Bevacizumab as adjuvant treatment of colon cancer: updated results from the S-AVANT phase III study by the GERCOR Group.

BACKGROUND: The bevacizumab-Avastin® adjuVANT (AVANT) study did not meet its primary end point of improving disease-free survival (DFS) with the addition of bevacizumab to oxaliplatin-based chemotherapy in stage III colon cancer (CC). We report here the long-term survival results (S-AVANT). PATIENTS AND METHODS: Patients with curatively resected stage III CC were randomly assigned to FOLFOX4, FOLFOX4-bevacizumab, or XELOX-bevacizumab. RESULTS: A total of 2867 patients were randomized: FOLFOX4: n = 955, FOLFOX4-bevacizumab: n = 960, XELOX-bevacizumab: n = 952. With a median of 6.73 years follow-up (interquartile range 5.51-10.54), 672 patients died, of whom 198 (20.7%), 250 (26.0%), and 224 (23.5%) were in the FOLFOX4, FOLFOX4-bevacizumab, and XELOX-bevacizumab arms, respectively. The 10-year overall survival (OS) rates were 74.6%, 67.2%, and 69.9%, (P = 0.003) and 5-year disease-free survival (DFS) rates were 73.2%, 68.5%, and 71.0% (P = 0.174), respectively. OS and DFS hazard ratios were 1.29 [95% confidence interval (CI) 1.07-1.55; P = 0.008] and 1.16 (95% CI 0.99-1.37; P = 0.063) for FOLFOX4-bevacizumab versus FOLFOX4 and 1.15 (95% CI 0.95-1.39; P = 0.147) and 1.1 (95% CI 0.93-1.29; P = 0.269) for XELOX-bevacizumab versus FOLFOX4, respectively. CC-related deaths (n = 542) occurred in 157 (79.3%) patients receiving FOLFOX4, 205 (82.0%) receiving FOLFOX4-bevacizumab, and 180 (80.4%) receiving XELOX-bevacizumab (P = 0.764), while non-CC-related deaths occurred in 41 (20.7%), 45 (18.0%), and 44 (19.6%) patients, respectively. Cardiovascular-related and sudden deaths during treatment or follow-up were reported in 13 (6.6%), 17 (6.8%), and 14 (6.3%) patients, in the FOLFOX4, FOLFOX4-bevacizuamb, and XELOX-bevacizumab arms, respectively (P = 0.789). Treatment arm, sex, age, histological differentiation, performance status, T/ N stages, and localization of primary tumor were independent prognostic factors of OS in stage III. CONCLUSIONS: S-AVANT confirms the initial AVANT report. No benefit of the bevacizumab addition to FOLFOX4 adjuvant therapy in patients with stage III CC was observed in terms of DFS with a negative effect in OS, without increase in non-CC related deaths. CLINICAL TRIAL IDENTIFICATION: NCT00112918.

Aminoguanidine prevents the impairment of cardiac pumping mechanics in rats with streptozotocin and nicotinamide-induced type 2 diabetes.

BACKGROUND AND PURPOSE: Aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been shown to prevent arterial stiffening and cardiac hypertrophy in streptozotocin (STZ) and nicotinamide (NA)-induced type 2 diabetes in rats. Our aims were to examine whether AG produced benefits on cardiac pumping mechanics in the STZ and NA-treated animals in terms of maximal systolic elastance (E(max)) and theoretical maximum flow (Q(max)). EXPERIMENTAL APPROACH: After induction of type 2 diabetes, rats received daily injections of AG (50 mg kg(-1), i.p.) for 8 weeks and were compared with age-matched, untreated, diabetic controls. Left ventricular (LV) pressure and ascending aortic flow signals were recorded to calculate E(max) and Q(max), using the elastance-resistance model. Physically, E(max) reflects the contractility of the myocardium as an intact heart, whereas Q(max) has an inverse relationship with the LV internal resistance. KEY RESULTS: Both type 2 diabetes and AG affected E(max) and Q(max), and there was an interaction between diabetes and AG for these two variables. The E(max) and Q(max) were reduced in rats with type 2 diabetes, but showed a significant rise after administration of AG to these diabetic rats. Moreover, the increase in Q(max) corresponded to a decrease in total peripheral resistance of the systemic circulation when the STZ and NA-induced diabetic rats were treated with AG. CONCLUSIONS AND IMPLICATIONS: AG therapy prevented not only the contractile dysfunction of the heart, but also the augmentation in LV internal resistance in rats with STZ and NA-induced type 2 diabetes.

