Combined treatment of pelvic exenterative surgery and intra-operative pelvic hyperthermochemotherapy for locally advanced rectosigmoid cancer: Report of a case

A huge rectosigmoidal cancer which extended into the urinary bladder in a 64-year-old man is herein described. The tumor occupied the pelvic and lower abdominal cavities, while the rectosigmoid was totally obstructed. No hepatic or pulmonary metastasis was evident. The ventral and flank sides of the peritoneum in the right lower abdomen, right common iliac vessels, bilateral ureters, terminal ileum, cecum, ascending colon, and urinary bladder were all directly invaded by the tumor, but the aorta, sacrum, and lower rectum were free of cancer. Consequently, an anterior pelvic exenteration was carried out along with an ileal conduit and a right hemicolectomy. Immediately after the exenteration, intra-pelvic hyperthermochemotherapy was performed using a 46–47°C perfusate containing 40 g/ml of mitomycin C (MMC) and 200 g/ml of cisplatin (CDDP), for 90 min, in an attempt to prevent any further local recurrence. A right hemicolectomy and a permanent colostomy were done simultaneously with the hyperthermia treatment. After an uneventful postoperative course, the patient was prescribed adjuvant chemotherapy, i.e., two administrations of 17 mg/m² and 21 mg/m² of MMC, and ten doses of 710 mg/m² of 5-fluorouracil (5-FU) followed by five doses of 535 mg/m² of 5-FU. At the time of this writing, the patient is still alive without recurrence at 21 months after surgery.     

Prediction of ACNU plasma concentration-time profiles in humans by animal scale-up

Summary Plasma concentration-time profiles of nimustine hydrochloride, 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), in the mouse, rat, rabbit, and dog were determined by high-performance liquid chromatographic analysis. The pharmacokinetic parameters for these four animal species and previously reported clinical data were analyzed for investigation of interspecies correlation. Loglog plots of body weight (W; kg) vs total plasma clearance (CLtot, p; ml/min) and steady-state distribution volume (Vd, ss; 1) for the four animal species were linear, with high correlation coefficients (r 0.996 for both parameters), despite the fact that the nonrenal clearance was >97% in these species. Linear regression on the plots excluding human data yielded allometric equations (CL_tot,p=50.6 W^0.957; Bd, ss=1.29 W^1.03) that were extrapolated to predict ACNU pharmacokinetic parameters in humans. For both parameters, however, there were 3-fold differences between the predicted and observed parametric values. To investigate these discrepancies, we measured serum protein binding of ACNU in these animal species and in humans. The values of CLtot,p and Vd,ss were converted into those of CL^u _tot,p and Vd,^u _ss, which correspond to the parameters for unbound ACNU. In this case, correlation coefficients of the log-log plots excluding human data (CL^u _tot,p=71.7 W^0.891; Bd,^u _ss=1.82 W^0.966) were also high (r0.991). The extrapolated values vs those observed in a 70-kg human were the following: CL^u _tot,p, 3,160 vs 2,290 ml/min; Vd,^u _ss, 110 vs 1061. Thus, the animal data were successfully extrapolated to yield better predictions of human pharmacokinetic parameters if the analysis was based on the unbound plasma concentration of ACNU. In addition, the predicted plasma concentration-time profile for humans also showed good agreement with the observed ones. These results suggest the importance of measuring unbound fractions of drugs for more accurate prediction of human pharmacokinetic parameters by extrapolation of animal data to the human situation.     

Risk estimation for hypertension based on follow-up health examination data in a small village in Kumamoto prefecture, Japan

The estimation of risk for incidence of hypertension was carried out by follow-up study in a small village in Kumamoto Prefecture, Japan (N=750, 48.2±15.2months). The most significant risk in both sexes was blood pressure at entry. As for other risks, age, total cholesterol, and BMI in females were significant risks for systolic and diastolic blood pressure changes to greater than the borderline level. These factors in males were not significant. From the results of analysis using Cox's proportional hazards model, drinking in males was shown to be a significant risk for diastolic change, and in females for systolic change. It was concluded that excessive drinking in both sexes and obesity in females led to important health problems associated with hypertension among the subjects of the study.     

