Can the parkland grading scale predict the difficulty of laparoscopic cholecystectomy? A new approach to validation.

BACKGROUND: The Parkland Grading Scale (PGS) is an intraoperative grading scale to stratify gallbladder disease severity during laparoscopic cholecystectomy (LC). We evaluated the usefulness of the PGS in predicting the difficulty levels of LC procedures using a novel approach. METHODS: A total of 261 patients diagnosed with cholelithiasis and cholecystitis who underwent LC were assessed. The PGS and the surgical difficulty grading system were used to evaluate surgical procedures by reviewing the operation videos. Clinical baseline characteristics and post-treatment outcomes were also recorded. Differences between the five PGS grades in terms of surgical difficulty scores were analyzed using the Jonckheere-Terpstra test. The relationship between PGS grades and surgical difficulty scores was assessed using Spearman's Rank correlation. Finally, the linear trends between morbidity scores and PGS grades were evaluated using the Mantel-Haenszel test. RESULTS: There was a significant difference in the surgical difficulty scores for the five PGS grades (p < 0.001). In pairwise comparison, each grade (1-5) was significantly different from the others (p < 0.05) in terms of surgical difficulty, except Grade 2 vs. 3 (p = 0.07) and Grade 3 vs. 4 (p = 0.08). There was a significant correlation between PGS grades and surgical difficulty scores (rs = 0.681, p < 0.001). There was also a significant linear association between morbidity and PGS grades (p < 0.001). Spearman's R value was 0.176 (p = 0.004). CONCLUSION: The PGS can accurately assess the surgical difficulty level of LC. The precision and conciseness of the PGS make it suitable for use in future research.

Increased difficulty and complications of delayed laparoscopic cholecystectomy following percutaneous transhepatic gallbladder drainage in acute cholecystitis: a retrospective study.

BACKGROUND: Percutaneous transhepatic gallbladder drainage (PTGBD) is a relatively less invasive alternative treatment to cholecystostomy. However, the influence of the difficulty of delayed laparoscopic cholecystectomy (DLC) after PTGBD on clinical outcomes remains unknown. This study aimed to evaluate the clinical effects of DLC following PTGBD. METHODS: The clinical data of 113 patients diagnosed with moderate (grade II) acute cholecystitis according to the 2018 Tokyo Guidelines in the acute phase and who underwent DLC in our hospital from January 2018 to February 2022 were retrospectively collected and separated into two groups according to whether they received PTGBD treatment in the acute stage. The PTGBD group comprised 27 cases, and the no-PTGBD group included 86 cases. The TG18 difficulty score was used to evaluate every surgical procedure in the cases by reviewing the surgical videos. The clinical baseline characteristics and post-treatment outcomes were also evaluated. RESULTS: Both groups showed significant differences in length of postoperative stay, blood loss, operation time, and difficulty score. The PTGBD group showed a significantly longer postoperative stay and operation time, more blood loss, and a much higher difficulty score than the no-PTGBD group. Conversion rates did not differ. The morbidity rate in the PTGBD group was statistically higher. CONCLUSIONS: PTGBD is an efficient way to relieve the symptoms of acute cholecystitis. However, it may increase the difficulty and complications of DLC.

The impact of COVID-19 pandemic on the treatment of acute appendicitis in China.

OBJECTIVE: This research aims to analyze the impact of the novel coronavirus pandemic on the hospital visits of patients with acute appendicitis. METHODS: The retrospective analysis was designed to look at the treatment of acute appendicitis in the Department of General Surgery in Beijing Jishuitan Hospital before and during the COVID-19 pandemic (2019-2020). Data was analyzed by the numbers of patients, sex, age, onset time, fever or not, laboratory examination, imaging test, and treatment. And we analyzed the differences between the "pre-COVID group" and "during-COVID group". RESULTS: Compared with the year 2019, the number of acute appendicitis patients has diminished substantially during the COVID-19 pandemic (2020), but the number elevated with the control of the pandemic. Even if we did not find the differences of the treatment before and during the pandemic (P = 0.932), the onset time to emergency was significantly longer (P < 0.001), and more patients had showed fever (P < 0.001) during the COVID-19 pandemic. And the total number of white blood cells and C reactive protein level were significantly higher in 2020 than those in 2019 (P = 0.006, 0.003). And the same result was found in patients with appendiceal fecalith (P = 0.047). CONCLUSION: During the pandemic of the new coronavirus pneumonia, the number of patients with acute appendix treatment dropped significantly, mainly because it took longer than before, and the condition was more severe. It can be seen that the new coronary pneumonia has a great impact on the patients' medical treatment behavior, and the active prevention and treatment of the new coronavirus pneumonia is currently an important and urgent issue.

