Impact of Drain Insertion After Perforated Peptic Ulcer Repair in a Japanese Nationwide Database Analysis.

BACKGROUND: Many perforated peptic ulcers (PPUs) require surgical repair due to diffuse peritonitis. However, few studies have examined the clinical effects of postoperative drainage after PPU repair. This study aimed to investigate the drain insertion rates in patients who underwent PPU repair in Japan, and to clarify the impact of drain insertion on the postoperative clinical course. METHODS: A retrospective nationwide cohort study was performed using administrative claims data of patients who had undergone PPU repair between 2010 and 2016. These patients were divided into two groups based on whether or not they had received a postoperative abdominal drain. Using propensity score matching, we compared the incidences of postoperative interventions for abdominal complications between both groups. RESULTS: A total of 4869 patients from 324 hospitals were analyzed. At the hospital level, drains were placed in all PPU repair patients in 229 (70.7%) hospitals. At the patient level, 4401 patients (90.4%) had drains inserted. The drain group was associated with a higher emergency admission rate, poorer preoperative shock status, longer anesthetic time, and a higher amount of intra-abdominal irrigation. In the propensity score-matched patients, the drain group had a significantly lower incidence of postoperative interventions than the no-drain group (1.9 vs. 5.6%; risk ratio = 0.35; 95% confidence interval 0.16-0.73; P = 0.003). CONCLUSION: Postoperative drainage was performed in the majority of patients who underwent PPU repair in Japan. Drainage following PPU repair may facilitate patient recovery by reducing the need for postoperative interventions.

Circulating Tumor Cells as an Independent Predictor of Survival in Advanced Gastric Cancer.

BACKGROUND: When the indication for surgery of highly advanced gastric cancer is considered, careful selection of the patients is important. In addition to tumor-node-metastasis factors and peritoneal lavage cytology (CY), which are important predictors of prognosis, detection of circulating tumor cells (CTCs) could be another potential marker. METHODS: This study prospectively evaluated CTCs using a semi-automated immunomagnetic separation system (CellSearch) for 136 patients with advanced gastric cancer to determine the frequency of CTC positivity. For 123 patients who also had their CY evaluated, the significance of both CTC and CY, was investigated as a potential biomarker to predict progression-free survival (PFS) or to monitor the therapeutic effect. RESULTS: In 25 patients (18.4 %), CTCs were positive. Positive CTC counts were more common for tumors with diffuse histologic type and distant metastasis. The PFS of CTC-positive patients was significantly shorter than that of CTC-negative patients (hazard ratio 2.03; P = 0.016). A multivariate analysis of 123 patients showed that CTC and CY as well as performance status and macroscopic distant metastasis were independent factors for PFS. When both CTC and CY were converted to negative values by therapeutic interventions, long-term PFS was achieved. CONCLUSIONS: Detection of CTCs was an independent predictor of a shorter PFS in advanced gastric cancer. For selecting patients who require intensive treatment, CTCs could be a valuable biomarker. The combined status of CTC and CY would be useful in selecting patients for radical surgery. Further investigation with a larger number of patients is necessary to establish the importance of CTCs.

Single-port versus needlescopic versus conventional laparoscopic cholecystectomy: a comparative study.

