Double Negativity of MRI-Detected and Pathologically-Diagnosed Extramural Venous Invasion is a Favorable Prognostic Factor for Rectal Cancer.

BACKGROUND: Extramural venous invasion (EMVI) is a prognostic factor in rectal cancer. There are two types: EMVI detected by magnetic resonance imaging (MRI) (mr-EMVI) and EMVI detected by pathology (p-EMVI). They have been separately evaluated, but they have not yet been concurrently evaluated. We therefore evaluate both mr-EMVI and p-EMVI in rectal cancer at the same time and clarify their association with prognosis. PATIENTS AND METHODS: Included were the 186 consecutive patients who underwent complete radical resection of tumors ≤ stage III at Wakayama Medical University Hospital, Japan, between 2010 and 2018. All underwent preoperative MRI examination, and were reassessed for EMVI by a radiologist. Surgically resected specimens were then reassessed for EMVI by a pathologist. We assessed the correlation between positivity of mr-EMVI and p-EMVI and prognosis, and the clinicopathological background behind them. RESULTS: Patients with double negativity for mr-EMVI and p-EMVI had better prognosis than patients with mr-EMVI or p-EMVI positivity (p < 0.0001). Positivity for mr-EMVI or p-EMVI was a poor independent prognostic factor in multivariate analysis. CONCLUSIONS: Combined analysis of mr-EMVI and p-EMVI may enable prediction of postoperative prognosis of rectal cancer. Patients with double negativity of mr-EMVI and p-EMVI had better prognosis than patients with some form of positivity. Stated differently, patients with positivity of mr-EMVI, p-EMVI, or both had a poorer prognosis than those with double negativity. Postoperative adjuvant chemotherapy may improve poor prognosis. Combined evaluation of mr-EMVI and p-EMVI may be used to predict clinical outcomes and may be an effective prognostic predictor of rectal cancer.

Randomized controlled trial comparing cosmetic results of midline incision versus off-midline incision for specimen extraction in laparoscopic colectomy.

PURPOSE: A notable advantage of laparoscopic colorectal surgery is that only a small incision at the extraction site is necessary, which is considered to be cosmetically beneficial. Meanwhile, the optimal extraction site for the resected specimen in laparoscopic colectomy is controversial in terms of cosmetic benefit. This randomized controlled trial compares midline and off-midline extraction sites in laparoscopic colectomy in patients with colon cancer, with consideration of cosmetic benefits as the primary endpoint. METHODS: Included were patients that underwent elective laparoscopic colectomy at WMUH between October 2014 and February 2017. Patients were randomly assigned to either midline incision group or off-midline incision group. Prospectively collected data included cosmetic results (patients and observer assessment scale) and complications including incidence of incisional hernia, SSI, and pain. This trial was registered with UMIN Clinical Trials (UMIN000028943). RESULTS: Finally, 98 patients with colorectal cancer were analyzed. No significant differences were found between the two groups in patient and observer assessment scales of cosmetic results (midline 8 ± 1.1 vs off-midline 11 ± 5.9 p = 0.16, midline 13.5 ± 6.6 vs off-midline 15 ± 11 p = 0.58, respectively) or in postoperative pain. However, incisional hernia occurred in four cases in the midline group (8%), which was significantly higher than that in the off-midline group (no cases, 0%). CONCLUSION: There was no significant difference in terms of cosmetic benefit, the primary endpoint, between the two groups. In this study, only the extraction site location was compared; future studies will examine differences depending on the incisional direction, including the incidence of incisional hernia.

New diagnostic strategy using narrow-band imaging (NBI) during laparoscopic surgery for patients with colorectal cancer.

