Difference in right and left cardio-ankle vascular index as a useful marker for evaluation of leg ischemia in patients with lower extremity arterial disease.

OBJECTIVES: Cardio-ankle vascular index (CAVI) is a blood pressure-independent measure of heart-ankle pulse wave velocity and is used as an indicator of arterial stiffness. However, there is a paradox that CAVI is inversely associated with leg ischemia in patients with lower extremity arterial disease (LEAD). The aim of this study was to clarify the significance of the absolute value of left and right difference in CAVI (diff-CAVI). METHODS: The subjects were 165 patients with LEAD who had received medication therapy. Relationships between diff-CAVI and leg ischemia were investigated. Leg ischemia was evaluated by decrease in leg arterial flow using ankle-brachial index (ABI) and by symptoms using the Rutherford classification. RESULTS: There was a significant inverse correlation between diff-CAVI and ABI. The odds ratio for low ABI of the 3rd versus 1st tertile groups of diff-CAVI was 7.03 with a 95% confidence interval of 2.71 ∼ 18.22. In ROC analysis, the cutoff value of diff-CAVI for low ABI was 1.05 with a sensitivity of 61.1% and a specificity of 87.1%. The median of diff-CAVI was significantly higher in subjects with grade 2 of the Rutherford classification than in subjects with its grade 1. CONCLUSIONS: diff-CAVI showed an inverse association with ABI and a positive association with symptoms of leg ischemia. Thus, diff-CAVI is thought to be a useful indicator of leg ischemia in LEAD patients.

Phase II clinical trial to study the safety and efficacy of combined S-1 + oxaliplatin therapy as neoadjuvant chemotherapy for locally advanced gastric cancer in older patients.

BACKGROUND: Gastrectomy with D2 dissection and adjuvant chemotherapy is the standard treatment for locally advanced gastric cancer (LAGC) in Asia. However, administering chemotherapy with sufficient intensity after gastrectomy is challenging. Several trials demonstrated the efficacy of neoadjuvant chemotherapy (NAC). However, limited studies explored the feasibility of NAC-SOX for older patients with LAGC. This phase II study (KSCC1801) evaluated the safety and efficacy of NAC-SOX in patients with LAGC aged ≥ 70 years. METHODS: Patients received three cycles of SOX130 (oxaliplatin 130 mg/m2 on day 1, oral S-1 40-60 mg twice daily for two weeks every three weeks) as NAC, followed by gastrectomy with lymph node dissection. The primary endpoint was the dose intensity (DI). The secondary endpoints were safety, R0 resection rate, pathological response rate (pRR), overall survival, and relapse-free survival. RESULTS: The median age of 26 enrolled patients was 74.5 years. The median DI in NAC-SOX130 was 97.2% for S-1 and 98.3% for oxaliplatin. Three cycles of NAC were administered in 25 patients (96.2%), of whom 24 (92.3%) underwent gastrectomy with lymphadenectomy. The R0 resection rate was 92.3% and the pRR (≥ grade 1b) was 62.5%. The major adverse events (≥ grade 3) were neutropenia (20.0%), thrombocytopenia (11.5%), anorexia (11.5%), nausea (7.7%), and hyponatremia (7.7%). Postoperative complications of abdominal infection, elevated blood amylase, and bacteremia occurred in one patient each. Severe diarrhea and dehydration caused one treatment-related death. CONCLUSIONS: NAC-SOX130 is a feasible therapy for older patients, although systemic management and careful monitoring of adverse events are necessary.

Phase II study of S-1 and oxaliplatin as neoadjuvant chemotherapy for locally advanced adenocarcinoma of the gastric or esophagogastric junction: KSCC1601.