Decision-making changes for patients and medical personnel in the management of acute appendicitis during the COVID-19 pandemic.

BACKGROUND: Acute appendicitis is the most common cause of acute abdomen. During the pandemic, to contain the spread of COVID-19, there were some integral changes in the medical processes based on the pandemic prevention policy, especially regarding emergency surgery. This study was conducted to investigate whether this pandemic also impacted the decision-making for both patients and medical personnel along with the treatment outcomes. METHODS: Patients of age 18 years or older who were diagnosed clinically and radiologically with acute appendicitis between Jan 1, 2017, and Dec 31, 202,0 were reviewed. The data of 1991 cases were collected and used for this study. Two groups were formed, one group before and the other group after the outbreak. The gathered data included gender, age, appendiceal fecalith, outcomes of treatment, and long-term outcomes of non-operation (8 months follow-up). We also collected details of surgical cases from the above two groups. This data also included age, gender, appendiceal fecalith, fever, jaundice, length of onset before presenting to an emergency department (ED), anesthesia, surgery, white cell count, pathology, complications, and length of stay. We compared the above data respectively and analyzed the differences. RESULTS: Compared to the period before the outbreak, patient visits for acute appendicitis remarkably dropped (19.8%), but surgical cases showed no change (dropped by roughly 5%). There were significant differences (P < 0.05) in failure of non-operation(after the pandemic 8.31% vs. before pandemic 3.22%), interval appendectomy(after pandemic 6.29% vs. before pandemic 12.84%), recurrence(after pandemic 23.27% vs. before pandemic 14.46%), and outcomes of recurrence. There was a significant difference (P < 0.05) in anesthesia method, surgery way, and complications( before pandemic 4.15% vs. after pandemic9.89% P < 0.05) in patients who underwent the surgery. There was no statistical difference (P > 0.05) concerning age, gender, fever, jaundice, appendiceal fecalith, white cell count, and length of onset before presenting to the ED. CONCLUSION: The current pandemic prevention policy is very effective, but some decision-making processes of doctor-patient have changed in the context of COVID-19 pandemic, that further influenced some treatment outcomes and might lead to a potential economic burden. It is essential to address the undue concern of everyone and optimize the treatment process.

A nomogram for predicting the likelihood of lymph node metastasis in early gastric patients.

BACKGROUND: Early gastric cancer is defined as a lesion confined to the mucosa or submucosa, regardless of the size or lymph node metastasis. Treatment methods include endoscopic mucosal resection or endoscopic submucosal dissection, wedge resection, laparoscopically assisted gastrectomy and open gastrectomy. Lymph node metastasis is strong related with survival and recurrence. Therefore, the likelihood of lymph node metastasis is one of the most important factors when determining the most appropriate treatment. METHODS: We retrospectively analyzed 597 patients who underwent D2 gastrectomy for early gastric cancer. The relationship between lymph node metastasis and clinicopathological features was analyzed. Using multivariate logistic regression analyses, we created a nomogram to predict the lymph node metastasis probability for early gastric cancer. Receiver operating characteristic analyses was performed to assess the predictive value of the model. RESULTS: In the present study, 58 (9.7%) early gastric cancer patients were histologically shown to have lymph node metastasis. The multivariate logistic regression analysis demonstrated that the age at diagnosis, differentiation status, the presence of ulcers, lymphovascular invasion and depth of invasion were independent risk factors for lymph node metastasis in early gastric cancer. Additionally, the tumor macroscopic type, size and histology type significantly correlated with these important independent factors. We constructed a predictive nomogram with these factors for lymph node metastasis in early gastric cancer patients, and the discrimination was good with the AUC of 0.860 (95% CI: 0.809-0.912). CONCLUSIONS: We developed an effective nomogram to predict the incidence of lymph node metastasis for early gastric cancer patients.

