Biomedical subjects
Publications and source records attributed to T Akasu.
Standard linear staplers for transverse occlusion of the rectum is sometimes too large to be applied in a narrow pelvis. A proximate TL 30 (Ethicon, Inc., Somerville, NJ) is easily introduced and applied twice for occlusion of the rectum, followed by anastomosis with a circular stapler. This triple-stapling technique is a safe and easy procedure for low colorectal anastomosis in a narrow pelvis.
PURPOSE: This study was designed to evaluate the accuracy of preoperative staging by transrectal ultrasonography (TRUS) and to clarify the limitations and pitfalls of TRUS by clinicopathologic analysis for staging errors. MATERIALS AND METHODS: Results of TRUS for 164 consecutive patients with rectal cancer were compared prospectively with histopathologic findings according to the newest TNM classification. Clinicopathologic factors that may influence staging errors were analyzed by reviewing both resected specimens and hard copies of TRUS. RESULTS: There were 13 patients histopathologically staged as pTis, 21 as pT1, 34 as pT2, 84 as pT3, 12 as pT4, 73 as pN0, and 91 as pN1-3. Of these, 85, 86, 56, 93, 75, 74, and 77 percent, respectively, were correctly staged by TRUS. Excluding 12 cases with incomplete examinations because of annular constricting tumors, overstaging of tumor invasion depth was mostly caused by tumor invasion close to the deeper uninvolved layer, inflammatory cell aggregation, desmoplastic change, and hypervascularity around the tumor, mimicking tumor invasion on TRUS. The understaging was mostly the result of microscopic invasion beyond the estimated layers and difficulties in examination because of the tumor location being close to the anal canal or on the Houston's valves or the tumor shapes being polypoid or bulky and fungating. Overstaging in lymph node status was caused by reactive lymph node swelling and understaging by the presence of only small involved node and metastasis in the extramesorectal nodes. CONCLUSIONS: An awareness of the limitations and pitfalls of TRUS, as demonstrated by the present study, should improve staging accuracy and contribute to optimum clinical decision-making.
A total of 448 patients with advanced lower rectal cancer who underwent curative wide lymphadenectomy with autonomic nerve preservation were reviewed with respect to surgical techniques, operative burdens, node status, survival rate, and mode of recurrence. Operative time and blood loss in patients who underwent lateral dissection were much greater than those encountered with conventional resection. According to the direction of lymphatic spread in patients with Dukes C disease, the incidence of upward spread was 94% and lateral spread 27%. The overall incidence of lateral metastasis was 14%. The overall 5-year survival was 70%. According to the Dukes classification, the 5-year survival rates were 92% for Dukes A, 79% for Dukes B, and 55% for Dukes C, whereas it was 43% in patients with lateral node metastasis. An analysis of the survival rate was carried out with regard to the number of node metastases, direction of lymphatic spread, and autonomic nerve preservation. The overall incidence of local recurrence was 9.3% and amounted to 16.0% in patients with Dukes C disease. The case of advanced lower rectal cancer was characterized by positive lymph nodes or circular lesions around the circumference (both diagnosed by endorectal ultrasonography). We recommend extended lymphadenectomy with lateral node dissection, as it preserves the autonomic nerve.
We report a case of sclerosing sweat duct carcinoma, a rare tumor, occurring in the peri-anal skin, a rare position. The patient, a 41-year-old Japanese woman, was admitted to our hospital with recurrence of sclerosing sweat duct carcinoma in the peri-anal skin, which had been initially resected at a local hospital. She underwent abdomino-perineal resection. No lymph node metastases or distant metastases were found. Although we allowed a 2-cm resection margin around the tumor, microscopy showed that the tumor had extended to within 2 mm of this margin at several sites, indicating that sclerosing sweat duct carcinoma is locally aggressive. An ample resection margin should therefore be taken at initial surgery for this type of tumor. Moreover, surgical excision that is wider and deeper than primary excision is required when this tumor recurs.