INTRODUCTION: Single-port laparoscopic cholecystectomy (LC) has been recently introduced to achieve clinical benefits over standard LC. However, surgical outcomes of this operation have been poorly described compared with current techniques. The purpose of this study is to evaluate the surgical outcomes of single-port LC compared with needlescopic and conventional LC. METHODS: We reviewed the surgical outcomes of consecutive patients with symptomatic gallbladder stone disease who underwent single-port LC (31 cases), needlescopic LC (26 cases) and conventional LC (32 cases) from March 2009 to January 2010. Operation time, hospital stay, conversion, complications, and postoperative pain using visual analog scale were analyzed. In addition, patients were interviewed for overall satisfaction and cosmetic results. RESULTS: BMI in the single-port group was significantly lower than in the conventional group (26.0 ± 4.0 vs 30.8 ± 7.3 kg/m(2) , P=0.0017). Operation time in the single-port group was significantly longer than in the conventional group (65.1 ± 20.1 minutes vs 52.2 ± 19.6 minutes, P=0.012). There was one conversion in the single-port group. In nine cases in the single-port group (29%), a Kirschner wire or a suture retractor helped visualization. There was one complication in the single-port group (wound infection) and one in the needlescopic group (bile leak, requiring laparoscopy). Hospital stay, visual analog scale scores, and overall satisfaction did not vary among these groups. Greater cosmetic satisfaction was shown in the single-port group compared with the conventional group (P=0.039). CONCLUSION: Single-port LC is feasible and secure, with better cosmetic results than conventional LC. Further prospective randomized studies are still required to show its superiority over current LC techniques.

Chemokine receptor CXCR3 promotes colon cancer metastasis to lymph nodes.

Chemokines and their receptors are essential for leukocyte trafficking, and also implicated in cancer metastasis to specific organs. We have recently demonstrated that CXCR3 plays a critical role in metastasis of mouse melanoma cells to lymph nodes. Here, we show that some human colon cancer cell lines express CXCR3 constitutively. We constructed cells that expressed CXCR3 cDNA ('DLD-1-CXCR3'), and compared with nonexpressing controls by rectal transplantation in nude mice. Although both cell lines disseminated to lymph nodes at similar frequencies at 2 weeks, DLD-1-CXCR3 expanded more rapidly than the control in 4 weeks. In 6 weeks, 59% of mice inoculated with DLD1-CXCR3 showed macroscopic metastasis in para-aortic lymph nodes, whereas only 14% of those with the control (P<0.05). In contrast, metastasis to the liver or lung was rare, and unaffected by CXCR3 expression. In clinical colon cancer samples, we found expression of CXCR3 in 34% cases, most of which had lymph node metastasis. Importantly, patients with CXCR3-positive cancer showed significantly poorer prognosis than those without CXCR3, or those expressing CXCR4 or CCR7. These results indicate that activation of CXCR3 with its ligands stimulates colon cancer metastasis preferentially to the draining lymph nodes with poorer prognosis.

Effects of MDR1/P-glycoprotein expression on prognosis in advanced colorectal cancer after surgery.

Resistance to chemotherapeutic agents is a major problem for successful cancer treatment. P-glycoprotein (Pgp), a product of the multidrug resistance (MDR)1 gene expressed in cancer cells, is one of the mechanism of MDR. However, there are few reports regarding the effects of Pgp on prognosis of colorectal cancer (CRC) after surgery. We examined a total of 80 patients (45 males and 35 females with an average age of 69 years) whose CRCs were classified into stage 2-4 and completely resected surgically in our institute between January 1990 and September 1999. To evaluate Pgp expression in CRC, immunohistochemical stain was performed with a monoclonal antibody. Relationships between Pgp expression and clinicopathological variables which may have affected prognosis were evaluated. Survival curves were calculated using the Kaplan-Meier method, and differences were evaluated with the log-rank test. The Cox's proportional hazards model was used in the univariate and multivariate survival analysis. Pgp expression showed a significant correlation with histological differentiation (p=0.023). However, no correlation was observed with gender, tumor location, lymph node metastasis, lymphatic invasion, venous invasion, and cancer stages. Survival rates after surgery tended (p=0.093) to be higher in Pgp (+) than Pgp (-) patients. Pgp was not a significant prognostic factor by univariate analysis and multivariate analysis adjusted for other clinicopathologic variables. Survival rates after surgery tended to be higher in Pgp (+) than Pgp (-) patients and Pgp expression was correlated with histological differentiation of CRC. Thus, a relative resistance of CRC to conventional chemotherapy may be partly caused by Pgp expressed in well or moderately differentiated CRC. However, Pgp expression was not a significant independent prognostic factor in advanced CRC after surgery.

