Development and validation of a nomogram for predicting internal mammary sentinel node metastasis in breast cancer patients.

OBJECTIVE: Internal mammary nodes are important in breast cancer prognosis, but their diagnosis is often missed in clinical practice, leading to inaccurate staging and treatment. We developed a validated nomogram to predict the presence of internal mammary sentinel nodes (IMSN) metastasis. METHODS: A total of 864 sequential IMSN biopsy procedures from a prospective studies database of 1505 cases were used for model development and validation. Multivariable logistic regression was performed on 519 sequential IMSN biopsy procedures from multi-center data between August 2018 and July 2022 to predict the presence of IMSN metastasis. A nomogram was developed based on the logistic regression model and subsequently applied to 345 sequential IMSN biopsy procedures from single-center data between November 2011 and July 2018. The model's discrimination was assessed using the area under the receiver operating characteristic curve. RESULTS: The overall frequency of IMSN metastasis was 17.0% in our study. A predictive model for IMSN metastasis was constructed using tumor size, tumor location, lymphovascular invasion, the number of positive axillary nodes (P < 0.05 for all variables in multivariate analysis), and histological grade (P < 0.05 only in univariate analysis). The nomogram was accurate, with a concordance index of 0.84 in the bootstrapping analysis and an area under the receiver operating characteristic curve of 0.80 in the validation population. CONCLUSION: Our nomogram provides an accurate and validated multivariable predictive model for estimating the individual likelihood of having IMSN metastasis. This may be useful for personalized treatment decisions regarding internal mammary radiotherapy in breast cancer patients.

High GP73 Expression Correlates with Poor Response to Neoadjuvant Chemotherapy and Survival in Gastric Cancer: A Tissue Microarray Study.

Golgi protein 73 (GP73) is a type II Golgi transmembrane protein which is overexpressed in several cancers, however, its role in gastric cancer is still unclear. The aim of this study is to investigate if high GP73 expression is associated with pathological tumor response to neoadjuvant chemotherapy and prognosis for patients with gastric cancer. A total of 348 patients with gastric cancer, who had undergone surgery between 1999 and 2011 were retrospectively reviewed, GP73 expression was examined in tumor tissues using tissue microarray and the correlations between its expression and pathological response to neoadjuvant chemotherapy as well as patients prognosis were analyzed. We found that GP73 expression was not associated with clinicopathologic features including tumor size, differentiation and TNM stage. High expression of GP73 was associated with less pathological tumor response to neoadjuvant chemotherapy and poor survival in gastric cancer, multivariate analysis showed GP73 expression was an independent predictive factor for pathological response to neoadjuvant chemotherapy and for prognosis in patients with gastric cancer. Our results suggest that GP73 expression correlates with the effect of neoadjuvant chemotherapy and is a promising biomarker to identify patients with poor prognosis.

Low level of serum high-density lipoprotein cholesterol in gastric cancer correlates with cancer progression but not survival.

BACKGROUND: The clinical significance of lipid profile in gastric cancer remains unclear. The aim of the present study was to investigate the correlation between serum lipid profiles and patient clinical parameters as well as prognosis in gastric cancer. METHODS: The preoperative plasma lipid profile levels of 358 gastric cancer patients, who were operated in between 2001 and 2009, were retrospectively evaluated, and the correlation between these factors and patient clinical parameters as well as survival were analyzed. RESULTS: There was a significant association between serum high-density lipoprotein cholesterol level (HDL-C <54.2 mg/dL) and cancer progression, Logistic regression analysis revealed that lower level of serum HDL-C was an independent risk factor for deeper cancer invasion, nodal metastasis as well as late stage in patients with gastric cancer. However, no significant association was reported between other lipid markers [triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein (VLDL) and apolipoprotein A (apoA)] and lymph node involvement as well as stage of disease. In univariate analysis and multivariate analyses regarding patient's survival, there was no significant association between the groups in terms of TG, TC, HDL-C, LDL-C, VLDL and apoA. CONCLUSIONS: Low level of serum HDL-C in gastric cancer correlates with cancer progression but not patient's survival.

Clinical features and prognosis of patients with benign thyroid disease accompanied by an incidental papillary carcinoma.

