Long-term effects of laparoscopic lateral pelvic lymph node dissection on urinary retention in rectal cancer.

BACKGROUND: The addition of lateral pelvic lymph node dissection (LPLND) in rectal cancer surgery has been reported to increase the incidence of post-operative urinary retention. Here, we assessed the predictive factors and long-term outcomes of urinary retention following laparoscopic LPLND (L-LPLND) with total mesorectal excision (TME) for advanced lower rectal cancer. METHODS: This retrospective single-institutional study reviewed post-operative urinary retention in 71 patients with lower rectal cancer who underwent L-LPLND with TME. Patients with preoperative urinary dysfunction or who underwent unilateral LPLND were excluded. Detailed information regarding patient clinicopathologic characteristics, post-void residual urine volume, and the presence or absence of urinary retention over time was collected from clinical and histopathologic reports and telephone surveys. Urinary retention was defined as residual urine > 100 mL and the need for further treatment. RESULTS: Post-operative urinary retention was observed in 25/71 patients (35.2%). Multivariate analysis revealed that blood loss ≥ 400 mL [odds ratio (OR) 4.52; 95% confidence interval (CI) 1.24-16.43; p = 0.018] and inferior vesical artery (IVA) resection (OR 8.28; 95% CI 2.46-27.81; p < 0.001) were independently correlated with the incidence of urinary retention. Furthermore, bilateral IVA resection caused urinary retention in more patients than unilateral IVA resection (88.9% vs 47.1%, respectively; p = 0.049). Although urinary retention associated with unilateral IVA resection improved relatively quickly, urinary retention associated with bilateral IVA resection tended to persist over 1 year. CONCLUSION: We identified the predictive factors of urinary retention following L-LPLND with TME, including increased blood loss (≥ 400 mL) and IVA resection. Urinary retention associated with unilateral IVA resection improved relatively quickly. L-LPLND with unilateral IVA resection is a feasible and safe procedure to improve oncological curability. However, if oncological curability is guaranteed, bilateral IVA resection should be avoided to prevent irreversible urinary retention.

Quantitative evaluation of the intratumoral distribution of platinum in oxaliplatin-treated rectal cancer: In situ visualization of platinum via synchrotron radiation X-ray fluorescence spectrometry.

Oxaliplatin (l-OHP), a platinum-based drug, is a key chemotherapeutic agent for colorectal cancer (CRC), but drug resistance and toxic effects have been major limitations of its use. Synchrotron radiation X-ray fluorescence spectrometry (SR-XRF) is a rapid, nondestructive technique for monitoring the distribution of metals and trace elements in cells or tissue samples. We applied SR-XRF to visualize the distribution of platinum and other elements in 30 rectal cancer specimens resected from patients who received l-OHP-based preoperative chemotherapy and quantified platinum concentration in the tumor epithelium and stroma, respectively, using calibration curves. The platinum concentration in rectal cancer tissue ranged 2.85-11.44 ppm, and the detection limit of platinum was 1.848 ppm. In the tumor epithelium, the platinum concentration was significantly higher in areas of degeneration caused by chemotherapy than in nondegenerated area (p < 0.001). Conversely, in the tumor stroma, the platinum concentration was significantly higher in patients with limited therapeutic responses than in those with strong therapeutic responses (p < 0.001). Furthermore, multivariate analysis illustrated that higher platinum concentration in the tumor stroma was an independent predictive factor of limited histologic response (odds ratio; 19.99, 95% confidence interval; 2.04-196.37, p = 0.013). This is the first study to visualize and quantify the distribution of platinum in human cancer tissues using SR-XRF. These results suggest that SR-XRF analysis may contribute to predicting the therapeutic effect of l-OHP-based chemotherapy by quantifying the distribution of platinum.

Application of ultrasonography to high-tie and low-tie vascular ligation of the inferior mesenteric artery in laparoscopic colorectal cancer surgery: technical notes.

