Clinical research progress on disappearing colorectal liver metastases / 中华胃肠外科杂志

Colorectal cancer is currently one of the most common digestive system tumors, and the liver is the most common metastatic site of colorectal cancer. In recent years, with the continuous development of the multidisciplinary treatment for colorectal cancer patients, there are quite a few cases of disappearing liver metastases (DLM) after receiving preoperative chemotherapy (or combined targeted drug therapy), and the diagnosis and treatment of DLM is currently still a very challenging and controversial topic. This article sorts out the related researches on DLM in recent years, mainly including the following 4 aspects: (1) The factors associated with DLM, including the size and number of liver metastases, chemotherapy regimens and cycles, targeted therapy drugs, and the pattern of liver metastases, Ras/Braf status and the location of the primary lesion. (2) The relationship between DLM and true complete response (pathological complete response and persistent clinical complete response), and the related predictive factors of pathological complete response. (3) Clinical evaluation of DLM: preoperative evaluation includes ultrasound, CT, MRI, and PET, while intraoperative evaluation includes intraoperative exploration, intraoperative ultrasound, and augmented reality. (4) DLM treatment strategies, including surgical treatment, local treatment, non-surgical treatment and individualized treatment.

Clinical analysis of 554 patients with colorectal diverticulosis / 中华胃肠外科杂志

Objective: Most patients with asymptomatic colorectal diverticulosis are easily overlooked. However, some of diverticulosis become diverticulitis, bleeding and even perforation, which cause extensive harm to patients. The purpose of this study is to analyze the incidence, clinical features, diagnosis and treatment of colorectal diverticulosis in order to improve the clinical understanding of diverticulosis and its related complications. Methods: A descriptive cohort study was carried out. Clinical data of 554 patients with colorectal diverticulosis confirmed by CT, colonoscopy, digestive tract radiography or operation in Peking University First Hospital from January 2009 to June 2019 were retrospectively analyzed. Patients with malignant tumors, autoimmune diseases, long term use of immunosuppressive drugs, chronic liver diseases and renal diseases, and mental disorders were excluded. The analysis parameters included gender, onset age, clinical symptoms, location of diverticulitis, treatment and prognosis. According to the criteria established by the World Society of Emergency Surgery (WSES), acute diverticulitis was divided into 5 stages based on the extension of the infectious process. Stage 0 was simple diverticulitis and stage 1-4 was complicated diverticulitis. Results: Among the 554 patients with colorectal diverticulosis, 358 (64.6%) were males, the median onset age was 63 years; 191 patients (34.5%) had various digestive symptoms, of whom 113 (20.4%) had chronic constipation and abdominal distension, 78 (14.1%) had chronic diarrhea and abdominal pain; the other 363 patients had no obvious abdominal symptoms. Four hundred and six patients were found by colonoscopy and 465 patients were found by CT. Twenty-five patients were diagnosed by lower gastrointestinal tract radiography and 3 were confirmed during operation. There were 339 patients with multiple diverticula (61.2%) and 215 patients with single diverticulum (38.8%). 76.5% (424/554) of diverticula were located in colon, 37.0% (205/554) in ascending colon, 21.3% (118/554) in multiple sites, and 2.2% (12/554) in rectum. The median diameter of diverticulum was 7 mm, and 78 cases (14.1%) was ≥30 mm. Forty-nine patients (8.8%) developed acute diverticulitis, including 13 patients with simple diverticulitis and 36 patients with complicated diverticulitis. Among 36 patients with complicated diverticulitis, 29 (80.6%) were males, 27 (75.0%) had recurrent abdominal pain and fever before onset; diverticula of 25 cases were located in sigmoid colon; 11 cases in ascending colon. Nine cases developed sigmoid colon perforation and 8 cases developed vesicocolonic fistula, and these 17 patients underwent surgical treatment. The other 19 cases with complicated diverticulitis developed gastrointestinal bleeding, of whom 18 cases were male, 11 cases were located in ascending colon; 13 cases were healed after conservative treatment, 4 cases received endoscopic hemostatic intervention, and 2 cases underwent surgery. Conclusions: Colorectal diverticulosis is more common in male patients, and CT and colonoscopy are main diagnostic methods. The symptoms of complicated colonic diverticulitis are related to the location of diverticulum. In addition to symptomatic treatment, surgical procedures are the most important treatments.

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.

