Takayuki Toyonaga

Blockade of constitutively activated Janus kinase/signal transducer and activator of transcription-3 pathway inhibits growth of human pancreatic cancer

Constitutive activation of signal transducer and activator of transcription (Stat) proteins has been demonstrated in a wide variety of malignancies. In this study, we elucidated the significance of Janus kinase (JAK) and the downstream transcription factor Stat3 signals on malignant potentials of pancreatic cancer. Electrophoretic mobility shift assay and immunohistochemical analysis revealed that Stat3 was constitutively activated in subsets of human pancreatic cancer tissues and cell lines (Panc1, Kp4, AsPC-1, BxPC-3). A JAK-specific inhibitor, tyrphostin AG490, markedly inhibited Stat3 activation and expression of cyclin D1, bcl-xL and vascular endothelial growth factor mRNAs estimated by RT-PCR, as followed by growth arrest (6.3-21.3% vs controls; P<0.001) of pancreatic cancer cells. Inactivation of Stat3 by dominant-negative Stat3 adenovirus partly suppressed the growth of pancreatic cancer cells on day 4 post-inoculation (P<0.05) but not the expression of these mRNAs. These results indicate that activation of the JAK/Stat3 signaling pathway plays an important role in the progression of pancreatic cancer and that blockade of JAK/Stat3 signals may provide a novel therapeutic strategy for pancreatic cancer.

Completion radical surgery after cholecystectomy for accidentally undiagnosed gallbladder carcinoma

Survival time of 73 patients with undiagnosed gallbladder carcinoma incidentally found after cholecystectomy treated between 1982 and 2000 was evaluated in relation to various variables, with special reference to the significance of the radical second resection. The most significant prognostic factor was the depth of tumor invasion as assessed by univariate and multivariate analyses (odds ratio 3.40, 95% CI 1.65–7.00, p < 0.001). None of the 23 pT1 patients received radical second resection, and all of them were doing well without recurrence at their last follow-up examination. The 3-year survival rate was 68% for patients with pT2 and 14% for patients with pT3. Patient characteristics for the 18 pT2 patients who underwent radical second resection were similar to the characteristics of the 25 pT2 patients who did not; nor did postoperative survival times differ significantly. Survival time was not correlated with the interval from initial to second surgery or the type of initial cholecystectomy (open vs laparoscopic). In 11 patients with pT2 whose surgical margin was judged positive at initial cholecystectomy, the radical second resection significantly lengthened survival time. Radical second resection tended to prolong the median survival period from 7 to 15 months in 7 patients with pT3, although the difference was not significant. In conclusion, patients with pT1 undiagnosed carcinoma need no further treatment. The redo surgery was found to prolong survival only in patients with pT2 with positive surgical margin at initial cholecystectomy.

Microbiological analysis and endoanal ultrasonography for diagnosis of anal fistula in acute anorectal sepsis

Background and aimsTreatment of anorectal sepsis requires prompt surgical drainage, but it is important to identify any associated anal fistula for preventing recurrence. We evaluated whether microbiological analysis and/or endoanal ultrasonography could be used to predict anal fistula in patients with acute anorectal sepsis.MethodsFive hundred fourteen consecutive patients with acute anorectal sepsis were studied. Clinical data, digital examination findings, endosonographic findings, and results of microbiological analysis were compared with definitive surgical findings of the presence or absence of anal fistula.ResultsAnorectal abscess with anal fistula was found in 418 patients, and anorectal abscess without anal fistula was found in 96 patients. Microbiological examination showed that Escherichia coli, Bacteroides, Bacillus, and Klebsiella species were significantly more prevalent in patients with fistula (P<0.01), and coagulase-negative Staphylococci and Peptostreptococcus species were significantly more prevalent in patients without fistula (P<0.01). Results of endoanal ultrasonography were concordant with the definitive surgical diagnosis in 421 (94%) of 448 patients studied.ConclusionAcute anorectal sepsis due to colonization of “gut-derived” microorganisms rather than “skin-derived” organisms is more likely to be associated with anal fistula. When the microbiological analysis yields gut-derived bacteria, but no fistula has been found in the initial drainage operation, repeat examinations during a period of quiescence, including careful digital assessment and meticulous endosonography, are warranted to identify a potentially missed anal fistula.

