Modified rubber band ligation for treatment of grade II/III hemorrhoids: clinical efficacy and safety evaluation-a retrospective study.

BACKGROUND: Massive, delayed bleeding (DB) is the most common major complication of Rubber Band Ligation (RBL) for internal hemorrhoids caused by premature band slippage. In this study we modified conventional RBL to prevent early rubber band slippage and evaluated its clinical efficacy and safety. METHODS: Study participants were consecutive patients with grade II or III internal hemorrhoids treated with RBL at Ningbo Medical Center of Lihuili Hospital from January 2019 to December 2020. Postoperative minor complications such as pain, swelling, anal edema, prolapse recurrence and major complications like DB were retrospectively reviewed. RESULTS: A total of 274 patients were enrolled, including 149 patients treated with modified RBL and 125 treated with conventional RBL. There was no statistically significant difference between the two groups at baseline. Five cases of postoperative DB have been observed in the conventional RBL group, compared to none in the modified ones, with a significant difference (P < 0.05). Within three months after surgery, 8 cases in the modified RBL group experienced a recurrence rate of 5.4%, whereas 17 patients in the conventional RBL group experienced a recurrence rate of 13.6%. The difference was statistically significant (P < 0.05). The VAS score, edema, and incidence of sensation of prolapse between the two groups were not significantly different at 3 and 7 days after surgery (P < 0.05). There were also no significant differences in HDSS and SHS scores between the two groups after surgery (P > 0.05). CONCLUSION: Modified RBL may be associated with a lower rate of complications, especially with lower DB rate in comparison with standard RBL. Further studies in larger samples and different design are necessary to confirm these results.

Predictive Value of Circulating Tumor Cells in Prognosis of Stage III/IV Colorectal Cancer After Oxaliplatin-based First-line Chemotherapy.

BACKGROUND/AIM: Insufficient data exist to support the concept of the circulating tumor cell (CTC) level as a prognostic factor for platinum-based first-line chemotherapy. This study investigated the impact of CTCs on the prognosis of patients with advanced colorectal cancer (CRC) after receiving platinum-based chemotherapy. Analyses were carried out of clinicopathological features and molecular phenotypes to clarify independent risk factors for a high CTC count. PATIENTS AND METHODS: Patients diagnosed with stage III/IV CRC (n=76) were included in the study. The blood samples of patients were evaluated for CTCs using the CellRich™ platform system. Immunohistochemistry (Ias used to analyze epithelial-mesenchymal transition-associated biomarkers E-cadherin and vimentin. Univariate and logistic regression analyses were then conducted to analyze the risk factors for CTC expression. Additionally, the influence of oxaliplatin on disease-free survival after first-line chemotherapy or during chemotherapy was analyzed through a 2-year follow-up. RESULTS: Patients in the CTC+ group experienced shorter DFS after receiving oxaliplatin first-line chemotherapy than patients in the CTC- group (p<0.01). In addition, univariate analysis revealed that the tumor M-stage, tumor location, RAS mutation, high expression of vimentin, and deletion of E-cadherin expression were correlated with a high CTC count. Multivariate analysis suggested that the presence of RAS gene mutations and high vimentin expression were independent risk factors for high CTC loads (p<0.01). CONCLUSION: CTC positivity can indicate the efficacy of first-line chemotherapy with oxaliplatin in stage III/IV colorectal cancer. This may be linked to tumor epithelial-mesenchymal transition in patients with CTCs. Moreover, RAS gene mutation and high expression of vimentin were identified as independent risk factors for a high CTC count.

Comparison of postoperative laparoscopic and open total mesorectal excision on lower urinary tract function in men with rectal cancer.

OBJECTIVES: This study investigated male voiding dysfunction (VD) or lower urinary tract function in rectal cancer (RC) patients after laparoscopic or open total mesorectal excision with pelvic autonomic nerve preservation (PANP). METHODS: One hundred and eighty-seven male RC patients admitted between January 2016 and May 2019 were enrolled in this study, 112 of whom underwent laparoscopic total mesorectal excision (LTME) and 75 underwent open total mesorectal excision (OTME). The International Prostatic Symptom Score (IPSS) was compared between the two groups. RESULTS: The postoperative IPSS in patients with RC was elevated on day 7 and gradually decreased during the first month after surgery. Compared with the OTME group, the IPSS scores decreased less in the LTME group at week 1, and months 1 and 3 postoperatively (6.82 ± 2.13 vs 10.15 ± 3.86, 5.70 ± 2.45 vs 7.21 ± 2.0, and 5.01 ± 2.09 vs 5.75 ± 2.55, respectively; P < 0.05). The VD rate was significantly lower in the LTME group than the OTME group at 1, 2, and 3 weeks postoperatively (21.4% vs 26.8%,13.4% vs 25.3%, and 9.8% vs18.6%, respectively; P < 0.05); however, there was no major difference in the incidence of VD 6 months postoperatively between the two groups (P > 0.05). VD was more frequent in the OTME group than the LTME group 6 months postoperatively, but the difference was not statistically significant (odds ratio = 1.857, 95% CI, 0.964-3.645, P = 0.064). CONCLUSIONS: LTME may be superior to OTME with respect to PANP of lower urinary tract function in males with RC.

