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BACKGROUND: The situation of Helicobacter pylori eradication therapy has been changing over time, owing to increases in antimicrobial-resistant strains, lifestyle improvements, and changes in indications for eradication. In Japan, eradication therapy is now available to all H. pylori-positive patients under the medical insurance system, and the potassium-competitive acid blocker vonoprazan has been used for eradication from 2015. Recently, with the aging of society, opportunities to provide eradication to elderly patients are increasing, but the current status and effectiveness of eradication in elderly patients remains unclear. Therefore, we aimed to investigate the trends of H. pylori eradication in a metropolitan area to determine the factors associated with successful H. pylori eradication in elderly patients older than 80 years. METHODS: Trends in the eradication rates of patients who received first- or second-line eradication at 20 hospitals in the Tokyo metropolitan area from 2013 to 2023 were investigated. RESULTS: The eradication rates in the per-protocol analysis were 82.3% (95% confidence interval [CI]: 81.2%-83.2%) for the first-line treatment (n = 6481), and 87.9% (86.9%-88.9%) for the second-line treatment (n = 4899). Multivariate analysis showed that independent factors for successful eradication in the first-line treatment were an age of older than 80 years (OR: 0.606; 95% CI: 0.448-0.822), peptic ulcers (vs. atrophic gastritis: 3.817; 3.286-4.433), and vonoprazan (vs. proton pump inhibiters (PPIs), 3.817; 3.286-4.433), and an age of older than 80 years (0.503; 0.362-0.699) and vonoprazan (1.386; 1.153-1.667) in the second-line treatment. CONCLUSION: After 2015, the eradication rate of both first- and second-line therapies were maintained at a higher level than before 2015, owing to the use of vonoprazan. As the H. pylori eradication rate in patients older than 80 years was low, an effective strategy for these patients needs to be developed in the future.
Assuntos
Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Idoso de 80 Anos ou mais , Masculino , Feminino , Estudos Retrospectivos , Helicobacter pylori/efeitos dos fármacos , Antibacterianos/uso terapêutico , Sulfonamidas/uso terapêutico , Resultado do Tratamento , Tóquio , Pirróis/uso terapêutico , Quimioterapia Combinada , Inibidores da Bomba de Prótons/uso terapêutico , Japão/epidemiologiaRESUMO
BACKGROUND: Intramural metastasis distant from the primary tumor is rare in colorectal cancer. Here, we present a notably rare and probably the first case of asynchronous intramural recurrence in the rectum after curative surgery for proximal sigmoid colon cancer. CASE PRESENTATION: A 44-year-old man underwent curative sigmoidectomy for proximal sigmoid colon cancer with T3N0M0, Stage IIA tubular adenocarcinomas. After 15 months, the tumor marker level had increased, and positron emission tomography-computed tomography (PET-CT) revealed abnormal fluorodeoxyglucose uptake in the rectum; colonoscopy revealed a submucosal tumor (SMT)-like lesion in the upper rectum, and biopsy revealed a tubular adenocarcinoma. We performed curative low anterior resection with tumor-specific mesorectal excision (TSME). The SMT-like tumor was located approximately 20 cm from the initial sigmoid colon anastomosis (i.e., at least 20 cm distal to the initial sigmoid colon cancer). The pathological findings revealed cancer cells with the same features as the initial sigmoid colon cancer, only in the intestinal wall but not in the mucosa and extramural tissue. Therefore, the lesion was determined to be an intramural recurrence. After 24 months, lung recurrence, and local recurrence, which might have involved the lymph nodes in the preserved mesorectum after TSME at the bottom of the pelvis was detected on PET-CT. Hence, we started systemic chemotherapy. CONCLUSIONS: This case report suggests that PET-CT and short-interval repeat colonoscopy may help detect a rare intramural recurrence. A long distal margin may be necessary to achieve local control in the rectal resection for intramural recurrence.
