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1.
Br J Surg ; 107(11): 1429-1439, 2020 10.
Article in English | MEDLINE | ID: mdl-32492186

ABSTRACT

BACKGROUND: Sentinel node navigation surgery reduces the extent of gastric and lymph node dissection, and may improve quality of life. The benefit and harm of laparoscopic sentinel node navigation surgery (LSNNS) for early gastric cancer is unknown. The SENORITA (SEntinel Node ORIented Tailored Approach) trial investigated the pathological and surgical outcomes of LSNNS compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection. METHODS: The SENORITA trial was an investigator-initiated, open-label, parallel-assigned, non-inferiority, multicentre RCT conducted in Korea. The primary endpoint was 3-year disease-free survival. The secondary endpoints, morbidity and mortality within 30 days of surgery, are reported in the present study. RESULTS: A total of 580 patients were randomized to LSG (292) or LSNNS (288). Surgery was undertaken in 527 patients (LSG 269, LSNNS 258). LSNNS could be performed according to the protocol in 245 of 258 patients, and a sentinel node basin was detected in 237 (96·7 per cent) Stomach-preserving surgery was carried out in 210 of 258 patients (81·4 per cent). Postoperative complications occurred in 51 patients in the LSG group (19·0 per cent) and 40 (15·5 per cent) in the LSNNS group (P = 0·294). Complications with a Clavien-Dindo grade of III or higher occurred in 16 (5·9 per cent) and 13 (5·0 per cent) patients in the LSG and LSNNS groups respectively (P = 0·647). CONCLUSION: The rate and severity of complications following LSNNS for early gastric cancer are comparable to those after LSG with lymph node dissection. Registration number: NCT01804998 ( http://www.clinicaltrials.gov).


ANTECEDENTES: La cirugía de navegación del ganglio centinela (sentinel node navigation surgery, SNNS) reduce la extensión de la resección gástrica y ganglionar, y puede mejorar la calidad de vida. Se desconoce el beneficio y el daño de la cirugía de navegación del ganglio centinela por vía laparoscópica (laparoscopic sentinel node navigation surgery, LSNNS) para el cáncer gástrico precoz. El ensayo clínico SENORITA investigó los resultados patológicos y quirúrgicos de LSNNS en comparación con la gastrectomía laparoscópica estándar (laparoscopic gastrectomy, LSG) con disección ganglionar (lymph node dissection, LND). MÉTODOS: El ensayo SENORITA fue un ensayo multicéntrico aleatorizado y controlado, iniciado por investigadores, abierto, con asignación a grupos paralelos y de no inferioridad llevado a cabo en Corea. El resultado primario fue la supervivencia libre de enfermedad a los 3 años. En el presente estudio, se describen los resultados secundarios correspondientes a morbilidad y mortalidad a los 30 días del postoperatorio. RESULTADOS: Un total de 580 pacientes fueron aleatorizados a LG (n = 292) o LSNNS (n = 288). La cirugía se realizó en 527 pacientes (LG 269, LSNNS 258). LSNNS pudo ser realizada de acuerdo con el protocolo en 245 de 258 pacientes y en 237 de 245 pacientes (96,7%) se detectó un ganglio centinela. La cirugía con preservación del estómago se realizó en 210 de 258 pacientes (81,4%). Las complicaciones postoperatorias se presentaron en 51 pacientes del grupo LSG (19,0%) y en 40 pacientes (15,5%) del grupo LSNNS (P = 0,294). Las complicaciones grado III o mayor de Clavien-Dindo se detectaron en 16 (5,9%) y 13 pacientes (5,0%) de los grupos LSG y LSNNS, respectivamente (P = 0,647). CONCLUSIÓN: El porcentaje y la gravedad de las complicaciones tras LSNNS para cancer gástrico precoz son comparables a la LSG con LND.


Subject(s)
Adenocarcinoma/surgery , Gastrectomy/methods , Laparoscopy/methods , Lymph Node Excision/methods , Sentinel Lymph Node/surgery , Stomach Neoplasms/surgery , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Follow-Up Studies , Humans , Intention to Treat Analysis , Male , Middle Aged , Neoplasm Staging , Postoperative Complications/epidemiology , Sentinel Lymph Node/pathology , Stomach Neoplasms/pathology , Treatment Outcome
3.
Insect Mol Biol ; 19(5): 599-615, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20561088

