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Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies. Recently developed molecular targeted therapies are not available for patients with ESCC. After curative surgical resection, patients frequently suffer distant metastasis and recurrence. Exploration of novel ESCC metastatic pathways may lead to the development of new treatment protocols for this disease. Accordingly, we have sequentially identified microRNA (miRNA)-mediated metastatic pathways in several cancers. Our past studies of miRNA expression signatures have shown that microRNA-375 (miR-375) is frequently reduced in several types of cancers, including ESCC. In the present study, we aimed to investigate novel miR-375-mediated metastatic pathways in ESCC cells. The expression of miR-375 was downregulated in ESCC tissues, and ectopic expression of this miRNA markedly inhibited cancer cell migration and invasion, suggesting that miR-375 acted as an antimetastatic miRNA in ESCC cells. Our strategies for miRNA target searching demonstrated that matrix metalloproteinase 13 (MMP13) was directly regulated by miR-375 in ESCC cells. Overexpression of MMP13 was observed in ESCC clinical tissues, and the expression of MMP13 promoted cancer cell aggressiveness. Moreover, oncogenic genes, including CENPF, KIF14 and TOP2A, were shown to be regulated downstream of MMP13. Taken together, these findings demonstrated that the antitumor miR-375/oncogenic MMP13 axis had a pivotal role in ESCC aggressiveness. These results provide novel insights into the potential mechanisms of ESCC pathogenesis.

Background/aim Maternal embryonic leucine zipper kinase (MELK) is categorized as a member of AMP-activated protein kinase families. Various MELK-associated cellular and biological processes affect multiple stages of tumorigenesis. The aim of the present study was to clarify the relationship between MELK expression and hepatocellular carcinoma (HCC) clinicopathological features. Materials and methods In thirty conserved frozen primary HCC and non-HCC samples MELK mRNA expression was examined by quantitative real-time polymerase chain reaction (PCR). Results HCC tissues exhibited significantly higher expression levels compared to non-cancerous tissues. MELK expression had a statistically parallel correlation between tumor diameter and protein induced by vitamin K absence or antagonist II (PIVKA-II). The overall survival (OS) and recurrence-free survival (RFS) of the low MELK mRNA expression group was significantly longer than that of the high MELK mRNA expression group. Conclusion MELK expression in HCC is extremely intense compared to its expression reported in other types of cancer. MELK could be a promising effective tumor marker of HCC and further consideration is needed.

AIM To compare adverse events and post-therapeutic clinical courses between stomach-partitioning gastrojejunostomy with Braun enteroenterostomy (SPGJ-BEE) and endoscopic metallic stent placement (EMSP) in patients with gastric outlet obstruction (GOO) caused by unresectable gastric cancer and assess the clinical utility of SPGJ-BEE. PATIENTS AND METHODS We retrospectively reviewed clinical data of 16 and 9 patients with GOO undergoing SPGJ-BEE and EMSP, respectively. RESULTS Re-obstruction caused by tumor overgrowth was identified in 3 (33.3%) out of 9 patients in the EMSP group. The GOO scoring system (GOOSS) revealed that its score after treatments was significantly higher in the SPGJ-BEE group than in the EMSP group (p

Objectives The aim of the present study was to investigate the effectiveness of serum carbohydrate antigen (CA) 19.9 and duke pancreatic monoclonal antigen type 2 (DUPAN-2) levels in the prediction of early hematogenous metastases and as indicators of neoadjuvant therapy in patients with pancreatic ductal adenocarcinoma (PDAC). Methods Of the 293 enrolled PDAC patients, 61 had hematogenous metastases at the initial evaluation. One hundred and twenty patients without metastases underwent surgical resection. Of the 120 patients who underwent surgical resection, 45 underwent preoperative treatment and 29 developed early hematogenous metastases within 1 year after the surgery. In patients who underwent preoperative therapy, serum CA 19.9 and DUPAN-2 levels were measured within 2 weeks before the preoperative therapy and the subsequent surgery. Results The elevated serum CA 19.9 and DUPAN-2 levels were significantly associated with hematogenous metastasis at initial evaluation and early hematogenous metastasis after surgery. The rate of early hematogenous metastasis and overall survival (OS) in patients with high CA 19.9 and/or high DUPAN-2 (CA 19.9 > 200 U/mL and/or DUPAN-2 >300 U/mL) were 46.3% and 18 months, respectively, whereas the metastatic rate and OS in patients with low CA 19.9 and DUPAN-2 were 12.7% and 37.5 months, respectively. Furthermore, in patients with high CA 19.9 and/or high DUPAN-2, preoperative therapy significantly reduced the rate of early hematogenous metastasis and prolonged the OS. Conclusions Serum CA 19.9 and DUPAN-2 levels are useful predictors of early hematogenous metastasis and indicators for effectiveness of neoadjuvant therapy in PDAC patients.

Due to its aggressive nature, pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal and hard-to-treat malignancies. Recently developed targeted molecular strategies have contributed to remarkable improvements in the treatment of several cancers. However, such therapies have not been applied to PDAC. Therefore, new treatment options are needed for PDAC based on current genomic approaches. Expression of microRNA-375 (miR-375) was significantly reduced in miRNA expression signatures of several types of cancers, including PDAC. The aim of the present study was to investigate the functional roles of miR-375 in PDAC cells and to identify miR-375-regulated molecular networks involved in PDAC aggressiveness. The expression levels of miR-375 were markedly downregulated in PDAC clinical specimens and cell lines (PANC-1 and SW1990). Ectopic expression of miR-375 significantly suppressed cancer cell proliferation, migration and invasion. Our in silico and gene expression analyses and luciferase reporter assay showed that zinc finger protein 36 ring finger protein-like 2 (ZFP36L2) was a direct target of miR-375 in PDAC cells. Silencing ZFP36L2 inhibited cancer cell aggressiveness in PDAC cell lines, and overexpression of ZFP36L2 was confirmed in PDAC clinical specimens. Interestingly, Kaplan-Meier survival curves showed that high expression of ZFP36L2 predicted shorter survival in patients with PDAC. Moreover, we investigated the downstream molecular networks of the miR-375/ZFP36L2 axis in PDAC cells. Elucidation of tumor-suppressive miR-375-mediated PDAC molecular networks may provide new insights into the potential mechanisms of PDAC pathogenesis.