C2GnT-M is downregulated in colorectal cancer and its re-expression causes growth inhibition of colon cancer cells.

Changes in carbohydrates on the cell surface are associated with tumor malignancy. The mucin-type core 2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT-M) is highly expressed in the gastrointestinal tract and catalyses the formation of core 2, core 4, and blood group I branches on O-glycans. In the present study, we evaluated the role of C2GnT-M in colorectal cancer. C2GnT-M downexpression was observed in 73.6% of the primary tumors from colorectal cancer patients (39 of 53) analysed by cancer profiling array. Consistently, the majority of colon cancer cell lines and primary colon tumors expressed lower levels of C2GnT-M than did normal colon tissues by RT-PCR. HCT116 cells stably transfected with C2GnT-M inhibited expression of the core 1 structure, Galbeta1,3GalNAcalpha1-Ser/Thr, on the cell surface. Moreover, C2GnT-M expression suppressed cell adhesion, motility, and invasion as well as colony formation ability. The growth of C2GnT-M-transfected HCT116 and SW480 cells was dramatically suppressed, and the cell death induced by C2GnT-M was demonstrated by an increase in the annexin V-positive cells. Interestingly, C2GnT-M inhibited cell adhesion to collagen IV and fibronectin, and decreased tyrosine phosphorylation of paxillin, indicating that the changes in cancer behavior may be partly mediated by integrin-signaling pathways. Tumor growth in vivo was also significantly suppressed by C2GnT-M in the xenografts of nude mice. These results demonstrate that C2GnT-M is frequently downregulated in colorectal cancer and suppresses colon cancer cell growth.

Aminoguanidine prevents fructose-induced deterioration in left ventricular-arterial coupling in Wistar rats.

BACKGROUND AND PURPOSE: Aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been identified as a prominent agent that prevents the fructose-induced arterial stiffening in male Wistar rats. Our aims were to examine whether AG produced benefits on the left ventricular (LV)-arterial coupling in fructose-fed (FF) animals in terms of the ventricular and arterial chamber properties. EXPERIMENTAL APPROACH: Rats given 10% fructose in drinking water (FF) were daily treated with AG (50 mg x kg(-1), i.p.) for 2 weeks and compared with the untreated FF group. In anaesthetised rats, LV pressure and ascending aortic flow signals were recorded to calculate LV end-systolic elastance (E(es), an indicator of myocardial contractility) and effective arterial volume elastance (E(a)). The optimal afterload (Q(load)) determined by the ratio of E(a) to E(es) was used to measure the coupling efficiency between the left ventricle and its vasculature. KEY RESULTS: There was a significant interaction between fructose and AG in their effects on E(a). Fructose loading significantly elevated E(a) and AG prevented the fructose-derived deterioration in arterial chamber elastance. Both fructose and AG affected E(es) and Q(load), and there was an interaction between fructose and AG for these two variables. Both E(es) and Q(load) exhibited a decline with fructose feeding but showed a significant rise after AG treatment in the FF rats. CONCLUSIONS AND IMPLICATIONS: AG prevented not only the contractile dysfunction of the heart caused by fructose loading, but also the fructose-induced deterioration in matching left ventricular function to the arterial system.

Elective laparoscopically assisted sigmoidectomy for the sigmoid volvulus.