BACKGROUND: Perioperative chemotherapy is the standard of care for locally advanced gastric cancer (LAGC). This phase II study investigated the efficacy and safety of S-1 and oxaliplatin (SOX) as neoadjuvant chemotherapy (NAC) for LAGC and esophagogastric junction cancer (EGJC). METHODS: Patients completed up to three cycles of SOX130 (oxaliplatin 130 mg/m2 on day 1, oral S-1 40-60 mg twice daily for 2 weeks every 3 weeks), followed by gastrectomy and D2 lymphadenectomy. The primary endpoint was the pathological response rate (pRR). The anastomosis leakage rate was the secondary endpoint in patients with EGJC, and other secondary endpoints were the R0 resection, overall survival (OS), and relapse-free survival (RFS) rates. RESULTS: Between April 2016 and July 2017, 47 patients (24 EGJC, 23 LAGC) were enrolled in this study. Forty-two patients (89.4%, 95% confidence interval [CI] = 76.9-96.5) underwent surgery, and R0 resection was achieved in 41 patients. The pRR was 59.5% (90% CI = 45.7-72.3). The major grade 3 or 4 toxicities were appetite loss in six patients (12.8%), thrombocytopenia in five patients (10.6%), and neutropenia and diarrhea in three patients (6.4%) each. The rate of severe anastomotic leakage (Clavien-Dindo classification grade III or higher) in 20 EGJC was 25.0% (90% CI = 10.4-45.6). The 3-year OS and RFS rate were 62.9% (95% CI = 47.2-75.1) and 53.2% (95% CI = 38.1-66.2), respectively. CONCLUSION: SOX130 demonstrated substantial benefit for LAGC and EGJC. However, special attention should be paid to anastomotic leakage during surgery for EGJC.

Phase II study of docetaxel and S-1 (DS) as neoadjuvant chemotherapy for clinical stage III resectable gastric cancer.

BACKGROUND: We conducted a phase II trial to evaluate the efficacy and safety of preoperative chemotherapy with docetaxel (DTX) plus S-1 for resectable advanced gastric cancer. PATIENTS AND METHODS: A total of 47 patients from 14 centers were centrally registered. Patients received DTX (35 mg/m(2)) on days 1 and 15, and daily oral administration of S-1 (80 mg/m(2)/day) for days 1-14 every 4 weeks for two courses, followed by gastrectomy with D2 lymphadenectomy. The primary endpoint was pathological response rate (pRR). This study was registered in the UMIN clinical trial registry (UMIN000000875). RESULTS: The primary endpoint pRR was 47 % (90 % confidence interval (CI), 34-60 %; p < 0.0001). The response rate to preoperative chemotherapy using Response Evaluation Criteria in Solid Tumors (RECIST) was 34 %. Forty-six patients (98 %) underwent surgery, and curative resection was performed in 44 patients. Thirty-seven patients completed the protocol treatment. The most common toxicities of neoadjuvant chemotherapy were grade 3/4 neutropenia (42 %), febrile neutropenia (4 %), grade 2 anorexia (21 %), and fatigue (15 %). Treatment-related death and operative mortality was not observed in this study. CONCLUSIONS: The combination of docetaxel and S-1 was well tolerated. This is promising as a preoperative chemotherapy regimen for patients with potentially resectable advanced gastric cancer.

[Tricuspid valve endocarditis following osteomyelitis; report of a case].

A 71-year-old man was admitted with complaints of high fever and lumbago. Echocardiography showed vegetation about 16×7 mm in size attached to the tricuspid valve. Magnetic resonance imaging showed osteomyelitis. As serial echocardiography showed the progression of valvular lesion despite antibiotic therapy, the patient underwent endoscopic removal of intervertebral disc 1st, and then tricuspid valve plasty was performed 3 days later. As of the last follow-up observation at 3 years, the patient has been doing well.

[Perforated aneurysm of the non-coronary cusp with aortic regurgitation in a patient with infective endocarditis; report of a case].

This case report describes a 77-year-old man who developed infective endocarditis resulting in perforated aneurysm of the non-coronary cusp with aortic regurgitation. Diagnosis was made by transesophageal echocardiogram and successful surgical valve replacement was performed.

[Successful laparoscopic repair of delayed traumatic abdominal wall hernia].