Nomogram for predicting lymph node metastasis rate of submucosal gastric cancer by analyzing clinicopathological characteristics associated with lymph node metastasis.

BACKGROUND: To combine clinicopathological characteristics associated with lymph node metastasis for submucosal gastric cancer into a nomogram. METHODS: We retrospectively analyzed 262 patients with submucosal gastric cancer who underwent D2 gastrectomy between 1996 and 2012. The relationship between lymph node metastasis and clinicopathological features was statistically analyzed. With multivariate logistic regression analysis, we made a nomogram to predict the possibility of lymph node metastasis. Receiver operating characteristic (ROC) analysis was also performed to assess the predictive value of the model. Discrimination and calibration were performed using internal validation. RESULTS: A total number of 48 (18.3%) patients with submucosal gastric cancer have pathologically lymph node metastasis. For submucosal gastric carcinoma, lymph node metastasis was associated with age, tumor location, macroscopic type, size, differentiation, histology, the existence of ulcer and lymphovascular invasion in univariate analysis (all P<0.05). The multivariate logistic regression analysis identified that age ≤50 years old, macroscopic type III or mixed, undifferentiated type, and presence of lymphovascular invasion were independent risk factors of lymph node metastasis in submucosal gastric cancer (all P<0.05). We constructed a predicting nomogram with all these factors for lymph node metastasis in submucosal gastric cancer with good discrimination [area under the curve (AUC) =0.844]. Internal validation demonstrated a good discrimination power that the actual probability corresponds closely with the predicted probability. CONCLUSIONS: We developed a nomogram to predict the rate of lymph node metastasis for submucosal gastric cancer. With good discrimination and internal validation, the nomogram improved individualized predictions for assisting clinicians to make appropriated treatment decision for submucosal gastric cancer patients.

Prognostic role of lymph node metastasis in early gastric cancer.

OBJECTIVE: To clarify the relationship between clinicopathological features and lymph node metastasis and to propose the potential indications of lymph node metastasis for prognosis in early gastric cancer (EGC) patients. METHODS: We retrospectively observed 226 EGC patients with lymph node resection, and analyzed the associations between lymph node metastasis and clinicopathological parameters using the chi-square test in univariate analysis and logistic regression analysis in multivariate analysis. Overall survival analysis was determined using the Kaplan-Meier and log-rank test. We conducted multivariate prognosis analysis using the Cox proportional hazards model. RESULTS: Of all the EGC patients, 7.5% (17/226) were histologically shown to have lymph node metastasis. The differentiation, lymphovascular invasion and depth of invasion were independent risk factors for lymph node metastasis in EGC. The 5- and 10-year survival rates were significantly lower in patients with lymph node metastasis than in those without and the patients also had shorter progress-free survival time. Lymph node metastasis and tumor size were independent prognostic factors for EGC. The status of the lymph nodes was a significant factor in predicting recurrence or metastasis after surgery. CONCLUSIONS: The undifferentiated carcinoma and lymphovascular and/or submucosal invasion were associated with a higher incidence of lymph node metastasis in EGC patients, whom need to perform subsequent D2 lymphadenectomy or laparoscopic lymph node dissection and more rigorous follow-up or additional chemotherapy/radiation after D2 gastrectomy for poor prognosis and high recurrence/metastasis rate.

Level of circulating PD-L1 expression in patients with advanced gastric cancer and its clinical implications.

OBJECTIVE: The programmed cell death-1 receptor/programmed cell death-1 ligand (PD-1/PD-L1) pathway plays a crucial role in tumor evasion from host immunity. This study was designed to evaluate the association between circulating PD-L1 expression and prognosis in patients with advanced gastric cancer. METHODS: Totally 80 advanced gastric cancer patients and 40 health controls from Beijing Cancer Hospital were enrolled in the present study. Circulating PD-L1 expression was tested by enzyme-linked immunosorbent assay (ELISA). The associations between the expression level of PD-L1 and clinicopathological features and prognosis were analyzed statistically. RESULTS: Expression of PD-L1 in advanced gastric cancer patients was significantly up-regulated compared with health people (P=0.006). The expression of PD-L1 was significantly correlated with differentiation and lymph node metastasis (P=0.026 and P=0.041, respectively). Although we didn't find significant difference in all advanced gastric cancer patients with different PD-L1 expression, the adenocarcinoma patients with higher up-regulated PD-L1 expression had much better prognosis than low expression patients (65.6% vs. 44.7%, P=0.028). CONCLUSIONS: PD-L1 was elevated in advance gastric cancer patients and may play an important role in tumor immune evasion and patients prognosis.