Background/Aim: Despite the fact that breast cancer patients are generally administered systemic chemotherapy after surgical treatment, predictive factors that allow optimization of chemotherapy are needed. The histoculture drug response assay (HDRA) is a clinically practical in vitro drug-response assay for identifying optimal anticancer agents. Patients and Methods: Thirty-eight primary breast cancer patients who underwent surgical treatment without receiving systemic neoadjuvant therapy were analyzed. We retrospectively examined the relationships between clinicopathological factors and the HDRA results of 5 anticancer agents (mitomycin C (MMC), 5-fluorouracil (5-FU), doxorubicin hydrochloride (ADM), cisplatin (CDDP) and paclitaxel (PTX)). Results: The relationships between the inhibition rates of anticancer drugs and clinicopathological factors were not significant, except for nuclear grade and venous invasion with the inhibition rate of 5-FU. We also established the threshold inhibition rate for PTX. The paclitaxel inhibition rate was significantly associated with disease-free survival (DFS). Conclusion: HDRA results were independent from the clinicopathological factors of breast cancer patients demonstrating that individualized treatment is needed.

This retrospective study was done to examine whether the heterogeneity in primary tumour F-18-fluorodeoxyglucose (The enrolled 52 patients with esophageal cancer underwentThirty four non-responders showed significantly higher MTV (p = 0.006), TLG (p = 0.007), intensity variability (IV; p = 0.003) and size-zone variability (SZV; p = 0.004) than 18 responders. The positive and negative predictive values for non-responders were 77 % and 69 % in MTV, 76 % and 100 % in TLG, 78 % and 67 % in IV and 78 % and 82 % in SZV, respectively. Although PFS and OS were significantly shorter in patients with high MTV (PFS, p = 0.018; OS, p = 0.014), TLG (PFS, p = 0.009; OS, p = 0.025), IV (PFS, p = 0.013; OS, p = 0.007) and SZV (PFS, p = 0.010; OS, p = 0.007) at univariate analysis, none of them was an independent factor, while lymph node status, stage and tumour response status were independent factors at multivariate analysis.Texture features IV and SZV, and volumetric parameters MTV and TLG can predict tumour response, but all of them have limited value in prediction of prognosis of patients with esophageal cancer treated by CRT.

Pancreatic neuroendocrine tumors (PNETs) are a rare type of malignancy with a prognosis that is relatively good, compared with that of pancreatic adenocarcinoma. However, a number of patients with PNETs have distant metastasis and a less favorable prognosis. Epithelial-mesenchymal transition (EMT) is essential for tumor progression and metastasis. Snail and E-cadherin serve key roles in the process of EMT in numerous tumor types, including gastric and pancreatic adenocarcinoma. However, the role of EMT in PNETs remains unclear. The aim of the present study was to investigate the significance of Snail and E-cadherin expression in PNETs. Tissue samples were obtained from 40 resected PNETs. The expression of Snail and E-cadherin was evaluated in the primary tumors using immunohistochemical staining. The association between protein expression and patient clinicopathological features was then analyzed. High and low Snail expression levels were observed in 11 (27.5%) and 29 (72.5%) patients, respectively. Preserved and reduced E-cadherin expression was observed in 19 (47.5%) and 21 (52.5%) patients, respectively. Patients with low Snail expression and preserved E-cadherin expression had a significantly lower risk of vascular invasion, lymphatic invasion, lymph node metastasis and liver metastasis and a lower WHO classification, as compared with the group that included patients with high Snail and reduced E-cadherin, high Snail and preserved E-cadherin, and low Snail and reduced E-cadherin expression. In addition, the patients with low Snail expression levels and preserved E-cadherin expression had more a favorable prognosis compared with the other group. The present study indicates that EMT serves an important role in tumor progression in PNETs. Immunohistochemical evaluation of Snail and E-cadherin is useful for predicting the risk of vessel invasion and metastasis in PNETs.

A 51-year-old man who had undergone distal gastrectomy for gastric cancer was admitted in Kagoshima University Hospital under the diagnosis of anastomotic recurrence of gastric cancer. From abdominal CT results, the recurred tumor was suspected to invade into the pancreas with regional node metastases. Because of the intense radicality of surgical intervention, we planned 3 courses of docetaxel, cisplatin, and S-1 triplet therapy(DCS therapy). After the chemotherapy, the recurred tumor and lymph node metastases shrunk drastically. Segmental gastrectomy with lymph node dissection was performed with curative intent. Final pathology revealed complete regression of both the recurred tumor and lymph node metastases. The patient's postoperative course was uneventful without tumor relapse. DCS therapy seems to be suitable to obtain drastic tumor regression before surgical intervention as a neoadjuvant chemotherapy for locally advanced gastric cancer.

Endoscopic thyroidectomy is a well-established surgical technique that is mainly performed for benign thyroid disease. We considered that endoscopic surgery could also be widely indicated for the treatment of thyroid cancer. We herein describe our new bidirectional approach of video-assisted neck surgery (BAVANS) for complete central node dissection in endoscopic thyroid cancer surgery.BAVANS involves two different directional pathways to the cervical lesion. Before lymph node dissection, we perform endoscopic thyroidectomy via a conventional gasless precordial or axillary approach. After thyroidectomy, the surgeon repositions by the head of the patient and inserts three ports in front of the upper neck lesion in the submandibular area to approach the paratracheal lesion from an overhead-to-caudal direction.BAVANS allows for an excellent craniocaudal view and easy access to the peritracheal lymph nodes. Sixteen patients with papillary thyroid cancer underwent BAVANS and progressed satisfactorily after surgery. Of those patients, eight underwent total or near total thyroidectomy, and five patients underwent bilateral central node dissection. The average number of retrieved lymph nodes with unilateral central node dissection was nine, which was higher than that achieved with conventional open surgery. All patients began oral intake within 5 h after surgery. Postoperative Horner syndrome occurred in one patient. No other complications were noted.BAVANS is a very effective surgical procedure that many endoscopic surgeons can perform safely and easily. It has both a cosmetic advantage and excellent curability in endoscopic thyroid cancer surgery.

The use of novel sequencing and high-throughput techniques has become widespread, and are now readily available to obtain the comprehensive transcription profile of the human genome. Noncoding RNAs (ncRNAs) are transcripts that have no apparent protein-coding capacity, but they have important roles in human physiology. Most research in this area has focused on micro-RNAs. However, the role of long ncRNAs (lncRNAs) as drivers of tumor suppression and oncogenic functions has recently been examined in numerous cancer types. Epigenetic alterations can reportedly deregulate the expression of any type of transcript. However, the exact mechanisms of epigenetic regulation of lncRNA are still unknown. In this review, the authors primarily focus on the epigenetic effects modulating ncRNA in colorectal cancer (CRC). The authors specifically discuss examples of oncogenic ncRNA in CRC pathobiology, as well as its extended diagnosis, prognosis and therapy.

