High frequency of bone recurrence as an initial recurrence site after radical surgery in T1N3 gastric cancer: a propensity score matching analysis.

PURPOSE: T1 gastric cancer (GC) with seven or more metastatic lymph nodes is extremely rare, and very few clinical studies have been conducted to evaluate the clinicopathological features of their recurrence. METHODS: We retrospectively analyzed the outcomes of T1 GC and T2-4 GC patients who had multiple nodal metastases after radical surgery from 2006 to 2020. Propensity score matching was performed to compare the two groups of patients. RESULTS: After propensity score matching, 18 of 22 patients in the T1 group and 36 of 144 patients in the T2-4 group were selected. Recurrence occurred in six patients (33.3%) in the T1 group. In the T1 group, the most common site of initial recurrence was bone (15.0%). The prevalence of bone recurrence was significantly higher in the T1 group than in the T2-4 group (P = 0.02). The median interval time between radical surgery and bone recurrence was 24 months, and the median survival time after bone recurrence was 14 months. CONCLUSION: Bone recurrence was more frequently identified as an initial recurrence site in T1 GC cases with multiple metastases after radical surgery compared with that in T2-4 GC cases. Careful attention should be paid to postoperative bone recurrence in the long-term postoperative course of these patients.

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.

Atypical clinical presentation of mechanical small bowel obstruction with superior mesenteric vein occlusion caused by a retained free intraperitoneal staple after laparoscopic appendectomy: A case report.

Mechanical small bowel obstruction (SBO) is a common postoperative complication, and most cases are caused by postoperative adhesions. We herein report a case of SBO with superior mesenteric vein occlusion caused by a metal staple after laparoscopic appendectomy. A 35-year-old Japanese woman presented to our department with severe upper abdominal pain and vomiting. She had undergone laparoscopic appendectomy using a linear stapler 7 years before. Abdominal CT showed mild small intestinal dilation with mesenteric edema and volvulus of the small bowel mesentery. Moreover, occlusion of the superior mesenteric vein was observed. Emergency exploratory laparoscopy revealed a strangulated SBO caused by a free unformed staple. The obstruction was released by a laparoscopic technique without bowel resection. The number of laparoscopic surgeries has recently been increasing, and complications specific to laparoscopic surgery have been recognized. All spilled and unformed staples should be removed to the greatest extent possible during laparoscopic operations.

Laparoscopic high anterior resection for triple colorectal cancers with persistent ascending and descending mesocolons: A case report.

Persistent mesocolon is an embryological anomaly of the colon resulting from failure of the primitive dorsal mesocolon to fuse with the parietal peritoneum. We herein present a case of laparoscopic high anterior resection for triple colorectal cancers with persistent ascending and descending mesocolons and a right-bound inferior mesenteric artery. Preoperative 3-D CT demonstrated that the sigmoid colon had shifted to the right abdomen and was located under the ascending colon. Moreover, the inferior mesenteric artery and vein traveled toward the right abdomen accompanied by the mesentery of the descending colon. Adhesiolysis between the ascending and sigmoid colon was initially performed, and the sigmoid colon was placed in its normal position. The inferior mesenteric artery was then divided with lymph node dissection using a medial approach, and high anterior resection was completed. An understanding of the anatomical characteristics of persistent mesocolon is important to ensure safe laparoscopic surgery.

[A long-term survivor case with good quality of life due to biliary bypass and gemcitabine for advanced pancreatic cancer].

A 54-year-old man was admitted to the hospital because of upper abdominal pain and anorexia. Physical examination revealed jaundice, and abdominal CT demonstrated a pancreatic mass and dilatation of bile duct. The patient was operated with the diagnosis of pancreatic cancer. However, the pancreatic cancer was unresectable because of invasion of the surrounding organs and metastasis to paraaortic lymph nodes, so a biliary bypass was performed. After operation, chemotherapy using gemcitabine was performed in the outpatient clinic. He survived for more than two years and eleven months without recurrence of jaundice. Combination of biliary bypass and gemcitabine is considered helpful for good quality of life and long-term survival of a patient with advanced pancreatic cancer.

