Publications by authors named "Hideo Baba"

1,287 Publications

  • Page 1 of 1

Intra-abdominal bleeding caused by amyloid transthyretin amyloidosis in the gastrointestinal tract: a case report.

Clin J Gastroenterol 2021 Nov 19. Epub 2021 Nov 19.

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.

Diagnosis of gastrointestinal (GI) amyloidosis is often very difficult because of its nonspecific symptoms. However, a few reports have indicated that serious symptoms such as fatal GI bleeding and obstruction or perforation sometimes lead to a diagnosis of GI amyloidosis. A 79-year-old man was transported to our emergency department with a 1-week history of worsening abdominal pain. Abdominal contrast-enhanced computed tomography showed extravasation from part of the transverse colon wall and moderate ascites. Because intra-abdominal bleeding was suspected, the patient urgently underwent partial resection of the transverse colon, which was the source of the bleeding. Postoperative pathological examination of the tissue specimens led to a diagnosis of amyloid transthyretin amyloidosis. This is the first reported case in which intra-abdominal bleeding led to a diagnosis of GI amyloidosis. We should consider the possibility of GI amyloidosis when intraperitoneal bleeding is observed in elderly patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12328-021-01551-yDOI Listing
November 2021

PD-L1 and PD-L2 expression status in relation to chemotherapy in primary and metastatic esophageal squamous cell carcinoma.

Cancer Sci 2021 Nov 12. Epub 2021 Nov 12.

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.

Immune checkpoint inhibitors have shown efficacy in various cancers. Although PD-L1/L2 expressions have been demonstrated as predictive biomarkers of response to immune checkpoint inhibitors and prognostic markers, whether PD-L1/L2 expression is altered in esophageal squamous cell carcinoma during the therapeutic course is unclear. Whether PD-L1/L2 expression in metastatic or recurrent lesions is consistent with that in primary tumors is also unknown. This study included 561 surgically resected esophageal squamous cell carcinoma and PD-L1/L2 expression was evaluated by immunohistochemistry. We investigated the influence of chemotherapeutic drugs (cisplatin and fluorouracil) on PD-L1/L2 expression and PD-L1/L2-related pathways in vitro. We also examined PD-L1/L2 expression in 18 surgically resected lymph node metastases and 10 recurrent lesions compared with primary lesions. The positive rate of PD-L1 was significantly higher in patients with preoperative chemotherapy than in those without preoperative therapy. The positive rate of PD-L2 expression showed no significant difference between patient groups. Cisplatin increased PD-L1 expression in cancer cell lines in vitro, but decreased PD-L2 in some cell lines. The effects of cisplatin on pSTAT1/3 also differed depending on cell lines. Fluorouracil increased PD-L1 and PD-L2 expression. PD-L1/L2 expression in lymph node metastases and recurrent lesions did not always match expression in primary lesions. PD-L1/L2 expression may be altered by preoperative chemotherapy, and PD-L1 /L2 expression in primary lesions does not always match that of metastatic/recurrent lesions. Thus, one-time evaluation is not sufficient to evaluate PD-L1/L2 expression as a biomarker in esophageal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.15198DOI Listing
November 2021

Overall survival after recurrence in stage I-III colorectal cancer patients in accordance with the recurrence organ site and pattern.

Ann Gastroenterol Surg 2021 Nov 14;5(6):813-822. Epub 2021 Jul 14.

Department of Gastroenterological Surgery Graduate School of Medical Sciences Kumamoto University Kumamoto Japan.

Aim: This study aimed to investigate the prognosis after recurrence in patients with stage I-III colon cancer (CC) and rectal cancer (RC).

Methods: Cancer recurred in 116 (15.2%) out of 763 patients with stage I-III colorectal cancer. The overall survival (OS) after recurrence was evaluated based on the recurrence organs and patterns.

Results: The first recurrence occurred in the lungs, livers, lymph nodes, and other sites in 32, 22, 12, and 2 patients, respectively. It was localized, disseminated, and involved two or more organs in 14, 9, and 25 patients, respectively. Patients with CC had a shorter OS after recurrence as compared to those with RC ( = .0103). Compared to other organ metastasis, liver metastasis was associated with an earlier recurrence ( = .0026) and shorter OS after recurrence (hazard ratio [HR]: 2.216; 95% confidence interval [CI]: 1.052-4.459;  = .0370). Lung metastasis was associated with a more favorable prognosis as compared to other organ recurrences (HR: 0.338; 95% CI: 0.135-0.741;  = .0057). One-organ recurrence and oligometastasis were observed in 78.4% and 49.1% of the patients, respectively. The 5-y OS rates of patients with one-organ recurrence and oligometastasis were 47.5% and 71.7%, respectively. Invasive treatment was associated with a favorable prognosis ( < .0001).

Conclusions: Liver metastasis and dissemination were associated with a shorter OS after recurrence. Approximately 50% of the patients experienced oligometastasis, which was associated with a favorable prognosis. Hence, to improve patient prognosis it is better to perform invasive treatments when possible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ags3.12483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560596PMC
November 2021

Impact of Type of Gastrectomy on Death from Pneumonia in Elderly Patients with Gastric Cancer Over the Long Term.

World J Surg 2021 Nov 8. Epub 2021 Nov 8.

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.