The occurrence of traumatic abdominal wall hernia secondary to blunt trauma is uncommon, and laparoscopic repair of such hernias is very rare. A 53-year-old man, who had sustained injuries to his right thigh and right abdomen 8 months previously, visited a hospital because of a bulge in the right lateral abdomen. An abdominal computed tomography scan revealed a rupture in the lateral abdominal muscle and herniation of the cecum into the subcutaneous space. Accordingly, delayed traumatic abdominal wall hernia was diagnosed, which was successfully repaired laparoscopically. Thus, a laparoscopic tension-free mesh repair was safely and effectively performed for delayed traumatic abdominal wall hernia.

Nonfixation of mesh in laparoscopic totally extraperitoneal inguinal hernia repair: A propensity score matched analysis.

BACKGROUND: Regarding the need for mesh fixation in total extraperitoneal inguinal hernia repair (TEP), several studies have found no significant differences in the recurrence rate between patients with and without fixation. Furthermore, there is no report on the outcome of this treatment from Japan. We aimed to analyze the outcomes of nonfixation TEP with those of fixation at our institute. METHODS: In May 2016, the nonfixation TEP technique was launched. The fixation group (165 patients) was compared to the nonfixation group (195 patients). Because of the significant bias between the two groups, a propensity score matched analysis was performed (with 109 patients in each group). Moreover, only ordinary cases (with 58 patients in each group) were compared, excluding bilateral, large, and impaction cases. RESULTS: One patient in the nonfixation group experienced recurrence. It was a hernia case with a large orifice. In the fixation group, seroma was more prevalent; however, no differences were observed between the two groups in propensity score matching. In unilateral cases, the nonfixation group had a shorter operation time and stayed in the hospital for a shorter time postoperatively. The ordinary cases, excluding cases of bilateral hernias, large hernias on visual examination, impactions, and large hernial orifices, showed no recurrence or significance in surgical complications. CONCLUSIONS: The nonfixation TEP was considered acceptable at least for ordinary hernial cases.

Associations of habitual alcohol drinking with HDL cholesterol and D-dimer in patients with peripheral arterial disease.

BACKGROUND: The risk of cardiovascular disease is lower in light-to-moderate alcohol drinkers than in nondrinkers in the general population. However, it remains to be clarified whether these beneficial effects of alcohol are shown in patients with peripheral arterial disease (PAD). METHODS: The subjects were 153 male outpatients with PAD and they were divided by frequency of drinking into nondrinkers, occasional drinkers (1-4 days/wk) and regular drinkers (5-7 days/wk). Relationships of alcohol drinking with variables related to progression of atherosclerosis and cardiovascular risk were investigated. RESULTS: The levels of HDL cholesterol and d-dimer were significantly higher and lower, respectively, in regular drinkers than in nondrinkers, while there were no significant differences in BMI, blood pressure, total cholesterol, LDL cholesterol, triglycerides, hemoglobin A1c, platelet count, fibrinogen, ankle brachial index and intima-media thickness of the carotid artery in non-, occasional and regular drinkers. Odds ratios of regular drinkers vs. nondrinkers for low HDL cholesterol (0.24 [0.08 âˆ¼ 0.70]) and high d-dimer (0.29 [0.14 âˆ¼ 0.61]) were significantly lower than the reference level. CONCLUSIONS: In patients with PAD, habitual alcohol drinking was associated with increase of HDL cholesterol and suppression of blood coagulability. However, progression of atherosclerosis was not different in nondrinkers and drinkers.

Paradox of the Relationship between Cardio-Ankle Vascular Index and Ankle-Brachial Index in Patients with Lower Extremity Artery Disease.

