Han-Shiang Chen

Synchronous and “early” metachronous colorectal adenocarcinoma

PURPOSE: We evaluated the accuracy of preoperative diagnostic examinations and determined whether patients with synchronous colorectal cancers differ from patients with a single colorectal malignancy in clinicopathologic factors, the possibility of early metachronous colorectal cancer, and postoperative outcome. METHODS: A retrospective evaluation of 1,780 patients with primary colorectal adenocarcinoma from 1987 to 1993 was performed. We divided patients into three groups: Group 1, single colorectal adenocarcinoma; Group 2, synchronous colorectal adenocarcinoma; and Group 3, early metachronous colorectal adenocarcinoma. RESULTS: There were 52 cases (3 percent) in Group 2 and 13 cases (1 percent) in Group 3 (<3 years from the index colorectal cancer operation). Differences in age, gender, and cancer-free rate among the three groups did not reached statistical significance. Compared with cancers in Group 1, significantly more proximal tumor locations and early cancer stage were noted for the second and third cancers in Group 2. In Group 3 a significantly more proximal tumor site was noted for the index colorectal cancer but cancer stage showed no significant difference from cancers in Group 1. Better histologic type was also noted in the index and second cancers in Group 2 than in cancers in Group 1. There was a higher incidence of associated benign adenoma in Group 2 (35vs. 15 percent in Group 1). The positivity rate of Group 2 was significantly higher by preoperative colonoscopy (71 percent) and incidental findings at surgery (58 percent) than barium enema examination (30 percent). CONCLUSION: Preoperative barium enema examination was an unsatisfactory tool for detecting synchronous tumors. Preoperative colonoscopy demonstrated a higher positivity rate, but it still failed to detect nearly 30 percent of cases with synchronous tumors. Intraoperative palpation of the whole colorectum could detect nearly 60 percent of unexpected synchronous tumors. We believe both colonoscopy and intraoperative palpation of the whole colorectum are crucial to the early detection of synchronous colorectal cancer.

Serum levels of matrix metalloproteinase 2 in patients with breast cancer

Matrix metalloproteinases (MMPs) have been reported to be associated with invasive and metastatic behaviors of human malignant tumors. However, there is still limited knowledge about the role of matrix metalloproteinases-2 (MMP-2) in breast cancer. This study was designed with the aim to elucidate the possible relationship between the preoperative circulating MMP-2 and breast cancer. Fifty-seven consecutive patients with invasive breast cancer undergoing surgery were prospectively included and evaluated. Venous blood samples were collected before the surgery. Sera were obtained by centrifugation, and stored at -70 degrees C until assayed. The control group consisted of 12 patients with benign breast tumor (six with fibrocystic disease and six with fibroadenoma). Serum concentrations of MMP-2 were measured by the quantitative sandwich enzyme immunoassay technique. The data on primary tumor stage, age, estrogen receptor, lymph node status, and TNM staging were reviewed and recorded. The mean value of serum MMP-2 in patients with invasive breast cancer was 694.3+/-140.5 ng/ml and those of control group were 593.3+/-134.0 ng/ml and the difference was significant (P=0.026). Furthermore, there were significantly higher serum levels of MMP-2 in the patients with more advanced primary tumor staging (P=0.005), in the patients with more advanced lymph node status(P=0.011) and in the patients with more advanced TNM staging (P<0.001). In multivariate analysis, TNM staging (P<0.001) appeared as independent factor regarding the significant higher serum levels of MMP-2. Patients with more advanced TNM staging were shown to have higher serum MMP-2 levels. Thus preoperative serum MMP-2 levels might reflect the severity of invasive breast cancer and deserve further evaluation.

Circulating soluble Fas in patients with breast cancer.

