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Purpose: This study explored the difficulty factors in robot-assisted low and ultra-low anterior resection, focusing on simple measurements of the pelvic anatomy., Methods: This was a retrospective analysis of the clinical data of 61 patients who underwent robot-assisted low and ultra-low anterior resection for rectal cancer between October 2018 and April 2023. The relationship between the operative time in the pelvic phase and clinicopathological data, especially pelvic anatomical parameters measured on X-ray and computed tomography (CT), was evaluated. The operative time in the pelvic phase was defined as the time between mobilization from the sacral promontory and rectal resection., Results: Robot-assisted low and ultra-low anterior resections were performed in 32 and 29 patients, respectively. The median operative time in the pelvic phase was 126 (range, 31-332) min. A multiple linear regression analysis showed that a short distance from the anal verge to the lower edge of the cancer, a narrow area comprising the iliopectineal line, short anteroposterior and transverse pelvic diameters, and a small angle of the pelvic mesorectum were associated with a prolonged operative time in the pelvic phase., Conclusion: Simple pelvic anatomical measurements using abdominal radiography and CT may predict the pelvic manipulation time in robot-assisted surgery for rectal cancer., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Patients with a history of colorectal cancer (CRC) are at increased risk of developing secondary synchronous/metachronous CRCs. The role of minimally invasive surgery (MIS) for multiple CRCs remains unclear. This study aimed to evaluate the short-term outcomes of MIS in patients with multiple CRCs and elucidate their clinical characteristics., Methods: This retrospective study reviewed CRC patients who underwent MIS between 2010 and 2023. Multiple CRC cases were categorized into synchronous and metachronous cohorts. Demographics, pathological findings, and perioperative outcomes were analyzed. Propensity score matching (PSM) analysis was performed as appropriate., Results: A total of 1,272 patients met the inclusion criteria, with 99 (7.8%) having multiple CRCs (75 synchronous and 24 metachronous). Multiple CRC patients had a higher prevalence of strong family history (8.1% vs. 1.0%, P < 0.001) and right-sided colon cancer (55.6% vs. 34.4%, P < 0.001) compared to solitary CRC patients. MSI-high/MMR-deficient status, including Lynch syndrome, was frequently observed among patients with multiple CRCs. Synchronous CRCs requiring double-anastomosis were associated with longer operation times (P = 0.03) and increased blood loss (P = 0.03) compared to those with a single-anastomosis. In the metachronous cohort, repeat operation patterns were categorized based on tumor location and sacrificed arteries. Preservation of the left-colic artery avoided extended colectomy in some patients. Patients with multiple CRC involving rectal cancer had a higher anastomotic leakage (AL) rate (17.6% vs. 5.7%, P < 0.01); however, this difference in AL rate disappeared after PSM (8.8% vs. 8.8%, P = 1.0). In patients with multiple CRCs, AL has not been observed ever since the indocyanine green fluorescence imaging was implemented., Conclusions: MIS is feasible for multiple CRCs, with perioperative outcomes comparable to those for solitary CRCs. Preservation of critical arteries may benefit patients at high risk of secondary CRCs, particularly those with a strong family history of CRC, right-sided tumors, or MSI-high/MMR-deficient profiles, including Lynch syndrome., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To establish if osteosarcopenia is related to postoperative complications, prognosis, and recurrence of colorectal cancer (CRC) after curative surgery., Methods: The clinical data of 594 patients who underwent curative resection for CRC between January, 2013 and December, 2018 were analyzed retrospectively to examine the relationship between clinicopathological data and osteosarcopenia. The following definitions were used: sarcopenia, low skeletal muscle mass index; osteopenia, low bone mineral density on computed tomography at the level of the 11th thoracic vertebra; and osteosarcopenia, sarcopenia with osteopenia., Results: Osteosarcopenia was identified in 98 patients (16.5%) and found to be a significant risk factor for postoperative complications (odds ratio 2.53; p = 0.011). The 5-year overall survival (OS) and recurrence-free survival (RFS) rates of the patients with osteosarcopenia were significantly lower than those of the patients without osteosarcopenia (OS: 72.5% and 93.9%, respectively, p < 0.0001; RFS: 70.8% and 92.4%, respectively, p < 0.0001). Multivariate analysis identified osteosarcopenia as an independent prognostic factor associated with OS (hazard ratio 3.31; p < 0.0001) and RFS (hazard ratio 3.67; p < 0.0001)., Conclusion: Osteosarcopenia may serve as a predictor of postoperative complications and prognosis after curative surgery for CRC., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background and Aim: Colitis-associated intestinal cancer (CAC) can develop in patients with inflammatory bowel disease; however, the malignant grade of CAC may differ from that of sporadic colorectal cancer (CRC). Therefore, we compared histological findings distinct from cancer stage between CAC and sporadic CRC to evaluate the features of CAC., Methods: We reviewed the clinical and histological data collected from a nationwide database in Japan between 1983 and 2020. Patient characteristics were compared to distinguish ulcerative colitis (UC), Crohn's disease (CD), and sporadic CRC. Comparisons were performed by using all collected data and propensity score-matched data., Results: A total of 1077 patients with UC-CAC, 297 with CD-CAC, and 136 927 with sporadic CRC were included. Although the prevalence of well or moderately differentiated adenocarcinoma (Tub1 and Tub2) decreased according to tumor progression for all diseases (P < 0.01), the prevalence of other histological findings, including signet ring cell carcinoma, mucinous carcinoma, poorly differentiated adenocarcinoma, or squamous cell carcinoma, was significantly higher in CAC than in sporadic CRC. Based on propensity score-matched data for 982 patients with UC and 268 with CD, the prevalence of histological findings other than Tub1 and Tub2 was also significantly higher in those with CAC. At pT4, mucinous carcinoma occurred at a significantly higher rate in patients with CD (45/86 [52.3%]) than in those with sporadic CRC (13/88 [14.8%]) (P < 0.01)., Conclusion: CAC, including early-stage CAC, has a higher malignant grade than sporadic CRC, and this difference increases in significance with tumor progression., (© 2024 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Familial adenomatous polyposis (FAP) is a heritable disease that increases the risk of colorectal cancer (CRC) development because of heterozygous mutations in APC. Little is known about the microenvironment of FAP. Here, single-cell RNA sequencing was performed on matched normal tissues, adenomas, and carcinomas from four patients with FAP. We analyzed the transcriptomes of 56,225 unsorted single cells, revealing the heterogeneity of each cell type, and compared gene expression among tissues. Then we compared the gene expression with that of sporadic CRC. Furthermore, we analyzed specimens of 26 FAP patients and 40 sporadic CRC patients by immunohistochemistry. Immunosuppressiveness of myeloid cells, fibroblasts, and regulatory T cells was upregulated even in the early stages of carcinogenesis. CD8 + T cells became exhausted only in carcinoma, although the cytotoxicity of CD8 + T cells was gradually increased according to the carcinogenic step. When compared with those in the sporadic CRC microenvironment, the composition and function of each cell type in the FAP-derived CRC microenvironment had differences. Our findings indicate that an immunosuppressive microenvironment is constructed from a precancerous stage in FAP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Beckwith-Wiedemann syndrome (BWS) is a genomic imprinting disorder caused by diverse genetic and/or epigenetic disorders of chromosome 11p15.5. BWS presents with a variety of clinical features, including overgrowth and an increased risk of embryonal tumors. Notably however, reports of patients with BWS and breast tumors are rare, and the association between these conditions is still unclear. Insulin-like growth factor-2 (IGF2) expression is known to be associated with the development of various cancers, including breast cancer, and patients with BWS with specific subtypes of molecular defects are known to show characteristic clinical features and IGF2 overexpression., Case Presentation: A 17-year-old girl who had been diagnosed with BWS based on an umbilical hernia, hyperinsulinemia, and left hemihypertrophy at birth, visited our department with a gradually swelling left breast. Her left breast was markedly larger than her right breast on visual examination. Imaging examinations showed two tumors measuring about 10 cm each in the left breast, and she was diagnosed with juvenile fibroadenoma following core needle biopsy. The two breast tumors were removed surgically and the patient remained alive with no recurrence. The final diagnosis was juvenile fibroadenoma without malignant findings. Immunohistochemical staining using IGF2 antibody revealed overexpression of IGF2 in the cytoplasm of ductal epithelial cells. Because of her clinical features and IGF2 overexpression, molecular defects of 11p15.5 including a possible genetic background of paternal uniparental disomy of chromosome 11 or hypermethylation of imprinting center 1 was suspected., Conclusions: In this case, overexpression of IGF2 suggested a possible relationship between BWS and breast tumors. Moreover, the characteristic clinical features and IGF2 staining predicted the subtype of 11p15.5 molecular defects in this patient., (© 2024. The Author(s).)

