Background
The long-term outcomes of type 4 and large type 3 gastric cancer patients with positive peritoneal lavage cytology (CY1) remain unsatisfying. We evaluated our treatment strategy of ...conversion therapy for CY1 patients without peritoneal dissemination (P0).
Methods
Diagnostic staging laparoscopy (DSL) was performed before treatment. Chemotherapy was applied for DSL-diagnosed P0CY1. The re-evaluation of peritoneal metastasis by staging laparoscopy (re-SL) was performed when a response to chemotherapy was identified by gastroscopy and/or CT. Gastrectomy with radical lymphadenectomy was applied as conversion therapy when peritoneal lavage cytology-negative (CY0) and P0 were diagnosed with re-SL, with the aim of achieving R0 resection. Chemotherapy was continued as palliative treatment in patients for whom re-SL was not applicable or when re-SL did not confirm P0CY0. The long-term outcomes were retrospectively evaluated.
Results
Between 2009 and 2015, 214 patients with type 4 and large type 3 gastric cancer underwent DSL in the Cancer Institute Hospital. Thirty-nine patients were initially diagnosed with P0CY1. Seven patients received palliative gastrectomy first due to outlet obstruction or other reasons. Thirty-two patients received chemotherapy first. Among them, 13 patients underwent gastrectomy as conversion therapy and 19 were treated with palliative chemotherapy. The 3-year survival rate of patients who underwent conversion therapy, palliative chemotherapy and palliative gastrectomy was 76.9% 95% confidence interval (CI) 47.8–92.4%, 10.5% (95% CI 1.9–42.3%), and 0%, respectively.
Conclusion
Conversion therapy might be a promising treatment for P0CY1 type 4 and large type 3 gastric cancer patients. Re-SL was useful for selecting candidates for R0 resection.
Cancer-associated antigens are not only a good marker for monitoring cancer progression but are also useful for molecular target therapy. In this study, we aimed to generate a monoclonal antibody ...that preferentially reacts with colorectal cancer cells relative to noncancerous gland cells. We prepared antigens composed of HT-29 colorectal cancer cell lysates that were adsorbed by antibodies to sodium butyrate-induced enterocytically differentiated HT-29 cells. Subsequently, we generated a monoclonal antibody, designated 12G5A, which reacted with HT-29 colon cancer cells, but not with sodium butyrate-induced differentiated HT-29 cells. Immunohistochemical staining revealed 12G5A immunoreactivity in all 73 colon cancer tissue specimens examined at various degrees, but little or no immunoreactivity in noncancerous gland cells. Notably, high 12G5A immunoreactivity, which was determined as more than 50% of colon cancer cells intensively stained with 12G5A antibody, exhibited significantly higher association with a poor overall survival rate of patients with colorectal cancer (
P
= 0.0196) and unfavorable progression-free survival rate of patients with colorectal cancer (
P
= 0.0418). Matrix-assisted laser desorption ionization time-of-flight mass spectrometry, si-RNA silencing analysis, enzymatic deglycosylation, and tunicamycin treatment revealed that 12G5A recognized the glycosylated epitope on annexin A2 protein. Our findings indicate that 12G5A identified a cancer-associated glycosylation epitope on annexin A2, whose expression was related to unfavorable colorectal cancer behavior.
Key message
• 12G5A monoclonal antibody recognized a colorectal cancer-associated epitope.
• 12G5A antibody recognized the N-linked glycosylation epitope on annexin A2.
• 12G5A immunoreactivity was related to unfavorable colorectal cancer behavior.
Aim
Much attention has been paid to conversion therapy for stage IV gastric cancer, however, its operative comorbidities and survival benefit have not yet been clarified. CONVO‐GC‐1, an international ...retrospective cohort study, was designed to investigate the role of conversion surgery in Japan, Korea, and China.
Methods
The rate of operative complications was the primary endpoint and the overall survival (OS), according to the four‐category criteria previously published (Gastric Cancer:19; 2016), was analyzed as the secondary endpoint.