BACKGROUND: The laparoscopic approach for the treatment of sigmoid volvulus has been a rare surgical indication. This phase 2 study investigated the feasibility and surgical outcomes of elective laparoscopic surgery for sigmoid volvulus. METHODS: Patients with sigmoid volvulus were first offered colonoscopic decompression for their acute colonic obstruction. If the colonic decompression was successful, complete bowel preparation was performed, followed by elective laparoscopically assisted sigmoidectomy. The details of the laparoscopic procedures are shown in the video. Briefly, the redundant sigmoid colon is totally mobilized by a laparoscopic medial-to-lateral dissection sequence, after which it is exteriorized, transected, and reconstructed by end-to-end anastomosis. In the authors' experience, the medial-to-lateral approach is highly efficient for the laparoscopic mobilization of the redundant sigmoid colon. We believe that the longer the lateral abdominal wall attachment of the sigmoid colon is preserved, the better the exposure and the easier the dissection. If the risk of anastomotic leakage is considered high in a specific case, protective ileostomy is selectively preformed. Before entering the current study, the patients were well informed about the advantages and disadvantages of laparoscopic surgery. The enrollment of patients was selective according to the appropriate eligibility criteria. This study was approved by the Institutional Review Board of the National Taiwan University Hospital. The patients' clinicopathologic data and surgical outcomes were prospectively evaluated. RESULTS: Between August 2001 and April, 2005, a total of 14 patients (10 men and 4 women) with sigmoid volvulus were treated with the described procedure. The age distribution of the patients was 68.4 +/- 12.2 years. The attack of sigmoid volvulus was the first episode for eight patients, the second episode for 4 patients, and the third episode (or more) for two patients. The body mass index (BMI) of the patients was 26.8 +/- 4.4 kg/m(2). The physical status (classification of American Society of Anesthesiology [ASA]) was 1 for five patients, 2 for eight patients, and 3 for 1 patient. During the laparoscopy, all the patients presented with the pathognomonic findings of sigmoid volvulus including redundant sigmoid colon, narrow sigmoid mesenteric pedicle, and mesosigmoiditis with mesenteric fibrosis and scarring, as shown in the video. The length of the resected colon was 32 +/- 6 cm. The operation time was 194.6 +/- 32.4 min, and the blood loss was 44.0 +/- 12.4 ml. The abdominal wound consisted of four 5 to 12 mm working ports and a 5 cm major wound for exteriorization of the sigmoid colon. Some surgeons have shown that a sigmoid volvulus can be resected through a 5-cm left lower quadrant incision with very little mobilization of the colon because of its redundancy. In this context, the laparoscopic approach competed with the minilaparotomy method in terms of adequate sigmoid resection, lysis of mesosigmoid adhesion, and tension-free colorectal anastomosis. Protective ileostomy was performed for the only patient with a physical status of ASA 3. There was no mortality in this case series. However, pneumonia developed postoperatively in one patient, acute myocardial infarction in one patient, and wound infection in two patients. Excluding the two patients who experienced postoperative pneumonia and acute myocardial infarction, the duration of the postoperative ileus was 48 +/- 12 h, the postoperative hospitalization was 7 +/- 1 days, and the degree of postoperative pain was 3.5 +/- 0.5 according to the visual analog scale. The return to partial activity required 18 +/- 2.5 days, and the return to full activity required 28.4 +/- 5.6 days. As compared with the overall costs for a conventional sigmoid colectomy, which are completely covered by the National Bureau of Health Insurance of Taiwan, the expenses for the patients undergoing laparoscopic procedures were significantly higher by approximately 24,000.0 NT dollars +/- 2,635.0 (1 U.S. dollar = 32 NT dollars). These higher expenses must be borne by the patients themselves. CONCLUSION: Considering that patients with sigmoid volvulus often are elderly and chronically ill, laparoscopic elective surgery after a successful colonoscopic decompression may be a good choice for a selected group of patients in terms of minimized surgical complications and quick convalescence.

Multimedia article. Laparoscopic abdominoperineal resection for lower rectal cancers: how do we do it?