Background: Gastric cancer (GC) is characterized by an immunosuppressive and treatment-resistant tumor immune microenvironment (TIME). Here, we investigated the roles of different immunosuppressive cell types in the development of the GC TIME., Methods: Single-cell RNA sequencing (scRNA-seq) and multiplex immunostaining of samples from untreated or immune checkpoint inhibitor (ICI)-resistant GC patients were used to examine the correlation between certain immunosuppressive cells and the prognosis of GC patients., Results: The results of the scRNA-seq analysis revealed that tumor-infiltrating monocytic myeloid-derived suppressor cells (TI-M-MDSCs) expressed higher levels of genes with immunosuppressive functions than other immunosuppressive cell types. Additionally, M-MDSCs in GC tissues expressed significantly higher levels of these markers than adjacent normal tissues. The M-MDSCs were most enriched in GC tissues relative to adjacent normal tissues. Among the immunosuppressive cell types assessed, the M-MDSCs were most enriched in GC tissues relative to adjacent normal tissues; moreover, their presence was most strongly associated with a poor prognosis. Immediate early response 3 (IER3), which we identified as a differentially expressed gene between M-MDSCs of GC and adjacent normal tissues, was an independent poor prognostic factor in GC patients (P = 0.0003). IER3 + M-MDSCs expressed higher levels of genes with immunosuppressive functions than IER3 - M-MDSCs and were abundant in treatment-resistant GC patients., Conclusions: The present study suggests that TI-M-MDSCs, especially IER3 + ones, may play a predominant role in the development of the immunosuppressive and ICI-resistant GC TIME., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Polymer fabrics are versatile materials used in various fields. Surface modification methods for hydrophobic polymer fibers have been developed to endow the materials with water wettability and functionality. Nevertheless, it remains a challenge to freely introduce functional groups to polymer fiber surfaces in a simple manner. Herein, we report the decoration of nonwoven fabric surfaces with azidated cello-oligosaccharide assemblies via molecular self-assembly. Cello-oligosaccharides with a terminal azido group were enzymatically synthesized and allowed to self-assemble in polyolefin, polyester, and vinylon nonwoven fabrics. It was found that the functional oligosaccharides formed bark-like assemblies on the nonwoven fiber surfaces, probably through heterogeneous nucleation. The hydrophilic oligosaccharide assemblies made the hydrophobic nonwoven surfaces water-wettable. Moreover, the azido group at oligosaccharide terminal was available for the post-functionalization of the modified nonwovens. In fact, an antigen was successfully conjugated to the modified nonwovens via the click chemistry. The antigen-conjugated nonwovens were useful for the specific and quantitative detection of a corresponding antibody. Our findings demonstrate the great potential of cello-oligosaccharide assembly for the functionalization of fabrics and other polymeric materials., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by National Institute for Materials Science in partnership with Taylor & Francis Group.)

Subcutaneous emphysema (SE) is a complication of laparoscopic surgery, potentially resulting in severe respiratory failure. No reports to date have focused on SE during robot-assisted (RA) rectal surgery. We aimed to reveal the risk factors and clinical significance of SE after RA/laparoscopic rectal surgery. We retrospectively reviewed 221 consecutive patients who underwent RA/laparoscopic rectal surgery. The occurrence of SE was evaluated on postoperative radiographs. Laparoscopic surgery was performed in 120 patients and RA in 101. SE developed in 55 (24.9%) patients. Logistic regression analysis identified RA surgery (odds ratio [OR]: 4.89, 95% confidence interval [CI] 2.13-11.22, p < 0.001), higher age (OR: 1.06, 95% CI 1.03-1.11, p < 0.001), lower body mass index (BMI) (OR: 0.79, 95% CI 0.67-0.93, p = 0.004), thinner subcutaneous layer (OR: 0.88, 95% CI 0.79-0.98, p = 0.02), and lateral lymph node dissection (OR: 9.43, 95% CI 2.44-36.42, p < 0.001) as risk factors for SE. Maximum end-tidal CO 2 was significantly higher in the SE than the non-SE cohort (p < 0.001). There was no difference in postoperative complication rate or length of hospital stay. Lower BMI (OR: 0.79, 95% CI 0.62-0.97, p = 0.02) and thinner subcutaneous layer (OR: 0.84, 95% CI 0.71-0.97, p = 0.01) were predictive factors in the RA cohort. SE occurs more frequently in RA compared with laparoscopic surgery. SE has a modest impact on short-term outcomes, but may occasionally cause severe problems. The indication of RA surgery should be considered carefully in high-risk elderly patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: There are several options for the treatment of gastrointestinal stricture, including endoscopic stent placement and bypass surgery. However, a benign stricture is difficult to manage in a reconstructed gastric tube in the thoracic cavity owing to the technical difficulty of bypass surgery, and the possibility of stent migration., Case Presentation: A 78-year-old woman was admitted to our hospital for treatment for her inability to eat. She had undergone video-assisted subtotal esophagectomy with retromediastinal gastric tube reconstruction 7 years earlier. At the current admission, there was a severely dilated gastric tube in the thoracic cavity with a soft stricture immediately anterior to the spine. Conservative therapy was ineffective; therefore, endoscopic stenting was performed. However, the stent migrated to the upper side of the stricture because the stricture was mild, and the stent was not fixed in the gastric tube. Next, endoscopic stent placement followed by laparoscopic stent fixation was performed. The stent was patent and worked well, and the patient's body weight increased. However, the stent collapsed 2 years later, with recurrence of symptoms. Stent-in-stent placement with an over-the-scope clip was performed, and the second stent was also patent and worked well., Conclusions: Laparoscopic stent fixation with endoscopic stent placement could be an effective option for patients with a benign stricture in the reconstructed gastric tube., (© 2023. The Author(s).)

