Chromosomal instability (CIN), characterized by aneuploidy, is a major molecular subtype of gastric cancer. The deubiquitinase USP44 is an important regulator of APC activation in the spindle ...checkpoint and leads to proper chromosome separation to prevent aneuploidy. Aberrant expression of USP44 leads CIN in cells; however, the correlation between USP44 and DNA aneuploidy in gastric cancer is largely unknown. We analyzed USP44 expression in 207 patients with gastric cancer by immunohistochemistry and found that the proportion of USP44 expression was higher in gastric cancer tumors (mean, 39.6%) than in gastric normal mucosa (mean, 14.6%) (P < 0.0001). DNA aneuploidy was observed in 124 gastric cancer cases and high USP44 expression in cancer strongly correlated with DNA aneuploidy (P = 0.0005). The overall survival was significantly poorer in the high USP44 expression group compared with the low USP44 group (P = 0.033). Notably, USP44 expression had no prognostic impact in the diploid subgroup; however, high USP44 expression was a strong poor prognostic factor for progression‐free survival (P = 0.018) and overall survival (P = 0.036) in the aneuploid subgroup. We also confirmed that stable overexpression of USP44 induced somatic copy‐number aberrations in hTERT‐RPE‐1 cells (50.6%) in comparison with controls (6.6%) (P < 0.0001). Collectively, our data show USP44 has clinical impact on the induction of DNA aneuploidy and poor prognosis in the CIN gastric cancer subtype.
High USP44 expression is an independent poor prognostic factor in aneuploid gastric cancer. In this paper, we report that USP44 overexpression induces chromosomal instability and poor prognosis in gastric cancer.
Remnant gastric cancer (RGC) after distal gastrectomy occurs in 1-2% of patients, while the biological features of RGC are unknown.
A total of 22 consecutive patients with RGC who underwent total ...gastrectomy were analyzed. Their disease history included either gastric cancer (n=16) or peptic ulcer (n=6). Overall, 18 underwent open total gastrectomy (OTG) and 4 underwent laparoscopic total gastrectomy (LTG).
The mean number of lymph nodes dissected and metastatic lymph nodes was larger in the Ulcer group than in the Carcinoma group (p<0.005). The mean operation time was longer in the LTG than OTG (p<0.005). The median blood loss tended to be smaller in the LTG (p=0.090). Five-year overall and recurrence-free survival rates were 94% and 81%, respectively.
The status of lymph node metastasis after surgery for RGC should be cautiously considered in the context of disease history. Both LTG and OTG can be treatment options for RGC.
Anal metastasis of colorectal cancer is very rare and is usually associated with a history of anal disease, including anal fistula, fissure, hemorrhoidectomy, and anastomotic injury. We report a case ...of rectal cancer with a synchronous anal metastasis consisting of adenocarcinoma of squamous cells without a history of anal disease. A 60-year-old woman had a chief complaint of melena. She had a 1.5-cm anal tumor on the perianal skin, and a Bollman type 2 rectal tumor on the Ra portion was found on colonoscopy. Biopsy of both tumors revealed a similar histology of well- to moderately differentiated adenocarcinoma. There was no sign of metastases in lymph nodes or other organs. For the purpose of diagnosis and treatment, transperineal local resection of the anal tumor was performed, and it was histologically identified as adenocarcinoma of squamous cells with no invasion to muscles, lymph ducts, or microvessels. The pathological margin was free. Then, to achieve radical cure, laparoscopic low anterior resection (LAR) with D3 lymphadenectomy was performed. The histological diagnosis of the anal tumor was adenocarcinoma of squamous cells without invasion to muscles, lymph ducts, or vessels. The surgical margin was completely free. Immunohistochemical analysis of both tumors revealed similar staining patterns, and the final diagnosis was rectal cancer with metastasis to the anal skin. The patient received no postoperative therapy, and no recurrences have been observed 12 months after surgery. We expect that our sphincter-preserving surgical strategy provided a good prognosis for the synchronous rectal cancer and anal metastasis. This is a rare report of a case with an anal metastasis of colorectal cancer on perianal squamous cells without a history of anal disease that was resected while preserving anal function.