It has been suggested that circulating soluble Fas (sFas) contributes to tumor progression. However, little is known about the role of sFas in breast cancer. This study was designed with the aim of elucidating the possible relation between sFas and breast cancer. A series of 57 consecutive patients with invasive breast cancer undergoing surgery were prospectively included in the study and evaluated. Venous blood samples were collected before surgery. Sera were obtained by centrifugation and stored at ?70°C until assayed. The control group consisted of 12 patients with benign breast tumors (6 with fibrocystic disease, 6 with fibroadenoma). Serum concentrations of sFas were measured by the quantitative sandwich enzyme immunoassay technique. The data on primary tumor staging, age, estrogen receptor status, lymph node status, tumor grading, and TNM staging were reviewed and recorded. The mean value of circulating sFas in patients with invasive breast cancer was 794.2 ± 183.0 pg/ml and that of the control group 582.1 ± 62.8 pg/ml; the difference was significant (p <0.001). Furthermore, there were significantly higher serum levels of sFas in the older patients (age ≥ 50) (p = 0.020) and in those with a more advanced TNM stage (p = 0.021). In the multivariate analysis, TNM stage (p = 0.005) appeared to be an independent factor for significantly higher circulating sFas in patients with invasive breast cancer. Thus circulating sFas levels may reflect the severity of invasive breast cancer. Hence the possible prognostic value of sFas for breast cancer deserves further elucidation and evaluation with long-term patient follow-up.

Total Pelvic Exenteration for Primary Local Advanced Colorectal Cancer

AbstractTotal pelvic exenteration (TPE) is an ultraradical operative procedure for locally advanced pelvic tumors with high morbidity and mortality rates. We retrospectively reviewed the results of TPE for primary locally advanced colorectal cancer in terms of mortality, morbidity, and long-term survival. Of 2952 patients with colorectal cancer, 50 underwent TPE for primary locally advanced colorectal cancer between 1986 and 1995. There was one operative death (2%). The other 49 cases were entered into a retrospective study. Thirty-two cases (65%) showed involvement of one or more adjacent organs. Thirty-one patients (97%) had urologic organs invaded by tumor. The overall 5-year survival rate was 49% and the overall morbidity was 37%. The survival rate for stage II was 62%, and that for stage III was 35%; there was no survival in stage IV. Early morbidity was noted in 24% of patients; late morbidity, in 15%. TNM stage appeared to be the only independent factor for survival (p = 0.022). Our study showed that TPE can be performed with relatively low operative mortality and acceptable morbidity. With thorough preoperative evaluation and adequate surgical dissection, satisfactory outcomes for a primary locally advanced colorectal cancer can be achieved, especially at the earlier stages.

Effect of Bile Acid Replacement on Endotoxin-induced Tumor Necrosis Factor-a Production in Obstructive Jaundice

There is a high incidence of perioperative morbidity and mortality in patients with obstructive jaundice due to sepsis. Tumor necrosis factor-a (TNF-a) is considered a crucial mediator in inducing and processing the inflammatory cascade. We hypothesize that obstructive jaundice leads to an increased endotoxin-induced TNF-a production and that intestinal bile acid replacement can prevent this phenomenon. Sprague-Dawley rats were randomized to three groups of 12 animals each. Group 1 underwent common bile duct ligation (CBDL) with oral intestinal bile acid (deoxycholic acid 5 mg/100 g body weight/3 times daily) replacement (CBDL + bile acid); group 2 underwent common bile duct ligation with the same amount of normal saline replacement orally (CBDL + saline); and group 3 underwent a sham operation (sham control). After 2 days, endotoxin was given to the animals, and after 90 minutes, tissues (liver and lung) and blood were collected for checking the TNF-a levels and biochemical analyses. Comparisons among these three groups were performed and recorded. While serum and tissue (liver and lung) TNF-a levels of group 2 (CBDL + saline) were significantly increased after endotoxin challenge, these elevations were reduced to control levels (sham control) following oral replacement of intestinal bile acid (CBDL + bile acid). Obstructive jaundice leads to an increased endotoxin-induced TNF-a production and intestinal bile acid replacement can inhibit this phenomenon.