Background: The aim of this study was to investigate the prognostic impact of postoperative infections in patients who underwent resection for biliary malignancy, including intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, gallbladder carcinoma, and carcinoma of the ampulla of Vater., Methods: This study was conducted in an 11-center retrospective cohort study. Patients with biliary tract cancer who underwent curative resection between April 2013 and March 2015 at 11 institutions in Japan were enrolled. We analyzed the prevalence of postoperative infection, infection-related factors, and prognostic factors., Results: Of the total 290 cases, 33 were intrahepatic cholangiocarcinoma, 60 were perihilar cholangiocarcinoma, 120 were distal cholangiocarcinoma, 55 were gallbladder carcinoma, and 22 were carcinoma of the ampulla of Vater. Postoperative infectious complications, including remote infection, were observed in 146 patients (50.3%), and Clavien-Dindo ≥III in 115 patients (39.7%). Postoperative infections occurred more commonly in the patients who received pancreaticoduodenectomy and bile duct resection. Patients with infectious complications had a significantly poorer prognosis than those without (median overall survival 38 months vs 62 months, P = .046). In a diagnosis-specific analysis, although there was no correlation between infectious complications and overall survival in intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, and carcinoma of the ampulla of Vater, infectious complications were a significantly poor prognostic factor in gallbladder carcinoma (P = .031)., Conclusion: Postoperative infection after surgery for biliary tract cancer commonly occurred, especially in patients who underwent pancreaticoduodenectomy and bile duct resection. Postoperative infection is relatively associated with the prognosis of patients with biliary malignancy, especially gallbladder carcinoma., (Copyright © 2023. Published by Elsevier Inc.)

Background/aim: Family history of colorectal cancer (CRC) is a known risk factor for CRC. However, its prognostic value in patients with CRC remains controversial. This study aimed to clarify the prognostic impact of a family history of CRC., Patients and Methods: We retrospectively reviewed the database from 1978 to 2018 and enrolled 3,655 consecutive patients with CRC. We investigated the clinicopathological factors of patients with CRC with and without a family history. After propensity score matching, we performed a survival analysis of patients with CRC with and without a family history., Results: Patients with CRC with a family history of CRC had a young onset (63.2 and 65.9; p<0.001), were more likely to be female (54.3% and 49.7%; p=0.042), had less symptomatic disease (76.9% and 80.8%; p=0.008), were more likely to have right-sided colon cancer (27.5% and 26.1%), and had less distant metastases (11.3% and 14.9%; p=0.023) and multiple CRCs (10.2% and 7.8%) compared with those without a family history of CRC. Prior to propensity score matching, CRC-specific survival analysis showed that a family history of CRC was a good prognostic factor (p=0.022). After propensity score matching, survival curves overlapped between the two groups., Conclusion: Patients with CRC with a family history of CRC had specific clinicopathological features including younger onset, female sex, proximal colon location, fewer symptoms, smaller number of distant metastases, likelihood of multiple diseases, and earlier cancer stage. Family history of CRC in patients with CRC was not a prognostic factor., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Although radical antegrade modular pancreatosplenectomy for pancreatic ductal adenocarcinoma (PDAC) has become the gold standard procedure in open distal pancreatectomy, there has been no gold standardized procedure for PDAC in minimally invasive distal pancreatectomy (MIDP). In this study, we analyzed our novel cranial-to-caudal approach (CC approach) for patients undergoing MIDP and provide a video clip illustrating the details of the CC approach., Methods: Ninety-four patients who underwent MIDP with splenectomy between 2016 and 2021 were included in this study. The CC approach was performed in 23 (24.5%) of the 94 patients. The concept of the CC approach is easy identification of Gerota's fascia from the cranial side of the pancreas and secure tumor removal (R0 resection) wrapped by Gerota's fascia. The short- and long-term outcomes were compared between the CC and non-CC approaches., Results: The median operation time and blood loss were similar between the two groups. The ratios of grade ≥ B postoperative pancreatic fistula and Clavien-Dindo grade ≥ III complications were also comparable. All patients in the CC approach group achieved R0 resection, and the R0 ratio was similar in the two groups (p = 0.345). The 2-year survival rate in CC and non-CC approach groups was 87.5% and 83.6%, respectively (p = 0.903)., Conclusions: The details of the CC approach for MIDP were demonstrated based on an anatomical point of view. This approach has the potential to become a standardized approach for left-sided PDAC., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Tertiary lymphoid structures (TLSs) are associated with a favorable prognosis in several cancers. However, the correlation between TLSs and outcomes of esophageal squamous cell carcinoma (ESCC) and the impact of TLSs on the tumor immune microenvironment (TIME) remain unknown., Methods: We pathologically evaluated the significance of TLSs in ESCC focusing on TLS maturation using 180 ESCC specimens and performed single-cell RNA sequencing (scRNA-seq) using 14 ESCC tissues to investigate functional differences of immune cells according to TLS presence., Results: TLS+ cases had better recurrence-free-survival (RFS) (p < 0.0001) and overall survival (OS) (p = 0.0016) compared with TLS- cases. Additionally, mature TLS+ cases had better RFS and OS compared with immature TLS+ cases (p = 0.019 and p = 0.015) and TLS- cases (p < 0.0001 and p = 0.0002). The scRNA-seq showed that CD8 + T cells in TLS+ tumors expressed high levels of cytotoxic signatures and antigen-presentation of dendritic cells (DCs) was enhanced in TLS+ tumors. Immunohistochemistry showed that the densities of tumor-infiltrating CD8 + T cells and DCs were significantly higher in TLS+ tumors than those in TLS- tumors., Conclusions: These data suggest the prognostic and functional significance of TLSs in ESCC and provides new insights into TLSs on the TIME., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Colorectal cancer (CRC) is one of the major life-threatening complications in patients with Crohn's disease (CD). Previous studies of CD-associated CRC (CD-CRC) have involved only small numbers of patients, and no large series have been reported from Asia. The aim of this study was to clarify the prognosis and clinicopathological features of CD-CRC compared with sporadic CRC., Methods: A large nationwide database was used to identify patients with CD-CRC (n = 233) and sporadic CRC (n = 129,783) over a 40-year period, from 1980 to 2020. Five-year overall survival (OS), recurrence-free survival (RFS), and clinicopathological characteristics were investigated. The prognosis of CD-CRC was further evaluated in groups divided by colon cancer and anorectal cancer (RC). Multivariable Cox regression analysis was used to adjust for confounding by unbalanced covariables., Results: Compared with sporadic cases, patients with CD-CRC were younger; more often had RC, multiple lesions, and mucinous adenocarcinoma; and had lower R0 resection rates. Five-year OS was worse for CD-CRC than for sporadic CRC (53.99% vs 71.17%, P < 0.001). Multivariable Cox regression analysis revealed that CD was associated with significantly poorer survival (hazard ratio 2.36, 95% confidence interval: 1.54-3.62, P < 0.0001). Evaluation by tumor location showed significantly worse 5-year OS and RFS of CD-RC compared with sporadic RC. Recurrence was identified in 39.57% of CD-RC cases and was mostly local., Discussion: Poor prognosis of CD-CRC is attributable primarily to RC and high local recurrence. Local control is indispensable to improving prognosis., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Malnutrition impacts the clinical course of Crohn's disease; however, there is little evidence of its influence on perioperative adverse events. We assessed whether nutritional indicators are associated with postoperative complications in surgical treatment of Crohn's disease., Methods: 137 patients with Crohn's disease who underwent surgical treatment between January 2011 and December 2020 were included. Skeletal muscle index was calculated by a single CT slice. We analyzed the risk factors for adverse events., Results: 37 % of patients had postoperative complications. Adverse events occurred more frequently in patients with high serum C-reactive protein, low serum albumin, prognostic nutritional index <38.3, skeletal muscle index <38.9 cm 2 /m 2 , abdominoperineal resection, long surgical duration, and mass hemorrhage. Among patients with skeletal muscle index <38.9 cm 2 /m 2 , patients who experienced adverse events had higher visceral fat index compared with those who did not (0.85 vs. 0.45, P  = 0.04). Multivariate analysis revealed that skeletal muscle index <38.9 cm 2 /m 2 and low serum albumin were the independent risk factors for postoperative complications (Odds ratio, 2.85; 95 % confidence interval, 1.13-7.16; P  = 0.03, 2.62; 1.09-6.26; P  = 0.03, respectively). Separated by sex, low serum albumin (<3.5 and <2.8 g/dL, male and female, respectively) and skeletal muscle index (<38.9 and <36.6 cm 2 /m 2 , male and female, respectively) were statistically related to postoperative complications., Conclusions: Skeletal muscle index is the most useful nutritional predictor of postoperative complications in Crohn's disease patients among other nutritional indices. We believe that these patients are at high risk of postoperative complications and need appropriate nutritional support in the perioperative period., Competing Interests: The authors have declared no conflicts of interest., (© 2023 The Authors.)