BACKGROUND: Accurate tumor stage diagnosis during laparoscopic surgery remains difficult. We clarify the impact of new diagnostic strategy using narrow-band imaging (NBI) during laparoscopic surgery for colorectal cancer compared with other strategies. METHODS: We defined angiogenesis (Ag) and fibrosis (Fib) grades using NBI laparoscopy (lap-NBI), and assessed the clinicopathological features associated with these grades for 67 patients with colorectal cancer who underwent surgery. We assessed vessel density and gray scale with computer software. RESULTS: NBI-Ag-grade and NBI-Fib-grade of the serosal surface of cancer lesions and peritoneal nodules correlated with vessel density and gray scale of those assessed by Image J computer software. NBI-Fib-grades of liver nodules also correlated with gray scale. NBI-Ag- grade and Fib-grade of the serosal surface of cancer lesions correlated with pathological depth of invasion. These NBI grades of pathological metastatic peritoneal nodules were higher than those of pathologically benign peritoneal nodules. NBI- Fib grades of pathological metastatic liver nodules were higher than those of pathologically benign liver nodules. In multivariate analysis, lap-NBI was associated with different diagnosis for T3, T4 and non-T3, and non-T4. Moreover, lap-NBI was associated with different diagnosis for T4 and non-T4. Predictive value for T4 by lap-NBI showed high sensitivity (85%) specificity (87%), positive predictive value (74%), negative predictive value (93%), and overall accuracy (87%). Sensitivity and overall accuracy of lap-NBI was superior to that of other diagnostic modalities. CONCLUSION: We clarified the usefulness of the new diagnostic strategy using lap-NBI during laparoscopic surgery for colorectal cancer in comparison with other strategies.

High visceral to subcutaneous fat area ratio predicts early postoperative small bowel obstruction after surgery for colorectal cancer.

PURPOSE: Risks for postoperative small bowel obstruction have been demonstrated in several reports, most of which indicated male sex was a risk factor, but with the reason remaining unknown. We tested the hypothesis that it could be because males have more visceral fat than females. This prospective observational study aims to examine risks of early postoperative small bowel obstruction (EPSBO) after colorectal cancer surgery and the association between visceral to subcutaneous fat area ratio (V/S ratio) and EPSBO. METHODS: Four hundred and seventy-four patients who underwent colectomy for colorectal cancer in our hospital were enrolled in this study. The influence of several factors including V/S ratio on the development of EPSBO was analyzed. RESULTS: Thirty-one of the 474 patients (6.5%) developed EPSBO. EPSBO occurred more frequently in males (p = 0.03) and cases who developed postoperative anastomotic leakage (p < 0.001) or wound infection (p = 0.02). Higher V/S ratio was strongly related to male sex (p < 0.001). Multivariate analysis revealed higher V/S ratio (OR 2.25; p = 0.049) and anastomotic leakage (OR 5.86; p < 0.001) were independent risk factors for EPSBO. CONCLUSION: Higher V/S ratio was significantly related to EPSBO, suggesting that one of the reasons EPSBO was more likely to occur in males because they have more visceral fat than females. Preoperative identification of this risk factor could help us watch out for this potential complication.

Neonatal congenital mesoblastic nephroma that caused respiratory oncologic emergency early after birth: a case report.

BACKGROUND: Congenital mesoblastic nephromas mainly present as asymptomatic abdominal masses, but some present hematuria, hypertension or hypercalcemia. Neonatal dyspnea in an early-birth neonate due to rapid tumor growth is reported here for the first time. CASE PRESENTATION: A renal tumor and polyhydramnios were detected by ultrasonography of a male fetus at 32 weeks and 3 days of gestation. The mother had abdominal distension due to the polyhydramnios and signs of imminent premature birth. Amniocentesis was performed and the signs of imminent preterm birth subsided, but growth of the renal tumor was noted as a potential cause of respiratory dysfunction. Cesarean section was performed at 36 weeks and 2 days of gestation. His birthweight was 2638 g and his 1 and 5 min APGAR scores were 2 and 4 points, respectively. There was no spontaneous breathing at birth and he had remarkable abdominal distention. He underwent cardiopulmonary resuscitation. After circulation stabilized, emergency surgery was performed because of progressive hypoxemia and respiratory acidosis. Laparotomy revealed a huge tumor arising from the right kidney and right nephrectomy was performed. Histopathological examination led to diagnosis of congenital mesoblastic nephroma. The respiratory condition and circulatory dynamics stabilized after the pressure on the thorax from the tumor was relieved by surgery. The postoperative course was uneventful. No recurrence or complications have been observed in the 36 months since the surgery. CONCLUSIONS: Congenital mesoblastic nephroma can rapidly increase in size from the fetal period and may cause respiratory oncologic emergency, although there is relatively good prognosis.

