Tetsuro Tominaga

Short-term outcomes of laparoscopic surgery for colorectal cancer in oldest-old patients.

Background/Aims: Oldest-old patients generally have several comorbidities, and laparoscopic-assisted colectomy (LAC) has not been performed on these patients. However, the surgical technique of LAC has improved, and its indications have been extended. The aim of this study was to evaluate the safety and effectiveness of LAC for patients over 85 years old. Methods: Fifty-eight patients over 85 years old who underwent colectomy were retrospectively analyzed. The patients were divided into two groups (LAC group n = 15; open surgery group (Open group) n = 43), and clinicopathological features, surgical characteristics, and outcomes were compared. Results: There were no significant differences in clinical background characteristics between the groups. The LAC group had longer operation time and greater lymph node dissection (both p < 0.01). Postoperatively, the use of analgesics (p = 0.01) was less and the start of oral liquid intake (p = 0.03) was faster in the LAC group. Postoperative complications occurred in 3 patients (20%) in the LAC group and 13 patients (30%) in the Open group (p = 0.66); delirium (n = 6) and sub-ileus (n = 4) developed only in the Open group. Conclusion: After LAC, elderly patients tended to have less postoperative pain and started oral liquid intake earlier. LAC can be safe and effective, preventing postoperative complications that occur specifically in oldest-old patients.

Does the placement of a cystic duct tube after a hepatic resection help reduce the incidence of post-operative bile leak?

BACKGROUND In this retrospective study, the effects of cystic duct (C) tube use on the incidence of post-hepatectomy bile leak were assessed. METHODS The subjects were 550 patients who underwent a hepatectomy during 1990-2011, with (n = 83) and without (n = 467) C tube drainage. The use of a C tube was based on the surgeons choice. RESULTS Bile leakage was observed in 44 (8%) patients, and its incidence post-operatively correlated with intrahepatic cholangiocarcinoma, parenchymal transection with forceps fracture and tie, a major hepatectomy, prolonged surgery and excessive blood loss (P < 0.050) but not with the use of a C tube. The incidence of an intra-abdominal infection was higher and the hospital stay was longer in the leak (49 days) than non-leak group (21 days, P < 0.001). ISGLS grade B and C bile leak post-hemi-hepatectomy and extended-hepatectomy were more frequent in the non-C than C tube group (P = 0.016). The duration of hospitalization was not different between the two groups; however, 7 patients in the non-C tube group had prolonged hospitalization (> 60 days) compared with none in the C tube group (P = 0.454). CONCLUSION The usefulness of the C tube in preventing post-hepatectomy bile leak could not be confirmed; however, both bile leak requiring clinical management and long hospitalization after a major hepatectomy could be reduced with C tube use.

High expression of dihydropyrimidine dehydrogenase in lung adenocarcinoma is associated with mutations in epidermal growth factor receptor: implications for the treatment of non--small-cell lung cancer using 5-fluorouracil.

BACKGROUND It has been shown that 5-fluorouracil (5-FU) sensitivity in patients with non-small-cell lung cancer (NSCLC) is associated with epidermal growth factor receptor (EGFR) mutation status. However, the relationship between dihydropyrimidine dehydrogenase (DPD), a 5-FU degrading enzyme, and EGFR mutation status is unknown. Here, we focus on clinicopathologic factors and in vitro correlations between DPD expression and EGFR mutation status. PATIENTS AND METHODS EGFR mutations and messenger RNA (mRNA) levels of DPD and thymidylate synthase (TS) were analyzed in 47 resected NSCLC tumors by laser-capture microdissection. In addition, relationships between EGFR mutation status and the immunohistochemical expression of DPD and TS in 49 patients with primary NSCLC who were treated with a 5-FU derivative of S-1 postoperatively were examined. Correlations among clinicopathologic factors were evaluated. The effect of epidermal growth factor on DPD expression was also investigated in vitro in various cell lines. RESULTS Adenocarcinoma in situ showed significantly higher DPD mRNA levels and more EGFR mutation frequency than other histological types (P < .05). DPD immunopositive cases were more frequently observed in adenocarcinoma, in females, and in nonsmokers. DPD immunopositive cases were correlated with EGFR mutation status (P < .003). The prognoses of wild-type EGFR and mutated EGFR populations were similarly favorable with postoperative S-1 treatment, which overcomes the problem of 5-FU degradation in mutated EGFR. In vitro, EGFR-mutated cell lines showed high DPD mRNA and protein expression. CONCLUSION High DPD expression was shown to be correlated with EGFR mutation in adenocarcinoma cells and tissues. Clinicians should take this finding into consideration when using 5-FU to treat patients with NSCLC.