PURPOSE: To investigate the clinical features and prognosis of papillary thyroid carcinoma (PTC) with a background of benign disease. METHOD: A total of 709 patients with papillary thyroid carcinoma undergoing surgical resection were analyzed retrospectively. In 147 patients who underwent surgery for benign thyroid disease, incidental PTC (IPC group) were identified by intraoperative or postoperative pathological examination of surgical specimens but were not detected by preoperative imaging studies. In the other group, according to the pathological examination with or without co-existing benign thyroid disease, 253 cases were clarified as concomitant PTC and 309 cases were clarified as dominant PTC. RESULTS: Incidental PTC was more common in women, about 85.7%, the mean age was 47.6±11.3 years old. Average tumor diameter was 4.4±2.2 mm, multiple lesions accounted for 12.9% (19/147), and the cervical lymph node metastasis rate was 6.1% (9/147). After radical resection 8 cases recurred, the median time of recurrence was about 12 months (0.5 to 162), there was no tumor-related death. The tumor-free survival rates were 97.3%, 95.9%, 91.5%, and 79.3% in 1, 5, 10 and 14 year respectively. CONCLUSION: Incidental PTC with a background of benign lesions is common, and the generally good prognosis can be attributed to tumor early detection and early treatment. On the intraoperative finding of incidental PTC, lobectomy (unilateral) or total thyroidectomy (bilateral) should be the first choice, but with a postoperative pathologic finding of incidental PTC, further treatment, such as completion thyroidectomy or immediate lymph dissection is not necessary. Central lymph node dissection is also not needed unless lymphadenectasis is present.

[Multifocal papillary thyroid carcinoma: clinical analysis of 168 cases].

OBJECTIVE: To investigate the clinical features and treatment of multifocal papillary thyroid carcinoma (PTC). METHODS: A retrospective survey was carried out in 648 patients with PTC who underwent surgery from January 1997 to December 2006. One hundred and sixty-eight cases of the patients presented with multiple tumor masses (> or = 2). The risk factors, including sex of the patients, age at diagnosis, family history of thyroid tumor, multiplicity and bilaterality of tumor, extra-thyroidal extension, lymph node involvement and other were analyzed between solitary PTC and multifocal PTC group. RESULTS: The mean age of the patients was 42 years (range, 14 - 78 years), included 49 male and 119 female. Tumor foci were found in both thyroid lobes in 117 cases (69.6%). Patients with multifocal PTC were characterized by a higher ratio of male (P = 0.004), family history of thyroid tumor (P = 0.031), neck lymph node metastasis (P = 0.008) and extra-thyroidal extension (P = 0.001). However, solitary PTC tended to be with a higher rate of benign goiters in pathologic examination. In multifocal PTC group, male, neck lymphadenectasis, > or = 3 tumor masses or bilaterality of tumor tended to presented with larger tumor, more neck lymph node metastasis and extra-thyroidal extension; And a less malignant tumor in the cases detected with benign goiters in histological examination. By the end of 2007, 164 cases (97.6%) completed follow-up with a mean period of 46.1 months (range, 2 - 127 months), 5 died in the meantime. One patient has been followed-up for 16 months for suspect of lung metastases by chest X-ray. Recurrence occurred in 8 patients and were re-resected, 2 in remnant thyroid and 6 in neck lymph nodes. The overall 1-, 2-, 5-, and 10-year survival rate was 98.2%, 97.4%, 96.5% and 96.5%, respectively. American Joint Committee on Cancer (AJCC) stage was associated with prognosis significantly (chi(2) = 168.832, P = 0.000). CONCLUSIONS: Multifocus is one of the clinical features of PTC and is more malignant than solitary PTC. Total thyroidectomy with central compartment neck dissection could be standard treatment. Lateral nodal dissection is not necessary except for the cases with lymph node metastasis. AJCC stage is still the best prognostic factor.

Calcitriol inhibits the growth of MHCC97 heptocellular cell lines by down-modulating c-met and ERK expressions.

BACKGROUND: Previous studies have demonstrated that Calcitriol or its analogs has an anti-tumour activity. This study was designed to determine the effect and mechanism of Calcitriol on MHCC-97 heptocellular cell lines. METHODS: MHCC97 cell lines were treated with Calcitriol of 10(-6) approximately 10(-9) M concentration and with Calcitriol in lipiodol ultra-fluid (LUF) respectively. The conditions of cell proliferation were analyzed by MTT method. The cell apoptosis and cycle were analyzed by using a flow cytometer. Hepatocyte growth factor (HGF) concentration in the cell supernatant was measured by using ELISA method. C-met and vitamin D receptor (VDR) mRNA in cells were determined by using RT-PCR method. VDR and ERK(1/2) proteins were determined by using Western Blotting method. RESULTS: Calcitriol inhibited the proliferation of MHCC97 cell lines with an accumulation of cells in the G(0)/G(1) phase and reduction of cells in S phase. Calcitriol dissolved in LUF resulted in a better and longer inhibitive effect on the cell lines than Calcitriol alone. MHCC97 cell lines secreted HGF and expressed c-met mRNA and ERK(1/2) proteins abundantly. Calcitriol remarkably inhibited the expressions of c-met mRNA and ERK(1/2) proteins. CONCLUSION: Calcitriol inhibits the growth of MHCC-97 heptocellular cell lines by down modulating c-met and ERK expressions.