Migration Capacity of Stem Cells from Human Exfoliated Deciduous Teeth Towards Glioma.

BACKGROUND: Stem cells from human exfoliated deciduous teeth (SHED) are a mesenchymal stem cell type and have recently attracted attention for their high proliferative rate, multipotency, and immunosuppressive properties. However, SHED have not yet been investigated for anticancer properties. We therefore investigated whether SHED can be used as a treatment modality, particularly for anti-glioma therapy. METHODS: In vitro, we examined the mobility of SHED and their ability to migrate towards glioma-conditioned medium and specific growth factors secreted by malignant gliomas. In vivo, we transplanted SHED into the left hemisphere of nude mice that had been previously implanted with human malignant glioma U87 cells into the right hemisphere. We assessed whether SHED had tumorigenic potential. RESULTS: SHED exhibited strong migration ability towards malignant glioma in both in vitro and in vivo assays. In vitro, SHED migrated towards glioma-conditioned medium and specific growth factors such as stem cell factor, platelet-derived growth factor BB, C-X-C motif chemokine ligand 12, and vascular endothelial growth factor. SHED were accumulated around tumor cells in the contralateral hemisphere 1 week after transplantation. Moreover, SHED remained in the brains of nude mice 150 days after transplantation. Finally, we verified that SHED had no malignant transformation or engraftment of SHED in the mouse brain. CONCLUSIONS: Our findings indicate that SHED can potentially be applied to track malignant glioma.

Tumor Sidedness Is Associated with Survival in Patients with Synchronous Colorectal Peritoneal Carcinomatosis.

BACKGROUND: Synchronous colorectal peritoneal carcinomatosis (SCPC) is not a rare entity, and the prognosis is extremely poor compared to other metastatic sites such as the liver and lung. Therefore, optimal treatment based on tumor characteristics is needed. Recently, the tumor sidedness of colorectal cancer has been reported as one of the prognostic factors and also as a key factor for the treatment strategy. The purpose of this study was to assess the clinical impact of tumor sidedness in patients with SCPC. METHODS: A total of 189 cases of SCPC were identified in a retrospective database at Wakayama Medical University Hospital (WMUH) between 1998 and 2014, and were analyzed with a special focus on tumor location. RESULTS: In multivariate analysis, a right-sided location (p = 0.02) and the presence of liver metastases (p < 0.001) were found to be the worst prognostic factors. The median survival time (MST) with right-sided and with left-sided SCPC was 10 and 16 months, respectively. The right-sided SCPC group included more aged patients (p = 0.045) and fewer patients who received postoperative chemotherapy (p = 0.034). When we focused on patients with macroscopically complete resection (n = 39), the MST and disease-free survival in the right-sided SCPC group was significantly shorter than in the left-sided SCPC group (p = 0.030 and p = 0.043, respectively). The MST of the right-sided and the left-sided SCPC patients among the completely resected patients was 24 and 73 months, respectively. CONCLUSION: Tumor sidedness may be a potent prognostic indicator for patients with SCPC. The survival time with right-sided SCPC is dramatically reduced compared to that with left-sided SCPC, especially among completely resected cases. We should change the treatment strategy according to the location of SCPC.

Optimization and biological evaluation of imidazopyridine derivatives as a novel scaffold for γ-secretase modulators with oral efficacy against cognitive deficits in Alzheimer's disease model mice.