Objectives: Measurements of ankle-brachial index (ABI) and toe-brachial index (TBI) are standard examinations for evaluating arterial blood flow in lower extremities and diagnosing lower extremity artery disease (LEAD). It remains to be clarified whether cardio-ankle vascular index (CAVI), a blood pressure-independent parameter of arterial stiffness, is associated with ABI and TBI in patients with LEAD. Methods: The subjects were 165 outpatients with LEAD. Arterial blood flow in lower extremities was evaluated by using ABI, TBI, and the degree of leg exercise-induced reduction of ABI (%). Results: CAVI showed significant positive correlations with ABI and TBI and showed significant inverse correlations with exercise-induced % decrease in ABI. CAVI was significantly higher in the 3rd tertile groups of ABI and TBI than that in the corresponding 1st tertile groups and was significantly lower in the 3rd tertile group of exercise-induced % decrease in ABI than that in the 1st tertile group. The above relationships remained significant after adjustment for age, body mass index, blood pressure, diabetes history, and habitual smoking. Conclusions: Although CAVI is a general parameter reflecting arterial stiffness, CAVI showed paradoxical associations, namely, positive associations with ABI and TBI and an inverse association with exercise-induced % decrease in ABI in patients with LEAD.

Peptides associated with hypertensive disorders of pregnancy as possible biomarkers for severity of lower extremity arterial disease.

BACKGROUND AND AIMS: Seven circulating peptides, consisting of 18-28 amino acids, were identified as possible biomarkers of hypertensive disorders of pregnancy (HDP) in our previous study. However, it is unknown whether these peptides are relevant to cardiovascular disease. The purpose of this study was to clarify the relationships between serum levels of these peptides and leg arterial blood flow in patients with lower extremity arterial disease (LEAD). METHODS: The subjects were 165 outpatients with LEAD. Patients with advanced LEAD (stages 5 and 6 of the Rutherford classification) were not included. Leg arterial blood flow was evaluated by ankle brachial pressure index (ABI) and % decrease in ABI after leg exercise induced by a leg loader or treadmill. Concentrations of the seven peptides with m/z 2081 (P-2081), 2091 (P-2091), 2127 (P-2127), 2209 (P-2209), 2378 (P-2378), 2858 (P-2858) and 3156 (P-3156) were measured simultaneously with a mass spectrometer. RESULTS: P-2081, P-2127 and P-2209 levels showed significant positive correlations with leg arterial blood flow, while P-2091, P-2378 and P-2858 levels showed significant inverse correlations with leg arterial blood flow. There was no significant correlation between P-3156 levels and leg arterial blood flow. The above positive and inverse associations between peptide levels and leg arterial blood flow were also found in logistic regression analysis using tertile groups divided by the concentrations of each peptide. CONCLUSIONS: Serum levels of six HDP-related peptides (P-2081, P-2091, P-2127, P-2209, P-2378 and P-2858) were associated with lower extremity arterial blood flow in patients with LEAD, and thus these peptides are possible biomarkers for severity of LEAD.

Evaluation of Chemotherapy-induced Dysgeusia in Patients With Gastrointestinal Cancer: A Pilot Study.

BACKGROUND/AIM: Dysgeusia, one of the adverse effects of cancer chemotherapy, and anorexia due to taste disorder can significantly impair the quality of life of patients. However, an evaluation method for dysgeusia has not yet been established. The present prospective study aimed to utilize a combination of subjective and objective assessment methods to evaluate dysgeusia in patients with gastrointestinal cancer initiating chemotherapy, to determine chemotherapeutic drugs and regimens causing dysgeusia, and to assess whether dysgeusia was associated with zinc deficiency. PATIENTS AND METHODS: A total of 21 patients with newly diagnosed gastrointestinal cancer were registered between August 2020 to March 2021. The following regimens were also included in the evaluation if the patients did not develop dysgeusia. A total 30 regimens were administered to the patients during the study period. A salt-impregnated test paper (Salsave®) was used as a subjective assessment, and the chemotherapy-induced taste alteration scale was used as an objective assessment. RESULTS: Based on physician interviews, dysgeusia was diagnosed in 8 of 21 patients (38%) treated with 8 of 30 regimens (27%). All regimens that resulted in dysgeusia contained platinum-based drugs. The patients who developed dysgeusia had higher controlling nutritional status scores at the start of chemotherapy compared to those who did not develop dysgeusia. In both subjective and objective assessments, the patients with dysgeusia performed significantly worse than those without dysgeusia. Six of the eight patients who developed dysgeusia were administered Novelzine, which did not improve the taste disorder despite the improvement of serum zinc levels. CONCLUSION: The combined approach using subjective and objective taste assessment methods was useful in assessing chemotherapy-induced dysgeusia. Mechanisms other than hypozincemia should be considered as contributors to taste disorders caused by platinum-based drugs.

