Preoperative parameters, including percent of positive biopsy cores, in predicting pathological findings after radical prostatectomy

OBJECTIVES: We investigated whether preoperative parameters predict pathological stage at radical prostatectomy for patients with clinically localized prostatic cancer. MATERIALS AND METHODS: We studied a total of 160 men with clinically localized prostatic cancer (less than or equal to clinical T2) who underwent radical rertropubic prostatectomy at Wakayama Medical University. Clinical Ts patients are not included in this study. Preoperative parameters include patient age, Body Mass Index, preoperative serum PSA value, biopsy Gleason score, clinical stage, the percent of positive biopsy cores (%PosBx) and the percent of positive biopsy cores on the dominant side (%DomPosBx). Univariate and multivariate analysis were performed to examine the prognostic significance of these preoperative parameters. Significant independent factors were combined to create a table to predict pathologically organ confined disease. RESULTS: Univariate analysis showed preoperative serum PSA value (p< 0.001), biopsy Gleason score (p =0.001), clinical stage (p = 0.026), %PosBx (p= 0.002) and %DomPosBx (p=0.003) were significantly related to the pathological stage. On multivariate analysis, serum PSA value (p< 0.01), biopsy Gleason score (p<0.05) and %DomPosBx (p<0.05) were significant independent predictors of pathological stage. CONCLUSION: We provide two model combinations using preoperative clinical factors, one is a combination of serum PSA and biopsy Gleason score and the other is a combination of serum PSA and %DomPosBx, which define a new preoperative model for predicting pathological organ confined prostatic cancer. These combinations are useful and provide important information for urologists to determine the appropriate treatment strategy for clinically localized prostatic cancer.     

Cytokeratin deposits in lymph nodes show distinct clinical significance from lymph node micrometastasis in human esophageal cancers

BACKGROUND: Cytokeratin immunostaining is the most common method used to identify micrometastatic cancer cells from the lymph nodes. However, contamination with hyalinized cytokeratin particles, frequently observed in the lymph nodes of esophageal cancer patients, can lead to misinterpretation of cytokeratin immunostaining. MATERIALS AND METHODS: Cytokeratin immunostaining (AE1/AE3) of surgically removed lymph nodes was performed for 41 cases of node-negative, but locally advanced (T3, T4), esophageal cancer patients. Cytokeratin immunoreactivity (CK) was classified as micrometastasis (MM) or cytokeratin deposit (CD) by the presence or absence of tumor nuclei in serial sections given hematoxylin-eosin staining. RESULTS: CK (+) was observed in 18 patients (44%), including 11 with MM (+) (27%) and 10 with CD (+) (24%). There was no correlation between MM and CD, and neither was associated with clinicopathological factors, except for a high incidence of preoperative chemotherapy in CD (+) patients. The presence of CK did not affect postoperative survival of esophageal cancer patients at this limited stage, showing a 5-year survival rate of 57% for CK (+) and 64% for CK (-) (P = 0.6064). Interestingly, patients with MM (+) showed poorer prognosis than MM (-) (5-year survival: 28% vs 79%, P = 0.0188), while CD (+) patients tended to display better prognosis than CD (-) ones (5-year survival: 78% vs 56%, P = 0.1860). CONCLUSIONS: Evaluation by cytokeratin immunostaining of lymph nodes requires careful discrimination of CD from MM, in order to allow MM to be used as a prognostic factor for esophageal cancer patients.     

Downregulation of matrix metalloproteinase-9 and attenuation of edema via inhibition of ERK mitogen activated protein kinase in traumatic brain injury