Background: Gastrectomy may induce significant postoperative disabilities and worsen the quality of life in elderly patients. Without a functioning esophagogastric junction (EGJ), swallowing is impaired because of the anatomical and physiological changes after surgery, which increases the risk of postoperative pneumonia. The aim of this study was to identify the impact of the type of surgical procedure on death from pneumonia in elderly patients with gastric cancer (GC) over the long term.

Methods: We analyzed the data of 343 patients with GC who underwent curative gastrectomy in our hospital. We divided the patients into elderly and non-elderly groups. Among them, 109 patients aged ≥ 75 years who underwent curative resection were analyzed, their clinicopathological factors and clinical outcomes were compared, and the impact of the type of surgical procedure on death from pneumonia over the long term was evaluated. The institutional scientific review board of Kumamoto University Hospital was approved for data collection and analysis (No. 1037).

Results: There were significantly higher levels of American Society of Anesthesiologists (ASA) and poor nutrition in the elderly group; however, gender, BMI and factors related to pneumonia did not differ significantly between groups. The median duration of follow-up time 1588 days. On the multivariate analysis, age and surgical procedure were selected as independent predictive factors for pneumonia-related survival.

Conclusion: Preservation of the EGJ as much as possible while maintaining curability is useful for reducing postoperative death from pneumonia over the long term in elderly patients with gastric cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00268-021-06352-5DOI Listing
November 2021

Pan-cancer methylome analysis for cancer diagnosis and classification of cancer cell of origin.

Cancer Gene Ther 2021 Nov 8. Epub 2021 Nov 8.

Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.

The accurate and early diagnosis and classification of cancer origin from either tissue or liquid biopsy is crucial for selecting the appropriate treatment and reducing cancer-related mortality. Here, we established the CAncer Cell-of-Origin (CACO) methylation panel using the methylation data of the 28 types of cancer in The Cancer Genome Atlas (7950 patients and 707 normal controls) as well as healthy whole blood samples (95 subjects). We showed that the CACO methylation panel had high diagnostic potential with high sensitivity and specificity in the discovery (maximum AUC = 0.998) and validation (maximum AUC = 1.000) cohorts. Moreover, we confirmed that the CACO methylation panel could identify the cancer cell type of origin using the methylation profile from liquid as well as tissue biopsy, including primary, metastatic, and multiregional cancer samples and cancer of unknown primary, independent of the methylation analysis platform and specimen preparation method. Together, the CACO methylation panel can be a powerful tool for the classification and diagnosis of cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41417-021-00401-wDOI Listing
November 2021

Association of cell death mechanisms and fibrosis in visceral white adipose tissue with pathological alterations in the liver of morbidly obese patients with NAFLD.

Adipocyte 2021 12;10(1):558-573

Department of Medicine, University Hospital, Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Bochum, Germany.

The role of visceral white adipose tissue (vWAT) in the progression of non-alcoholic liver disease (NAFLD) with its sub entities non-alcoholic fatty liver and steatohepatitis (NAFL; NASH) is underinvestigated. We thus explored mechanisms of fibrosis and regulated cell death in vWAT and liver tissue. In NAFLD, women displayed significantly more fibrosis in vWAT than men, and collagen 1α mRNA expression was significantly upregulated. The degrees of fibrosis in vWAT and liver tissue correlated significantly. The size of vWAT-resident adipocytes in NAFLD correlated negatively with the local degree of fibrosis. The extent of apoptosis, as measured by circulating M30, positively correlated with the degree of fibrosis in vWAT; necrosis-associated HMGB1 mRNA expression was significantly downregulated in vWAT and liver tissue; (iii) necroptosis-related RIPK-3 mRNA expression was significantly upregulated in vWAT; and autophagy-related LC3 mRNA expression was significantly downregulated in vWAT, while upregulated in the liver. Thus, the different cell death mechanisms in the vWAT in NAFLD are regulated independently while not ruling out their interaction. Fibrosis in vWAT may be associated with reduced adipocyte size and thus partially protective against NAFLD progression. ATG5: autophagy related 5; BAS: bariatric surgery; BMI: body mass index; ELISA: enzyme-linked immunosorbent assay; EtOH: ethanol; FFAs: free fatty acids; HCC: hepatocellular carcinoma; HMGB1: high-mobility group box 1 protein; IHC: immunohistochemistry; IL: interleukin; LC3: microtubule-associated proteins 1A/1B light chain 3B; M30: neoepitope K18Asp396-NE displayed on the caspase-cleaved keratin 18 fragment; M65: epitope present on both caspase-cleaved and intact keratin 18; NAFL: non-alcoholic fatty liver; NAFLD: non-alcoholic fatty liver disease; NAS: NAFLD activity score; NASH: non-alcoholic steatohepatitis; NLRP3: nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3; qRT-PCR: quantitative real-time polymerase-chain reaction; r: Pearson's correlation coefficient (r); r: Spearman's rank correlation coefficient; RIPK3: receptor-interacting serine/threonine-protein kinase 3; T2DM: type 2 diabetes mellitus (T2DM); TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling; vWAT: visceral WAT; WAT: white adipose tissue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21623945.2021.1982164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583086PMC
December 2021

Investigation of risk factors for postoperative seroma/hematoma after TAPP.

Surg Endosc 2021 Oct 28. Epub 2021 Oct 28.

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.

