Yongchuan Deng

Colorectal cancer lymph node staining by activated carbon nanoparticles suspension in vivo or methylene blue in vitro

AIM To investigate whether activated carbon nanoparticles suspension (ACNS) or methylene blue (MB) can increase the detected number of lymph nodes in colorectal cancer. METHODS Sixty-seven of 72 colorectal cancer patients treated at our hospital fulfilled the inclusion criteria of the study which was conducted from December 2010 to February 2012. Seven patients refused to participate. Eventually, 60 patients were included, and randomly assigned to three groups (20 in each group): ACNS group (group A), MB group (group B) and non-stained conventional surgical group (group C). In group A, patients received subserosal injection of 1 mL ACNS in a 4-quadrant region around the mass. In group B, the main artery of specimen was identified and isolated after the specimen was removed, and 2 mL MB was slowly injected into the isolated, stretched and fixed vessel. In group C, no ACNS and MB were injected. All the mesentery lymph nodes were isolated and removed systematically by visually inspecting and palpating the adipose tissue. RESULTS No difference was observed among the three groups in age, gender, tumor location, tumor diameter, T-stage, degree of differentiation, postoperative complications and peritoneal drainage retention time. The total number of detected lymph nodes was 535, 476 and 223 in the three groups, respectively. The mean number of detected lymph nodes per patient was significantly higher in group A than in group C (26.8 ± 8.4 vs 12.2 ± 3.2, P < 0.001). Similarly, there were significantly more lymph nodes detected in group B than in group C (23.8 ± 6.9 vs 12.2 ± 3.2, P < 0.001). However, there was no significant difference between group A and group B. There were 50, 46 and 32 metastatic lymph nodes dissected in 13 patients of group A, 10 patients of group B and 11 patients of group C, without significant differences among the three groups. Eleven of the 60 patients had insufficient number of detected lymph nodes (< 12). Only one patient with T(4a) rectal cancer had 10 lymph nodes detected in group B, the other 10 patients were all from group C. Based on the different diameter categories, the number of detected lymph nodes in groups A and B was significantly higher than in group C. However, there was no statistically significant difference between group A and group B. The metastatic lymph nodes were not significant different among the three groups. Similarly, tumor location, T stage and tumor differentiation did not affect the staining results. Body mass index was a minor influencing factor in the two different staining methods. The stained lymph nodes can easily be identified from the mesenteric adipose tissues, and the staining time for lymph nodes was not significantly different compared with unstained group. None of the patients in groups A and B had drug-related complications. CONCLUSION Both activated carbon nanoparticles suspension in vivo and methylene blue in vitro can be used as tracers to increase the detected number of lymph nodes in colorectal cancer.

Honokiol synergizes chemotherapy drugs in multidrug resistant breast cancer cells via enhanced apoptosis and additional programmed necrotic death

Multidrug resistance (MDR) is a major challenge in cancer therapy. Apoptosis tolerance is one of the key mechanisms of MDR. Honokiol, a small-molecule pharmacologically active component, exhibits competent cytotoxicity in a variety of human cancer cells through apoptosis and other forms of programmed cell death (such as programmed necrosis). Although much work has been done on its antitumor effects, little attention has been paid on systemic evaluation of efficacy of honokiol combined with other chemotherapeutic agents, especially in drug‑resistant cell lines. Here, we systematically and quantitatively assess its combinational effect with different chemotherapeutic agents using the combination index (CI) equation. We found that honokiol synergized with chemotherapeutic agents both in sensitive and resistant, solid and non-solid (MCF-7, HL-60, MCF-7/ADR and HL-60/ADR) cell lines. Honokiol (40 µg/ml) induced necrotic cell death in MCF-7/ADR cells with characterized morphological and biochemical features. Co-incubation with honokiol and etoposide (VP-16) activated a complex death modality, which was composed of necrotic cell death and apoptosis. This dual-death pathway was shut down when pretreated with pan-caspase inhibitor (z-VAD-fmk) and cyclophilin D inhibitor (cyclosporin A). Western blot analysis results proved that honokiol also enhanced VP-16-induced apoptosis potentially via blocking nuclear factor‑κB (NF-κB) activation. Our data for the first time quantitatively demonstrate that honokiol synergizes frequently-used chemotherapeutic agents via enhanced apoptosis and additional programmed necrotic death. These findings indicate a promising way to circumvent MDR and apoptosis tolerance.

Diaphragmatic perforation with colonic herniation due to hepatic radiofrequency ablation: A case report and review of the literature

Radiofrequency ablation (RFA) has been widely accepted as an alternative treatment for unresectable primary and metastatic hepatic tumors, with satisfactory rates of local response and significant improvements in rates of overall survival. Numerous large series studies have shown that RFA is safe and effective, with a low mortality rate and a low major complication rate. Major complications, including diaphragmatic perforation and hernia, have rarely been previously reported. The current case report presents a case of diaphragmatic hernia with perforation of the incarcerated colon in the thoracic cavity 12 months following hepatic RFA, and reviews nine previously reported cases of diaphragmatic hernia. Comprehensive analysis of the nine cases demonstrated possibilities leading to diaphragmatic hernia following diaphragmatic thermal injury as a consequence of hepatic RFA. Clinicians and radiologists must consider diaphragmatic thermal damage following hepatic RFA for liver tumors adjacent to the diaphragm, particularly for patients with symptoms of ileus, dyspnea, chest pain, pleural effusion and right shoulder pain.