Anti-epidermal growth factor receptor antibody therapy alone or in combination with irinotecan is recognized as a standard third-line treatment for KRAS wild-type unresectable metastatic colorectal cancer. However, in some cases, it is difficult to administer irinotecan after third-line treatment. Therefore, we examined the efficacy and safety of the combination of cetuximab and S-1 in patients with KRAS wild-type unresectable metastatic colorectal cancer who were previously treated with irinotecan, oxaliplatin, and fluoropyrimidines.The study was designed as a phase II, non-randomized, open-label, multicenter trial. Cetuximab was initially administered at 400 mg/m(2), followed by weekly infusion at 250 mg/m(2). S-1 was administered at a fixed dose of 80 mg/m(2) orally twice daily for 28 days followed by a 14-day break, resulting in a 6-week treatment course. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the overall response rate (ORR), overall survival (OS), disease control rate (DCR), time to treatment failure, dose intensity, safety, and BRAF mutation status.Thirty-seven patients were eligible. The median PFS was 5.5 months, the median OS was 13.5 months, the ORR was 29.7 %, and the DCR was 73.0 %. The relative dose intensity was 86.8 % for cetuximab and 88.1 % for S-1. Grade 3-4 adverse events that occurred in10 % of the patient population included rash, dry skin, diarrhea, paronychia, anorexia, fatigue, mucositis, and neutropenia.Combination therapy with cetuximab and S-1 was effective and well tolerated in patients with irinotecan-, oxaliplatin-, and fluoropyrimidine-refractory metastatic colorectal cancer.

Therapeutic effectiveness against metastatic or even locally advanced pancreatic ductal adenocarcinoma (PDAC) is dismal, with 5-year survival less than 5%. Even in patients who undergo potentially curative resection, most patients' tumors recur in the liver. Improving therapies targeting or preventing liver metastases is crucial for improving prognosis. To identify genes suppressing metastasis, a genome-wide shRNA screen was done using the human non-metastatic PDAC cell line, S2-028. After identification of candidates, functional validation was done using intrasplenic and orthotopic injections in athymic mice. HMP19 strongly inhibited metastasis but also partially attenuated tumor growth in the pancreas. Knockdown of HMP19 increased localization of activated ERK1/2 in the nucleus, corresponding to facilitated cell proliferation, decreased p27(Kip1) and increased cyclin E1. Over-expression of HMP19 exerted the opposite effects. Using a tissue microarray of 84 human PDAC, patients with low expression of HMP19 showed significantly higher incidence of liver metastasis (p = 0.0175) and worse prognosis (p = 0.018) after surgery. HMP19, a new metastasis/tumor suppressor in PDAC, appears to alter signaling that leads to cell proliferation and appears to offer prognostic value in human PDAC.

A 67-year-old man who was hospitalized at a mental hospital because of schizophrenia was admitted to our hospital with a complaint of dysphagia and vomiting. He was found to have advanced cancer in the middle thoracic esophagus. With the cooperation of a radiologist, a psychiatrist, and a nurse, we successfully performed chemoradiation therapy with S-1 and CDDP. The patient had adverse events of esophagitis and anuria during chemoradiation therapy. However, such adverse events were well controlled through the cooperation with a palliative care team and a urologist. Finally, we were able to enforce chemoradiation therapy with S-1 and CDDP without interruption.

Pancreatic cancer is a deadly disease with a poor prognosis. Recently, miRNAs have been reported to be abnormally expressed in several cancers and play a role in cancer development and progression. However, the role of miRNA in cancer stem cells remains unclear. Therefore, our aim was to investigate the role of miRNA in the CD133(+) pancreatic cancer cell line Capan-1M9 because CD133 is a putative marker of pancreatic cancer stem cells. Using miRNA microarray, we found that the expression level of the miR-30 family decreased in CD133 genetic knockdown shCD133 Capan-1M9 cells. We focused on miR-30a, -30b, and -30c in the miR-30 family and created pancreatic cancer cell sublines, each transfected with these miRNAs. High expression of miR-30a, -30b, or -30c had no effect on cell proliferation and sphere forming. In contrast, these sublines were resistant to gemcitabine, which is a standard anticancer drug for pancreatic cancer, and in addition, promoted migration and invasion. Moreover, mesenchymal markers were up-regulated by these miRNAs, suggesting that mesenchymal phenotype is associated with an increase in migration and invasion. Thus, our study demonstrated that high expression of the miR-30 family modulated by CD133 promotes migratory and invasive abilities in CD133(+) pancreatic cancer cells. These findings suggest that targeted therapies to the miR-30 family contribute to the development of novel therapies for CD133(+) pancreatic cancer stem cells.

We have reported excellent results for immediate volume replacement using autologous tissues. In particular, volume replacement using a free dermal fat graft from the lower abdomen is thought to be appropriate for treating patients with breast cancer in the upper inner quadrant area. We have modified this technique and report the results of oncoplastic surgery in four Japanese patients with early breast cancer. Their breasts were non-ptotic, and each lesion was considered to be suitable for breast conservative surgery. Immediate volume replacement therapy using a free dermal fat graft from the lateral abdomen into the breast cavity was performed as breast-conserving surgery. The technique was easy to perform, and the cosmetic outcome was excellent.

Our previous study reported a frequent detection of human papillomavirus (HPV) genome in primary lung adenocarcinomas of the recurrent patients who were responsive to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, suggesting that HPV presence in lung cancer may be related to a genetic background related to EGFR mutations. The present study examined the association between the HPV presence and mutations in exons 19 and 21 of EGFR gene in Japanese lung cancer patients. Thirteen (31%) out of 42 cases had EGFR mutations. Although these mutations were tended to be observed in females, non-smokers, or adenocarcinomas, there was no statistically significant associations. HPV DNA was found in 7/42 (17%) lung tumors. The frequency of HPV presence did not differ in histological types. The presence of HPV DNA was significantly related to EGFR mutations (P=0.021), especially in adenocarcinomas of the lung (P=0.014). HPV-positive lung tumors accounted for 38% and 7% of those with and without EGFR mutations, respectively. Our results suggest that EGFR mutations are associated with HPV presence in Japanese patients with lung cancer.