Gamma-secretase modulators (GSMs) selectively lower amyloid-ß42 (Aß42) and are therefore potential disease-modifying drugs for Alzheimer's disease (AD). Here, we report the discovery of imidazopyridine derivatives as GSMs with oral activity on not only Aß42 levels but also cognitive function. Structural optimization of the biphenyl group and pyridine-2-amide moiety of compound 1a greatly improved GSM activity and rat microsomal stability, respectively. 5-{8-[(3,4'-Difluoro[1,1'-biphenyl]-4-yl)methoxy]-2-methylimidazo[1,2-a]pyridin-3-yl}-N-methylpyridine-2-carboxamide (1o) showed high in vitro potency and brain exposure, induced a robust reduction in brain Aß42 levels, and exhibited undetectable inhibition of cytochrome p450 enzymes. Moreover, compound 1o showed excellent efficacy against cognitive deficits in AD model mice. These findings suggest that compound 1o is a promising candidate for AD therapeutics.

Discovery of N-ethylpyridine-2-carboxamide derivatives as a novel scaffold for orally active γ-secretase modulators.

Gamma-secretase modulators (GSMs) are promising disease-modifying drugs for Alzheimer's disease because they can selectively decrease pathogenic amyloid-ß42 (Aß42) levels. Here we report the discovery of orally active N-ethylpyridine-2-carboxamide derivatives as GSMs. The isoindolinone moiety of 5-[8-(benzyloxy)-2-methylimidazo[1,2-a]pyridin-3-yl]-2-ethyl-2,3-dihydro-1H-isoindol-1-one hydrogen chloride (1a) was replaced with a picolinamide moiety. Optimization of the benzyl group significantly improved GSM activity and mouse microsomal stability. 5-{8-[([1,1'-Biphenyl]-4-yl)methoxy]-2-methylimidazo[1,2-a]pyridin-3-yl}-N-ethylpyridine-2-carboxamide hydrogen chloride (1v) potently reduced Aß42 levels with an IC50 value of 0.091 µM in cultured cells without inhibiting CYP3A4. Moreover, 1v demonstrated a sustained pharmacokinetic profile and significantly reduced brain Aß42 levels in mice.

Ultrasound findings for spontaneous regression of omphalomesenteric remnant after birth.

We report a rare case of spontaneous regression of omphalomesenteric remnant after birth. Unlike previously reported cases, no surgery was required. The omphalomesenteric duct sometimes persists at birth. Its regression after birth, however, is extremely rare. A neonate passed a bloody stool 3 minutes after birth. Meckel's scan detected slight technetium-99 m uptake around the umbilicus. Sonographic examination detected a luminal structure connected to the small bowel, which gradually regressed, however, and was no longer visible by the 52nd day after birth. Careful follow-up is required after occurrence of bloody stool and intestinal obstruction from Meckel's diverticulum.

Structure-function analysis of myomaker domains required for myoblast fusion.

During skeletal muscle development, myoblasts fuse to form multinucleated myofibers. Myomaker [Transmembrane protein 8c (TMEM8c)] is a muscle-specific protein that is essential for myoblast fusion and sufficient to promote fusion of fibroblasts with muscle cells; however, the structure and biochemical properties of this membrane protein have not been explored. Here, we used CRISPR/Cas9 mutagenesis to disrupt myomaker expression in the C2C12 muscle cell line, which resulted in complete blockade to fusion. To define the functional domains of myomaker required to direct fusion, we established a heterologous cell-cell fusion system, in which fibroblasts expressing mutant versions of myomaker were mixed with WT myoblasts. Our data indicate that the majority of myomaker is embedded in the plasma membrane with seven membrane-spanning regions and a required intracellular C-terminal tail. We show that myomaker function is conserved in other mammalian orthologs; however, related family members (TMEM8a and TMEM8b) do not exhibit fusogenic activity. These findings represent an important step toward deciphering the cellular components and mechanisms that control myoblast fusion and muscle formation.