Systemic immune response after laparoscopic and open cholecystectomy

The laparoscopic approach is thought to reduce the postoperative immunologic and metabolic effects of an open operation. This study was designed with the aim of comparing the systemic immune response after laparoscopic and open cholecystectomy. Seventeen patients with gallbladder stones were assigned to undergo either a laparoscopic (n=9) or open (n=8) approach. The postoperative immune response was assessed by measuring the serum levels of soluble Fas (sFas), soluble L-selectin (sL-selectin), and transforming growth factor-β1 (TGFβ1) preoperatively and 2 hours, 1 day, and 2 days postoperatively. Both approaches resulted in a significant decrease in sFas levels 1 and 2 days postoperatively. The open approach evoked a transient increase in sL-selectin levels 2 hours postoperatively. Moreover, the open approach resulted in a persistent, significant increase in TGFβ1 levels postoperatively. Comparison of open versus laparoscopic cholecystectomy has shown no significant difference in sFas level and a statistically significant increase of sL-selectin (within 2 hours) and TGFβ levels after open surgery. Although both laparoscopic and open cholecystectomy evoked an alteration of the systemic immune response, our data showed that such immune response may be less after the laparoscopic approach.RésuméOn pense que l’approche laparoscopique réduit les effets immunitaires et métaboliques postopératoires par rapport à la laparotomie. Cette étude a été élaborée avec l’intention de comparer la réponse immunitaire systémique après cholécystectomie laparoscopique ou par laparotomie. Dix-sept patients avec une lithiase vésiculaire ont eu soit une cholécystectomie laparoscopique (n=9) soit par laparotomie (n=8). On a mesuré, en préopératoire, à deux heures, un jour et deux jours en post-opératoire, la réponse immunitaire postopératoire par le dosage des taux sériques de Pas soluble (Pass), de la L-sélectine soluble (L-sélectine S) et du facteur de croissance facteur-β1 (TGFβ1). On a noté une diminution significative en Pass aux jours postopératoires un et deux. La laparotomie a provoqué une augmentation transitoire en L-sélectine deux heures après l’intervention. Cependant, après laparotomie, on a noté, en postopératoire, une augmentation persistante, et significative, de TGFβ1. En ce qui concerne les taux de PASS, il n’y avait aucune différence significative entre la cholécystectomie laparoscopique et par laparotomie; par contre, les taux de L-sélectine s (en moins de deux heures) et les taux de TGFβ1 étaient significativement plus élevés après chirurgie traditionnelle. Bien que la chirurgie laparoscopique et par laparotomie aient provoqué toutes deux une réponse systémique immunitaire, nos données suggèrent que cette réponse est moindre après laparoscopie.ResumenSe considera que el abordaje laparoscópico para colecistectomía reduce el impacto immunitario y metabólico en comparación con la operación abierta. El presente estudio fue diseñado con el propósito de comparar la respuesta immunitaria luego de colecistectomía laparoscópica o abierta; 17 pacientes con colelitiasis fueron asignadas a colecistectomía laparoscópica (n=9) o abierta (n=8). La respuesta inmunitaria fue determinada mediante la medición de los niveles séricos de Pas soluble (sPas), selectina-L soluble (selectina-sL) y factor transformador de crecimiento-β1 (TGFβ1) en la fase preoperatoria, a las dos horas y en el primero y en el segundo días postoperatorios. Ambos abordajes resultaron en una disminución significante de los niveles de sPas en el primero y segundo días postoperatorios. El abordaje abierto provocó un incremento transitorio de los niveles de selectina-sL a las dos horas postoperatorias. Además, resulto en un incremento persistente y significativo de los niveles postoperatorios de TGFβ1. La comparación entre el abordaje abierto y el laparoscópico ha demostrado diferencia significante en el nivel de sPas, y un incremento significante en los niveles de selectina-sL (en las primeras dos horas) y de TGFβ1 en la cirugía abierta. Aunque tanto la colecistectomía laparóscopica como la abierta indujeron una alternación en la respuesta inmune sistémica, nuestros datos señalan que tal respuesta inmunitaria podría ser menos marcada con el abordaje laparoscópico.

DNA index and S-phase fraction in curative resection of colorectal adenocarcinoma: Analysis of prognosis and current trends

