Prevention of gastroduodenal content reflux and delayed gastric emptying after esophagectomy: gastric tube reconstruction with duodenal diversion plus Roux-en-Y anastomosis.

Reflux of gastroduodenal contents and delayed gastric emptying are the most common and serious problems after esophagectomy with gastric reconstruction. However, attempts to reduce the above symptoms, surgically as well as non-surgically, had no or limited effect. To address this issue, we performed retrosternal gastric reconstruction with duodenal diversion plus Roux-en-Y anastomosis (RY) in eight patients with thoracic esophageal cancer and compared the outcomes with control patients who underwent standard reconstruction. The procedure is simple, safe, and not associated with any postoperative complications. The pancreatic amylase concentrations in the gastric juice samples on postoperative day 2 were slightly lower in the non-RY group than in the RY group (1884 ± 2152 vs. 25,790 ± 23,542IU/mL, respectively, P= 0.07). Postoperative endoscopic examination showed neither reflux esophagitis nor residual gastric content in the RY group. Quality of life assessed by the Dysfunction After Upper Gastrointestinal Surgery-32 questionnaire postoperatively was significantly better in the RY group than in the non-RY group for 'decreased physical activity,''symptoms of reflux,''nausea and vomiting,' and 'pain.' The results of this pilot study suggest that gastric reconstruction with duodenal diversion plus RY seems effective in improving both the reflux and delayed gastric emptying. The benefits of this procedure need to be further assessed in a large-scale, randomized controlled trial.

The significance of abdominal para-aortic lymph node metastasis in patients with lower thoracic esophageal cancer.

Para-aortic lymph node (PALN) recurrence is often seen in patients with lower thoracic esophageal cancer treated by esophagectomy with extended lymph node dissection. However, the clinicopathological characteristics of patients with PALN metastasis and the significance of PALN dissection are unknown. A total of 283 patients with lower thoracic esophageal cancer underwent esophagectomy with lymphadenectomy at our hospital between April 1984 and March 2007. Among these 283 patients, 60 patients were enrolled in this retrospective study according to following criteria: (i) clinical T2 to T4 tumor, (ii) no clinical PALN metastasis, and (iii) received PALN dissection. PALN dissection was indicated by a tumor depth of at least T2 and no severe complications. The clinicopathological data, recurrence pattern, and overall survival were compared between patients with PALN and without PALN metastasis. The mean length of surgery was 587 min and the mean blood loss was 1383 mL. The morbidity was 33.3% and mortality was 5% in this series. Sixteen patients (26.7%) had PALN metastasis; these showed significantly more lymph node metastases (15.8 ± 13.2 vs. 3.0 ± 3.2, P < 0.0001) and significantly worse survival rates (53.3% vs. 79.9% at 1 year, 6.7% vs. 62.0% at 3 years, P < 0.0001) than patients without PALN metastasis. The incidence of lymph node recurrence (P < 0.0001) and hematogenous recurrence (P= 0.0487) was also higher in patients with PALN metastasis than in patients without PALN metastasis. Among the 16 patients with PALN metastasis, a univariate analysis revealed total number of metastatic nodes < 8 (P= 0.0325) to be a significant prognostic factor. A multivariate logistic regression analysis of the regional lymph nodes identified the invasion of the lower mediastinal nodes (hazard ratio = 6.120) and retroperitoneal nodes (hazard ratio = 15.167) to be significantly correlated with PALN metastasis. PALN metastasis is suggested to be related to the systemic spread of lymphatic metastasis even in lower thoracic esophageal cancer. PALN dissection for pathological PALN(+) patients should not be performed. It remains to be determined in future prospective studies whether patients without pathological PALN metastasis, but showing PALN micrometastasis, could achieve improved survival with PALN dissection.

Novel prognostic prediction models for patients with stage IV colorectal cancer after concurrent curative resection.

