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Anastomotic leakage (AL) is a serious complication after esophagectomy for esophageal cancer. The objective of this study was to identify the risk factors for AL.Patients with esophageal cancer who underwent curative esophagectomy and cervical esophagogastric anastomosis between 2009 and 2019 (N = 346) and those between 2020 and 2022 (N = 17) were enrolled in the study to identify the risk factors for AL and the study to assess the association between the risk factors and blood flow in the gastric conduit evaluated by indocyanine green (ICG) fluorescence imaging, respectively.AL occurred in 17 out of 346 patients (4.9%). Peptic or endoscopic submucosal dissection (ESD) ulcer scars were independently associated with AL (OR 6.872, 95% CI 2.112-22.365) in addition to diabetes mellitus. The ulcer scars in the anterior/posterior gastric wall were more frequently observed in patients with AL than in those without AL (75.0% vs. 17.4%, P = 0.042). The median flow velocity of ICG fluorescence in the gastric conduits with the scars was significantly lower than in those without the scars (1.17 cm/s vs. 2.23 cm/s, P = 0.004).Peptic or ESD ulcer scarring is a risk factor for AL after esophagectomy in addition to diabetes mellitus. The scars in the anterior/posterior gastric wall are significantly associated with AL, impairing blood flow of the gastric conduit. Preventive interventions and careful postoperative management should be provided to minimize the risk and severity of AL in patients with these risk factors.

BACKGROUND: Activin A receptor type 2A (ACVR2A) is one of the most frequently mutated genes in microsatellite instability-high (MSI-H) gastric cancer. However, the clinical relevance of the ACVR2A mutation in MSI-H gastric cancer patients remains unclear. The aims of this study were to explore the effect of ACVR2A mutation on the tumor behavior and to identify the clinicopathological characteristics of gastric cancer patients with ACVR2A mutations. METHODS: An in vitro study was performed to investigate the biological role of ACVR2A via CRISPR/Cas9-mediated ACVR2A knockout MKN74 human gastric cancer cells. 124 patients with gastric cancer were retrospectively analyzed and relations between MSI status, ACVR2A mutations, and clinicopathological factors were evaluated. RESULTS: ACVR2A knockout cells showed less aggressive tumor biology than mock-transfected cells, displaying reduced proliferation, migration and invasion (P < 0.05). MSI mutations were found in 10% (13/124) of gastric cancer patients, and ACVR2A mutations were found in 8.1% (10/124) of patients. All ACVR2A mutations were accompanied by MSI. The 5-year overall survival rates of ACVR2A wild-type patients and ACVR2A-mutated patients were 57% and 90%, respectively (P = 0.048). Multivariate analysis revealed that older age (P = 0.015), distant metastasis (P < 0.001), and ACVR2A wild-type status (P = 0.040) were independent prognostic factors for overall survival. CONCLUSIONS: Our study demonstrated that gastric cancer patients with ACVR2A mutation has a significantly better prognosis than those without. Dysfunction of ACVR2A in MKN74 human gastric cancer cells caused less aggressive tumor biology, indicating the importance of ACVR2A in the progression of MSI-H tumors.

The 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system provided a specific ‘ypTNM’ stage grouping for patients with esophageal cancer. This study aimed to evaluate the clinical utility of the AJCC 8th edition ypTNM stage grouping for patients with esophageal squamous cell carcinoma (ESCC). We enrolled 152 patients with ESCC who underwent surgery after neoadjuvant cisplatin plus 5-fluorouracil (CF) therapy between June 2005 and December 2011. ypStage was evaluated according to the AJCC 7th and 8th editions. Predictive performance for disease-specific survival (DSS) and overall survival (OS) was compared between both editions. The prognostic significance of ypTNM stage grouping was evaluated using univariate and multivariate analyses. Revision of the AJCC 7th edition to the 8th edition was associated with a change in ypStage in 96 patients (63.2%). The AJCC 8th edition revealed a better predictive performance than the 7th edition in terms of DSS (Akaike’s information criterion [AIC] 499 vs. 513; Bayesian information criterion [BIC] 505 versus 519; concordance index [C-index] 0.725 versus 0.679) and OS (AIC 662 vs. 674; BIC 669 vs. 681; C-index 0.662 vs. 0.622). On univariate and multivariate analyses, ypStage in the 8th edition was an independent prognostic factor for both DSS and OS. ypTNM stage grouping in the AJCC 8th edition provided a better predictive performance for DSS and OS than that in the 7th edition. ypStage in the 8th edition was the most reliable prognostic factor for ESCC patients who underwent surgery after neoadjuvant CF therapy.

Various surgical interventions are known to result in postoperative swallowing dysfunction. This preliminary study aimed to comprehensively assess the swallowing function before and after abdominal surgery including thoracoabdominal esophagectomy and to explore the factors associated with swallowing dysfunction. Forty-five participants underwent swallowing function tests including a repetitive saliva swallowing test and modified water swallowing test, and their maximum phonation time and tongue pressure were measured before and after the operation. The pre- and postoperative results of these tests were compared, and correlations between the changes in the results of each test and clinicopathological characteristics were assessed. The maximum phonation time and tongue pressure were significantly decreased after the operation (P

Nearly 50% of primary lung carcinoma patients present with distant metastasis at their first visit. However, gastrointestinal tract (GIT) metastasis is an infrequent impediment. Herein, we report a case of progressive dysphagia and epigastralgia as an initial manifestation of recurrence as gastric metastasis of primary lung squamous cell carcinoma (SCC) after curative surgery. A 64‐year‐old man was diagnosed with primary lung SCC of the right lower lobe, and underwent thoracoscopic lower lobectomy. One year after lobectomy, computed tomography (CT) scan showed a gastric fundal mass located in the gastric cardia which measured 5 cm. Endoscopic biopsies and histopathology subsequently confirmed that tumor was SCC. The patient then underwent proximal gastrectomy with resection of the diaphragmatic crus. Following surgery, histopathological examination revealed gastric metastasis from primary lung SCC. Key points Gastric metastasis of primary lung carcinoma is one of the rarest phenomena. Gastrointestinal symptoms should raise suspicion of the presence of advanced metastatic disease with poor prognosis.