Background Endoscopic thyroidectomy is a well-established surgical technique. We have been utilizing precordial video-assisted neck surgery (VANS) with a gasless anterior neck skin lifting method. Recently, natural orifice transluminal endoscopic surgery (NOTES) has generated excitement among surgeons as potentially scar-free surgery. We developed an innovative gasless transoral technique for endoscopic thyroidectomy that incorporated the concept of NOTES in a VANS-technique. Methods Incision was made at the vestibulum under the inferior lip. From the vestibulum to the anterior cervical region, a subplatysmal tunnel in front of the mandible was created and cervical skin was lifted by Kirschner wires and a mechanical retracting system. This method without CO2 insufflation created an effective working space and provided an excellent cranio-caudal view so that we could perform thyroidectomy and central node dissection safely. Results Beginning with our first clinical application of TOVANS in September 2009, we have performed eight such procedures. Three of the eight patients had papillary microcarcinoma and received central node dissection after thyroidectomy. All patients began oral intake 1 day after surgery. The sensory disorder around the chin persisted more than 6 months after surgery in all patients. Recurrent laryngeal nerve palsy revealed in one patient. Nobody had mental nerve palsy, and no infection developed with use of preventive antibacterial tablets for 3 days. Conclusions We developed a new method for gasless transoral endoscopic thyroidectomy with a premandible approach and anterior neck-skin lifting. TOVANS makes possible complete endoscopic radical lymphadenectomy for papillary thyroid cancer. We believe that this method is innovative and progressive and has not only a cosmetic advantage but also provides easy access to the central node compartment for dissection in endoscopic thyroid cancer surgery.

Gastric cancers with portal tumor thrombosis (GCPTs) are a rare entity, often concomitant with hematogenous metastases, and chemotherapy is mainly used to treat them. However, the outcome of GCPT is reported to be dismal. We experienced a case of GCPT with splenic metastases. A 53-year-old man was admitted for anorexia. Upper gastrointestinal scope revealed type 3 gastric cancer of the stomach. Abdominal computed tomography showed a huge tumor thrombus in the splenic vein extending to the hepatic hilus and multiple metastases to the spleen. S-1 was given orally from day 1 to day 21 and 60 mg of CDDP was administered intravenously. The cancerous thrombosis in the portal system and splenic metastases disappeared due to chemotherapy. Total gastrectomy with lymphadenectomy and splenectomy was carried out with curative intent after 10 courses of chemotherapy. Intraoperatively, no tumor thrombosis was identified and the gastric tumor was surgically removed. After surgery, the patient received adjuvant chemotherapy of S-1. After 6 months he is well and has not suffered from tumor relapse. A combination of CDDP + S-1 plus intervention surgery seems to be a promising option for GCPT.

Pancreatic cancer is a lethal disease as current chemotherapies with gemcitabine (GEM) are still insufficient. Accumulating evidence suggests that cancer stem cells (CSC) are responsible for chemoresistance and that CD133 is one of the CSC markers in pancreatic cancer. Interferon‐alpha (IFN‐α), a cytokine with pleiotropic effects, has direct cytotoxic and cytostatic effects on tumor cells. The aim of the present study was to investigate whether IFN‐α can modulate the chemosensitivity of a human pancreatic cancer cell line, Capan‐1, to GEM. Cell cycles were evaluated for response to GEM with and without IFN‐α by BrdU assay. GEM inhibited Capan‐1 cell growth in a dose‐dependent manner. GEM (IC (50); 100 ng/mL) treatment reduced the number of both CD133(+) and CD133(−) cells in the S phase, induced apoptosis of CD133(−) cells more than that of CD133(+) cells and increased accumulation of CD133(+) cells into the G0/G1 phase. These results infer that CD133(+) cells take shelter into the G0/G1 phase from GEM treatment. IFN‐α modulated CD133(+) cells from the G0/G1 phase to the S phase. Consequently, apoptosis was accelerated in both CD133(+) and CD133(−) cells after IFN‐α combined with GEM treatment. Furthermore, GEM combined with IFN‐α treatment showed a significant tumor suppressive effect in the in vivo study. Importantly, CD133(+) cells showed CSC‐like properties, such as generation of spheres, highly invasive ability and high tumorigenesis. These results suggest that IFN‐α, as a modulator, could contribute to the treatment of CD133(+) cancer cells and be effective in combined chemotherapies with GEM for pancreatic cancer stem‐like cells. (Cancer Sci 2012; 103: 889–896)

Purpose The efficacy of immediate breast reconstruction using a free dermal fat graft (FDFG) was evaluated clinically. Patients and methods A total of 22 breasts in 21 patients who underwent partial mastectomy for early breast cancer involving mainly the inner upper quadrant were enrolled in this study. The defect was reconstructed immediately by filling it with an autologous FDFG. At 6 months and 1, 2, 3, 4, and 5 years postoperatively, the width (horizontal length) and thickness (distance perpendicular to skin) of the FDFG on computed tomography (CT) scans were measured. Histologic samples from the implanted FDFG were collected by core needle biopsy (CNB). The correlations between clinical findings and volume of the FDFG on CT and the proportion of fatty tissue in the CNB were examined statistically. Cosmetic results were also evaluated. Results On CT, the mean width of the FDFG was 95%, 81%, 79%, 73%, 68%, and 47% and the mean thickness were 125%, 121%, 120%, 115%, 104%, and 103% at 6 months, and 1–5 years postoperatively, respectively. In the CNB samples, the mean fatty tissue distribution was 76%, 63%, and 54% at 1 year, 1–4 years, and >4 years postoperatively, respectively. The percent change in the width of the FDFG at 6 months after the operation displayed a significant negative correlation with the postmenopausal period and a significant positive correlation with the maximum surgical margin. On CT, thickness was negatively correlated with the size of the resected breast tissue, and thickness of the implanted FDFG. No clinicopathologic factors or technical factors were related to FDFG outcome and the proportion of fat tissue in the CNB sample, except for axillary dissection. Nineteen of 21 patients had good to excellent cosmesis. Conclusion FDFG implanted into breast defects after partial mastectomy undergo mild resorption and degeneration to fibrous tissue, but most patients have good to excellent cosmesis.

Since antitumor immune reactions between tumors and intratumoral immunocytes have been verified in several human tumors, immunological therapeutic strategies must be considered to obtain the proper efficacy of tumor shrinkage under these conditions. Human leukocyte antigen (HLA) class I expression in cancer cells and degree of infiltration of regulatory T cells (Tregs) in the stroma have been regarded as important markers of antitumor immune reactions in the context of independent immunological mechanisms. In the current study, we investigated HLA class I expression and Treg cells infiltration in gastric cancer and discussed the clinical implications of this combinatory analysis in gastric cancer. A total of 141 gastric cancer patients who received R0 gastrectomy at Kagoshima University Hospital were studied. Immunohistochemically, in 141 gastric cancer patients, HLA class I expression and Treg cell infiltration in cancerous tissue were evaluated using HLA class I (EMR8-5) and forkhead box p3 (FOXP3) monoclonal antibodies. The correlation between clinical factors and tumor-infiltrating Treg cells was analyzed. HLA class I expression was positively associated with depth of tumor invasion (P