Background: Seroma/hematoma formation is the most common postoperative complication after laparoscopic inguinal hernia repair. The occurrence of seroma/hematoma remains unclear. The aim of this study was to determine the risk factors for seroma/hematoma formation after transabdominal preperitoneal patch plasty (TAPP).

Methods: The study enrolled 359 groin hernia patients treated by TAPP at Kumamoto Medical Center between 2014 and 2019. The primary outcome was risk factors for postoperative seroma/hematoma formation after TAPP. The secondary outcomes included recurrence of hernia, postoperative complications, and hospital stay.

Results: Among the 359 patients, the incidence rate of seroma/hematoma was 16% (n = 69 patients), and the recurrence rate was 0.3% (n = 1 patient, both sides). In total, there were 452 lesions. Japan Hernia Society (JHS) type II was present in 23% (n = 106) of the total cases but was significantly more common in the postoperative seroma/hematoma group (40%; P = 0.0082). Meanwhile, JHS type I-3 comprised 27% of the total JHS type I group but was significantly higher in the postoperative seroma/hematoma JHS type I group (40%; P = 0.016). Compared with JHS type I, the multivariable odds ratio for postoperative seroma/hematoma formation in JHS type II was 2.77 (95% CI 1.54-4.95). Compared with JHS grade 1/2, the multivariable odds ratio for postoperative seroma/hematoma formation in JHS grade 3 was 2.27 (95% CI 1.28-4.03).

Conclusions: Internal inguinal hernia and hernia size ≥ 3 cm were considered risk factors for postoperative seroma/hematoma formation after TAPP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00464-021-08814-2DOI Listing
October 2021

Cellular senescence in the tumor microenvironment and context-specific cancer treatment strategies.

FEBS J 2021 Oct 15. Epub 2021 Oct 15.

Gastrointestinal Cancer Biology, International Research Center for Medical Sciences (IRCMS), Kumamoto University, Japan.

Cellular senescence in cancer development is known to have tumor-suppressive and tumor-promoting roles. Recent studies have revealed numerous molecular mechanisms of senescence followed by senescence-associated secretory phenotype induction and showed the significance of senescence on both sides. Cellular senescence in stromal cells is one of the reasons for therapeutic resistance in advanced cancer; thus, it is an inevitable phenomenon to address while seeking an effective cancer treatment strategy. This review summarizes the molecular mechanisms regarding cellular senescence, focusing on the dual roles played by senescence, and offers some direction toward successful treatments targeting harmful senescent cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/febs.16231DOI Listing
October 2021

Cancer-associated fibroblast senescence and its relation with tumour-infiltrating lymphocytes and PD-L1 expressions in intrahepatic cholangiocarcinoma.

Br J Cancer 2021 Oct 6. Epub 2021 Oct 6.

Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.

Background: Caveolin-1 (CAV1) in cancer-associated fibroblasts (CAFs) has pro- or anti-tumourigenic effect depending on the cancer type. However, its effect in intrahepatic carcinoma (ICC) remains unknown. Therefore, this study aimed to investigate the relationship between CAV1 in CAFs and tumour-infiltrating lymphocyte (TIL) numbers or PD-L1 levels in ICC patients.

Methods: Consecutive ICC patients (n = 158) were enrolled in this study. The levels of CAV1 in CAFs, CD8 + TILs, Foxp3+ TILs and PD-L1 in cancer cells were analysed using immunohistochemistry. Their association with the clinicopathological factors and prognosis were evaluated. The correlation between these factors was evaluated.

Results: CAV1 upregulation in CAFs was associated with a poor overall survival (OS) (P < 0.001) and recurrence-free survival (P = 0.008). Clinicopathological factors were associated with high CA19-9 levels (P < 0.001), advanced tumour stage (P = 0.046) and lymph node metastasis (P = 0.004). CAV1 level was positively correlated with Foxp3+ TIL numbers (P = 0.01). There were no significant correlations between CAV1 levels and CD8 + TIL numbers (P = 0.80) and PD-L1 levels (P = 0.97). An increased CD8 + TIL number and decreased Foxp3+ TIL number were associated with an increased OS. In multivariate analysis, positive CAV1 expression in CAFs (P = 0.013) and decreased CD8 + TIL numbers (P = 0.021) were independent poor prognostic factors.

Conclusion: Cellular senescence, represented by CAV1 levels, may be a marker of CAFs and a prognostic indicator of ICC through Foxp3+ TIL regulation. CAV1 expression in CAFs can be a therapeutic target for ICC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41416-021-01569-6DOI Listing
October 2021

Mutant KRAS as a prognostic biomarker after hepatectomy for rectal cancer metastases: Does the primary disease site matter?

J Hepatobiliary Pancreat Sci 2021 Oct 6. Epub 2021 Oct 6.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Background: The prognostic implication of mutant KRAS (mKRAS) among patients with primary disease in the rectum remains unknown.

Methods: From 2000 to 2018, patients undergoing hepatectomy for colorectal liver metastases at 10 collaborating international institutions with documented KRAS status were surveyed.