In vivo myomaker-mediated heterologous fusion and nuclear reprogramming.

Knowledge regarding cellular fusion and nuclear reprogramming may aid in cell therapy strategies for skeletal muscle diseases. An issue with cell therapy approaches to restore dystrophin expression in muscular dystrophy is obtaining a sufficient quantity of cells that normally fuse with muscle. Here we conferred fusogenic activity without transdifferentiation to multiple non-muscle cell types and tested dystrophin restoration in mouse models of muscular dystrophy. We previously demonstrated that myomaker, a skeletal muscle-specific transmembrane protein necessary for myoblast fusion, is sufficient to fuse 10T 1/2 fibroblasts to myoblasts in vitro. Whether myomaker-mediated heterologous fusion is functional in vivo and whether the newly introduced nonmuscle nuclei undergoes nuclear reprogramming has not been investigated. We showed that mesenchymal stromal cells, cortical bone stem cells, and tail-tip fibroblasts fuse to skeletal muscle when they express myomaker. These cells restored dystrophin expression in a fraction of dystrophin-deficient myotubes after fusion in vitro. However, dystrophin restoration was not detected in vivo although nuclear reprogramming of the muscle-specific myosin light chain promoter did occur. Despite the lack of detectable dystrophin reprogramming by immunostaining, this study indicated that myomaker could be used in nonmuscle cells to induce fusion with muscle in vivo, thereby providing a platform to deliver therapeutic material.-Mitani, Y., Vagnozzi, R. J., Millay, D. P. In vivo myomaker-mediated heterologous fusion and nuclear reprogramming.

Discovery of novel scaffolds for γ-secretase modulators without an arylimidazole moiety.

Gamma-secretase modulators (GSMs) selectively inhibit the production of amyloid-ß 42 (Aß42) and may therefore be useful in the management of Alzheimer's disease. Most heterocyclic GSMs that are not derived from nonsteroidal anti-inflammatory drugs contain an arylimidazole moiety that potentially inhibits cytochrome P450 (CYP) activity. Here, we discovered imidazopyridine derivatives that represent a new class of scaffold for GSMs, which do not have a strongly basic end group such as arylimidazole. High-throughput screening identified 2-methyl-8-[(2-methylbenzyl)oxy]-3-(pyridin-4-yl)imidazo[1,2-a]pyridine (3a), which inhibited the cellular production of Aß42 (IC50 = 7.1 µM) without changing total production of Aß. Structural optimization of this series of compounds identified 5-[8-(benzyloxy)-2-methylimidazo[1,2-a]pyridin-3-yl]-2-ethylisoindolin-1-one (3m) as a potent inhibitor of Aß42 (IC50 = 0.39 µM) but not CYP3A4. Further, 3m demonstrated a sustained pharmacokinetic profile in mice and sufficiently penetrated the brain.

CEACAM1 is associated with recurrence after hepatectomy for colorectal liver metastasis.

BACKGROUND: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is re-expressed at the invasion front of colorectal cancer. CEACAM1 expression at metastatic sites remains to be investigated. The current study aims to clarify the association between CEACAM1 expression and recurrence after hepatectomy of colorectal liver metastasis and to address whether CEACAM1 induces tumor-initiating properties needed for growth at metastatic sites. METHODS: Immunohistochemical analyses for CEACAM1 were performed in 67 patients with liver metastasis of colorectal cancer who had undergone curative hepatectomy. The risk factors for postoperative recurrence were calculated based on a CEACAM1 cytoplasmic domain isoform at the primary tumor invasion front. To investigate the effects of CEACAM1 cytoplasmic isoforms on HT29 and HCT116 colorectal cancer cells, Western blotting for CD44 and CD133, flow cytometry for ALDH1 activity, and soft-agar colony formation assay were performed. RESULTS: CEACAM1 long (CEACAM1-L) and short (CEACAM1-S) cytoplasmic domain isoforms are strongly expressed on cancer cells in the liver metastases. Enhanced CEACAM1-S expression in the state of CEACAM1-L dominance at the primary tumor invasion front was an independent factor for colorectal cancer recurrence after curative hepatectomy. CEACAM1-4S-transfected HT29 and HCT116 cells had significantly higher CD44 expression and ALDH1 activity and increased the growth in anchorage-independent condition. CONCLUSIONS: High expression of CEACAM1-S at the primary lesion invasion front is associated with recurrence and prognosis of patients with colorectal liver metastasis after curative hepatectomy. The expression of CEACAM1-4S enhances the tumor-initiating property of colorectal cancer cells.