A 70-year-old female with liver metastases from gastrointestinal stromal tumor(GIST)that were found 3 months after partial gastrectomy for the primary GIST underwent Auchincloss operation for left breast cancer with ipsilateral axillary lymph node metastases. The diagnosis was microinvasive ductal cancer that was pT1miN1M0, pStage ⅡA, hormone receptor negative, and HER2 positive. Given the impact of this cancer on the prognosis of liver metastases of GIST, imatinib therapy, but not adjuvant chemotherapy, was started promptly for breast cancer after surgery. Four months after the surgery, left subclavian lymph node recurrence of breast cancer was found. Since the liver metastases of GIST had been stable, imatinib was discontinued, and paclitaxel and anti-HER2 therapy were administered. After confirming tolerability, imatinib was carefully added in combination. Because the lymph nodes shrank and liver metastases of GIST were stable, both anti-HER2 therapy and imatinib were continued. There are few reports of combined chemotherapy for synchronous double cancer, and we report our experience in which careful treatment was required.

The patient was a 64-year-old man with diagnosis of pancreatic head cancer. Initially, abdominal CT showed pancreatic head tumor with bile duct invasion and no distant metastases including para-aortic lymph nodes(PALN). Although, subtotal stomach-preserving pancreatoduodenectomy(SSPPD)and PALN sampling was performed, intraoperative frozen section examination revealed PALN metastasis. He had chronic kidney disease and was unsuitable for standard chemotherapy, SSPPD and PALN dissection was performed instead of standard chemotherapy. Histopathological examination of the resected specimens revealed invasive ductal carcinoma in the pancreatic head region and 11 nodes out of the 17 dissected PALN. Adjuvant chemotherapy with S-1 was performed. 22 months after surgery, intraabdominal lymph nodes metastasis and lung metastasis was found. 24 months after surgery, palliative radiation therapy at a dose of 40 Gy was performed. Systemic chemotherapy with gemcitabine alone was performed, but he was dead 67 months after the initial therapy.

Clinical N category (cN) is generally assessed by measuring the nodal diameter by CT before the initiation of primary treatment in esophageal squamous cell carcinoma (ESCC). The short-axis diameter is recommended for evaluating treatment response in solid tumors by RECIST. This study aimed to elucidate the prognostic implication of the maximum short-axis diameter of lymph node (cN-size) before preoperative chemotherapy for ESCC. Methods We enrolled a total of 152 patients who underwent preoperative cisplatin/5-fluorouracil therapy (CF) followed by esophagectomy from 2005 to 2011. There were 127 men and 25 women with a median age of 65 years (range: 47–79 years). Clinically metastatic node was defined as follows; the node with cN-size ≥10 mm or that with 5 mm ≤ cN-size Results The number of patients with cN0 and cN1–3 was 60 and 92, respectively. Twenty-seven and 65 patients with cN1–3 were classified into cN-size Conclusion The maximum short-axis diameter of lymph node before preoperative chemotherapy is significantly associated with OS in patients with ESCC. Lymph node with 5 mm ≤ cN-size

Background Esophageal involvement length (EIL) is a promising indicator of metastasis or recurrence in mediastinal lymph nodes (MLNs) in adenocarcinoma of the esophagogastric junction (EGJ). This study aimed to elucidate the accuracy of the preoperative endoscopic evaluations of EIL and its clinical significance in this disease. Materials and methods In total, 75 patients with Siewert type II (N = 53) or III (N = 22) adenocarcinoma of the EGJ, who underwent surgical resection without preoperative therapy between 1995 and 2016 were enrolled. We retrospectively examined the accuracy of the preoperative endoscopic evaluations of EIL (preoperative EIL), compared to the pathologically evaluated EIL. Finally, we investigated the association between preoperative EIL and metastasis or recurrence in MLNs. Results The accuracy of the preoperative EIL within a 1-cm interval was only 53.3%. Among patients with discordance between the pre- and postoperative evaluations, 68.6 % had the underestimation in the preoperative EIL. pN1–3 (OR = 5.85, 95% CI: 1.03–33.17) and undifferentiated histologic type (OR = 2.52, 95% CI: 0.89–7.14) were potential risk factors for the discordance. Regarding metastasis or recurrence in MLNs, preoperative EIL of 2–3 cm (OR = 10.41, 95% CI: 1.35–80.11) and >3 cm (OR = 8.33, 95% CI: 1.09–63.96) were independent predictors. Conclusion Although the accuracy of the endoscopic evaluations of EIL is insufficient with many underestimations, EIL should be assessed in preoperative staging because of significant predictive power for metastasis or recurrence in MLNs.

Lymphatic spread is the main mode of progression of esophageal squamous cell carcinoma (ESCC). Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid mediator, which produced by sphingosine kinase 1 (SphK1) activated by phosphorylation. The SphK1-S1P axis has a crucial role in lymphangiogenesis. However, the significance of phospho-SphK1 (pSphK1) in the progression of ESCC has not been fully investigated.We evaluated pSphK1 expression in 92 surgically resected tumor tissues of ESCC by the immunohistochemistry. Fifty-nine (64%) patients with moderate or strong expression and 33 (36%) with negative or weak expression were classified in the pSphK1-high and pSphK1-low groups, respectively.Higher pathological N category (pN) was more frequently observed in the pSphK1-high group (P 0.01). The median number of lymph node metastasis (pSphK1-high: 2 versus pSphK1-low: 0; P 0.01), the proportion of patients with lymphatic invasion (69% versus 18%; P 0.01) and that with intramural metastasis (27% versus 3%; P 0.01) were significantly higher in the pSphK1-high group. The presence of lymphatic invasion (odds ratio [OR] 5.63; P 0.01) and pN1-3 (OR 3.26; P = 0.04) were independently associated with high pSphK1 expression. The 5-y overall survival rate of the pSphK1-high group was significantly lower than that of the pSphK1-low group (50.8% versus 67.3%; P = 0.01). High pSphK1 expression was not identified as a significant independent prognostic factor.We provide the first evidence of the association between high expression of pSphK1 and both lymphatic spread and patient outcomes in ESCC.