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Adenocarcinoma , Neoplasias Retais , Neoplasias do Colo Sigmoide , Adenocarcinoma/patologia , Adulto , Biomarcadores Tumorais , Humanos , Masculino , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Pelve/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Reto/cirurgia , Neoplasias do Colo Sigmoide/patologia , Neoplasias do Colo Sigmoide/cirurgiaRESUMO
The reported patient was a 90-year-old woman with anorexia. She was diagnosed with advanced gallbladder cancer that occurred concurrently with stomach cancer. Subsequent to intestinal bypass surgery, S-1(80mg/day)was administered for 14 days, followed by 7 days of rest for one course. Tumor marker levels returned to normal after 4 months. Computed tomography results indicated that, in regard to the gallbladder cancer, the patient had stable disease after 8 months. In addition, gastroscopy revealed a complete response of the gastric cancer after a year. The patient was able to continue treatment as an outpatient until she experienced aspiration pneumonia. The administration of S-1 was terminated after 4 years and 4 months. Treatment with S-1 monotherapy is considered safe for elderly patients, and has the additional benefit that it is deliverable as an outpatient treatment.
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Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias Primárias Múltiplas/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Tegafur/uso terapêutico , Idoso de 80 Anos ou mais , Combinação de Medicamentos , Evolução Fatal , Feminino , Humanos , Fatores de TempoRESUMO
BACKGROUND AND AIM: Helicobacter pylori (H. pylori) infection is a strong risk factor for the development of gastric cancer. In 2013, the Japanese government approved H. pylori eradication therapy in patients with chronic gastritis as well as peptic ulcer. However, the continuing decline in eradication rates for first-line H. pylori eradication therapies is an urgent problem. In this study, we investigated changes in the first-line eradication rate from 2001 to 2010. METHODS: Eradication rates for 7-day triple therapy [proton pump inhibitor (rabeprazole 20 mg, lansoprazole 60 mg, or omeprazole 40 mg)+amoxicillin 1500 mg + clarithromycin (CAM) 400 or 800 mg, daily] were collated from 14 hospitals in the Tokyo metropolitan area. The urea breath test was used for the evaluation of eradication. The cut-off value was less than 2.5%. RESULTS: The yearly eradication rates (intention to treat/per protocol) were 78.5/79.5% (2001, n=242), 71.2%/72.9% (2002, n=208), 67.8%/70.5% (2003, n=183), 75.6%/84.6% (2004, n=131), 56.4%/70.5% (2005, n=114), 70.5%/75.8% (2006, n=271), 67.4%/82.0% (2007, n=135), 64.0%/76.3% (2008, n=261), 60.5%/74.3% (2009, n=329), and 66.5%/78.8% (2010, n=370), respectively. Examination of eradication rates according to CAM dosage revealed an eradication rate of 65.6% (383/584) for CAM 400 mg daily, and 68.5% (1124/1642) for CAM 800 mg daily, with no significant difference seen between dosages. CONCLUSION: In recent years, eradication rates for first-line triple therapy have obviously decreased, but no noticeable decrease has occurred after 2001.
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Amoxicilina/administração & dosagem , Claritromicina/administração & dosagem , Erradicação de Doenças/estatística & dados numéricos , Gastrite/microbiologia , Gastrite/prevenção & controle , Infecções por Helicobacter , Helicobacter pylori , Lansoprazol/administração & dosagem , Omeprazol/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Rabeprazol/administração & dosagem , Doença Crônica , Feminino , Gastrite/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Tóquio/epidemiologiaRESUMO
BACKGROUND: In Japan, the eradication rate of first-line therapy for Helicobacter pylori (H. pylori) with a proton pump inhibitor (PPI), amoxicillin (AMPC) and clarithromycin (CAM) has been decreasing because of a high prevalence of CAM resistance. A possible decrease of the eradication rate for second-line therapy with a PPI, AMPC and metronidazole (MNZ) is of concern. The aim of this study is to assess the trends in second-line eradication therapy for H. pylori in Japan. MATERIALS AND METHODS: We accumulated data retrospectively on patients administered second-line eradication therapy for Helicobacter pylori with a PPI, AMPC, and MNZ for 1 week after failure of first-line eradication therapy with a PPI, AMPC and CAM at 15 facilities in the Tokyo metropolitan area in Japan from 2007 to 2011. Trends for second-line eradication rates in modified intention-to-treat (ITT) analyses were investigated. Second-line eradication rates were categorized by three PPIs (rabeprazole (RPZ), lansoprazole (LPZ) or omeprazole (OMZ)) and evaluated. RESULTS: We accumulated data on 1373 patients. The overall second-line eradication rate was 92.4%. Second-line eradication rates in 2007, 2008, 2009, 2010 and 2011 were 97.7, 90.6, 94.5, 91.8 and 91.8%, respectively, with no significant trends revealed. Second-line eradication rates categorized by three PPIs for the entire 5-year period were 91.6, 93.4 and 92.4% (RPZ, LPZ and OPZ, respectively) with no significant differences among the three PPIs. CONCLUSIONS: From 2007 to 2011, there were no significant trends in the second-line eradication rates and the rates remained consistently high. From the viewpoint of high prevalence of CAM resistance in Japan, triple therapy with PPI, AMPC and MNZ may be a better strategy for first-line therapy compared to triple therapy with PPI, AMPC and CAM.