Perineural Invasion Is Associated with Poor Survival after Preoperative Chemoradiation Therapy for Advanced Lower Rectal Cancer.

BACKGROUND: Preoperative chemoradiation therapy (pCRT) is a standard procedure for patients with advanced lower rectal cancer. It has been reported that pCRT cannot prolong the survival of patients with advanced lower rectal cancer. The aim of this study is to address the controllable and uncontrollable pathological factors of pCRT in predicting local and distant recurrences. METHODS: One hundred two patients with stages 2 and 3 cancer were consecutively enrolled to the study. The first 51 patients (October 2008-August 2010) underwent curative resection without pCRT. The latter 51 patients (September 2010-May 2015) underwent curative resection after pCRT. Pathological factors of patients were evaluated to assess the association between local and distant recurrences. RESULTS: Multivariate analyses for local and distant recurrences of patients without pCRT revealed that the independent risk factors were tumor deposit and perineural invasion respectively. pCRT was able to diminish circumferential resection margin, tumor deposit, venous invasion, and lymphatic permeation but not neural invasion and lymph node involvement. Kaplan-Meier curve of local and distant recurrence-free survival of patients with pCRT illustrated that tumor deposit is controllable, whereas perineural invasion is uncontrollable by pCRT. CONCLUSION: pCRT-uncontrollable perineural invasion may be a factor for distant recurrence of advanced rectal cancer patients, leading to poor survival.

P4H9-detected molecule expression on spindle-shaped fibroblasts indicates malignant phenotype of colorectal cancer.

BACKGROUND: Our previous study using a mammary fat pad mouse model showed that P4H9, produced by the ß2 integrin epitope, detected a molecule on fibroblasts in response to carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1)-expressing cancer cells. P4H9-detected molecule (PDM) expression appeared to be associated with myofibroblast differentiation. In this study, we investigated whether PDM is expressed on fibroblasts and cancer cells in clinical tissue samples, and whether the presence of PDM-expressing colorectal cancer cells is correlated with clinicopathological features of patients. METHODS: Immunohistochemistry was conducted to detect P4H9 on clinical tissue samples from 156 patients with colorectal cancer. Risk factors for metastases and survival were calculated for clinical implication of PDM-expressing spindle-shaped fibroblasts. RESULTS: Multivariate analysis showed that PDM-expressing spindle-shaped fibroblasts were an independent risk factor for lymph node metastasis, hematogenous metastasis, and poor survival. A Kaplan-Meier survival curve indicated that PDM-expressing spindle-shaped fibroblasts were associated with shorter survival time (P<0.0001). Immunofluorescence showed PDM expression on CCD-18Co fibroblasts and two colorectal cancer cell lines (HCT116 and HCT-15). CONCLUSIONS: PDM-expressing spindle-shaped fibroblasts are associated with metastasis and shorter survival in colorectal cancer patients. PDM-expressing spindle-shaped fibroblasts may have a role in eliciting the malignant phenotype of colorectal cancer.

Clinical characteristics of anastomotic leakage after an anterior resection for rectal cancer by assessing of the international classification on anastomotic leakage.