Results
A total of 1206 patients underwent surgery after chemotherapy with curative intent. Operative complications were observed in 290 (24.0%) patients in all grades, including pancreatic fistula and surgical site infection. The median survival time (MST) of all resected patients was 36.7 mo (M) and those of R0, R1, and R2 resection were 56.6 M, 25.8 M, and 21.7 M, respectively. Moreover, the MST of R0 patients were 47.8 M, 116.7 M, 44.8 M in categories 1, 2, and 3, respectively, and not reached in category 4. Interestingly, the MST of P1 patients was as favorable as that of P0CY1 patients if R0 resection was achieved. The MST of patients with liver metastasis was also favorable regardless of the number of lesions, and the MST of patients with para‐aortic lymph node (LN) No 16a1/b2 metastasis was not inferior to that of patients with para‐aortic LN No 16a2/b1 metastasis.
Conclusion
Conversion therapy for stage IV gastric cancer is safe and could be a new therapeutic strategy to improve the survival of patients, especially those with R0 resection.
R0 resection of conversion therapy can be a new strategy for gastric cancer.
LDLR-related protein 1B (LRP1B) is believed to internalize ligands through receptor-mediated endocytosis. Previous epigenetic and genetic studies have indicated that impaired
LRP1B
mRNA expression ...might be related to gastric carcinogenesis. However, expression and prognostic significance of LRP1B protein remain to be elucidated. This study aimed to unravel the clinicopathological characteristics of LRP1B protein expression in gastric cancer. Immunohistochemical staining with antibodies specific to LRP1B peptide, which has an EXXXLL motif-containing region in the C-terminal flexible loop for intracellular sorting, was performed with 100 gastric cancer tissue specimens. Out of 100 tissue specimens, 45 exhibited cytoplasmic localization of LRP1B immunoreactivity. This cytoplasmic localization of LRP1B was significantly higher (
P
= 0.044) in intestinal-type gastric cancer (25 of 44) than in diffuse-type gastric cancer (20 of 56). Notably, cytoplasmic LRP1B immunoreactivity was significantly associated with low clinicopathological stage and favorable prognosis of patients with diffuse-type gastric cancer (
P
= 0.014), but nor with intestinal-type gastric cancer (
P
= 0.994). Multivalent analysis revealed that cytoplasmic LRP1B immunoreactivity had an independent favorable prognostic value in diffuse-type gastric cancer (
P
= 0.046; hazard ratio 3.058, 95% confidence interval 1.022–9.149). In contrast, no significant relation of cytoplasmic LRP1B immunoreactivity to patients’ prognosis was found in intestinal-type gastric cancer. Double immunocytochemical staining demonstrated that cytoplasmic LRP1B was co-localized with RAB11FIP1, which constituted the endocytic recycling compartments in diffuse-type gastric cancer cells. The findings of this study indicated that impaired endocytosis of the cytoplasmic domain of LRP1B, resulting in insufficient ligand internalization, is related to poor prognosis of patients with diffuse-type gastric cancer.
This study was designed to unravel the pathobiological role of impaired ARID1A expression in gastric carcinogenesis. We examined ARID1A expression immunohistochemically in 98 gastric cancer tissue ...specimens with regard to the clinicopathological features. Based on the proportion and intensity of ARID1A immunoreactivity at the cancer invasion front, we subdivided the specimens into low- and high-expression ARID1A groups. Notably, low ARID1A expression was significantly correlated with overall survival of the patients. Subsequently, we determined the molecular signature that distinguished ARID1A low/poor prognosis from ARID1A high/good prognosis gastric cancers. A comprehensive gene profiling analysis followed by immunoblotting revealed that a mitochondrial apoptosis mediator, Harakiri, was less expressed in ARID1A low/poor prognosis than ARID1A high/good prognosis gastric cancers. siRNA-mediated ARID1A downregulation significantly reduced expression of the Harakiri molecule in cultured gastric cancer cells. Interestingly, downregulation of ARID1A conferred resistance to apoptosis induced by the mitochondrial metabolism inhibitor, devimistat. In contrast, enforced Harakiri expression restored sensitivity to devimistat-induced apoptosis in ARID1A downregulated gastric cancer cells. The present findings indicate that impaired ARID1A expression might lead to gastric carcinogenesis, putatively through gaining resistance to the Harakiri-mediated apoptosis pathway.