Phosphatase of regenerating liver-3 (PRL-3) is associated with metastasis and poor prognosis in gastric carcinoma.

BACKGROUND: PRL-3 is a member of phosphatases of regenerating liver family, characterized by phosphatase active domain and C-terminal prenylation motif. Overexpression of PRL-3 has been implicated in multiple cancers. Here we examined the clinical significance of PRL-3 in gastric cancer together with its metastatic biological functions utilizing different structural mutants. METHODS: PRL-3 expression was analyzed immunohistochemically in 196 gastric cancer patients and 21 cases of liver metastasis. A series of wild type PRL-3 or its mutant plasmids were expressed in BGC823 cells to investigate the relationship between its catalytic activity, cellular localization and metastatic potential in vitro. RESULTS: Positive staining of PRL-3 was observed in 19.4% (38/196) gastric cancer tissues compared with 76.2% (16/21) in liver metastasis. Statistical analysis revealed that PRL-3 expression correlated with lymph node metastasis and vascular invasion (P<0.05). Patients with high PRL-3 expression showed poorer 5-year overall survival (P=0.011). Wild type PRL-3 expressing cells resulted in enhanced migration and invasion ability, which were greatly crippled in form of PRL-3(C104S) or PRL-3(ΔCAAX) mutants accompanied with its alteration in subcellular localization. CONCLUSIONS: Metastasis associated protein PRL-3 may serve as a potential prognostic biomarker in human gastric cancer. Both the phosphatase catalytic activity and cellular localization are critical for its function.

Lymphatic vascular invasion is an independent correlated factor for lymph node metastasis and the prognosis of resectable T2 gastric cancer patients.

The objective of this study was to investigate the independent correlated factors for lymph node metastasis (LNM) and prognosis in T2 gastric cancer patients. A total of 135 pathologically confirmed T2 gastric cancer patients who received a gastrectomy at the Beijing University Cancer Hospital from Dec 1999 to Dec 2006 were studied retrospectively. The potential correlated factors for LNM and patients' prognosis were analyzed, including gender, age, tumor location and size, depth of invasion, lymphatic vascular invasion (LVI), differentiation grade, histological type, Borrmann type, LNM, distant metastasis, TNM stage, and whether the patient was treated with a radical gastrectomy. LNM occurred in 69 patients, which represents a rate of LNM of 51.1 %. Multivariate logistic regression analysis showed that LVI and TNM stage were independent risk factors for LNM (p values were 0.002 and 0.029, respectively). The median follow-up time was 60.3 months. Multivariable survival analysis revealed that age (<60 vs. ≥ 60), TNM stage and LVI were independent prognostic factors for gastric cancer patients (p values were <0.001, 0.047, and 0.001, respectively). In conclusion, LVI was an independent factor for LNM and the prognosis of resectable T2 gastric cancer patients.

Clinicopathological and prognostic differences between mucinous gastric carcinoma and signet-ring cell carcinoma.

