós-operatória em hepatectomias extremas por causar hipertrofia do fígado contralateral. No entanto, sua repermeabilização tem sido demonstrada pela presença de anastomose porto-portal intra-hepática, que pode determinar diminuição da hipertrofia esperada ou necessária. Como objetivo, documentamos um caso clínico de repermeabilização da veia porta intra-hepática, um evento indesejado de hepatectomia em dois estágios para o tratamento de metástases hepáticas bilobares de origem colorretal, e descrevemos alternativas para evitar ou tratar essa repermeabilização.