ABSTRACT

The human body louse, Pediculus humanus humanus, has one of the smallest insect genomes, containing ∼10 775 annotated genes. Annotation of detoxification [cytochrome P450 monooxygenase (P450), glutathione-S-transferase (GST), esterase (Est) and ATP-binding cassette transporter (ABC transporter)] genes revealed that they are dramatically reduced in P. h. humanus compared to other insects except for Apis mellifera. There are 37 P450, 13 GST and 17 Est genes present in P. h. humanus, approximately half the number found in Drosophila melanogaster and Anopheles gambiae. The number of putatively functional ABC transporter genes in P. h. humanus and Ap. mellifera are the same (36) but both have fewer than An. gambiae (44) or Dr. melanogaster (65). The reduction of detoxification genes in P. h. humanus may be a result of this louse's simple life history, in which it does not encounter a wide variety of xenobiotics. Neuronal component genes are highly conserved across different insect species as expected because of their critical function. Although reduced in number, P. h. humanus still retains at least a minimum repertoire of genes known to confer metabolic or toxicokinetic resistance to xenobiotics (eg Cyp3 clade P450s, Delta GSTs, B clade Ests and B/C subfamily ABC transporters), suggestive of its high potential for resistance development.


Subject(s)
Genes, Insect , Models, Animal , Pediculus/genetics , Pediculus/metabolism , Xenobiotics/metabolism , ATP-Binding Cassette Transporters/metabolism , Amino Acid Sequence , Animals , Cytochrome P-450 Enzyme System/genetics , Esterases/chemistry , Esterases/genetics , Genes, Mitochondrial , Glutathione Transferase/genetics , Inactivation, Metabolic , Insecta/genetics , Insecticide Resistance , Molecular Sequence Data , Multigene Family , Pediculus/enzymology , Phylogeny , Receptors, Nicotinic/metabolism , Sequence Alignment , Sodium Channels/metabolism
4.
Hernia ; 14(5): 523-5, 2010 Oct.
Article in English | MEDLINE | ID: mdl-19894020

ABSTRACT

A 47-year-old female complained of abdominal pain in the epigastrium for about 2 h after a meal. At the initial abdominal radiograph, there were no findings of remarkable bowel loops. On the following day of hospitalization, the pain became worse; moreover, it could not be controlled by medicine. Also, a dilated bowel loop was detected on the imaging studies. When exploring the peritoneal cavity, we found a strangulated small bowel that protruded through the lesser omental sac within the defects of the gastrocolic or gastrohepatic ligaments. After performing manual reduction, the restoring viability of herniated small bowel failed; consequently, extensive small bowel resection was mandatory. Herein we reported a case of extensive small bowel hemorrhagic infarction due to a double omental hernia that was not diagnosed at the time of visiting the emergency department.


Subject(s)
Diagnostic Errors , Hernia/diagnosis , Infarction/diagnosis , Intestine, Small/blood supply , Laparotomy/methods , Omentum , Peritoneal Diseases/diagnosis , Diagnosis, Differential , Female , Follow-Up Studies , Hernia/complications , Herniorrhaphy , Humans , Infarction/etiology , Infarction/surgery , Middle Aged , Peritoneal Diseases/complications , Peritoneal Diseases/surgery , Radiography, Abdominal , Tomography, X-Ray Computed
5.
Ann Oncol ; 19(3): 520-6, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18029971

ABSTRACT

BACKGROUND: This phase III trial was to compare 5-fluorouracil (5-FU), adriamycin, and polyadenylic-polyuridylic acid (poly A:U) against 5-fluorouracil plus adriamycin (FA) for operable gastric cancer. PATIENTS AND METHODS: From 1984 to 1989, patients who had D(2-3) curative resection were randomly assigned to receive chemotherapy or chemoimmunotherapy. Chemotherapy consisted of 12 mg/kg 5-FU every week for 18 months and 40 mg/m2 adriamycin every 3 weeks for 12 cycles. Chemoimmunotherapy consisted of FA plus 100 mg of poly A:U weekly for six cycles and was followed 6 months later by six weekly 50-mg booster injections. RESULTS: A total of 292 patients were enrolled. After excluding 12 ineligible patients, 142 and 138 patients were allocated to each treatment. Patients were balanced with prognostic variables: age, sex, tumor location, differentiation, degree of tumor invasion (T2-T4a), and lymph node status (N0-N2). During the 15-year follow-up, chemoimmunotherapy significantly prolonged overall (P = 0.013) and recurrence-free (P = 0.005) survivals compared with chemotherapy alone. The survival benefits were prominent in the subset of patients with T3/T4a, N2, or stage III. Treatments were generally well tolerated in both arms. CONCLUSIONS: These results indicate a survival advantage of chemoimmunotherapy with a regimen of FA and poly A:U in curatively resected gastric adenocarcinoma.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/surgery , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Adenocarcinoma/mortality , Adenocarcinoma/secondary , Adjuvants, Immunologic/administration & dosage , Adult , Aged , Chemotherapy, Adjuvant , Colorectal Neoplasms/secondary , Disease-Free Survival , Doxorubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Immunotherapy , Male , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local/epidemiology , Neoplasms, Second Primary/epidemiology , Poly A-U/administration & dosage , Prognosis , Stomach Neoplasms/mortality , Survival Rate
6.
Poult Sci ; 86(9): 2034-41, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17704395