Results: A total of 834 (65.8%) patients with primary colon cancer and 434 (34.2%) patients with primary rectal cancer were included. In patients with primary colon cancer, mKRAS served as a reliable prognostic biomarker of poor overall survival (OS) (hazard ratio [HR]: 1.58, 95% CI 1.28-1.95) in the multivariable analysis. Although a trend towards significance was noted, mKRAS was not found to be an independent predictor of OS in patients with primary rectal tumors (HR 1.34, 95% CI 0.98-1.80). For colon cancer, the specific codon impacted in mKRAS appears to reflect underlying disease biology and oncologic outcomes, with codon 13 being associated with particularly poor OS in patients with left-sided tumors (codon 12, HR 1.56, 95% CI 1.22-1.99; codon 13, HR 2.10 95% CI 1.43-3.08;). Stratifying the rectal patient population by codon mutation did not confer prognostic significance following hepatectomy.

Conclusions: While the left-sided colonic disease is frequently grouped with rectal disease, our analysis suggests that there exist fundamental biologic differences that drive disparate outcomes. Although there was a trend toward significance of KRAS mutations for patients with primary rectal cancers, it failed to achieve statistical significance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jhbp.1054DOI Listing
October 2021

The Impact of Histologic Liver Inflammation on Oncology and the Prognosis of Patients Undergoing Hepatectomy for Hepatocellular Carcinoma.

Ann Surg Oncol 2021 Sep 30. Epub 2021 Sep 30.

Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan.

Background: Liver inflammation is a reaction to disease-causing stress in the liver that induces fibrosis and cirrhosis. However, its prognostic impact after hepatectomy remains unclear. This study aimed to evaluate the prognostic and oncologic impacts of liver inflammation on patients after curative hepatectomy for hepatocellular carcinoma (HCC).

Methods: The study enrolled 500 consecutive patients with primary HCC who underwent curative and primary hepatectomy. Patient characteristics and prognoses were evaluated according to histologic liver inflammation assessed by the New Inuyama Classification.

Results: Severe liver inflammation (A3) was observed in 97 patients (19.4%) and nonsevere liver inflammation (A0-2) in 403 patients (80.6%). The patients with A3 had a significantly poorer prognosis than those with A0-2 in terms of relapse-free survival (p < 0.0001, log-rank) and overall survival (p = 0.0013, log-rank). The study showed that A3 is an independent poor prognostic factor (hazard ratio, 1.36; 95% confidence interval [Cl], 1.02-1.81; p = 0.039), and that Child-Pugh grade B and multiple tumors are associated with relapse-free survival. Furthermore, The significant predictors of early recurrence (within 2 years after hepatectomy) were A3 (odds ratio, 2.10; 95% CI, 1.25-3.55; p = 0.005), a des-γ-carboxyprothrombin level higher than 40 mAU/mL, and multiple tumors.

Conclusions: Severe liver inflammation was associated with poor short- and long-term prognoses independently of cirrhosis. Controlling liver inflammation in the perioperative period may be essential to improving the prognosis of patients with HCC after hepatectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-021-10706-7DOI Listing
September 2021

Pancreaticoduodenectomy at a Non-high-volume Center and Efforts to Perform Safe Surgery.

Anticancer Res 2021 Oct;41(10):5223-5229

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

Aim: The aim of the current study was to investigate whether the artery-first approach (AFA) improved surgical outcomes of pancreaticoduodenectomy (PD) at our non-high-volume center.

Patients And Methods: We retrospectively reviewed data on 121 consecutive patients who underwent PD between January 2009 and December 2018. The perioperative data of 49 patients who underwent conventional PD (conventional group) and 72 patients who underwent PD via artery-first approach were analyzed and compared to assess the effectiveness of the AFA.

Results: Although no significant difference was observed between the two groups overall, in those with pancreatic cancer, the duration of surgery, intraoperative blood loss and transfusion rate in the AFA group (n=33) were significantly lower than those for the conventional group (n=11) (p=0.011, p=0.021 and p=0.038 respectively).

Conclusion: AFA can be used to reduce the operative time, intraoperative blood loss, and transfusion rate in patients with pancreatic cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.15341DOI Listing
October 2021

Preoperative transferrin level is a novel indicator of short- and long-term outcomes after esophageal cancer surgery.

Int J Clin Oncol 2021 Sep 29. Epub 2021 Sep 29.

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.

Background: This study aimed to examine whether preoperative serum transferrin, a rapid-turnover protein, correlates with short- and long-term outcomes after esophagectomy.

Methods: Preoperative transferrin levels, calculated by summing serum iron and unsaturated iron-binding capacity, were evaluated in 224 patients who underwent esophagectomy for stage I-III esophageal cancer without preoperative treatment. Transferrin levels are directly proportional to total iron-binding capacity (TIBC), and we defined TIBC < 250 μg/dL as low transferrin. We evaluated the relationship between preoperative transferrin levels and short- and long-term outcomes after esophagectomy using univariate and multivariate Cox proportional hazards analyses.

Results: Of all patients, 25 (11.2%) had low preoperative transferrin levels. Low preoperative transferrin levels were strongly correlated with worse preoperative performance status, advanced pathological T stage, and more open esophagectomy (p = 0.0078, 0.0001, and 0.013, respectively). Patients with low preoperative transferrin levels experienced significantly more frequent postoperative pneumonia in univariate and multivariate analysis [hazard ratio (HR) 3.30, 95% confidence interval (CI) 1.032-10.033, p = 0.0443]. Additionally, these patients were significantly correlated with worse overall survival (OS) in univariate and multivariate analyses (HR 2.75, 95% CI 1.018-7.426, p = 0.0460). Furthermore, we investigated the relationship between OS and postoperative pneumonia to elucidate why low preoperative transferrin, which is an independent risk factor for postoperative pneumonia, leads to poor prognosis. Patients with postoperative pneumonia were strongly associated with a shorter OS (p = 0.0099).