[A case of rheumatoid arthritis associated with pernicious anemia and bronchiolitis obliterans organizing pneumonia].

A case of rheumateid arthritis (RA) with pernicious anemia (PA) and wandering multiple patchy densities in bilateral lung fields is reported. A 72-year-old woman was hospitalized in February 1994, because of cough. She had already advanced RA (Class IV, Stage IV). She showed macrocytic and hyperchromic anemia as follows ; red-cell count (RBC), 176 x 10(4)/microliters; hemoglobin (Hb),7.2 g/dl; hematocrit (Ht), 21.0% ; MCV, 119.3 fl; and MCH, 40.9 pg. Chest roentgenogram revealed multiple patchy densities in bilateral lung fields and there was no response to the administration of antibiotic agents. From these clinical pictures bronchiolitis obliterans organizing pneumonia (BOOP) was highly suspected. After steroid injection into the joint space, the abnormal lung shadows disappeared. Anemia had been recovering spontaneously, but recurred in July. The results of blood examination were as follows ; RBC, 162 x 10(4)/microliters; Hb, 6.7ng/dl; Ht, 19.1%; MCV, 117.9 fl; and MCH, 41.4 pg. Anti-intrinsic factor antibody was positive. The level of serum vitamin B12 was low, 76 pg/ml. Sternal bone marrow aspiration showed magaloblastic changes with hypersegmentation of granulocytes. PA was diagnosed and improvement was noted after the intramuscular administration of vitamin B12. Subjective symptoms based on RA did not change during the clinical course. It is suggested that the pathogenesis about the combination of RA, BOOP and PA is related to common immunological abnormalities in our patient. A case of RA with PA and BOOP has not been reported previously, thus this case is considered clinically valuable.

Non-insulin-dependent diabetes mellitus complicated with idiopathic hypoparathyroidism.

We report a case of non-insulin-dependent diabetes mellitus (NIDDM) complicated with idiopathic hypoparathyroidism. A 74-year-old male was hospitalized because of diplopia. He was revealed to have NIDDM. The levels of serum Ca and intact-PTH were 6.3 mg/dl and < 5 pg/ml, respectively. Brain computed tomography revealed abnormal calcification in the cerebral basal ganglia and the cerebellum. After recovery from hypocalcemia, the endogenous insulin secretion was normalized. It is suggested that the pathogenesis of NIDDM in this patient may have been related to an insulin secretory defect as a result of hypocalcemia in addition to the hereditary risk.

Stimulatory effects of gamma-aminohydroxybutyric acid (GABOB) on growth hormone, prolactin and cortisol release in man.

Healthy male volunteers injected subcutaneously with 200 mg L-GABOB showed no significant changes in plasma GH, prolactin and cortisol levels. On the other hand, an intrathecal injection of 300 mg D, L-GABOB to cerebrovascular patients caused significant increases in plasma GH, prolactin and cortisol levels at 60 min after injection. These results indicate that GABOB may elicit the secretion of GH, prolactin and ACTH via the central nervous system.

Concomitant increases in serum growth hormone and hypothalamic somatostatin in rats after injection of gamma-aminobutyric acid, aminooxyacetic acid, or gamma-hydroxybutyric acid.

gamma-Aminobutyric acid (GABA; 50 or 500 microgram/10 microliter) was injected into the right lateral ventricle of urethane- or pentobarbital-anesthetized male rats. The animals were decapitated 15 min after injection. Serum GH and hypothalamic somatostatin (SRIF) concentration were measured by specific RIAs. Intraventricular GABA caused a dose-related increase in GH and SRIF. In another study, aminooxyacetic acid (5 or 20 mg) was injected ip into urethane-anesthetized rats. Aminooxyacetic acid at 20 mg produced a significant increase in both serum GH and hypothalamic SRIF. Furthermore, 12.5 mg gamma-hydroxybutyric acid (GHB) injected ip into urethane- or pentobarbital-anesthetized rats elicited a significant increase in both serum GH and hypothalamic SRIF. Pretreatment with 20 mg L-dopa produced decreases in the GHB-induced serum GH increase and in hypothalamic SRIF in pentobarbital-anesthetized rats. These results show that GABA and GHB stimulated GH secretion, which was accompanied by increased hypothalamic SRIF. Thus, the GH release induced by GABA or GHB may be partly involved in inhibiting the release of hypothalamic SRIF. As the GHB-induced GH release was inhibited by L-dopa, the stimulatory effect of GHB on GH secretion might be mediated by inhibition of the dopaminergic mechanism.