A 73-year-old man presented with anemia, and gastroscopy showed a nonpigmented tumor in the esophagogastric junction. The result of the tumor biopsy initially suspected poorly differentiated adenocarcinoma. However, additional immunohistochemical examination revealed malignant melanoma. The final diagnosis was amelanotic malignant melanoma of the esophagogastric junction with adrenal and spinal metastasis. Although immunotherapy was performed, the patient died 132 days after diagnosis.

A 72-year-old man was referred to our hospital for treatment for rectal cancer. Digital rectal examination and colonoscopy revealed a 4 cm tumor located at the anterior rectal wall 5 cm away from the anal verge, and pathological examination confirmed that the tumor was adenocarcinoma. A computed tomography scan detected neither regional lymph node metastasis nor distant metastasis. Hence, he was diagnosed with cT3N0M0, cStage Ⅱa rectal cancer. The preoperative general examination revealed bradyarrhythmia and severe emphysema, and he was considered to be high risk for general anesthesia. After placement of a pacemaker, preoperative capecitabine-based chemoradiotherapy(CRT)(50.4 Gy in 28 fractions of 1.8 Gy each)was implemented. The digital rectal examination and imaging evaluation 4 weeks after preoperative CRT revealed that the tumor disappeared, and pathological examination showed no malignant findings. Considering the risks of general anesthesia, the"watch and wait therapy"approach was adopted with sufficient informed consent. At present, 15 months after preoperative CRT, no evidence of regrowth or distant metastasis has been detected under rigorous follow- up evaluations.

A 64-year-old man with liver dysfunction was given a diagnosis of perihilar cholangiocarcinoma(Bismuth type Ⅳ). The tumor was predominantly right-sided and invaded to the bifurcation of the right and left portal veins. After confirming sufficient liver functional reserve and future liver remnant, the patient underwent extended right hepatectomy, extrahepatic bile duct resection, and portal vein resection and reconstruction. Intraoperative examination of frozen sections revealed the presence of residual invasive carcinoma on both the hepatic and duodenal sides of the ductal resection margins. However, we did not perform pancreaticoduodenectomy or additional resection of the margin-positive proximal bile duct considering the curability and invasiveness of these procedures. He received postoperative chemotherapy with biweekly gemcitabine plus cisplatin for 1 year, followed by gemcitabine monotherapy for 1 year, and S-1 monotherapy has been performed since then. He remains alive and well with no evidence of disease 63 months after surgery.

This study aimed to elucidate the impact of anatomic location of residual disease (RD) after initial cholecystectomy on survival following re-resection of incidental gallbladder cancer (IGBC). Patients with pT2 or pT3 gallbladder cancer (36 with IGBC and 171 with non-IGBC) who underwent resection were analyzed. Patients with IGBC were classified as follows according to the anatomic location of RD after initial cholecystectomy: no RD (group 1); RD in the gallbladder bed, stump of the cystic duct, and/or regional lymph nodes (group 2); and RD in the extrahepatic bile duct and/or distant sites (group 3). Timing of resection (IGBC vs. non-IGBC) did not affect survival in either multivariate or propensity score matching analysis. RD was found in 16 (44.4%) of the 36 patients with IGBC; R0 resection following re-resection was achieved in 32 patients (88.9%). Overall survival (OS) following re-resection was worse in group 3 (n = 7; 5-year OS, 14.3%) than in group 2 (n = 9; 5-year OS, 55.6%) (p = 0.035) or in group 1 (n = 20; 5-year OS, 88.7%) (p < 0.001). There was no survival difference between groups 1 and 2 (p = 0.256). Anatomic location of RD was independently associated with OS (group 2, HR 2.425, p = 0.223; group 3, HR 9.627, p = 0.024). The anatomic location of RD independently predicts survival following re-resection, which is effective for locoregional disease control in IGBC, similar to resection for non-IGBC. Not all patients with RD have poor survival following re-resection for IGBC.

Background Solitary fibrous tumor (SFT), a mesenchymal fibroblastic tumor with a hypervascular nature, rarely develops in the pelvis. Resection of a giant SFT occupying the pelvic cavity poses an increased risk of developing massive hemorrhage during resection, although surgical resection is the most effective treatment method for this tumor to achieve a potential cure. SFT rarely develops with Doege–Potter syndrome, which is known as a paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia (NICTH) secondary to SFT that secretes insulin-like growth factor-II (IGF-II). We present a case of a giant pelvic SFT with Doege–Potter syndrome, which was successfully treated with transcatheter arterial embolization (TAE) followed by surgical resection. Case presentation A 46-year-old woman presented with a disorder of consciousness due to refractory hypoglycemia. Images of the pelvis showed a giant and heterogeneously hypervascular mass displacing and compressing the rectum. Endocrinological evaluation revealed low serum levels of insulin and C-peptide consistent with NICTH. Angiography identified both the inferior mesenteric artery and the bilateral internal iliac artery as the main feeders of the tumor. To avoid intraoperative massive bleeding, super-selective TAE was performed for the tumor 2 days prior to surgery. Hypoglycemia disappeared after TAE. The tumor was resected completely, with no massive hemorrhage during resection. Histologically, it was diagnosed as IGF-II-secreting SFT. Partial necrosis of the rectum in the specimen was observed due to TAE. The patient was followed up for 2 years and no evidence of disease has been reported. Conclusions Preoperative angiography followed by TAE is an exceedingly helpful method to reduce intraoperative hemorrhage when planning to resect SFT occupying the pelvic cavity. Complications related to ischemia should be kept in mind after TAE, which needs to be planned within 1 or 2 days before surgery. TAE for tumors may be an option in addition to medical and surgical treatment for persistent hypoglycemia in Doege–Potter syndrome.