BACKGROUND: Two ligation techniques can be applied in laparoscopy for left-sided colorectal cancer: (1) high-tie (HT), transection at the level of the inferior mesenteric artery (IMA); and (2) low-tie (LT), transection below the IMA, at the level of superior rectal artery (SRA), preserving the left colic artery (LCA). However, even with preoperative images, it can still be a challenge to identify these structures due to intraoperative individual conditions. In this study, we assess the use intraoperative ultrasonography (IOUS) to aid us in identifying the IMA and its branches to the SRA, LCA, and sigmoid artery. METHODS: We performed IOUS in 18 patients diagnosed with left-sided colorectal cancer. Preoperatively, a three-dimensional computed tomography (3D-CT) angiography was obtained in majority of the patients, to visualize the IMA and its branches. Two patients were contraindicated to receive a contrast study, hence, was unable to undergo 3D-CT angiography. The resected specimen was grossly examined for the study. The bifurcation types were identified and compared using different modalities: preoperative 3D-CT, IOUS, and gross examination of the resected specimen. RESULTS: The branching of the IMA revealed by IOUS was consistent to the findings preoperatively by the 3D-CT and postoperatively by the resected specimen. The IOUS result of the two patients without preoperative 3D-CT evaluation was also consistent with the post-operative bifurcation type. CONCLUSIONS: IOUS is an easy and feasible modality which aids in detecting the branching of the IMA during LT and HT ligation in laparoscopic left-sided colorectal surgery. It can serve as an adjunct modality for 3D-CT angiography and can also be considered a safe alternative option for cases wherein 3D-CT angiography is unavailable.

Transancestral fine-mapping of four type 2 diabetes susceptibility loci highlights potential causal regulatory mechanisms.

To gain insight into potential regulatory mechanisms through which the effects of variants at four established type 2 diabetes (T2D) susceptibility loci (CDKAL1, CDKN2A-B, IGF2BP2 and KCNQ1) are mediated, we undertook transancestral fine-mapping in 22 086 cases and 42 539 controls of East Asian, European, South Asian, African American and Mexican American descent. Through high-density imputation and conditional analyses, we identified seven distinct association signals at these four loci, each with allelic effects on T2D susceptibility that were homogenous across ancestry groups. By leveraging differences in the structure of linkage disequilibrium between diverse populations, and increased sample size, we localised the variants most likely to drive each distinct association signal. We demonstrated that integration of these genetic fine-mapping data with genomic annotation can highlight potential causal regulatory elements in T2D-relevant tissues. These analyses provide insight into the mechanisms through which T2D association signals are mediated, and suggest future routes to understanding the biology of specific disease susceptibility loci.

Calpain inhibitor calpeptin suppresses pancreatic cancer by disrupting cancer-stromal interactions in a mouse xenograft model.

Desmoplasia contributes to the aggressive behavior of pancreatic cancer. However, recent clinical trials testing several antifibrotic agents on pancreatic cancer have not shown clear efficacy. Therefore, further investigation of desmoplasia-targeting antifibrotic agents by another mechanism is needed. Calpeptin, an inhibitor of calpains, suppressed fibroblast function and inhibited fibrosis. In this study, we investigated the anticancer effects of calpeptin on pancreatic cancer. We investigated whether calpeptin inhibited tumor progression using a mouse xenograft model. We used quantitative RT-PCR to evaluate the expression of calpain-1 and calpain-2 mRNA in pancreatic cancer cells (PCCs) and pancreatic stellate cells (PSCs). We also undertook functional assays, including proliferation, migration, and invasion, to evaluate the inhibitory effects of calpeptin on PCCs and PSCs. Quantitative RT-PCR indicated that PCCs and PSCs expressed calpain-2 mRNA. Calpeptin reduced tumor volume (P = 0.0473) and tumor weight (P = 0.0471) and inhibited the tumor desmoplastic reaction (P < 0.001) in xenograft tumors in nude mice. Calpeptin also inhibited the biologic functions of PCCs and PSCs including proliferation (P = 0.017), migration (P = 0.027), and invasion (P = 0.035) in vitro. Furthermore, calpeptin reduced the migration of PCCs and PSCs by disrupting the cancer-stromal interaction (P = 0.0002). Our findings indicate that calpeptin is a promising antitumor agent for pancreatic cancer, due not only to its suppressive effect on PCCs and PSCs but also its disruption of the cancer-stromal interaction.

Genome-wide association study identifies three novel loci for type 2 diabetes.