The DNA index (DI) and S-phase fraction (SPF) have been said to be independent factors in colorectal adenocarcinoma and have a different distribution from the clinicohistologic parameters. This study assesses the real efficacy of DI and SPF for curative resection of colorectal adenocarcinomas with respect to the prognosis and the clinicohistologic parameters. From July 1991 to October 1994 a total of 666 patients underwent curative resection of colorectal adenocarcinoma and DNA flow cytometry in Kaohsiung Chang Gung Memorial Medical Center Hospital, Taiwan. We defined diploid tumors as having a DI of τ; 0.9 but<1.1 and a nondiploid tumor as having a DI of <0.9 or >1.1. A high SPF was defined as being more than the median value for the total SPF. Altogether, 495 cases (74.32%) had a 5-year cancer-free survival. Tumor stage, DI, tumor location, and tumor morphology were associated with significant cancer-free survival in the univariate analysis (p=0.0295,<0.001, 0.0357, and<0.001, respectively). After all factors were entered into the multivariate analysis, the independent factors for cancer-free survival were found to be stage, tumor location, and morphology (p<0.001, 0.012, and 0.044, respectively). In cases distinguished by the DI, diploid tumors had significantly more frequent right colon locations (p<0.001). After cases were separated by the SPF (median value 18.4%), better histology (well differentiated adenocarcinoma) was noted with a low SPF (p=0.017). No other clinicohistologic parameters had significant differences shown by the DI or SPF. Thus DI and SPF failed to appear as independent factors for 5-year cancer-free survival. The independent factors for curative colorectal adenocarcinoma were tumor stage, location, and morphology. Diploid tumors were located at the right colon more often, and low SPF indicated better histology in the univariate analysis.RésuméOn a dit que l’indexe d’ADN (ID) et la fraction de phase-S (FPS) étaient des facteurs prédictifs indépendants du cancer colorectal dont la distribution varie selon les différents paramètres clinicohistologiques. Cette étude a comme but d’évaluer l’efficacité réelle de l’ID et de la FPS après résection à visée curatrice du cancer colorectal en ce qui concerne le pronostic et les paramètres clinicohistologiques. Entre juillet 1991 et Oct 1994, 666 cas d’adénocarcinome colorectal opérés à visée curatrice à l’hôpital du Centre Médical Kaohsiung Chang Gung Memorial à Taiwan ont eu également une cytometric de flux pour l’ADN. Nous avons défini la tumeur dipioïde comme 0.9 ID<1.1 et une tumeur non-diploïde comme ID<0.9 ou τ; 1.1. Le taux de FPS était dit élevé lorsqu’il était supérieur à la médiane de toutes les valeurs de FPS. La survie à 5 ans sans cancer a été de 495 cas (74.32%). Le stade tumoral, l’ID, le site tumoral et la morphologie tumorale étaient tous associés à une survie sans cancer significative en analyse univariée (respectivement, p=0.0295,<0.001, 0.0357, et<0.001). Après avoir introduit tous ces facteurs en analyse multivariée, les facteurs indépendants de survie sans cancer ont été le stade, le site tumoral et la morphologie (respectivement, p<0.001, 0.012, et 0.044). Dans les cas individualisés par l’ID, les tumeurs diploïdes étaient localisées plus souvent à droite (p<0.001). Selon la séparation en groupes au-dessus et en dessous de la valeur médiane limite de HPS (valeur médiane: 18.4%), on a noté une meilleure histologie (adénocarcinome bien différencié) pour les valeurs basses de FPS (p=0.017). Aucune autre différence significative dans les paramètres clinicohistologiques n’a été mise en évidence selon les critères ID ou FPS. Ni l’ID ni le FSP n’apparat comme facteur indépendant de survie à 5 ans sans cancer. Les facteurs indépendants pour résection à visée curatrice de i’adénocarcinome colorectal étaient le stade tumoral, le site et la morphologie. Les tumeurs diploïdes sont localisées plus souvent à droite et une valeur basse de la FPS est associée à une histologie plus favorable en analyse univariée.ResumenSe ha sostenido que el Índice de ADN (DI) y la fracción de la fase S (SPF) eran factores independientes en el adenocarcinoma colorrectal con diferente distribución por lo que a los parámetros clínico-histológicos se refiere. Este estudio investiga la eficacia real del DI y SPF, tras resección curativa del adenocarcinoma colorrectal, por lo que al pronóstico y parámetros clínico-histológicos atañe. En el hospital Kaohsiung Chang Gung Memorial Center de Taiwan, desde julio de 1991 a octubre de 1994 se efectuaron 666 resecciones curativas por adenocarcinomas colorrectales, realizándose retrospectivamente una citometría de flujo ADN. Se consideró que un tumor era diploide cuando 0.9< DI >1.1 y no-diploide cuando el DI<0.9 o DI τ; 1.1. Se consideró que la SPF estaba alta cuando la fracción SPF era mayor al valor medio de la SPF total. 495 casos (74.32%) sobrevivieron 5 años libres de enfermedad neoplásica. El estadio tumoral, el Índice de ADN (DI), la localización y morfología de la neoplasia se correlacionaron significativamente, en un análisis univariante, con la supervivencia libre de enfermedad neoplásica (p=0.0295, <0.001, 0.0357, y<0.001 respectivamente). Si todos estos parámetros se estudian mediante análisis multivariante constataremos que los factores independientes para la supervivencia libre de cáncer son: el estadio, la localización y la morfología del cáncer (p<0.001, 0.012, y 0.044). Si se diferencian los casos por el DI se constata, que los tumores diploides asientan preferentemente en el colon derecho (p<0.001). Si se estudian los casos en relación con la SPF (valor medio: 18.3%) registraremos que SPF bajos se observan en adenocarcinomas bien diferenciados (p=0.017). El estudio del DI y SPF no permite ninguna otra diferenciación clínico-histopatológica significativa. El DI y la SPF parecen no tener valor alguno como factores independientes para la supervivencia a los 5 años libres de enfermedad neoplásica. Los factores independientes por lo que a la resección curativa de los adenocarcinomas colorrectales se refiere son: el estadio, la localización y la morfología tumoral. Los tumores diploides se localizan preferentemente en colon derecho y una SPF baja indica un mejor pronóstico histológico en análisis univariantes.