Here, we report about a woman in her 30s who had peritoneal dissemination and multiple colon cancer with high-frequency microsatellite instability(MSI-H). Her father, paternal grandfather, and maternal grandmother had a history of colorectal cancer treatment. Thus, Lynch syndrome was suspected. We performed R0 resection for peritoneal dissemination and subsequent peritoneal dissemination. A 435-gene panel testing using a next-generation sequencer identified MSH2 and other mutations in the tumor. Hence, we speculated that she could have a germline mutation of MSH2, which causes Lynch syndrome. In the future, if she wishes to receive genetic counseling and undergo germline testing for variants to confirm the diagnosis of Lynch syndrome, we will perform them after receiving informed consent.

AIM The role of preoperative frailty assessment in patients with gastrointestinal (GI) disease remains unclear. This study aimed to clarify the relationship between frailty and postoperative outcomes in patients with GI disease. METHODS This study investigated 42 patients (aged ≥65 years) with GI disease who underwent abdominal surgery. The frailty status was analyzed using the Japanese version of the Cardiovascular Health Study criteria. We also investigated postoperative outcomes. RESULTS Of the 42 patients, seven (16.7%) were robust, 24 (57.1%) were prefrail and 11 (26.2%) were frail. Postoperative complications were observed in 45.5% and 63.6% of prefrail and frail patients, respectively, whereas no complications were found in robust patients (P = 0.026). The median hospital stay was 15, 19.5 and 27 days in robust, prefrail and frail patients, respectively (P

A 66-year-old man with middle thoracic esophageal squamous cell carcinoma with supraclavicular lymph node metastasis visited our hospital. He underwent 3 courses of preoperative chemotherapy with docetaxel, cisplatin, and 5-FU(DCF)with a clinically-determined partial response. Minimally-invasive esophagectomy with 3-fieldlymphad enectomy was subsequently performed. Histopathologic examination revealedno viable tumor cells in the resectedesophagus andsupraclavicular lymph node. DCF is a promising preoperative chemotherapy regimen for locally advanced esophageal cancer because of its higher complete response rate comparedto that for cisplatin plus 5-FU.

A 65-year-old woman was referred for further examination following positive results on a fecal occult blood test. Colonoscopy revealed type 0-Ⅱa cancer, with a lesion measuring 2 cm in diameter in the rectosigmoid colon, and type 5 cancer, with a lesion measuring 6 cm in diameter in the upper rectum. Computed tomography(CT)and positron emission tomography (PET)-CT revealed mesorectal lymph node metastases. Therefore, she was diagnosed with rectosigmoid colon cancer(Stage Ⅰ)and upper rectal cancer(Stage Ⅲa). However, PET-CT also revealed slight fluorodeoxyglucose uptake in the paraaortic and lateral lymph node lesions; hence, the possibility ofmetastasis could not be ruled out. Given that chemotherapy was restricted due to renal dysfunction, low anterior resection was performed as the first choice. Analysis of intraoperative frozen sections showed paraaortic and lateral lymph node metastases; thus, we performed lymph node dissection of these lesions. Pathological examination ofthe resected lymph nodes revealed that 21 of 37 lesions were cancer metastases. S-1 was administered as adjuvant chemotherapy for 5 months. Mediastinal lymph node metastases was suspected on chest CT 5 months and 3 years post-surgery; thus, panitumumab was administrated. These lymph nodes decreased in size immediately. Six years after the first surgery, the patient was well without any signs of recurrence.

A 62-year-old man was admitted with complaints of bloody stool. Colonoscopy revealed a 5 cm diameter type 2 tumor in the lower rectum close to the anal canal. Tumor biopsy indicated a well-differentiated tubular adenocarcinoma. Computed tomography revealed locally advanced rectal cancer with mesorectal lymph node metastases(cT3N1P0M0, Stage Ⅲa, JSCCR 8th). The patient was treated with neoadjuvant chemotherapy(NAC)after transverse colostomy as an anus-preserving procedure. For the NAC, 12 courses of capecitabine plus oxaliplatin(CapeOX)and bevacizumab(BV)were administered. Colonoscopy after NAC revealed that the main tumor had considerably shrunk. No malignant tissues were found on biopsy. However, rectal wall thickness remained unchanged. Therefore, response evaluation for chemotherapy indicated partial response. Intersphincteric resection(ISR)with diverting loop ileostomy was performed as an anus-preserving surgical procedure. No remnant tumor in the rectum or lymph node metastases were found upon the pathological examination of resected specimens. Ileostomy closure was performed at 6 months post-ISR. At 12 months post-ISR, the patient was well and showed no signs of recurrence. This case demonstrated that NAC with CapeOX and BV can be a promising option for treating locally advanced lower rectal cancer and preserving the anus.