Laparoscopic treatment of duodenal carcinoid tumor. Wedge resection of the duodenal bulb under endoscopic control.

Abstract. A 46-year-old man with epigastralgia and slight elevation of urinary 5-hydroxyindole acetic acid (5HIAA) was found to have a well-demarcated carcinoid tumor in the duodenal bulb. The tumor measured 8 mm in size, and showed submucosal involvement but no metastasis to the liver and regional lymph nodes. After laparoscopic exposure and lifting of the duodenal wall around the tumor, wedge resection of the duodenal bulb including the tumor was performed successfully with a laparoscopic endostapler under direct endoscopic control. The postoperative course of the patient was uneventful. Laparoscopic wedge resection of the duodenum would be an appropriate minimally invasive treatment for selected duodenal neoplasms with special preoperative assessments and intraoperative considerations.

Anal Canal Duplication Associated with Presacral Cyst in an Adult

Anal canal duplication (ACD) is a rare congenital malformation, usually detected early in life. We report a case of a 67-year-old female with symptomatic ACD associated with a presacral cyst. Physical examination revealed an accessory opening located in the midline, posterior to the true anus. Imaging examinations, including fistulography, endoanal ultrasonography, and magnetic resonance imaging, revealed a blind-ending fistulous tract without connecting with the rectum and a presacral cyst posterior to the rectum. Complete surgical excision of the tract with cyst was performed through a posterior sagittal approach. Histologic examination revealed squamous epithelium lining and smooth muscle bundles, thereby confirming ACD. The postoperative course was uneventful, and the patient was doing well; no recurrence was observed 4 years after surgery. ACD can present for the first time in infants, children, and adults. Imaging examinations are useful for the diagnosis and preoperative assessment of ACD. Therefore, ACD should be considered in the differential diagnosis, even in adults, when a posterior perineal orifice is encountered, particularly in female patients. Once ACD is suspected, intense imaging inspection is recommended to visualize the ACD and associated anomalies, and surgical removal is warranted to prevent inflammatory complications or malignant changes.

Endoanal Ultrasonography of Mucinous Adenocarcinoma Arising from Chronic Fistula-in-ano: Three Case Reports

Mucinous adenocarcinoma arising in chronic fistula-in-ano is rare, and diagnosing it at an early stage is difficult. The role of endoanal ultrasonography in diagnosing the condition has not been discussed in the study. Herein, we report three cases of mucinous adenocarcinoma arising from anal fistulas in which endosonography played an important role in diagnosing malignant change. Three male patients with a 5- to 20-year history of anal fistula were referred to our hospital due to perianal induration, progressive anal pain, or mucopurulent secretion. In all three patients, endosonography revealed a multiloculated complex echoic mass with isoechoic solid components communicating with a trans-sphincteric fistula and sonography-guided biopsy under anesthesia revealed mucinous adenocarcinoma. All patients underwent abdominoperineal resection with lymph node dissection. One patient with a local recurrence died 3 years after surgery and two have remained disease-free for >6 years. These observations suggest that endosonography may be a reliable technique for the diagnosis of mucinous adenocarcinoma arising from chronic fistula-in-ano. Sonography-guided biopsy is useful for the definitive diagnosis of malignancy. Therefore, periodic endosonography assessment should be recommended for patients with persistent anal fistula, especially those with progressive clinical symptoms. Once malignancy is suspected, aggressive sonography-guided biopsy under anesthesia should be performed, which may enable an early diagnosis, curative treatment, and favorable long-term results.