OBJECTIVE: To analyze the differences in clinicopathologic characteristics and prognosis between mucinous gastric carcinoma (MGC) and signet-ring cell carcinoma (SRCC). METHODS: Clinicopathologic and prognostic data of 1,637 patients with histologically confirmed MGC or SRCC who received surgical operations in the Department of Gastroenterological Surgery, Beijing Cancer Hospital between December 2004 and December 2009 were retrospectively collected and analyzed. The clinicopathological features were analyzed statistically using χ(2) test. Survival was analyzed using the Kaplan-Meier method and multivariate analysis of Cox proportional hazards regression model (backward, stepwise). RESULTS: A total of 181 patients with gastric cancer (74 MGC, 107 SRCC) were included. MGC, when compared with SRCC, was featured by senile patients, stage III and IV, upper third stomach, large tumor size, positive lymph node metastasis, and positive lymphatic vascular invasion (P<0.05). The overall 5-year survival rate showed no difference between the two groups (48.8% vs. 44.8%, P>0.05). However, the survival rate for MGC patients was significant lower than that for SRCC patients when compared among the age <60 years, negative distant metastasis, and tumor localized at upper third stomach (P<0.05). Multivariate Cox proportional hazards models revealed that distant metastasis was a significant independent prognostic indicator in MGC group, and lymph node metastasis and distant metastasis was significant independent prognostic indicators in SRCC group. CONCLUSIONS: While compared with SRCC, MGC is associated with a more aggressive tumor biologic behavior. There is no statistically significant difference in distant metastasis, an independent prognostic indicator for both MGC and SRCC, which might be the reason for no significant difference of the overall survival rate between the patients with MGC and SRCC.

LGR5 is a promising biomarker for patients with stage I and II gastric cancer.

OBJECTIVE: To investigate Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) expressions in gastric cancer and to evaluate its clinical significance. METHODS: LGR5 expression was assessed by immunohistochemistry in 257 gastric cancer patients after surgery. The relationships between LGR5 expression and clinicopathological features and patients prognosis were statistically analyzed. RESULTS: The expression of LGR5 was significantly higher in gastric cancers as a cancer stem cell marker than in adjacent normal tissues (P<0.001), and more frequently in patients with intestinal type, well-moderate differentiation and stage I and II (P<0.05). Although we found gastric cancer patients with LGR5 positive expression had a poorer prognosis, it didn't meet statistical significance (P>0.05). LGR5 negative expression was significantly related to the favorable overall survival in stage I and II gastric cancer patients (P<0.05). Furthermore, patients with high LGR5 expression tended to be more likely to get progression and have poorer progress-free survival (P<0.05). Multivariate Cox regression analysis revealed that LGR5 expression was an independent factor of overall survival for the patients with stage I and II gastric cancer (P<0.05). CONCLUSIONS: Our results show that LGR5 may play an important role in tumorigenesis and progression and would be a powerful marker to predict the prognosis of patients with stage I and II gastric cancer.

Complete colonic duplication presenting as hip fistula in an adult with pelvic malformation: A case report.

BACKGROUND: Alimentary tract duplication (ATD) is a rare congenital anomaly. Thus, a case of ATD with a complete colonic duplication isolated in the abdominal cavity with a fistula and multiple malformations is very distinctive. These characteristics show the variability of this disease and explain why it tends to be challenging to diagnose and treat. CASE SUMMARY: A 25-year-old woman with a history of a fistula opening in her right hip since birth presented with the irregular discharge of foul fluid from the fistula and intermittent abdominal pain. Contrast-enhanced computed tomography and magnetic resonance imaging findings revealed a duplicated tube isolated in her abdominal pelvic cavity along with a pelvic malformation and double ureter. Right foot radiographic examination showed pes cavus. During surgery, the tube appeared to be an almost complete colonic structure and was verified to be connected to the fistula. All of the involved tissue and fistula were removed, and the defect in the pelvic floor was closed by suturing after surgery. After 8 mo, the postoperative follow-up has been uneventful. CONCLUSION: ATD may be a differential diagnosis in sinus tract cases. Laparoscopy combined with open surgery is a viable treatment option.

Excessive proliferation and apoptosis of parathyroid cells contribute to primary hyperparathyroidism in rabbit model.

To explore the molecular pathogenesis of primary hyperparathyroidism (PHPT), we investigated the proliferation and apoptosis of parathyroid cells in a rabbit model of diet-induced PHPT. A total of 120 adult Chinese rabbits were randomly divided into normal diet (Ca:P, 1:0.7) group (control group) or a high-phosphate diet (Ca:P, 1:7) group (experimental group). The thyroid and parathyroid complexes were harvested for 1-month interval from month 1 to month 6. The expression of proliferation markers, including proliferating cell nuclear antigen (PCNA) and cyclin-D1, and B cell lymphoma-2 (Bcl-2), were evaluated by immunohistochemistry in thyroid and parathyroid tissues. Apoptosis was quantified by DNA-fragment terminal labeling. Our results demonstrated that parathyroid cells in the experimental group started proliferating from the end of the 2nd month, the expression of PCNA, Bcl-2, and cyclin-D1 were significantly higher in the PHPT group than those of the control group (p<0.05). Furthermore, the apoptosis index (AI) was positively correlated with the glandular cell count and expression of PCNA in the 6th month in the PHPT group. Overall, our results suggested that excessive proliferation and apoptosis of parathyroid cells may contribute to the pathogenesis of PHPT through PCNA-related, Bcl-2-related, and cyclin-D1-related pathways.