BACKGROUND: The appropriateness of the laparoscopic approach for the resection of rectal cancer has been controversial, although it is well established in colon cancer. This is a phase II study of laparoscopic abdominoperineal resection (APR) in the treatment of lower rectal cancers. METHODS: Patients with lower rectal adenocarcinoma located within 6 cm above the anal verge were recruited and subjected to laparoscopic APR. The surgical principle included en bloc resection with high ligation of inferior mesenteric vessels by no-touch isolation and total mesorectal excision. Details of the surgical procedures are presented in the video. The technical efficiency and outcome of this surgical approach were evaluated prospectively. This study was approved by the institutional review board of National Taiwan University Hospital (NTUH). RESULTS: A total of 22 patients were enrolled in the study from January 2003 to December 2004 under the ethical guidelines of clinical trials in NTUH. There were 12 females and 10 males, with an age distribution of 62.5 +/- 10.4 years. The body mass index was 24.8 +/- 4.0 kg/m2. Physical status (American Society of Anesthesiology classification) was class I in 12, class II in eight, and class III in two patients. Tumor size was 44.0 +/- 12.0 mm in diameter. Two patients were in pathologic TNM stage I, 14 in stage II, and six in stage III. The operation time was 214.0 +/- 28.4 min. Blood loss was 54.0 +/- 14.0 ml. Because the tumor specimen was retrieved from a perineal wound, the five 5 to 12 mm working ports constituted the abdominal wound. There were no major complications. However, wound infection of port sites was detected in one patient. The patients had a quick convalescence, as evaluated by the length of postoperative ileus (48.0 +/- 12.0 h), length of hospitalization (8.0 +/- 2.0 days), and degree of postoperative pain (3.5 +/- 0.5 visual analogue scale). Return to partial activity, full activity, and work was 2.0 +/- 0.5, 4.0 +/- 0.8, and 6.0 +/- 0.5 weeks, respectively. The number of cleared lymph nodes was 14.0 +/- 2.0. During follow-up (median, 18 months; range, 6-30), lung metastasis and local pelvic recurrence developed in one and two patients, respectively. Besides the expenses covered by the National Bureau of Health Insurance of Taiwan, the additional payment by patients undergoing laparoscopic procedures was NTD 24,000 +/- 3000 (1 U.S. dollar = 32 NTD). CONCLUSIONS: In our clinical setting, laparoscopic APR can be performed with good technical efficiency, quick functional recovery, and mild disability. The short-term oncologic results of laparoscopic APR seem to be acceptable, but further long-term follow-up for these patients is mandatory to define the oncologic outcomes of this approach.

Color Doppler vascularity index can predict distant metastasis and survival in colon cancer patients.

The purpose of this study was to investigate the clinical usefulness of the color Doppler vascularity index (CDVI) in patients with colon cancer before surgery. Forty-four patients with sonographically visible tumor mass of colon cancer were investigated. The CDVI of each tumor was determined using transabdominal color Doppler ultrasound. The CDVI was defined as the ratio of the number of the colored pixels within a tumor section to the number of total pixels in that specific tumor section and was calculated by using Encomate software (Electronic Business Machine Co. Ltd., Taipei, Taiwan). The correlation between the CDVI and clinicopathological factors, mode of recurrence, and patient survival was studied. For comparison, microvessel density (the mean number of microvessels in three areas of highest vascular density at x200 magnification) of the tumors of these 44 patients was also evaluated by using immunohistochemical staining of surgical specimens with anti-CD34. The microvessel density was not correlated with Dukes' classification, clinicopathological factors, and survival. The CDVI was significantly higher in the patients with lymph node metastases and vascular invasion than in those without such metastases and invasion (P = 0.006 and P = 0.0098, respectively). Moreover, in patients with a high CDVI (> 15%) and positive vascular invasion, survival was significantly poorer than in those with low CDVI (< or = 15%) and negative invasion (P = 0.0037 and 0.0039, respectively). Multivariate analysis indicated that liver metastasis, vascular invasion, and CDVI are independent prognostic factors in the patients with colon cancer. According to the mode of recurrence in 36 patients who underwent curative resection, the frequency of the distant organ recurrence was significantly higher in the high CDVI group (40%) than in the low CDVI group (0%). The CDVI is a good preoperative indicator of recurrence and patient survival in colon cancer. Thus, the CDVI may be helpful in stratifying patients for adjuvant therapy.

Neurophysiological effects of recurrent laryngeal and thoracic vagus nerves on mediating the neurogenic inflammation of the trachea, bronchi, and esophagus of rats.

