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.

Answering to the domesticability of exotic options and strategies in managing Africa's urban landscapes for sustainability beyond 2015.

This study aims at critically assessing the land management strategies that can be instrumental in bringing sound governance to urban landscapes in Africa with the view of mapping the potential, minimum conditions for success and constraints to doing so. This study is qualitative by approach and case study based by design, assesses practices in land management from a few cities (Nairobi, Abuja, Harare, Kigali, Johannesburg and Addis Ababa). Peculiarities and differences in the practices of land management in these cities is the basis for their purposeful selection. The evaluation of the land management practices in these cities is in terms of the current realities and the possibility for the acceptability of new, exotic but deemed sustainable urban land management styles. Noted strongly in this current discourse is that Africa is a region with varied of contexts requiring a critical assessment of issues before policy strategies are implemented in terms of land tenure, land administration corruption, political will and receptivity of the so-called foreign philosophies in urban land governance. The study recommends relevant training of the land and planning experts in Africa. In addition, there is general need to balance between 'place prosperity' with 'people prosperity' as they relate to land management noting that space and capital make the difference in sustainable human habitats' creation and management.

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.

[A patient with esophageal cancer with subcutaneal abscess and esophago-tracheal fistula who survived more than 2 years following treatment by drainage and chemoradiation therapy].

A 48-year-old man presented at the hospital because of neck swelling and pain. A diagnosis of esophageal cancer with subcutaneous abscess was made based on examination and biopsy results. The cancer was Ce T4NxMx Stage III-IVa. Curative surgery was considered impossible, so chemoradiation therapy was performed (5-FU 500 mg + CDDP 5 mg/day + 2 Gy/day x 31 days) after drainage. During the therapy, an esophago-tracheal fistula was observed, but it later vanished. After chemoradiation therapy, the abscess and tumor vanished. No serious adverse reactions were observed. Now, 2 years after therapy, no recurrence has been found. The patient is now in good health with no symptoms and undergoes regular check-ups. Chemoradiation therapy is effective for inoperable advanced esophageal cancer.

[Diagnosis of the postoperative local recurrence of rectal cancer by FDG-PET--a case report].

Positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) as the tracer of glucose metabolism was performed to identify a postoperative recurrent lesion of rectal cancer. A 66-year-old-man underwent trans-sacral local resection of the rectum for rectal cancer in 1992. A local recurrent mass was discovered, and abdomino-perineal resection of the rectum was performed in 1999. The serum CEA level increased gradually August in 2000, but there was no sign of recurrence on CT or MRI. FDG-PET was performed to reveal a presacral recurrent lesion. Total pelvic evisceration combined with resection of the sacrum, and a bilateral ureterostomy were performed in April 2001. The beneficial role of FDG-PET in the diagnosis of the postoperative local recurrence of rectal cancer is emphasized.

[A case of recurring breast cancer causing pericardial metastasis showing a good response following local treatment with methotrexate].

A 52-year-old woman was admitted with a chief complaint of dyspnea. She had undergone right mastectomy for Stage IIB breast cancer 2 years and five months earlier. Chest roentgenogram revealed cardiomegaly and bilateral pleural effusion, and a cardiac echogram showed marked retention of pericardial effusion. A diagnosis of cardiac tamponade was made and pericardiocentesis for continuous drainage was carried out cytologically, the effusion was class V and showed evidence of pericardial metastasis of breast cancer. Pericardiocentesis followed by methotrexate instillation 6 times in a dose of 110 mg successfully controlled the cardiac tamponade, after which the catheter could be removed from the pericardial space. Systemic chemotherapy (CEF) was started at the same time. The patient was discharged very much improved after these treatments, but she died of brain metastasis after 9 months. This case suggests that intrapericardial application of methotrexate may be very useful in the management of carcinomatous cardiac tamponade without any serious side effects.

[A case of locally advanced breast cancer successfully resected after selective intra-arterial chemotherapy].