The effect of glibenclamide on the production of interstitial adenosine by inhibiting ecto-5′-nucleotidase in rat hearts

1. Adenosine exerts cardioprotective effects on the ischaemic myocardium. The production of adenosine in the ischaemic myocardium is attributed primarily to the enzymatic dephosphorylation of adenosine 5′-monophosphate (AMP) by 5′-nucleotidase. We determined the activity of 5′-nucleotidase in rat hearts. The objective of the study was to determine the effects of ATP-sensitive K⁺ (K_ATP) channel antagonists (glibenclamide and 5-hydroxydecanoate) on the production of adenosine, by use of a flexibly mounted microdialysis technique.
2. Rats were anaesthetized and the microdialysis probe was implanted in the left ventricular myocardium, followed by perfusion with Tyrode solution. The baseline level of dialysate adenosine was 0.51±0.09 μM (n=16). Introduction of AMP (100 μM) through the probe increased the dialysate adenosine markedly to 9.79±0.43 μM (n=12, P<0.001 vs baseline), and this increase was inhibited by the ecto-5′-nucleotidase inhibitor, α,β-methyleneadenosine 5′-diphosphate (100 μM), to 0.76±0.12 μM (n=8). Thus, the dialysate adenosine noted during the perfusion of AMP originated from dephosphorylation of AMP by ecto-5′-nucleotidase, and the dialysate level of adenosine attained reflects the ecto-5′-nucleotidase activity in the tissue in situ.
3. Glibenclamide (0.1–100 μM) decreased the adenosine concentration measured during the perfusion of AMP (100 μM) in a concentration-dependent manner (IC₅₀=10.5 μM). In contrast, 5-hydroxydecanoate (10–100 μM) did not affect the concentrations of dialysate adenosine, measured in the presence of AMP (100 μM). These results suggest that glibenclamide inhibits the activity of endogenous ecto-5′-nucleotidase and decreases the concentration of adenosine in the interstitial space of rat ventricular muscles in situ.

     

Anaesthetic management of a neonate with prenatally diagnosed cervical tumour and upper airway obstruction

We report the anaesthetic management of a mother, and airway management of a neonate with a prenatal diagnosis of cervical cystic hygroma causing upper airway obstruction. The mortality of such neonates due to upper airway obstruction is reported to exceed 20% following deliveries. Elective Caesarean section was performed under general anaesthesia, and in utero tracheal intubation of the neonate was accomplished under uninterrupted maternal-fetal circulation. By utilizing isoflurane and ritodrine, the heart rate of the neonate remained between 120 to 150 bpm for four minutes following uterine incision. We believe that it is important that a multidisciplinary approach be initiated for planning of airway management of the neonate soon after the diagnosis is made. Laryngoscopy blades larger than normal for neonates, and a portable Doppler to monitor the viability of the neonate were found to be useful in the management of the neonate during in utero tracheal intubation. Although estimated blood loss was not increased, nor did uterine atony occur postoperatively despite the use of ritodrine during Caesarean section, the efficacy and safety of ritodrine to delay placental detachment have not been proved.     

Pathophysiology of dogs after 84% hepatectomy with emphasis on prostaglandin metabolites and the effect of a thromboxane A2 synthesis inhibitor and a prostaglandin I2 analog

The pathophysiological conditions following 84% hepatectomy were examined in terms of the changes in thromboxane A₂ (TxA₂) and prostaglandin I₂ (PGI₂) in canine model. OKY-046, TxA₂ inhibitor, and OP-2507, a PGI₂ analog, were administered to evaluate the possibility of extending hepatic resection. The 2-week survival rate following 84% hepatectomy significantly improved after the administration of OKY-046 and OP-2507, from 12.5% to 58.3% and 75.0%, respectively. Furthermore, OP-2507 significantly improved impaired hepatocyte and sinusoidal endothelial cell function after 84% hepatectomy, resulting in a satisfactory recovery to the preoperative levels. Within 24 h after 84% hepatectomy, the plasma levels of thromboxane B₂ (TxB₂) increased significantly, and the 6-keto-prostaglandin F_l (6-KF) levels became slightly elevated. OKY-046 and OP-2507 decreased TxB₂ and increased 6-KF in the plasma, resulting in the maintenance of sufficient blood flow in the portal vein and hepatic tissue and the mitigation of microcirculatory disorders. Moreover, the cytoprotective effects of the two drugs inhibited functional impairment of the residual liver. In conclusion, abnormal prostaglandin metabolites were produced after 84% hepatectomy, being involved in residual liver disorders. However, the administration of either an inhibitor of TxA₂ synthesis or PGI₂ analog ameliorated the functional impairment of the residual liver, which suggests their potential value for extending the resectability of the liver from what is presently feasible.An abstract of this study was presented at the 92nd Annual Meeting of the Japan Surgical Society held in 1992.     