Conclusion: Preoperative serum transferrin levels may be a novel indicator of postoperative pneumonia and OS after esophagectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-021-02031-6DOI Listing
September 2021

Adapted systemic inflammation score as a novel prognostic marker for esophageal squamous cell carcinoma patients.

Ann Gastroenterol Surg 2021 Sep 15;5(5):669-676. Epub 2021 Jun 15.

Department of Gastroenterological Surgery Graduate School of Medical Sciences Kumamoto University Kumamoto Japan.

Background: The adapted systemic inflammation score (aSIS), calculated from serum albumin and the lymphocyte-to-monocyte ratio, has been reported to be a novel prognostic marker for some types of cancers. However, the prognostic impact of aSIS in patients with esophageal squamous cell carcinoma (ESCC) remains controversial. This study aimed to examine the prognostic effects of aSIS in a large cohort of 509 ESCC patients.

Methods: Preoperative aSIS was retrospectively calculated for 509 ESCC patients who underwent curative resection. Time-dependent receiver operating characteristics (t-ROC) curves were used for comparing the prognostic impact.

Results: Patients with high aSIS showed significantly poorer overall survival (OS) than patients with low aSIS (log rank  < .001). The multivariate analysis revealed that aSIS was an independent prognostic factor for overall survival (multivariate hazard ratio 1.76; 95% confidence interval 1.13-2.75;  = .013). The t-ROC analysis showed that aSIS was more sensitive than other nutritional prognostic factors (controlling for nutritional status, systemic inflammation score, and the neutrophil-to-lymphocyte ratio).

Conclusion: Preoperative aSIS may be a useful prognostic biomarker in ESCC patients who underwent curative resection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ags3.12464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452479PMC
September 2021

Optimal patient selection for successful two-stage hepatectomy of bilateral colorectal liver metastases.

Ann Gastroenterol Surg 2021 Sep 6;5(5):634-638. Epub 2021 May 6.

Centre Hépato-Biliaire AP-HP Hôpital Universitaire Paul Brousse Villejuif France.

Two-stage hepatectomy (TSH) is one of the specific surgical techniques that can expand the pool of resectable patients with initially unresectable colorectal liver metastases (CRLM). The indication of TSH for CRLM is only bilateral, multinodular disease, which cannot be resected by a single hepatectomy. TSH is nowadays considered an effective treatment for selected patients, with acceptable morbidity/mortality rates and promising long-term outcomes. However, not all eligible patients can benefit from the TSH strategy. One of the most important issues is dropout from the strategy (failure to complete both of the two sequential procedures), because the survival of such patients is drastically worse compared with patients who can complete both stages. Another important issue is the early recurrence rate and subsequent poor survival even after completion of TSH. Thus, the selection of appropriate patients who can really benefit from the TSH strategy is crucial. This review discusses the optimal patient selection for TSH, which should be helpful for the development of treatment strategies for patients with extensive CRLM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ags3.12465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452472PMC
September 2021

A Great Success! 5.164 Is the First Impact Factor for AGSurg.

Authors:
Hideo Baba

Ann Gastroenterol Surg 2021 Sep 13;5(5):588. Epub 2021 Sep 13.

Department of Gastroenterological Surgery Graduate School of Medical Sciences Kumamoto University Kumamoto Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ags3.12502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452470PMC
September 2021

Real-world safety and effectiveness of nivolumab in Japanese patients with unresectable advanced or recurrent gastric/gastroesophageal junction cancer that has progressed after chemotherapy: a postmarketing surveillance study.

Gastric Cancer 2021 Sep 28. Epub 2021 Sep 28.

Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.

Background: This postmarketing surveillance study evaluated the real-world safety and effectiveness of nivolumab as salvage (after ≥ 2 lines) therapy in Japanese patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer.

Methods: This multicenter, observational study was conducted at 158 centers in Japan. Patients with unresectable advanced or recurrent G/GEJ cancer were registered between Nov 1, 2017, and Oct 31, 2018, and observed for 6 months after treatment initiation with nivolumab. Correlation of background characteristics with treatment-related adverse events (TRAEs) and tumor response was explored.

Results: Overall, 654 patients were registered (safety analysis set, n = 650; effectiveness analysis set, n = 636; response evaluation set, n = 516). The incidences of all TRAEs and grade ≥ 3 TRAEs were 31.5 and 11.2%, respectively. TRAEs significantly correlated with the absence of peritoneal metastasis; C-reactive protein level < 1; prior G/GEJ cancer surgery; and past or concomitant pulmonary, thyroid, or renal disease (each p < 0.05). The incidence of TRAEs was significantly lower in patients with higher Glasgow prognostic scores (p < 0.05). No new safety signals were observed. Complete response, partial response, stable disease, and progressive disease were observed in 1.2, 10.1, 27.1, and 58.3% of the response evaluation set, respectively. Patients aged ≥ 65 years (13.9 vs 5.3%, p = 0.0083) and ≥ 75 years (18.8 vs 9.2%, p = 0.0036) showed a higher response rate than their younger counterparts.