On the status and comparison of glucose intolerance in female breast cancer patients at initial diagnosis and during chemotherapy through an oral glucose tolerance test.

AIMS: This study is to estimate the status and comparison of glucose intolerance in female breast cancer patients at initial diagnosis and during chemotherapy through an oral glucose tolerance test (OGTT), as well as to learn the effect of chemotherapy on the glucose metabolism of breast cancer patients. METHODS: All the 79 breast cancer patients at initial diagnosis, with the mean age of 53.2 years, and 96 breast cancer patients before the 5th or 6th cycle of chemotherapy, with the mean age of 51.5 years, participated in the study from December 2012 to October 2013. After an overnight fast, participants underwent OGTT test, and fasting and 2-hour glucose levels were measured to identify undiagnosed diabetes and prediabetes (i.e., impaired fasting glucose or impaired glucose tolerance) in them. Previously diagnosed diabetes among the female breast cancer patients was determined on the self-report and the medical record. RESULTS: The overall incidences of total normal glucose tolerance, prediabetes, diabetes in female breast cancer patients at initial diagnosis and during chemotherapy were 24.1% and 38.5% (p<0.05), 50.6% and 28.1% (p<0.05), and 25.3% and 33.3% (p>0.05), respectively, and the differences of normal glucose tolerance and prediabetes instead of diabetes between the two groups were statistically significant. About 84% of the total diabetes and prediabetes in the female breast cancer patients at initial diagnosis and 79.7% of those during chemotherapy need to be diagnosed with OGTT. CONCLUSIONS: Breast cancer patients have high incidences of diabetes and prediabetes. After chemotherapy even with steroids, some breast cancer patients with abnormal glucose metabolism may even become normal. Isolated hyperglycemia 2 hours after glucose loading is common, and OGTT should be made for breast cancer patients at initial diagnosis and during chemotherapy.

On the status of ß-cell dysfunction and insulin resistance of breast cancer patient without history of diabetes after systemic treatment.

To estimate the status of ß-cell dysfunction and insulin resistance of breast cancer (BC) patient without history of diabetes mellitus (DM) after systemic treatment through an oral glucose tolerance test (OGTT) and insulin releasing test (IRT). All the 128 BC patients without history of DM after systemic treatment underwent OGTT and IRT test. Fasting and 2-h glucose levels were measured to confirm undiagnosed DM and prediabetes. Insulin sensitivity was estimated by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index and disposition index (IGI/HOMA-IR). Insulin secretion was estimated by the insulinogenic index (IGI) [Δ insulin/Δ glucose (30-0 min)]. Insulin concentrations during the OGTT and IRT at baseline were used to derive the patterns of insulin secretion curve (pattern 1, pattern 2, pattern 3, pattern 4 and pattern 5), which were used to estimate the risk of developing DM. Of 128 BC patients without history of DM after systemic treatment, there were 46 cases (35.9%) of NGT, 60 cases (46.9%) of prediabetes and 22 cases (17.2%) of DM. The BMI of prediabetes and DM were higher than NGT groups with statistical significance. After adjusted for BMI, IGI was significantly lower in DM group but not significantly different between NGT group and prediabetes group. HOMA-IR, Matsuda index and disposition index were significantly different in DM group compared with NGT group and prediabetes and also significantly different between NGT and prediabetes groups. The total rates of patterns 4 and 5 in NGT and prediabetes groups were 15.3% (10.9 and 4.4%) and 48.3% (31.6 and 16.7%), respectively. ß-Cell dysfunction and insulin resistance may appear in BC patients after systemic treatment. BC patients have high risk in development of DM even in NGT and prediabetes groups confirmed by OGTT.

Discordance and clinical significance of ER, PR, and HER2 status between primary breast cancer and synchronous axillary lymph node metastasis.

