Hidefumi Higashi

Risk Factors Associated with Surgical Site Infection in Upper and Lower Gastrointestinal Surgery

PurposeTo assess the risk factors of surgical site infection (SSI) in gastrointestinal surgery.MethodsSurgical site infection surveillance was conducted in 27 hospitals.ResultsThe incidence of SSI in the 941 patients studied was 15.5%. The factors associated with SSI were body mass index (BMI), comorbidity, emergency procedures, wound classification, blood loss, the suture material used for intra-abdominal ligation, the method of subcutaneous incision, the frequency of glove changes, and the absence of subcutaneous sutures. In lower alimentary tract procedures, additional factors influencing the incidence of SSI were sex, smoking status, operating time, the suture material used for abdominal wound closure and seromuscular sutures, and the combined resection procedures. According to a multiple logistic regression analysis, the independent risk factors for SSI were as follows: the type of operation, blood loss, wound classification, emergency procedures, the frequency of glove changes, the use of subcutaneous sutures, combined resection procedures, and the material used for seromuscular suturing.ConclusionStrict asepsis and minimal blood loss were associated with a lower incidence of SSI following gastrointestinal surgery. The use of absorbable suture material may be involved in reducing the risk of SSI.

Reduced Expression of PTEN Protein and Its Prognostic Implications in Invasive Ductal Carcinoma of the Breast

Objective: The PTEN tumor suppressor gene has been demonstrated to be inactivated in a variety of human tumors. In breast cancer, the PTEN gene mutation is not commonly found whereas loss of heterozygosity affecting the PTEN locus is frequently found. The aim of this study was to analyze PTEN protein expression in breast cancer and to evaluate the prognostic significance of PTEN protein expression. Methods: Paraffin-embedded sections ofinvasive ductal carcinoma of the breast were immunohistochemically stained for PTEN protein expression in 236 breast cancers. The immunohistochemical expression of breast cancer cells was judged to be either normal or reduced compared with the PTEN protein expression of the normal mammary gland. Results: The expression of PTEN protein was found to have decreased in 67 (28%) of 236 breast cancers. The reduced expression correlated with lymph node metastasis (p = 0.0371), but not with tumor size, nuclear grade, MIB-1 counts or p53 protein expression. Univariate analysis indicated that patients with a reduced PTEN expression had a shorter disease-free survival (DFS) than those with a normal PTEN expression (p = 0.0174). Univariate analyses also determined tumor size, lymph node metastases, nuclear grade, MIB-1 counts, p53 protein as well as PTEN protein expression to be significant factors for DFS, while multivariate analysis determined lymph node metastases and the MIB-1 counts to be independent significant factors for DFS. Conclusions: The inactivation of PTEN, demonstrated by a reduced expression of PTEN protein by immunohistochemistry, was found in about one third of all breast cancers. The reduced expression of PTEN protein correlated with lymph node metastases and a worse prognosis in the patients with breast cancer.

Angiopoietin 2 expression in invasive ductal carcinoma of the breast: its relationship to the VEGF expression and microvessel density

SummaryAngiopoietin (Ang) is a ligand for the endothelium-specific tyrosine kinase receptor Tie-2, while a shift in the Ang-1:Ang-2 expression ratio in favor of Ang-2 was found to be associated with tumor angiogenesis. In the present study, we analyzed the immunohistochemical expression of Ang-2 in a series of 198 breast cancers, in which VEGF expression and microvessel density (MVD) were previously determined. Ang-2 expression was negative in 24 (12%), positive in 50 (25%) and strongly positive in 124 (63%) of 198 cases. A significant correlation was found between Ang-2 and VEGF expressions (p=0.0004) and between Ang-2 expression and MVD (p=0.0006), while a high MVD was found in 10 (77%) of 13 tumors with a strongly positive VEGF and positive Ang-2 expression and in 40 (71%) of 56 tumors with a strongly positive VEGF and strongly positive Ang-2 expression. Although there was no difference in the disease free survival (DFS) stratified according to Ang-2 expression alone, the 69 patients with a strongly positive VEGF and a strongly positive or positive Ang-2 expression had a significantly (p=0.0316) worse DFS than those with other combinations of VEGF and Ang-2 expressions. A multivariate analysis indicated lymph node metastasis and MVD to be independently significant prognostic factors for DFS, while the combination of VEGF and Ang-2 expressions was not a significant factor for DFS. In conclusion, the Ang-2 expression was found to be closely correlated with VEGF expression and MVD in breast cancer, while a high MVD was frequently found in tumors with a high expression of both VEGF and Ang-2. The survival analysis demonstrated a high MVD, which was induced by a high expression of both VEGF and Ang-2, to therefore have a strong prognostic significance in breast cancer.