The present study aims to investigate the neurophysiological effects of recurrent laryngeal nerve and thoracic vagus nerve on the non-cholinergic regulation of neurogenic plasma extravasation of the rat trachea, bronchi, and esophagus. Through thoracotomy, three nerve components, the right thoracic vagal trunk, thoracic vagus nerve, and recurrent laryngeal nerve, were identified. The experiment was sequentially conducted in four steps. First, the individual nerve component was electrically stimulated and the induced inflammatory responses, as quantified by the area density of India ink-labelled blood vessels in the trachea, bronchial trees and esophagus, were compared. Second, we assessed the relative importance of medial and lateral side of the right thoracic vagus nerve in inducing the inflammatory responses by alternative stimulation of one side with simultaneous severance of the other side of this nerve. Third, we examined the effects of transection of the lateral half of the right thoracic vagus nerve on the degeneration of axon fibers located at the following three sites: the nerve segment proximal to cutting site, bronchial and esophageal nerve branches. Finally, we directly observed the inflammatory histopathology of the right lower trachea after stimulation of the medial half of the right thoracic vagus nerve with transection of its lateral half. In this study, we found that the right recurrent laryngeal nerve was predominant in mediating the neurogenic inflammatory responses of upper and dorsal portions of trachea, whereas the right thoracic vagus nerve was predominant in mediating those of the right lower ventral wall of trachea, right main bronchus, and right lobar bronchial trees. The axon fibers of the right thoracic vagus nerve responsible for mediating the neurogenic inflammatory responses of the right lower ventral trachea were mainly accumulated in the medial half, whereas those innervating the right main bronchus, right lobar bronchial trees, and lower esophagus were largely in the lateral half of this nerve. Transection of the lateral half of the right thoracic vagus nerve resulted in significant degeneration of myelinated fibers in its bronchial and esophageal nerve branches. Histopathological examination of the right lower trachea after electrical stimulation of the medial half of thoracic vagus nerve demonstrated the silver-stained leaky venules with accumulations of inflammatory cells. We thus concluded that afferent C-fibers to upper and dorsal portions of trachea were mainly from recurrent laryngeal nerve. In contrast, the neurogenic inflammatory responses of the right lower trachea were predominantly mediated by the medial half of the right thoracic vagus nerve, and those of the right main bronchus, bronchial trees and lower esophagus were largely by the lateral half of this nerve.

Fulminant hepatic failure in a renal transplant recipient with positive hepatitis B surface antigens: a case report of fibrosing cholestatic hepatitis.

This 28-year-old male, a hepatitis B virus (HBV) carrier, received cadaveric renal transplantation and was maintained on cyclosporin A and prednisolone. Jaundice occurred 8 months after the transplantation and he died 2 weeks later due to hepatic failure. The liver histologic findings were compatible with fibrosing cholestatic hepatitis (FCH), which is caused by HBV and has only been reported in liver allografts of orthotopic liver transplantations. This is the first case of FCH developing in a renal transplant recipient. The report illustrates that (1) FCH is also a unique histologic entity in renal transplantations; (2) FCH might occur in a liver chronically infected by HBV without co-existing hepatitis D virus; and (3) FCH can cause fulminant hepatic failure within one year after transplantation while the patient is still in an immunosuppressed state.

Modified surgical techniques for the superlow anterior resection.

BACKGROUND/AIMS: Superlow anterior resection remains a technical challenge because it involves bowel resection and anastomosis in deep, limited pelvic space. Some modifications of the standard double stapling technique are thus needed to facilitate the procedure, making it safer, easier and more reliable. METHODOLOGY: A Roticulator is applied to make the first staple if the pelvic space is wide enough. A puncture hole is made manually in the closed rectal stump with the anvil tip under direct vision. If the pelvis is too narrow to apply a Roticulator, a purse-string suture is first placed before bowel resection, and is then tied securely around the anvil shaft to close the rectal stump. In either condition, the anvil and the attached sigmoid colon are pushed manually to evert the closed rectal stump. The stapled end-to-end anastomosis is then made outside the anus. RESULTS: From July 1994 to June 1996, 42 superlow anterior resections were performed using the modified techniques. There were only 2 cases of anastomotic leakage. The function results were acceptable. CONCLUSIONS: The modified techniques are safe, effective and easy to perform. Their major advantages are that the stapled anastomosis is made under direct vision and without the hindrance of pelvic tissue.

