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1.
Cancer Sci ; 115(4): 1184-1195, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38297479

ABSTRACT

A significant association exists between the gut microbiome and colorectal carcinogenesis, as well as cancer progression. It has been reported that Escherichia coli (E. coli) containing polyketide synthetase (pks) island contribute to colorectal carcinogenesis by producing colibactin, a polyketide-peptide genotoxin. However, the functions of pks+ E. coli in initiation, proliferation, and metastasis of colorectal cancer (CRC) remain unclear. We investigated the clinical significance of pks+ E. coli to clarify its functions in CRC. This study included 413 patients with CRC. Pks+ E. coli of tumor tissue and normal mucosal tissue were quantified using droplet digital PCR. Pks+ E. coli was more abundant in Stages 0-I tumor tissue than in normal mucosal tissue or in Stages II-IV tumor tissue. High abundance of pks+ E. coli in tumor tissue was significantly associated with shallower tumor depth (hazard ratio [HR] = 5.0, 95% confidence interval [CI] = 2.3-11.3, p < 0.001) and absence of lymph node metastasis (HR = 3.0, 95% CI = 1.8-5.1, p < 0.001) in multivariable logistic analyses. Pks+ E. coli-low and -negative groups were significantly associated with shorter CRC-specific survival (HR = 6.4, 95% CI = 1.7-25.6, p = 0.005) and shorter relapse-free survival (HR = 3.1, 95% CI = 1.3-7.3, p = 0.01) compared to the pks+ E. coli-high group. Pks+ E. coli was abundant in Stages 0-I CRC and associated with CRC prognosis. These results suggest that pks+ E. coli might contribute to carcinogenesis of CRC but might not be associated with tumor progression.


Subject(s)
Colorectal Neoplasms , Polyketides , Humans , Escherichia coli/genetics , Neoplasm Recurrence, Local , Mucous Membrane , Carcinogenesis
2.
Surg Endosc ; 38(10): 5514-5527, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39210057

ABSTRACT

BACKGROUND: A bridge to surgery (BTS) after self-expandable metallic stent (SEMS) placement is a widely recognized treatment strategy for obstructive colorectal cancer. However, there is still a lack of evidence for the efficacy and safety of laparoscopic surgery following SEMS placement. The aim of this systematic review and meta-analysis was to compare the short-term and long-term outcomes of laparoscopic surgery with those of open surgery following SEMS placement in patients with obstructive colorectal cancer. METHODS: An electronic literature search through to December 2022 was performed to identify studies comparing short-term and long-term outcomes between laparoscopic and open surgery following SEMS placement for obstructive colorectal cancer. The main outcome measures were postoperative complication rates and mortality. Secondary outcome measures were the 3-year recurrence-free survival (RFS) and 3-year overall survival (OS) rates. The meta-analysis was performed using fixed-effect or random-effects methods to calculate odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: The meta-analysis included 15 studies and 883 patients, of whom 467 (52.9%) underwent laparoscopic surgery and 416 (47.1%) underwent open surgery following SEMS placement. The postoperative complication rate was significantly lower in the laparoscopic surgery group than in the open surgery group (OR 0.47, 95% CI 0.32-0.67, P < 0.001). There was no significant difference in the 3-year RFS rate or 3-year OS rate between the laparoscopic and open surgery groups (3-year RFS, OR 0.78, 95% CI 0.50-1.24, P = 0.30; 3-year OS, OR 0.68, 95% CI 0.41-1.12, P = 0.13). CONCLUSION: This meta-analysis found that the short-term outcome was better in patients who underwent laparoscopic surgery following SEMS placement than in those who underwent open surgery. Furthermore, there was no significant difference in long-term outcomes between the two groups. Laparoscopic surgery following SEMS placement may be a safe and effective treatment option for obstructive colorectal cancer.


Subject(s)
Colorectal Neoplasms , Intestinal Obstruction , Laparoscopy , Self Expandable Metallic Stents , Humans , Laparoscopy/methods , Colorectal Neoplasms/surgery , Colorectal Neoplasms/complications , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Treatment Outcome , Postoperative Complications/epidemiology , Postoperative Complications/etiology
3.
Surg Today ; 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38598170