Specificity of cultured anterior pituitary cells in detecting corticotropin releasing factor(s): the effect of biologically active peptides and neurotransmitter substances on ACTH release in pituitary cell cultures.

Biologically active peptides and neurotransmitter substances were added to anterior pituitary cell cultures to examine the presence of corticotropin releasing factor (CRF)-like activity. Hypothalamic extract (HE) induced significant dose-related increase of ACTH, and the lowest effective dose was 0.01 HE/ml. Other tested substances including luteinizing hormone-releasing hormone, thyrotropin releasing hormone, melanocyte stimulating hormone release inhibiting factor, somatostatin, substance P, neurotensin, beta-endorphin. leu-enkephalin, met-enkephalin, bradykinin, norepinephrine, dopamine, serotonin, acetylcholine, histamine, gamma-amino butyric acid or gamma-hydroxy butyric acid showed no CRF-like activity. Relatively high doses of lysine vasopressin, arginine vasopressin and angiotensin II increased the release of ACTH in pituitary cell cultures, but the maximal ACTH response was markedly less than with HE. These results indicate that cultured anterior pituitary cells are sensitive and fairly specific in detecting CRF(s) comparing with other detecting procedures.

[Measurement of rat serum corticosterone using radiostereoassay kit for cortisol (author's transl)].

A very simple technique for measurement of rat serum corticosterone with radiostereoassy kit using 75Se-cortisol was devised. Only 25--50 microliter serum was required for this assay. The serum sample was first diluted to 300 microliter with water and heated in a glass tube to denature the endogeneous cortisol binding protein. Then an aliquot of the sample was transferred into an assay vial containing 75Se-cortisol, cortisol binding protein and adsorbent granules. After rotated, an aliquot of the supernatant was taken for counting. High level of rat serum corticosterone was measured with satisfying accuracy by dilution with water. Serum corticosterone levels in 7 normal female Sprague-Dawley rats (7 weeks old, Ca 200g body weight) at 2.00 pm were 29.5 +/- 12.2 microgram/dl (mean +/- SD). The levels were lower and higher in rats treated with dexamethasone and with 1-18 ACTH, respectively.

Effect of glucagon on growth hormone secretion in rats.

Gentled rats injected subcutaneously with glucagon (20 microgram/100 g body weight) showed a significant decrease in plasma growth hormone (GH) at 15 min after glucagon injection. A subcutaneous injection of 50% glucose did not cause the early suppression as shown at 15 min after glucagon injection, but at 30 min after glucose injection a tendency to decrease in plasma GH was observed. In urethane anesthetized rats, a subcutaneous administration of glucagon (1 microgram or 10 microgram/100 g body weight) failed to elicit an increase in plasma GH. In vitro incubation of anterior pituitary fragments with glucagon failed to decrease the release of GH, suggesting that glucagon does not act directly on the anterior pituitary.

Transient appearance of a provocative growth hormone response to L-dopa following incomplete adenomectomy in an acromegalic patient.

A 33-year female patient with active acromegaly and hyperthyroidism was examined before and after incomplete removal of a pituitary adenoma. Before adenomectomy the mean basal plasma GH level was 786+/-189 ng/ml. After surgery this value decreased to 251+/-22 ng/ml. Before surgery L-dopa decreased the plasma GH levels, but after adenomectomy normal GH responses were transiently observed to L-dopa. At 10 months after incomplete surgery the GH response to L-dopa became abnormal again despite a lower GH concentration. These findings suggest that the abnormal GH response to L-dopa may be due to a short-loop negative feedback system which was reset by an elevated GH level.