Overexpression of microRNA-5100 decreases the aggressive phenotype of pancreatic cancer cells by targeting PODXL.

Metastasis is the main cause of cancer-associated death, and metastasis of pancreatic cancer remains difficult to treat because of its aggressiveness. MicroRNAs (miRNAs) play crucial roles in the regulation of various human transcripts, and many miRNAs have been reported to correlate with cancer metastasis. We identified an anti-metastatic miRNA, miR-5100, by investigating differences in miRNA profiling between highly metastatic pancreatic cancer cells and their parental cells. Overexpression of miR-5100 inhibited colony formation (P<0.05), cell migration (P<0.0001) and invasion (P<0.0001) of pancreatic cancer cells. In addition, we identified a possible target of miR-5100, podocalyxin-like 1 (PODXL), and demonstrated miR-5100 directly binds to the 3' untranslated region of PODXL and post-transcriptionally regulates its expression in pancreatic cancer cells. Silencing PODXL resulted in diminished cell migration (P<0.0001) and invasion (P<0.05). We also clarified the close relationship between expression of PODXL in human pancreatic cancer specimens and liver metastasis (P=0.0003), and determined that post-operative survival was longer in the low-PODXL expression group than in the high-PODXL expression group (P<0.05). These results indicate that miR-5100 and PODXL have considerable therapeutic potential for anti-metastatic therapy and could be potential indicators for cancer metastases in patients with pancreatic cancer.

Novel bactericidal surface: Catechin-loaded surface-erodible polymer prevents biofilm formation.

We developed a novel bactericidal surface based on a catechin-loaded surface-erodible polymer. (-)-Epigallocatechin-3-gallate (EGCg), which is the main constituent of tea catechins, showed a dose-dependent inhibitory effect on Escherichia coli biofilm formation and a dose-dependent enhanced destructive effect on biofilm. EGCg-immobilized surfaces were prepared by photopolymerization of liquid biodegradable polyesters. The releasing rate was enhanced with an increase in surface-erosion rate of photocured polymers. Polymers with high releasing capacity dose-dependently reduced biofilm formation on the surfaces. The confocal laser scanning microscopic and scanning electron microscopic observations revealed that EGCg induced biofilm-destructing activities, which include bacterial membrane damage, degradation of exopolysaccharides, and detachment of colonized cells. From these results, potential advantages of the clinical use of catechin-loaded polymer-coated implants or catheters are discussed in terms of a reduced occurrence of biomaterial-centered infections without substantial toxicity or adverse effects.

Trans-tissue, sustained release of gemcitabine from photocured gelatin gel inhibits the growth of heterotopic human pancreatic tumor in nude mice.

PURPOSE: Although gemcitabine, a deoxycytidine analogue, recently demonstrated improvements in the response rate for pancreatic cancer, the median survival for patients is limited to 4-6 months. The purpose of the present study was to develop trans-tissue delivery of gemcitabine, which is based on photocured gelatin gel immobilized with gemcitabine, and to validate whether such a system inhibits the growth of the pancreatic tumor in vivo. EXPERIMENTAL DESIGN: The in vitro release profile of gel-embedded gemcitabine from a gel was examined based on in vitro chemosensitivity of AsPC1 cell (human pancreatic cancer cell line) for gemcitabine. The permeation of gel-embedded rhodamine B (used as a model drug) into tissues and inhibitory effect of tumor growth of photocured gelatin gel immobilized with gemcitabine were examined using in vivo s.c. tumor model of athymic mice. RESULTS: The release profile was characterized as an initial burst of release, followed by a gradual release, irrespective of gelatin concentration. Rhodamine B permeated into the tumor and retained for at least 10 days. Photocured gelatin gel immobilized with gemcitabine significantly reduced the tumor volume compared with gemcitabine injection. Therapeutic success was correlated with decreased cell proliferation and increased cell apoptosis in tumor cells, supported by proliferating cell nuclear antigen and terminal deoxynucleotidyltransferase-mediated nick end labeling staining. Blood analysis and body weight measurement showed that little side effect was observed in this therapy. CONCLUSIONS: In situ trans-tissue gemcitabine delivery on the tissue with possibly remnant cancer cells using the drug-releasing matrix developed here is expected to reduce the rate of local recurrence for patients with pancreatic cancer.

