Intraoperative Indocyanine Green Imaging for the Evaluation of Blood Perfusion Area in Cancer of the Splenic Flexure With an Occluded Inferior Mesenteric Artery: A Report of Two Cases.

Radical resection for cancer of the splenic flexure requires careful consideration of the dissection line so that blood flow in the remnant bowel is maintained, particularly when the root of the inferior mesenteric artery (IMA) is already occluded. Intraoperative indocyanine green (ICG) imaging is a promising method for evaluating blood perfusion of organs and vessels. However, there are few reports on the use of ICG to determine the dissection line in patients with altered blood flow. In this article, we describe two cases of successful resection of splenic flexure cancer (SFC) in patients with an occluded IMA under ICG guidance. Case one was a 76-year-old man with a diagnosis of stage III SFC who had previously undergone endovascular aortic repair without reimplantation of the IMA. Intraoperative ICG imaging revealed that the left side of the colon was perfused mainly by the left branch of the middle colic artery (MCA). We performed a hemicolectomy with preservation of the MCA-left colic artery (LCA) arcade and resected an enlarged lymph node en bloc. Case two was a 77-year-old man with a diagnosis of stage II SFC in whom the root of the IMA appeared to be occluded by arteriosclerosis. Computed tomography showed that the LCA was anastomosed to the accessory middle colic artery (AMCA) while the left branch of the MCA was joined to the marginal artery. Intraoperative ICG imaging revealed that the left side of the colon was perfused by the AMCA and not the MCA. By preserving the AMCA-LCA arcade, we were able to safely divide the left branch of the MCA. Both patients were discharged with no symptoms of bowel ischemia or recurrence of cancer during follow-up. Interindividual variation in vessel branching patterns and dominant vessels in the descending and distal transverse colon may result from congenital factors or acquired disease. Detailed information on blood perfusion is required to avoid postoperative bowel ischemia. This report is the first to focus on patients with SFC and altered blood flow. We show that ICG imaging might be a reasonable option for determining an adequate surgical dissection area.

Perioperative Management and Surgical Outcomes of Colorectal Cancer Patients Undergoing Peritoneal Dialysis for End-Stage Kidney Disease.

INTRODUCTION: Despite the fact that the number of peritoneal dialysis (PD) patients is increasing, there is little evidence on the surgical outcomes of PD patients who have colorectal cancer surgery, and there is no consensus on the safety and practicality of continuing PD. METHODS: We retrospectively evaluated the short- and long-term results, as well as the feasibility of continuing PD, in eight patients with PD who had colorectal cancer surgery at our institution between January 2010 and January 2021. RESULTS: The scheduled open-fashioned resection was performed in one patient, whereas the other seven surgeries were all conducted laparoscopically, with no intraoperative conversion to laparotomy necessary. Except for one patient with a history of recurring PD-related peritonitis, the PD catheter was kept in seven of the eight cases. Five of the seven patients continuing PD underwent temporary postoperative hemodialysis. At a median of 24.5 months of postoperative monitoring, no infectious complications were observed, six cases continued PD, and no recurrence of colorectal cancer was observed in all cases. CONCLUSIONS: Routine curative-intent colorectal cancer surgery with the preservation of the PD catheter is possible and safe in individuals receiving PD. This patient population's short- and long-term oncological results are comparable to general surgical outcomes of those without chronic kidney disease. PD can be maintained for a long period of time following major colorectal cancer surgery.

A phase ΙI study of five peptides combination with oxaliplatin-based chemotherapy as a first-line therapy for advanced colorectal cancer (FXV study).