[Study on the prognostic value of hepatocyte growth factor and c-met for patients with hepatocellular carcinoma].

OBJECTIVE: To analyze the prognostic value of hepatocyte growth factor (HGF) and c-met for patients with hepatocellular carcinoma (HCC) after hepatectomy. METHODS: Twenty-five patients undergoing partial hepatectomy for HCC were studied. Serum HGF level was determined using ELISA kit before and after operation respectively. c-met protein and mRNA expression in cancerous and paracancerous tissues were detected by immunohistochemical and RT-PCR methods respectively. The correlations of clinical-pathologic parameters with the HGF level in serum and c-met expression in cancerous tissue were analyzed respectively. RESULTS: HCC patients had a significantly higher concentration of serum HGF than normal controls and chronic hepatitis B respectively [(1.03 +/- 0.09) ng/ml vs (0.69 +/- 0.02) ng/ml and (0.74 +/- 0.09) ng/ml]. No significant difference in serum HGF was observed between HCC and cirrhosis patients with Child-Pugh score B/C [(1.03 +/- 0.09) ng/ml vs (1.04 +/- 0.11) ng/ml]. Serum HGF concentrations were positively correlated with tumor size (> 5 cm), node cirrhosis, portal vein tumor thrombi (PVTT) and preoperative alpha-fetoprotein (AFP) level (> or = 400 microg/L). After the resection of tumor, serum HGF concentration had a peak on the third postoperative day (POD), and then declined, but did not return to normal level on the tenth POD. From preoperative day to third POD, HGF concentration had a higher elevation in patients with major resection than with local resection. Moderately or strongly positive expression of c-met protein was observed in 21 cancerous regions (21/25), and only in 5 paracancerous regions. The intensive expression of c-met mRNA was 100% (25/25) detectable in the cancerous tissues, but only 24% (6/25) in the paracancerous tissues. The expression extent of c-met protein was correlated with portal vein tumor thrombi (PVTT). In paracancerous tissues, the expression of c-met protein was more intense in patients with cirrhosis than those without cirrhosis. The patients with recurrence or metastases after operation had a higher level of serum HGF and more intensive expression of c-met than other patients. No significant association was observed between HGF in serum and c-met expression in cancerous tissue. CONCLUSIONS: The over-expression of HGF and its receptor c-met indicate an adverse prognosis for HCC patients. The sustained high level of serum HGF after hepatectomy may be a factor related to early tumor recurrence and metastasis.

Apoptosis induced by preoperative oral 5'-DFUR administration in gastric adenocarcinoma and its mechanism of action.

AIM: To study the apoptosis induced by preoperative oral 5'-DFUR administration in gastric adenocarcinoma and its mechanism of action. METHODS: Sixty gastric cancer patients were divided randomly into three groups (20 each group) before operation: group one:5'-DFUR oral administration at the dose of 800-1200 mg/d for 3 - 5 d, group two: 500 mg 5-FU + 200 mg/d CF by venous drip for 3 - 5 d,group three (control group). One or two days after chemotherapy, the patients were operated. Fas/FasL,PD-ECGF and PCNA were examined by immunohistochemistry and apoptotic tumor cells were detected by in situ TUNEL method. Fifty-four patients received gastrectomy, including 12 palliative resections and 42 radical resections. Six patients were excluded. Finally 18 cases in 5'-DFUR group, 16 cases in CF+5-FU group, and 20 cases in control group were analyzed. RESULTS: There was no significant difference in patient mean age, gender, white blood cell count, haematoglobin (HB),thromboplastin, perioperative complication incidence, radical or palliation resection, invasion depth (T), lymphonode involvement (N),metastasis (M) and TNM staging among the three groups. However,the PCNA index (PI) in 5'-DFUR group (40.51+/-12.62) and 5-FU+CF group (41.12+/-15.26) was significantly lower than that in control group (58.33+/-15.69) (F=9.083, P=0.000). The apoptotic index (AI) in 5'-DFUR group (14.39+/-9.49) and 5-FU+CF group (14.11+/-9.68)was significantly higher than that in control group (6.88+/-7.37) (F=4.409, P=0.017).The expression rates of Fas and FasL in group one and group three were 66.7% (12/18) and 50% (9/18), 43.8% (7/16) and 81.3% (13/16), 45.0% (9/20) and 85% (17/20), respectively. The expression rate of FasL in 5'-DFUR group was significantly lower than that in the other two groups (chi2=6.708, P=0.035). Meanwhile, the expression rate of PD-ECGF was significantly lower in 5'-DFUR group (4/18,28.6%) than in CF+5-FU group(9/16,56.3%)and control group (13/20,65.0%) (chi2=7.542, P=0.023). The frequency of Fas expression was significantly correlated with palliative or radical resection (chi2=7.651, P=0.006), invasion depth (chi2=8.927, P=0.003), lymphatic spread (chi2=4.488, P=0.034) and UICC stages (chi2=8.063, P=0.045) respectively. By the end of March 2005,45 patients were followed up. The 0.5-, 1-, 2-, 3-year survival rates were 96%,73%,60%,48%, respectively, which were related with T, N, M and Fas expression, but not with PD-ECGF and FasL expression. CONCLUSION: Preoperative oral 5'-DFUR administration may induce apoptosis of gastric carcinoma cells and decrease tumor cell proliferation index,but cannot improve the prognosis of patients with gastric cancer.Down-regulation of FasL and PD-ECGF expression mediated by 5'-DFUR may be one of its anti-cancer mechanisms.Fas expression correlates with the progression of gastric carcinoma and may be an effective prognostic factor.