Neo-expression of N-cadherin in cancer cells is regarded as a significant event in tumor progression via epithelial-mesenchymal transition (EMT). No reports have detailed the clinical impact of N-cadherin expression in gastric cancer. We retrospectively examined the co-expression of N-cadherin and E-cadherin in human gastric carcinoma and analyzed the clinicopathological significance of N-cadherin expression. One hundred and forty-six gastric cancer patients who received curative gastrectomy were enrolled. E-cadherin and N-cadherin immunoreactivity in cancer tissue was evaluated by the avidin-biotin-peroxidase complex technique. The correlation between N-cadherin and E-cadherin expression and clinicopathological parameters were analyzed. N-cadherin-positive and -negative expression were found in 31 and 115 patients, respectively. N-cadherin expression positively correlated with hematogenous recurrence (P < 0.01) and negatively correlated with patients' postoperative outcomes (P < 0.05). Moreover, only in the E-cadherin-preserved group was prognostic significance found according to N-cadherin expression (P < 0.01). We could not show a significant relationship between N-cadherin expression and EMT in gastric cancer. However, neo N-cadherin expression significantly affected patient's survival in gastric cancer. Therefore, we concluded that neo N-cadherin expression may be a useful prognostic marker independent of E-cadherin expression.

Definitive evaluation of surgical specimens obtained after neoadjuvant chemoradiation therapy (CRT) is important for assessing additional treatment or prognosis in patients with esophageal squamous cell carcinoma (ESCC). In this study, we examined the histological prognostic factors for ESCC patients treated with CRT and determined an appropriate strategy for their evaluation. The present study involved 38 consecutive ESCC patients who underwent CRT followed by curative operation. CRT consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. We examined histological variables as follows: CRT effect on primary tumor (T-effect: T-effective/T-ineffective), tumor depth (pT), lymph node metastases (pN: pN0/N1), number of lymph node metastases (number-pN), lymphatic invasion, and venous invasion. Univariate and multivariate analyses were performed to examine the independent prognostic factors. Survivals and mode of recurrence were then evaluated according to the independent prognostic factors. In the univariate analyses, T-effect, pN, number-pN, lymphatic invasion, and venous invasion were found to be prognostic factors with p

Background Recently, neoadjuvant chemoradiation therapy (CRT) has been introduced for treatment of esophageal squamous cell carcinoma (ESCC). This study was performed to investigate the usefulness of endoscopic ultrasonography (EUS) in comparison with EUS findings before and after CRT, and histologic findings. Methods There were 33 patients with potentially resectable ESCC who underwent neoadjuvant CRT. Preoperative EUS and histologic findings were compared. EUS criteria were established on the basis of low and high echoic regions. Resected specimens were examined by hematoxylin-eosin, azan, and cytokeratin immunohistochemical staining. Results Azan and cytokeratin staining clearly delineated fibrous changes and residual tumor. Low echoic regions corresponded to residual tumor and high echoic spots corresponded to fibrosis. All 12 patients classified as grade 1 on EUS diagnosis had histologic grade 1 tumors. Nineteen of 21 cases that presented with high echo were grade 2 or 3. The prognosis according to EUS diagnosis was similar to the histologic effect. Conclusions Preoperative EUS findings reflected the histologic effect after neoadjuvant CRT. EUS is a useful tool to assess the effect for CRT and to predict the prognosis in ESCC patients.

Background and Objecties Phenotypic plasticity of cancer cells via epithelial–mesenchymal transition (EMT) and mesenchymal–epithelial transition (MET) is essential for tumor progression and metastasis. Methods Tissue samples were obtained from 76 pancreatic head cancers. We assessed the expression of E-cadherin, vimentin, ZEB-1, and ZEB-2 by immunohistochemical and immunofluorescence staining. Next, 147 metastatic lymph nodes from 45 pancreatic cancers with low expression of E-cadherin were obtained and divided into two categories according to the maximum diameter of the metastases: 2 mm or more and less than 2 mm. Results High expressions of ZEB-1 and ZEB-2 in the primary tumors were significantly associated with repression of E-cadherin (P = 0.0007), and poorer prognosis (P = 0.0322). Forty-three (29.3%) of the 147 metastatic tumors from pancreatic cancers with low expression of E-cadherin showed high E-cadherin expression. Cancer cells in the larger metastases showed high expression of E-cadherin (P = 0.0061) and low expression of ZEB-1 (P = 0.0170) and ZEB-2 (P = 0.0036) compared with those in the smaller metastases. Conclusions In primary pancreatic tumors and metastatic lymph nodes, high and low expression of ZEB-1 and ZEB-2 was associated with mesenchymal and epithelial phenotype of cancer cells, respectively. J. Surg. Oncol. 2012; 105:655–661. © 2011 Wiley Periodicals, Inc.

Purpose As laparoscopy can detect imaging-occult metastatic lesions, it has been validated as a means of improving the assessment of tumor staging. Although controversy exists as to whether the procedure should be used routinely or selectively in pancreatic cancer patients, patients considered for treatment protocols for locally unresectable pancreatic cancer should be staged laparoscopically before initiation of therapy. We evaluate the feasibility and safety of advanced staging laparoscopy including peritoneal lavage cytology, laparoscopic ultrasound sonography (LUS), and LUS-guided biopsy through a single incision for locally advanced pancreatic cancer. Methods Staging laparoscopy was performed in 44 patients with pancreatic cancer for deciding on treatment strategy. Our procedures included extensive peritoneal lavage of abdominal cavity for cytology, LUS for small metastasis detection, and tissue sample excision including LUS-guided biopsy. Eleven consecutive patients were treated with a single-incision staging laparoscopy approach (SI-SL group). The clinical parameters were compared between the SI-SL group and the multi-incision staging laparoscopy group (multi-incision group). Results The mean operating time was longer and bleeding volume was less in the SI-SL group, although the differences were without statistical significance. The conversion rates to laparotomy were 9% in the SI-SL group and 30% in the multi-incision group. There were no severe postoperative complications. LUS-guided biopsy revealed malignancy for 3 patients in the SI-SL group. Conclusions Advanced SI-SL is a feasible and safe alternative to the multi-incision approach for pancreatic cancer.