Although over 60 loci for type 2 diabetes (T2D) have been identified, there still remains a large genetic component to be clarified. To explore unidentified loci for T2D, we performed a genome-wide association study (GWAS) of 6 209 637 single-nucleotide polymorphisms (SNPs), which were directly genotyped or imputed using East Asian references from the 1000 Genomes Project (June 2011 release) in 5976 Japanese patients with T2D and 20 829 nondiabetic individuals. Nineteen unreported loci were selected and taken forward to follow-up analyses. Combined discovery and follow-up analyses (30 392 cases and 34 814 controls) identified three new loci with genome-wide significance, which were MIR129-LEP [rs791595; risk allele = A; risk allele frequency (RAF) = 0.080; P = 2.55 × 10(-13); odds ratio (OR) = 1.17], GPSM1 [rs11787792; risk allele = A; RAF = 0.874; P = 1.74 × 10(-10); OR = 1.15] and SLC16A13 (rs312457; risk allele = G; RAF = 0.078; P = 7.69 × 10(-13); OR = 1.20). This study demonstrates that GWASs based on the imputation of genotypes using modern reference haplotypes such as that from the 1000 Genomes Project data can assist in identification of new loci for common diseases.

A single-nucleotide polymorphism in ANK1 is associated with susceptibility to type 2 diabetes in Japanese populations.

To identify a novel susceptibility locus for type 2 diabetes, we performed an imputation-based, genome-wide association study (GWAS) in a Japanese population using newly obtained imputed-genotype data for 2 229 890 single-nucleotide polymorphisms (SNPs) estimated from previously reported, directly genotyped GWAS data in the same samples (stage 1: 4470 type 2 diabetes versus 3071 controls). We directly genotyped 43 new SNPs with P-values of <10(-4) in a part of stage-1 samples (2692 type 2 diabetes versus 3071 controls), and the associations of validated SNPs were evaluated in another 11 139 Japanese individuals (stage 2: 7605 type 2 diabetes versus 3534 controls). Combined meta-analysis using directly genotyped data for stages 1 and 2 revealed that rs515071 in ANK1 and rs7656416 near MGC21675 were associated with type 2 diabetes in the Japanese population at the genome-wide significant level (P < 5 × 10(-8)). The association of rs515071 was also observed in European GWAS data (combined P for all populations = 6.14 × 10(-10)). Rs7656416 was in linkage disequilibrium to rs6815464, which had recently been identified as a top signal in a meta-analysis of East Asian GWAS for type 2 diabetes (r(2) = 0.76 in stage 2). The association of rs7656416 with type 2 diabetes disappeared after conditioning on rs6815464. These results indicate that the ANK1 locus is a new, common susceptibility locus for type 2 diabetes across different ethnic groups. The signal of association was weaker in the directly genotyped data, so the improvement in signal indicates the importance of imputation in this particular case.

Reliability, validity, and responsiveness of the Japanese version of the EORTC QLQ-ELD14 in evaluating the health-related quality of life of elderly patients with cancer.

PURPOSE: This study evaluated the reliability, validity, and responsiveness of the Japanese version of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-ELD14 and measured the health-related quality of life (HRQOL) of elderly Japanese patients with cancer aged ≥ 60 and ≥ 70 years. METHODS: The study recruited elderly Japanese patients with cancer aged ≥ 60 (≥ 70) years (n = 1803 [n = 1236]). The EORTC QLQ-ELD14 was evaluated for reliability, validity, responsiveness, and correlations of changes in score between the EORTC QLQ-ELD14 and the EORTC QLQ-C30 before and after the commencement of the COVID-19 pandemic. RESULTS: In both age groups, the proportion of missing items was low (< 3%). Cronbach's α was good at ≥ 0.70, except for two of the seven items. All the intraclass coefficient constants were good at ≥ 0.70. The concurrent validity was good but correlation with the EORTC QLQ-C30 was not strong, except for the hypothesis items. Regarding the assessment of responsiveness, only one item ("maintaining purpose") of the EORTC QLQ-ELD14 worsened (- 6.14 ± 29.20, standard response of mean > 0.2) after the commencement of the COVID-19 pandemic. The changes in score between the EORTC QLQ-ELD14 and the "global health status/QOL" and "summary score" of the EORTC QLQ-C30 had moderate-to-high negative correlations for all items, except two. Hypotheses to evaluate construct validity were accepted at 90%, while responsiveness was accepted at 80%. CONCLUSION: The Japanese version of the EORTC QLQ-ELD14 questionnaire appears to have acceptable reliability, validity, and responsiveness to evaluate HRQOL in elderly Japanese people with cancer.

Significance of combination therapy of zoledronic acid and gemcitabine on pancreatic cancer.