Reappraisal of K-ras and p53 gene mutations in the recurrence of Dukes' B2 rectal cancer after curative resection.

BACKGROUND/AIMS: Recurrence of rectal cancer remains a major clinical problem. This study was conducted to evaluate the impact of K-ras and p53 mutations on the recurrence of rectal cancer. METHODOLOGY: A total of 166 resected Dukes' B2 stage rectal carcinomas were collected between January 1990 and April 1994. The stored frozen tissues were retrieved for immunocytochemistry of p53 and genomic analysis of K-ras and p53 genes. The data of K-ras and p53 gene mutations were correlated with clinicopathological variables. The concordance of immunocytochemistry with genomic analysis in the survey of p53-mutations was examined. The follow-up data were analyzed by Kaplan-Meier estimator. RESULTS: Sixty-nine patients (41.6%) developed recurrent tumor. A significantly higher recurrence rate (p = 0.0013) and shorter median recurrence time were noted in p53 mutated than non-mutated cancers. Mutations in K-ras gene do not significantly increase the risk of tumor recurrence (p = 0.1702). K-ras and p53 mutations are not associated with clinicopathological parameters (p > 0.05). Kappa statistic indicates highly significant reproducibility between immunocytochemistry and genomic analysis for p53 mutations (p < 0.0001). CONCLUSIONS: Presence of p53 mutation significantly increases the recurrence rate and shortens the recurrence time of the resected rectal cancers. Pre-operative routine check for p53 mutations by immunocytochemistry may be beneficial in choosing the optimal surgical strategy for rectal cancer.

Clinicopathologic and carcinogenetic appraisal of DNA replication error in sporadic T3N0M0 stage colorectal cancer after curative resection.

BACKGROUND/AIMS: DNA replication error (RER) was found to play a role in the carcinogenesis of a subset of sporadic colorectal cancers. This study was conducted to evaluate the clinicopathologic implications of RER in T3N0M0 stage colorectal cancers. To better understand the carcinogenesis of sporadic colorectal cancer, the RER status was further correlated with the alterations of K-ras, p53 and deleted in colorectal cancer (DCC) genes which were frequently involved in the adenoma-carcinoma sequence. METHODOLOGY: Seventy-eight patients with curatively resected T3N0M0 stage sporadic colorectal cancer were accumulated. The stored frozen tissues were retrieved for analyses of 1) microsatellite instability at 7 distinct chromosomal loci, 2) loss of heterozygosity at DCC gene, 3) K-ras gene mutation, 4) p53 expression, and 5) DNA content. The RER status was correlated with various clinicopathologic and molecular genetic factors. The survival of patients stratified by RER status was analyzed by Kaplan-Meier estimator. RESULTS: The RER-positive tumor was detected in 32.1% (25/78) of patients. The RER-positive cancer patients presented with distinct clinicopathologic features including young age of tumor onset, proximal tumor location, mucin production in histology, a higher rate of synchronous and metachronous colorectal cancers, and an increased incidence of extracolonic primary cancer. Patients with RER-positive tumor were found to have an improved prognosis with the 5-year survival probability of 76% and 45% in RER-positive and RER-negative groups, respectively (p < 0.05). The RER-positive tumors tended to have normal p53 expression, DNA diploidy, and a lower DNA index. The rate for the loss of heterozygosity of DCC gene was significantly lower in RER-positive tumors. RER status was not associated with K-ras mutation. CONCLUSIONS: The clinicopathologic features and carcinogenesis of RER-positive sporadic colorectal cancers were considered different from those of RER-negative tumors. The presence of RER may identify a subset of less aggressive tumors with good prognosis in T3N0M0 stage colorectal cancers.

Neurophysiological basis of sympathetic nerve-preserving surgery for lower rectal cancer--a canine model.