The prognosis of patients with unresectable liver metastases is poor, even if hepatic arterial infusion chemotherapy (HAI) or systemic chemotherapy is administered. A pilot study was performed to evaluate the feasibility and efficacy of multimodality therapy with hepatectomy after HAI and portal embolization for such patients. Eight patients with colorectal carcinoma and synchronous unresectable liver metastases underwent resection of the primary tumor and placement of a pump, followed by HAI with 5-fluorouracil and mitomycin C. Owing to shrinkage of the liver metastases, two patients could undergo extended right hepatic lobectomy after portal embolization, which was deemed to be essential to prevent post-operative hepatic failure. The median survival time of the eight patients was 30 months, with a response rate of 75%. Complications including sclerosing cholangitis and duodenal ulcer were observed in five patients (63%). Additional hepatectomy could be performed successfully after portal embolization without morbidity in two patients. These two patients are still alive more than 6 years after initiation of HAI and have been free of disease for more than 5 years after hepatectomy. Hepatectomy after HAI and portal embolization is feasible and may be an option to cure selected patients with initially unresectable liver metastases.
Properties of ligand-gated K+ channels were examined in neurons of rat dorsolateral septal nucleus (DLSN). Application of muscarine (30 microM), 5-hydroxytryptamine (5-HT, 10 microM), adenosine (100 microM), baclofen (10 microM) and norepinephrine (NE, 10 microM) to DLSN neurons caused hyperpolarizing responses associated with decreased membrane resistance. Hyperpolarizations induced by muscarine increased their amplitudes at membrane potential between -70 and -50 mV. Baclofen- and NE-induced hyperpolarizations were less sensitive to voltage. The agonist-induced hyperpolarizations decrease in amplitudes and reversed at a membrane potential between -90 and -100 mV. Ba2+ (1 mM) blocked all agonist-induced hyperpolarizations in DLSN neurons. Tetraethylammonium (TEA, 3 mM) blocked the muscarine-induced hyperpolarization but not the hyperpolarizations induced by the other agonists. Extracellular Cs+ and glibenclamide did not block the agonist-induced hyperpolarizations. These results suggest that muscarine, 5-HT, adenosine, baclofen and NE cause the hyperpolarization by increasing the activity of Ba(2+)-sensitive K+ channels, probably the GTP-binding protein (G-protein) activated inward rectifier K+ (GIRK) channels in DLSN neurons.
Receptors responsible for the tachykinin-induced depression of gamma-aminobutyric acid-A (GABAA) receptors in neurons of bullfrog dorsal root ganglia (DRG) were investigated by using whole-cell voltage-clamp techniques. Substance P (10 nM-1 microM) depressed the inward current produced by GABA (GABA current) in a concentration-dependent manner. Substance P did not change the reversal potential of the GABA current. Neurokinin A also depressed the GABA current with potency similar to those of substance P. [D-Arg1, D-Trp7,9, Leu11]substance P (spantide, 1 microM) shifted the concentration-inhibition curve of substance P to the right. Spantide (1 microM) increased the IC50 from 56 nM to 210 nM. Lineweaver-Burk plot, a reciprocal plot of the concentration-inhibition curve, showed that spantide did not change the maximum response (Vmax) to substance P but increased the apparent dissociation constant (Kd). CP99994 (1 microM), an neurokinin-1 (NK1) receptor antagonist, inhibited the substance P-induced depression of the GABA current. These results suggest that the tachykinin-induced depression of the GABAA receptor sensitivity is mediated by NK1 receptors in neurons of bullfrog DRG.