Emerging data suggest that matrix metalloproteinase-9 (MMP-9) plays a critical role in the pathophysiology of brain injury. However, the regulatory mechanisms involved in vivo remain unclear. In this study, we focus on a mitogen activated protein kinase (MAPK) pathway that may trigger MMP-9 after traumatic brain injury. We aim to show that inhibition of the extracellular signal regulated kinase (ERK) would attenuate MMP-9 levels, reduce blood-brain barrier damage, and attenuate edema after trauma induced by controlled cortical impact in mouse brain. Western blots showed that phospho-ERK was rapidly upregulated after trauma. Treatment with U0126, which inhibits MEK, the kinase upstream of ERK, effectively prevented the activation of ERK. After trauma, gelatin zymography showed an increase in MMP-9. U0126 significantly reduced trauma-induced MMP-9 levels. Correspondingly, U0126 ameliorated the degradation of the tight junction protein ZO-1, which is an MMP-9 substrate, and significantly attenuated tissue edema. At 7 days after trauma, traumatic lesion volumes were significantly reduced by U0126 compared with saline-treated controls. These data indicate that the ERK MAPK pathway triggers the upregulation in MMP-9 after trauma, and further suggest that targeting the upstream signaling mechanisms that regulate deleterious MMP-9 activity may reveal new therapeutic opportunities for traumatic brain injury.     

Mucinous cystic neoplasm of the pancreas presenting with hemosuccus pancreaticus: Report of a case

Hemosuccus pancreaticus (HP) is mostly induced by a ruptured pseudoaneurysm or hemorrhage from a pseudocyst in chronic pancreatitis. We herein report a rare case with HP induced by tumor hemorrhage. The present patient is a 71-year-old woman referred to us with a diagnosis of severe progressive anemia. Endoscopy revealed hemorrhage from the papilla of Vater. Computed tomography showed a multilocular cystic tumor in the tail of the pancreas. The patient underwent a distal pancreatectomy. The histopathological diagnosis was carcinoma in mucinous cystadenoma. No cancer infiltration into the pancreatic duct was detected. Pancreatography of the resected specimen demonstrated an overt communication between the main pancreatic duct and the cystic cavity of the tumor, which was not demonstrated preoperatively by endoscopic retrograde pancreatography. Although the cause of HP is mainly acute or chronic pancreatitis, we should bear in mind that a pancreatic tumor may be a possible cause of HP and that, as such, prompt and proper treatment is mandatory.     

Perioperative Allogeneic Blood Transfusion Is Associated With Surgical Site Infection After Abdominoperineal Resection—a Space for the Implementation of Patient Blood Management Strategies

Allogeneic blood transfusion (ABT) has been reported as a major risk factor for surgical site infection (SSI) in patients undergoing colorectal surgery. However, the association of ABT with SSI in patients undergoing abdominoperineal resection (APR) and total pelvic exenteration (TPE) still remains to be evaluated. Here, we aim to elucidate this association. The medical records of all patients undergoing APR and TPE at our institution in the period between January 2000 and December 2012 were reviewed. Patients without SSI (no SSI group) were compared with patients who developed SSI (SSI group), in terms of clinicopathologic features, including ABT. In addition, data for 262 patients who underwent transabdominal rectal resection at our institution in the same period were also enrolled, and their data on differential leukocyte counts were evaluated. Multivariate analysis showed that intraoperative transfusion was an independent predictive factor for SSI after APR and TPE (P = 0.004). In addition, the first–operative day lymphocyte count of patients undergoing APR, TPE, and transabdominal rectal resection was significantly higher in nontransfusion patients compared with transfusion ones (P = 0.026). ABT in the perioperative period of APR and TPE may have an important immunomodulatory effect, leading to an increased incidence of SSI. This fact should be carefully considered, and efforts to avoid allogeneic blood exposure while still achieving adequate patient blood management would be very important for patients undergoing APR and TPE as well.Key words: Colorectal cancer, Abdominoperineal resection, Surgical site infection, Allogeneic blood transfusion, Patient blood managementPostoperative surgical site infection (SSI) is one of the most frequent complications associated with various surgical procedures, and it results in adverse outcomes, including longer hospital stay, higher health care costs, and increased surgical mortality.¹ It is one of the most frequent nosocomial complications, accounting for almost one fifth of all health care–associated infections.² Colon surgery and rectal surgery are associated with higher SSI rates compared with most other abdominal procedures, with 5% to 25% of colon and rectal surgery patients developing incisional and organ/space SSI.^3–5 Moreover, the incidence of overall SSI was reported to be higher in rectal surgery patients (17%–28%) than in colonic surgery patients (9%–23%),^3,5,6 with especially higher overall SSI rates observed in patients undergoing abdominoperineal resection (APR; 12%–51%).^7–9 These are attributed to the high infection rates of the perineal wound, reported to be as high as 21%.¹⁰ Thus, the incidence of SSI associated with APR should be the highest among the various abdominal operative procedures.Various risk factors for postoperative SSI in colorectal surgery were reported previously. Open surgery,^10–12 perioperative allogeneic blood transfusion (ABT),^4,10,12 and prolonged operation time^4,9 have been found to be risk factors for SSI in a number of studies. Although several preceding reports have investigated the risk factors for SSI associated with APR, the reported independent risk factors varied among the studies. Although a number of studies have reported on the role of ABT as a strong risk factor for incisional SSI in colorectal surgery,^13,14 only one study has investigated on its relevance to the onset of incisional SSI after APR procedure; but this study failed to demonstrate a significant association. Presently, therefore, the role of ABT as a potential risk factor for incisional SSI in APR remains to be elucidated, and doing so will be very important for the implementation of measures to achieve patient blood management in this group of patients.In this study, we aimed to elucidate the risk factors for SSI in patients receiving APR, especially focusing on ABT.     