BACKGROUND: We previously conducted a phase I trial for advanced colorectal cancer (CRC) using five HLA-A*2402-restricted peptides, three derived from oncoantigens and two from vascular endothelial growth factor (VEGF) receptors, and confirmed safety and immunological responses. To evaluate clinical benefits of cancer vaccination treatment, we conducted a phase II trial using the same peptides in combination with oxaliplatin-based chemotherapy as a first-line therapy. METHODS: The primary objective of the study was the response rates (RR). Progression free survival (PFS), overall survival (OS), and immunological parameters were evaluated as secondary objective. The planned sample size was more than 40 patients for both HLA2402-matched and -unmatched groups. All patients received a cocktail of five peptides (3 mg each) mixed with 1.5 ml of IFA which was subcutaneously administered weekly for the first 12 weeks followed by biweekly administration. Presence or absence of the HLA-A*2402 genotype were used for classification of patients into two groups. RESULTS: Between February 2009 and November 2012, ninety-six chemotherapy naïve CRC patients were enrolled under the masking of their HLA-A status. Ninety-three patients received mFOLFOX6 and three received XELOX. Bevacizumab was added in five patients. RR was 62.0% and 60.9% in the HLA-A*2402-matched and -unmatched groups, respectively (p=0.910). The median OS was 20.7 months in the HLA-A*2402-matched group and 24.0 months in the unmatched group (log-rank, p=0.489). In subgroup with a neutrophil/lymphocyte ratio (NLR) of <3.0, patients in the HLA-matched group did not survive significantly longer than those in the unmatched group (log-rank, p=0.289) but showed a delayed response. CONCLUSIONS: Although no significance was observed for planned statistical efficacy endpoints, a delayed response was observed in subgroup with a NLR of <3.0. Biomarkers such as NLR might be useful for selecting patients with a better treatment outcome by the vaccination. TRIAL REGISTRATION: Trial registration: UMIN000001791.

Evaluation of modified estimation of physiologic ability and surgical stress in patients undergoing surgery for choledochocystolithiasis.

BACKGROUND: The incidence of complicated choledochocystolithiasis is increasing with the aging of society in Japan. We evaluated the utility of our prediction rule modified estimation of physiologic ability and surgical stress (mE-PASS) in predicting postoperative adverse events in patients with choledochocystolithiasis. METHODS: A total of 4,329 patients who underwent elective surgery for choledochocystolithiasis in 44 referral hospitals between April 1987 and April 2007 were analyzed for mE-PASS along with postoperative events. The discrimination power of mE-PASS was assessed by the area under the receiver operating characteristic curve (AUC). The correlation between ordinal and interval variables was quantified by the Spearman rank correlation (ρ). The ratio of observed-to-estimated mortality rates (OE ratio) was used as a metric of surgical quality. RESULTS: Postoperative in-hospital mortality rates were 0 % (0/3,442) for laparoscopic cholecystectomy, 0.19 % (1/521) for open cholecystectomy, 1.6 % (1/63) for laparoscopic choledochotomy, 1.1 % (3/264) for open choledochotomy, and 5.1 % (2/39) for plasty or resection of the common bile duct. mE-PASS demonstrated a high discrimination power to predict in-hospital mortality; AUC, 95 % confidence interval (CI) of 0.96, 0.94-0.99. The predicted mortality rates significantly correlated with the severity of postoperative complications (ρ = 0.278, p < 0.0001) and length of hospital stay (ρ = 0.479, p < 0.0001). The OE ratios (95 % CI) improved slightly over time; 1.5 (0.25-9.0) between 1987 and 2000, and 0.40 (0.078-2.1) between 2001 and 2007. CONCLUSIONS: The present study suggests that mE-PASS can predict postoperative risks in patients who have undergone choledochocystolithiasis. mE-PASS may be useful in surgical decision making and evaluating the quality of care.

[Ten-year survival of a patient with advanced gastric cancer with no. 16 lymph node metastases after total gastrectomy and paraaortic lymphadenectomy].

When no other non-curative treatment options are available, R0 resection can be achieved with paraaortic lymphadenectomy for patients with advanced gastric cancer with No.16 lymph node metastases. Herein, we report of a patient who underwent R0 resection for gastric cancer with No.16 lymph node metastases and who achieved long-term survival.

Combination phase II study of weekly paclitaxel and 5'-DFUR for unresectable or recurrent gastric cancer.

BACKGROUND: Paclitaxel and 5'-deoxy-5-fluorouridine (5'-DFUR) have single-agent activity in gastric cancer and have distinct mechanisms of action and no overlap of key toxicities. To evaluate the efficacy and safety of their combination, we conducted a combination phase II study of paclitaxel and 5'-DFUR in patients with unresectable or recurrent gastric cancer who had received up to one prior chemotherapy. PATIENTS AND METHODS: Treatment included paclitaxel at 70 mg/m(2) i.v. on days 1, 8 and 15 every four weeks, and 5'-DFUR at 600 mg p.o. every day. The primary end-point was the response rate (RR) and secondary end-points were overall survival (OS), progression-free survival (PFS), time-to-treatment failure (TTF) and rate of adverse events. RESULTS: In 42 eligible patients, the RR was 40.5%. OS, PFS and TTF were 371 days, 170 days, and 147 days, respectively. Adverse events were relatively mild. Commonly observed grade 3/4 adverse events were neutropenia (26.2%), anorexia (4.8%), neuropathy (4.8%) and fatigue (4.8%). CONCLUSION: The combination of weekly paclitaxel and 5'-DFUR chemotherapy is active and well-tolerated.