New infusion device for trans-tissue, sustained local delivery of anticancer agent to surgically resected tissue: potential use for suppression of local recurrence of pancreatic cancer.

Local recurrence is a major cause of death of patients who have undergone resection for pancreatic cancer. To reduce the incidence of local recurrence, a new drug-infusion device, which is fixed on resected tissues immediately after surgery, was devised for trans-tissue, sustained local delivery. The drug-infusion device proposed here has the following functions: tight adhesion of the device on resected tissues, sustained drug infusion to the tissue, drug reloading, and easy removal from the body after use. The fabricated prototype experimental device, described here, was a thin infusion pouch made of a thin elastomer film (segmented polyurethane), which is connected to an elastomeric tube for drug reloading. The suppressive effect of the device delivering the anticancer agent, gemcitabine (GEM), was examined using subcutaneous tumor-bearing athymic mouse. A low-dose, local sustained GEM delivery using the device significantly suppressed the tumor growth and regrowth after surgery. The preliminary model experimental result appears to provide a promising therapeutic procedure for increased survival rate of the patients undergoing surgery for pancreatic cancer.

Novel strategic therapeutic approaches for prevention of local recurrence of pancreatic cancer after resection: trans-tissue, sustained local drug-delivery systems.

Local recurrence and hepatic metastasis are still the major causes of death of patients who have undergone resection for pancreatic cancer. To decrease the incidence of local recurrence, we have proposed and devised several trans-tissue and local delivery systems, all of which could be applied immediately after surgery at the resected sites: (1) System I: a drug-loaded photocured gelatinous tissue-adhesive gel (bioactive substance reservoir) that enables the sustained release of a drug, protein, or gene-encoding adenovirus, (2) System II: an anti-cytokine antibody-fixed photocured gelatinous, tissue-adhesive gel (cytokine barrier) that prevents cytokine permeation into the resected tissue, (3) System III: a gene-modified cell sheet that enables the sustained release of a very costly protein produced by gene-transduced cells and (4) System IV: a percutaneous drug-delivery device that enables continuous drug infusion and easy removal from the body. This review article is a summary of our several years of efforts and attempts, which are composed of integrated disciplines including active biomaterials and genetic- and tissue-engineerings, to overcome the recurrence of pancreatic cancer. Here, we outline our proposed strategies and therapeutic devices/materials and discuss their potential therapeutic effectiveness, promises and challenges in the clinical settings.

Confocal imaging of biofilm formation process using fluoroprobed Escherichia coli and fluoro-stained exopolysaccharide.

We developed a novel method of evaluating biofilm architecture on a synthetic material using green fluorescent protein-expressing Escherichia coli and red fluorescence staining of exopolysaccharides. Confocal laser scanning microscopy observation revealed the time course of the change in the in situ three-dimensional structural features of biofilm on a polyurethane film without structural destruction: initially adhered cells are grown to form cellular aggregates and secrete exopolysaccharides. These cells were spottily distributed on the surface at an early incubation time but fused to form a vertically grown biofilm with incubation time. Fluorescence intensity, which is a measure of the number of cells, determined using a fluorometer and biofilm thickness determined from confocal laser scanning microscopy vertical images were found to be effective for quantification of time-dependent growth of biofilms. The curli (surface-located fibers specifically binding to fibronectin and laminin)-producing Escherichia coli strain, YMel, significantly proliferated on fibronectin-coated polyurethane, whereas the curli-deficient isogenic mutant, YMel-1, did not. The understanding of biofilm architecture in molecular and morphological events and new fluorescence microscopic techniques may help in the logical surface design of biomaterials with a high antibacterial potential.