ABSTRACT

The effect of irradiation or organic acid treatment of raw chicken breast and thigh meat to control inoculated microorganisms and the production of biogenic amines (BA) was studied. Bacillus cereus, Enterobacter cloacae, and Alcaligenes faecalis were selected and inoculated into raw ground chicken breast and thigh meat at approximately 10(7) cfu/g. The samples were irradiated at 0, 0.5, 1, and 2 kGy or mixed with a 0.2 M solution of acetic, citric, or lactic acid (1 mL for 10 g of meat sample) for 24 h at 4 degrees C. Viable cell counts and BA contents were determined. Irradiation was effective in reducing the inoculated bacteria: 0.5 kGy achieved approximately a 2-log reduction, and no viable cells were detected at a dose of 2 kGy. In contrast, only up to a 1-log reduction was achieved by organic acid treatment except for citric acid, which achieved approximately a 3-log reduction of E. cloacae. Both the irradiation and organic acid treatment of raw chicken breast and thigh reduced the BA content, but the rate of BA reduction differed by inoculated organism and treatment (irradiation or organic acid). Although irradiation was an excellent method for controlling inoculated microorganisms, the content of BA produced was similar to that of the organic acid treatment of raw chicken breast and thigh meat.


Subject(s)
Bacteria/drug effects , Bacteria/radiation effects , Biogenic Amines/analysis , Food Irradiation , Food Microbiology/standards , Meat/microbiology , Meat/radiation effects , Acetic Acid/pharmacology , Animals , Chickens , Citric Acid/pharmacology , Colony Count, Microbial , Dose-Response Relationship, Radiation , Food Irradiation/methods , Food Preservation/methods , Lactic Acid/pharmacology , Meat/analysis
7.
Meat Sci ; 64(4): 383-90, 2003 Aug.
Article in English | MEDLINE | ID: mdl-22063118

ABSTRACT

Various blends of spent hen meat and grains (potato starch, corn starch, and rice flour) were popped using a popping machine. Lowest bulk density was observed in the snack with 1:2 ratio of meat and potato starch. Except for the popped snack with meat and rice flour, as the starch content increased, bulk density decreased gradually. Popped snacks with grains only were higher in L* value than those with meat and grains. The a* and b* values increased with increasing meat content. All popped snacks were significantly different (P<0.001) in bulk density, color, and breaking force. As the grain content of snacks increased, the size of the air cells also increased. Results of scanning electron microscopic and optical microscopic observations revealed the popping degree of snack with starch and spent hen meat was affected by the presence of meat. The optimum ratios of meat to grain for high expansion ratio were determined to be 1:2 and 1:3 of meat to corn starch and potato starch.

8.
Int J Colorectal Dis ; 16(4): 234-7, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11515683

ABSTRACT

We evaluated the functional and oncological outcome of ultralow anterior resection and coloanal anastomosis (CAA), which is a popular technique for preserving anal sphincter in patients with distal rectal cancer. Forty-eight patients were followed up for 6-100 months regarding fecal or gas incontinence, frequency of bowel movement, and local or systemic recurrence. The main operative techniques were total mesorectal excision with autonomic nerve preservation; the type of anastomosis was straight CAA, performed by the perianal hand sewn method in 38 cases and by the double-stapled method in 10. Postoperative complications included transient urinary retention (n=7), anastomotic stenosis (n=3), anastomotic leakage (n=3), rectovaginal fistula (n=2), and cancer positive margin (n=1; patient refused reoperation). Overall there were recurrences in seven patients (14.5%): one local and one systemic recurrence in stage B2; and one local, two systemic, and two combined local and systemic in C2. The mean frequency of bowel movements was 6.1 per day after 3 months, 4.4 after 1 year, and 3.1 after 2 years. The Kirwan grade for fecal incontinence was 2.7 after 3 months, 1.8 after 1 year, and 1.5 after 2 years. With careful selection of patients and good operative technique, CAA can be performed safely in distal rectal cancer. Normal continence and acceptable frequency of bowel movements can be obtained within 1 year after operation without compromising the rate of local recurrence.