The C-Reactive Protein to Albumin Ratio as a Predictor of Severe Side Effects of Adjuvant Chemotherapy in Stage III Colorectal Cancer Patients.

Background/Aims Adjuvant chemotherapy (AC) has been reported to improve the prognosis for patients with Stage III colorectal cancer (CRC). However, some patients experience severe side effects and must stop AC. The C-reactive protein (CRP) to albumin ratio (CAR) is a novel inflammation-based score that could reflect the patient’s general condition. The aim of this study was to evaluate the predictive value of the CAR for side effects of AC in CRC. Methods A total of 136 CRC patients who received AC were retrospectively analyzed. The patients were subdivided into two groups by the CAR level (CAR ≥0.1, n = 30; CD < 0.1, n = 106). Results The presence of lymphatic invasion, severe side effects, and discontinuation of AC were associated with high CAR levels (p = 0.02, <0.01, and 0.02; respectively). High levels of the Glasgow Prognostic Score (GPS) and the neutrophil to lymphocyte ratio (NLR) appeared to be associated with the CAR (p = 0.04, p<0.01; respectively). Multivariate analysis identified CAR≥0.1 (HR: 7.06, 95% CI: 2.51–19.88, p<0.01) as a significant determinant of severe side effects of AC. CAR had the highest area under the curve (0.79) among several inflammation-based scores. Conclusion The present study showed that the CAR is a novel and promising inflammation-based score for ≥ grade 3 side effects of AC in node-positive CRC.

Usefulness Of Three-Dimensional Printing Models for Patients with Stoma Construction.

The use of patient-specific organ models in three-dimensional printing systems could be helpful for the education of patients and medical students. The aim of this study was to clarify whether the use of patient-specific stoma models is helpful for patient education. From January 2014 to September 2014, 5 patients who underwent colorectal surgery and for whom a temporary or permanent stoma had been created were involved in this study. Three-dimensional stoma models and three-dimensional face plates were created. The patients’ ages ranged from 59 to 81 years. Four patients underwent stoma construction because of rectal cancer, and 1 underwent stoma construction because of colon stenosis secondary to recurrent cancer. All patients were educated about their stoma and potential stoma-associated problems using three-dimensional stoma models, and all practiced cutting face plates using three-dimensional face plates. The models were also used during medical staff conferences to discuss current issues. All patients understood their problems and finally became self-reliant. The recent availability of three-dimensional printers has enabled the creation of many organ models, and full-scale stoma and face plate models are now available for patient education on cutting an appropriately individualized face plate. Thus, three-dimensional printers could enable fewer skin problems than are currently associated with daily stomal care.

Epidermal growth factor signals regulate dihydropyrimidine dehydrogenase expression in EGFR-mutated non-small-cell lung cancer

BackgroundIt has been shown that epidermal growth factor receptor (EGFR) mutation status is associated with 5-fluorouracil (5-FU) sensitivity in non-small-cell lung cancer (NSCLC). However, the relationship between EGFR mutation status and dihydropyrimidine dehydrogenase (DPD), a 5-FU degrading enzyme, is unknown.MethodsWe elucidated the crosstalk among the EGFR signal cascade, the DPD gene (DPYD), and DPD protein expression via the transcription factor Sp1 and the effect of EGFR mutation status on the crosstalk.ResultsIn the PC9 (exon19 E746-A750) study, EGF treatment induced up-regulation of both Sp1 and DPD; gefitinib, an EGFR-tyrosine kinase inhibitor (EGFR-TKI), and mithramycin A, a specific Sp-1 inhibitor, suppressed them. Among EGFR-mutated (PC9, HCC827; exon19 E746-A750 and H1975; exon21 L858R, T790M, gefitinib resistant) and -non-mutated (H1437, H1299) cell lines, EGF administration increased DPYD mRNA expression only in mutated cells (p < 0.05). Accordingly, gefitinib inhibited DPD protein expression only in PC9 and HCC827 cells, and mithramycin A inhibited it in EGFR-mutated cell lines, but not in wild-type. FU treatment decreased the level of cell viability more in gefitinib-treated EGFR-TKI sensitive cell lines. Further, combination treatment of FU and mithramycin A suppressed cell viability even in a gefitinib resistant cell line.ConclusionsThe EGFR signal cascade regulates DPD expression via Sp1 in EGFR mutant cells. These results might be a step towards new therapies targeting Sp1 and DPD in NSCLC with different EGFR mutant status.