Effects of APRIL (TNFSF13) polymorphisms and splicing isoforms on the secretion of soluble APRIL.

Functional APRIL (TNFSF13) is a secreted trimer generated by furin protease cleavage. We previously reported the association of APRIL haplotypes formed by two nonsynonymous polymorphisms, Gly67Arg and Asn96Ser, with systemic lupus erythematosus. Here, we tested the hypothesis that polymorphisms and/or alternative splicing may influence the generation of soluble APRIL (sAPRIL). HEK 293T cells were transfected with plasmids containing one of the six combinations of splicing isoforms (α or ß) and haplotypes (susceptible, neutral, or protective). APRIL concentrations were quantitated in the cell lysates and supernatants using an enzyme-linked immunosorbent assay (ELISA). The association between splicing efficiency and polymorphisms was analyzed using quantitative reverse transcription polymerase chain reaction (RT-PCR). The efficiency of cleavage by furin protease was analyzed using western blotting. Although both splicing isoforms were cleaved by furin protease, sAPRIL was not detected in the supernatant of the cells transfected with the ß isoform, regardless of the haplotype. This suggested that, similarly to B-cell activating factor (BAFF), one of the major APRIL splicing isoforms may not be secreted as a functional molecule. Furthermore, the secretion of sAPRIL was decreased in the transfectants expressing the protective haplotype. An association between the polymorphisms and splicing efficiency or furin cleavage efficiency was not detected. In conclusion, these observations suggested that both alternative splicing and polymorphisms may affect the generation of functional sAPRIL.

Cumulative association of eight susceptibility genes with systemic lupus erythematosus in a Japanese female population.

Although large-scale studies established many susceptibility genes to systemic lupus erythematosus (SLE), effect of each gene is not sufficiently large to be used alone to identify individuals with strong genetic predisposition. In this study, we analyzed the cumulative number of risk alleles at eight established susceptibility loci, HLA-DRB1, IRF5, STAT4, BLK, TNFAIP3, TNIP1, FCGR2B and TNFSF13, in 282 Japanese female SLE and 222 healthy female controls. The average number of risk alleles was significantly increased in SLE (8.07±1.60) than healthy controls (7.02±1.64) (P=1.63 × 10(-12)). Significant gene-gene interaction was not detected. When the subjects carrying seven risk alleles were used as a reference, the odds ratio (OR) for individuals carrying 10 and 11-13 risk alleles were 4.17 (95% confidence interval (CI) 1.89-9.19, P=0.0002) and 8.77 (95% CI 1.92-40.0, P=0.0016), respectively. In contrast, subjects with ≤4 risk alleles were significantly decreased in SLE (OR 0.15, CI 0.03-0.67, P=0.007). The proportion of the patients with neurologic disorder was significantly increased in those carrying ≥10 risk alleles than those with <10 (OR 2.30, CI 1.09-4.83, P=0.025). This study suggested that the cumulative number of risk alleles may efficiently distinguish groups with high and low genetic predisposition to SLE and its severe manifestation.

Maximal sterile barrier precautions do not reduce catheter-related bloodstream infections in general surgery units: a multi-institutional randomized controlled trial.

OBJECTIVE: To investigate whether maximal sterile barrier precautions (MSBPs) during central venous catheter (CVC) insertion are truly effective in preventing catheter-related bloodstream infections (CRBSIs) in patients in general surgical units. SUMMARY BACKGROUND DATA: The reported effectiveness of MSBPs was based on the results of a single-center randomized controlled trial by Raad et al and the majority of the patients (99%) in the study were chemotherapy outpatients. METHODS: Between March 14, 2004 and December 28, 2006, the patients scheduled for CVC insertion in surgical units at 9 medical centers in Japan were randomly assigned to either an MSBP group (n = 211) or a standard sterile barrier precaution (SSBP) group (n = 213). This study was registered in the UMIN Clinical Trials Registry (registration ID number: UMIN000001400). RESULTS: The median (range) duration of catheterization was 14 days (0-92 days) in the MSBP group and 14 days (0-112 days) in the SSBP group. There were 5 cases (2.4%) of CRBSI in the MSBP group and 6 cases (2.8%) in the SSBP group (relative risk, 0.84; 95% confidence interval, 0.26-2.7; P = 0.77). The rate of CRBSIs per 1000 catheter days was 1.5 in the MSBP group and 1.6 in the SSBP group. There were 8 cases (3.8%) of catheter-related infections in the MSBP group and 7 cases (3.3%) in the SSBP group (relative risk, 1.2; 95% confidence interval, 0.43-3.1; P = 0.78). The rate of catheter-related infection per 1000 catheter days was 2.4 in the MSBP group and 1.9 in the SSBP group. CONCLUSIONS: This study is larger in sample size than the one performed by Raad et al and could not demonstrate better prevention of CRBSIs by MSBP compared with SSBP. A large randomized controlled trial or at least a meta-analysis of any other studies in the literature is necessary to reach to a conclusion on this issue.