Conclusions: The real-world safety and effectiveness of nivolumab as salvage (after ≥ 2 lines) therapy in Japanese patients with unresectable advanced or recurrent G/GEJ cancer were consistent with those observed in the phase 3 ATTRACTION-2 study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10120-021-01244-yDOI Listing
September 2021

Endometrial stromal sarcoma of the sigmoid colon: a case report and literature review.

Int Cancer Conf J 2021 Oct 14;10(4):294-299. Epub 2021 Jul 14.

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556 Japan.

Endometrial stromal sarcoma (ESS) is a rare mesenchymal tumor of the uterus that accounts for 7-25% of uterine sarcomas and < 1% of uterine tumors. Previously reported sites include the ovary, bowel wall, abdomen, peritoneum, pelvis, and vagina; however, ESS in the extrauterine area is rare. We report a rare case of endometrial stromal sarcoma that developed in the sigmoid colon along the gonadal vasculature, which was difficult to distinguish from colon cancer. A large polyp was found in the sigmoid colon of a 74-year-old woman during a routine medical examination and was diagnosed as tubular adenoma. On colonoscopy 7 months later, the tumor had grown and blocked the lumen, causing stenosis. She was referred to our hospital for surgery. Although detailed examination at our hospital did not yield a definitive diagnosis, bowel obstruction was considered likely and we performed laparoscopic low anterior resection under a preoperative diagnosis of sigmoid colon cancer. The tumor protruded into the sigmoid colon from the stump of the ovarian arteries and veins outside the intestinal tract. As the left ovarian artery and vein were involved in the tumor, we extracted them as a lump. The tumor was diagnosed as low-grade ESS (LG-ESS). She had a history of hysterectomy and left salpingo-oophorectomy for uterine myoma 25 years ago, and radiation therapy was performed after surgery for an unknown reason. The postoperative course was uneventful, and follow-up was continued at the request of the patient. We report a rare case of ESS infiltrating the sigmoid colon, which was probably a lesion derived from endometriosis of the ovarian arteriovenous stump remaining after surgery 25 years ago.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13691-021-00493-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421480PMC
October 2021

Prophylactic laparoscopic total gastrectomy for gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): the first report in Asia.

Gastric Cancer 2021 Sep 23. Epub 2021 Sep 23.

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto-city, 860-8556, Japan.

A 41-year-old woman was admitted to our hospital for epigastralgia. She had been admitted to another hospital for fundic gland polyposis (FGP) without any symptoms, and no malignancy had been noted in her previous endoscopy. However, a biopsy performed at our hospital revealed adenocarcinoma, and computed tomography (CT) revealed multiple liver and peritoneal metastases. We clinically suspected gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) and indicated genetic testing. The point mutation in exon 1B of APC was revealed. She was diagnosed with GAPPS with multiple liver metastases and underwent systemic chemotherapy. She has two older brothers who also have FGP. The same genomic mutation was observed in both brothers and their mother, and they were also diagnosed with GAPPS. The brothers underwent prophylactic laparoscopic total gastrectomy with D1 lymph-node dissection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10120-021-01253-xDOI Listing
September 2021

ISOlation Procedure vs. conventional procedure during Distal Pancreatectomy (ISOP-DP trial): study protocol for a randomized controlled trial.

Trials 2021 Sep 16;22(1):633. Epub 2021 Sep 16.

Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, Japan.

Background: Radical antegrade modular pancreatosplenectomy (RAMPS) is an isolation procedure in pancreatosplenectomy for pancreatic body/tail cancer. Connective tissues around the bifurcation of the celiac axis are dissected, followed by median-to-left retroperitoneal dissection. This procedure has the potential to isolate blood and lymphatic flow to the area of the pancreatic body/tail and the spleen to be excised. This is achieved by division of the inflow artery, transection of the pancreas, and then division of the outflow vein in the early phases of surgery. In cases of pancreatic ductal adenocarcinoma (PDAC), the procedure has been shown to decrease intraoperative blood loss and increase R0 resection rate by complete clearance of the lymph nodes. This trial investigates whether the isolation procedure can prolong the survival of patients with pancreatic ductal adenocarcinoma who undergo distal pancreatosplenectomy (DPS) compared with those that undergo the conventional approach.

Methods/design: Patients with PDAC scheduled to undergo DPS are randomized before surgery to undergo either a conventional procedure (arm A) or to undergo the isolation procedure (arm B). In arm A, the pancreatic body, tail, and spleen are mobilized, followed by removal of the regional lymph nodes. The splenic vein is transected at the end of the procedure. The timing of division of the splenic artery (SA) is not restricted. In arm B, regional lymph nodes are dissected, then we transect the root of the SA, the pancreas, then the splenic vein. At the end of the procedure, the pancreatic body/tail and spleen are mobilized and removed. In total, 100 patients from multiple Japanese high-volume centers will be randomized. The primary endpoint is 2-year recurrence-free survival by intention-to-treat analysis. Secondary endpoints include intraoperative blood loss, R0 resection rate, and overall survival.

Discussion: If this trial shows that the isolation procedures can improve survival with a similar R0 rate and with a similar number of lymph node dissections to the conventional procedure, the isolation procedure is expected to become a standard procedure during DPS for PDAC. Conversely, if there were no significant differences in endpoints between the groups, it would demonstrate justification of either procedure from surgical and oncological points of view.

Trial Registration: UMIN Clinical Trials Registry UMIN000041381 . Registered on 10 August 2020. ClinicalTrials.gov NCT04600063 . Registered on 22 October 2020.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13063-021-05523-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447574PMC
September 2021

Borderline resectable for colorectal liver metastases: Present status and future perspective.

