CAF-associated genes putatively representing distinct prognosis by in silico landscape of stromal components of colon cancer.

Comprehensive understanding prognostic relevance of distinct tumor microenvironment (TME) remained elusive in colon cancer. In this study, we performed in silico analysis of the stromal components of primary colon cancer, with a focus on the markers of cancer-associated fibroblasts (CAF) and tumor-associated endothelia (TAE), as well as immunological infiltrates like tumor-associated myeloid cells (TAMC) and cytotoxic T lymphocytes (CTL). The relevant CAF-associated genes (CAFG)(representing R index = 0.9 or beyond with SPARC) were selected based on stroma specificity (cancer stroma/epithelia, cS/E = 10 or beyond) and expression amounts, which were largely exhibited negative prognostic impacts. CAFG were partially shared with TAE-associated genes (TAEG)(PLAT, ANXA1, and PTRF) and TAMC-associated genes (TAMCG)(NNMT), but not with CTL-associated genes (CTLG). Intriguingly, CAFG were prognostically subclassified in order of fibrosis (representing COL5A2, COL5A1, and COL12A1) followed by exclusive TAEG and TAMCG. Prognosis was independently stratified by CD8A, a CTL marker, in the context of low expression of the strongest negative prognostic CAFG, COL8A1. CTLG were comprehensively identified as IFNG, B2M, and TLR4, in the group of low S/E, representing good prognosis. Our current in silico analysis of the micro-dissected stromal gene signatures with prognostic relevance clarified comprehensive understanding of clinical features of the TME and provides deep insights of the landscape.

Early administration of postoperative BCAA-enriched PPN may improve lean body mass loss in gastric cancer patients undergoing gastrectomy.

BACKGROUND: It has been reported that weight loss or lean body mass (LBM) loss after gastrectomy for gastric cancer is associated with prognosis and nutritional support alone is insufficient to prevent LBM loss. Branched-chain amino acids (BCAA) play an important role in muscle catabolism, however their clinical effects on suppression of LBM loss in gastric cancer patients undergoing gastrectomy remains elusive. In this current study, we investigated the effect of our original PPN regimen including BCAA (designated to BCAA-regimen) on LBM loss. METHODS: We conducted a randomized controlled trial (RCT) at a single institution where patients undergoing gastrectomy were assigned to either receive a five-day early postoperative course of the BCAA-regimen (BCAA group) or conventional nutrition. The primary endpoint was the % reduction in LBM at postoperative day 7. The secondary endpoints included the % reduction in LBM at 1 and 3 months postsurgery. RESULTS: At postoperative day 7, LBM loss in the BCAA group tended to be lower than in the control group (0.16% vs. 1.7%, respectively; P = 0.21), while at 1 month postsurgery, LBM loss in the BCAA group was significantly different to that of the control group (- 0.3% vs. 4.5%, respectively; P = 0.04). At 3 months postgastrectomy, however, LBM loss was similar between the BCAA and the control groups. CONCLUSION: Our RCT clinical trial clarified that early administration of the postoperative BCAA regimen improved LBM loss at 1 month after surgery in gastric cancer patients undergoing gastrectomy.

Improved anastomotic technique for esophagojejunal anastomosis using circular stapler.

PURPOSE: In total gastrectomy, Roux-en-Y reconstruction with esophagojejunal anastomosis has been widely used in gastrointestinal reconstruction. In the case of anastomotic leakage of RY reconstruction, esophagojejunal anastomosis should be paid attention, and esophageal fragility is considered the reason for the leakage. Here, we introduce an atraumatic and innovative technique for esophagojejunostomy. METHODS: We prospectively performed routine novel esophagojejunal anastomosis using circular stapler device and reviewed the records of 14 consecutive patients with gastric cancer who underwent open total gastrectomy at Kitasato University Hospital from April 2019 to March 2020. By placing about 10 stay sutures around the entire esophageal stump, the esophageal stump can be opened to the maximum diameter. The forceps grasping the tissue was not necessary for these procedures, consequently preventing either tears the esophageal stump tissue or narrowing the esophageal lumen. RESULTS: These 14 cases were far advanced cases of gastric cancer, 6 cases of splenectomy and 3 cases of distal pancreatectomy. No technical problems such as esophageal tear were observed in all cases. Postoperative complications were observed in 6 patients (42.9%), and their contents varied. However, they all improved conservatively. Regarding anastomotic complications, anastomotic leakage of Clavien-Dindo-II was observed in one case, but it improved conservatively. CONCLUSION: Our new atraumatic anastomosis technique could abolish problems such as tear of esophagus wall due to introduce a larger-sized anvil, trauma of esophageal wall by grasping with forceps such as Alice or Babcock. Consequently, the atraumatic and innovative technique might make the esophagojejunostomy safe. This method might prevent anastomotic leakage and other complications effectively.