[Ascending aortic aneurysm associated with von recklinghausen disease].

We report a case of ascending aortic aneurysm complicated with von Recklinghausen disease. A 57-year-old man was referred to our institution for further evaluation of the atrial fibrillation. Computed tomography (CT) revealed an aneurysm of the ascending aorta. The patient underwent resection of aneurysm to prevent rupture. Vascular complications in von Recklinghausen disease and the treatment for the vessels were discussed.

[Thoracoabdominal aortic thrombi as a source of peripheral embolization; report of a case].

We reported a case of peripheral embolization arising from diffuse thoracoabdominal aortic thrombi with minimal evidence for atherosclerosis or other aortic pathology. After the patient was treated with anticoagulation therapy, surgical removal of peripheral embolus was performed.

[Residual inferior sinus venosus atrial septal defect after surgical closure of atrial septal defect; report of a case].

Sinus venosus atrial septal defect( SVD) represent 5~10% of atrial septal defect( ASD). In contrast to the more common superior type in which the superior vena cava overrides the pathological interatrial communication, the inferior type with overriding inferior vena cava is extremely rare. We describe a case of residual inferior SVD after surgical closure of ASD.

[Mixed type ( type + pseudo) left ventricular aneurysm; report of a case].

True left ventricular aneurysms are thought to arise from the expansion and thinning of the transmural infarct area, whereas false aneurysms result from containment of ventricular rupture by pericardial adhesions. We reported a case of true left ventricular aneurysm with pseudoaneurysm( mixed type aneurysm) which was treated surgically.

A phase II multicenter trial assessing the efficacy and safety of first-line S-1 + ramucirumab in elderly patients with advanced/recurrent gastric cancer: KSCC1701.

BACKGROUND: The mainstream first-line chemotherapy for advanced/recurrent gastric cancer (ARGC) is combination therapy including platinum-based agents. With the progressive aging of the society, the incidence of gastric cancer in elderly patients is increasing. However, elderly patients cannot tolerate these agents because of renal dysfunction or low quality of life. The KSCC1701 study explored the efficacy and safety of S-1 + ramucirumab in elderly patients with ARGC. PATIENTS AND METHODS: Chemotherapy-naive patients aged ≥70 years with ARGC were eligible. Patients received S-1 (40-60 mg twice daily for 4 weeks in 6-week cycles) and ramucirumab (8 mg/kg every 2 weeks) until disease progression. The primary end-point was the 1-year overall survival (OS) rate. The anticipated lower threshold of 1-year survival was set at 40% in light of previous S-1-based regimens. The secondary end-points included progression-free survival (PFS), OS, the overall response rate (ORR) and safety. RESULTS: Between September 2017 and November 2019, 48 patients (34 men and 14 women) were enrolled in this study. The median patient age was 77.5 years, and all patients had a performance status of 0 (n = 20) or 1 (n = 28). The 1-year OS rate was 65.2%, which met the primary end-point. The median survival time and median PFS were 16.4 and 5.8 months, respectively. The ORR was 41.9%. The most frequent grade 3/4 (≥15%) adverse events were neutropenia, anorexia and anaemia. CONCLUSION: Considering these findings, S-1 + ramucirumab appears to be an excellent treatment option for elderly patients with ARGC. (250 words). This trial has been registered with the Japan Registry of Clinical Trials Registry under the number jRCTs071180066.

Prognostic Nutritional Index Considering Resection Range Is Useful for Predicting Postoperative Morbidity of Hepatectomy.