This study aimed to determine surgical outcomes in patients with gynecological cancers for whom surgery was performed by gynecologists and digestive surgeons.Seventy-three patients who underwent surgery for a gynecological malignant tumor from January 2010 to December 2014 were included in this retrospective study. Data on the definitive diagnosis, operative procedures, postoperative complications, stoma settings, length of hospital stay, and prognosis was collected for each patient.The median age of this female-only cohort was 60 years. Emergency surgery was performed in 8(11.0%)patients. Ovarian cancer was diagnosed in 56(76.7%)patients, and among these patients, the clinical disease Stage was Ⅰ, Ⅱ, Ⅲ, and Ⅳ in 4, 4, 20, and 11 patients, respectively. Moreover, 17 patients had recurrent ovarian cancer. Intestinal resection with anastomosis was performed in 25(34.2%)patients. Stoma formation was performed in 22 (30.1%)patients, however no patient underwent stoma closure surgery in the current study. The median operative time was 252 minutes, and the median blood loss was 1,190 mL. Regarding postoperative complications, ileus, pelvic abscess, and anastomotic leakage developed in 6(8.2%), 4(5.5%), and 2(2.7%)patients, respectively. The postoperative median survival time in patients with ovarian cancer was 1,399 days.These results suggest that tumor debulking, including intestinal tract resection, may contribute to the prolonged prognosis of gynecological tumors, although stoma closure is difficult to perform.

Background: Tripartite motif-containing protein 37 (TRIM37) is an oncogenic histone H2A ubiquitin ligase that is overexpressed in a subset of breast cancers. TRIM37 was suggested to be associated with chemotherapy resistance and metastasis of triple-negative breast cancer (TNBC) in in vivo and in vitro studies. Breast cancer with TRIM37 amplification is sensitive to polo-like kinase 4 (PLK4) inhibition. On the other hand, clinical relevance of TRIM37 in breast cancer was never investigated. Material and Methods: Total of 6836 breast cancer patients from three large patient cohorts (Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), The Cancer Genome Atlas (TCGA), GSE96058, GSE25066 and GSE20194. Gene set enrichment analysis (GSEA) was performed. The high and low expression of TRIM37 gene were divided by median. Results: TRIM37 expression was significantly associated with worse survival (disease-free (DFS), disease-specific (DSS), and overall survival (OS)) in ER-positive/HER2-negative breast cancer (p=0.012, p=0.011, and p=0.003, respectively), but not in the other subtypes. TRIM37 expression was higher in HER2-positive among the subtypes. TRIM37 expression correlated with Nottingham histological grade (p Citation Format: Junko Tsuchida, Rongrong Wu, Maiko Endo, Kazuki Moro, Chie Toshikawa, Yu Koyama, Hiroshi Ichikawa, Takaaki Hanyu, Yamato Takabe, Kazuyasu Takizawa, Yoshifumi Shimada, Takashi Kobayashi, Takashi Ishikawa, Jun Sakata, Toshifumi Wakai, Kazuaki Takabe. Clinical relevance of TRIM37 gene expression in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-01-15.

e13618Background: Approximately 5% of gastric cancer (GC) is associated with inherited cancer predisposition syndrome. Pathogenic germline BRCA1/2 mutations predispose, not only to breast and ovari...

Background Sphingosine-1-phosphate, a pleiotropic bioactive lipid mediator, is an important player in cancer progression. Previous studies suggested that sphingosine-1-phosphate produced by sphingosine kinase 1, which is activated by phosphorylation, plays important roles in the progression of disease and metastasis. The association between phospho-sphingosine-1-phosphate produced by sphingosine kinase 1 and clinical parameters in human gastric cancer have not been fully investigated to date. Methods We created phospho-sphingosine-1-phosphate produced by sphingosine kinase expression profiles by immunohistochemistry for 136 patients who underwent operative intervention for gastric cancer in 2007–2009. Phospho-sphingosine-1-phosphate produced by sphingosine kinase expression and compared clinicopathologic factors by univariate and multivariate analyses. Results The univariate analysis revealed that phospho-sphingosine-1-phosphate produced by sphingosine kinase expression was correlated significantly with depth of tumor invasion, lymph node metastasis, distant metastasis, histologic type, and lymphatic invasion. The multivariate analysis revealed that the diffuse type (odds ratio 2.210; 95% confidence interval, 1.045–4.671, P = .038) and the presence of lymphatic invasion (odds ratio 3.697; 95% confidence interval, 1.161–8.483, P = .002) were associated independently with phospho-sphingosine-1-phosphate produced by sphingosine kinase expression in patients with gastric cancer. The 5-year rate of disease-specific survival was 79.3% in patients with phospho-sphingosine-1-phosphate produced by sphingosine kinasephospho-sphingosine-1-phosphate produced by sphingosine kinase-positive expression and 98.3% in those with phospho-sphingosine-1-phosphate produced by sphingosine kinase-negative expression (P = .002). In multivariate analysis, however, high phospho-sphingosine-1-phosphate produced by sphingosine kinase expression was not an independent prognostic factor for disease-specific survival (hazard ratio 5.540; 95% confidence interval, 0.717–42.81, P = .100). Conclusion We provide the first evidence that diffuse histologic type and lymphatic invasion were independently associated with high phospho-sphingosine-1-phosphate produced by sphingosine kinase expression in gastric cancer patients, indicating a role of sphingosine-1-phosphate in disease progression among patients with gastric cancer. (Surgery 2017;160:XXX-XXX.)

Background Esophagectomy for esophageal cancer is known to lead to deterioration in respiratory function (RF). The aim of this study was to assess long-term trends in RF after esophagectomy and the impact of different operative procedures. Methods A total of 52 patients with thoracic esophageal cancer who were scheduled for esophagectomy from 2003 to 2012 were enrolled. We prospectively evaluated patients for vital capacity (VC), forced expiratory volume in 1 s (FEV1.0), and 6-min walk distance (6MWD) before and after esophagectomy at 3, 6, 12, 24, and 60 mo. Results Patients had mostly recovered their VC and FEV1.0 after 12 mo. After that point, VC and FEV1.0 declined again, reaching levels lower than baseline at 60 mo, with a median change ratio of 0.85 and 0.86, respectively. Although the 6MWD after open esophagectomy declined, patients treated with transhiatal esophagectomy and minimally invasive esophagectomy maintained above baseline levels throughout the follow-up period. Furthermore, we identified transhiatal esophagectomy (odds ratio [OR] = 0.03, 95% confidence interval [CI] 0.002-0.43, P = 0.01) and minimally invasive esophagectomy (OR = 0.14, 95% CI 0.02-0.94, P = 0.04) as favorable factors and postoperative pulmonary complication (OR = 9.14, 95% CI 1.22-68.6, P = 0.03) as an unfavorable factor for RF after 12 mo. Operative procedures had no significant impact on RF after 60 mo. Conclusions Our results support the notion that RF does not recover to the baseline level, and operative procedures have no significant impact on RF at late phase after esophagectomy.

