Short-term outcomes of a multicentre randomized clinical trial comparing laparoscopic pylorus-preserving gastrectomy with laparoscopic distal gastrectomy for gastric cancer (the KLASS-04 trial).

BACKGROUND: There remain concerns about the safety and functional benefit of laparoscopic pylorus-preserving gastrectomy (LPPG) compared with laparoscopic distal gastrectomy (LDG). This study evaluated short-term outcomes of a randomized clinical trial (RCT) comparing LPPG with LDG for gastric cancer. METHODS: The Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS)-04 trial was an investigator-initiated, open-label, parallel-assigned, superiority, multicentre RCT in Korea. Patients with cT1N0M0 cancer located in the middle third of the stomach at least 5 cm from the pylorus were randomized to undergo LPPG or LDG. Participants, care givers and those assessing the outcomes were not blinded to group assignment. Outcomes were 30-day postoperative morbidity rate and death at 90 days. RESULTS: Some 256 patients from nine institutions were randomized (LPPG 129 patients, LDG 127 patients) between July 2015 and July 2017 and outcomes for 253 patients were analysed. Postoperative complications within 30 days were seen in 19.3 and 15.5 per cent in the LPPG and LDG groups respectively (P = 0·419). Postoperative pyloric stenosis was observed in nine (7.2 per cent) and two (1·5 per cent) patients in the LPPG and LDG groups (P = 0·026) respectively. In multivariable analysis higher BMI was a risk factor for postoperative complications (odds ratio 1·17, 95 per cent c.i. 1·04 to 1·32; P = 0·011). Death at 90 days was zero in both groups. CONCLUSION: Postoperative complications and mortality was comparable in patients undergoing LPPG and LDG. Registration number: NCT02595086 (http://www.clinicaltrials.gov).

Suppressing stathmin-l can inhibit chkl protein expression and reduce the invasion and tumorigenicity of cervical cancer cells.

The purpose of this study was to evaluate the effects of stathmin-l on chkl protein expression in cervical cancer cells and the influ- ences on the cells' invasion and tumorigenicity. Suppressed stathmin-l expression in Hela cells and C33A cells by lentiviral vector were utilized. Real time PCR and Western blot were used to examine the expression of chkl. Cell proliferation and invasion were stud- ied using MTT assays and transwell migration assays.The differences of tumorigenicity in vivo were explored using xenograft experi- ments. In addition, stathmin-l expressions in 24 cervical cancer patients were studied without regional lymph nodes metastasis and 16 metastatic patients by immunohistochemistry assays and real time PCR. This study found downregulating stathmin-l reduced chkl ex- pressions and the proliferation and invasion in cervical cancer cells and reduced the tumorigenicity of tumor cells.

PPP1R1B-STARD3 chimeric fusion transcript in human gastric cancer promotes tumorigenesis through activation of PI3K/AKT signaling.

Fusion genes act as potent oncogenes, resulting from chromosomal rearrangements or abnormal transcription in many human cancers. Although multiple gastric cancer genomes have been sequenced, the driving recurrent gene fusions have not been well characterized. Here, we used paired-end transcriptome sequencing to identify novel gene fusions in 18 human gastric cancer cell lines and 18 pairs of primary human gastric cancer tissues and their adjacent normal tissues. Multiple samples revealed expression of PPP1R1B-STARD3 fusion transcript. The presence of PPP1R1B-STARD3 correlated with elevated levels of PPP1R1B mRNA. PPP1R1B-STARD3 fusion transcript was detected in 21.3% of primary human gastric cancers but not in adjacent matched normal gastric tissues. Based on reverse transcription PCR analysis of DNA, unlike other fusions described in gastric cancer, the PPP1R1B-STARD3 appears to be generated by RNA processing without chromosomal rearrangement. Overexpression of PPP1R1B-STARD3 in MKN-28 significantly increased cell proliferation and colony formation. This increased proliferation was mediated by activation of phosphatidylinositol-3-kinase (PI3K)/AKT signaling. Furthermore, expression of PPP1R1B-STARD3 fusion transcript enhanced the tumor growth of MKN-28 cells in athymic nude mice. These findings show that PPP1R1B-STARD3 fusion transcript has a key role in subsets of gastric cancers through the activation of PI3K/AKT signaling.

Validation of limited lymphadenectomy for lower-third gastric cancer based on depth of tumour invasion.

BACKGROUND: This study aimed to determine the appropriate extent of lymph node (LN) dissection in gastric cancer by analysing LN metastasis patterns from prospectively collected topographical data on nodal status at Seoul National University Hospital, Korea. METHODS: The metastasis rate for each LN station was analysed according to the depth of tumour invasion in patients with primary lower-third gastric cancer who underwent curative gastrectomy. The Maruyama Index of unresected disease (MI) was calculated using the WinEstimate(®) program with simulation of various extents of LN dissection. RESULTS: LN metastasis in mucosal cancer was rare; 2·6 per cent of patients had a MI of more than 5 with simulation of D1 plus station 7 dissection, whereas 0·9 per cent had a MI above 5 with D1 plus stations 7 and 8a. In submucosal cancer, 3·3 per cent of tumours metastasized to level 2 LN stations outside the range of D1 plus stations 7, 8a and 9. The proportion of patients with a MI above 5 was 9·0 per cent with D1 plus stations 7, 8a and 9 dissection. The nodal metastasis rate was higher at level 1 and 2 for muscularis propria or deeper cancers. CONCLUSION: D1 dissection plus stations 7 and 8a for mucosal cancer, and D2 dissection for cancers of the muscularis propria or deeper seems appropriate. For submucosal cancer, an expanded dissection to the D2 level should be considered to ensure complete removal of metastatic LNs.