Clinical implications of DLL4 expression in gastric cancer

BACKGROUND: Delta-like ligand 4 (DLL4)-Notch signaling plays a key role in tumor neovascular development and angiogenesis during tumor growth. The clinical significance of DLL4 expression in gastric cancer has not been clarified. METHODS: Gastric cancer cell lines and 180 gastric cancer patients were enrolled. DLL4 expression in gastric cancer cells and stroma was identified and evaluated immunohistochemically. The association between DLL4 and clinicopathological factors was also assessed. RESULTS: DLL4 expression was identified in the cellular membrane and cytoplasm of gastric cancer cells by immunoblotting and immunohistochemical staining. DLL4 positivity in cancer cells and stroma was found in 88 (48%) and 41 (22%) of the 180 gastric cancer patients respectively. Both cancer and stromal DLL4 expression significantly correlated with more advanced tumor depth, nodal involvement, and lymphatic and venous invasion. A strongly positive association between cancerous and stromal DLL4 expression was identified (p < 0.01). Both cancerous and stromal DLL4 expression were prognostic markers in gastric cancer as determined by univariate analysis. CONCLUSIONS: Cancerous and stromal DLL4 expression was found in 48% and 22% in gastric cancer, and significantly affected postoperative clinical outcomes. Cancerous and stromal DLL4 expression may be an effective target of anti-DLL4 treatment in gastric cancer

Prognostic impact of CD168 expression in gastric cancer

<p>Abstract</p> <p>Background</p> <p>Interactions of stromal hyaluronic acid (HA) with its binding protein RHAMM (receptor for HA-mediated motility) (CD168) have been reported to affect tumor extension and the migration of crucial molecules to promote tumor progression and metastases. Cancerous CD168 expression is correlated with aggressive biological features in several cancers. However, the clinical implications of CD168 positivity in gastric cancer have remained unclear.</p> <p>Methods</p> <p>We examined the CD168 expression of 196 consecutive gastric cancer patients by immunohistochemistry. According to CD168 positivity, the 196 gastric cancer patients were divided into two groups (57 CD168-positive and 139 CD168-negative patients). The correlation between CD168 expression and clinicopathological factors (age, sex, histology, tumor depth, lymph node status, and vessel invasion) was evaluated according to the Japanese Classification of Gastric Carcinoma.</p> <p>Results</p> <p>Cancerous CD168 expression was detectable in 57 of the 196 tumors (29%). CD168 positivity was significantly correlated with the depth of invasion, nodal involvement, and vessel invasion (p < 0.01). Survival analysis of the 196 gastric cancer patients showed that the CD168-positive group had a significantly higher mortality than the CD168-negative group (p < 0.01). In terms of a correlation with CD168 positivity at separate clinical stages, a significance difference was only found in stages II and III. Multivariate analysis revealed that CD168 expression was a significant independent prognostic marker (p = 0.013) after depth of invasion (p < 0.005) and nodal involvement (p < 0.01).</p> <p>Conclusion</p> <p>Our results suggest that cancerous CD168 positivity is strongly related to the invasion and metastasis of gastric cancer tumors. These results suggest that cancerous CD168 expression can be used as a prognostic marker of gastric cancer owing to its interactions with stromal hyaluronic acid.</p

Utility of the sentinel node concept for detection of lateral pelvic lymph node metastasis in lower rectal cancer

Abstract Background There are two lymphatic flows in lower rectal cancer; one along the inferior mesenteric artery and another towards the internal iliac artery. The benefit of dissection of lateral pelvic (LP) lymph nodes (LPLN) remains controversial. This study aimed to clarify the possibility of detecting the sentinel node (SN) of the LP region (LPSN) and examine metastasis, including micrometastasis, using a radio isotope (RI) method. Methods In total, 62 patients with clinical (c)T1-T4 rectal cancer were enrolled in this study (11, 16 and 35 patients had tumor located in the upper, middle and lower rectal third, respectively). LPSNs were detected using a radio-isotope method in which 99 m technetium-tin colloid was endoscopically injected into the submucosa in patients with cT1, and into the muscularis propria in patients with cT2, cT3 and cT4. All patients underwent curative resection with lymphadenectomy. LPSN metastases were diagnosed by HE staining, immunohistochemical staining using AE1/AE3 as a primary antibody and by RT-PCR using CEA as a marker. Results Of the lower rectal (c)T2–4 tumors, 38.4% had lateral pelvic lymphatic flow that was significantly greater than that of cT1 tumors in the upper and middle thirds of the rectum (p = 0.0074). HE and immunohistochemical staining did not detect LPSN metastases but RT-PCR detected micrometastasis of three SNs. The remaining half of LPSNs were immunohistochemically re-examined; in all three cases, isolated tumor cells were detected. Conclusion The SN concept may be useful for detecting lateral pelvic lymphatic flow and LPSN metastases, including micrometastasis in lower rectal cancer

The Diagnostic and Prognostic Value of a Liquid Biopsy for Esophageal Cancer: A Systematic Review and Meta-Analysis