Sphincter saving procedure (SSP) was applied when, for tumor which were a localized type and well or moderate differentiated adenocarcinoma, distal clearance margin (AW) more than 2 cm was obtained and when, for tumor which was a infiltrated type or adenocarcinoma with other pathological grades, AW more than 3 cm was obtained. Between 1984 and 1993, 209 patients with rectal carcinomas, the lower border of which was located below the peritoneal reflexion, underwent curative surgery: SSP in 114 and abdominoperineal resection (APR) in 95. The APR group included more advanced cases both in the depth of invasion and in lymph node metastases (p = 0.011, p = 0.059, respectively). During the median follow-up of 68.6 months, recurrent tumors were developed in 17.5% of the SSP and in 30.5% of the APR (p = 0.027). The patients with SSP showed better prognosis than those with APR(p = 0.0007), with the 5 year survival rate of 80.2% and 70.0%, respectively. The difference may be due to higher incidence of hematogenous metastases in the APR (26.3%) than in the SSP (13.2%). There was no difference in local recurrences between them. When function after SSP was compared with that after anterior resection for middle or upper rectal carcinomas, no difference was observed between them, although most patients of the both groups complained of increased frequency of defecation and occasional soiling. The criteria of SSP for low located rectal carcinoma may be adequate with the acceptable oncological outcome, but altered function after SSP should be improved.
BACKGROUND: Serious problems in the surgical treatment of patients with rectal carcinoma are local failure and urinary and sexual dysfunction. To resolve these problems, pelvic autonomic nerve preservation (PANP) combined with lateral lymph note dissection has been introduced. METHODS: Of 238 consecutive patients with middle or low rectal carcinoma who underwent potentially curative surgery between 1987 and 1992, 214 underwent PANP according to pre- and intraoperative staging. PANP was evaluated from the perspectives of oncologic outcome and urinary and male sexual function with a retrospective questionnaire in a group of patients followed prospectively. RESULTS: During the median follow-up of 53 months, local recurrence developed in 5.6% of patients; no local recurrence was observed in Dukes Stage A or Dukes Stage B patients. The 5-year survival rates of Dukes Stage A (n = 55), Dukes Stage B (n = 72), and Dukes Stage C (n = 87) patients were 96.4%, 84%, and 67.3%, respectively. Of patients undergoing preservation of the unilateral pelvic plexus alone, 93.5% maintained the ability to void spontaneously. Of patients who had complete preservation of the autonomic nerve system, 70.4% maintained male sexual function, and of patients who had removal of the hypogastric nerves and preservation of the pelvic nerve plexuses, 66.7%, were capable of erection and intercourse without normal ejaculation. CONCLUSIONS: Early stage rectal carcinoma should be treated both with local cure and complete preservation of urinary and sexual function. In high risk patients with suspected perirectal lymph node metastases and tumors invading the perirectal fat, the appropriate PANP should be applied with consideration of the balance between achieving a cure and preserving autonomic function.
1. The effects of substance P (SP) and related tachykinins on the function of gamma-aminobutyric acid-A (GABAA) receptors were examined in acutely dissociated neurones of bullfrog dorsal root ganglia (DRG) by using whole-cell voltage-clamp techniques. 2. Application of SP (10 nM to 1 microM) depressed inward currents produced by GABAA receptor activation (IGABA). Neurokinin A (NKA) and neurokinin B (NKB) also depressed IGABA; the rank order of agonist potency was SP > NKA > NKB. Spantide ([D-Arg1, D-Trp7,9,Leu11]SP) and L-703,606, NK1 receptor antagonists, blocked the SP-induced depression of IGABA. 3. SP irreversibly depressed IGABA, when neurones were intracellularly dialysed with GTP gamma S. Intracellular application of GDP beta S prevented the SP-induced depression of IGABA. Pertussis toxin (PTX) did not block the inhibitory effect of SP on IGABA. 4. The depression of IGABA produced by SP was inhibited by H-7 and PKC(19-36), protein kinase C (PKC) inhibitors, but not by H-9 and HA-1004, protein kinase A inhibitors. IGABA was suppressed by application of sn-1,2-dioctanoyl glycerol (DOG), a PKC activator. 5. It is concluded that activation of neurokinin-1 (NK1) receptors downregulates the function of the GABAA receptor of primary sensory neurones through a PTX-insensitive G-protein. PKC may be involved in the transduction pathway of the tachykinin-induced inhibition of the GABAA receptor.