[A case of advanced gastric cancer with histological complete response after S-1 chemotherapy].

A 58-year-old man of unresectable gastric cancer was treated with S-1 (120 mg/body/day) after gastrojejunostomy. After 5 courses of orally administration of S-1 for 4 weeks and withdrawal for 2 weeks, partial response (PR) was obtained clinically and distal gastrectomy was performed. The histological diagnosis showed no residue of carcinoma with both HE and immunohistochemical staining. The patient has been in good health and no recurrence has occurred for about 4 years and 4 months after resection.

[A case of long-term survival of recurrent gastric cancer successfully treated with multidisciplinary therapy].

A 73-year-old male patient underwent total gastrectomy for advanced gastric cancer in December 2000. The final diagnosis was 1 MU, ant, type 3, 67x47 mm, pT2 (ss), pN1 (#1, 3, 4d), sP0, sH0, CY0, cM0, fStage II, tub 2, int, inf beta, ly3, v3, 2 L, post, type 2, 42x40 mm, pT2 (mp), pN1 (#1, 3, 4d), sP0, sH0, CY0, cM0, fStage II. Although we began adjuvant chemotherapy with UFT 300 mg/day, a solitary liver metastasis in the S6 sub-segment of the liver was diagnosed 15 months after the first operation. He received RFA for liver metastasis, and the protocol was changed to S-1. Two-time recurrence of S6 was controlled by RFA but liver metastasis recurred again. So we performed posterior segmentectomy of the liver 30 months after the first operation. CT showed a solitary paraaortic lymph node metastasis 60 months after the first operation (24 months after hepatectomy). He showed a stable disease for 1 year, so he was given radiation of paraaortic lymph node metastasis at a total dose of 36 Gy (4.5 Gyx8 times) after 72 months from the first operation. One hundred two months passed from first operation. The patient remains alive without any recurrence, and this multidisciplinary therapy proved to be effective.

Estimation of surgical costs using a prediction scoring system: estimation of physiologic ability and surgical stress.

HYPOTHESIS: Our predictive scoring system, Estimation of Physiologic Ability and Surgical Stress, can estimate surgical costs. DESIGN: Multicenter cohort study for 1 year. SETTING: Six national hospitals in Japan. PATIENTS: A consecutive series of 929 patients who underwent elective gastrointestinal operations. MAIN OUTCOME MEASURES: The preoperative and the comprehensive risk scores of the Estimation of Physiologic Ability and Surgical Stress were determined preoperatively and immediately after the operation, respectively. Estimated costs were computed using the following equation: costs = US $10,160 + (US $13,470 x comprehensive risk score). Data on length of stay, costs for surgical admission, and severity of postoperative complications were collected at hospital discharge. RESULTS: The comprehensive risk score significantly correlated with the severity of the postoperative complications (Spearman rank correlation = 0.54, P<.001), the length of stay (Spearman rank correlation = 0.69, P<.001), and the costs (Spearman rank correlation = 0.72, P<.001). The ratio of real to estimated costs varied from 0.82 to 1.17 at the various ranges of the comprehensive risk score, resulting in 0.93 in the total 929 patients. This ratio varied from 0.71 to 1.12 among the hospitals, the smallest of which was attributed to the hospital that primarily used the clinical pathways. A significant increase in the costs was observed according to the preoperative risk score for open colectomy (P =.009) and distal gastrectomy (P =.002). When we simulated the hospital revenue where different payment rates were set according to the preoperative risk score, the revenue seemed to improve in the hospitals that treated more high-risk patients, compared with the fixed payment system. CONCLUSION: The Estimation of Physiologic Ability and Surgical Stress scoring system may be useful for estimating surgical costs, making a benchmark analysis, and determining the rate in a risk-based payment system.