Subject(s)
Anal Canal/surgery , Colon/surgery , Rectal Neoplasms/surgery , Adult , Aged , Anastomosis, Surgical/methods , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Postoperative Complications , Treatment Outcome
9.
Cancer ; 91(11): 2016-25, 2001 Jun 01.
Article in English | MEDLINE | ID: mdl-11391580

ABSTRACT

BACKGROUND: The authors evaluated the efficacy of adjuvant chemotherapy with 5-fluorouracil (5-FU) plus doxorubicin in gastric carcinoma after D2-3 curative resection. They also evaluated the effect of dose-related factors (delivered total dose/m(2), actual dose intensity [ADI], relative dose intensity [RDI]) of this regimen on patient survival. METHODS: A total of 301 patients with Stage II to IV (en bloc resected T4b; 1984 American Joint Committee on Cancer staging) were accrued between 1984 and 1996. Chemotherapy was started within 4 weeks of surgery according to the following schedule: intravenous bolus injection of doxorubicin 40 mg/m2 every 3 weeks for 12 cycles and 5-FU 400 mg/m2 weekly for 60 weeks. The toxicity and survival were evaluated. RESULTS: The median follow-up duration was 58 months. Sixty-four percent of the total patients and 71.7% of the patients who did not experience recurrence during the chemotherapy finished the protocol completely with acceptable toxicities. The 5- and 10-year disease free survival rates of total 301 patients were 58.4% and 46.5%, and the overall survival rates were 62.1% and 50.5%, respectively. Treatment completion group showed survival benefit over the early termination group in 5-year survival (75.2% vs. 52.9%; P = 0.0005). The median ADI of 5-FU and doxorubicin were 349 and 11 mg/m2/week, and the median RDIs of 5-FU and doxorubicin were 0.87 and 0.83, respectively. Multivariate analysis demonstrated that completion of chemotherapy is an independent prognostic factor of both disease free and overall survival. However, ADI and RDI did now show any effect on survival. CONCLUSIONS: Adjuvant chemotherapy with 5-FU plus doxorubicin for 60 weeks after D2-3 dissection induced promising survival duration with acceptable toxicities. Full administration of the planned dosage of the combined drugs is recommendable as opposed to early termination of the chemotherapy in gastric carcinoma.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/drug therapy , Adenocarcinoma/surgery , Adult , Aged , Chemotherapy, Adjuvant , Doxorubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Infusions, Intravenous , Injections, Intravenous , Male , Middle Aged , Stomach Neoplasms/surgery , Survival Analysis , Treatment Outcome
10.
Ann Surg Oncol ; 8(5): 402-6, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11407513

ABSTRACT

BACKGROUND: In the treatment of gastric cancer, splenectomy is performed for effective lymph node dissection around the splenic artery and splenic hilum. The purpose of this study was to clarify the long-term outcome of splenectomy in the treatment of gastric cancer. METHODS: The effect of splenectomy on recurrence and prognosis was examined in a retrospective analysis of 665 patients who had undergone curative total gastrectomy for gastric carcinoma from 1987 to 1996. The risk factors associated with recurrence and prognosis were investigated by univariate and multivariate analysis. RESULTS: The splenectomy group showed more advanced lesions and a higher recurrence rate than the spleen-preserved group. However, after adjusting for the TNM (tumor, node, metastasis) stage, there was no significant difference in recurrence rate and pattern between the two groups. Logistic regression analysis revealed that gross type, serosal invasion, and nodal metastasis were independent risk factors for recurrence while splenectomy was not. When comparing patients with the same TNM (tumor, node, metastasis) stages, no significant difference in the 5-year survival rates was apparent. Multivariate analysis demonstrated that age, serosal invasion, and nodal metastasis were independent prognostic factors whereas splenectomy was not. CONCLUSIONS: These data suggest that splenectomy for lymph node dissection in gastric cancer is not effective regarding long-term patient prognosis.


Subject(s)
Adenocarcinoma/surgery , Lymph Node Excision , Splenectomy , Stomach Neoplasms/surgery , Adenocarcinoma/pathology , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Risk Factors , Stomach Neoplasms/pathology , Survival Rate , Time Factors , Treatment Outcome
11.
Ann Surg Oncol ; 8(5): 418-24, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11407516

ABSTRACT

BACKGROUND: Concurrent chemoradiotherapy (CCRT) for locally advanced rectal cancer is an important modality for curative resection, but tumors show wide spectrum response. The purpose of this study was to investigate any correlation among related genetic mutations, proliferative index, and tumor response after CCRT. METHODS: This study included 23 patients with rectal cancer, who were preoperatively staged as at least T3 N1 or T4 (determined by transrectal ultrasonography and MRI). Enrolled patients were given 5-FU 450 mg/m2/day and leucovorin 20 mg/m2/day intravenously for 5 days during weeks 1 and 5 of radiotherapy (45-54 Gy). Surgical resection was performed 4 weeks after completion of the scheduled treatment. Tumor response was classified as CR (complete response), PR (partial response: 50% diminution of tumor volume and downstaging), and NR (no response). Paraffin-embedded tissue obtained before chemoradiotherapy was studied by immunohistochemical staining for p53, BCL-2, and Ki-67. The extent of tumor response was correlated with proliferative activity and was measured by immunostaining Ki-67 proliferative antigen and the expression of p53 and BCL-2 oncoproteins. RESULTS: All patients were resectable. CR was obtained in 4 patients, PR in 10 patients, and NR in 9 patients. The p53 mutation was noted in 16 patients: NR in 5 patients, PR in 9 patients, and CR in 2 patients (P = .638). BCL-2 expression was noted in 11 patients: NR in 4 patients, PR in 3 patients, and CR in 4 patients (P = .799). The Ki-67 labeling index was NR: 615.4+/-47.2; PR: 663.2+/-20.4; and CR: 765.5+/-58.3 (CR + PR vs. NR, P = .029). CONCLUSIONS: Immunohistochemical expression of p53 and BCL-2 does not correlate with tumor response after CCRT, but Ki-67 labeling may be a useful parameter for radiosensitive tumors selected for CCRT.