Whole-cell voltage-clamp recordings were made from cultured bullfrog sympathetic neurons to measure the steady-state activation curve of M-type potassium current. When measured with a calcium-deficient (10 nM) pipette solution M-conductance was 4.8 nS at -35 mV having the 50%-activation voltage at-20 mV. Respective values were 17.2 nS at -35 mV with the 50%-activation voltage at -42 mV when measured with a calcium-rich (1 microM) solution, indicating the hyperpolarizing displacement of the activation curve with high internal calcium. It is suggested that intracellular calcium ions can modulate kinetics of M-current which thereby regulate the number of M-channels being open at given membrane potentials.
The effect of N-methyl-D-aspartate (NMDA) on the function of GABAA receptors was examined in acutely dissociated neurons of bullfrog dorsal root ganglia (DRG) by using whole-cell patch clamp methods. The application of NMDA (100 microM) to DRG neurons suppressed the inward currents produced by GABA (100 microM) and muscimol (100 microM). DL-2-Amino-5-phosphonovaleric acid (APV; 100 microM) antagonized the NMDA-induced depression of the GABA current in a competitive manner. Kainic acid (100 microM) did not depress the GABA current. NMDA induced no depression of the GABA current in a nominally Ca(2+)-free solution containing 5 mM Mg2+. These data indicate that the activation of the NMDA receptor inhibits the GABAA receptor-mediated current via a Ca(2+)-dependent process.
The mechanism underlying the over-recovery of an M-type potassium current following the washout of muscarine (20 microM) has been examined. Whole-cell recordings were made from single neurons dissociated from bullfrog sympathetic ganglia. During over-recovery, the maximum M-conductance decreased by about 2.8 nS while the steady-state M-current activation curve was displaced in the hyperpolarizing direction by about 13 mV. These data suggest that a hyperpolarizing shift in the kinetics of M-current causes over-recovery in amphibian autonomic neurons.
The effects of tachykinins on primary afferent neurons of bullfrog dorsal root ganglia (DRG) were examined by using whole-cell patch-clamp methods. Neurokinin A (NKA) caused inward current (INKA) in a concentration-dependent manner. Concentration-response curve showed that the EC50 for NKA was 6 nM. The INKA showed strong tachyphylaxis, when NKA was continuously applied for more than 1 min. Substance P (SP) also produced inward current with potency similar to that of NKA. Neurokinin B (NKB) was less effective in producing the inward current. The order of agonist potency was NKA = SP >> NKB. Spantide ([D-Arg1, D-Trp7.9, Leu11]SP), a non-selective peptide antagonist at tachykinin receptors, reduced the tachykinin-induced current. CP-99,994, a selective non-peptide antagonist for neurokinin-1 (NK1) receptor, inhibited the inward currents produced by NKA and SP. The INKA was associated with decrease in K+ conductance. NKA suppressed both a voltage-dependent K+ current, the M-current (IM), and a voltage-independent background K+ current, IK(B). Intracellular dialysis with GTP gamma S (100 nM) or GDP beta S (100 microM) depressed the INKA. Pre-treatment of DRG neurons with pertussis toxin (PTX) did not prevent the INKA. Depletion of intracellular ATP depressed the INKA. These results suggest that the tachykinin-induced inward current is mediated through the NK1 receptor which mainly couples to PTX-insensitive G-protein in bullfrog primary afferent neurons.