In the present study, we examined the cytotoxic effects of combination therapy with zoledronic acid (ZOL) and gemcitabine (GEM) on pancreatic cancer cells in vitro and in vivo. Four human pancreatic cancer cell lines were treated with ZOL, GEM or a combination of both, and the effects of the respective drug regimens on cell proliferation, invasion and matrix metalloproteinase (MMP) expression were examined. A pancreatic cancer cell line was also intrasplenically or orthotopically implanted into athymic mice and the effects of these drugs on tumor metastasis and growth in vivo were evaluated by histological and immunohistochemical analyses. Combination treatment with low doses of ZOL and GEM efficiently inhibited the proliferation (P < 0.001) and invasion (P < 0.001) of pancreatic cancer cells in vitro. Western blotting assay revealed that MMP-2 and MMP-9 expression levels were decreased after ZOL treatment. In vivo, combined treatment significantly inhibited tumor growth (P < 0.05) and the development of liver metastasis (P < 0.05). These data revealed that ZOL and GEM, when used in combination, have significant antitumor, anti-metastatic and anti-angiogenic effects on pancreatic cancer cells. The present study is the first to report the significance of the combination treatment of ZOL and GEM in pancreatic cancer using an in vivo model. These data are promising for the future application of this drug regimen in patients with pancreatic cancer.

Variations with modest effects have an important role in the genetic background of type 2 diabetes and diabetes-related traits.

The aim of the present study was to explore the role of variations with modest effects (previously identified by a large-scale meta-analysis in European populations) in the genetic background of type 2 diabetes (T2D) and diabetes-related traits in a Japanese population. We enrolled 2632 Japanese subjects with T2D and 2050 non-diabetic subjects. We analyzed nine single-nucleotide polymorphisms (SNPs), including rs340874 (PROX1), rs4607517 (GCK), rs2191349 (DGKB-TMEM195), rs7034200 (GLIS3), rs10885122 (ADRA2A), rs174550 (FADS1), rs11605924 (CRY2), rs10830963 (MTNR1B) and rs35767 (IGF1). rs340874 (PROX1) and rs174550 (FADS1) were significantly associated with T2D (P=0.0078, OR: 1.12; and P=0.0071, OR: 1.12, respectively). Subjects with more risk alleles related to nine SNPs had an increased risk of T2D (P=0.0017), as well as a higher fasting plasma glucose level (P=0.018), higher HbA(1c) level (P=0.013) and lower HOMA-ß (P=0.033) compared with subjects who had fewer risk alleles. We identified a significant association of a SNP of FADS1 and a SNP near PROX1 with T2D in a Japanese population. The present findings suggest that inclusion of SNPs with a tendency to increase the disease risk captured more of the genetic background of T2D than that revealed by only assessing significant SNPs.

Claudin-4 expression predicts survival in pancreatic ductal adenocarcinoma.

BACKGROUND: Identification of prognostic markers would be useful in the clinical management of patients with pancreatic ductal adenocarcinoma (PDAC). The clinical relevance of claudin-4 (CLDN4), recently identified as overexpressed in PDAC, is unknown. METHODS: Using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), we analyzed CLDN4 mRNA expression in a panel of 9 pancreatic cancer cell lines and formalin-fixed paraffin-embedded (FFPE) tissues from 100 patients with PDAC. The CLDN4 expression levels were then correlated with clinicopathological variables and patient outcome. We also performed immunohistochemical analysis in 20 FFPE samples of PDAC to investigate the expression of CLDN4 protein. RESULTS: Increased expression of CLDN4 was confirmed in all the pancreatic cancer cell lines tested compared with normal ductal epithelial cells and fibroblasts. We found that low expression of CLDN4 was significantly associated with shorter survival in patients with PDAC (hazard ratio; 1.362, 95% confidence interval; 1.011-1.873, P = 0.0419). Patients with high CLDN4 expression survived longer for a median of 63.0 months, compared with 14.7 months in patients with low CLDN4 expression (P = 0.0067). In immunohistochemical analysis, the level of CLDN4 mRNA expression was significantly correlated with the expression of CLDN4 protein (P = 0.0168). CONCLUSION: Increased expression of CLDN4 mRNA predicts better prognosis in PDAC.

Insig2 is overexpressed in pancreatic cancer and its expression is induced by hypoxia.