Obstructive Jaundice Alters LFA-1α Expression in Rat Small Intestine

Translocation of bacteria and endotoxtin has long been documented in obstructive jaundice, and altered intestinal barrier function is considered to be one of the important mechanisms for this phenomenon. The regulation of gastrointestinal mucosal response to injury is thus of important clinical as well as biological relevance. Integrins play a critical role in enterocyte migration, which is essential to mucosal healing. This study is designed to evaluate the integrins status in obstructive jaundice. Male Sprague-Dawley rats (N = 37) were randomized to three groups. Group 1 (N = 12) underwent common bile duct ligation (CBDL), group 2 (N = 12) underwent common bile duct ligation with oral glutamine administration (CBDL + G), and group 3 (N = 13) underwent a sham operation (sham control). After seven days, segments of proximal jejunum and distal ileum were harvested, and cell surface immunohistochemical expression of LFA-1α and VLA-6 were evaluated and recorded. The staining intensities were graded on a scale of 0–4. Comparisons among the three groups were performed. There was no significant difference in VLA-6 staining on small intestine among the three groups (P < 0.05). There was also no significant difference in LFA-1α staining the on jejunum between grouP1 (CBDL) and grouP3 (sham control) (P < 0.05). However, the LFA-1α staining on the ileum in grouP1 (CBDL) significantly decreased when compared with grouP3 (sham control) (P = 0.008). With oral glutamine administration (0.2 g/kg body weight, once daily), LFA-1α staining on the ileum was significantly restored in grouP2 (CBDL + G). In conclusion, obstructive jaundice for one week down-regulates LFA-1α expression on rat ileum. With oral glutamine administration, such down-regulation of LFA-1α expression on rat ileum can be restored. Such a phenomenon is intriguing and deserves further evaluation and elucidation.

Aspiration in transtracheal oxygen insufflation with different insufflation flow rates during cardiopulmonary resuscitation in dogs.

We investigated whether transtracheal insufflation of oxygen with different insufflation flow rates protects against aspiration of gastric contents during cardiopulmonary resuscitation (CPR). Its ventilation and oxygenation effects were also evaluated. Cardiac arrest was induced in anesthetized and paralyzed 18 mongrel dogs. Chest compression using an automatic thumper was performed while the dogs randomly received no mechanical ventilation (Group I, n = 6) or were transtracheally insufflated with 4 L/min oxygen (Group II, n = 6) or 10 L/min oxygen (Group III, n = 6). Blood samples were drawn every 5 min for 20 min for blood gas analysis. the mouths of the dogs were then filled with 70 mL mixed barium, and 10 min after chest compression, chest radiographs were taken to evaluate the incidence of pulmonary aspiration. Results showed that pulmonary aspiration occurred in all dogs of Group I and three of the six dogs in Group II, whereas dogs in Group III were free from pulmonary aspiration. Both transtracheal oxygen insufflation groups maintained oxygen saturation significantly better than Group I, but mild hypercapnia was observed in all groups after 20 min of CPR. We conclude that transtracheal oxygen insufflation, but not chest compression alone, was able to maintain oxygenation for 20 min during CPR in dogs with cardiac arrest. Mild hypercapnia was noted in all groups. Chest compression alone caused pulmonary aspiration, whereas insufflation of 10 L O2/min provided better protection against pulmonary aspiration than that of 4 L O2/min. Implications In case of difficult airway during cardiopulmonary resuscitation, insertion of an IV catheter through the trachea is easy, and insufflation of 10 L/min of oxygen through the needle can not only maintain the oxygenation but also prevent aspiration.