BACKGROUND/AIMS: The relative contribution and interrelated compensation of sympathetic signals among sympathetic components in pelvic plexus remain undefined. This study was designed to investigate the genitourinary function in response to autonomic nerve preservation and severance using a canine model. METHODOLOGY: Eighteen mongrel dogs were randomly divided into 3 groups which received severance of the hypogastric nerves on either the right side, left side, or on both sides. The hypogastric nerves and sacral sympathetic trunks were electrically stimulated and the contraction pressure of the internal urethral orifice was measured immediately, at 1- and 3-month intervals. The ejaculation function and the length of time required to reach sexual orgasm were evaluated by manual penis-stimulation. RESULTS: The difference between the left and right sides of the normal hypogastric nerve in contribution to sympathetic signals was insignificant. Compared with the hypogastric nerve, the bilateral sacral sympathetic trunks were functionally trivial in controlling the closure of the internal urethral orifice. The preserved side of the hypogastric nerve compensated for the loss of sympathetic signals of the severed side within 1 month and, thereafter, remained stationary. In contrast, the functional compensation of bilateral sacral sympathetic trunks for the severed bilateral hypogastric nerves was insignificant. When the hypogastric nerve was preserved in one or both sides, all dogs maintained normal antegrade ejaculation. If bilateral hypogastric nerves were severed, 50.0% (3/6) of the dogs lost both emission and ejaculation function; 33.3% (2/6) presented with retrograde ejaculation; and, 16.7% (1/6) presented with combined retrograde ejaculation and reduced antegrade ejaculation. The time required to reach sexual orgasm was not affected by the severance of the hypogastric nerve. CONCLUSIONS: The normal genitourinary function could be maintained only when at least one side of the hypogastric nerve was preserved.

Flat adenoma of the colon: two cases.

Flat adenoma has been frequently reported to have a higher potential for malignant change than other polypoid adenomas. It is an endoscopically visible sessile lesion that consists histologically of an adenomatous change of the colonic mucosa. Detection, diagnosis, and treatment of flat adenoma has not previously been reported in Taiwan. We found such lesions in two patients during colonoscopic examinations as patches of discolored and irregular mucosa. Histopathologic studies revealed adenomas with mild to moderate dysplasia. Patient 1 underwent segmental colectomy; patient 2 underwent an endoscopic strip biopsy. Focal malignant changes were noted in patient 1. Both patients received close follow-up at the outpatient clinic. No recurrence has been seen in patient 1. Patient 2 developed an enlarged sessile lesion with a histologic picture showing a tubular adenoma without malignancy but refused further surgical treatment. This paper outlines the endoscopic and pathologic characteristics of flat adenoma in two patients, and should alert physicians to the importance of early detection and treatment of this lesion.

Colorectal surgery using a biofragmentable anastomotic ring.

To compare the efficacy of the biofragmentable anastomotic ring (Valtrac-BAR, Davis and Geck, Medical Device Division, Danbury, CT, USA) with conventional anastomotic techniques, 30 patients who underwent colorectal surgery from August 1993 to March 1995 were retrospectively studied. The use of the BAR was also compared with conventional techniques including hand-sewn sutures in 30 patients and an end-to-end anastomosis (EEA) stapler in 24 patients. There were 17 men and 13 women in the BAR group with ages ranging from 37 to 80 years, 18 men and 12 women in the hand-sewn group with ages ranging from 41 to 82 years and 14 men and 10 women in the EEA group with ages ranging from 38 to 72 years. Surgical indications included: 25 colon cancers and five rectal cancers in the BAR group; 27 colon cancers and three rectal cancers in the hand-sewn group; and six colon cancers and 18 rectal cancers in the EEA group. There was no conversion to other anastomotic methods. Most of the patients tolerated a low-residual diet from the fifth post-operative day. No clinical leakage or stricture was noted. Only seven patients were aware of the passage of BAR fragments. The mean hospital stay was 14.1 days. There were no significant differences among these techniques in the return of bowel function, the incidence of surgical complications, including anastomotic leakage, or the length of hospitalization. BAR anastomosis was more time efficient than conventional techniques. Our results confirmed that BAR was an ideal sutureless alternative for anastomosis in colorectal surgery.