Haploinsufficiency by minute MutL homolog 1 promoter DNA methylation may represent unique phenotypes of microsatellite instability-gastric carcinogenesis.

Promoter DNA methylation of MutL homolog 1 (MLH1) is considered to play a causative role in microsatellite instability (MSI) carcinogenesis in primary gastric cancer, and a high MSI status is associated with treatment sensitivity to human cancers. Nevertheless, clinicopathological analysis is defective for MLH1 methylation status in a quantitative manner. We newly developed quantitative methylation specific PCR using a TaqMan probe and applied it to 138 patients with primary gastric cancer who underwent gastrectomy in addition to basic molecular features such as MSI, Epstein Barr virus, and other DNA methylation status. (1) In primary gastric cancer, median methylation value was 0.055, ranging from 0 to 124.3. First, MLH1 hypermethylation was strongly correlated with MSI-High/MSI-Low status and suppressed immunostaining (P < 0.0001). (2) The MLH1 hypermethylation was associated with advanced age (P = 0.0048), antral location (P = 0.0486), synchronous multiple gastric cancer (P = 0.0001), and differentiated histology (P = 0.028). (3) Log-rank plot analysis identified the most relevant cut-off value (0.23) to reflect gentle phenotypes in MLH1 hypermethylation cases (P = 0.0019), especially in advanced gastric cancer (P = 0.0132), which are designated as haploinsufficiency of MSI (MSI-haplo) phenotype in this study. (4) In synchronous multiple gastric cancer, MLH1 hypermethylation was not necessarily confirmed as field cancerization. (5) MSI-haplo defined by MLH1 methylation status represented distinct prognostic phenotype even after molecular classifications. MLH1 hypermethylation designated as MSI-haplo may represent unique prognostic phenotype during gastric carcinogenesis.

Laparoscopic and endoscopic cooperative surgery for advanced gastric cancer as palliative surgery in elderly patients: a case report.

BACKGROUND: The number of elderly patients with gastric cancer is increasing, with the very elderly often refusing radical gastrectomy with lymph node dissection. Such a patient presented to us and we proposed a palliative surgery involving gastric local resection using laparoscopy endoscopy cooperative surgery (LECS). CASE PRESENTATION: An 89-year-old woman presented to our hospital with progressing anemia. She had an aortic arch replacement for aortic dissection 6 months previously and was taking antithrombotic drugs for atrial fibrillation. She was diagnosed with advanced gastric cancer, and we presented a radical resection treatment plan involving distal gastrectomy with lymph node dissection. However, she strongly refused undergoing radical gastric cancer resection. We believed that at least local control of the tumor could be effective in preventing future bleeding or stenosis due to tumor progression. Therefore, we proposed a local gastrectomy with LECS as an optional treatment, and she agreed to this treatment. The surgery was performed with minimal blood loss, and no postoperative complications were observed. Histopathological examination revealed a 45 × 31-mm, Type 2, poorly differentiated adenocarcinoma (pT4a, ly0, v1a), and the resected margin was negative. The patient was alive 2 years after surgery without apparent recurrence or other illness. In addition, her weight was maintained, together with her daily activity. CONCLUSION: Local resection of gastric cancer with LECS might be an option for the palliative treatment of patients who refuse radical resection of gastric cancer.

[An Analysis of Surgery for Colorectal Cancer Lung Metastasis].