The Chinese classification system compared with TNM staging in prognosis of patients with primary hepatic carcinoma after resection.

BACKGROUND: The life expectancy of a patient with primary hepatic carcinoma (PHC) is hard to predict, and it is related to many prognostic factors. The Chinese classification system including five parameters: tumor, vascular thrombosis, lymph node metastasis, distant metastasis and Child-Pugh stage developed in 1999 was adopted by the 8th National Conference on Liver Cancer of the Chinese Anti-Cancer Association in 2001. In this study, the discriminatory ability of the Chinese classification system was compared with that of the TNM staging in patients for resection of PHC, in addition to the evaluation of prognostic value. METHODS: The data of 246 patients who had undergone resection of PHC from January 1986 to December 2000 (average age, 51 years; male/female ratio, 213/33) were retrospectively studied. Among the 246 patients, 227 were followed up for at least 3 years. RESULTS: The 1-, 3-, 5-, 7-, and 10-year tumor-free survival rates were 55%, 30%, 25%, 20% and 18%, respectively. The Chinese classification system was better than the TNM staging system in predicting survival rate of patients with PHC, as confirmed by survival curves shown by the Kaplain-Meier method. The mean survival time was 155, 70, 39, 16, and 4 months in patients with the Chinese classification stages Ia, Ib, IIa, IIb, and III, respectively. The 1-, 3-, 5-, 7-, and 10-year tumor-free survival rates of the Chinese classification system and TNM staging were statistically significant and had a slightly positive relationship. The predictive capacity of the Chinese classification system was confirmed in any two subgroups of patients undergoing operation. COX proportional hazards regression analysis showed that the Chinese classification system was the only independent prognostic factor for survival. CONCLUSIONS: Taking both tumor extension and liver function into account, we consider that the Chinese classification system making up for the deficiency of UICC TNM staging is more precise in predicting the prognosis of patients with resection of PHC.

Survival factors after resection of small hepatocellular carcinoma.

BACKGROUND: Early resection of hepatocellular carcinoma is a key measure to prolong the survival of patients. This study was designed to summarize our experience in surgical resection of small hepatocellular carcinoma (HCC), and to analyze the factors influencing the postoperative survival of patients. METHODS: The clinicopathologic data of 105 patients with small HCC after resection from 1986 through 2003 were analyzed; the patients had been followed up for more than half a year (median 33 months). Nine clinicopathologic factors, preoperative alpha-fetoprotein (AFP) level, liver cirrhosis, Child-Pugh score, tumor size (>2 cm vs. < or = 2 cm) and number (single vs. multiple), capsule formation, portal vein tumor thrombi (PVTT), Edmondson tumor grade and surgical method, were analyzed by the log-rank test and the Cox proportional harzards model analysis. RESULTS: The cumulative 1-, 3- and 5-year survival rates after the operation were 86.5%, 70.3% and 55.2%, respectively, and the 1-, 3- and 5-year disease-free survival rates were 78%, 58.9% and 45.6%, respectively. One patient died from esophagogastric varices hemorrhage in 2 weeks after reoperation. Thirty-six patients had intrahepatic recurrence or metastasis postoperatively and 34 patients died. The Kaplan-Meier method and the Cox proportional harzards model analysis indicated that poor Child-Pugh score, tumor more than 2 cm in diameter, PVTT and multiple lesions (including satellitic lesions) were adverse factors affecting postoperative survival. The Cox proportional harzards model analysis indicated that tumor size, PVTT and multiple lesions were the factors influencing postoperative disease-free survival. CONCLUSIONS: Limited hepatectomy with a margin more than 1 cm is an appropriate surgical approach. Adverse preoperative Child-Pugh score and postoperative intrahepatic recurrences are the main factors leading to the death of patients with small HCC.