BACKGROUND: We developed a prediction tool for recurrence and survival in patients with stage IV colorectal cancer (CRC) following surgically curative resection. PATIENTS AND METHODS: From January 1983 to December 2012, 113 patients with CRC and synchronous liver and/or lung metastatic CRC were investigated at the Osaka Medical Center for Cancer and Cardiovascular Diseases. All patients underwent curative resection of primary and metastatic lesions. In the group of patients who underwent surgery from 1983 to 2008, a Cox regression model was used to develop prediction models for 1-year, 3-year and 5-year cancer-specific survival (CSS) and relapse-free survival (RFS). In the other group of patients who underwent surgery from 2009 to 2012, the developed prediction model was validated. RESULTS: Univariate analysis of clinicopathological factors showed that the following factors were significantly correlated with CSS and RFS: preoperative serum carcinoembryonic antigen level, tumour location, pathologically defined tumour invasion and lymph node metastasis, and synchronous metastatic lesions. Using these variables, novel prediction models predicting CSS and RFS were constructed using the Cox regression model with concordance indexes of 0.802 for CSS and 0.631 for RFS. The prediction models were validated by external data sets in an independent patient group. CONCLUSIONS: We developed novel and reliable personalised prognostic models, integrating tumour, node, metastasis (TNM) factors as well as the preoperative serum carcinoembryonic antigen level, tumour location and metastatic lesions, to predict patients' prognosis following surgically curative resection. This individualised prediction model may help clinicians in the treatment of postoperative stage IV CRC following surgically curative resection.

Responses of parabrachial nucleus neurons to chemical stimulation of posterior tongue in chorda tympani-sectioned rats.

Responses of parabrachial nucleus (PBN) neurons (n = 43) to chemical stimulation of the posterior tongue were recorded in chorda tympani (CT)-sectioned rats and compared with those (n = 45) in CT-intact. The chemical stimuli used were 0.5 M sucrose, 0.5 M sodium chloride (NaCl), 0.03 M hydrochloric acid (HCl), 0.01 M quinine hydrochloride, and distilled water. These stimuli were applied to an area posterior to the intermolar eminence of the tongue. Neurons of CT-sectioned rats responsive to the chemical stimuli were located in more caudal areas of the PBN compared with those of CT-intact. Numbers of responses to the five stimuli and breadth of responsiveness to the four basics were not different between both groups of rats. However, average response magnitudes of the neurons in CT-sectioned rats were lower than those in CT-intact. In both groups of rats, the response magnitudes to NaCl and HCl were larger than those to the other three stimuli, and responses to NaCl and those to HCl were highly correlated. It is suggested that glossopharyngeal fibers responding strongly to acids and salts are likely to be the main source of PBN responses from the posterior tongue.

Response characteristics of three taste nerves in mice.

Gustatory responses from 3 nerves, the chorda tympani, glossopharyngeal and superior laryngeal nerves were investigated in the mouse. Stimuli were NH4Cl, NaCl, KCl, HCl, quinine-HCl, sucrose, urea, glucose and distilled water. The 3 nerves responded differently to these stimuli. The chorda tympani responded strongly to HCl and sucrose, but weakly to quinine-HCl, while the glossopharyngeal responded well to quinine-HCl rather than to either HCl or sucrose. The order of effective stimulation was NH4Cl greater than NaCl greater than KCl for the chorda tympani, whereas NH4Cl greater than KCl greater than NaCl for the glossopharyngeal nerve. The responses of the superior laryngeal nerve were remarkably different from those of the others. Water was the most effective stimulus for the nerve and the response to water was depressed by either electrolytes or non-electrolytes added in water. These results suggest dissimilar contributions of the 3 nerves to the physiological functions.

Facilitation of adrenal sympathetic efferent nerve activity induced by mechanical stimulation of teeth in the rat.