Assuntos
Antibacterianos/uso terapêutico , Erradicação de Doenças , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Adulto , Idoso , Amoxicilina/uso terapêutico , Claritromicina/uso terapêutico , Quimioterapia Combinada , Feminino , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/fisiologia , Humanos , Lansoprazol , Masculino , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Omeprazol/uso terapêutico , Estudos Retrospectivos , Tóquio/epidemiologia , Adulto JovemRESUMO
INTRODUCTION AND IMPORTANCE: The standard treatment for locally advanced colon cancer (LACC) without distant metastasis is curative surgery followed by adjuvant chemotherapy, but the long-term outcomes of this strategy are not satisfactory. Neoadjuvant chemotherapy (NAC) is a promising novel option to overcome this issue. Tumor regression is an expected effect of NAC for LACC, but pathological complete response (pCR) is rare. In this report, we present a rare case of pCR after NAC with FOLFOX for LACC in the sigmoid colon. PRESENTATION OF CASE: A 66-year-old woman presented to our hospital with fever and abdominal pain. The diagnosis was LACC in the sigmoid colon with possible invasion of the uterus and pelvic wall, stage IIIC (T4bN1bM0). Furthermore, the tumor was complicated by diverticulitis. A colostomy was performed, followed by NAC with FOLFOX. Six cycles were completed without significant adverse events, and the lesion shrunk remarkably. We performed a curative sigmoidectomy without any postoperative complications. Pathological examination revealed no viable cancer cells, indicating pCR. DISCUSSION: To the best of our knowledge, this is the first report of pCR after NAC for LACC complicated by diverticulitis. Colostomy before NAC, regimen, and cycle of NAC may be the key to this favorable course. CONCLUSION: We present a rare case of pathological complete after neoadjuvant chemotherapy with FOLFOX for locally advanced colon cancer in the sigmoid colon complicated by diverticulitis. Our experience may be valuable in determining the optimal treatment strategy for LACC complicated by diverticulitis.
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Few cases of gastric carcinoma with infiltrating multi-nucleated giant cells (MGCs) have been reported, and giant cells infiltrating the gastric carcinoma were previously described as osteoclast-like giant cells (OGCs). However, hepatoid adenocarcinomas have never been reported previously, and the present case is extremely rare. A 100-year-old Japanese man with gastralgia was found to have a mass in his gastric body. Histological examination showed a poorly differentiated adenocarcinoma with infiltration of MGCs. Vascular and lymphatic invasion were noted but there were no metastases. Almost all the tumor comprised cells with hepatoid-like features. The MGCs proliferated, with infiltration of lymphoid cells. A few MGCs contained mucous material in their cytoplasm, indicating these were foreign-body giant cells. Immunohistochemically, the hepatoid-like components were positive for AFP, and staining with polyclonal antibodies against carcinoembryonic antigen (CEA) showed the canalicular pattern. We concluded that this component was hepatoid adenocarcinoma. The MGCs were positive for CD68, and surrounding infiltrating lymphoid cells were diffusely positive for CD3. Infiltration of MGCs in gastric cancer may represent a cellular immune response against gastric cancer invasion. Further studies are required to elucidate the etiology of MGCs in gastric cancer.