Background: A prospective randomized study was performed to investigate the validity of intravenous carnitine administration during postoperative parenteral nutrition (PN) with lipid emulsion. Methods: Patients undergoing surgery for gastric or colorectal cancer were enrolled in the study and were randomly divided into two groups (n = 8 in each group): 1) group L, who received a peripheral PN (PPN) solution of 7.5% glucose, 30% amino acid, and 20% lipid emulsion; and 2) group LC, who received the same PPN solution, as well as carnitine intravenously. PPN was performed from postoperative day (POD) 1 to POD4. Clinical and laboratory parameters were compared between the two groups; statistical significance was set at P < 0.05. Results: Serum carnitine concentrations were significantly higher in group LC on POD3 (P < 0.01) and POD7 (P = 0.01). Postoperative changes in laboratory parameters and morbidity were comparable between the two groups. However, the decrease in C-reactive protein from POD3 to POD7 was significantly greater in group LC than in group L (P = 0.011). Conclusion: The results show that intravenous carnitine administration in addition to PN is safe and may be beneficial for recovery from postoperative inflammatory reactions. J Clin Med Res. 2017;9(10):831-837 doi: https://doi.org/10.14740/jocmr3113w

A 74-year-old woman with cT4aN2M0, cStage ⅢB gastric cancer underwent neoadjuvant chemotherapy comprising 2 courses of S-1 plus cisplatin, and the clinical response was determined as non-CR/non-PD according to RECIST ver 1.1. Although distal gastrectomy with D2 lymphadenectomy was planned, the tumor was considered as unresectable with peritoneal metastases during laparotomy. After the subsequent chemotherapy with 1 course of capecitabine plus cisplatin, tumor bleeding, and obstruction due to rapid tumor progression occurred. We performed palliative distal gastrectomy; however, the patient died 17 days after gastrectomy. A comprehensive genomic analysis using cancer-gene panel identified the tumor as a microsatellite instability-high(MSI-H). Recently post hoc analysis of the large-scale clinical trials showed no clinical benefit of perioperative chemotherapy in MSI-H gastric cancer. MSI status has a potential to optimize the perioperative treatment strategy in gastric cancer.

We present a case of long-term survival in a patient with advanced ascending colon cancer and multiple liver metastases after receiving multimodality therapy, which included hepatic atrial infusion(HAI)and 4 hepatectomies. At diagnosis, the 65- year-old woman underwent right hemicolectomy for advanced ascending colon cancer with multiple liver metastases (T3N1M1[H2], Stage Ⅳ). The 11 liver metastatic lesions were treated by weekly HAI of 5-fluorouracil(5-FU). The lesions reduced in size(response rate 28.9%)immediately following treatment, and no new lesions were detected, but 10 months after treatment the size of the S2 tumor had increased. Systemic chemotherapy with irinotecan and S-1 was administered. Continued development of the S2 tumor in the liver prompted a radical lateral segment hepatectomy. Four months later, a computed tomography(CT)scan revealed a S6 tumor of the liver, for which a posterior segment hepatectomy was performed. A CT scan showing a S1 tumor in the liver 9 months later resulted in chemotherapeutic treatment with CapeOX, followed by mFOLFOX6. Despite treatment, the S1 tumor developed further, prompting a S1 partial hepatectomy. A further partial S8 hepatectomy was performed 7 years after surgery for the primary lesion following a CT scan that revealed a S8 tumor in the liver. There has been no recurrence of tumors in the 5 years and 5 months since this last hepatectomy.

Background Surgical stress and inflammation can cause hyperbilirubinemia, which sometimes occurs after esophagectomy for esophageal cancer (EC). The aim of this study was to elucidate the clinical significance of postoperative hyperbilirubinemia in the management of EC patients. Materials and methods We retrospectively reviewed records of 81 EC patients who underwent esophagectomy from 2009 to 2014. We compared the clinicopathological and perioperative factors, including the presence of hyperbilirubinemia (total bilirubin ≥1.5 mg/dL), between patients with postoperative infectious complications (PIC group) and those without (Non-PIC group). Results PIC developed in 52 patients (64.2%). There were significant differences in incidence of postoperative hyperbilirubinemia between the PIC group and the non-PIC group (34.6% vs. 3.4%, P = 0.002), as well as the approach of esophagectomy (P = 0.045), the surgical duration (469 vs. 389 min, P, Highlights • Hyperbilirubinemia was related to the infectious complications after esophagectomy. • Hyperbilirubinemia preceded the infectious complications became apparent. • Total bilirubin level might be a useful indicator for the infectious complications.