A 25-year-old female with a large tumor on her left breast was examined at our hospital from August, 1999. Ipsilateral supraclavicular, infraclavicular and axillary lymph nodes were swollen. She was diagnosed as having locally advanced breast cancer of stage IIIb by fine needle aspiration cytology. After the administration of docetaxel (60 mg/m2/3 weeks x 3) failed to improve her condition, we changed the treatment to selective intra-arterial chemotherapy with THP-ADR (60 mg/body/day, day 1 & 8, 41 & 48) by Seldinger's method. The target vessels were the internal thoracic, lateral thoracic, thoracodorsal and deep cervical arteries. We also combined 5-FU 500 mg/body div and CPA 500 mg/body i.v. on the same days with intra-arterial chemotherapy. As a result, the main tumor and metastatic lymph node swelling was remarkably reduced (down-staging was obtained). No recurrence was found for 5 months after curative resection.

[Repetitive chemo-embolization with degradable starch microspheres (DSM) to each left and replaced right hepatic artery in a patient with multiple liver metastases of colon cancer].

In a patient with a right hepatic artery arising from the superior mesenteric artery bearing multiple liver metastases from colon cancer, hepatic arterial chemo-embolization was performed in combination with degradable starch microspheres (DSM) administered independently to the left and replaced right hepatic artery via a percutaneal approach. As the first line chemotherapy from hepatic artery with DSM 300 mg, 5-FU 500 mg and MMC 10 mg resulted in PD. DSM 300 mg, epirubicin (EPI) 50 mg, MMC 4 mg was administered with the RHA:LHA ratio of 3:1 as a second line. Four weeks later it was evaluated as NC by angiography and by tumor-marker dropped extremely. The same regimen was repeated every four weeks, and the NC status remained for 20 weeks in total. Each time, the left and replaced right hepatic artery got perfect re-perfusion and DSM enabled an effective whole liver distribution of anti-cancer drugs and repetitive administrations of them. This regimen could be an alternative choice for patients with a replaced right hepatic artery who have liver metastasis of colon cancer.

[A case of locally advanced rectal carcinoma with liver metastasis treated with a combination of CRT, HAI, and systemic chemotherapy].

A 55-year-old man with locally advanced rectal carcinoma and liver metastasis was treated with a combination of chemo-radiotherapy (5-FU suppository 100 mg/day and 63 Gy of RT), hepatic arterial infusion chemotherapy (5-FU 1,000 mg/3 h, biweekly), and systemic chemotherapy (5'-DFUR 800 mg/day + cimetidine 800 mg/day). His rectal tumor was reduced and his symptoms such as pain and bleeding had markedly decreased. The river metastasis did not change during the entire course. HAI and administration of 5-FU suppository, 5'-DFUR, and cimetidine were continued. As of 18 months after the onset of the combination therapy, NC has been maintained, and the general condition of the patient is favorable.

[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.

[Palliative chemo-radiotherapy for abdominal recurrence of esophageal carcinoma--case report].

A 71-year-old man with stage IV esophageal carcinoma was treated by chemo-radiotherapy (5-FU 500 mg/day + CDDP 10 mg/day for 4 weeks and 67.6 Gy of RT). The esophageal tumor showed a complete response to the treatment. Six months later, he had obstructive jaundice due to an abdominal recurrent mass. A secondary (palliative) CRT was performed (5-FU 500 mg/day + CDDP 10 mg/day for 3 weeks and 45 Gy of RT). The abdominal tumor became remarkably smaller and jaundice disappeared. Though the patient died from pulmonary carcinomatous lymphangitis, the primary lesion showed CR. CRT was very effective for local treatment and for palliative therapy.

[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.

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.

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.

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.

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.

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.

Swallowing reflex elicited by water and taste solutions in humans.

We investigated whether water and taste solutions are adequate stimuli for elicitation of the swallowing reflex from the pharyngolaryngeal region in humans. Subjects were five healthy males. Small amounts of water and taste solutions were applied to the posterior tongue of the subject as he reclined on a dental chair. The latency between the onset of application of the stimuli and the occurrence of swallowing was measured. Water was a most effective stimulus for elicitation of the swallowing reflex. The stimulatory effect was altered by anions, particularly Cl-, added to the water. Gustatory factors affected the latency of swallowing. The results suggest that humans have water-sensitive receptors in the pharyngolaryngeal region and that these receptors are responsible for initiation of the swallowing reflex by water.