Assuntos
Adenocarcinoma/patologia , Células Gigantes/patologia , Neoplasias Gástricas/patologia , Idoso de 80 Anos ou mais , Proliferação de Células , Humanos , MasculinoRESUMO
PURPOSE: The purpose of this clinical study was to be the first to explore whether ART-123, a recombinant human soluble thrombomodulin, prevents oxaliplatin-induced peripheral neuropathy (OIPN). METHODS: This randomized, phase IIa trial enrolled stage II/III colon cancer patients who received adjuvant mFOLFOX6 chemotherapy. Participants were randomly allocated to 3 arms in a double-blind manner: placebo (placebo: days 1-3); 1-day ART (ART-123: day 1, placebo: days 2-3); and 3-day ART (ART-123: days 1-3). ART-123 (380 U/kg/day) or placebo was infused intravenously before each 2-week cycle of mFOLFOX6. OIPN was assessed with the Functional Assessment of Cancer Therapy/Gynecological Oncology Group-Neurotoxicity-12 (FACT/GOG-Ntx-12) score by participants and the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) by investigators. RESULTS: Seventy-nine participants (placebo n = 28, 1-day ART n = 27, 3-day ART n = 24) received study drugs. The least-squares mean FACT/GOG-Ntx-12 scores at cycle 12 from the mixed effect model for repeated measures were 28.9 with placebo, 36.3 with 1-day ART (vs. placebo: 7.3 [95% CI 1.9 to12.8, p = 0.009]), and 32.3 with 3-day ART (vs. placebo: 3.4 [95% CI -.1 to 9.0, p = 0.222]). The cumulative incidence of NCI-CTCAE grade ≥ 2 sensory neuropathy at cycle 12 was 64.3% with placebo, 40.7% with 1-day ART (vs. placebo: -23.5 [95% CI -48.4 to 4.0], p = 0.108), and 45.8% with 3-day ART (vs. placebo: -18.5 [95% CI -44.2 to 9.4], p = 0.264). Common adverse events were consistent with those reported with mFOLFOX6; no severe bleeding adverse events occurred. CONCLUSION: ART-123 showed a potential preventive effect against OIPN with good tolerability. A larger study with 1-day ART is warranted. NCT02792842, registration date: June 8, 2016.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Oxaliplatina/efeitos adversos , Doenças do Sistema Nervoso Periférico/prevenção & controle , Trombomodulina/administração & dosagem , Adulto , Idoso , Esquema de Medicação , Feminino , Fluoruracila/efeitos adversos , Humanos , Incidência , Infusões Intravenosas , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/epidemiologia , Placebos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Autorrelato/estatística & dados numéricos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
We reported previously that a new Western-style diet (NWD) for 18 months, consisting of elevated lipids and decreased calcium, vitamin D and methyl-donor nutrients, induced colonic tumors in normal C57Bl/6 mice [Newmark, H.L. et al. (2001) A Western-style diet induces benign and malignant neoplasms in the colon of normal C57Bl/6 mice. Carcinogenesis, 22, 1871-1875], suggesting a new mouse model for human sporadic colon cancer. Here, we have extended this study during a longer feeding period of 2 years wherein tumor formation, tumor inhibition by addition of dietary calcium and vitamin D and their effects on gene expression were determined. We also similarly tested individual supplements of methyl donor (transfer) nutrients (folic acid, choline, methionine and dietary fiber), but these had no significant effect on colonic tumor incidence or multiplicity, whereas supplementation with combined calcium and vitamin D produced significant decrease in both colon tumor incidence and multiplicity, during 2 years of feeding. No visible colonic tumors were found at 6 months, very few at 12 months, more at 18 months and significantly at 24 months. In a related study of gene changes of the mouse colonic mucosa at 6 months of feeding taken from this study, long before any tumors were visibly detectable, indicated altered profiles of gene expression linked to later risk of dietary initiation of colon tumor formation. This type of early genetic altered profile, an indication of increased risk of later colonic tumor development, may become a useful tool for prediction of colon tumor risk while the colon grossly still appears histologically and physiologically normal.