Subject(s)
Adenocarcinoma/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ki-67 Antigen/analysis , Proto-Oncogene Proteins c-bcl-2/analysis , Tumor Suppressor Protein p53/analysis , Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Humans , Immunohistochemistry , Prognosis
12.
Int J Radiat Oncol Biol Phys ; 50(2): 435-9, 2001 Jun 01.
Article in English | MEDLINE | ID: mdl-11380231

ABSTRACT

PURPOSE: The use of oral chemotherapeutic agents in chemoradiotherapy provides several advantages. Doxifluridine, an oral 5-FU prodrug, has been shown to be effective in colorectal cancer. We attempted a Phase II trial of preoperative chemoradiotherapy with doxifluridine plus a low-dose oral leucovorin in unresectable primary rectal cancer patients. In this study, toxicity and efficacy were evaluated. METHODS AND MATERIALS: There were 23 patients with primary unresectable rectal cancer in this trial, 21 of whom were available for analysis. The patients were treated with oral doxifluridine (900 mg/day) plus oral leucovorin (30 mg/day) from days 1 to 35, and pelvic radiation of 45 Gy over 5 weeks. Surgical resection was performed 5-6 weeks after the treatment. RESULTS: Acute toxicity involved thrombocytopenia, nausea/vomiting, diarrhea, and skin reaction. All were in Grade 1/2, except diarrhea, which was not only the most frequent (7 patients, 33.3%), but also the only toxicity of Grade 3 (2 patients). The clinical tumor response was shown in 5 patients (23.8%) as a complete response and 13 patients (61.9%) as a partial response. A complete resection with negative resection margin was done in 18 patients (85.7%), in 2 of whom a pathologic complete response was shown (9.5%). The overall downstaging rate in the T- and N-stage groupings was 71.4% (15 patients). CONCLUSION: This study demonstrated the efficacy and low toxicity of chemoradiotherapy with doxifluridine. Currently, a Phase III randomized trial of chemoradiotherapy is ongoing at our institute to compare the therapeutic efficacy of oral 5-FU with respect to i.v. 5-FU in locally advanced and unresectable rectal cancer.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Adenocarcinoma/surgery , Administration, Oral , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Combined Modality Therapy , Diarrhea/chemically induced , Diarrhea/etiology , Female , Floxuridine/administration & dosage , Floxuridine/adverse effects , Humans , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Middle Aged , Preoperative Care , Radiotherapy/adverse effects , Rectal Neoplasms/surgery , Thrombocytopenia/chemically induced , Thrombocytopenia/etiology
13.
Cancer Lett ; 167(2): 215-24, 2001 Jun 26.
Article in English | MEDLINE | ID: mdl-11369143

ABSTRACT

We investigated the dose-related effect of the 5-fluorouracil (5-FU)/leucovorin regimen on survival in 139 colon cancer patients with Dukes' B2 and C2 stage disease. Chemotherapy consisted of 400 mg/m(2) of 5-FU and 20 mg/m(2) of leucovorin injected daily for 5 days in every 4 weeks for a maximum of 12 cycles. The total dose of 5-FU administered per body surface area had a significant effect on the 5-year disease-free survival and 5-year overall survival in stage B2 and C2 colon cancer patients (P=0.0018, P=0.0011). Analysis with reference to the median DSDI demonstrated that there was a significant difference in 5-year survival in Dukes' C2 (P=0.0016), but survival was not affected by the dose intensity. Multivariate analysis demonstrated that only the total dose of 5-FU administered per surface area affected the 5-year disease-free survival and 5-year overall survival (P=0.0016, P=0.0007, respectively). It can be concluded that the total dose of 5-FU administered is important in planned dosage schedule of adjuvant chemotherapy in colon cancer.