World J Gastrointest Surg 2021 Aug;13(8):756-763

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.

Surgical resection for colorectal liver metastases (CRLM) may offer the best opportunity to improve prognosis. However, only about 20% of CRLM cases are indicated for resection at the time of diagnosis (initially resectable), and the remaining cases are treated as unresectable (initially unresectable). Thanks to recent remarkable developments in chemotherapy, interventional radiology, and surgical techniques, the resectability of CRLM is expanding. However, some metastases are technically resectable but oncologically questionable for upfront surgery. In pancreatic cancer, such cases are categorized as "borderline resectable", and their definition and treatment strategies are explicit. However, in CRLM, although various poor prognosis factors have been identified in previous reports, no clear definition or treatment strategy for borderline resectable has yet been established. Since the efficacy of hepatectomy for CRLM was reported in the 1970s, multidisciplinary treatment for unresectable cases has improved resectability and prognosis, and clarifying the definition and treatment strategy of borderline resectable CRLM should yield further improvement in prognosis. This review outlines the present status and the future perspective for borderline resectable CRLM, based on previous studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4240/wjgs.v13.i8.756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394381PMC
August 2021

Metabolic shift to serine biosynthesis through 3-PG accumulation and PHGDH induction promotes tumor growth in pancreatic cancer.

Cancer Lett 2021 Dec 9;523:29-42. Epub 2021 Sep 9.

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; Gastrointestinal Cancer Biology, International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan. Electronic address:

Cancer cells craftily adapt their energy metabolism to their microenvironment. Nutrient deprivation due to hypovascularity and fibrosis is a major characteristic of pancreatic ductal adenocarcinoma (PDAC); thus, PDAC cells must produce energy intrinsically. However, the enhancement of energy production via activating Kras mutations is insufficient to explain the metabolic rewiring of PDAC cells. Here, we investigated the molecular mechanism underlying the metabolic shift in PDAC cells under serine starvation. Amino acid analysis revealed that the concentrations of all essential amino acids and most nonessential amino acids were decreased in the blood of PDAC patients. In addition, the plasma serine concentration was significantly higher in PDAC patients with PHGDH-high tumors than in those with PHGDH-low tumors. Although the growth and tumorigenesis of PK-59 cells with PHGDH promoter hypermethylation were significantly decreased by serine starvation, these activities were maintained in PDAC cell lines with PHGDH promoter hypomethylation by serine biosynthesis through PHGDH induction. In fact, DNA methylation analysis by pyrosequencing revealed that the methylation status of the PHGDH promoter was inversely correlated with the PHGDH expression level in human PDAC tissues. In addition to PHGDH induction by serine starvation, PDAC cells showed enhanced serine biosynthesis under serine starvation through 3-PG accumulation via PGAM1 knockdown, resulting in enhanced PDAC cell growth and tumor growth. However, PHGDH knockdown efficiently suppressed PDAC cell growth and tumor growth under serine starvation. These findings provide evidence that targeting the serine biosynthesis pathway by inhibiting PHGDH is a potent therapeutic approach to eliminate PDAC cells in nutrient-deprived microenvironments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2021.09.007DOI Listing
December 2021

Evaluating the effect of Neoadjuvant chemotherapy for esophageal Cancer using the RECIST system with shorter-axis measurements: a retrospective multicenter study.

BMC Cancer 2021 Sep 9;21(1):1008. Epub 2021 Sep 9.

Department of Surgery, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.

Background: Evaluating the effect on primary lesions is important in determining treatment strategies for esophageal cancer. The Response Evaluation Criteria in Solid Tumors system, which employs the longest diameter for measuring tumors, is commonly used for evaluating treatment effects. However, the usefulness of these criteria in assessing primary esophageal tumors remains controversial. Thus, we evaluated this issue by measuring not only the longest diameter but also the shorter axis of the tumor.

Methods: We retrospectively reviewed data from 313 patients with esophageal cancer treated with neoadjuvant chemotherapy followed by esophagectomy at three major high-volume centers in Japan. All patients underwent contrast-enhanced computed tomography before and after chemotherapy. The longest and shortest tumor diameters were measured in each case. Treatment effects were adapted to the Response Evaluation Criteria in Solid Tumors system. Correlations between pathological and survival data were also analyzed.

Results: Inter-observer discrepancies were examined for changes in the longest diameter and shorter axis of the tumor (the intraclass correlation coefficients were 0.550 and 0.624, respectively). The shorter axis was correlated with the pathological response in the multivariate analysis (p < 0.001). The shorter axis was significantly associated with overall survival and disease-free survival (both p < 0.001), whereas this association was not observed for the longest tumor diameter.

Conclusions: This multicenter study demonstrated that the Response Evaluation Criteria in Solid Tumors system is useful for predicting pathological response and survival by incorporating the shorter axis of the primary esophageal tumor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-021-08747-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428108PMC
September 2021

ASO Author Reflections: Development of Useful Predictive Markers for Postoperative Morbidity Aiming to Improve Short-Term and Long-Term Outcomes After Esophageal Cancer Surgery.

Ann Surg Oncol 2021 Sep 3. Epub 2021 Sep 3.