Vergleich der Genauigkeit von klinischer Untersuchung und endoanalem Ultraschall zur präoperativen Beurteilung akuter und chronischer Analfisteln

ZusammenfassungFragestellung:Diese Studie wurde zur Überprüfung der Zuverlässigkeit des endoanalen Ultraschalls bei der präoperativen Beurteilung von Analfisteln durchgeführt, insbesondere im Hinblick auf die Unterschiede zwischen akuten und chronischen Fisteln.Patienten und Methodik:Untersucht wurden 401 Patienten, die im Zeitraum von Januar bis Dezember 2005 wegen akuter oder chronischer anorektaler Entzündung kryptoglandulären Ursprungs behandelt worden waren. Bei allen Patienten wurden eine klinische Untersuchung sowie ein endoanaler Ultraschall durchgeführt. Die Übereinstimmungen zwischen den klinischen und endosonographischen Ergebnissen und den tatsächlichen chirurgischen Befunden wurden evaluiert, mit besonderer Berücksichtigung der Klassifikation des Primärtrakts und der Hufeisenausdehnung sowie der Lokalisation der inneren Öffnung. Ebenso wurden die Unterschiede bei der Genauigkeit der endosonographischen Untersuchung zwischen akuten und chronischen Fisteln evaluiert.Ergebnisse:Die Genauigkeit des endoanalen Ultraschalls war signifikant höher als die der klinischen Untersuchung hinsichtlich der Auffindung des Primärtrakts (88,8% vs. 85,0%; p = 0,0287) und der Hufeisenausdehnung (85,7% vs. 58,7%; p < 0,0001) und bei der Lokalisierung der inneren Öffnung (85,5% vs. 69,1%; p < 0,0001). Darüber hinaus war die Lokalisierung der inneren Öffnung durch die Endosonographie bei den chronischen Fisteln signifikant genauer als bei den akuten Fisteln (89,5% vs. 76,8%; p < 0,0001), obwohl sich die Genauigkeit bei der Auffindung des Primärtrakts und der Hufeisenausdehnung nicht signifikant unterschied.Schlussfolgerung:Die endoanale Sonographie ist verlässlich und nützlich bei der präoperativen Untersuchung von Analfisteln, insbesondere zur Auffindung einer Hufeisenausdehnung und zur Lokalisierung der inneren Öffnung. Die endosonographische Untersuchung liefert in den Phasen der chronischen Entzündung eine bessere Darstellung der inneren Öffnung als in den Phasen der Abszessbildung. Bei Patienten mit akuter anorektaler Entzündung könnte eine primäre Drainage mit anschließender Fisteloperation anstelle einer einstufigen Fisteloperation ratsam sein, um eine fehlerhafte Identifizierung der inneren Öffnung zu vermeiden.AbstractPurpose:This study was undertaken to evaluate the accuracy of endoanal ultrasonography for preoperative assessment of anal fistula, with special reference to the difference between acute and chronic fistula.Patients and Methods:The subjects comprised 401 patients treated for acute or chronic anorectal sepsis of cryptoglandular origin during the period January through December 2005. All patients underwent physical examination and endoanal ultrasonography. Agreement between the physical and endosonographic findings and the definitive surgical findings were evaluated with special reference to classification of the primary tract and horseshoe extension and localization of the internal opening. The difference in accuracy of endosonographic assessment between acute and chronic fistula was also evaluated.Results:The accuracy of endoanal ultrasonography was significantly higher than that of physical examination in detecting the primary tract (88.8% vs. 85.0%; p = 0.0287) and horseshoe extension (85.7% vs. 58.7%; p < 0.0001) and in localizing the internal opening (85.5% vs. 69.1%; p < 0.0001). Furthermore, localization of the internal opening by endosonography was significantly more accurate in chronic fistula than in acute fistula (89.5% vs. 76.8%; p < 0.0001), although the accuracy in detecting the primary tract and horseshoe extension was not significantly different.Conclusion:Endoanal ultrasonography is reliable and useful for preoperative assessment of anal fistula, particularly for detecting horseshoe extension and localizing the internal opening. Endosonographic assessment provides clearer depiction of the internal opening during periods of quiescence than during the period of abscess formation. For patients with acute anorectal sepsis, initial surgical drainage and subsequent fistula surgery, rather than one-stage fistula surgery, may be advisable to avoid misidentification of the internal opening.