The effects of afferent signals from the periodontal mechanoreceptors and muscle spindles of jaw-closing muscles on adrenal nerve activity were examined using anesthetized rats. The adrenal nerve activity increased with pressure stimulation of the teeth and by biting a wooden stick. However, after denervation of the periodontal ligament, the facilitation due to the stick-biting was not observed. These results indicate that periodontal afferents facilitate adrenal nerve activity.

Hypotonic diuresis following oropharyngeal stimulation with water in humans.

The role of oropharyngeal mechanisms in body water regulation was studied in 12 human males by measuring urine output and osmolality before and after drinking a very small volume of distilled water (0.15 ml/kg b.w.t.). Hypotonic diuresis was resulted only in the subjects (n = 6) who drank only sufficient water to keep their oropharynx moist continually over a 20 min period but not in those who (n = 6) drank the same volume of water within several seconds. Sham verbal instructions on drinking induced no changes in subjects examined. These results suggest that oropharyngeal afferents alone, and neither gastric afferents nor psychosomatic effects, may account for hypotonic diuresis following water intake in man.

Responses of neurons in the parabrachial region of the rat to electrical stimulation of the superior laryngeal nerve and chemical stimulation of the larynx.

The responsiveness of the parabrachial region to electrical stimulation of the superior laryngeal nerve was first examined in anesthetized rats. Action potentials were recorded in 30 parabrachial sites by single and train electrical pulses to the superior laryngeal nerve. The average latency, from the onset of stimulation to the first action potentials, was 9.9 ms (range, 6.5-18.8 ms). The responsiveness of parabrachial neurons to chemical stimulation of the laryngeal region was next examined using anesthetized, immobilized, and artificially ventilated rats in which the chorda tympani and glossopharyngeal nerves were bilaterally sectioned. Taste stimuli were applied to the laryngeal region through a tracheal tube and rinsed with 0.15 NaCl. A total of 66 responses were recorded from 26 neurons. The most effective stimulus for these neurons was 0.03 M hydrochloric acid, followed by 0.01 M quinine hydrochloride, 0.5 M sodium chloride, 0.5 M sucrose, and distilled water. Seven responses were derived from 0.15 NaCl. These neurons were mainly located in a posterodorsolateral part of the parabrachial nucleus. These results suggest that chemical signals from the laryngeal region are transmitted to the parabrachial nucleus through the superior laryngeal nerve.

Diuresis mediated by the superior laryngeal nerve in rats.

Diuresis mediated by the superior laryngeal nerve (SLN) was investigated using pentobarbital-anesthetized rats. A marked increase in urine flow was induced by application of water to the larynx. The diuretic effect of water was conspicuous during the first 30 min after the application and lasted for more than 1 hr. In contrast, a 160 mM solution of NaCl produced only slight diuresis. After bilateral sectioning of the SLNs, water-induced diuresis was considerably reduced. The results suggest that water fibers contained in the SLN may make a major contribution to the diuresis.

Changes in water intake following pharyngolaryngeal deafferentation in the rat.

The role of afferent information arising from the pharyngolaryngeal region in the regulation of water intake was evaluated in rats. The animals received picric application to the mucosa of either the pharyngolaryngeal or the hard palate region. Water intake of the pharyngolaryngeal treated animals was reduced significantly, while no reduction in water intake was shown in the control and hard palate treated animals.

Interlaboratory validation of the in vitro eye irritation tests for cosmetic ingredients. (11) EYTEX(TM).

EYTEX(TM) is an in vitro test system for predicting the ocular irritation potential of chemicals and formulations. This method was evaluated as an alternative method to the Draize eye irritation test (Draize test) for the eye irritation potential of several cosmetic ingredients in a three-phase validation study conducted at five to seven laboratories. Thirty-nine test substances were used as coded samples. The test procedures were controlled under the same standard operating procedure (SOP) at all participating laboratories. The interlaboratory coefficient of variation (CV) was 20.8%. The correlation coefficient between EYTEX scores and the maximal average Draize total score (MAS) was 0.313. Irritancy classifications were established based on the results of 54 EYTEX tests and the EYTEX/Draize equivalent was calculated. Thirty-eight EYTEX test results concurred with the results of the Draize test, substantial equivalence was 70.4%. These results indicate that EYTEX provides a rough method of classification rather than providing absolute values. The present results also indicate that EYTEX has the following characteristics: (1) intensely coloured substance may not be compatible; (2) some cationic surfactants may be underestimated; (3) EYTEX can be applied to most test substances under the same conditions as the in vivo tests.