Hypothalamic pituitary adrenal function in patients with anorexia nervosa.

Hypothalamic pituitary adrenal function was studied in 14 patients with anorexia nervosa. Although basal plasma cortisol levels in the morning were elevated in most cases, basal plasma ACTH levels were not suppressed. Oral administration of 1 mg dexamethasone 10 hr before blood sampling failed to suppress plasma ACTH and cortisol levels in most patients with anorexia nervosa. Apparent biological half-life of exogenous cortisol was prolonged in all 4 patients with anorexia nervosa tested. The cortisol response to insulin-induced hypoglycemia and exogenous ACTH appeared to be blunted in these patients. It is concluded that anorexia nervosa has dysfunctions of hypothalamic pituitary adrenal axis, especially an abnormal feedback mechanism on ACTH secretion.

Plasma immunoassayable ACTH levels during and after hydrocortisone infusion in patients with Cushing's disease.

The plasma ACTH responses to hydrocortisone infusion were compared in patients with Cushing's disease and primary adrenocortical insufficiency. In 4 patients with primary adrenocortical insufficiency, plasma ACTH levels were suppressed exponentially after administration of a relatively large dose of hydrocortisone (1.0 mg/kg/1.5 hr-3.0 mg/kg/2 hr). In patients with post-adrenalectomized Cushing's disease (4, bilateral; 1, unilateral), plasma ACTH suppression was delayed. Plasma ACTH levels, expressed as a percentage of the basal concentrations, were significantly less suppressed in patients with Cushing's disease than in patients with primary adrenocortical insufficiency 90 (p less than 0.05) and 120 (p less than 0.05) min after the beginning of infusion. When 0.5 mg/kg hydrocortisone was infused over a period of 1.5 hr, suppression was also delayed in Cushing's disease, and plasma ACTH levels were less suppressed in 4 patients with Cushing's disease than in 4 patients with primary adrenocortical insufficiency at 30 (p greater than 0.05), 45 (p greater than 0.05) 60 (p less than 0.05) min.

[In vitro assay for ACTH-releasing activity using ACTH radioimmunoassay: ACTH releasing activities by various drugs (author's transl)].

Several procedures have been reported for the assay of corticotrophine-releasing factor (CRF), each having its advantages and disadvantages. This report deals with an in vitro assay of ACTH releasing activity utilizing pituitary incubation combined with ACTH radioimmunoassay. Rat half pituitary was preincubated in 2 ml Krebs Ringer bicarbonate buffer containing 0.2% glucose and 0.25 % BSA (KRBG-BSA) for 1.5 hr (45 min X 2). The medium was replaced by 1 ml KRBG-BSA and incubated for 30 min. Then the medium was again replaced by 1 ml KRBG-BSA or KRBG-BSA containing test materials and incubated for another 30 min. The amount of ACTH assayed by radioimmunoassay in the 2nd 30 min incubation was compared with in the 1st 30 min incubation and expressed as percentage. In ACTH radioimmunoassay, anti-ACTH serum was diluted to 1 : 1,500-3,000. The 125I-alpha 1-24ACTH-antibody system was not affected by lysine-vasopressin (LVP), arginine-vasopressin (AVP), rat's pituitary LH, GH and prolactin. Human 1-39ACTH was used as ACTH standard, and the dilution curve of incubation medium was paralleled with the standard curve. Repeatability of immunoassayable ACTH within-assay was 174 +/- 5.0 pg/tube (CV = 2.9%). A log dose-relationship was observed between the amounts of stalk median eminence extracts (SME ; NIAMDD) added to the incubation medium and its ACTH releasing activities. The sensitivity of this assay method was at least 0.1 SME or 10 mU of LVP and AVP. Using this method, it found that LVP, AVP, norepinephrine (100 ng/ml200 ng/ml) and 5-hydroxytryptophane (1 mug/ml) had ACTH releasing activities but LH-RH, TRH, glucagon, dopamine, phentolamine, propranolol, haloperidol, prostaglandin E1 and indomethacin did not affect the release of ACTH.