Background
The application of laparoscopic subtotal gastrectomy (LsTG) in the management of early gastric cancer located in the upper third of the stomach creates an extremely small remnant stomach ...(SRS). However, it is unclear whether retaining such an SRS improves patients’ postoperative outcomes in a similar manner to a conventional remnant stomach (CRS).
Methods
Four hundred and nine of 878 patients undergoing laparoscopic distal gastrectomy (LDG) between 2006 and 2012 underwent Roux-en-Y reconstruction. Among them, we selected 73 patients who underwent LsTG with an SRS (SRS group), and 83 patients with the tumor in the lower third of the stomach who underwent LDG with a CRS (CRS group). The surgical outcomes at 1 and 6 months, 1, 2, and 3 years after gastrectomy were retrospectively analyzed and compared between the two groups.
Results
One year after gastrectomy, the postoperative:preoperative bodyweight ratio of the SRS group was 2% lower than that of the CRS group. Both groups had comparable total protein and albumin levels, and incidence of reflux esophagitis; however, hemoglobin was lower in the SRS group. This difference in hemoglobin level between the SRS and CRS groups became larger over time, although the total protein and albumin levels of the two groups remained similar.
Conclusion
An SRS slightly decreases bodyweight and hemoglobin level compared with a CRS. Several objective outcomes of the SRS group are almost equal to those of the CRS group, which suggests LsTG is worth performing even though its remnant stomach is very small.
Gastric cancer presenting gastric outlet obstruction (GC-GOO) is associated with two problems to be considered in its treatment: peritoneal metastasis and an inability to intake food. Because ...peritoneal metastasis is difficult to identify in standard examinations, laparoscopic gastrojejunostomy (LGJ), which consecutively follows diagnostic staging laparoscopy (DSL), may be a minimally invasive solution to these diagnostic and therapeutic problems. However, whether GC-GOO is a new candidate for DSL has been not evaluated.
GC-GOO patients who were surgically treated at our department between 2005 and 2014 were recruited. Patient backgrounds, preoperative and surgical findings for distant metastasis, and surgical curability were retrospectively evaluated. To predict peritoneal metastasis, the sensitivity, specificity, and positive and negative predictive values of preoperative factors were calculated. The survival outcomes were also evaluated according to surgical curability and non-curative factors.
A total of 237 patients with GC-GOO were included in this study. Among them, 167 patients had no distant metastasis identified preoperatively. Seventy-one of 167 patients underwent curative surgery while 75 (44.9%) had peritoneal metastasis including positive lavage cytology. Ascites and large type 3 or type 4 tumors indicated high specificity (86.9% and 76.1%, respectively) and the involvement of gastric angle presented high sensitivity (90.7%) for peritoneal metastasis. The overall survival of patients with incurable surgery was worse than that of patients with curative surgery, regardless of their incurable factors.
GC-GOO is a new candidate for DSL. DSL followed by LGJ may be proposed, utilizing preoperative predictive factors for peritoneal metastasis.