Assuntos
Cálcio/administração & dosagem , Neoplasias do Colo/etiologia , Dieta , Modelos Animais de Doenças , Vitamina D/administração & dosagem , Animais , Peso Corporal , Neoplasias do Colo/prevenção & controle , Feminino , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
We have previously reported that sulindac, a non-steroidal anti-inflammatory drug, inhibited tumor formation in the small intestine but increased tumors in the colon of Apc(Min/+) mice, a model of human familial adenomatous polyposis. To further explore intestinal regional responses, we studied effects of sulindac on additional gene-targeted mouse models of human intestinal tumorigenesis; these were (i) Apc(1638N/+) mouse (chain termination mutation in exon 15 of the Apc gene); (ii) Mlh1(+/-) mouse (DNA mismatch repair deficiency, a mouse model of human hereditary non-polyposis colorectal cancer) and (iii) double-heterozygous Mlh1(+/-)Apc(1638N/+) mutant mouse. Mice were fed AIN-76A control diet with or without 0.02% sulindac for 6 months. Intestinal regional tumor incidence, multiplicity, volume and degree of inflammation were used as end points. The results showed the following: (i) sulindac inhibited tumor development in the small intestine of Apc(1638N/+) mice; (ii) in contrast, sulindac increased tumors in the small intestine of Mlh1 mutant mice, a neoplastic effect which persisted in heterozygous compound Mlh1(+/-)Apc(1638N/+) mutant mice; (iii) sulindac increased tumors in the cecum of all mice regardless of genetic background; (iv) sulindac decreased inflammation in the small intestine of Apc(1638N/+) mice, but it increased inflammation in the small intestine of Mlh1(+/-) mice and Mlh1(+/-)Apc(1638N/+) mice and (v) sulindac enhanced inflammation in the cecum of all mutant mice. Findings indicate that the effects of sulindac in the intestine of these mutant mouse models are probably related to genetic background and appear to be associated with its inflammatory-inducing response.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteína da Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Neoplasias Colorretais Hereditárias sem Polipose , Mutação , Proteínas Nucleares/genética , Sulindaco/efeitos adversos , Sulindaco/farmacologia , Polipose Adenomatosa do Colo/induzido quimicamente , Polipose Adenomatosa do Colo/tratamento farmacológico , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/patologia , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Antineoplásicos/uso terapêutico , Ceco/efeitos dos fármacos , Ceco/patologia , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Neoplasias Colorretais Hereditárias sem Polipose/induzido quimicamente , Neoplasias Colorretais Hereditárias sem Polipose/tratamento farmacológico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Modelos Animais de Doenças , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Camundongos , Proteína 1 Homóloga a MutL , Sulindaco/uso terapêuticoRESUMO
BACKGROUND: The environment surrounding Helicobacter pylori eradication treatment is dramatically changing. Recently, vonoprazan, a first-in-class potassium-competitive acid blocker (P-CAB), was introduced onto the market in 2015. The aging of Japan's demographic structure is becoming pronounced. In this study, we examined the trend of the eradication rate of H. pylori in the metropolitan area and examined factors concerning successful eradication. METHODS: We collected data from 20 hospitals in the Tokyo metropolitan area on patients who received first-line eradication therapy with a proton-pump inhibitor (PPI)/P-CAB, amoxicillin, and clarithromycin for 1 week and second-line eradication therapy with a PPI/P-CAB, amoxicillin, and metronidazole for 1 week from 2013 to 2018. The annual eradication rate and associated factors for successful eradication were analyzed. RESULTS: We collected data of 4097 and 3572 patients in the first- and second-line eradication therapies, respectively. The eradication rate decreased from 2013 to 2014 and increased again from 2015 to 2018 with the first-line therapy [the eradication rates in 2013, 2014, 2015, 2016, 2017 and 2018 were 71.8%, 63.7%, 78.5%, 84.6%, 89.7 and 90.1%, respectively, in the per protocol (PP)]. The second-line eradication rates were 90.0%, 82.6%, 88.8%, 87.5%, 91.8% and 90.1% in 2013, 2014, 2015, 2016, 2017 and 2018, respectively, in PP. Vonoprazan was an independent factor for successful eradication in not only first-line, but also second-line eradication. Age over 75 years was an independent factor for eradication failure in both first- and second-line eradication therapies. CONCLUSION: The eradication rate improved from 2015 to 2018 with the first-line therapy because of the introduction of vonoprazan in the market. The eradication rates with first- and second-line regimens in elderly patients were lower than those in younger patients.