Adrenal androgen levels as predictors of outcome in castration‐resistant prostate cancer patients treated with combined androgen blockade using flutamide as a second‐line anti‐androgen

Objectives: To analyze the clinical effects of flutamide as a second‐line anti‐androgen for combined androgen blockade in patients with castration‐resistant prostate cancer (CRPC) initially treated with bicalutamide as a first‐line anti‐androgen. Methods: Our study population consisted of 16 patients with CRPC who were treated with flutamide (375 mg daily) as second‐line hormonal therapy. Dehydroepiandrosterone (DHEA), androstenedione, androstenediol, testosterone and dihydrotestosterone were measured to investigate the relationship between plasma androgens and outcome following treatment. Furthermore, adrenal androgen levels in a medium of adrenal cancer cell line were also measured. Results: Second‐line hormonal therapy using flutamide resulted in a reduction of the prostate‐specific antigen (PSA) level in 14 (87.5%) of 16 patients. A PSA decline greater than 50% was observed in 8 (50%) of the 16 patients. The duration of median responsiveness was 6.25 months. PSA elevation of baseline androstenediol level was a predictive factor of PSA responsiveness. The lower DHEA group improved the duration of responsiveness to flutamide. In vitro, 3 µmol/L flutamide suppressed DHEA, androstenedione and androstenediol synthesis compared with bicalutamide in a medium of adrenal cancer cell line. Conclusions: Our data show that flutamide suppresses the adrenal androgens in comparison with bicalutamide. The responsiveness and response duration of flutamide can be predicted in patients with a higher baseline androstenediol level and a lower DHEA level. Metabolites from adrenal androgens contribute to the progression of prostate cancer.     

Effect of Different Slopes of the Lower Leg during the Nordic Hamstring Exercise on Hamstring Electromyography Activity

The purpose of this study was to examine whether the NHE with an increased lower leg slope angle would enhance hamstring EMG activity in the final phase of the descend. The hamstring EMG activity was measured, the biceps femoris long head (BFlh) and the semitendinosus (ST). Fifteen male volunteers participated in this study. Subjects performed a prone leg curl with maximal voluntary isometric contraction to normalize the hamstring EMG activity. Subsequently, subjects performed the NHE, with the help of a certified strength and conditioning specialist, while the lower leg slope angle were randomly set at 0° (NH), 20° (N20), and 40° (N40). To compare hamstring EMG activity during the NHE variations, the knee flexion angle was set in the range from 0° to 50°, divided into five phases (0–10°, 10–20°, 20–30°, 30–40° and 40–50°), where 0° indicated that the knee was fully extended. To calculate the knee extension angular velocity, the knee flexion angle divided by time, and break point angle (BPA) was the angle at which 10°/s was exceeded. In the statistical analysis, a two-way repeated measures ANOVA was used for the hamstring EMG activity and a one-way repeated measures ANOVA was used for the BPA. The EMG activity of the BFlh and the ST in N20 and N40 was significantly higher than in NH at knee flexion angle of 0–20° (p < 0.05). For the BPA, NH (57.75° ± 13.28°), N20 (36.27° ± 9.89°) and N40 (16.26° ± 9.58°) were significantly higher in that order (p < 0.05). The results of this study revealed that the NHE with an increased lower leg slope angle shifted the BPA to the lower knee flexion angle and enhanced the hamstring EMG activity in the final phase of the descent.Key points