The aim of this study was to assess the clinical outcomes of palliative interventions for patients with incurable locally advanced or metastatic esophageal carcinoma. A total of 131 patients with thoracic esophageal carcinoma who underwent palliative interventions were enrolled. Insertion of a self-expandable metallic stent (SEMS), tube enterostomy for enteral nutrition (EN), and palliative esophagectomy (PE) were performed in 38, 65, and 28 patients, respectively. The clinicopathological characteristics and clinical outcomes of each group were retrospectively reviewed. Patients in the EN group frequently received chemoradiotherapy (P

This study aimed to evaluate the health-related quality of life(QOL)using EQ-5D-5L scores for patients who underwent surgery for colorectal cancer. A total of 30 consecutive patients(14 men and 16 women; median age: 67.5 years)from the outpatient clinic of our institute in January 2017 were eligible for this study. The primary tumor was located in the colon(n= 18)or rectum/anu(s n=12). Twelve patient(s 40.0%)had cancer recurrence, and 3 patient(s 10.0%)had a stoma. In addition, 11 patients(36.7%)underwent chemotherapy. The median EQ-5D-5L score for all the patients was 0.867(range, 0.324- 1.000). The EQ-5D-5L score of patients with recurrence was significantly lower(0.820)than that of patients without recurrence( 0.948)(p=0.002). Furthermore, the EQ-5D-5L score of women(0.834)was significantly lower than that of men (0.942)(p=0.015). No significant difference was noted between the EQ-5D-5L score and other factors, such as age, cancer stage, location of primary tumor, absence/presence of chemotherapy, and absence/presence of stoma. In conclusion, using EQ-5D-5L scores, female gender and cancer recurrence were found to be associated with low QOL of patients after surgery for colorectal cancer.

Lymph node metastasis has a poor prognosis in patients with hepatocellular carcinoma(HCC). We report a case of HCC with lymph node metastasis successfully treated by multidisciplinary treatment. An 81-year-old woman who was followed up for liver cirrhosis received a diagnosis of HCC, which was detected by CT as a solitary tumor 20mm in diameter in the couinaud segment 7 of the liver. She underwent transcatheter arterial chemoembolization(TACE)twice for HCC because of her advanced age and no intention to undergo hepatectomy. Some 12 months later, local recurrence was managed by repeat TACE and paraaortic lymph node metastasis by surgical resection. The patient received radiotherapy for mediastinal nodal disease 6 months after the resection. She remains alive and well without no evidence of disease 84 months after the initial treatment. This case and a review of the literature suggest that multidisciplinary treatment with TACE, surgical resection and radiotherapy may provide a survival benefit for selected patients with HCC with isolated lymph node metastasis.

An 81-year-oldwoman with advancedgastric cancer was referredto our hospital. Preoperative contrast-enhancedCT revealeda roundcalcification of the splenic hilum with 15mm in diameter as a splenic artery aneurysm. She underwent transcatheter arterial embolization(TAE)for the splenic artery aneurysm. Celiac artery angiography showedcollateral arterial network of the spleen from left gastric artery. Surgery for the gastric cancer was performed1 4 days after TAE. We cut the right gastric andbilateral epigastric arteries. After the left gastric artery clamping, we performedintraoperative indocyanine green(ICG)fluorography. ICG fluorography confirmedthat the bloodflow of the upper thirdof the stomach andspleen were maintained. We safely performed distal gastrectomy, and the postoperative course was uneventful.

We sought to determine the prognostic significance of intraoperative peritoneal lavage cytology (CY) at 3 different abdominal cavities and establish the optimal treatment for gastric cancer patients with positive peritoneal cytology (CY1).A total of 1,039 patients with primary gastric adenocarcinoma who underwent CY at 3 cavities (Douglas' pouch, left subphrenic cavity, and right subhepatic cavity) were enrolled; 116 (11%) patients had at least one positive cavity. We retrospectively analyzed the clinicopathologic characteristics and survival of these 116 patients with CY1.Seventeen (15%) of the patients had negative cytology at Douglas' pouch but positive cytology at one or both of the other cavities. The 116 patients' overall 2-year survival rate was 22.9%, with the median survival time of 11 months. The overall 2-year survival rates for the patients with positive cytology at 1, 2, and 3 cavities were 41.9%, 35.8%, and 15%, with median survival times of 17, 18, and 9 months, respectively (P.01). A multivariate analysis revealed that macroscopic type 4 tumor, R2 resection, lymph node metastasis, and postoperative chemotherapy were independent prognostic factors. Among the CY1 patients with type 4 tumors, there was no substantial difference in survival between the patients who underwent R1 or R2 resection, although the statistical power of this subgroup analysis was low.CY at 3 cavities might be a useful method to decrease the false-negative rate. Palliative gastrectomy for CY1 patients with type 4 tumors is still controversial.

Abdominal wall emphysema is a common complication of laparoscopic surgery. This condition is usually harmless; however, if an infection occurs, it can develop into a serious condition such as necrotizing fasciitis. We report a case of a 51-year-old woman suffering from severe cellulitis that spread from an area of abdominal wall emphysema after laparoscopic surgery for sigmoid colon cancer. Recognizing this complication, early diagnosis, and prompt treatment are cornerstones for successful management of this potentially fatal disease.

The aims of this study were to identify prognostic factors of patients with submucosa-invasive (T1b) gastric cancer and to verify the validity of adjuvant chemotherapy for this disease.We retrospectively examined the cases of 1,236 consecutive patients in our prospectively maintained database with T1b gastric cancer who underwent gastrectomy in 1995-2012. We used 11 clinicopathologic characteristics to identify prognostic factors by univariate and multivariate analyses. We compared the survival of the 160 node-positive T1b gastric cancer patients with that of 133 patients in the same database who had node-positive muscularis propria-invasive (T2) gastric cancer and had undergone gastrectomy without adjuvant chemotherapy during the same period, as a reference cohort.The 5-year overall survival rate was 91.4% for all 1,236 patients. Advanced age (hazard ratio [HR] 4.51; 95% confidence interval [CI] 3.26-6.24; P.01), male sex (HR 2.26; 95% CI 1.56-3.26; P.01), and the presence of lymph node metastasis (HR 1.89; 95% CI 1.33-2.70; P.01) were independent prognostic factors. The 5-year overall survival rates were 92.5% in node-negative patients, 84.5% in patients with 1 or 2 metastatic nodes, and 80.1% in patients with 3 or more metastatic nodes (P.01). The 5-year overall survival rates of the node-positive T1b and T2 gastric cancer patients were 83.6% and 81.2%, respectively (P = .73).The prognosis of node-positive T1b gastric cancer patients after curative gastrectomy was unsatisfactory. Adjuvant chemotherapy should be considered for these patients, especially those with 3 or more metastatic nodes.