Fewer than 1 % of gastrointestinal stromal tumors (GISTs) are of the esophagus. This report describes a 63-year-old female diagnosed with mixed spindle/epithelioid cell GIST of the esophagus. She was ...admitted to our hospital with symptoms of nausea and hematemesis. Preoperative imaging showed a huge submucosal tumor in the lower thoracic and abdominal esophagus. Pathologic examination of an endoscopic biopsy sample suggested squamous cell carcinoma. She underwent subtotal esophagectomy and reconstruction with a gastric tube. Postoperative pathological diagnosis revealed a mixed spindle/epithelioid cell type GIST. The tumor measured 8 × 6 cm, with 30–50 mitotic counts per high power field, immunohistochemical positivity for C-kit (CD117) and CD34 and high risk by modified Fletcher classification. Adjuvant chemotherapy with imatinib mesylate was started 3 months after surgery. Preoperative pathological examination, including staining for CD117 and CD34, of biopsy samples of apparently stromal tumors may be required to rule out rare subtypes of GIST.
Background
Perianal Paget’s disease (pPD) is uncommon, with only about 180 cases documented in the literature. Anorectal carcinoma with pagetoid spread is even rarer.
Case presentation
An 81-year-old ...woman underwent rectal cancer extirpation with a transanal approach 17 years prior. She has since undergone two reoperations for local rectal cancer recurrence. Then, warts frequently appeared on the vulva on several occasions. Warts appeared on the vulva 1 year ago, which were diagnosed as pPD by biopsy. She underwent perineal tumor resection, and the final histological diagnosis was rectal cancer recurrence with pagetoid spread. The resected stump was positive for cancer cells, and tumor progression was rapid. She underwent additional abdominoperineal resection (Miles’ operation) with lymph node dissection. However, disease progression was rapid and she died 7 months after the Miles’ operation.
Conclusions
There are some case reports describing anorectal carcinoma with pagetoid spread, however, almost of all those cases were synchronous primary anorectal cancer. Here, we report the first case of metachronous recurrence rectal cancer with pagetoid spread arising 17 years after surgery.
OBJECTIVE:The objective of this study was to elucidate the impact of postoperative complications on long-term survival after curative resection for esophageal squamous cell carcinoma.
BACKGROUND:The ...relation between postoperative complications and long-term survival after curative surgery for esophageal squamous cell carcinoma is controversial; thus, this issue should be resolved with a large-scale, well-designed study.
METHODS:Clinicopathological features and survival of 580 consecutive patients who received curative resection for esophageal squamous cell carcinoma were investigated according to the development of postoperative pulmonary complications and anastomotic leakage.
RESULTS:The 5-year survival rates of patients with pStage 0, I, and II disease with postoperative complications (n = 116) were significantly poorer than those of patients without postoperative complications (n = 288) (overall 69.6% vs 46.9%, P < 0.0001; disease-specific; 76.7% vs 58.9%, P = 0.0022), whereas no differences were found in patients with pStage III and IV disease (n = 176). In the univariate and multivariate analyses for disease-specific survival, pT3, pT4, pN positivity, and development of postoperative complications were significant prognostic factors in all patients. Also, when the analysis was limited to the pStage 0, I, and II patients, development of postoperative complications, and pT3, pT4, and pN positivity, were found to be independent poor prognostic factors in multivariate analyses (hazard ratio1.56, 95% confidence interval, 1.01–2.41, P = 0.0476).
CONCLUSIONS:The development of postoperative complications is an independent disease-specific poor prognostic factor after curative resection for patients with less-advanced esophageal squamous cell carcinoma.
Immunotherapy is reportedly effective in colorectal cancers (CRCs) with high microsatellite instability (MSI‐H); however, the specific cell types that respond to immune checkpoint therapy are ...unclear. Herein, we aimed to examine the expression of programmed cell death‐ligand 1 (PD‐L1) and related proteins in MSI‐H and microsatellite‐stable (MSS) CRCs to investigate the immune microenvironment at the tumor's invasive front. The MSI status was retrospectively assessed in 499 patients undergoing surgical resection of primary CRC; of these, 48 were classified as MSI‐H. Propensity score matching was performed, and tissues from 36 and 37 patients with MSI‐H and MSS CRCs, respectively, were immunohistochemically evaluated for PD‐L1, PD‐1, CD8 and CD68. PD‐L1 expression was evaluated separately for tumor cells (PD‐L1 T) and tumor‐infiltrating myeloid cells in the stroma (PD‐L1 I). PD‐L1 (T) was positive in only 5.4% and 36.1% of MSS and MSI‐H CRCs, while PD‐L1 (I) was positive in 27% and 72.2% of these CRCs, respectively. The PD‐L1 (T) and PD‐L1 (I) expression levels in MSI‐H CRCs significantly correlated with poor differentiation, lymphatic invasion and vascular invasion (p < 0.05), and with early‐stage adenocarcinoma and high budding grade (p < 0.05), respectively. Significantly more PD‐L1 (I), CD8‐positive cells and CD68‐positive macrophages were present at the invasive front than in the central tumor in MSI‐H CRCs (p < 0.005). PD‐L1 was expressed on both tumor cells and CD68/CD163‐positive (M2) macrophages at the invasive front of MSI‐H CRCs. In conclusion, PD‐L1‐positive tumor cells and M2‐type tumor‐associated macrophages may contribute to tumor invasion and immune escape at the invasive front.