Laparoscopic splenectomy for idiopathic thrombocytopenic purpura: Comparison of laparoscopic surgery and conventional open surgery

In chronic idiopathic thrombocytopenic purpura (ITP), the two main therapeutic choices are steroid treatment or splenectomy. The adult form of ITP is described as a disease found primarily in young adults, with a female predominance. Treatment with steroids effects a complete response in less than 30% of patients, whereas splenectomy is successful in more than 60% of patients who undergo it. The minimal access afforded by laparoscopic splenectomy is considered highly desirable for these patients. The purpose of this study was to compare the clinical benefits of a laparoscopic splenectomy with those of conventional open surgery for patients with ITP. From 1968 to 1993, splenectomy was performed on 51 patients: 10 operations done laparoscopically and 41 performed conventionally. Complications, postoperative pain, recovery, and hospital charges were then compared. Laparoscopic splenectomy involved minimal incisions, and a significantly lower frequency of analgesia was required for postoperative abdominal pain (1.3 vs. 3.3); hospital stay was shorter (8.2 vs. 20.1 days) (p < 0.005). Operative time was significantly longer for the laparoscopic surgery (249.2 vs. 99.8 min) (p < 0.0001), but blood loss was less (176.0 vs. 511.7 g) (p < 0.01). No intraoperative or postoperative major complications occurred with the laparoscopic procedures, compared with 46.3% with conventional surgery. Finally, the total hospital costs were lower with laparoscopic splenectomy, especially for postoperative care (p < 0.05). A laparoscopic splenectomy may well be considered the surgical treatment of choice for patients requiring a splenectomy in view of both quality of life and economy.

Increased prostacyclin content in gastric mucosa of cirrhotic patients with portal hypertensive gastropathy

Plasma levels and gastric mucosal contents of prostaglandin (PG) E2 and prostacyclin were determined in cirrhotic patients with portal hypertensive gastropathy (PHG), in cirrhotic patients without PHG and in healthy controls. PGE2 and 6-keto-PGF1 alpha (a stable metabolite of prostacyclin) levels were measured in 30 cirrhotic patients and 10 controls, using radioimmunoassay. Of 30 cirrhotics, 13 had PHG of the fundus and the corpus. Plasma concentrations of 6-keto-PGF1 alpha in the cirrhotic patients were significantly higher than in the controls (p < 0.01), but there was no significant difference between cirrhotics and controls with regard to plasma levels of PGE2. The gastric mucosal contents of 6-keto-PGF1 alpha in the fundus was significantly higher in cirrhotics with PHG than those without PHG (p < 0.05) and controls (p < 0.01). However, the gastric mucosal contents of PGE2 in the fundus were not significantly different in cirrhotics with and without PHG. The gastric mucosal contents of 6-keto-PGF1 alpha significantly correlated to the plasma levels (r = 0.37, p < 0.05), but there was no significant correlation between plasma levels and gastric mucosal contents of PGE2. Since prostacyclin has vasodilator and gastric acid inhibitory effects, we speculate that high contents of prostacyclin in the gastric mucosa may have some role in the pathogenesis of PHG.