[Prognostic factors influencing postoperative survival in patients with

OBJECTIVE: To summarize the experience of surgical resection, and to analyze the prognostic factors that can influence the postoperative survival in patients with small hepatocellular carcinoma (small HCC) of 2 cm vs.

Prediction of recurrence and prognosis in patients with hepatocellular carcinoma after resection by use of CLIP score.

AIM: The survival time of patients with hepatocellular carcinoma (HCC) after resection is hard to predict. Both residual liver function and tumor extension factors should be considered. A new scoring system has recently been proposed by the Cancer of the Liver Italian Program (CLIP). CLIP score was confirmed to be one of the best ways to stage patients with HCC. To our knowledge, however, the literature concerning the correlation between CLIP score and prognosis for patients with HCC after resection was not published. The aim of this study is to evaluate the recurrence and prognostic value of CLIP score for the patients with HCC after resection. METHODS: A retrospective survey was carried out in 174 patients undergoing resection of HCC from January 1986 to June 1998. Six patients who died in the hospital after operation and 11 patients with the recurrence of the disease were excluded at 1 month after hepatectomy. By the end of June 2001, 4 patients were lost and 153 patients with curative resection have been followed up for at least three years. Among 153 patients, 115 developed intrahepatic recurrence and 10 developed extrahepatic recurrence, whereas the other 28 remained free of recurrence. Recurrences were classified into early (< or =3 year) and late (>3 year) recurrence. The CLIP score included the parameters involved in the Child-Pugh stage (0-2), plus macroscopic tumor morphology (0-2), AFP levels (0-1), and the presence or absence of portal thrombosis (0-1). By contrast, portal vein thrombosis was defined as the presence of tumor emboli within vascular channel analyzed by microscopic examination in this study. Risk factors for recurrence and prognostic factors for survival in each group were analyzed by the chi-square test, the Kaplan-Meier estimation and the COX proportional hazards model respectively. RESULTS: The 1-, 3-, 5-, 7-,and 10-year disease-free survival rates after curative resection of HCC were 57.2%, 28.3%, 23.5%, 18.8%, and 17.8%, respectively. Median survival time was 28, 10, 4, and 5 mo for CLIP score 0, 1, 2, 3, and 4 to 5, respectively. Early and late recurrence developed in 109 patients and 16 patients respectively. By the chi-square test, tumor size, microsatellite, venous invasion, tumor type (uninodular, multinodular, massive), tumor extension (< or = or >50% of liver parenchyma replaced by tumor), TNM stage, CLIP score, and resection margin were the risk factors for early recurrence, whereas CLIP score and Child-Pugh stage were significant risk factors for late recurrence. In univariate survival analysis, Child-Pugh stages, resection margin, tumor size, microsatellite, venous invasion, tumor type, tumor extension, TNM stages, and CLIP score were associated with prognosis. The multivariate analysis by COX proportional hazards model showed that the independent predictive factors of survival were resection margins and TNM stages. CONCLUSION: CLIP score has displayed a unique superiority in predicting the tumor early and late recurrence and prognosis in the patients with HCC after resection.

Thirty-one patients with primary hepatocellular carcinoma survived for more than 5 years after hepatectomy.

OBJECTIVE: To investigate the factors affecting prognosis of patients with primary hepatocellular carcinoma (PHC) after resection. METHODS: From 1976 to 1992, 213 patients with PHC treated with hepatectomy were followed up for more than 5 years. Thirty-one of the patients who had survived for more than 5 years were compared with 56 patients who had survived for less than 5 years. RESULTS: Early detection of tumor, radical resection, number of tumors, capsule formation, operation safe distance, presence of portal tumor embolus, presence of cirrhosis and tumor size were important factors affecting the prognosis of patients with PHC. The proportion of small liver cancer in the patients who had survived for more than 5 years was greatly larger than that in the control group. CONCLUSIONS: Early detection of tumor and radical resection are of value in raising the 5-year survival rate. Much remains to be investigated about the relationship between safe margin distance and prognosis of patients with PHC.