Subject(s)
Antineoplastic Agents/therapeutic use , Colonic Neoplasms/drug therapy , Fluorouracil/therapeutic use , Leucovorin/therapeutic use , Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Chemotherapy, Adjuvant , Colonic Neoplasms/mortality , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Middle Aged , Recurrence , Survival Analysis
14.
Jpn J Clin Oncol ; 31(1): 25-9, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11256837

ABSTRACT

BACKGROUND: Preoperative radiation treatment with concomitant intravenous infusion of 5-fluorouracil (5-FU) is known to be effective in shrinking and downstaging of tumors. However, chemotherapy has often been limited by its toxicity and poor patient compliance. Oral 5-FU is known to have several advantages over conventional intravenous 5-FU infusion such as lower toxicity and higher quality of life without compromising the efficacy of the treatment. The aim of this study was to compare intravenous 5-FU with oral doxifluridine with respect to tumor response, toxicity and quality of life. METHODS: Twenty-eight patients with rectal cancer, staged as over T3N1 or T4 by transrectal ultrasonography between July 1997 and December 1998, were included in this study. Intravenous 5-FU (450 mg/m2) and leucovorin (20 mg/m2) were given for five consecutive days during the first and fifth weeks of radiation therapy (50.4 Gy) (n = 14). Oral doxifluridine (700 mg/m2/day) and leucovorin (20 mg/m2) were given daily during radiation treatment (n = 14). Quality of life was scored according to 22 activity items (good, >77; fair, >58; poor, <57). Surgical resection was performed 4 weeks after completion of concurrent chemoradiation treatment. Tumor response was classified into CR (complete remission), PR (partial response; 50% diminution of tumor volume or downstaging ) and NR (no response). RESULTS: Tumor response was CR 3/14 (21.4%), PR 7/14 (50%) and NR 4/14 (28.6%) in the IV arm versus CR 2/14 (14.2%), PR 6/14 (42.9%) and NR 6/14 (42.9%) in the Oral arm (p = 0.16, 0.23, 0.24), respectively. The quality of life was poor (36.4% versus 33.3%), fair and good (63.6% versus 66.7%) between the IV arm and Oral arm, respectively. Gastrointestinal toxicity was 2/14 (14.3%) in the IV arm versus 5/14 (35.7%) in the Oral arm, respectively. Stomatitis was only observed in the IV arm (1/14, 7.1%). Hematological toxicity was 3/14 (21.4%) in the IV arm versus 4/14 (28.5%) in the Oral arm, respectively. Systemic recurrence during the follow-up periods were 1/14 (7.1%) in the IV arm and 2/14 (14.3%) in the Oral arm, respectively (p = 0.307). One local recurrence was observed in the Oral arm. CONCLUSION: Even though the results were not entirely reliable owing to the small number of patients enrolled, oral doxifluridine-based chemotherapy as preoperative chemoradiation for advanced rectal cancer did not show any significant advantages over intravenous infusion.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Floxuridine/therapeutic use , Fluorouracil/therapeutic use , Rectal Neoplasms/therapy , Administration, Oral , Combined Modality Therapy , Female , Humans , Infusions, Intravenous , Leucovorin/administration & dosage , Male , Middle Aged , Prospective Studies , Quality of Life , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/surgery
15.
Cancer Res ; 61(1): 36-8, 2001 Jan 01.
Article in English | MEDLINE | ID: mdl-11196187

ABSTRACT

Microsatellite instability (MSI) and frameshift mutations in genes containing nucleotide repeats have been reported in a subset of colorectal and gastric carcinomas. This study describes the analysis of MSI-positive colorectal (39 cases) and gastric carcinomas (36 cases) for the presence of frameshift mutations of the six genes known to be involved in DNA repair and containing mononucleotide repeats in their coding region. Our mutational study of the 75 MSI-positive tumors revealed frequent mutations in hRAD50 (23 cases, 31%), BLM (16 cases, 21%), and hMSH6 (16 cases, 21%); rare mutations in BRCA1 (1 case, 1%) and ATM (3 cases, 4%); and no mutation in NBS1. In contrast, no frameshift mutation was found in 60 MSI-negative colorectal and gastric carcinomas. The mutation of hRAD50, a gene that is involved in the response to cellular DNA damage and forms a complex with hMRE11 and NBS1, has not been reported previously. Our results suggest that frameshift mutations of hRAD50, BLM, and hMSH6 are selected and play a role in the tumorigenesis of colorectal and gastric carcinomas with MSI. The MSI targeting of the hRAD50 and BLM genes represents an additional link between MSI and DNA repair because alteration of these genes could accelerate defective DNA repair.