Restoration of ATP Contents in the Transplanted Liver Closely Relates to Graft Viability in Dogs

Searching for a marker of graft viability, adenosine triphosphate (ATP) content in the graft tissue was measured sequentially during orthotopic liver transplantation (OLT) in 24 adult mongrel dogs. According to the survival period, 12 recipients were divided into two groups: group I - early-death group (n = 6), death within 3 days after OLT and group II - survival group (n = 6), survived more than 7 days after OLT (average 12 days). Serum biochemical findings showed no differences between the two groups except that the prothrombin time on the first postoperative day in group I was significantly longer (p less than 0.05). The ATP content ratio (% of initial value) was significantly higher in group II, compared to that of group I (p less than 0.05), 94 versus 53% at 10 min after perfusion, 31 versus 17% at just before recirculation, respectively. The ATP content ratio recovered significantly to more than 80% at 10 min after recirculation in group II but only to less than 50% in group I. These results suggest that restoration of ATP content in the liver after graft recirculation reflects the viability of the graft and can serve as an appropriate prognostic marker in cases of OLT.

Bcl-2 protein expression is associated with p27 and p53 protein expressions and MIB-1 counts in breast cancer

BackgroundRecent experimental studies have shown that Bcl-2, which has been established as a key player in the control of apoptosis, plays a role in regulating the cell cycle and proliferation. The aim of this study was to investigate the relationship between Bcl-2 and p27 protein expression, p53 protein expression and the proliferation activity as defined by the MIB-1 counts. The prognostic implication of Bcl-2 protein expression in relation to p27 and p53 protein expressions and MIB-1 counts for breast cancer was also evaluated.MethodsThe immunohistochemical expression of Bcl-2 protein was evaluated in a series of 249 invasive ductal carcinomas of the breast, in which p27 and p53 protein expressions and MIB-1 counts had been determined previously.ResultsThe Bcl-2 protein expression was found to be decreased in 105 (42%) cases. A decreased Bcl-2 protein expression was significantly correlated with a nuclear grade of III, a negative estrogen receptor, a decreased p27 protein expression, a positive p53 protein expression, positive MIB-1 counts and a positive HER2 protein expression. The incidence of a nuclear grade of III and positive MIB-1 counts increased as the number of abnormal findings of Bcl-2, p27 and p53 protein expressions increased. A univariate analysis indicated a decreased Bcl-2 protein expression to be significantly (p = 0.0089) associated with a worse disease free survival (DFS), while a multivariate analysis indicated the lymph node status and MIB-1 counts to be independently significant prognostic factors for the DFS.ConclusionThe Bcl-2 protein expression has a close correlation with p27 and p53 protein expressions and the proliferation activity determined by MIB-1 counts in invasive ductal carcinoma of the breast. The prognostic value of Bcl-2 as well as p27 and p53 protein expressions was dependent on the proliferation activity in breast cancer.

Postoperative management using intensive patient-controlled epidural analgesia and early rehabilitation after an esophagectomy.

PurposePatient-controlled epidural analgesia (PCEA) was developed for use after surgery for thoracic esophageal cancer to relieve wound pain, introduce early rehabilitation, and provide an uneventful postoperative recovery.MethodsThis retrospective study investigated 22 patients who underwent esophageal surgery to determine the efficacy of postoperative management with PCEA. In the PCEA group (n = 12), patients had two epidural catheters inserted to cover both the thoracic and abdominal incision with a patient-controlled bolus capability.ResultsPostoperative mechanical ventilation was administered in all cases in the control group (n = 10). On the other hand, this was only necessary in two patients in the PCEA group. The amount of time the patients stayed in the intensive care unit and the hospital was significantly shorter in the PCEA group than in the control group (P < 0.001 and P < 0.01, respectively). Respiratory complications occurred in four patients in the control group, and none in the PCEA group. The mean number of supplemental analgesics administered for breakthrough pain until the 7th postoperative day was 5.5 in the control group, and 1.3 in the PCEA group (P < 0.001).ConclusionsEarly rehabilitation is facilitated with intensive PCEA, while it also improves postoperative management and reduces hospitalization after esophageal surgery.