Background: Palliative endoscopic stent placement may be considered in patients with malignant gastrointestinal obstruction. Stent migration is a potential complication, particularly for those placed at a surgical anastomosis or across a stricture caused by extra-alimentary tract factors. We report a patient with left renal pelvis cancer and gastrojejunostomy obstruction who underwent endoscopic stent placement and laparoscopic stent fixation., Case Presentation: A 60-year-old male with peritoneal dissemination of a left renal pelvis cancer was admitted for treatment of upper gastrointestinal obstruction. A laparoscopic gastrojejunostomy had been previously performed for cancer invasion of the duodenum. Imaging showed gastroduodenal dilation and impaired passage of contrast medium through the efferent loop of the gastrojejunostomy. Gastrojejunostomy anastomosis site obstruction due to dissemination of left renal pelvis cancer was diagnosed. Conservative treatment failed and endoscopic stent placement with laparoscopic stent fixation was performed. After surgery, the patient was able to tolerate oral intake and he was discharged without complications. The patient gained weight and was able to resume chemotherapy, indicating the procedure was effective., Conclusions: Endoscopic stent placement with laparoscopic stent fixation for malignant upper gastrointestinal obstruction appears effective in patients with a high risk of stent migration., (© 2023. The Author(s).)

Background: In recent years, the number of minimally invasive pancreatoduodenectomy (MIPD) has been increasing; however, the procedure has not been widely accepted due to its complexity and difficulty. We have developed a technique to mobilize the pancreas head using a left-sided approach with a focus on the complete dissection of the Treitz ligament., Methods: This technique focuses on the secure mobilization of the pancreas head using a left-sided approach. First, the transverse mesocolon is flipped upward and the anterior side of the mesojejunum is excised to expose the first jejunal artery (1st JA) from the distal side to its origin. During the procedure, the left sides of the SMA and Treitz ligament are exposed. The Treitz ligament is retracted to the left side and dissected anteriorly. Thereafter, the jejunum is flipped to the right side and the retroperitoneum around the origin of the jejunum and duodenum is dissected to identify the inferior vena cava (IVC). The rest of the Treitz ligament is dissected posteriorly and complete resection of the Treitz ligament releases the limitation of duodenal immobility. Thereafter, dissection proceeds along the anterior wall of the IVC, and mobilization of the pancreas head is completed from the left side., Results: A total of 75 consecutive patients underwent MIPD from April 2016 to July 2022. The median operation times of laparoscopic and robotic procedures were 528 min (356-757 min) and 739 min (492-998 min), respectively. The volume of blood loss during laparoscopic and robotic procedures was 415 g (60-4360 g) and 211 g (17-1950 g), respectively. There was no mortality in any of the cases., Conclusion: Mobilization of the pancreas head and left-sided approach using a caudal view will be a safe and useful technique for MIPD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: There are few reports describing the unusual origin of the inferior mesenteric artery (IMA). We report a rare case of advanced sigmoid colon cancer with the IMA arising from the superior mesenteric artery., Case Presentation: A 59-year-old man with diarrhea and abdominal distention was diagnosed with advanced sigmoid colon cancer. Colonoscopy revealed a semi-circumferential cancer lesion in the sigmoid colon. Enhanced CT scan and CT angiography showed that the IMA directly originated from the superior mesenteric artery at the level of the second lumbar vertebra. PET-CT suggested metastases in the para-intestinal lymph nodes and the liver, but not in the central lymph nodes along the IMA. Preoperative diagnosis was sigmoid colon cancer cT4aN2aM1a cStage IVA(UICC, 8th edition). We performed laparoscopic complete resection as the radical treatment of the primary region prior to resection of the liver metastases. Intraoperative findings showed that the IMA was running parallel to the abdominal aorta; meanwhile, the colonic autonomic nerve was supplied from the lumbar splanchnic nerve at the caudal side of the duodenum. Central lymph nodes around the colonic autonomic nerve were dissected en bloc with the regional lymph nodes. Pathological radical resection including the regional lymph nodes metastasis was achieved. Two months later, complete resection of the liver metastasis was performed. After the adjuvant chemotherapy, no recurrence was observed 1.5 years after the liver resection was performed., Conclusions: Preoperative confirmation of the anatomy helped us to safely complete radical surgery in a patient with unusual bifurcation of the IMA., (© 2023. The Author(s).)