OBJECTIVES: Resection of lung metastasis in colorectal cancer leads to a good prognosis; therefore, surgical treatment for resectable metastases is recommended by the Japanese Society for Cancer of the Colon and Rectum Guidelines for the treatment of colorectal cancer. In this study, we investigated the factors that affect the prognosis of resection of such lung cancers. RESULTS: Outcomes of 23 cases of lung resection performed from 2000 to 2019 were investigated. The 5-year overall survival rate after lung resection was 55.5%, and the 5-year relapse-free survival rate after liver resection was 27.0%. Univariate analysis identified sex(p=0.024), tumor size(p=0.0129)and complications(p=0.0129)as prognostic factors, while multivariate analysis revealed sex(p=0.0278, relative risk=5.38)to be a prognostic factor. CONCLUSION: In this study, sex was identified as a poor prognostic factor. Further evidence from cases is needed to ascertain the effects of other factors.

[Laparoscopic Partial Hepatectomy for the Liver Metastasis of Gastric Cancer after Nab-Paclitaxel plus Ramucirumab Combination Therapy-A Case Report].

We report a case of laparoscopic partial hepatectomy after nab-paclitaxel plus ramucirumab(nab-PTX plus RAM)combination therapy for postoperative liver recurrence of gastric cancer. The patient was a 50's man who underwent laparoscopic distal gastrectomy, D2 lymph node dissection, and Billroth-I reconstruction for gastric cancer. The pathological findings were L, Gre, Post, Type 3, por>tub2, pT3N3a, M1(CY1), fStage Ⅳ. Postoperative chemotherapy with S-1 was performed. The CT examination 6 months after the operation revealed a total of 3 tumors(maximum diameter of 5×4 cm)in liver segments S6, 7, and 8. We started nab-PTX plus RAM combination therapy for liver metastases and performed laparoscopic partial hepatectomy when 12 courses of the treatment were completed. The postoperative course was uneventful, and the patient was discharged on postoperative day 7. Pathological results suggested that the tumor was exposed on the cut surface, and 6 courses of nab-PTX plus RAM combination therapy were administered postoperatively. The patient has been recurrence-free 12 months after the operation.

Expression of Kita-Kyushu Lung Cancer Antigen-1 as Detected by a Novel Monoclonal Antibody in Gastric Cancer.

BACKGROUND/AIM: Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is a known cancer/testis antigen. Our group has previously shown KK-LC-1 gene expression in gastric cancer. However, could not be detected the KK-LC-1 protein due to the lack of an appropriate antibody. Here, we assessed our original monoclonal antibody (Kmab34B3) and, using it, assessed the expression of KK-LC-1 in gastric cancer. PATIENTS AND METHODS: We evaluated an original monoclonal antibody against KK-LC-1 (Kmab34B3), and used this antibody to compare KK-LC-1 protein expression in tumour and non-tumour stomach cells from gastric cancer patients. RESULTS: Kmab34B3 stained testicular germ cells, and tumour cells in nine out of 11 (82%) specimens. In non-tumorous areas, Kmab34B3 stained 13 out of 29 (45%) pyloric gland specimens. Furthermore, Kmab34B3 also stained intestinal metaplasia positive and negative areas. CONCLUSION: Kmab34B3 was able to detect KK-LC-1 protein within tumour cells and the pyloric gland where the gene has been shown to be expressed. Therefore, it might be an attractive tool for detecting KK-LC-1 expression in precancerous and cancerous stomach cells.

[A Case of Sigmoid Colon Cancer with Complete Visceral Inversion].

Complete visceral inversion occurs in 1/5,000 individuals. In 64%of cases, complete visceral inversion is complicated by the malformation of other organs. Careful attention is required when performing surgeries. In recent years, with the development of laparoscopic surgery, some cases of laparoscopic surgery with complete visceral inversion have been reported. Herein, we report a case of safely performed laparoscopic surgery for sigmoid colon cancer with complete visceral inversion along with a relevant discussion.

[A Case of Recurrent Gastric Cancer with Clinical Complete Response after Ramucirumab plus Paclitaxel Therapy].