What's new?
Immunotherapy is reportedly effective in colorectal cancers (CRCs) with high microsatellite instability (MSI‐H); however, the specific cell types that respond to immune checkpoint therapy remain unclear. Our study examined the expression of programmed cell death‐ligand 1 (PD‐L1) and related proteins in MSI‐H and microsatellite‐stable CRCs to investigate the immune microenvironment at the tumor's invasive front. The data suggest that CRC cases with both PD‐L1‐positive tumor cells and M2‐type tumor‐associated macrophages are associated with tumor invasion and immune escape at the invasive front. Thus, PD‐L1‐positive M2‐type macrophages at the invasive front may be a potential therapeutic target for immune checkpoint inhibitors.
The objective of this study was to elucidate the impact of postoperative complications on long-term survival after curative resection for esophageal squamous cell carcinoma.
The relation between ...postoperative complications and long-term survival after curative surgery for esophageal squamous cell carcinoma is controversial; thus, this issue should be resolved with a large-scale, well-designed study.
Clinicopathological features and survival of 580 consecutive patients who received curative resection for esophageal squamous cell carcinoma were investigated according to the development of postoperative pulmonary complications and anastomotic leakage.
The 5-year survival rates of patients with pStage 0, I, and II disease with postoperative complications (n = 116) were significantly poorer than those of patients without postoperative complications (n = 288) (overall 69.6% vs 46.9%, P < 0.0001; disease-specific; 76.7% vs 58.9%, P < 0.0022), whereas no differences were found in patients with pStage III and IV disease (n = 176). In the univariate and multivariate analyses for disease-specific survival, pT3, pT4, pN positivity, and development of postoperative complications were significant prognostic factors in all patients. Also, when the analysis was limited to the pStage 0, I, and II patients, development of postoperative complications, and pT3, pT4, and pN positivity, were found to be independent poor prognostic factors in multivariate analyses (hazard ratio: 1.56, 95% confidence interval, 1.01-2.41, P = 0.0476).
The development of postoperative complications is an independent disease-specific poor prognostic factor after curative resection for patients with less-advanced esophageal squamous cell carcinoma.
Background
The association between sarcopenia and postoperative outcomes for patients with gastrointestinal malignancies remains controversial. This study aimed to assess the impact of sarcopenia on ...short- and long-term outcomes after surgery for esophagogastric junction cancer (EGJC) or upper gastric cancer (UGC).
Methods
The study reviewed 148 patients with EGJC or UGC who underwent surgical resection. The patients were categorized into the sarcopenia group or the non-sarcopenia group according to their skeletal muscle index calculated using abdominal computed tomography images. The study compared clinicopathologic factors, postoperative complications, and prognosis between the two groups.
Results
Sarcopenia was present in 19 patients (32.2%) with EGJC and 23 patients (25.8%) with UGC. The 5-year overall survival (OS) and recurrence-free survival (RFS) rates were significantly poorer in the sarcopenia group than in the non-sarcopenia group (OS 85.5 vs 54.8%,
P
= 0.0010; RFS 78.7 vs 51.7%,
P
= 0.0054). The development of postoperative complications did not differ significantly between the two groups. Both the uni- and multivariate analyses showed that N stage (
P
< 0.0001) and sarcopenia (
P
= 0.0024 and 0.0293, respectively) were independent poor prognostic factors for OS.
Conclusions
Sarcopenia was strongly associated with a poor long-term prognosis for patients with EGJC or UGC who underwent surgery. The results suggest that special attention might be needed during the development of treatment strategies for patients with sarcopenia who intend to undergo operations for EGJC and UGC.
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