Although chemotherapy has been an essential treatment for cancer, the development of immune checkpoint blockade therapy was revolutionary, and a comprehensive understanding of the immunological tumor microenvironment (TME) has become crucial. Here, we investigated the impact of neoadjuvant chemotherapy (NAC) on immune cells in the TME of human esophageal squamous cell carcinoma using single cell RNA-sequencing. Analysis of 30 fresh samples revealed that CD8+/CD4+ T cells, dendritic cells (DCs), and macrophages in the TME of human esophageal squamous cell carcinoma showed higher levels of an anti-tumor immune response in the NAC(+) group than in the NAC(-) group. Furthermore, the immune cells of the NAC(+) group interacted with each other resulting in enhanced anti-tumor immune response via various cytokines, including IFNG in CD8+/CD4+ T cells, EBI3 in DCs, and NAMPT in macrophages. Our results suggest that NAC potentially enhances the anti-tumor immune response of immune cells in the TME., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Purpose: A diagnostic and treatment strategy for appendiceal tumors (ATs) has not been established. We aimed to evaluate our treatment strategy in ATs, including laparoscopic surgery (LS), and to identify preoperative malignancy predictors., Methods: A total of 51 patients between 2011 and 2021 were retrospectively reviewed. Data, including tumor markers and imaging findings, were compared between carcinoma and non-carcinoma patients. Validity of planned operation was evaluated based on pathological diagnosis., Results: Twenty-five patients were diagnosed with carcinoma, 13 with low-grade mucinous neoplasm, and 13 with other diseases. Symptoms were more commonly present in carcinoma patients than in non-carcinoma patients (68.0% vs. 23.1%, p = 0.001). Elevated CEA and CA19-9 were more frequently observed in carcinoma patients than in non-carcinoma patients (p < 0.01 and p = 0.04, respectively). Five carcinoma patients had malignancy on biopsy, compared with zero non-carcinoma patients. Significant differences were noted in the percentages of carcinoma and non-carcinoma patients with solid enhanced mass (41.7% vs. 0%, p < 0.001) and tumor wall irregularity (16.7% vs. 0%, p = 0.03) on imaging. Although the sensitivity was not high, the specificity and positive predictive value of these findings were 100%. Forty-two patients (82.4%) underwent LS as minimally invasive exploratory and/or radical operation, of whom 2 were converted to open surgery for invasion of adjacent organ. No patients had intraoperative complications or postoperative mortality., Conclusion: Clinical symptoms, elevated tumor markers, and worrisome features of solid enhanced mass and tumor wall irregularity on imaging can be malignancy predictors. For management of ATs, LS is feasible and useful for diagnosis and treatment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To determine whether N3 nodal involvement predicts outcomes and whether its prognostic implications vary with tumor location in patients with Stage III colon cancer (CC)., Methods: We defined N3 as lymph node metastases near the bases of the major feeding arteries. We retrospectively examined recurrence rates and patterns by tumor location and sites of lymph node metastases in 57 patients with N3 CC who had undergone curative resections between January 2000 and March 2019. Survival analysis was performed to compare the prognoses of patients with and without N3 lymph node metastasis., Results: Most N3 patients had large tumors (T ≥ 3); five had T2 disease. Recurrence occurred quickly in one patient with T2N3M0 disease. Multivariate survival analysis demonstrated that N3 lymph node metastasis is an independent predictor of poor prognosis in Stage III CC patients (P < 0.001). Categorizing N3 patients according to UICC-TNM staging system does not stratify risk of recurrence (P = 0.970). To investigate the impact of tumor location on recurrence risk, we classified N3 CC into two subtypes according to tumor location: metastasis at the base of the superior mesenteric artery in right-sided CC and inferior mesenteric artery in left-sided CC. The former was found to have a statistically significant poorer prognosis than the latter (P = 0.091)., Conclusion: N3 is a robust prognostic marker in CC patients. Recurrence risk varies by tumor location. N3 right-sided CCs with lymph node metastasis at the base of the superior mesenteric artery have poorer prognoses than do N3 left-sided CCs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Tumour immune microenvironment is related with carcinogenesis and efficacy of immunotherapy. B cells play major roles in humoral immunity, but detailed functions of tumour-infiltrating B lymphocytes (TIL-Bs) are unknown. Therefore, our aim was to investigate the functional heterogeneity of TIL-Bs in oesophageal squamous cell carcinoma (ESCC) and lymph nodes (LNs) during chemotherapy., Methods: Single-cell transcriptome analysis was performed on 23 specimens. We also performed immunohistochemical analysis of immunoglobulin κ C (IGKC), an antibody-secreting cell (ASC) marker, in 166 ESCC samples and evaluated the implication of IGKC in 2-year recurrence free survival (RFS) and 3-year overall survival (OS)., Results: A total of 81,246 cells were grouped into 24 clusters. We extracted B cell clusters based on canonical markers and identified 12 TIL-B subtypes in ESCC. We found that several functions, such as co-stimulation and CD40 signalling, were enhanced in TIL-Bs after chemotherapy. The proportion of naive B cells (NBCs) decreased and B cell activation genes were up-regulated in NBCs after chemotherapy. The proportion of ASCs in tumours increased with the loss of migratory abilities and antibody production in ASCs was promoted after chemotherapy. Differentially expressed genes up-regulated with chemotherapy in ASCs correlated with prolonged survival with oesophageal cancer (p = .028). In a metastatic LN, the ASC proportion increased and B cell differentiation was enhanced. In immunohistochemical analysis, RFS and OS of high IGKC expression cases were significantly better than those of low IGKC expression cases (RFS: p < .0001, OS: p < .0001). And in multivariable analysis, the expression of IGKC was an independent favourable prognostic factor for RFS (hazard ratio (HR): 0.23, 95% confidence interval (CI): 0.12-0.45, p < .0001) and OS (HR: 0.20, 95% CI: 0.086-0.47, p = .0002) in ESCC., Conclusions: Our findings provide novel insights for the heterogeneity of TIL-Bs during chemotherapy and will be useful to understand the clinical importance of TIL-Bs., (© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: Patients with longstanding inflammatory bowel disease are at high risk of developing intestinal cancers. In this study, we aimed to elucidate the differences between intestinal cancers associated with ulcerative colitis and Crohn's disease., Methods: Intestinal cancers in ulcerative colitis and Crohn's disease patients treated between 1983 and 2020 at 43 Japanese institutions were retrospectively analyzed.., Results: A total of 1505 intestinal cancers in 1189 ulcerative colitis and 316 Crohn's disease patients were studied. Almost all of ulcerative colitis-associated cancers (99%) were in the colon and rectum, whereas half of Crohn's disease-associated cancers (44%) were in the anus, with 11% in the small intestine. Ulcerative colitis-associated cancers were diagnosed more frequently by surveillance (67% vs. 25%, P < 0.0001) and at earlier stages (stages 0-1, 71% vs. 27%, P < 0.0001) compared with Crohn's disease-associated cancers. Colorectal cancers associated with Crohn's disease showed a significantly worse 5-year overall survival rate than those associated with ulcerative colitis (stage 2, 76% vs. 89%, P = 0.01, stage 3, 18% vs. 68%, P = 0.0009, and stage 4, 0% vs. 13%, P = 0.04). Surveillance correlated with earlier diagnoses for ulcerative colitis- and Crohn's disease-associated intestinal cancers, whereas shorter intervals between endoscopic examinations correlated with an earlier cancer diagnosis in ulcerative colitis patients but not in Crohn's disease patients., Conclusions: The clinical and oncological features of ulcerative colitis- and Crohn's disease-associated cancers were very different. Crohn's disease-associated cancers were diagnosed at more advanced stages and were detected less frequently by surveillance. Additionally, they showed a significantly poorer prognosis., (© 2022. Japanese Society of Gastroenterology.)

TP53 is a tumor suppressor gene and, when dysfunctional, it is known to be involved in the development of cancers. Li-Fraumeni syndrome (LFS) is a hereditary tumor with autosomal dominant inheritance that develops in people with germline pathogenic variants of TP53. LFS frequently develops in parallel to tumors, including breast cancer. We describe a novel germline mutation in TP53 identified by performing a multi-gene panel assay in a breast cancer patient with bilateral breast cancer., (© 2022. The Author(s).)