We herein describe the case of a 61-year-old man with stage II esophageal cancer who experienced chylothorax after esophagectomy. He was successfully treated with thoracic duct clipping and octreotide administration. Previously the patient had had a head and neck cancer treated with multimodality treatment: neoadjuvant chemoradiation therapy, operation, and adjuvant CRT. Then, esophagectomy with lymph node dissection without resection of the thoracic duct was performed via a right thoraco-abdominal approach. On postoperative day 1, enteral nutrition was started. On day 5, the chest tube drainage increased to 2000 ml per day. On day 7, the drainage fluid increased to 3000 ml per day, and its color turned cloudy white. We then performed lymphoscintigraphy and diagnosed the patient as having chylothorax. Immediately we administered intermittent subcutaneous octreotide 100 μg × 3 per day; however, it could not stop the leakage. On day 13, we performed an operation: a fat-rich supplement was administered through the jejunostomy tube before the operation, the thoracic duct injury was readily identified, and we clipped the thoracic duct in the superior mediastinum, followed by 300 μg per day octreotide treatment. On day 16, however, 400 ml per day of chyle leaked from the drain again, and we increased the dose of octreotide to 600 μg per day. On day 18, the drainage stopped, and the patient was discharged on day 38. Octreotide administration combined with surgical treatment should be considered as a treatment option for chylothorax, which is a rare complication of esophagectomy.

Background Significance and timing of drain removal after pancreatic surgery remain unclear. The aim of this study was to identify optimal indicators to predict severe intra-abdominal complications and determine the appropriate timing of prophylactic drain removal after pancreatoduodenectomy. Materials and methods This study included 151 consecutive patients who underwent pancreatoduodenectomy. We investigated associations between postoperative intra-abdominal complications, drain amylase levels, and duration of postoperative inflammatory response. Results Patients who developed severe intra-abdominal complications showed re-elevation of drain amylase levels after postoperative d 3 and prolonged postoperative inflammatory response, which were most pronounced in patients with severe pancreatic fistula and intra-abdominal abscess, respectively. In contrast, patients with a steady decline in drain amylase levels and short-term postoperative inflammatory response did not develop severe complications, and safe drain removal was possible even when the drain amylase value was more than three times the upper limit of normal serum amylase. Conclusion A combination of trends in the drain amylase level and duration of the inflammatory response in the postoperative period may be optimal indicators for early detection of severe intra-abdominal complications and appropriate timing of drain removal.

This report presents the results of oncoplastic surgery in three Japanese patients with breast cancer lesions involving the lower pole of the breast. Their breasts were ptotic, and their lesions were considered to be suitable for breast conservation surgery. There were treated with partial mastectomy resection using vertical-scar mammaplasty, with reduction surgery and recentralization of the nipple-areola complex. Two patients underwent a mirror-image biopsy on the contralateral breasts to determine the symmetry. The remaining patient had periareolar incision mastopexy without reduction added for the contralateral breast. A large surgical margin was used to remove excessive skin and parenchymal tissue. Ideal symmetry was achieved by performing reduction and/or mastopexy on the contralateral breast.

Background Bone morphogenetic proteins (BMPs) are secreted signaling molecules belonging to the transforming growth factor-β (TGF-β) superfamily of growth factors. Recent studies have shown that the influence of the expression of BMP7 was altered in several tumors. The purpose of the current study was to examine the expression of BMP7 in esophageal squamous cell carcinoma and to clarify the clinical impact of BMP7 expression in esophageal squamous cell carcinoma (ESCC). Methods A total of 180 patients with ESCC who underwent surgical resection from 1991 to 2004 were eligible for this study. The expression of BMP7 in esophageal tumor tissues was examined immunohistochemically. Results BMP7 expression was found in the cytoplasm of cancer cells. BMP7 positivity was observed in 61.7% of tumors. The BMP7-positive group had deeper progression, more advanced stages, and greater venous invasion than those without BMP7 expression (p

S-1 is a new oral fluoropyrimidine anticancer agent shown to be effective for pancreatic cancer. In a previous phase I trial, we evaluated the safety of S-1 combined with radiotherapy to determine the maximum tolerated dose and dose-limiting toxicity in patients with unresectable pancreatic cancer. The recommended dose of S-1 for phase II trials of chemoradiotherapy was determined as 80 mg/m(2)/day given on days 1-21 of a 28-day cycle. This phase II study was conducted to further evaluate the efficacy and toxicity of radiotherapy combined with S-1 (UMIN000004794).Eligible patients had locally advanced and unresectable pancreatic cancer without distant metastases, an Eastern Cooperative Oncology Group performance status of 0-1, adequate organ and marrow functions, and no prior anticancer therapy. Patients initially received 4 weeks of chemoradiotherapy. S-1 was given orally at a dose of 80 mg/m(2)/day twice daily on days 1-21. Radiotherapy was delivered in fractions of 1.25 Gy twice daily, 5 days per week for 4 weeks (total dose: 50 Gy in 40 fractions). One month after the completion of chemoradiotherapy, S-1 was administered for 14 days followed by a 14-day rest period. This cycle was repeated as maintenance therapy until disease progression or unacceptable toxicity.Fifty patients were enrolled in this phase II study. Median follow-up was 14.6 months (range 5.4-58.9 months). Forty-three patients (86%) completed the scheduled course of chemoradiotherapy. There was no treatment-related death or grade 4 toxicity. The major toxic effects were leukopenia and nausea. The objective tumor response according to the Response Evaluation Criteria in Solid Tumours criteria was partial response in 15 patients (30%) (95% confidence interval (CI), 18-45%), stable disease in 23 (46%), and progressive disease in 12 (24%). Median progression-free survival and median overall survival were 6.7 months (95% CI, 4.7-11.2 months) and 14.3 months (95% CI, 10.8-20.8 months), respectively. Survival rates at 1 and 2 years were 62 and 27%, respectively.Combination therapy with S-1 and radiation in patients with locally advanced and unresectable pancreatic cancer is considered a promising, well-tolerated regimen that can be recommended as an effective treatment for locally advanced pancreatic cancer.

Background The roles of infiltrating macrophages within the tumor microenvironment are complex because of their functional variety. The aim of this study is to examine the role and prognostic significance of tumor-associated macrophages (TAMs) that have an M2 polarized function in pancreatic cancer. Materials and Methods Formalin-fixed, paraffin-embedded blocks were obtained from 76 patients with pancreatic head cancer. All patients underwent macroscopic curative resection. We assessed the number of infiltrating macrophages within the tumor invasive front by not only CD68 but also by CD163 and CD204, which are specific receptors on M2-polarized macrophages. Furthermore, to evaluate lymphangiogenesis, we measured the density of lymphatic vessels in the tumor invasive front by using D2-40. Results High incidence of lymph node metastasis was shown in cases with a high number of CD163- or CD204-positive macrophages. Significantly increased lymphatic vessel density (LVD) was shown in cases with lymph node metastasis compared with cases without lymph node metastasis (P = 0.0094). Significantly increased LVD (P = 0.0175) and a poor prognosis (P = 0.0171) were shown in cases with a high number of macrophages that express CD163 or CD204, however, there was no significant difference according to the number of CD68-positive macrophages. Conclusions M2-polarized TAMs in the invasive front of pancreatic cancer are associated with a poor prognosis due to accelerated lymphatic metastasis, and inhibition of the functional interaction between M2-polarized TAMs and tumor cells may improve the prognosis.