Stem cell therapy: A promising treatment for COVID-19.

Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. SARS-CoV-2 is an RNA virus and has a glycosylated spike (S) protein used for genome encoding. COVID-19 can lead to a cytokine storm and patients usually have early respiratory signs and further secondary infections, which can be fatal. COVID-19 has entered an emergency phase, but there are still no specific effective drugs for this disease. Mesenchymal stem cells (MSCs) are multipotent stromal cells, which cause antiapoptosis and can repair damaged epithelial cells. Many clinical trials have proved that MSC therapy could be a potential feasible therapy for COVID-19 patients, especially those with acute respiratory distress syndrome, without serious adverse events or toxicities. However, more studies are needed in the future, in order to confirm the effect of this therapy.

Significance of HER2 protein expression and HER2 gene amplification in colorectal adenocarcinomas.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is an oncogenic driver, and a well-established therapeutic target in breast and gastric cancers. While the role of HER2 as a prognostic biomarker in colorectal adenocarcinomas (CRCs) remains uncertain, its relevance as a therapeutic target has been established. We undertook the present study to evaluate the frequency of HER2 expression in CRC and to correlate it with various clinicopathological variables. AIM: To correlate HER2 protein expression and HER2 gene amplification with clinicopathological features and survival in surgically resected CRC. METHODS: About 1195 consecutive surgically resected CRCs were analyzed by immunohistochemical staining (IHC) to assess HER2 protein expression, and 141 selected tumors were further evaluated by fluorescence in situ hybridization (FISH) to assess HER2 gene amplification. Follow-up information was available for 1058 patients, and using this information we investigated the prevalence of HER2 protein overexpression and gene amplification in a large series of surgically resected CRCs, and evaluated the relationship between overexpression and clinicopathological parameters and prognosis. RESULTS: HER2 IHC scores of 3+, 2+, 1+, and 0 were seen in 31 (2.6%), 105 (8.8%), 475 (39.7%), and 584 (48.9%) tumors, respectively. HER2 gene amplification was seen in 24/29 tumors with an IHC score of 3+ (82.8%; unreadable in 2/31), 12/102 tumors with an IHC score of 2+ (11.8%; unreadable in 2/104), and 0 tumors with IHC score of 1+ (0/10). HER2 gene amplification was seen in 36/1191 tumors (3.0%; unreadable in 4/1195). Among the tumors with HER2 IHC scores of 3+ and 2+, the mean percentage of tumor cells with positive IHC staining was 90% (median 100%, range 40%-100%) and 67% (median 75%, range 5%-95%), respectively (P < 0.05). Among tumors with IHC scores of 2+, those with HER2 gene amplification had a higher number of tumors cells with positive IHC staining (n = 12, mean 93%, median 95%, range 90%-95%) than those without (n = 90, mean 70%, median 50%, range 5%-95%) (P < 0.05). HER2 gene status was significantly associated with distant tumor metastasis and stage (P = 0.028 and 0.025). HER2 protein overexpression as measured by IHC or HER2 gene amplification as measured by FISH was not associated with overall survival (OS) or disease-specific survival for the overall group of 1058 patients. However, further stratification revealed that among patients with tubular adenocarcinomas who were 65 years old or younger (n = 601), those exhibiting HER2 gene amplification had a shorter OS than those without (mean: 47.9 mo vs 65.1 mo, P = 0.04). Among those patients with moderately to poorly differentiated tubular adenocarcinomas, those with positive HER2 tumor IHC scores (2+, 3+) had a shorter mean OS than those with negative HER2 IHC scores (0, 1+) (47.2 mo vs 64.8 mo, P = 0.033). Moreover, among patients with T2 to T4 stage tumors, those with positive HER2 IHC scores also had a shorter mean OS than those with negative HER2 IHC scores (47.1 mo vs 64.8 mo, P = 0.031). CONCLUSION: HER2 protein levels are correlated with clinical outcomes, and positive HER2 expression as measured by IHC confers a worse prognosis in those patients 65 years old or younger with tubular adenocarcinomas.