Purpose: Preoperative sarcopenia worsens postoperative outcomes in various cancer types including colorectal cancer. However, we often experienced postoperative anastomotic leakage in muscular male patients such as Judo players, especially in rectal cancer surgery with lower anastomosis. It is controversial whether the whole skeletal muscle mass impacts the potential for anastomotic failure in male rectal cancer patients. Thus, the purpose of this study was to clarify whether skeletal muscle mass impacts anastomotic leakage in rectal cancer in men., Methods: We reviewed the medical charts of male patients suffering from rectal cancer who underwent colo-procto anastomosis below the peritoneal reflection without a protective diverting stoma. We measured the psoas muscle area and calculated the psoas muscle index., Results: One hundred ninety-seven male rectal cancer patients were enrolled in this study. The psoas muscle index was significantly higher in patients with anastomotic leakage (P<0.001). Receiver operating characteristic curve determined the optimal cut-off value of the psoas muscle index for predicting anastomotic leakage as 812.67 cm2/m2 (sensitivity of 60% and specificity of 74.3%). Multivariate analysis revealed that high psoas muscle index (risk ratio [RR], 3.933; P<0.001; 95% confidence interval [CI], 1.917-8.070) and super low anastomosis (RR, 2.792; P=0.015; 95% CI, 1.221-6.384) were independent predictive factors of anastomotic leakage., Conclusion: This study showed that male rectal cancer patients with a large psoas muscle mass who underwent lower anastomosis had a higher rate of postoperative anastomotic leakage.

Aim: To investigate the impact of postoperative infection (PI), surgical site infection, and remote infection (RI), on long-term outcomes in patients with colorectal cancer (CRC)., Methods: The Japan Society for Surgical Infection conducted a multicenter retrospective cohort study involving 1817 curative stage I/II/III CRC patients from April 2013 to March 2015. Patients were divided into the No-PI group and the PI group. We examined the association between PI and oncological outcomes for cancer-specific survival (CSS) and overall survival (OS) using Cox proportional hazards models and propensity score matching., Results: Two hundred and ninety-nine patients (16.5%) had PIs. The 5-year CSS and OS rates in the No-PI and PI groups were 92.8% and 87.6%, and 87.4% and 83.8%, respectively. Both the Cox proportional hazards models and propensity score matching demonstrated a significantly worse prognosis in the PI group than that in the No-PI group for CSS (hazard ratio: 1.60; 95% confidence interval: 1.10-2.34; P  = .015 and P  = .031, respectively) but not for OS. RI and the PI severity were not associated with oncological outcomes. The presence of PI abolished the survival benefit of adjuvant chemotherapy., Conclusions: These results suggest that PI after curative CRC surgery is associated with impaired oncological outcomes. This survival disadvantage of PI was primarily derived from surgical site infection, not RI, and PI induced lower efficacy of adjuvant chemotherapy. Strategies to prevent PI and implement appropriate postoperative treatment may improve the quality of care and oncological outcomes in patients undergoing curative CRC surgery., (© 2022 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterology.)

For stage II and III esophageal squamous cell carcinoma (ESCC), neoadjuvant chemotherapy (NAC) followed by esophagectomy is recommended in the Japanese guidelines for the diagnosis and treatment of esophageal cancer. However, recurrence of ESCC is common regardless of the NAC regimen and surgical method, and NAC demonstrates limited efficacy against recurrence. Therefore, the present study was conducted to identify risk factors of recurrence of ESCC with surgery after NAC. The outcomes of 51 patients who underwent esophagectomy for ESCC after NAC from 2010 to 2017 at Kyushu University Hospital were retrospectively analyzed. A total of 52 patients with ESCC without NAC followed by esophagectomy from 2001 to 2017 were selected for comparison. Among patients who underwent NAC followed by surgery, only lymphatic invasion (LY; hazard ratio, 2.761; 95% CI, 1.86-6.43, P=0.018) was an independent factor significantly associated with 3-year recurrence-free survival in the multivariate analysis. In patients with pathologic lymph node metastasis (pN) and no LY after NAC, there was significantly less recurrence compared with patients with pN and LY (P=0.0085), whereas in patients without LY after NAC, the presence of pN was not significantly associated with recurrence (P=0.2401). There were significantly fewer LY (+) patients in the NAC (+) group (P=0.0158) compared with those in the NAC (-) group. The presence of LY was an independent risk factor for recurrence of ESCC after esophagectomy following NAC. Overall, adjuvant treatment after surgery may be required in cases with remnant LY after NAC., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Okuda et al.)

Background/aim: Hereditary tumors are estimated to account for approximately 5-10% of all tumors. In Europe and the United States, multi-gene panel testing (MGPT) is the standard method used for identifying potential causative genes. However, MGPT it is still not widely used in Japan. The aim of this study was to assess the risk of hereditary tumors in Japanese cancer patients using germline MGPT and provide an overview of MGPT in the Japanese medical system., Patients and Methods: We used the myRiskTM, a 35-gene panel that determines the risk for eight hereditary cancers: breast, ovarian, gastric, colorectal, prostate, pancreatic, malignant melanoma, and endometrial cancers., Results: From June 2019 to March 2020, 21 patients who were suspected to have hereditary tumors were included, based on their family or medical history. Pathogenic variants were found in 7 patients [BRCA1 (5), MSH6 (1), TP 53 (1)]., Conclusion: In this study, despite the small number of participants, we were able to show the significance of MGPT in Japan. Therefore, MGPT should be used for evaluating hereditary tumors in clinical practice., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A 71-year-old man was admitted to our institution complaining of abdominal pain and constipation. Barium enema examination revealed narrowing, cobble stoning, and longitudinal ulcerations in the sigmoid colon and upper rectum. Conventional colonoscopy, magnifying narrow-band imaging endoscopy, and magnifying chromoendoscopy revealed edematous mucosa, longitudinal ulcerations with luminal narrowing, and multiple pseudopolyps. The histologic examination of the biopsy specimens showed thick-walled (arterialized) capillaries and subendothelial fibrin deposits in the mucosa and submucosa. Based on a preoperative diagnosis of idiopathic myointimal hyperplasia of mesenteric veins (IMHMV), he underwent a laparoscopic resection of the sigmoid colon and upper rectum. The histologic examination of the resected specimens showed marked proliferation of venous walls with marked myointimal thickening and luminal occlusion from the submucosa to the mesentery throughout the entire resected tissue section. The final diagnosis was IMHMV., (© 2022. Japanese Society of Gastroenterology.)