Subject(s)
Adenocarcinoma/genetics , Colorectal Neoplasms/genetics , DNA Repair Enzymes , DNA-Binding Proteins/genetics , Frameshift Mutation , Microsatellite Repeats/genetics , Stomach Neoplasms/genetics , Acid Anhydride Hydrolases , Adenosine Triphosphatases/genetics , Ataxia Telangiectasia Mutated Proteins , Cell Cycle Proteins , DNA Helicases/genetics , DNA Mutational Analysis , DNA Repair/genetics , Genes, BRCA1/genetics , Humans , Nuclear Proteins/genetics , Protein Serine-Threonine Kinases/genetics , RecQ Helicases , Tumor Suppressor Proteins
16.
Oncology ; 60(1): 24-30, 2001.
Article in English | MEDLINE | ID: mdl-11150904

ABSTRACT

OBJECTIVE: The long-term survival of patients who undergo surgery for stage IV gastric cancer is poor, due to metastatic spread of the tumor. Intraperitoneal chemotherapy (IPT) as a possible treatment for peritoneal dissemination has been investigated in a number of different tumors. The aim of this study was to investigate the toxicity and impact of early postoperative IPT on the survival of patients with advanced gastric cancer. METHODS: Between 1993 and 1997, a total of 91 patients with stage IV gastric cancer who underwent potentially curative or palliative resection received intraperitoneal mitomycin C before closure of the abdominal wound. 5-Fluorouracil and cisplatin were administered intraperitoneally on postoperative days 1-4, and this was repeated at 4-week intervals. RESULTS: All patients received a median of 3 IPT perfusions. There were 24 (26.4%) postoperative complications and 1 (1.1%) mortality. The most frequent hematologic toxicity (grade 3-4) was leukopenia. The major nonhematologic toxicities (grade 3-4) were emesis and nephrotoxicity. After a median follow-up period of 26 months, 14 patients remain alive without evidence of recurrence, whereas 75 patients died due to recurrence or progression of disease. The median survival period for all 91 patients was 15.4 months. When survival according to the residual tumor was analyzed, median survival was 36.0 months in the R0 (curative resection) group, 20.6 months in the R1 group (margins of resected specimens showing microscopic residual tumor or diameter of each residual tumor less than 3 mm) and 9.0 months in the R2 group (macroscopic residual tumor larger than 3 mm) (p < 0.001). CONCLUSIONS: IPT was found to be safe, and it appears to improve the prognosis in patients with minimal residual tumors. However, complete cytoreductive surgery is mandatory for achieving the beneficial effect of IPT.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Gastrectomy , Peritoneal Neoplasms/prevention & control , Stomach Neoplasms/drug therapy , Adult , Antibiotics, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Feasibility Studies , Female , Fluorouracil/administration & dosage , Humans , Infusions, Parenteral , Lymphatic Metastasis , Male , Middle Aged , Mitomycin/administration & dosage , Neoplasm Invasiveness , Neoplasm Staging , Peritoneal Neoplasms/secondary , Proportional Hazards Models , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Survival Analysis , Time Factors , Treatment Failure , Treatment Outcome
17.
Hepatogastroenterology ; 48(42): 1793-6, 2001.
Article in English | MEDLINE | ID: mdl-11813626

ABSTRACT

BACKGROUND/AIMS: The purpose of this study was to evaluate the prognostic significance of ploidy patterns as determined by flow cytometry in terms of clinical usefulness. METHODOLOGY: 270 patients with a diagnosis of advanced gastric carcinoma were studied with fresh specimens obtained from multiple site avoiding nonviable or nonneoplastic tissues by DNA flow cytometry. DNA ploidy and clinicopathologic factors were compared and survival was analyzed. RESULTS: The mean age of the patients was 56.1 +/- 11.6 years (25-80 years). There were 195 males and 75 females. Aneuploidy was shown in 93 (35.9%) patients. Male sex and differentiated tumor were more frequent in aneuploidy than diploidy (P = 0.011, < 0.001, respectively). By univariate analysis, tumor location, size, extent of resection, curative resection, serosa invasion, lymph node involvement, and distant metastasis significantly affected survival but not aneuploidy. Significant independent prognostic factors by multivariate analysis were curative resection, serosa invasion and lymph node involvement (P = 0.0001, 0.0114, 0.0262, respectively). CONCLUSIONS: DNA ploidy patterns of advanced gastric carcinoma are of limited clinical significance, therefore not a clinically applicable prognosticator.


Subject(s)
DNA/genetics , Stomach Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Female , Flow Cytometry , Humans , Male , Middle Aged , Neoplasm Metastasis , Ploidies , Prognosis , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology
18.
Hepatogastroenterology ; 48(42): 1802-5, 2001.
Article in English | MEDLINE | ID: mdl-11813628

ABSTRACT

BACKGROUND/AIMS: In the UICC staging system, stage IV contains not only those patients with distant metastasis but also patients with far-advanced T and N status but without distant metastasis. We investigated the prognostic factors of stage IV gastric carcinoma patients, without distant metastasis after curative resection and the role of surgery. METHODOLOGY: One hundred and ninety stage IV gastric carcinoma patients, without distant metastasis were reviewed after curative resection in our hospital from January 1987 to December 1996. RESULTS: Male sex, distal third location, diffuse or infiltrative type and histologically undifferentiated type were common. Of the 190 patients, 52 (27.4%) patients lived more than 3 years. The lymph node ratio (positive lymph node/retrieved lymph node) and combined resection independently affected survival (P = 0.0013, 0.0061, respectively). The perigastric lymph node ratio was well correlated with overall lymph node ratio (r = 0.794, P < 0.001). CONCLUSIONS: With the involvement of an adjacent organ and knowing the perigastric lymph node ratio, the surgeon can decide upon the extent of dissection and postoperative treatment. However, a prospective study is warranted.