Computed tomographic lymphography predicts the difficulty of sentinel lymph node biopsy with dye.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has been a method of choice for treating breast cancer. Computed tomographic lymphography (CT-LG) provides a view of the sentinel lymph node (SLN) with the detailed lymphatic anatomy preoperatively, and the SLN is easily identified during SLNB. In this article, we examined the usefulness of CT-LG to predict the difficulty of SLNB with the dye method. METHODS: A total of 41 consecutive patients who underwent CT-LG were enrolled in this study. Each CT-LG image was reviewed by one of our co-authors. The images of lymph vessels (LVs) and SLNs were assorted into three categories: not visualized, poorly visualized, and well visualized. The time engaged in SLNB with the dye method was recorded in 30 patients. RESULTS: The time engaged in SLNB between two groups was compared: patients in whom both the SLN and LVs were well visualized (n = 16) and the remaining patients (n = 14). The former required a significantly shorter time than the latter (12.6 ± 4.1 vs. 17.6 ± 6.7 min, respectively; p = 0.025 by Mann-Whitney U test). CONCLUSIONS: Our study clearly demonstrates that the CT-LG findings of well-visualized LVs and SLNs predict the easy access to the stained LVs and SLNs. This information provides several advantages, including the fact that an easy SLNB case can be selected for a doctor with little experience in SLNB, and the volume of dye and/or length of massage can be changed for better identification of stained LVs and SLNs during SLNB.

Feasibility and safety of intracorporeal esophagojejunostomy after laparoscopic total gastrectomy: inverted T-shaped anastomosis using linear staplers.

BACKGROUND: Although laparoscopic distal gastrectomy has been widely accepted in clinical practice, laparoscopic total gastrectomy (LTG) is not yet familiar because of the difficulty in esophagojejunostomy. The purpose of this study was to evaluate perioperative and short-term outcomes of our procedure of intracorporeal gastrojejunostomy using linear staplers after LTG. METHODS: Of 98 consecutive patients who underwent LTG for gastric cancer in our department between August 2002 and December 2010, 94 patients underwent esophagojejunostomy with a linear stapling device. After October 2007, we modified the esophagojejunostomy; ie, the most recent 57 patients underwent transection of the esophagus in the ventrodorsal direction and insertion of a linear stapler from the anterior wall of the Roux limb to the posterior wall so as to make an inverted T-shaped anastomosis. We evaluated the results in these 57 patients (recent group) and compared them with the results in the earlier 37 patients (early group). RESULTS: The mean operative time in the recent group was 368 to 94.6 min, and the mean estimated blood loss was 57 to 33 g; both were comparable with those in the early group. Neither open conversion nor intraoperative complications were encountered. Two patients experienced anastomotic leakage in the earlier group, but anastomotic leakage did not occur in the recent group. No mortality was encountered. CONCLUSION: We herein report our procedure of intracorporeal gastrojejunostomy using linear staplers after LTG. Our procedure of esophagojejunostomy using linear staplers is safe and feasible and has acceptable morbidity.

Improvement of quality of life and survival using self-expandable metal stent placement for severe malignant stenosis of the gastric body: a case report.

INTRODUCTION: Advanced gastric carcinoma often decreases quality of life because of upper gastrointestinal tract stenosis. Self-expandable metal stents have been thought to be an effective, minimally invasive treatment for stenosis. However, the effectiveness of self-expandable metal stent placement for carcinomatous stenosis of the gastric body and antrum has not been clarified, and there have been few reports of such cases. CASE PRESENTATION: A 74-year-old Japanese woman developed stenosis of the gastric body and antrum caused by advanced gastric cancer during first-line chemotherapy. She developed weight loss and poor nutrition due to inadequate intake. Self-expandable metal stent placement for stenosis of the gastric body and antrum ameliorated her symptoms rapidly and improved her general condition and quality of life. Eight days after self-expandable metal stent placement, second-line chemotherapy could be administered safely. Oral intake and nutritional status were maintained for 117 days after self-expandable metal stent placement, and she died of gastric cancer 176 days after self-expandable metal stent placement and initiation of second-line chemotherapy. CONCLUSIONS: Self-expandable metal stent placement for carcinomatous stenosis in the gastric body and antrum could be an effective therapeutic strategy for patients with inadequate oral uptake. It may provide rapid improvement of the patient's general condition and oral intake with minimal complications, comparatively long-term symptom relief, and a survival benefit by allowing second-line chemotherapy.