Discordance of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status between primary breast cancer, metastatic lesion and synchronous axillary lymph node metastasis has been reported in the series studies. Systemic treatment of primary invasive breast cancer patients with synchronous axillary metastasis is currently based on the biomarker characteristics of the primary tumor; however, hormone receptors and HER2 status may change throughout tumor progression from the primary tumor to the synchronous axillary metastasis. As local metastasis, the synchronous axillary lymph node metastasis may represent the potentially metastatic breast cancer cells much better than the primary tumor. Hence, the determination of hormone receptors and HER2 status should be routinely performed in synchronous axillary nodal metastasis, together with primary tumor, to guide therapy management and evaluate the recurrent risk of primary invasive breast cancer patients with synchronous axillary nodal metastasis, which may even change the postoperative risk categories (St. Gallen consensus) of breast cancer in these patients. This article will review the studies on the discordance and clinical significance of ER, PR, and HER2 receptor status between primary breast cancer and synchronous axillary lymph node metastasis.

Clinicopathologic features of breast cancer patients with type 2 diabetes mellitus in southwest of China.

The aim of this study was to study the prevalence and clinicopathologic features of breast cancer patients with type 2 diabetes mellitus in southwest of China for providing clinical guidance and prognosis appreciation for these patients. Through a case-control study of 3,381 primary breast cancer patients initially diagnosed from January 2007 to May 2013, one case group (164 female breast cancer patients with type 2 diabetes) and two control groups (first control group consists of 328 randomly selected nondiabetic breast cancer patients and second control group consists of 279 nondiabetic breast cancer patients without diabetes-related diseases such as cardiovascular or cerebrovascular diseases) were selected. The clinicopathological features between them were statistically analyzed. (1) Of 3,381 primary breast cancer patients with the average age of 50.5, ranging from 21 to 97 years of age, 164 (4.9 %) cases (with the average age of 60.7) suffered diabetes (previously diagnosed diabetes). (2) The differences of clinicopathologic features between the case group and first control group (with the average age of 61.5) were the ratio of hypertension (41.5 vs 26.1 %, P = 0.001) and axillary lymph node metastasis (51.1 vs 38.1 %, P = 0.046); and the differences of clinicopathologic features between the case group and second control group (with the average age of 64.3) were axillary lymph node metastasis (51.1 vs 35.8 %, P = 0.017), tumor size (≥ T2: 62.3 vs 53.1 %, P = 0.019) and p53 expression (51.0 vs 62.7 %, P = 0.018). No statistical significances (P > 0.05) of histological type, histological grade, or the expressions of estrogen receptor (ER), progesterone receptor, human epidermal growth factor 2 (HER2) and Ki67 were found between them. (3) The clinicopathologic features of ER-positive and ER-negative patients in each group were as follows: (1) In the case group, the ER-negative patients have more advanced tumor histological grade (G3, 19.0 vs 2.8 %, P = 0.012), more positive expression of Her-2 (16.9 vs 8.1 %, P = 0.029) and more axillary lymph node metastasis (63.3 vs 44.4 %, P = 0.048). (2) In the first control group, the same results with tumor histological grade (G3, 15.6 vs 6.2 %, P = 0.025) and positive expression of Her-2 (16.7 vs 4.3 %, P = 0.001), and more positive expression of Ki67 (65.1 vs 52.0 %, P < 0.001) were found. (3) In the second control group, the ER-negative patients have more positive expression of Ki67 (70.5 vs 55.7 %, P = 0.009) and fewer family history of malignancy (1.9 vs 10.0 %, P = 0.013). Diabetes has a high incidence in breast cancer patients and is more common with postmenopausal patients. It is suggested that initially diagnosed breast cancer patients should undertake oral glucose tolerance test screening for occult diabetes and prediabetes. More concerns should be put onto diabetic patients with breast cancer.

Incidences of diabetes and prediabetes among female adult breast cancer patients after systemic treatment.

Patients with cancer frequently show glucose intolerance. This study is to estimate the status of total diabetes and prediabetes in breast cancer patients after systemic treatment through an oral glucose tolerance test (OGTT) in China. All the 119 breast cancer patients more than 3 months after systemic treatment with surgery and chemotherapy participated in the study. All the patients without the diagnosis of diabetes underwent OGTT, and fasting and 2-h glucose levels were measured to identify undiagnosed diabetes and prediabetes. Previously diagnosed diabetes were determined on the self-report and the medical record. Of the 119 breast cancer patients, with the median age of 50.1 years and the mean age of about 48 years when they were initially diagnosed with breast cancer, which showed the similar characters of China and Asia breast cancer patients, the overall incidences of total diabetes and prediabetes were 21.8 and 43.7 %, respectively. About 80 % of the diabetes were previously undiagnosed. About 80.0 % of the cases of undiagnosed diabetes and prediabetes met the criteria for elevated 2-h plasma glucose levels through OGTT but not the criteria for elevated fasting glucose levels. Our study firstly documents high incidences of previously undiagnosed diabetes and prediabetes in breast cancer patients during follow-up after systemic treatment through OGTT, indicating that greater diabetes screening, especially through OGTT, prevention, and treatment strategies among breast cancer patients, after systemic treatment for these patients is needed.