We report a case of a 61-year-old man who underwent open total gastrectomy and D2 lymph node dissection for gastric cancer. The pathological findings were suggestive of pT2N3M0, fStage ⅢA. S -1 was administered for 1 year post-surgery. One year and 9 months after the operation, an epigastralgia was found, and the PET-CT showed an increase of SUVmax 3.80 around the celiac artery. S -1 plus CDDP therapy was initiated. However, due to the occurrence of neutropenia, the therapy was changed to ramucirumab plus paclitaxel. After 20 courses of the same regimen, no PET-CT uptake was observed. We thus considered it cCR and discontinued further chemotherapy. The patient has been alive for 15 months without recurrence. By performing effective chemotherapy at an early stage, cCR could be observed after a secondary treatment. Therefore, longterm survival could be expected for post-operative recurrence of gastric cancer.

Laparoscopy-assisted Distal Gastrectomy for Gastric Cancer in Elderly Patients: Surgical Outcomes and Prognosis.

BACKGROUND/AIM: Elderly patients usually have various comorbidities. Laparoscopic gastrectomy as a minimally-invasive treatment might be feasible for these patients. The aim of this study was to evaluate the safety and efficacy of laparoscopy-assisted distal gastrectomy (LADG) in elderly patients with gastric cancer by comparing the surgical outcomes and prognosis. PATIENTS AND METHODS: We analyzed 136 patients who had undergone LADG between January 2013 and December 2014. We compared elderly patients (75 years old or more) with non-elderly patients. RESULTS: The incidence of all postoperative complications did not differ between groups, and there were no significant differences in the time to first oral intake or the duration of postoperative hospital stay. The 3-year overall and recurrence-free survival rates were not significantly different between the groups. CONCLUSION: LADG is a safe and less invasive treatment for gastric cancer in elderly patients, who have a greater incidence of comorbidity.

[The Efficacy of Definitive Chemoradiotherapy for Thoracic Esophageal Cancer on the Point of View Salvage Surgery].

INTRODUCTION: Salvage surgery(S-surgery)was performed for residual or relapse tumor after definitive chemoradiotherapy (dCRT)for resectable esophageal cancer. When it becomes possible to perform surgery after dCRT for unresectable cases is called conversion surgery(C-surgery). OBJECTIVE: To examine the outcomes of S-surgery and C-surgery after dCRT for thoracic esophageal cancer and clarify the significance as a multidisciplinary treatment. MATERIAL AND METHODS: We reviewed 27 patients who underwent S-surgery for thoracic esophageal cancer in our hospital. 23 cases were residual tumor, 4 were relapse after complete response. Sixteen cases(59%)were C-surgery. RESULTS: Five cases(19%)had non-radical resection. Two cases were postoperative hospital death(7%). Postoperative complications(Clavien-Dindo classification Grade II and more) 11 cases(41%). Four cases were anastomotic leakage, 4 cases vocal cord paralysis, etc. Pathological complete response cases 6 cases(22%). The recurrence cases were 7 except for 5 cases of non-radical resection. Three-year overall survival rate was 47%. Twelve cases(75%)in C-surgery could perform radical resection by down stage. CONCLUSIONS: The postoperative hospital mortality and complications can be considered as acceptable. dCRT is a powerful pre-operative treatment for such cases, and S-surgery plays an important role.

Successful treatment of refractory complete separation of an esophagojejunal anastomosis after laparoscopic total gastrectomy: a case report.

BACKGROUND: Anastomotic leakage after total gastrectomy occurs despite improvements in surgical techniques and patient management. Although many cases of dehiscence can be managed non-operatively, major leakage requires a second surgery and can potentially lead to death. Therefore, accurate and immediate diagnosis and treatment are essential. CASE PRESENTATION: In this report, we describe a 66-year-old Japanese man who was diagnosed with a complete separation of an esophagojejunal anastomosis after laparoscopic total gastrectomy with oral contrast radiography using Gastrografin®. The severe complication was successfully treated by re-anastomosis after two emergency drainage surgeries. After the second surgery, the esophageal end formed a fistula with the jejunum, but balloon dilation failed to open the fistula. Therefore, oral ingestion and conservative treatment were considered unsuitable, and we performed esophagojejunal re-anastomosis 7 months after the first surgery. At a follow-up examination 2 years after re-anastomosis, the patient weighed 47 kg, and his ingestion had recovered to 80% of that before surgery. CONCLUSIONS: Complete separation of an esophagojejunal anastomosis is a rare but severe complication of total gastrectomy. Therefore, we consider that once separation is diagnosed, aggressive and urgent re-operation and effective drainage are useful. Moreover, it is necessary to take great care to minimize the operative morbidity associated with esophagojejunal anastomosis.