The development of a small bowel volvulus in the early postoperative period following a distal gastrectomy: Report of a case

A 51-year-old Japanese man who underwent a standard distal gastrectomy for cancer of the stomach developed abdominal pain when oral intake was commenced on the 6th postoperative day after an uneventful postoperative course. Complete obstruction of the jejunum led to a sudden deterioration in his general condition and a laparotomy was performed, revealing counterclockwise rotation of the mesenterium. The necrotic portion of the small intestine was removed, while 10 cm of the upper jejunum and 100 cm of the terminal ileum were preserved. His second postoperative course was uneventful apart from the development of intestinal hurry, which is now under medical control 9 months after his second laparotomy.     

A study on how a 6-month aerobic exercise program can modify coronary risk factors depending on their severity in middle-aged sedentary women

It is well known that physical exercise can reduce coronary risk factors. But how an aerobic exercise modifies coronary risk factors in relation to severity and physical fitness is still controversial. Fifty-four middle-aged women (mean age, 55 years) completed a 6-month on-site and home-based anaerobic threshold-level exercise program. The changes in coronary risk factor profiles were observed during the pre-intervention and intervention periods. Before the intervention (during control period), most coronary risk factors showed a rather unfavorable trend. After the program, their mean body weight decreased from 56.7 to 55.7 kg (p>0.05) and the proportion of body fat from 30.9 to 27.9% (p>0.05) without any reduction in lean body mass. Systolic blood pressure (SBP) decreased from 129.0 to 125.0 mm Hg (p>0.05) and diastolic blood pressure from 79.5 to 76.6 mm Hg (p>0.05). Fasting plasma glucose (FPG) declined from 109.6 to 103.4 mg/dl (p>0.05). Changes in SBP and FPG were most remarkable in their respective worst tertile. Serum lipids improved only modestly. Maximum oxygen uptake increased from 23.6 to 26.1 ml/kg/min (p>0.01). However, no significant correlations were found between changes in coronary risk factors and those in physical fitness. We conclude that the 6-month aerobic exercise program would modify women’s coronary risk factors depending on their initial values, probably independently of the changes in physical fitness.     

Fecal incontinence successfully managed by antegrade continence enema in children: A report of two cases

Two children with intractable fecal incontinence after correction of high anorectal malformations were successfully managed by the daily administration of a glycerin enema into the cecum via an appendicocecostomy or tubularized cecostomy, according to the method of Malone's antegrade continence enema (ACE). Fluoroscopic defecography performed during this procedure in each patient disclosed that the glycerin enema promptly evoked cecal peristalsis, which was transmitted to the distal colon and rectum, and squeezed out almost all the fecal matter, evacuating it from the anus. However, two enemas within a short interval were required to achieve a complete washout of feces. Although this report describes only two patients, our experience confirmed that the ACE was very effective and that adding the word continence to antegrade enema was justifiable. Moreover, fluoroscopic defecography was proven to play a significant role in determining the appropriate regimens of this technique to achieve complete washout of the feces.     

Completely covered cloacal exstrophy: recognition of a new clinical sub-entity

A case showing many of the typical visceral features of cloacal exstrophy is reported. The patient had fn imperforate anus, a cecal-cloacal fistula, dehiscence of the pubiic symphysis, and lumbosacral spina bifida with synsingomyelia, but the lower abdominal wall was intact without any visceral extroversion. The pertinent literature was reviewed, and it was found that this case corresponded to t typical case of completely covered cloacal exstrophy. Only six cases, including the present one, have so far been reported in the literature. From a clinical viewpoint, it apparently occupies an intermediate position in the wide spectrum of cloacal anomalies between classical cloacal exstrophy and imperforate anus with recto-cloacal fistula, but anatomatically and embryologically it is definitely a variant of cloacal exstrophy. In other words, it looks like an imperforate anus with recto-cloacal exstrophy, but should be treated as a variant of loacal exstrophy. The anatomy, classification, embryology, diagnosis, and management of this peculiar surgical condition are discussed, and recognition of this entity is urged.