Implication from thyroid function decreasing during chemotherapy in breast cancer patients: chemosensitization role of triiodothyronine.

BACKGROUND: Thyroid hormones have been shown to regulate breast cancer cells growth, the absence or reduction of thyroid hormones in cells could provoke a proliferation arrest in G0-G1 or weak mitochondrial activity, which makes cells insensitive to therapies for cancers through transforming into low metabolism status. This biological phenomenon may help explain why treatment efficacy and prognosis vary among breast cancer patients having hypothyroid, hyperthyroid and normal function. Nevertheless, the abnormal thyroid function in breast cancer patients has been considered being mainly caused by thyroid diseases, few studied influence of chemotherapy on thyroid function and whether its alteration during chemotherapy can influence the respose to chemotherapy is still unclear. So, we aimed to find the alterations of thyroid function and non-thyroidal illness syndrome (NTIS) prevalence druing chemotherapy in breast cancer patients, and investigate the influence of thyroid hormones on chemotherapeutic efficacy. METHODS: Thyroid hormones and NTIS prevalence at initial diagnosis and during chemotherapy were analyzed in 685 breast diseases patients (369 breast cancer, 316 breast benign lesions). The influence of thyroid hormones on chemotherapeutic efficacy was evaluated by chemosensitization test, to compare chemotherapeutic efficacy between breast cancer cells with chemotherapeutics plus triiodothyronine (T3) and chemotherapeutics only. RESULTS: In breast cancer, NTIS prevalence at the initial diagnosis was higher and increased during chemotherapy, but declined before the next chemotherapeutic course. Thyroid hormones decreased signigicantly during chemotherapy. T3 can enhance the chemosensitivity of MCF-7 to 5-Fu and taxol, with progression from G0-G1 phase to S phase. The similar chemosensitization role of T3 were found in MDA-MB-231. We compared chemotherapeutic efficacy among groups with different usage modes of T3, finding pretreatment with lower dose of T3, using higher dose of T3 together with 5-Fu or during chemotherapy with 5-Fu were all available to achieve chemosensitization, but pretreatment with lower dose of T3 until the end of chemotherapy may be a safer and more efficient therapy. CONCLUSIONS: Taken together, thyroid hormones decreasing during chemotherapy was found in lots of breast cancer patients. On the other hand, thyroid hormones can enhance the chemotherapeutic efficacy through gatherring tumor cells in actively proliferating stage, which may provide a new adjuvant therapy for breast cancer in furture, especially for those have hypothyroidism during chemotherapy.

MG132-mediated inhibition of the ubiquitin-proteasome pathway ameliorates cancer cachexia.

PURPOSE: To evaluate the effect of proteasome inhibitor MG132 in cancer cachexia and to delineate the molecular mechanism underlying. METHODS: We established an experimental cancer cachexia model by subcutaneously implanting colon 26 cells into the armpits of BALB/c mice. Following administration of MG132 at various time points, body weight, food intake, gastrocnemius muscle weight, spontaneous activity and survival of tumor-bearing mice were examined along with tumor growth. Moreover, cachectic markers including glucose, triglyceride, albumin and total proteins as well as levels of the proinflammatory cytokines TNF-α and IL-6 in serum and gastrocnemius tissue were measured. Finally, mRNA and protein levels of p65, IκBα, and ubiquitin E3 ligases MuRF1 and MAFbx in gastrocnemius muscle were assessed. RESULTS: MG132 treatment significantly alleviated cancer cachexia as demonstrated by attenuated weight loss, altered carbohydrate metabolism and muscle atrophy and increased spontaneous activity and survival time of tumor-bearing mice. MG132 reduced tumor growth and the levels of TNF-α and IL-6 in serum and gastrocnemius tissue. NF-κB, MuRF1 and MAFbx were also inhibited by MG132. Unexpectedly, MG132 was more efficient when administrated during the early stages of cachexia. MG132 had no effect on food intake of tumor-bearing mice. CONCLUSION: Our results demonstrate that MG132-induced inhibition of the ubiquitin-proteasome pathway in cancer cachexia decreased the activity of NF-κB and the degradation of IκBα, and reduced the levels of TNF-α and IL-6 in serum and gastrocnemius tissue, accompanied by downregulation of MuRF1 and MAFbx. These data suggest that MG132 is a potential therapeutic and preventive agent for cancer cachexia.