It is important to predict the development of clinically relevant pancreatic fistula (grade B/C) in the early period after pancreaticoduodenectomy (PD). This study has been carried out as a project study of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHPBS) to evaluate the predictive factors associated with clinically relevant pancreatic fistula (grade B/C).The data of 1,239 patients from 11 medical institutions who had undergone PD between July 2005 and June 2009 were retrospectively analyzed to review patient characteristics and perioperative and postoperative parameters.A drain amylase level4,000 IU/L on postoperative day (POD) 1 was proposed as the cut-off level to predict clinical relevant pancreatic fistula by the receiver operating characteristic (ROC) curve. The sensitivity, specificity, and accuracy of this cut-off level were 62.2, 89.0, and 84.8%, respectively. A multivariate logistic regression analysis revealed that male [odds ratio (OR) 1.7, P = 0.039], intraoperative bleeding1,000 ml (OR 2.5, P = 0.001), soft pancreas (OR 2.7, P = 0.001), and drain amylase level on POD 14,000 IU/L (OR 8.6, P 0.001) were the significant predictive factors for clinical pancreatic fistula.The four predictive risk factors identified here can provide useful information useful for tailoring postoperative management of clinically relevant pancreatic fistula (grade B/C).

Esophageal achalasia is a primary motility disorder of the esophagus. Although various treatments can relieve the symptoms, esophageal cancer arising in patients with achalasia is the most important problem for long-term survivors. We encountered 2 cases of esophageal squamous cell carcinoma co-existing with achalasia that had been diagnosed 27 and 30 years earlier, respectively. Neither patient had been aware of dysphagia due to dilatation of the esophagus. Both patients underwent esophagectomy via right thoracotomy. Although esophagectomy with radical lymphadenectomy was performed successfully in one case of submucosal cancer, the primary tumor in the other case was more invasive and aggressive than indicated by the preoperative clinical diagnosis, and could not be completely resected. Regular endoscopic examination should be scheduled for long-term survivors of achalasia in order to detect esophageal cancer early and evaluate any changes in the esophagus carefully.

We report a case of early breast cancer, which was treated successfully by oncoplastic surgery. A 65-year-old Japanese woman was referred to us for investigation of a grouped calcification on mammography of her left breast, detected during mass screening for breast cancer. No mass lesion was palpated, but we suspected that the grouped calcification seen on the mammography was a malignant lesion in the lower area of the left breast. Ultrasonography and magnetic resonance imaging revealed ductal carcinoma in situ, restricted to the inner quadrant of the left breast. Achieving a good symmetrical outcome after partial mastectomy would have been made difficult by the degree of ptosis. Thus, we performed partial mastectomy followed by an amputation-type reduction operation with free nipple-areola complex grafting, which achieved good cosmetic and oncologic results.

Background: Bone morphogenetic protein-7 (BMP-7) is a signalling molecule belonging to the transforming growth factor--superfamily. Recent studies have demonstrated the clinical impact of BMP-7 expression in various human cancers. However, there have been few reports detailing this in gastric cancer. Methods: We immunohistochemically investigated the expression of BMP-7 in 233 gastric cancer patients to disclose the clinicopathological features of BMP-7-positive gastric cancer. Results: Immunohistochemically, in human gastric cancer, BMP-7 expression was identified in cellular membranes but also in the cytoplasm of cancer cells. Bone morphogenetic protein-7-positive expression was found in 129 of 233 patients (55%). Bone morphogenetic protein-7 expression was correlated with tumour size, nodal involvement, lymphatic invasion, venous invasion and histology (P

症例は83歳，女性．2008年12月に左乳房腫瘤を自覚．近医での針生検で肉芽腫所見を認め，抗結核剤による治療目的で呼吸器内科へ紹介された．呼吸器内科医は，抗結核剤使用のために抗酸菌（結核菌）の同定が必要と判断し，喀痰，針生検組織，浸出液などについて種々の細菌学的検査を追加したが，いずれの検体からも陽性所見は得られず，腫瘤切除や組織生検を目的に当科へ紹介された．視触診で左乳房全体を占拠する6cm大の腫瘤が大胸筋や前鋸筋に固定して可動性不良．超音波検査で，不整形な低エコーの腫瘤が境界不明瞭に乳腺から大胸筋に広がっていた．結核性の場合での創傷治癒遅延を懸念し，切除やOpen Biopsyを避けて正常部分を介した針生検を行ったが，塗抹やPCRでも抗酸菌は証明されなかった．その過程で，喀痰の抗酸菌2カ月培養検査陽性との報告が届いた．INH/RFP/EBによる治療が開始され，9カ月後には腫瘤が著明に縮小し，可動性も良好となった．

症例は71歳，男性．直腸内にIsポリープを認め，内視鏡的粘膜切除術を施行し，高分化型腺癌かつ深達度smであり，追加切除として腹腔鏡補助下低位前方切除術を行った．術後1年目に便秘が出現し，仙骨前面に径5cm大の球形の腫瘍を認めた．リンパ節転移や腹膜播種を疑い，開腹手術を行った．腫瘍は広範に小腸に浸潤しており広範小腸切除および腫瘍切除を行った．最終病理診断で，腹腔内デスモイド腫瘍の診断であった．術後補助療法としてホルモン製剤の投与を行い，腫瘍制御は良好であったが，大量小腸切除による栄養不良の状態となり，敗血症のため，術後3年5カ月で死亡した．家族性大腸腺腫症を伴わない腹腔内手術後の腹腔内デスモイド腫瘍の報告はこれまでに21例の報告と少なく，腹腔鏡術後発生も2例目と非常に稀であり，若干の文献的考察を加え報告する．

Pagetoid phenomenonを伴った肛門管癌の2例を報告する．症例1は72歳，女性．肛門周囲のびらんと違和感を主訴に来院され，pagetoid phenomenonを伴う肛門管癌と診断された．肛門周囲の皮膚浸潤と左鼠径部リンパ節腫大があり，直腸切断術と左鼠径リンパ節郭清を行った．免疫組織学的検査で，GCDFP-15弱陽性，CK-20陽性，CK-7陰性であった．術後9カ月現在，再発なく外来で経過観察中である．症例2は65歳，男性．肛門痛と排便時出血が主訴で，pagetoid phenomenonを伴う肛門管癌と診断された．術前より両側鼠径リンパ節への転移が判明しており，直腸切断術と両側リンパ節郭清を行った．免疫組織学的検査で，GCDFP-15陰性，CK-20陰性，CK-7陽性であった．術後5カ月目に腸閉塞で，緊急手術を行った際に腹膜播種が判明し，抗癌剤治療を行ったが初回手術後9カ月目に死亡した．