The number of patients with remnant gastric cancer following resection of gastric cancer may increase. The aims of this study were to investigate the development of remnant gastric cancer after distal gastrectomy for gastric cancer and to examine its cumulative incidence, clinicopathological characteristics, and risk factors. We examined 437 patients with relapse-free survival for 5 years or more after distal gastrectomy with Billroth I reconstruction for gastric cancer performed between 1985 and 2005. A total of 17 patients suffered from remnant gastric cancer. The cumulative incidence was 3.7% at 10 years and 5.4% at 20 years. The median time until development of remnant gastric cancer was 79 months (range 30–209 months). The presence of synchronous multiple gastric cancers was a significant independent risk factor for remnant gastric cancer (hazard ratio 4.036; 95% confidence interval 1.478–11.02; P = 0.006). Of the 17 patients, the 13 whose remnant gastric cancer was detected via regular endoscopy showed better prognoses than the patients detected by other means (P

Background Benign esophageal tumors are uncommon, comprising approximately 2% of esophageal tumors. Esophageal schwannomas constitute an even rarer entity, with few cases reported in the literature. Case presentation We present a 66-year-old male who was referred for dysphagia. A computed tomography scan showed a well-demarcated, enhancing, and homogenous esophageal tumor measuring 50 mm. The tumor was hypermetabolic on positron emission tomography, and an endoscopic ultrasound-guided fine needle aspiration demonstrated the presence of benign spindle cells. We performed an uncomplicated, simple, tumor enucleation through a cervical approach. Histology revealed spindle-shaped cells in a fasciculated, disarrayed pattern. Immunohistochemistry demonstrated positive staining for S-100 protein and negative staining for KIT, CD34, desmin, and α-smooth muscle actin. These findings were consistent with a benign esophageal schwannoma. Conclusions We report our experience with esophageal schwannoma, a rare but benign diagnosis of the esophagus.

Aim To investigate the appropriate extent of lymphadenectomy for squamous cell carcinoma (SCC) of the esophagogastric junction (ECJ). Methods We retrospectively reviewed the cases of 52 patients with SCC of the ECJ who underwent extended mediastinal lymphadenectomy. We assessed potential risk factors for lymph node metastasis (LNM) in the upper/middle mediastinum by conducting univariate and multivariate analyses, and a receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value. Survival rates were calculated using the Kaplan-Meier method, and the therapeutic value index of each nodal basin dissection was calculated by multiplying the frequency of metastasis at the basin and the 5-year overall survival rate of patients with metastasis at that basin. Results Twenty patients (38%) had mediastinal LNM; 13 (25%) had metastasis in the upper/middle mediastinum, and 13 (25%) had metastasis in the lower mediastinum. Tumor length ( P = 0.03) and pathological nodal status ( P = 0.01) were independent risk factors for upper/middle mediastinal LNM. The optimal ROC cutoff value of tumor length was 54 mm. The 5-year overall survival rate of the patients with LNM in the upper/middle mediastinum was 46%. The therapeutic value index of upper/middle mediastinal lymphadenectomy was 11.6, which was inferior to that of perigastric lymphadenectomy at 17.3, but superior to that of lower mediastinal lymphadenectomy at 5.8. Conclusion An upper/middle mediastinal lymphadenectomy may be required for patients with tumors that are ≥54 mm long, and in those with suspected LNM.

Prognostic markers are urgently needed to optimize the postoperative treatment strategies for gastrointestinal stromal tumors (GIST). GIST of the small intestine (I-GIST) show more aggressive behavior than those of the stomach (S-GIST), and the molecular background of the malignancy in I-GIST may include potential prognostic biomarkers. We conducted integrated proteomic and transcriptomic analysis to identify genes showing differential expressions according to the tumor site. We generated protein expression profiles for four cases each of surgically resected I-GIST and S-GIST using label-free proteomic analysis. For proteins showing differential expressions, global mRNA expression was compared between 9 I-GIST and 23 S-GIST. Among the 2555 genes analyzed, we found that promyelocytic leukemia (PML), a tumor suppressor gene, was significantly downregulated in I-GIST at both the protein and mRNA levels (P

The number of patients cured of esophageal cancer after esophagectomy is gradually increasing owing to advances in surgical techniques, perioperative management, and adjuvant therapies. This study assessed the clinical course and sought to identify the prognostic factors of these patients.A series of 220 consecutive patients who underwent esophagectomy and survived for more than 5 years with no relapse were enrolled. Survival analysis was performed using 25 variables including patient characteristics and operative and perioperative factors. Potential prognostic factors were identified by univariate and multivariate analyses, and the development of other primary cancers and the causes of death were retrospectively reviewed.The overall 10-, 15-, and 20-year survival rates were 71.6, 50.1, and 32.2 %, respectively, with a median survival time of 180 months (range, 61-315 months). The negative independent prognostic factors identified were age at surgery [hazard ratio (HR), 1.05; P.01], being male (HR, 2.62; P = .02), pulmonary comorbidities (HR, 2.03; P = .02), synchronous presence of other cancers (HR, 2.35; P.01), colonic/jejunal interposition (HR, 1.76; P = .03), perioperative blood transfusion (HR, 1.92; P = .02), development of pulmonary complications (HR, 1.71; P = .02), and adjuvant radiotherapy (HR, 2.13; P = .01). Pulmonary diseases and other primary cancers were found to be the most common causes of death.Careful follow-up including the surveillance of other primary cancers is required for long-term survivors of esophageal cancer after esophagectomy.