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Orange peel is a rich source of flavonoids with polymethoxyflavones as major constituents, compounds associated with potential antioxidant, anti-inflammatory, and antitumor activities. We studied the effect of an orange peel extract (OPE) on intestinal tumor growth in Apc(Min/+) mice, a mouse model for human familial adenomatous polyposis (FAP). The OPE contained 30% polymethoxyflavones, a mixture that included tangeretin (19.0%), heptamethoxyflavone (15.24%), tetramethoxyflavone (13.6%), nobiletin (12.49%), hexamethoxyflavone (11.06%), and sinensitin (9.16%). Apc(Min/+) mice were fed one of four diets: (1) AIN-76A control diet; (2) a new Western-style diet (NWD), i.e., AIN-76A diet modified with decreased calcium, vitamin D, and methyl-donor nutrients and increased lipid content); (3) NWD with 0.25% OPE; and (4) NWD with 0.5% OPE, with all additives premixed in the diet. After 9 weeks of feeding NWD to the Apc(Min/+) mice, tumors increased mainly in the colon, with tumor multiplicity increasing 5.3-fold and tumor volume increasing 6.7-fold. After feeding 0.5% OPE in NWD, the development of tumors markedly decreased, with multiplicity decreasing 49% in the small intestine and 38% in the colon. NWD also led to increased apoptosis in intestinal tumors, and 0.5% OPE in NWD further increased apoptosis in tumors of the small and large intestine. Findings indicated that OPE inhibited tumorigenesis in this preclinical mouse model of FAP, and increased apoptosis may have contributed to this effect.
Assuntos
Anticarcinógenos/administração & dosagem , Citrus sinensis/química , Frutas/química , Neoplasias Intestinais/prevenção & controle , Extratos Vegetais/administração & dosagem , Polipose Adenomatosa do Colo/genética , Animais , Apoptose , Neoplasias do Colo/patologia , Neoplasias do Colo/prevenção & controle , Dieta , Neoplasias Intestinais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , FitoterapiaRESUMO
Mutations in the human DNA mismatch repair gene MSH2 are associated with hereditary nonpolyposis colorectal cancer as well as a significant proportion of sporadic colorectal cancer. The inactivation of MSH2 results in the accumulation of somatic mutations in the genome of tumor cells and resistance to the genotoxic effects of a variety of chemotherapeutic agents. Here we show that the DNA repair and DNA damage-induced apoptosis functions of Msh2 can be uncoupled using mice that carry the G674A missense mutation in the conserved ATPase domain. As a consequence, although Msh2(G674A) homozygous mutant mice are highly tumor prone, the onset of tumorigenesis is delayed as compared with Msh2-null mice. In addition, tumors that carry the mutant allele remain responsive to treatment with a chemotherapeutic agent. Our results indicate that Msh2-mediated apoptosis is an important component of tumor suppression and that certain MSH2 missense mutations can cause mismatch repair deficiency while retaining the signaling functions that confer sensitivity to chemotherapeutic agents.
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Apoptose/genética , Reparo do DNA/genética , Proteínas de Ligação a DNA , Mutação Puntual , Proteínas Proto-Oncogênicas/genética , Alanina , Substituição de Aminoácidos , Animais , Pareamento Incorreto de Bases/genética , Cromossomos Artificiais Bacterianos , Cisplatino/toxicidade , Códon/genética , Dano ao DNA/genética , Fibroblastos/fisiologia , Glicina , Camundongos , Proteína 2 Homóloga a MutS , Deleção de SequênciaRESUMO
BACKGROUND: The efficacy of intrahepatic arterial chemotherapy for liver metastasis from biliary tract or pancreatic cancer remains uncertain. PATIENTS AND METHODS: Five patients with bilio-pancreatic liver metastasis underwent continuous hepatic arterial infusion chemotherapy. One treatment course basically consisted of a 14-day infusion period during which continuous infusions of 5-fluorouracil and intermittent bolus injections of cisplatin were given, and a subsequent 14-day intermission. After two consecutive courses, these drugs were administered bi-weekly. RESULTS: One complete and three partial responses were observed (response rate, 80%). In responders, the responses persisted until or even after the cessation of chemotherapy. The median survival was 15 months after the start of chemotherapy. The longest survivor has been disease-free for 46 months since a liver tumour remaining despite chemotherapy was eradicated by further treatment. Toxicity was acceptable. CONCLUSION: 5-Fluorouracil and cisplatin-based continuous hepatic arterial infusion chemotherapy may serve as a promising treatment for bilio-pancreatic liver metastasis.