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuoku, Kumamoto, 860-8556, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-021-10756-xDOI Listing
September 2021

Clinical Significance of Pretreatment Red Blood Cell Distribution Width as a Predictive Marker for Postoperative Morbidity After Esophagectomy for Esophageal Cancer: A Retrospective Study.

Ann Surg Oncol 2021 Sep 1. Epub 2021 Sep 1.

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Chuoku, Kumamoto, Japan.

Background: Clinical significance of red blood cell distribution (RDW) as a predictive marker for the incidence of postoperative morbidity after esophagectomy for esophageal cancer has not been established.

Methods: This study included 634 consecutive patients who underwent three-incisional esophagectomy with lymphadenectomy for esophageal cancer between April 2005 and November 2020. Correlation between pretreatment RDW and patient background, cancer background, and short-term outcome after esophagectomy were retrospectively investigated.

Results: Eighty patients (12.6%) had a high pretreatment RDW (> 14.2), which correlated with malnutrition estimated by body mass index, hemoglobin, total lymphocyte count, albumin, and total cholesterol. High pretreatment RDW was an independent risk factor for postoperative severe morbidity of grade IIIb or higher based on the Clavien-Dindo classification (hazard ratio [HR] 3.90, 95% confidence interval [CI] 1.707-8.887; p = 0.0012) and reoperation (HR 4.39, 95% CI 1.552-12.390; p = 0.0053) after open esophagectomy (OE). However, RDW was not associated with postoperative morbidity incidence after minimally invasive esophagectomy (MIE).

Conclusions: Pretreatment RDW may be a surrogate marker for nutritional status and could be a predictive marker for postoperative severe morbidity, reoperation, and possibly pneumonia after OE. On the contrary, the lower invasiveness of MIE may have reduced the effect of pretreatment malnutrition on morbidity incidence, which could explain the insignificant relationship between RDW and poor short-term outcomes in MIE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-021-10719-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407934PMC
September 2021

EpiPanGI Dx: A Cell-free DNA Methylation Fingerprint for the Early Detection of Gastrointestinal Cancers.

Clin Cancer Res 2021 Nov 31;27(22):6135-6144. Epub 2021 Aug 31.

Center for Gastrointestinal Research, Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute, Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas.

Purpose: DNA methylation alterations have emerged as front-runners in cell-free DNA (cfDNA) biomarker development. However, much effort to date has focused on single cancers. In this context, gastrointestinal (GI) cancers constitute the second leading cause of cancer-related deaths worldwide; yet there is no blood-based assay for the early detection and population screening of GI cancers.

Experimental Design: Herein, we performed a genome-wide DNA methylation analysis of multiple GI cancers to develop a pan-GI diagnostic assay. By analyzing DNA methylation data from 1,781 tumor and adjacent normal tissues, we first identified differentially methylated regions (DMR) between individual GI cancers and adjacent normal, as well as across GI cancers. We next prioritized a list of 67,832 tissue DMRs by incorporating all significant DMRs across various GI cancers to design a custom, targeted bisulfite sequencing platform. We subsequently validated these tissue-specific DMRs in 300 cfDNA specimens and applied machine learning algorithms to develop three distinct categories of DMR panels RESULTS: We identified three distinct DMR panels: (i) cancer-specific biomarker panels with AUC values of 0.98 (colorectal cancer), 0.98 (hepatocellular carcinoma), 0.94 (esophageal squamous cell carcinoma), 0.90 (gastric cancer), 0.90 (esophageal adenocarcinoma), and 0.85 (pancreatic ductal adenocarcinoma); (ii) a pan-GI panel that detected all GI cancers with an AUC of 0.88; and (iii) a multi-cancer (tissue of origin) prediction panel, EpiPanGI Dx, with a prediction accuracy of 0.85-0.95 for most GI cancers.

Conclusions: Using a novel biomarker discovery approach, we provide the first evidence for a cfDNA methylation assay that offers robust diagnostic accuracy for GI cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-21-1982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595812PMC
November 2021

Relationship between Fusobacterium nucleatum and antitumor immunity in colorectal cancer liver metastasis.

Cancer Sci 2021 Nov 23;112(11):4470-4477. Epub 2021 Sep 23.

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Fusobacterium nucleatum has been detected in 8%-13% of human colorectal cancer, and shown to inhibit immune responses against primary colorectal tumors in animal models. Thus, we hypothesized that the presence of F. nucleatum might be associated with reduced T cell density in colorectal cancer liver metastases (CRLM). We quantified F. nucleatum DNA in 181 CRLM specimens using quantitative PCR assay. The densities of CD8 T cells, CD33 cells (marker for myeloid-derived suppressor cells [MDSCs]), and CD163 cells (marker for tumor-associated macrophages [TAMs]) in CRLM tissue were determined by immunohistochemical staining. Fusobacterium nucleatum was detected in eight (4.4%) of 181 CRLM specimens. Compared with F. nucleatum-negative CRLM, F. nucleatum-positive CRLM showed significantly lower density of CD8 T cells (P = .033) and higher density of MDSCs (P = .001). The association of F. nucleatum with the density of TAMs was not statistically significant (P = .70). The presence of F. nucleatum is associated with a lower density of CD8 T cells and a higher density of MDSCs in CRLM tissue. Upon validation, our findings could provide insights to develop strategies that involve targeting microbiota and immune cells for the prevention and treatment of CRLM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.15126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586672PMC
November 2021
-->