Physicochemical study of receptive mechanism of laryngeal water fibers in the rabbit.

The effects of various cations on the water unit activity were studied by recording unitary discharges in the superior laryngeal nerve fibers of the rabbit. Chloride salts of Li+, Na+, K+, Cs+ depressed the water response, while sulfate salts of Li+, Na+, NH4+, K+ facilitated it. Cations were less effective in stimulating action than anions. The depression of the water response in the laryngeal nerve has been thought to be caused by permeation of the stimulating anions through the receptor membrane and/or by destruction of the water structure on the membrane surface induced by adsorbed anions (SHINGAI, 1977 a). In order to differentiate these two possible actions of anions, the effects of benzenesulfonate and trichloroacetate were examined, because these anions were expected to be impermeant through the receptor membrane and to have a water structure-breaking effect. These anions showed no effect on the water response in concentrations below 320 mM. Measurements of the viscosity and the density of the electrolyte solutions showed that benzenesulfonate had a strong water structure-breaking effect. These results suggested that impermeant anions having water structure-breaking actions do not influence the excitability of the water receptor and that the depression of the water response by anions in the stimulating solution is caused by a hyperpolarization generated by permeation of the anions through the receptor membrane.

Water fibers in the superior laryngeal nerve of the rat.

Water responses elicited by application of water on the laryngeal mucosa were observed in the superior laryngeal nerve fibers in the rat. The response was augmented by K+ ions and was depressed by Na+ ions, while anions (Cl--, F--, SO42--, benzoate) showed no noticeable effect.

Ionic mechanism of water receptors in the laryngeal mucosa of the rabbit.

The effects of various ions on water response was studied by recording unitary discharges in single superior laryngeal nerve fibers of the rabbit. The water response was strongly influenced by anions. The inorganic anions used were divided into two groups. One group consisted of anions which depress the water response (depressing anions), the depressing action sequence being SCN- greater than Br- greater than than Cl- greater than I- greater than NO-3. Another one consisted of anions which facilitate the water response (facilitating anions), the facilitating action sequence being citrate greater than SO34- greater than IO-3 greater than F- greater than BrO-3 greater than acetate. Physicochemically, facilitating anions belong to "the water structure-making ions" group; on the other hand, depressing anions belong to "the water structure-breaking ions" group. SO34- weakened the depressing effect of Cl- when the concentration of Cl- was below 60 mM, and enhanced it when the concentration was above 60 mM. Na+ and Li+ had no appreciable effect on the water unit activity, but K+ had a weakly stimulating effect. It is concluded that an outflux of anions through the membrane stimulates the water receptor while an influx of anions depresses it, and SO34- facilitates Cl- permeability. The mechanism of the facilitating effect of SO24- on Cl- permeation is discussed in terms of the interaction between the water structure surrounding the ions and the receptor membrane.

Reflex swallowing elicited by water and chemical substances applied in the oral cavity, pharynx, and larynx of the rabbit.