BACKGROUND: Poor preoperative nutritional and immunological status are major risk factors for postoperative complications in patients with various malignancies. Lower preoperative prognostic nutrition index (PNI) is associated with higher rates of postoperative complications and poorer prognosis in those patients. The aim of this study was to analyze the predictive value of the PNI for post-hepatectomy complications in patients with hepatocellular carcinoma (HCC), and evaluate its utility in the surgical procedure. METHODS: This retrospective study included 510 patients who underwent open hepatectomies for HCC. The predictive value of the preoperative nutritional and immunological status for postoperative complications was assessed using the PNI. Postoperative complications were defined as grade II or higher per the Clavien-Dindo classification. Postoperative complication rates were compared according to surgical procedure (major hepatectomy vs minor hepatectomy). RESULTS: Patients with postoperative complications had significantly lower PNIs than those without (43.1 ± 5.5 vs 47.0 ± 5.7, P < 0.001). In the multivariate analysis, low preoperative PNI (< 45) was an independent risk factor for postoperative complications after hepatectomy (hazard ratio, 3.85). When patients were classified per their PNI (high vs low) and extent of surgical procedures (major vs minor), there were more complications among patients with low PNI than those with high PNI, regardless of the extent of surgical procedures. Specifically, the group of patients with low PNI who underwent major hepatectomy had significantly higher rates of postoperative complications than the other groups. CONCLUSIONS: Adding the resection range to the PNI is useful for predicting the postoperative morbidities of hepatectomy patients.

Curative surgery improves the survival of patients with perforating colorectal cancer.

PURPOSE: Colorectal cancers that manifest as a perforation are generally regarded as carrying a poor prognosis. We conducted this study to assess the outcome of colorectal cancer complicated by perforation. METHODS: Between 1996 and 2004, 848 patients underwent surgery for colorectal cancers in our department. We reviewed 22 (2.6%) consecutive patients who presented with perforation at one institution. RESULTS: Fifteen (69%) patients underwent potentially curative resection. The overall operative morbidity and mortality rates were 50% and 9%. The overall 5-year survival rate was 17.4%, although by excluding patients who either had stage IV disease at diagnosis or who died during or soon after surgery (n = 7), the 5-year survival rate increased to 32% (n = 15). Furthermore, the 5-year survival rate of patients who underwent a potentially curative resection (36.9%) was significantly better than that of those who underwent a noncurative resection (0%, P = 0.0093). CONCLUSIONS: Perforating colorectal cancers are associated with high postoperative mortality and poor long-term survival. However, the intensive management of radical lymph node dissection and surgical resection are recommended to improve the long-term prognosis.

Extended total gastrectomy after nivolumab for unresectable multivisceral invasive gastric cancer.

BACKGROUND: Chemotherapy has been considered the main treatment for stage IV gastric cancer (GC). However, advances in chemotherapy have provided new clinical approaches, permitting conversion surgery with the aim of R0 resection after resolving unresectability issues. CASE PRESENTATION: A 70-year-old man with gastric cancer invading the pancreatic tail and spleen and with periaortic lymph-node enlargement was admitted to our hospital. After 24 courses of nivolumab as third-line chemotherapy, periaortic lymph-node enlargement was resolved, and conversion surgery was planned. Intraoperatively, we found no peritoneal metastasis, but the distal pancreas, splenic hilum, and transverse colon were adhered to the gastric body. Therefore, we performed D2 total gastrectomy with distal pancreatosplenectomy and partial transverse colectomy. The pathological diagnosis was type III moderately differentiated tubular adenocarcinoma (tub2) with signet ring cells, stage ypT1b (SM), ly0, and v0. The pathological proximal and distal tumor margins were negative. One lymph-node metastasis was observed (No. 4d; 1/23). Postoperatively, no recurrence was observed over 7 months, without adjuvant chemotherapy. CONCLUSIONS: Nivolumab may allow R0 resection in patients with unresectable gastric cancer. Conversion surgery should be considered even after third-line nivolumab treatment.