Combined oxidized cellulose and cyanoacrylate glue in the management of severe presacral bleeding

Massive presacral bleeding is a severe complication during a resection of the rectum. The combination of oxidized cellulose and cyanoacrylate glue can quickly control presacral bleeding. This report presents nine cases since 2002 of presacral hemorrhage treated using this method. There was no recurrent bleeding during the postoperative period. All patients were followed for 6–12 months, and there were no other complications reported.

New clinical application of high-intensity focused ultrasound: local control of synovial sarcoma

High-intensity focused ultrasound (HIFU) is playing an increasingly important role in cancer therapy. Primary synovial sarcomas of the chest wall are extremely rare. We report the first case of noninvasive HIFU therapy for the control of synovial sarcoma. A 51-year-old man was diagnosed with spindle cell sarcoma on the left chest wall through lumpectomy. After four cycles of chemotherapy, local recurrence of the sarcoma was detected. Subsequent extended resection confirmed synovial sarcoma. After five cycles of a new chemotherapy option, the sarcoma relapsed again. Then the patient received five courses of HIFU; this completely ablated the sarcoma without complications. No chemotherapy, radiotherapy, or biological therapy has been applied since. Now the patient is stable and has a high quality of life.

Enhanced lymph node retrieval from colorectal cancer resections using a simple lymphatic staining method.

BACKGROUND/AIMS This study evaluated the effect of lymphatic staining on the number of lymph nodes (LNs) examined and staging in patients with colorectal cancer. METHODOLOGY Sixty-two consecutive specimens from patients with colorectal cancer resected between February 2009 and April 2010 were randomized to the stained group or the control unstained. Differences in the retrieval, number and size of nodes, and time for retrieval were measured. RESULTS LN harvest differed significantly with 30±12 and 13±5 (p<0.01) nodes in the stained and the control groups, respectively. Insufficient LN harvest (less than 12 nodes) occurred in 14 cases of the control group and only in 1 case of the stained group (p<0.01). Metastases were confirmed in 57 LNs occurring in 17 cases of the stained group and in 39 nodes occurring in 15 cases of the control group. The mean time for LN retrieval in the stained and control groups were comparable, 27.6±6.9min and 24.7±6.0min (p>0.05), respectively, yet there was a significant difference in the number of LNs (<2mm) (294 vs. 59, respectively, p<0.01) as well as in the number of LNs 2-5mm in size (474 vs. 220, respectively, p<0.01). CONCLUSIONS By lymphatic staining method, more and smaller LNs could be detected, which significantly improved the LN harvest of resected colorectal specimens and reduced cases of insufficient LN harvest.

mTOR signaling pathway is inhibited downstream of the cyclophilin D-mediated mitochondrial permeability transition in honokiol-triggered regulated necrosis

Honokiol (HNK) is a pharmacologically active small molecule that is isolated from the traditional Chinese medicinal herb, houpu. It may induce diversified types of regulated cell death, which are dependent on different cell types and varying concentrations of therapeutic agent. We previously reported that HNK triggers a cyclophilin D (CypD)-mediated regulated necrosis in various cell lines at certain concentrations (two‑fold higher than its half maximal inhibitory concentration). Subsequent study revealed that HNK induced cell death transition from early apoptosis to regulated necrosis in parallel with the increase of HNK dose. In the current study, a lower concentration of HNK (30 µg/ml) than previously reported also induced simplex CypD‑mediated mitochondrial permeability transition (MPT)‑associated regulated necrosis in the HEK‑293 human embryonic kidney cell line. HNK, at concentration of 30 µg/ml, induced necrotic cell death in HEK‑293 cells, which was demonstrated by positive staining for propidium iodide. No DNA ladder patterns or apoptotic bodies were detected in cells that underwent this type of necrotic cell death. Caspase‑8 and ‑3 were not activated during the process of HNK‑induced necrosis. In addition, pan‑caspase inhibitor, z‑VAD‑fmk and receptor‑interacting protein 1 inhibitor, necrostatin‑1 did not inhibit HNK‑induced necrosis. However, CypD inhibitor, cyclosporin A (CsA), blocked HNK‑induced necrosis. These findings indicate that 30 µg/ml HNK induced simplex CypD-mediated MPT‑associated regulated necrosis in HEK‑293 cells. Furthermore, the findings demonstrated that during HNK-triggered regulated necrosis the mammalian target of rapamycin (mTOR) signaling pathway is also inhibited. Pretreatment with CsA, therefore, inhibits HNK‑triggered regulated necrosis and reverses dephosphorylation of Akt, eIF4E‑binding protein 1 and S6 kinase. This indicated that the mTOR signaling pathway is effective downstream of the CypD‑mediated MPT and before the onset of plasma membrane breakdown during the regulated necrosis process. Therefore, it has been demonstrated for the first time, to the best of our knowledge, that the mTOR signaling pathway was inhibited downstream of the CypD-mediated MPT in the process of HNK-induced regulated necrosis.