HEMODYNAMIC AND BIOCHEMICAL CHANGES DURING NORMOTHERMIC AND HYPOTHERMIC SANGUINOUS PERFUSION OF THE PORCINE HEPATIC GRAFT

Using an ex vivo liver sanguinous perfusion system, hemodynamic and biochemical changes of the porcine livers were studied, which were preserved cold (4 degrees C) for 24 hr in University of Wisconsin solution and reperfused with normothermic (37 degrees C) (n = 8) or hypothermic (32 degrees C) (n = 8) blood for 3 hr. Six more livers were reperfused with normothermic blood (37 degrees C) immediately after procurement as controls. The total hepatic blood flow was adjusted to 1 ml/min/g liver weight, in which hepatic artery and portal vein flows were administered at a 1:2 ratio. In livers stored cold for 24 hr in UW solution and perfused normothermically, a statistically higher hepatic artery resistance was exhibited at 30 and 60 min after reperfusion (P less than 0.05), and there was lower bile output (P less than 0.05) at 90 and 120 min as compared to the controls. In livers stored cold for 24 hr in UW solution and perfused hypothermically, as compared to ones perfused normothermically, statistically higher hepatic-artery and portal-vein resistances (P less than 0.05) were observed throughout the perfusion period and 60 min after reperfusion, respectively. In addition, bile output and oxygen consumption of these livers were statistically lower than those of ones perfused normothermically (P less than 0.05). In contrast, chemistries of the perfusate of livers perfused hypothermically were comparable to ones perfused normothermically. Histologic examination of the liver perfused hypothermically demonstrated hepatic arterial and/or portal venous congestion and mild-to-moderate hemorrhage in the portal triads. This study suggests that livers preserved for a prolonged period of time demonstrate a high hepatic arterial resistance shortly after revascularization, and that recipient hypothermia after revascularization may be a risk factor for the development of hepatic arterial thrombosis following liver transplantation.

Severe sepsis caused by Aeromonas hydrophila in a patient using tocilizumab: a case report

IntroductionAeromonas species do not commonly cause disease in humans. However, when disease is seen, it often occurs in patients with underlying immunosuppression or malignancy and has a high fatality rate.Case presentationA 72-year-old Japanese woman with rheumatoid arthritis treated with tocilizumab (which has an immunosuppressive effect) presented with severe epigastric pain. She had a fever with chills, hypotension and jaundice. She was diagnosed with acute suppurative cholangitis and treated with cefoperazone-sulbactam and an endoscopic drainage was performed. Jaundice was slightly improved, but the shock state and inflammatory reactions were prolonged as typical of septic shock. On the second day after admission, an electrocardiogram showed ST segment elevation and echocardiography showed ventricular wall dysfunction. Coronary arteries were patent in coronary angiography and she was diagnosed with stress-induced cardiomyopathy. Blood cultures showed Aeromonas hydrophila. A stool culture was negative for A. hydrophila. On day six, her white blood cell count and neutrophils were normalized and cefoperazone-sulbactam treatment was halted. Left ventricular function normalized on day twelve and a laparoscopic cholecystectomy for cholelithiasis was performed on the 16th day of hospitalization. A culture from the bile showed A. hydrophila. Eighteen days after surgery, tocilizumab treatment was restarted and there were no complications. Two months after restarting tocilizumab, our patient is stable without any serious events.ConclusionWe present a rare case of A. hydrophila sepsis and acute suppurative cholangitis in an elderly patient with gallstones and rheumatoid arthritis using tocilizumab. This clinical course may suggest that preemptive treatment for cholelithiasis prior to using molecular-targeting agents might be feasible in elderly patients.