Subject(s)
Gastrectomy , Stomach Neoplasms/mortality , Stomach Neoplasms/surgery , Female , Humans , Lymph Node Excision , Lymphatic Metastasis , Male , Middle Aged , Prognosis
19.
Cancer Res Treat ; 33(6): 520-6, 2001 Dec.
Article in English | MEDLINE | ID: mdl-26680832

ABSTRACT

PURPOSE: We evaluated the treatment efficacy including survival and recurrence, and factors associated with recurrence in osteosarcoma patients treated with preoperative chemotherapy, surgery, and adjuvant chemotherapy. MATERIALS AND METHODS: Forty nine patients with osteosarcoma were treated with preoperative chemotherapy with intra-arterial cisplatin and adriamycin infusion for 3 cycles, followed by surgery. According to the pathologic response, if tumor was necrotized more than 90%, the same adjuvant chemotherapy was reintroduced for 3 cycles, and if the response was not enough, then the salvage regimen was introduced. Plain chest film and chest CT scan were taken monthly and every 3 months, respectively. When tumor recurred, the metastasectomy was performed whenever possible. RESULTS: Forty three patients were evaluable with amedian follow up of 53 months. Five-year disease-free and overallsurvival rate was 47.0% and 66.9%, respectively. The recurrence was observed in 22 patients (51.2%) with median time of 12.5 months. Baseline alkaline phosphatase (ALP) was the only significant factor for recurrence (p=0.03) and the patients with the possibility of metastasectomy recurrence showed higher post-relapse survival compared to other treatment modalities (26 momths vs 5~12 months). CONCLUSION: These results indicates that pre- and postoperative chemotherapy with intra-arterial cisplatin and adriamycin infusion showed comparable treatment efficacy and acceptable toxicities.

20.
Ann Surg Oncol ; 7(10): 732-7, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11129420

ABSTRACT

BACKGROUND: Preoperative staging is essential for planning of optimal therapy for patients with rectal cancer. Recently, magnetic resonance imaging (MRI) is used frequently because of its benefits of clear pelvic image are better than other diagnostic methods. The purpose of this study was to determine accuracy rates and clinical usefulness of MRI in preoperative staging of rectal cancer. METHODS: Between February, 1997, and December, 1999, 217 patients with histologically proven rectal cancer were staged preoperatively and had surgical resections performed. MRI criteria for depth of invasion was determined by the degree of disruption of the rectal wall. Metastatic perirectal lymph nodes were considered to be present if they showed heterogenous texture, irregular margin, and enlargement (>10 mm). RESULTS: The accuracy of the MRI for determining depth of invasion was 176/217 (81%) and regional lymph node invasion was 110/217 (63%). In the T stage, accuracy rate of T1 was 3/4 (75%), T2 was 20/37 (54%), T3 was 141/162 (87%), and T4 was 12/14 (86%), respectively. The specificity of lymph node invasion was 45/110 (41%) and the sensitivity was 91/107 (85%). The accuracy rate of regional lymph node involvement was 136/217 (63%). T1 and T2 were overstaged in 1/4 (25%) and 17/37 (46%), respectively, and T3 was understaged in 15/162 (9.2%). The accuracy rate to detect metastatic lateral pelvic lymph node was 4/14 (29%) after lateral pelvic lymph node dissection was done in 14 patients under MRI. The accuracy rate in assessing levator ani muscle tumor involvement was 8/11 (72%). CONCLUSIONS: MRI showed a good, comparable accuracy rate for determining depth of tumor invasion, compared with transrectal ultrasonography, which still has a low accuracy rate for detecting metastatic lymph node. MRI with endorectal coil may increase the accuracy rate of T1 and T2 lesions. In addition, clear sagittal and coronal sectional pelvic images can give a lot of information about adjacent organ invasion or any invasion of levator ani muscle. MRI can be useful for choosing an appropriate extent of lymph node dissection and type of surgery.


Subject(s)
Magnetic Resonance Imaging , Neoplasm Staging/methods , Rectal Neoplasms/pathology , Adult , Female , Humans , Lymph Node Excision , Male , Middle Aged , Neoplasm Invasiveness/pathology , Rectal Neoplasms/diagnosis
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