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma in which microenvironmental (niche) factors promote PDAC progression. In mouse models, reduction of the stroma increased the proportion of poorly differentiated PDAC with a worse prognosis. Here, we aimed to clarify the effects of stroma on PDAC that may define the PDAC phenotype and induce distinct therapeutic responses., Methods: The molecular features of PDAC based on differentiation grade were clarified by genome and transcriptome analysis using PDAC organoids (PDOs). We identified the dependency on niche factors that might regulate the differentiation grade. A three-dimensional co-culture model with cancer-associated fibroblasts (CAFs) was generated to determine whether CAFs provide niche factors essential for differentiated PDAC. PDOs were subtyped based on niche factor dependency, and the therapeutic responses for each subtype were compared., Results: The expression profiles of PDOs differed depending on the differentiation grade. Consistent with the distinct profiles, well differentiated types showed high niche dependency, while poorly differentiated types showed low niche dependency. The three-dimensional co-culture model revealed that well differentiated PDOs were strongly dependent on CAFs for growth, and moderately differentiated PDOs showed plasticity to change morphology depending on CAFs. Differentiated PDOs upregulated the expression of mevalonate pathway-related genes correlated with the niche dependency and were more sensitive to simvastatin than poorly differentiated PDOs., Conclusions: Our findings suggest that CAFs maintain the differentiated PDAC phenotype through secreting niche factors and induce distinct drug responses. These results may lead to the development of novel subtype-based therapeutic strategies., (© 2022. The Author(s).)

Background: In contrast to open-surgery abdominoperineal excision (APE) for rectal cancer, postoperative perineal hernia (PPH) is reported to increase after extralevator APE and endoscopic surgery. In this study, therefore, we aimed to determine the risk factors for PPH after endoscopic APE., Methods: A total 73 patients who underwent endoscopic APE for rectal cancer were collected from January 2009 to March 2020, and the risk factors for PPH were analyzed retrospectively., Results: Nineteen patients (26%) developed PPH after endoscopic APE, and the diagnosis of PPH was made at 9-393 days (median: 183 days) after initial surgery. Logistic regression analysis showed that absence of pelvic peritoneal closure alone increased the incidence of PPH significantly (odds ratio; 13.76, 95% confidence interval; 1.48-1884.84, p = 0.004)., Conclusions: This preliminary study showed that pelvic peritoneal closure could prevent PPH after endoscopic APE., (© 2022. The Author(s).)

Background: The addition of lateral pelvic lymph node dissection (LPLND) in rectal cancer surgery has been reported to increase the incidence of post-operative urinary retention. Here, we assessed the predictive factors and long-term outcomes of urinary retention following laparoscopic LPLND (L-LPLND) with total mesorectal excision (TME) for advanced lower rectal cancer., Methods: This retrospective single-institutional study reviewed post-operative urinary retention in 71 patients with lower rectal cancer who underwent L-LPLND with TME. Patients with preoperative urinary dysfunction or who underwent unilateral LPLND were excluded. Detailed information regarding patient clinicopathologic characteristics, post-void residual urine volume, and the presence or absence of urinary retention over time was collected from clinical and histopathologic reports and telephone surveys. Urinary retention was defined as residual urine > 100 mL and the need for further treatment., Results: Post-operative urinary retention was observed in 25/71 patients (35.2%). Multivariate analysis revealed that blood loss ≥ 400 mL [odds ratio (OR) 4.52; 95% confidence interval (CI) 1.24-16.43; p = 0.018] and inferior vesical artery (IVA) resection (OR 8.28; 95% CI 2.46-27.81; p < 0.001) were independently correlated with the incidence of urinary retention. Furthermore, bilateral IVA resection caused urinary retention in more patients than unilateral IVA resection (88.9% vs 47.1%, respectively; p = 0.049). Although urinary retention associated with unilateral IVA resection improved relatively quickly, urinary retention associated with bilateral IVA resection tended to persist over 1 year., Conclusion: We identified the predictive factors of urinary retention following L-LPLND with TME, including increased blood loss (≥ 400 mL) and IVA resection. Urinary retention associated with unilateral IVA resection improved relatively quickly. L-LPLND with unilateral IVA resection is a feasible and safe procedure to improve oncological curability. However, if oncological curability is guaranteed, bilateral IVA resection should be avoided to prevent irreversible urinary retention., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Postoperative adjuvant chemotherapy for patients with stage III colon cancer (CC) is regarded as the standard treatment worldwide for outcome improvement and relapse prevention. Similarly, high-risk stage II CC requires adjuvant chemotherapy because of its high recurrence rate. Previous randomized controlled trials showed that oxaliplatin (OX), in addition to fluorinated pyrimidine-based therapy for patients with stage II/III CC, significantly improves cancer survival but it remains controversial as to which patient groups should receive OX-containing regimens. Among 1,150 consecutive patients who underwent curative resection for stage II/III CC between 2009 and 2016 at two tertiary hospitals, 349 patients treated with only peroral (PO) fluorinated pyrimidine-based chemotherapy and 149 patients who received fluorinated pyrimidine-based chemotherapy with OX as adjuvant chemotherapy were retrospectively reviewed. The primary outcome was recurrence-free survival (RFS). Clinicopathological factors were more advanced in patients treated with OX than in patients treated only with PO fluorinated pyrimidine agents. Multivariate analysis for 5-year RFS showed that T4 [hazard ratio (HR), 2.947; P=0.0001], N2 (HR, 2.704; P=0.0075), vessel or lymphatic invasion (HR, 1.675; P=0.0437) and high cancer antigen (CA)19-9 (HR 3.367, P=0.0002) levels were independent risk factors of cancer relapse. Propensity score matching analysis was performed to match clinicopathological differences between the PO and OX groups. After matching, subgroup analysis of the patients showed that greater effects of OX on cancer survival were observed in patients in the OX group with high CA19-9 levels and tended to be associated with T4 and N2 compared with the PO group. Thus, OX-containing regimens should be recommended for patients with CC with these factors in an adjuvant setting., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

Background: Delta-shaped anastomosis is an established procedure for intracorporeal Billroth-I reconstruction (B-I). However, this procedure has several technical and economic problems. The aim of the current study was to present the technique of B-I using an overlap method (overlap B-I), which is a side-to-side intracorporeal gastroduodenostomy in laparoscopic distal gastrectomy (LDG), and to evaluate the short- and long-term outcomes of this overlap B-I procedure., Methods: We retrospectively reviewed the medical records of 533 patients who underwent LDG with overlap B-I (n = 247) or Roux-en-Y reconstruction (R-Y) (n = 286). Patients with overlap B-I were propensity score matched to patients with R-Y in a 1:1 ratio. Short- and long-term outcomes of the two procedures were compared after matching., Results: In the total cohort, anastomosis-related complications occurred in 2.4% of patients with overlap B-I, and 3.2% of those with R-Y (P = 0.794). Morbidity rate, including anastomosis-related complications, and postoperative course were comparable after overlap B-I performed by qualified versus general surgeons. Of 247 patients with overlap B-I, 169 could be matched. After matching, morbidity rate and postoperative course were comparable between the two procedures. Median operation time was significantly shorter for overlap B-I (205 min) than R-Y (252 min; P < 0.001). The incidence of readmission due to gastrointestinal complications was significantly lesser after overlap B-I (2.4%) compared with R-Y (21.9%; P < 0.001). The main causes of readmission after R-Y were bowel obstruction (7.3%) and gallstones (8.0%). Regarding the development of common bile duct (CBD) stones, 11 patients (3.8%) who underwent R-Y were readmitted due to CBD stones, whereas no patients who underwent B-I developed CBD stones., Conclusions: Overlap B-I is feasible and safe, even when performed by general surgeons. B-I was superior to R-Y concerning operation time and readmission due to gastrointestinal complications.