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Antineoplásicos/administração & dosagem , Neoplasias do Sistema Biliar/tratamento farmacológico , Artéria Hepática/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Pancreáticas/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/patologia , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pancreáticas/patologia , Recidiva , Fatores de Tempo , Resultado do TratamentoRESUMO
We report a rare case of intra-abdominal fibromatosis of the jejunal mesentery. A 71-year-old man, who was incidentally diagnosed with left hydronephrosis, was found to have a tumor near the duodeno-jejunal junction. The tumor appeared to invade the intestinal wall and was obstructing the left ureter. The tumor was indefinite in diagnosis preoperatively. The patient underwent an en-bloc excision of the tumor by a partial duodeno-jejunectomy combined with a left nephrectomy. Microscopic examination of the tumor showed that non-dysplastic fibroblasts proliferating in the jejunal mesentery had infiltrated into the adjacent small intestines and ureter, resulting in a diagnosis of intra-abdominal fibromatosis. This diagnosis was supported by findings of immunohistochemical analyses showing positive staining for vimentin and smooth muscle actin and negativity for keratin, CD34, C-kit and S-100. To our knowledge, this is the first documented case of intra-abdominal fibromatosis of the jejunal mesentery completely resected with the operative procedure described herein. In cases of a preoperatively undiagnosed retroperitoneal or mesenteric tumor that invades adjacent structures, it is important to consider intra-abdominal fibromatosis as a possible differential diagnosis. This may be helpful in planning the appropriate therapeutic strategies including extended multi-organ resection in selected patients.
Assuntos
Fibromatose Abdominal/cirurgia , Neoplasias Renais/secundário , Neoplasias Renais/cirurgia , Invasividade Neoplásica/patologia , Neoplasias Peritoneais/cirurgia , Idoso , Anastomose Cirúrgica , Biópsia por Agulha , Duodeno/cirurgia , Fibromatose Abdominal/patologia , Seguimentos , Humanos , Hidronefrose/diagnóstico , Hidronefrose/cirurgia , Imuno-Histoquímica , Jejuno/cirurgia , Imageamento por Ressonância Magnética/métodos , Masculino , Mesentério/patologia , Estadiamento de Neoplasias , Nefrectomia/métodos , Neoplasias Peritoneais/secundário , Medição de Risco , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Escherichia coli cells expressing fusion proteins consisting of beta-galactosidase and bacterial heat-shock protein (HSP) 60 of E. coli, Yersinia enterocolitica or Helicobacter pylori were constructed, and designated as HY1, HY2 or HY3, respectively. Fusion proteins prepared from HY2 and HY3 induced secretion of interleukin-8 (IL-8) from human gastric epithelial KATOIII cell cultures. On the other hand, the parent strain (E. coli pop2136), PEX (pop2136 transformed by vector) and fusion protein prepared from HY1 did not induce IL-8 secretion from KATOIII cells. Other human gastric (MKN45) and non-gastric cell lines (Int 407 and A549) did not secrete IL-8 following treatment with these proteins. These results indicate that H. pylori HSP60 induces IL-8 secretion from human gastric cells and the levels of IL-8 differ among the various gastric cell lines, suggesting that HSP60 might be an important virulence factor associated with chronic gastric inflammation following H. pylori infection in man.