LAPTM4B-35, a cancer-related gene, is associated with poor prognosis in TNM stages I-III gastric cancer patients.

BACKGROUND: Lysosome-associated transmembrane protein 4ß-35 (LAPTM4B-35), a member of the mammalian 4-tetratransmembrane spanning protein superfamily, has been reported to be overexpressed in several cancers. However the expression of LAPTM4B-35 and its role in the progression of gastric cancer (GC) remains unknown. The aim of this study was to investigate LAPTM4B-35 expression in GC, its potential relevance to clinicopathologic parameters and role of LAPTM4B-35 during gastric carcinogenesis. METHODS: In the present study, paraffin-embedded specimens with GC (n = 240, including 180 paired specimens) and 24 paired fresh frozen tissues were analyzed. qRT-PCR and immunohistochemistry (IHC) were used to analyze the expression of LAPTM4B-35 in GC. The effects of LAPTM4B-35 on GC cell proliferation, migration and invasion were determined by overexpression and knockdown assays. RESULTS: IHC showed that LAPTM4B-35 was expressed in 68.3% (123/180) of GC tissues, while in 16.1% (29/180) of their paired adjacent noncancerous gastric tissues (P = 0.000). LAPTM4B-35 mRNA levels in GC tissues were also significantly elevated when compared with their paired adjacent noncancerous tissues (P = 0.017). Overexpression of LAPTM4B-35 was significantly associated with degree of differentiation, depth of invasion, lymphovascular invasion and lymph node metastasis (P<0.05). Kaplan-Meier survival curves revealed that patients with LAPTM4B-35 expression had a significant decrease in overall survival (OS) in stages I-III GC patients (P = 0.006). Multivariate analysis showed high expression of LAPTM4B-35 was an independent prognostic factor for OS in stage I-III GC patients (P = 0.025). CONCLUSION: These findings indicate that LAPTM4B-35 overexpression may be related to GC progression and poor prognosis, and thus may serve as a new prediction marker of prognosis in GC patients.

Intestinal stem cell marker LGR5 expression during gastric carcinogenesis.

AIM: To investigate the differential expression of leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) in gastric cancer tissues and its significance related to tumor growth and spread. METHODS: Formalin-fixed biopsy specimens of intestinal metaplasia (n = 90), dysplasia (n = 53), gastric adenocarcinoma (n = 180), metastases in lymph nodes and the liver (n = 15), and lesion-adjacent normal gastric mucosa (controls; n = 145) were obtained for analysis from the Peking University Cancer Hospital's Department of Pathology and Gastrointestinal Surgery tissue archives (January 2003 to December 2011). The biopsied patients' demographic and clinicopathologic data were retrieved from the hospital's medical records database. Each specimen was subjected to histopathological typing to classify the tumor node metastasis (TNM) stage and to immunohistochemistry staining to detect the expression of the cancer stem cell marker LGR5. The intergroup differences in LGR5 expression were assessed by Spearman's rank correlation analysis, and the relationship between LGR5 expression level and the patients' clinicopathological characteristics was evaluated by the χ(2) test or Fisher's exact test. RESULTS: Significantly more gastric cancer tissues showed LGR5(+) staining than normal control tissues (all P < 0.01), with immunoreactivity detected in 72.2% (65/90) and 50.9% (27/53) of intestinal metaplasia and dysplasia specimens, respectively, 52.8% (95/180) of gastric adenocarcinoma specimens, and 73.3%% (11/15) of metastasis specimens, but 26.9% (39/145) of lesion-adjacent normal gastric mucosa specimens. Comparison of the intensity of LGR5(+) staining showed an increasing trend that generally followed increasing dedifferentiation and tumor spread (normal tissue < dysplasia, < gastric adenocarcinoma