The role of glucose in synaptic transmission was examined in the rat dorsolateral septal nucleus (DLSN) with single-microelectrode voltage-clamp and slice-patch technique. Removal of glucose from the oxygenated Krebs solution caused an outward current associated with an increased membrane conductance. The current-voltage relationship (I-V curve) showed that the hypoglycemia-induced outward current was reversed in polarity at the equilibrium potential for K+. Exposure of DLSN neurons to the glucose-free solution for 5-20 min depressed the excitatory postsynaptic current (EPSC), the inhibitory postsynaptic current (IPSC), and the late hyperpolarizing current (LHC). Replacement of glucose with 2-deoxy-D-glucose (2DG), an antimetabolic substrate, mimicked the deprivation of glucose. Mannoheptulose (10 mM) and dinitrophenol, inhibitors of glucose metabolism, also depressed the PSCs, even in the presence of 10 mM glucose. Glucose-free perfusion did not significantly depress the glutamate-induced inward current, indicating that the inhibition of the EPSC by the glucose-free perfusion was presynaptic. gamma-Aminobutyric acid (GABA)-induced outward currents were depressed by the glucose-free solution. Intracellular dialysis of DLSN neurons with a patch-pipette solution containing 5 mM ATP attenuated the hypoglycemia-induced outward current. Glucose-free superfusion consistently inhibited the IPSC and the LHC without changing the GABA-induced outward current in ATP-treated DLSN neurons. It is suggested that glucose metabolism directly regulates the release of both excitatory amino acids and GABA from the presynaptic nerve terminals.
A 27-year-old woman with a small rectal carcinoid tumor was examined by transrectal ultrasonography (TRUS) for preoperative staging. TRUS revealed regional lymph node involvement, in addition to a 10-mm hypoechoic tumor invading into not through, the submucosa. The lymph node involvement was confirmed preoperatively by TRUS-guided needle biopsy. Although the digital examination findings indicated local excision was appropriate, in accordance with TRUS and TRUS-guided biopsy findings, the patient underwent radical surgery. The TRUS findings of lymph node involvement and depth of invasion were confirmed histologically. The patient is alive and disease-free 35 months postoperatively. These observations suggest that TRUS reveals the regional lymph node involvement and the depth of invasion of rectal carcinoid tumors accurately and, therefore, helps in selecting appropriate treatment.
In 1991, the Japan Research Society for Cancer of the Colon and Rectum proposed clinical criteria (Japanese criteria) for hereditary nonpolyposis colorectal cancer (HNPCC). According to the Japanese and Amsterdam criteria, three groups of patients are defined: 1) those diagnosed as having HNPCC using the Amsterdam criteria (Amsterdam HNPCC); 2) those classified as Japanese criteria category A (putative HNPCC-A) and 3) those classified as Japanese criteria category B (putative HNPCC-B). In order to evaluate the prognosis of HNPCC and the role of the Japanese criteria, the clinicopathological characteristics, recurrence and survival rates of Amsterdam HNPCC (n 14) and putative HNPCC-A (n 31) and B (n 100) patients were studied, and compared with those of patients with sporadic colorectal cancer (controls, n 1604). The Amsterdam clinicopathological characteristics and those of putative HNPCC were the same as those reported previously. Neither local nor distant recurrences were observed in the Amsterdam HNPCC and putative HNPCC-A during a median follow-up period of 137 months. The 5-year survival rates of the Amsterdam HNPCC, putative HNPCC-A, B, and control patients were 92.3%, 81.2%, 66.5% and 60.0%, respectively, and those of the former two groups were significantly better than those of the others (P<0.05). These results show that the prognosis of HNPCC is better than that of sporadic colorectal cancer, and that the Japanese criteria, especially for category A, can be used to select putative HNPCC patients from among those with sporadic colorectal cancers.
In order to confirm the presence of cancer cells in mesenteric venous blood and to examine their relationship with the occurrence of liver metastases, we attempted to detect K-ras codon 12 point mutations in perioperative mesenteric blood using enriched polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) analysis in 25 patients with primary colorectal tumors carrying K-ras point mutations. Among these patients, three with synchronous liver metastases were included. The same K-ras point mutation (substitution of GAT for GGT) was detected in both the blood and the primary tumor in a Dukes' C patient. We confirmed this result by colony hybridization and estimated the tumor-to-normal cell ratio to be 1:400. This patient has no liver metastases two years after surgery and her carcinoembryonic antigen (CEA) level remains normal. We demonstrated that considerable numbers of cancer cells can be found in mesenteric venous blood during colorectal cancer surgery. However, their potential role in the formation of liver metastases remains unclear.