[Hypothalamic-hypophyseal-adrenocortical dysfunction in patients with anorexia nervosa (author's transl)].

Hypothalamic-pituitary-adrenocortical function was investigated in 14 patients with anorexia nervosa. Impaired suppression of plasma cortisol by dexamethasone was revealed. In 14 patients with anorexia nervosa, circadian rhythm of plasma cortisol, insulin tolerance test, rapid ACTH test and overnight dexamethasone suppression test were examined. Levels of plasma cortisol were higher than those in control subjects throughout the day, and normal circadian rhythm of plasma cortisol was not observed. Basal levels of plasma ACTH were within normal range. tthe response of plasma cortisol to insulin-induced hypoglycemia was lower than that in control subjects, while the response of plasma cortisol in rapid Acth test was normal. In overnight suppression tests, in which one mg dexamethasone was administered orally, 11 of 14 patients showed no suppression of plasma cortisol and 3 other patients showed incomplete suppression. Elevated levels of plasma cortisol and the absence of normal circadian rhythm in patients with anorexia nervosa and malnutrition have already been reported by other investigators, and these abnormalities were ascribed to the delayed half life of plasma cortisol due to impaired cortisol metabolism. However, according to our investigation, it is difficult to explain the failure of dexamethasone to suppress cortisol only by the delayed half life of plasma cortisol, and it is supposed that some kind of abnormal hypothalamic control is also involved.

Suppression of serum growth hormone levels by glucagon in patients with active acromegaly.

One mg of glucagon was given subcutaneously to eight patients with active acromegaly. Seven out of eight patients had a rapid decrease in serum growth hormone (GH) levels at 30 min after the glucagon injection. In two out of seven patients a rebound increase in serum GH following the early GH reduction was observed. On the other hand, oral administration of 50 g glucose which caused a comparable increase in blood glucose to that after the glucagon injection elicited no early suppression in serum GH levels in the same patients. These data suggest that the inhibition of GH release induced by glucagon could not be related to the increase in blood glucose by glucagon.

[Comparison with growth hormone responses to various drugs or substances in patients with active acromegaly (author's transl)].

Growth hormone (GH) responses to L-dopa, 2-Br-alpha-ergocryptine (CB-154), thyrotropine-releasing hormone (TRH), luteinizing hormone-releasing hormone (LH-RH), glucagon and glucose were investigated in six patients with active acromegaly. The following results were obtained. 1) Subcutaneous injection of 1 mg glucagon caused a clear-cut decrease in plasma GH levels in 5 out of 6 active acromegalic patients at 30 minutes after the injection. In 2 out of 6 patients a rebound of plasma GH was observed. 2) In three out of six patients with active acromegaly, oral administration of 0.5 g L-dopa caused a significant suppression of plasma GH levels. 3) CB-154 (2.5mg) administered orally elicited a marked decrease in plasma GH levels in the same three patients who showed a significant suppressive GH reponse to L-dopa, and the inhibitory effect of CB-154 on GH secretion lasted for 6 hours. These patients who had a GH response to L-dopa or CB-154 were named "responders". 4) Intravenous administration of TRH resulted in a significant increase in plasma GH in 4 patients 3 of whom were responders and the other a non-responder. 5) Pretreatment with CB-154 did not modify the TRH-induced GH increase in all patients who had a positive response to TRH. 6) A significant increase in plasma GH was elicited by the intravenous injection of 100 mug LH-RH in 3 out of 6 patients with acromegaly. 7) When oral administration of CB-154 had been given 2 hours before LH-RH, the GH response to LH-RH was blunted in two of three patients who had a LH-RH-induced increase in plasma GH levels.