Mitochondria-eating protein (Mieap) plays a critical role in mitochondrial quality control (MQC) and functions as a p53-inducible tumor suppressor. This study aimed to examine its role in gastric ...cancer (GC) and esophageal cancer (EC). GC cells were infected with Mieap-overexpressing adenovirus (Ad-Mieap) and subjected to fluorescence-activated cell sorting (FACS), western blotting, and caspase assays. Thereafter, we evaluated the potential disruption of the p53/Mieap-regulated MQC pathway in vivo. Methylation-specific PCR (MSP) for Mieap, NIX, and BNIP3 promoters was performed and p53 mutations were detected using cryopreserved surgical specimens. Exogenous Mieap in GC cells induced the formation of vacuole-like structures (called MIVs, Mieap-induced vacuoles) and caspase-dependent cell death, with the activation of both caspase-3 and caspase-9. Of the 47 GC patients, promoter methylation in Mieap, BNIP3, and NIX was identified in two (4.3%), 29 (61.7%), and zero (0%) specimens, respectively. In total, 33 GC patients (70.2%) inactivated this MQC pathway. Amazingly, BNIP3 promoter in the normal epithelium was highly methylated in 18 of the 47 GC patients (38.3%). In EC patients, this MQC pathway was also inactivated in ten of 12 patients (83.3%). These results indicate that p53/Mieap-regulated MQC plays an important role in upper gastrointestinal (GI) tumor suppression, possibly, in part, through the mitochondrial apoptotic pathway.
•p53 suppresses the tumor progression via mitochondria-eating protein (Mieap).•p53/Mieap-regulated mitochondrial quality control (MQC) is impaired in GI cancers.•BNIP3, a cofactor of p53/Mieap in regulating MQC, is critical in GI cancers.
Background
The occurrence of postoperative complications may have a significant negative impact on the prognosis of patients with gastrointestinal cancers. The inflammatory response releases systemic ...cytokines, which may induce residual cancer cell growth. Recently, neoadjuvant chemotherapy (NAC) was found to improve the prognosis of advanced gastric cancer (GC). We hypothesize that when postoperative complications occur after gastrectomy, NAC treatment of micrometastases can prevent residual cancer cell growth.
Methods
This study included 101 patients who underwent curative resection after NAC for GC from 2005 to 2015. Clinical data, including intraoperative parameters, were collected retrospectively. Overall survival (OS) and relapse-free survival (RFS) were compared between the patients with complications and those without complications.
Results
Of the 101 patients, 35 (34.7%) had grade 2 or higher complications. Among those with complications, the 3- and 5-year OS rates were 63.5 and 58.2% and the 3- and 5-year RFS rates 41.7 and 41.7%, respectively. Among those without complications, the 3- and 5-year OS rates were 65.9 and 56.3% and the 3- and 5-year RFS rates 51.1 and 43.9%, respectively. There was no significant difference in prognosis between the patients with complications and those without complications.
Conclusion
Our study is the first to demonstrate the potential of NAC to abolish the poor prognosis induced by postoperative complications after curative resection for GC.
Esophageal squamous cell carcinoma is characterized by field cancerization, wherein multiple cancers occur in the esophagus, head and neck, and stomach. Synchronous esophageal and colorectal cancers ...are also encountered with a certain frequency. A good prognosis can be expected if the tumors in both locations can be safely and completely removed. For patients with multiple cancers that occur simultaneously with esophageal cancer, it is necessary to perform a staged operation, taking into consideration the associated surgical invasiveness. It is also necessary to select multidisciplinary treatment depending on the degree of progression of the multiple lesions. We report our rare experience with a staged operation for a patient with synchronous advanced cancers of the esophagus and cecum who had previously undergone total gastrectomy with reconstruction by jejunal interposition for gastric cancer.
A 71-year-old man with a history of reconstruction by jejunal interposition after total gastrectomy was diagnosed as having multiple synchronous esophageal and cecal cancers. After neoadjuvant chemotherapy, we performed a planned two-stage operation, with esophagectomy and jejunostomy in the first stage and ileocecal resection and jejunal reconstruction with vascular anastomosis in the second. Postoperatively, the patient was relieved without major complications, and both tumors were amenable to curative pathologic resection.
Our procedure reported here may be recommended as an option for staged resection and reconstruction in patients with simultaneous advanced esophageal and cecal cancer after total gastrectomy.
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