• The NHE with an increased lower leg slope angle enhances the hamstring EMG activity in the final phase of the descent.
• The NHE with an increased lower leg slope angle shifts the BPA to the lower knee flexion angle.
• The NHE with an increased lower leg slope angle may be an important rehabilitation exercise to prevent recurrence of HSIs.

Key words: Sports injuries, injury recurrence, hamstring muscles, electromyography, rehabilitation exercise, resistance training     

Wall Stress Studies of Abdominal Aortic Aneurysm in a Clinical Model

To estimate when an abdominal aortic aneurysm (AAA) may rupture, it is necessary to understand the forces responsible for this event. We investigated the wall stresses in an AAA in a clinical model. Using CT scans of the AAA, the diameter and wall thickness were measured and the model of the aneurysm was created. The wall stresses were determined using a finite element analysis in which the aorta was considered isotropic with linear material properties and was loaded with a pressure of 120 mmHg. The AAA was eccentric with a length of 10.5 cm, a diameter of 2.5 to 5.9 cm, and a wall thickness of 1.0 to 2.0 mm. The aneurysm had specific areas of high stress. On the inner surface the highest stress was 0.4 N/mm2 and occurred along two circumferentially oriented belts--one at the bulb and the other just below. The stress was longitudinal at the anterior region of the bulb and circumferential elsewhere, suggesting that a rupture caused by this stress will result in a circumferential tear at the anterior portion of the bulb and a longitudinal tear elsewhere. In the mid-surface the highest stress was 0.37 N/mm2 and occurred at two locations: the posterior region of the bulb and anteriorly just below. The stress was circumferential, suggesting that the rupture caused by this stress will produce a longitudinal tear. The location and orientation of the maximum stress were influenced more by the tethering force than by the wall thickness, luminal pressure, or wall stiffness. In conclusion, the rupture of an AAA is most likely to occur on the inner surface at the bulb. Such analytical approaches could lead to a better understanding of the aneurysm rupture and may be instrumental in planning surgical interventions.     

Possibility of "distraction arthrogenesis": first report in rabbit model

We investigated the possibility of articular cartil-age distraction for use in reconstructing joint structure and for increasing the donor site of osteochondral grafts. Intraarticular osteotomy was performed at the femoral condyle in 12 Japanese white rabbits. The bone segment was fixed with a specially designed external fixator. After a 3-week waiting period, distraction was performed intermittently for 3 weeks (0.7 mm × 3 times per week) in the distraction group (n = 7) and, in the remaining animals (gap group; n = 5), a gap of 6.3 mm in length was made at surgery. All rabbits received etidronate injections (20 mg/kg ×2 times per week) for 5 weeks, to slow mineralization. The femoral condyle was harvested 9 weeks postoperatively and decalcified sagittal sections were stained and evaluated, using a histological grading scale. In the distraction group, distraction of 4.2 ± 1.4 mm was achieved, and the distracted cartilage area was filled with regenerated cartilage, without any gap between the regenerated and the adjacent articular cartilage. This regenerated cartilage showed metachromasia with toluidine blue. In the gap group, newly formed cartilage tissue was folded from the edge of the osteotomy site and fibrous tissue was interposed in the gap. The histological grading score was significantly lower in the distraction group (P < 0.02). Our preliminary results demonstrated the possibility of cartilage distraction; however, long-term observation will be necessary to confirm the characteristics of the distracted cartilage. We may call the process "distraction arthrogenesis", because the entire articular entity, which consists of cartilage, subchondral bone, and bone, could be distracted at once. Received: April 5, 2001 / Accepted: July 15, 2001