Water and various chemical solutions were applied to the oral cavity, pharynx, and larynx of anesthetized rabbits to study their effects on the swallowing reflex. Laryngeal stimulation: Water was an effective stimulus in eliciting reflex swallowing; NaCL depressed this reflex. The effect of salt solutions on swallowing was dependent on anion species. Weakly hydrated anions had a depressing effect while greatly hydrated anions had a facilitating effect. The order of the depressing effect of the anions was Br-greater than SCN- greater than CL- congruent to NO3 -, and the order of the facilitating effect of anions was citrate greater than SO42 - greater than HCO3-. Oral and pharyngeal stimulation: Water elicited swallowing; however, this effect was less marked than that in the larynx. NaCL in concentrations lower than 200 mM had a depressing effect while at higher concentration it had a facilitating effect. Sucrose, acetic acid, and alcohol evoked successive swallowing in the first two or three trials. It was found that water applied to the laryngeal region had the marked effect of eliciting reflex swallowing and that most gustatory substances infused into the oral and pharyngeal regions had a facilitating effect on the initation of swallowing.

Sensation of thirst in normal and laryngectomized man.

The purpose of this study was to evaluate the role of the larynx in sensation of thirst and to identify precise areas responsible for the sensation in normal and laryngectomized groups. The present analysis showed that the laryngectomized group was less aware of the sensation and less able to localize it than the normal group. Both groups localized the sensation from the base of the tongue to the larynx as well as in the pharynx.

Differences in drinking behavior between normal and laryngectomized man.

The properties of drinking in normal and laryngectomized groups were examined. Drinking associated with meals was more frequent in the 76 young and 37 older normal subjects than the 25 laryngectomized persons. The laryngectomized group preferred tea and coffee to water to alleviate thirst sensation, while such a preference was hardly seen in either normal group. Results suggest that the larynx may contribute not only to thirst sensation but may be associated with preference in drinking.

[A case of multiple bone metastases from advanced breast cancer effectively treated with pamidronate].

A 57-year-old woman, with bone, lymph node and skin metastases underwent mastectomy and extirpation of skin tumors. Chemoenderine-therapy was performed from the 15th day after operation, with a toremifene and CEF regimen consisting of cyclophosphamide, epirubicin and 5-fluorouracil. She had nausea and neurological symptoms from hypercalcemia (21.5 mg/dl) on the 28th day after operation. Her serum PTHrP level was found to be high at 214 pmol/l. We administered pamidronate in a dose of 45 mg biweekly, and she improved. The CEF regimen and pamidronate therapy was continued for 6 cycles and the regions of bone metastases were reduced on the bone scintography. Thereafter she has been administered pamidronate 30 mg/4 weeks as an outpatient with no further symptoms, and serum Ca and PTHrP have remained normal. In conclusion, pamidronate combined with chemotherapy can be a therapeutic option for not only hypercalcemia but also bone metastases of breast cancer.

[Evaluation of intermittent hepatic arterial infusion chemotherapy for multiple liver metastasis of colorectal cancer].

Five patients with synchronous multiple hepatic metastasis of colorectal cancer were treated with hepatic arterial infusion chemotherapy. All cases received intermittent 5-FU infusion (5-FU 250-1,000 mg/2-3 hrs/1-2 weeks) on an outpatient basis. In the evaluation of 5 cases, 3 PR and 1 NC were observed. One case administered arterial infusion for adjuvant chemotherapy has no recurrence in liver. In two patients, extra-hepatic metastases were found. In conclusion, this therapy was effective and useful for hepatic metastasis. Moreover, other forms of treatment for extra-hepatic metastasis must be used.

[Intraperitoneal cisplatinum chemotherapy in patients with carcinomatous peritonitis due to colorectal scirrhous cancer--case report].

Two patients received intraperitoneal cisplatinum chemotherapy for carcinomatous ascites due to colorectal cancer recurrence. The patients were a 47-year-old man who had rectal cancer and 51-year-old woman who had colon cancer. They had received the operation and adjuvant chemoradiation therapy and chemotherapy respectively. However, five months and two years after resection, respectively, they presented massive ascites due to carcinomatous peritonitis and were given cisplatin injection intraperitoneally. The amount of ascites was significantly diminished. One patient had been discharged and been able to stay at home, and the other patient underwent gastrostomy for ileus. The results suggested that intraperitoneal cisplatinum chemotherapy may be useful for the patient with carcinomatous ascites due to colorectal cancer.