Assuntos
Proteínas de Bactérias/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Helicobacter pylori/patogenicidade , Interleucina-8/metabolismo , Proteínas de Bactérias/genética , Linhagem Celular , Relação Dose-Resposta a Droga , Eletroforese em Gel de Poliacrilamida , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Mucosa Gástrica/metabolismo , Helicobacter pylori/metabolismo , Humanos , Immunoblotting , Dados de Sequência Molecular , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/farmacologia , Transfecção , VirulênciaRESUMO
Cronkhite-Canada syndrome is generally accepted to be a benign disorder, with 374 reported cases to the present. Worldwide, there have been 18 previously reported cases of Cronkhite-Canada syndrome associated with gastric cancer. In this report we describe a case of a 52-year-old man with the clinical features of Cronkhite-Canada syndrome combined with gastric cancer. Although the gastric tumor was located at the antrum of the stomach, we performed a total gastrectomy because of the edematous swelling and high risk of malignancy in the remnant stomach. As Cronkhite-Canada syndrome may be a premalignant condition for gastric cancer, as well as for colorectal cancer, we suggest periodic examination of the stomach, colon, and rectum for patients with Cronkhite-Canada syndrome.
RESUMO
We previously reported hyperproliferation and hyperplasia in C57Bl/6 mouse mammary gland after feeding a Western-style diet (WD); these findings decreased after supplementing WD with increased calcium and vitamin D(3). We now again fortified WD with increased calcium and vitamin D(3) from two sources: (1) a food source, calcium- and vitamin D(3)-enriched yogurt (WD(y) diet) or (2) adding calcium and vitamin D(3) directly to WD (WD(CaD) diet). After 6 months of feeding the number of mammary ducts was higher in mice consuming WD compared to WD(y) (216.0 vs. 202.7, P <.05) and WD(CaD) (216.0 vs. 194.9, P <.001). The percentage of small ducts increased in WD compared to AIN-76A controls (23.3% vs. 17.4%) but was lower in the WD(y) (17.1%) and WD(CaD) (14.8%) groups. WD mice had higher numbers of epithelial cells per duct than WD(y) (33.2 vs. 27.4, P <.001) and WD(CaD) (33.2 vs. 27.8, P <.001) mice, and AIN-76A-fed mice had higher numbers than WD(y) (31.1 vs. 27.4, P <.005) or WD(CaD) (31.1 vs. 27.8, P <.01) mice. Mitotic index was higher in WD than in WD(CaD) mice (0.0020 vs. 0.0009, P <.001). Thus, small mammary gland ductules and mitosis increased after feeding WD and decreased after supplementing the diets with increased calcium and vitamin D(3), administered either in a dairy food (yogurt) or directly as calcium carbonate plus vitamin D(3) in WD, suggesting further study of these nutrients for their possible relationship to breast cancer prevention.
Assuntos
Cálcio/administração & dosagem , Dieta , Alimentos Fortificados/análise , Glândulas Mamárias Animais/efeitos dos fármacos , Vitamina D/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Contagem de Células , Células Epiteliais , Feminino , Glândulas Mamárias Animais/citologia , Camundongos , Camundongos Endogâmicos C57BL , Mitose/efeitos dos fármacosRESUMO
A defined rodent "new Western diet" (NWD), which recapitulates intake levels of nutrients that are major dietary risk factors for human colon cancer, induced colonic tumors when fed to wild-type C57Bl/6 mice for 1.5 to 2 years from age 6 weeks (two-thirds of their life span). Colonic tumors were prevented by elevating dietary calcium and vitamin D(3) to levels comparable with upper levels consumed by humans, but tumorigenesis was not altered by similarly increasing folate, choline, methionine, or fiber, each of which was also at the lower levels in the NWD that are associated with risk for colon cancer. The NWD significantly altered profiles of gene expression in the flat colonic mucosa that exhibited heterogeneity among the mice, but unsupervised clustering of the data and novel statistical analyses showed reprogramming of colonic epithelial cells in the flat mucosa by the NWD was similar to that initiated by inheritance of a mutant Apc allele. The NWD also caused general down-regulation of genes encoding enzymes involved in lipid metabolism and the tricarboxylic acid cycle in colonic epithelial cells before tumor formation, which was prevented by the supplementation of the NWD with calcium and vitamin D(3) that prevented colon tumor development, demonstrating profound interaction among nutrients. This mouse model of dietary induction of colon cancer recapitulates levels and length of exposure to nutrients linked to relative risk for human sporadic colon cancer, which represents the etiology of >90% of colon cancer in the United States and other Western countries.