Nicotine protects against DSS colitis through regulating microRNA-124 and STAT3 / 中国药理学与毒理学杂志

OBJECTIVE Although it is generally believed that nicotine accounts for the beneficial effect of smoking on ulcerative colitis, the underlying mechanisms remain not well understood. Our previous finding that nicotine inhibits inflammatory responses through inducing miRNA-124 prompted us to ask whether the miRNA is involved in the protective action of nicotine on UC. METHODS MiR-124 expres-sion in colon tissues and cells was determined by q-PCR and in situ hybridization.The effect of miR-124 on protective role of nicotine in ulcerative colitis was evaluated in DSS-treated mice and IL-6-treated Caco-2 colon epithelial cells. Expression of p-STAT3/STAT3 was detected by immunohistochemistry and Western-blot analysis. RESULTS miR-124 expression is upregulated in colon tissues from UC patients and DSS-induced colitis mice. Nicotine treatment further elevated miR-124 level in lympho-cytes isolated from human ulcerative colonic mucosa and ulcerative colon tissues from DSS mice,both in infiltrated lymphocytes and epithelial cells. Administration of nicotine also reduced weight loss, improved DAI and decreased HE score in DSS-induced colitis mice.Moreover,knockdown of miR-124 in vivo significantly diminished the beneficial effect of nicotine on murine colitis, and in vitro on IL-6-treated Caco-2 colon epithelial cells.Further analysis indicated that nicotine inhibited STAT3 activation in vivo and in IL-6-treated Caco-2 colon epithelial cells and Jurkat human T lymphocytes,in which miR-124 knockdown led to increased activation of STAT3. Blocking STAT3 activity alone is beneficial for DSS colitis and also abolished nicotine′s protective effect in this model.CONCLUSION These data indicated that nicotine exerts its protective action in UC through inducing miR-124 and its effect on STAT3, and suggest that the miR-124/STAT3 system is a potential target for the therapeutic intervention of UC.

Estrogen weakens muscle endurance via estrogen receptor-p38 MAPK-mediated orosomucoid (ORM) suppression

Gender differences in fatigue manifest as females being more prone to feel exhaustion and having lower muscle endurance. However, the mechanisms of these effects remain unclear. We investigated whether orosomucoid, an endogenous anti-fatigue protein that enhances muscle endurance, is involved in this regulation. Female rats exhibited lower muscle endurance, and this gender difference disappeared in orosomucoid-1-deficient mice. Female rats also exhibited weaker orosomucoid induction in serum, liver and muscle in response to fatigue compared with male rats. Ovariectomy elevated orosomucoid levels and increased swimming time, and estrogen replenishment reversed these effects. Exogenous estrogen treatment in male and female mice produced opposite effects. Estrogen decreased orosomucoid expression and its promoter activity in C2C12 muscle and Chang liver cells in vitro, and estrogen receptor or p38 mitogen-activated protein kinase blockade abolished this effect. Therefore, estrogen negatively regulates orosomucoid expression that is responsible for the weaker muscle endurance in females.

Muscle fatigue: general understanding and treatment

Muscle fatigue is a common complaint in clinical practice. In humans, muscle fatigue can be defined as exercise-induced decrease in the ability to produce force. Here, to provide a general understanding and describe potential therapies for muscle fatigue, we summarize studies on muscle fatigue, including topics such as the sequence of events observed during force production, in vivo fatigue-site evaluation techniques, diagnostic markers and non-specific but effective treatments.

Therapy progression in surgery of inflammatory bowel diseases / 中华胃肠外科杂志

The inflammatory bowel diseases (IBDs), consisting of ulcerative colitis (UC) and Crohn's disease (CD), are characterized by idiopathic, chronic inflammation of the gastrointestinal tract. The overall incidence of IBDs is constantly increasing in eastern countries. In comparison with the data from western nations, in China, the incidence of male IBDs is relatively higher, the onset age is older. The severity of most cases is mild to moderate. The occurrence of fistula and peri-anal involvement are rare. Although significant improvements of IBDs therapy have been achieved in recent years, there are still over 30% UC and 70% CD cases need at least one surgery throughout their life span. Here we review the literatures published in recent years about the surgical management of IBDs.

Surgical outcomes for 187 patients with locally recurrent rectal cancer and analysis of prognostic factors / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the surgical outcomes for patients with locally recurrent rectal cancer (LRRC) and to analyze the prognostic factors.</p><p><b>METHODS</b>Clinical data of 187 patients with LRRC undergoing surgery at the First Hospital of peking University from January 1985 to December 2009 were retrospectively reviewed.</p><p><b>RESULTS</b>Procedures performed included local resection(n=34), abdominoperineal resection (n=35), posterior pelvic exenteration (n=17), total pelvic exenteration(TPE, n=98), TPE with sacrectomy (n=2), and TPE with internal hemipelvectomy (n=1). The operation was R0 in 87 patients, R1 in 60, and R2 in 40. The degree of radical resection was associated with the initial surgery and the degree of pelvic fixation (P<0.05). The pelvic recurrence rate was 44.4%(64/144). The operative morbidity and mortality were 47.5%(89/187) and 2.7%(5/187), respectively. The overall 3- and 5-year survival rates were 42.2% and 30.7%, respectively. The degree of radical resection and lymph node metastasis were independent risk factors associated with prognosis. The 5-year survival rates of R0, R1 and R2 were 42.6%, 17.2% and 0, respectively(P<0.01). The 5-year survival rates of patients with and without lymph node metastasis were 5.6% and 40.5%(P<0.01) respectively.</p><p><b>CONCLUSION</b>Accurate evaluation of extent of pelvic fixation and achievement of R0 resection are critical to improve the surgical outcomes for LRRC.</p>