A hypoxic microenvironment is a characteristic feature of pancreatic cancer, and induces the expressions of various genes involved in malignant behaviors. Insulin-induced gene 2 (Insig2) has recently been shown to be correlated with cellular invasion in colon cancer. However, there have been no reports regarding its expression in pancreatic cancer. In this study, we evaluated Insig2 mRNA expression and the biological function of Insig2 in pancreatic cancer. We measured Insig2 mRNA expression in cultured pancreatic cancer cell lines and invasive ductal carcinoma (IDC) cells, normal pancreatic epithelial cells, and pancreatic intraepithelial neoplasia cells obtained by laser-capture microdissection. We also investigated the effects of Insig2-targeting siRNAs on the cell proliferation and cell invasion of pancreatic cancer cell lines. All pancreatic cancer cell lines expressed Insig2 mRNA. The PANC-1 and MIA PaCa-2 pancreatic cancer cell lines showed >2-fold higher Insig2 mRNA expression levels under hypoxic conditions (1% O2) than under normoxic conditions (21% O2 ). Cell proliferation was significantly decreased in SUIT-2 cells and cell invasion was significantly decreased in SUIT-2, Capan-2, and CFPAC-1 cells after transfection of the Insig2-targeting siRNAs. In analyses of microdissected cells, cells from IDC tissues expressed significantly higher levels of Insig2 mRNA than normal pancreatic cells (P < 0.001) and pancreatic intraepithelial neoplasia cells (P = 0.082). In analyses of IDC cells, the levels of Insig2 mRNA expression were significantly higher in late-stage patients than in early-stage patients. The present data suggest that Insig2 is associated with the malignant potential of pancreatic cancer under hypoxic conditions.

Tumor-stroma interactions reduce the efficacy of adenoviral therapy through the HGF-MET pathway.

Many preclinical studies have shown the potential of adenovirus-based cancer gene therapy. However, successful translation of these promising results into the clinic has not yet been achieved. Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant desmoplastic stroma, and tumor-stromal cell interactions play a critical role in tumor progression. Therefore, we hypothesized that tumor-stroma interactions reduce the efficacy of adenoviral therapy. We investigated the effect of fibroblasts on adenovirus-based gene therapy using SUIT-2 and PANC-1 pancreatic cancer cells cultured with or without fibroblast-conditioned culture supernatant then infected with Ad-LacZ. After 48 h, the cells were stained for ß-galactosidase. The results showed that the number of ß-galactosidase-positive cells was significantly reduced after culture with fibroblast-conditioned supernatant (P < 0.05). Because the hepatocyte growth factor (HGF)/MET pathway plays an important role in tumor-stroma interactions we next investigated the involvement of this pathway in tumor-stroma interactions leading to the decreased efficacy of adenoviral therapy. SUIT-2 cells were cultured with or without SU11274 (a MET inhibitor) and/or fibroblast-conditioned culture supernatant, then infected with Ad-GFP. After 48 h, GFP-positive cells were counted. The number of GFP-positive cells in cultures containing fibroblast-conditioned supernatant plus SU11274 was significantly greater than in cultures without SU11274. In conclusion, our results suggest that stromal cells in PDAC reduce the efficacy of adenoviral therapy through a mechanism involving the HGF/MET pathway. Control of such tumor-stroma interactions may lead to improvements in adenoviral gene therapy for PDAC.

CD10+ pancreatic stellate cells enhance the progression of pancreatic cancer.

BACKGROUND & AIMS: Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer by producing extracellular matrix and soluble factors. However, the functional heterogeneity of PSCs has not been identified until now. Detailed characterization of the PSCs in human pancreatic cancer would provide a set of potential targets for stroma-directed therapy. METHODS: We isolated PSCs from fresh pancreatic ductal adenocarcinoma tissue and sorted them by flow cytometry according to cell surface expression of CD10, which is a stromal prognostic marker for various tumors. We analyzed the functional differences between CD10(+) PSCs and CD10(-) PSCs. RESULTS: Immunohistochemical analysis showed that the frequency of CD10 expression by PSCs was markedly higher in tumor tissue than in normal tissue (33.7% vs 0%, respectively, P = .028). In pancreatic ductal adenocarcinoma, CD10 expression by PSCs was associated with positive nodal metastases (P = .011) and a shorter survival time (P < .001). In vitro coculture experiments showed that CD10(+) PSCs promoted the invasiveness of pancreatic cancer cell lines, SUIT-2 and Panc-1 cells more intensively than CD10(-) PSCs. CD10(+) PSCs significantly increased the tumor growth and invasiveness of SUIT-2 cells in a murine cotransplantation model. CD10(+) PSCs secreted higher levels of matrix metalloproteinase 3 than CD10(-) PSCs, and knockdown of matrix metalloproteinase 3 in cocultured PSCs reduced the invasion of SUIT-2 and Panc-1 cells. CONCLUSIONS: CD10(+) PSCs enhance the progression of pancreatic cancer cells. CD10(+) PSCs may be a candidate for selective therapeutic targeting in the treatment of pancreatic cancer.