PURPOSE: The International Study Group of Rectal Cancer (ISREC) has proposed a new definition of anastomotic leakage (AL) which was simply classified into three grades; however, these criteria have not been assessed well. The aims of this study are to assess the new definition and to show the clinical features of AL after an anterior resection for rectal cancer. METHODS: Fifty consecutive patients developed AL after an anterior resection for rectal cancer was retrospectively assessed. AL was defined by the ISREC criteria. RESULTS: Twenty-seven (54 %) patients with AL were diagnosed by drain contents. The postoperative day of diagnosis for AL was later in grade A versus grades B and C (p = 0.038 vs p = 0.006, respectively). Permanent stoma (PS) was significantly more frequent in patients with grade C but not grade B compared to the patients with no AL (p < 0.001 and p = 0.171, respectively). In patients without diverting stoma, there was more serious grade of AL (p < 0.001). CONCLUSIONS: Differences were observed in the postoperative day of diagnosis, the creation rate of PS, and impact on diverting stoma after AL between each grade of leakage. The new classification was easy and reasonable to evaluate AL. As a result, it should be widely used in future studies.

CEACAM1 long cytoplasmic domain isoform is associated with invasion and recurrence of hepatocellular carcinoma.

BACKGROUND: The two isoforms of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), 1 with a long cytoplasmic domain (CEACAM1-L) and 1 with a short (CEACAM1-S), are involved in different signaling pathways. ß2-spectrin (ß2SP) is an adaptor protein that plays critical roles in the proper control of Smad access to activate receptors involved in regulation of TGF-ß signaling. In this study, we examined the association between CEACAM1 isoform balance and hepatocellular carcinoma (HCC) malignant potential and investigated the possibility of a molecular interaction between CEACAM1 and ß2SP. METHODS: Immunohistochemical analysis was carried out with CEACAM1-L or CEACAM1-S antibodies on 154 HCC tissues to correlate with the factors of malignancy. Invasion assay was performed for the effect of CEACAM1 expression on HCC cell lines. Moreover, immunohistochemical analysis and immunoprecipitation analysis were performed to investigate the association between CEACAM1 isoform balance and ß2SP. RESULTS: In immunohistochemical analysis, CEACAM1-L expression dominance was a risk factor for HCC recurrence (p = 0.04) and was significantly associated with a shorter survival compared with CEACAM1-S expression dominance. Invasion assay indicated that CEACAM1-4L-transfected HLF and PLC/PRF/5 cells showed significantly increased invasion (p < 0.0001) and CEACAM1-4S-transfected HLF cells showed significantly decreased invasion. Immunohistochemical analysis of ß2SP suggested that the HCCs with CEACAM1-L-dominant expression were more strongly stained with ß2SP than the HCCs with CEACAM1-S-dominant expression (p = 0.013), and coprecipitation assays indicated that CEACAM1-L could bind to ß2SP. CONCLUSIONS: CEACAM1-L may enhance the HCC invasiveness through an interaction with ß2SP and subsequent effects on TGF-ß signaling.

Survival benefit of lateral lymph node dissection according to the region of involvement and the number of lateral lymph nodes involved.

PURPOSE: The effectiveness of lateral lymph node dissection for extending the survival of patients with advanced lower rectal cancer remains unclear. The purpose of this study was to clarify the survival benefit of lateral lymph node dissection according to the region of involvement and the number of lateral lymph nodes involved. METHODS: We reviewed 131 consecutive patients with advanced lower rectal cancer, who had undergone curative resection with total mesorectal excision plus extended lateral lymph node dissection at Wakayama Medical University Hospital. Twenty-six (19.1 %) of these patients had lateral lymph involvement. We performed univariate and multivariate analyses for the 3-year disease-free and overall survival of these patients. RESULTS: Multivariate analysis revealed that the number (>1) and the region (common iliac artery region or external iliac artery region) of lateral lymph node metastasis are independent predictive factors for recurrence and survival. The Kaplan-Meier analysis demonstrated that patients with one lymph node metastasis in the internal iliac artery or obturator region had better survival. CONCLUSIONS: Lateral lymph node dissection resulted in survival benefit for patients with single lateral lymph node involvement in the internal iliac artery region or the obturator region.