[A Case of Laparoscopic Remnant Gastrojejunal Bypass Surgery for Postoperative Peritoneal Recurrence of Gastric Cancer].

A 77-year-old female case who underwent laparoscopic distal gastrectomy with D2 dissection, Billroth I reconstruction for gastric cancer. Since the stage was III A, she received an adjuvant chemotherapy with S-1 after surgery. However, about 2 years after surgery, she was referred to our hospital for anorexia and vomiting. As a result of the examination, we diagnosed stenosis due to peritoneal recurrence near the anastomotic site. We performed laparoscopic remnant gastrojejunal bypass (Billroth II method, with Braun anastomosis). A camera port was inserted into a median umbilical incision. Following this, 4 additional ports(1 ports of 12mm in diameter and 3 ports of 5mm in diameter)were inserted under laparoscopic imaging into the right lower, right upper, left upper, and left lower quadrants. We first detached the adhesion considered as the influence of the previous surgery, and the anastomosis of remnant stomach and jejunum and the Braun anastomosis were performed by the linear stapler. The postoperative course was good. She started oral intake from the day after surgery, was discharged on the 6 days after operation, and received chemotherapy promptly. This procedure was effective for recurrent gastric cancer with stenosis which is difficult to resect and it was considered to be a minimally invasive method with a view to initiating chemotherapy early after operation.

[A Case Report of Laparoscopy Assisted Distal Gastrectomy for Gastric Cancer with an Adachi Type VI Anomaly (Group 27)Institution].

We report the case of a 79-year-old man, with gastric cancer detected on upper gastrointestinal endoscopic examination performed by a nearby medical clinic, and referred to our hospital, in April 201X. He was diagnosed with gastric cancer(ML, less, 0- II a+ II c, tub 1-2, cT1bN0M0, cStage I A). We performed laparoscopy assisted distal gastrectomy, D1+lymph node dissection, and Billroth I (B- I )reconstruction. Abdominal CT scan before surgery confirmed vascular anomaly of the celiac artery. We diagnosed Adachi type VI, preserved hepato-gastric artery trunk, and performed D1 plus dissection plus B- I reconstruction with small incision in the epigastrium. The operation time was 244 minutes and the blood loss was 5 mL. There were no postoperative complications, and the patient was discharged from hospital 7 days after the surgery. Pathological findings revealed pT4aN0M0, pStage II B, and the patient has been treated with TS-1®postoperative adjuvant chemotherapy. At present, there is no recurrence. As vascular anomalies of the celiac artery branch exhibit various forms, occasional blood vessel preventing surgery is required. Examining blood vessels through CT scan before the surgery made it possible to perform Laparoscopic gastrectomy safely.

[The Clinical Outcome of Conversion Surgery for Unresectable Gastric Cancers in Our Institution].

BACKGROUND: In recent years, the development of chemotherapy has been remarkable. Some cases of conversion surgery for unresectable gastric cancer have been reported. METHODS: The clinical outcome of 11 patients with far advanced gastric cancer who underwent conversion surgery in our hospital from January 2013 to May 2017 were analyzed retrospectively. RESULTS: The median survival time was 592 days(355-1,460). Four patients died of recurrent gastric cancer. Patients with undifferentiated carcinoma dominant had significantly poor survival rather than with differentiated carcinoma dominant(p= 0.039). Meanwhile, the pathological responders for chemotherapy did not have significantly better survival rather than nonresponders. CONCLUSIONS: Although the short term outcome of conversion surgery was acceptable, recurrent rate was still high. To improve the prognosis, clarifying the optimal timing of operation and more effective adjuvant chemotherapy are mandatory.