Recent studies have shown that intraoperative blood loss and blood transfusions promote postoperative recurrence of hepatocellular carcinoma (HCC). Hyperbaric oxygen therapy (HBOT) is a specific method of oxygen administration, which is independent of fluid therapy or blood transfusion. The aim of the present study was to assess the usefulness of acute HBOT after liver resection for patients with HCC in order to minimize the requirement for perioperative blood transfusions. Forty-one consecutive patients who showed Hb level < 9.0 mg/dl at the end of hepatic resection were randomly assigned to a control group (n = 21) or an HBOT group (n = 20). HBOT at 2.0 atm. with inhalation of 100% oxygen for a duration of 60 min was performed at 3, 24, and/or 48 h after the end of the hepatectomy. Regarding postoperative hepatic hemodynamics, liver function tests, and outcome data, prospective comparisons were completed in both groups. The two groups of patients were similar with respect to results from preoperative assessments. In six patients from the HBOT group, who experienced intraoperative major bleeding or showed fatal hepatic hypoxia (ShvO2 < 50%), the levels of ShvO2 and serum lactate were significantly improved after HBOT. When compared to the control group, the HBOT group showed better changes of ShvO2, serum lactate, and bilirubin levels for the first 3 postoperative days following surgery. Additionally, the HBOT group did not experience any fatal complications and had a lower incidence of postoperative hyperbilirubinemia than the control group. We also observed that postoperative NK cell activity and cancer-free survival in the HBOT group tended to be better than in the control group, although the differences did not reach significance. These results suggest that acute HBOT after hepatectomy, aimed at reducing perioperative erythrocyte transfusions, may be employed for overcoming deficiencies in systemic and hepatic oxygen supply and thus diminishing postoperative complications. As an added benefit, such therapy may affect postoperative immunological responses and long-term survival after liver resection in HCC patients. Further analyses of the use of HBOT is warranted to confirm surgical outcome data and to assess the economic impact on healthcare costs.

In terms of timing of resection for synchronous liver metastases from colon cancer, some reports recommend leaving an interval (e.g., 3 months) after primary colorectal resection, because of reports of occasional and rapid remnant recurrence of residual liver metastases after simultaneous colorectal and liver resection (LR). For patients with metachronous liver metastasis (MLM), we prospectively examined the appropriateness of a 3-month interval to LR (i.e., delayed resection) following initial detection of hepatic lesions from the viewpoints of (1) detection of new metastases during this interval and (2) postoperative outcome.Seventy-nine consecutive patients with modified Japanese criteria H1 class MLM (i.e., ≤4 nodules, 6 cm or less in diameter) and without obvious extrahepatic lesions, presenting between 1990 and 2008, were included in this study. Between 1990 and 2001, 52 patients were treated by LR without an interval (i.e., nondelayed group); from 2002, 27 patients were prospectively scheduled for LR at an interval of 3 months after initial detection of metastases (i.e., delayed group). During the 3-month interval, no adjuvant chemotherapy was given. Just prior to LR, patients were re-evaluated using computed tomography (CT) and deoxy-2-[(18)F]fluoro-D: -glucose positron emission tomography (FDG-PET) to exclude cases unsuitable for surgery.Out of 27 patients in the delayed group, 2 (7.4%) did not undergo LR after the 3-month interval and were excluded from the analysis: one because of multiple nodules in the bilateral lobe of the liver with pulmonary metastases and another because of para-aortic lymph node metastasis. Of the 25 patients for whom LR was indicated, 24 underwent LR as initially planned. In the remaining patient, after the 3-month interval, invasion of the tumor had occurred into the inferior vena cava (IVC) and other surgery in addition to the planned operation was required. When comparing the postoperative outcome data of the delayed group (n = 25) with the nondelayed group (n = 52), overall early recurrence within 1 year after LR was noticed in 30.9% (16/52) of the nondelayed group and 28.0% (7/25) of the delayed group; the incidence of only early extrahepatic recurrence decreased 5.1% in the delayed group (21.1% versus 16.0%, respectively). When comparing disease-free survival after liver resection, however, there was no significant difference between the groups.Delayed LR for MLM patients after initial detection of hepatic lesions is of no clinical benefit. Only in cases when extrahepatic lesions with MLM are suspected could an interval make such lesions clearer and assist in deciding on a suitable management plan.

Background MicroRNAs (miRNAs) belong to a group of small non-coding RNA molecules that act as pivotal agents responsible for fine-tuning RNA expression in a sequence-dependent manner. A large number of studies showed that dysregulated miRNAs are deeply involved in the development of cancer cells, as well as their metastasis and drug resistance. Based on our original miRNA expression signatures by RNA-sequencing revealed that both strands of miR-150–5p (the guide strand) and miR-150–3p (the passenger strand) was downregulated in several cancers. The general concept of miRNA biogenesis posits that the passenger strand of miRNA (the minor strand or miRNA*) derived from duplex miRNA is degraded and does not regulate gene expression. Here, we aimed that to investigate functional significance of these miRNAs in esophageal squamous cell carcinoma (ESCC). Methods Cancer cell proliferation, migration and invasion abilities were performed by using mature miRNAs or siRNAs. Genome-wide gene expression analyses and in silico analyses were applied to identify miRNA target genes in ESCC cells. Results Expression levels of miR-150–5p and miR-150–3p were significantly reduced in ESCC clinical specimens and cell lines. Cancer cell aggressiveness was inhibited by ectopic expression of these miRNAs. A total of 12 genes were identified as oncogenic targets by both miR-150–5p and miR-150–3p in ESCC cells. SPOCK1 (SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 1) was directly regulated by both miR-150–5p and miR-150–3p by luciferase reporter assay. Overexpression of SPOCK1 was detected in ESCC specimens and knockdown of SPOCK1 by siRNA significantly inhibited cancer cell migration and invasion abilities. Conclusion Both strands of miR-150-duplex (miR-150–5p and miR-150–3p) acted as anti-tumor miRNAs in ESCC. Overexpression of SPOCK1 was enhanced cancer cell aggressiveness. Involvement of passenger strand of miRNA in cancer pathogenesis is novel concept in cancer research. We suggest that identification of novel function of passenger strands of miRNAs and the RNA networks they regulate might enhance our understanding of the molecular pathogenesis of ESCC. Disclosure All authors have declared no conflicts of interest.