Expression of claudin-4 (CLDN4) mRNA in intraductal papillary mucinous neoplasms of the pancreas.

Claudin-4, encoding a protein for tight junction formation and function, is highly overexpressed in pancreatic ductal adenocarcinoma and is also associated with invasive adenocarcinomas arising in intraductal papillary mucinous neoplasms of the pancreas. However, the expression pattern of claudin-4 during neoplastic progression of intraductal papillary mucinous neoplasms remains unknown. Using quantitative real-time reverse transcription-PCR, we analyzed claudin-4 mRNA in a panel of 14 pancreatic cancer cell lines and in formalin-fixed paraffin-embedded tissues from 80 patients with intraductal papillary mucinous neoplasms of different histological grades and papillary subtypes. Increased expression of claudin-4 was confirmed in all the pancreatic cancer cell lines tested as compared with normal ductal epithelial cells and fibroblast cultures. The claudin-4 expression was significantly higher in high-grade intraductal papillary mucinous neoplasms (borderline neoplasm and carcinoma) than in low-grade intraductal papillary mucinous neoplasms (adenoma) (P<0.0001). In addition, claudin-4 mRNA levels were significantly higher in intestinal-type intraductal papillary mucinous neoplasms than in non-intestinal-type intraductal papillary mucinous neoplasms based on papillary subclassification (P<0.0001). Our findings suggest that claudin-4 expression is associated with neoplastic progression of intraductal papillary mucinous neoplasms and, especially, with a distinct pathway to intestinal differentiation.

MicroRNA expression as a predictive marker for gemcitabine response after surgical resection of pancreatic cancer.

BACKGROUND: To improve the prognosis of patients after resection of pancreatic cancer, the most appropriate and efficient treatment should be provided to specific subsets of patients. Our aim was to identify promising microRNAs as markers to predict responses to gemcitabine in patients with resected pancreatic cancer. METHODS: Two gemcitabine-resistant pancreatic cancer cell lines were established, and global microRNA expression analyses was performed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Eleven miRNAs were selected as putative predictive markers and analyzed by means of macrodissected formalin-fixed, paraffin-embedded samples obtained from 90 patients with or without gemcitabine treatment after resection of pancreatic cancer. RESULTS: We identified 24 microRNAs whose expression was altered in gemcitabine-resistant cells. qRT-PCR analyses showed that patients with high miR-142-5p and miR-204 expression had significantly longer survival times than those with low miR-142-5p (P = 0.0077) and miR-204 (P = 0.0054) expression in the gemcitabine-treated group. This was not seen in the nontreated group. Multivariate analyses showed that miR-142-5p expression was an independent prognostic marker only in patients treated with gemcitabine (P = 0.034). CONCLUSIONS: miR-142-5p is a promising predictive marker for gemcitabine response in patients with resected pancreatic cancer.

Successful Management of a Severe Sacral Pressure Injury Penetrating to the Retroperitoneum.

INTRODUCTION: Reports of retroperitoneal infection related to a sacral pressure injury (PI) are rare, and none of the reports described the direct spread of infection through the sacrum to the retroperitoneum. The authors present, to their knowledge, the first report of a severely infected PI that showed full-thickness sacral destruction and direct retroperitoneal penetration. CASE REPORT: A 63-year-old female was referred for management of a stage 4 sacral PI complicated by a retroperitoneal abscess. The patient's comorbidities were diabetes mellitus and pemphigus foliaceus with steroid therapy-induced immunosuppression. Upon admission, the patient presented with a sacral PI producing copious purulent discharge that measured 5 cm × 3 cm. Magnetic resonance imaging revealed full-thickness sacral bone destruction and a massive retroperitoneal abscess, suggesting the sacral PI directly penetrated to the retroperitoneal space. Antibiotics were administered, and surgical debridement and sequestrectomy were performed. Negative pressure wound therapy (NPWT) with continuous saline irrigation was initiated. The patient's mesorectum was exposed within the retroperitoneal space. Therefore, a nonadhesive wound dressing was applied before placing the irrigation tube to avoid perforating the rectum. Because the patient had fragile skin secondary to long-standing pemphigus foliaceus and steroid treatment, a liquid skin protectant and hydrocolloid wound dressing were applied. The infection was successfully controlled with NPWT with saline irrigation. The patient experienced no rectal injury or skin rupture, and surgical closure was performed after 75 days. Although partial wound dehiscence occurred because of the poor condition of the skin, the resultant open wound was managed conservatively. The patient showed no retroperitoneal abscess recurrence 6 months later. CONCLUSIONS: A rare case of an intractable sacral PI complicated by retroperitoneal abscess was successfully managed in an immunocompromised patient. Notably, NPWT with saline irrigation was useful in controlling the patient's severe retroperitoneal infection.