Clinical significance of the C‑reactive protein‑to‑albumin ratio for the prognosis of patients with esophageal squamous cell carcinoma

The aim of the present study was to investigate the prognostic value of the C-reactive protein-to-albumin ratio (CAR) and compare it with other inflammation-based prognostic scores (Glasgow prognostic score, modified Glasgow prognostic score, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, prognostic nutritional index and prognostic index) in patients with esophageal squamous cell cancer (ESCC). A database of 116 patients with primary ESCC who underwent treatment at the Division of Surgical Oncology at Nagasaki University Hospital between January 2007 and August 2014 was retrospectively reviewed and the correlations between CAR and overall survival (OS) were investigated. Kaplan-Meier and Cox regression analyses were used to assess independent prognostic factors. The area under the curve (AUC) was used to compare the prognostic value of different scores. According to the receiver operator characteristics analysis, the recommended cut-off value for CAR was 0.042, with an AUC of 0.678 (sensitivity 31.1%, specificity 66.7%). Thus, patients were dichotomized into low (<0.042) and high (≥0.042) CAR groups. On multivariate analysis, CAR was found to be significantly associated with OS in patients with ESCC [hazard ratio (HR)=2.350; 95% confidence interval (CI): 1.189-4.650; P=0.014], as was tumor-node-metastasis stage (HR=3.059; 95% CI: 1.422-6.582; P=0.004). In addition, CAR had a higher AUC value (0.678) compared with several other systemic inflammation-based prognostic scores (P<0.001). This study suggested that CAR is a novel and promising inflammation-based prognostic score in patients with ESCC. Due to its simplicity, affordability and availability, CAR may be important for improving clinical decision-making and may contribute to more rational study design and analyses.

A case of multiple synchronous quadruple cancers of the stomach, sigmoid colon, rectum, and pancreas

Highlights • The increased screening results in more pick up multiple primary tumors and that they are being reported more.• Diagnosis and treatment of multiple primary tumors is usually difficult.• A cancer board can be useful for this process.

Indocyanine green identification for tumor infiltration or metastasis originating from hepatocellular carcinoma

Highlights • The indocyanine green-photodynamic eye (ICG-PDE) system was useful to clearly detect metastasis or tumor thrombus, as well as main tumor, originated from hepatocellular carcinoma and all lesions could be resected.• This system may be applied to improve determining the location of metastasis or tumor thrombus.• Tumor thrombus originated from hepatocellular carcinoma (HCC) in the portal vein or inferior vena cava could be well identified by ICG-PDE. The metastasized HCC lesion in an adrenal gland was clearly detected. All lesions could be completely resected.• ICG-PDE is a useful tool for detecting the precise tumor location even in extrahepatic tumor lesions or tumor thrombus, which is useful for deciding which parts to resect.

Simultaneous laparoscopic left hemicolectomy and spleen-preserving distal pancreatectomy for descending colon cancer with pancreatic invasion: Lap colectomy with distal pancreatectomy

Here, we describe laparoscopic colectomy with spleen‐preserving distal pancreatectomy for descending colon cancer with pancreatic tail invasion. A 69‐year‐old man with descending colon cancer staged as clinical state IIIC (cT4b [pancreas] N1M0) underwent definitive laparoscopic surgery that was performed in collaboration with surgeons who specialize in laparoscopic colorectal and hepatobiliary‐pancreatic laparoscopy. After the left colon was mobilized, tumor infiltration of the pancreas, but not the splenic vessels, was confirmed, and the spleen was preserved. The procedures were safely completed laparoscopically, without intraoperative and postoperative complications. Laparoscopic multivisceral resection could be a treatment option for similar patients but only when performed by multidisciplinary specialists.