Background/aim: Metabolomics is widely used for biomarker discovery, but conventional mass-spectrometry extraction procedures lose the spatial localization of metabolites. In this study, we directly analyzed breast carcinoma tissues embedded in frozen tissue microarrays (fTMAs) using MALDI mass-spectrometry imaging (MALDI-MSI)., Materials and Methods: A total of 119 breast tissues (84 carcinoma and 35 normal) were used. MSI data were extracted from each tissue., Results: Overall, 185 of 1,915 peaks which were commonly detected in 60% of target areas were subjected to further analysis. One hundred and fifty-two peaks of carcinoma showed significantly higher intensity than normal. Comparing metabolite profiles from carcinoma and normal tissues, energy charge (EC) and the sum of adenosine phosphate compound (AXP) indicated significantly higher intensities in cancerous tissues than normal. But comparisons of EC and AXP among lymph node metastasis, tumor size and tumor subtypes indicated no significant differences., Conclusion: Breast carcinoma tissues had higher EC and AXP values than normal. MALDI-MSI could be a tool for characterizing breast carcinoma., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

In intraductal papillary mucinous neoplasms (IPMNs), the presence of a mural nodule showing a papillary or nodular proliferation of tumor cells in the dilated pancreatic duct is an indication for resection of IPMN. Solute carrier family 2, facilitated glucose transporter member 1, known as glucose transporter type 1 (SLC2A1/GLUT1) mediates cellular glucose uptake in many carcinomas and is correlated with increased 18 F-fluorodeoxyglucose ( 18 F-FDG) uptake. We examined SLC2A1/GLUT1 expression in the mural nodules of 180 IPMN specimens to distinguish malignant/benign tumors. A mural nodule was detected in 80 (44.4%) of the IPMNs, and was detected in 18.6% (13/70) of the IPMN-low (dysplasia) specimens, 36.1% (13/36) of the IPMN-int, 93.3% (28/30) of the IPMN-high, and 59.1% (26/44) of the IPMN-inv (with an associated invasive carcinoma) specimens. The sensitivity for detecting mural nodules was 81.7% by endoscopic ultrasonography, 70% by contrast-enhanced computed tomography and 54% by endoscopic retrograde cholangiopancreatography. SLC2A1/GLUT1 expression in the mural nodules was recognized in the basal and basolateral cytomembrane of tumor cells and was expressed in 15.4% (2/13) of the IPMN-low, 15.4% (2/13) of the IPMN-int, 71.4% (20/28) of the IPMN-high and 84.6% (22/26) of the IPMN-inv groups. The SLC2A1/GLUT1 expression was significantly higher in the IPMN-high and IPMN-inv mural nodules than in those of the IPMN-low and IPMN-int groups. Our findings suggest that SLC2A1/GLUT1 is expressed late in the adenoma-carcinoma sequence during carcinogenesis in IPMN, and SLC2A1/GLUT1 act as therapeutic target for malignant IPMN., (Copyright © 2017. Published by Elsevier Inc.)

Background & Aims: Pancreatic stellate cells (PSCs) change from a quiescent to activated state in the tumor environment and secrete extracellular matrix (ECM) molecules and cytokines to increase the aggressiveness of tumors. However, it is not clear how PSCs are activated to produce these factors, or whether this process can be inhibited. PSCs have morphologic and functional similarities to hepatic stellate cells, which undergo autophagy to promote fibrosis and tumor growth. We investigated whether autophagy activates PSCs, which promotes development of the tumor stroma and growth of pancreatic tumors in mice., Methods: We used immunofluorescence microscopy and immunohistochemistry to analyze pancreatic tumor specimens from 133 patients who underwent pancreatectomy in Japan from 2000 to 2009. PSCs were cultured from pancreatic tumor tissues or tissues of patients with chronic pancreatitis; these were analyzed by immunofluorescence microscopy, immunoblots, quantitative reverse transcription polymerase chain reaction, and in assays for invasiveness, proliferation, and lipid droplets. Autophagy was inhibited in PSCs by administration of chloroquine or transfection with small interfering RNAs. Proteins were knocked down in immortalized PSCs by expression of small hairpin RNAs. Cells were transplanted into pancreatic tails of nude mice, and tumor growth and metastasis were quantified., Results: Based on immunohistochemical analyses, autophagy was significantly associated with tumor T category (P = .018), histologic grade (P = .001), lymph node metastases (P < .001), stage (P = .009), perilymphatic invasion (P = .001), and perivascular invasion (P = .003). Autophagy of PSCs was associated with shorter survival times of patients with pancreatic cancer. PSC expression of microtubule-associated protein 1 light chain 3, a marker of autophagosomes, was associated with poor outcomes (shorter survival time, disease recurrence) for patients with pancreatic cancer (relative risk of shorter survival time, 1.56). Immunoblots showed that PSCs from pancreatic tumor samples expressed higher levels of markers of autophagy than PSCs from chronic pancreatitis samples. Inhibitors of autophagy increased the number of lipid droplets of PSCs, indicating a quiescent state of PSCs, and reduced their production of ECM molecules and interleukin 6, as well as their proliferation and invasiveness in culture. PSCs exposed to autophagy inhibitors formed smaller tumors in nude mice (P = .001) and fewer liver metastases (P = .018) with less peritoneal dissemination (P = .018) compared to PSCs not exposed to autophagy inhibitors., Conclusions: Autophagic PSCs produce ECM molecules and interleukin 6 and are associated with shorter survival times and disease recurrence in patients with pancreatic cancer. Inhibitors of PSC autophagy might reduce pancreatic tumor invasiveness by altering the tumor stroma., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Pancreatic cancer progression involves components of the tumor microenvironment, including stellate cells, immune cells, endothelial cells, and the extracellular matrix. Although peripancreatic fat is the main stromal component involved in extra-pancreatic invasion, its roles in local invasion and metastasis of pancreatic cancer remain unclear. This study investigated the role of adipose tissue in pancreatic cancer progression using genetically engineered mice (Pdx1-Cre; LSL-KrasG12D; Trp53R172H/+) and an in vitro model of organotypic fat invasion. Mice fed a high fat diet had significantly larger primary pancreatic tumors and a significantly higher rate of distant organ metastasis than mice fed a standard diet. In the organotypic fat invasion model, pancreatic cancer cell clusters were smaller and more elongated in shape and showed increased fibrosis. Adipose tissue-derived conditioned medium enhanced pancreatic cancer cell invasiveness and gemcitabine resistance, as well as inducing morphologic changes in cancer cells and increasing the numbers of lipid droplets in their cytoplasm. The concentrations of oleic, palmitoleic, and linoleic acids were higher in adipose tissue-derived conditioned medium than in normal medium, with these fatty acids significantly enhancing the migration of cancer cells. Mature adipocytes were smaller and the concentration of fatty acids in the medium higher when these cells were co-cultured with cancer cells. These findings indicate that lipolytic and fibrotic changes in peripancreatic adipose tissue enhance local invasiveness and metastasis via adipocyte-released fatty acids. Inhibition of fatty acid uptake by cancer cells may be a novel therapy targeting interactions between cancer and stromal cells.