MicroRNA, hsa-miR-200c, is an independent prognostic factor in pancreatic cancer and its upregulation inhibits pancreatic cancer invasion but increases cell proliferation.

BACKGROUND: Recently, the microRNA-200 family was reported to affect cancer biology by regulating epithelial to mesenchymal transition (EMT). Especially, the expression of miR-200c has been shown to be associated with upregulating the expression of E-cadherin, a gene known to be involved in pancreatic cancer behavior. However, the significance of miR-200c in pancreatic cancer is unknown. METHODS: In the present study, we investigated the relationship between E-cadherin and miR-200c expression in a panel of 14 pancreatic cancer cell lines and in macro-dissected formalin-fixed paraffin-embedded (FFPE) tissue samples obtained from 99 patients who underwent pancreatectomy for pancreatic cancer. We also investigated the effects of miR-200c on the proliferation and invasion of pancreatic cancer cells. RESULTS: We found that patients with high levels of miR-200c expression had significantly better survival rates than those with low levels of miR-200c expression. We also found a remarkably strong correlation between the levels of miR-200c and E-cadherin expression. CONCLUSIONS: These data indicate that miR-200c may play a role in the pancreatic cancer biology and may be a novel marker for the prognosis of pancreatic cancer.

MicroRNA-203 expression as a new prognostic marker of pancreatic adenocarcinoma.

BACKGROUND: Detection of aberrant microRNA (miR) expression may contribute to diagnosis and prognosis of various cancers. The aim of this study is to evaluate the correlation between miR-203 expression and prognosis of patients with pancreatic adenocarcinoma after curative resection. METHODS: A total of 113 formalin-fixed paraffin-embedded tissue samples of pancreatic adenocarcinoma, 20 samples of chronic pancreatitis, and 8 samples of normal pancreas were obtained. We investigated the association of miR-203 expression measured by quantitative reverse-transcription polymerase chain reaction assays with clinicopathological parameters and survival times. RESULTS: miR-203 was overexpressed in pancreatic adenocarcinoma samples compared with chronic pancreatitis (P < 0.001) and normal pancreas (P = 0.001) samples. An association between miR-203 expression and clinicopathological factors of pancreatic adenocarcinoma was not observed. On univariate analysis, the high-miR-203 group and the subgroup (20%) of cases with the highest miR-203 overexpression had significantly shorter survival time (P = 0.048 and P = 0.024, respectively). Multivariate analysis revealed that miR-203 expression was an independent predictor of poor prognosis in cases with no residual tumor (relative risk 2.298, P = 0.027). CONCLUSIONS: miR-203 expression is a new prognostic marker in pancreatic adenocarcinoma patients.

Laparoscopic spacer placement for recurrent sacral chordoma before carbon ion radiotherapy: A case report.

Recently, several scholars have demonstrated the efficacy of carbon ion radiotherapy (CIRT). To treat abdominal or pelvic tumors by CIRT, it is necessary to separate the tumor from the adjacent organs. Surgical placement of a GORE-TEX sheet as a spacer has been reported as a separation method. Usually, surgical spacer placement is done by open surgery. Here, we report a case of surgical spacer placement undertaken by a "pure" laparoscopic procedure. A 47-year-old man with recurrent sacral chordoma was referred for surgical spacer placement before CIRT. Laparoscopic dissection of the rectum and placement of a GORE-TEX sheet as a spacer were successfully performed. Surgical spacer placement by a pure laparoscopic procedure was safe and effective, and it seems to play an important part before CIRT.