Esophageal cancer is among the most aggressive diseases, and circulating tumor cells (CTCs) have been recognized as novel biomarkers for various cancers over the past two decades, including esophageal cancer. CTCs might provide crucial clinical information for predicting cancer prognosis, monitoring therapeutic responses or recurrences, or elucidating the mechanism of metastasis. The isolation of CTCs is among the applications of a &ldquo;liquid biopsy&rdquo;. There are various technologies for liquid biopsies, and they are classified into two main methods: cytometric or non-cytometric techniques. Here, we review a total of 57 eligible articles to summarize various technologies for the use of a liquid biopsy in esophageal cancer and perform a meta-analysis to assess the clinical utility of liquid biopsies as a prognostic and diagnostic biomarker technique. For prognostic evaluation, the pooled hazard ratio in the cytometric assay is relatively higher than that of the non-cytometric assay. On the other hand, a combination of multiple molecules, using a non-cytometric assay, might be a favorable biomarker technique for the early diagnosis of esophageal cancer. Although determining strong evidence for a biomarker by using a liquid biopsy is still challenging, our meta-analysis might be a milestone for the future development of liquid biopsies in use with esophageal cancer

Radial incision and cutting method using a transanal approach for treatment of anastomotic strictures following rectal cancer surgery: a case report

Abstract Background Development of an anastomotic stricture following rectal cancer surgery is not uncommon. Such strictures are usually managed by manual or instrumental dilatation techniques that are often insufficiently effective, as evidenced by the high recurrence rate. Various surgical procedures using minimally invasive approaches have also been reported. One of these procedures, endoscopic radial incision and cutting (RIC), has been extensively reported. However, RIC by transanal minimally invasive surgery (TAMIS) is yet to be reported. We here report a novel application of TAMIS for performing RIC for anastomotic rectal stenosis. Case presentation A 67-year-old man had suffered from constipation for 6 years after undergoing low anterior resection for stage II rectal cancer 7 years ago. Colonoscopy showed a 1-cm diameter stricture in the lower rectum. Balloon dilatation was performed many times because of repeated recurrences. Thus, surgical management was considered and the stricture was successfully excised via a RIC method using a TAMIS approach. Postoperatively, the patient had minimal leakage that resolved with conservative treatment. Conclusions A RIC method using a TAMIS approach is an effective minimally invasive means of managing anastomotic strictures following rectal cancer surgery

Management of horizontal duodenal perforation: a report of three cases and review of literature

Abstract Background Perforation of the horizontal duodenum is very rare due to the presence in retroperitoneal space. It depicts an unusual clinical picture and is difficult to diagnose, leading to increased morbidity and mortality. The treatment strategies are usually varied and based on small series of cases, literature reviews, and expert opinions. Case presentation Here, we presented three cases of horizontal duodenal perforation in three different clinical processes. The first case, a 30-year-old male patient, presented with abdominal pain and hematemesis after experiencing a physical assault on the previous day. Computed tomography (CT) scan showed rupture of the horizontal duodenum. It was repaired by side-to-side duodenojejunostomy. Postoperatively, he had anastomotic leakage, disseminated intravascular coagulation, and pulmonary failure and recovered after a long hospital stay. The second case, an 81-year-old female, had duodenal perforation with endoscopic coagulation of the bleeding diverticulum. Segmental resection of the duodenum and side-to-side duodenojejunostomy were performed. Postoperatively, there was slight anastomotic leakage, but surgical intervention was not needed. The third case, an 89-year-old female, was a patient with obstructive jaundice due to pancreas head carcinoma, who developed perforation of the horizontal duodenum during endoscopic retrograde cholangiopancreatography (ERCP). After unsuccessful conservative management, duodenojejunostomy at the perforated site and gastric bypass were performed. The postoperative course was uneventful. Conclusion Early suspicion and investigation is necessary for cases of abdominal injuries. CT scan is the investigation of choice. The management options should be based on the clinical condition of the patient, comorbidities, surgical expertise, existing guidelines, and available resources

Successful subtotal gastrectomy and hepatectomy for HER2-positive gastric cancer with liver metastasis after trastuzumab-based chemotherapy: a case report

Abstract Background Conversion surgery (CS) after chemotherapy is weakly recommended as a promising tool for improving prognoses in patients with unresectable gastric cancer. Moreover, several investigators have demonstrated the clinical efficacy of subtotal gastrectomy (sTG) with a small remnant stomach for the nutritional status and surgical outcome compared with total gastrectomy. Here, we report a patient with liver metastasis from human epidermal growth factor receptor 2 (HER2)-positive gastric cancer who underwent sTG and hepatectomy after trastuzumab-based chemotherapy. Case presentation An 84-year-old male patient was diagnosed with HER2-positive gastric cancer with a single liver metastasis. He was treated with eight courses of trastuzumab in combination with S-1 and oxaliplatin as first-line chemotherapy. The primary tumor and liver metastasis shrank significantly. The metastatic liver lesion’s reduction rate was 65%. According to the Response Evaluation Criteria in Solid Tumors, the patient had a partial response. Therefore, he underwent an sTG with D2 lymphadenectomy and partial hepatectomy of segment 2. Histopathological examination revealed a grade 3 histological response without lymph node metastases from the primary tumor. No viable cancer cells were observed in the resected liver specimens. The patient received adjuvant chemotherapy with S-1. The postoperative quality of life (QOL) evaluated using the Postgastrectomy Syndrome Assessment Scale-45 was maintained, and the patient was still alive 8 months after the CS without recurrence. Conclusions An sTG with a small remnant stomach might be clinically useful for preventing a decline in QOL and improving prognoses in patients with stage IV gastric cancer after chemotherapy