ABSTRACT

PURPOSE: Emergency surgery (ES) for complicated appendicitis (CA) is associated with high morbidity. Interval appendectomy (IA) decreases this rate; however, nonoperative management (NOM) is not always successful. Some patients require unplanned ES due to NOM failure (IA failure: IA-F). This study aimed to verify the benefits of IA and to evaluate the risk factors for NOM failure. METHODS: Patients diagnosed with CA who underwent surgery between January 2012 and December 2021 were included in this study. We compared the surgical outcomes of the ES group with those of the IA success (IA-S) and IA-F groups. We also analyzed 14 factors that predicted NOM failure. RESULTS: Among 302 patients, the rate of severe complications (Clavien-Dindo grade ≥ III) was significantly higher in the ES group (N = 165) than in the IA-S group (N = 102). The rates were equal between the ES (N = 165) and IA-F (N = 35) groups. NOM was successful in 110 patients and failed in 27. Lack of abscesses, comorbidities, high WBC count, and free air were independent risk factors for NOM failure. CONCLUSIONS: Considering the benefits of IA and the non-inferior surgical outcomes of IA-F compared to ES, IA is a good therapeutic strategy for CA. However, in patients exhibiting four independent risk factors for NOM failure, careful monitoring of unplanned ES is necessary.

4.
Surg Today ; 54(9): 1093-1103, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38526561

ABSTRACT

PURPOSE: Self-expandable metallic stent (SEMS) placement is widely used as a bridge to surgery (BTS) procedure for obstructive colorectal cancer. However, evidence regarding the optimal interval between SEMS placement and elective surgery is lacking. METHODS: We retrospectively collected data from patients with BTS between January 2013 and October 2021. Inverse probability treatment-weighted propensity score analyses were used to compare short- and long-term outcomes between the short-interval (SI) and long-interval (LI) groups, using a cutoff of 20 days. RESULTS: In total, 138 patients were enrolled in this study (SI group, n = 63; LI group, n = 75). In the matched cohort, the patients' backgrounds were well balanced. The incidence of Clavien-Dindo grade ≥ II postoperative complications was not significantly different between the SI and LI groups (19.0% vs. 14.0%, P = 0.47). There were no significant differences between the SI and LI groups in the 3-year recurrence-free survival (68.0% vs. 76.4%, P = 0.73) or 3-year overall survival rates (86.0% vs. 90.6%, P = 0.72). CONCLUSIONS: A longer interval did not deteriorate the oncological outcomes. Individual perioperative management with an appropriate interval to improve the patient's condition is required to ensure safe surgery.


Subject(s)
Colorectal Neoplasms , Intestinal Obstruction , Postoperative Complications , Humans , Colorectal Neoplasms/surgery , Colorectal Neoplasms/complications , Retrospective Studies , Male , Female , Aged , Intestinal Obstruction/surgery , Intestinal Obstruction/etiology , Time Factors , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Treatment Outcome , Propensity Score , Elective Surgical Procedures/methods , Self Expandable Metallic Stents , Survival Rate , Time-to-Treatment , Stents , Aged, 80 and over
5.
J Vasc Interv Radiol ; 34(8): 1430-1434, 2023 08.
Article in English | MEDLINE | ID: mdl-37127177

ABSTRACT

This study aimed to survey the practice preferences of obstetricians/gynecologists (OB/GYNs) that may be contributing to the underutilization of uterine fibroid embolization (UFE) in the treatment of symptomatic uterine fibroids (SUFs). A 22-question survey was created using the Qualtrics XM software and distributed to an obstetrics/gynecology-specific social media group of resident or attending OB/GYNs practicing in the United States. One hundred twelve responses met the inclusion criteria. For patients with SUFs, UFE was offered as a first-choice option <2% of the time. For patients with SUFs seeking to maintain fertility, UFE was recommended only 1% of the time after medical therapy (54%) and myomectomy (42%). Respondents reported lower rates of confidence (selecting "strongly agree" or "agree") regarding risks and benefits of UFE (77%) in comparison with those of myomectomy (99%) or hysterectomy (100%). Because UFE was seldom recommended by respondents, further, more robust polling of OB/GYNs is warranted.


Subject(s)
Leiomyoma , Uterine Neoplasms , Pregnancy , Female , Humans , Uterine Neoplasms/therapy , Gynecologists , Obstetricians , Leiomyoma/diagnostic imaging , Leiomyoma/therapy , Surveys and Questionnaires
6.
Surg Today ; 53(8): 890-898, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36707435

ABSTRACT

PURPOSE: To investigate a prognostic score for stage II-III colorectal cancer (CRC) based on post-CEA and pT4 levels. METHODS: Two cohorts of stage II-III CRC patients who underwent curative surgery between 2011 and 2017 were included. The prognostic score (T-CEA score) was calculated as follows: T-CEA-0, post-CEA ≤ 5 ng/mL and pT1-3; T-CEA-1, post-CEA > 5 ng/mL or pT4; T-CEA-2, post-CEA > 5 ng/mL and pT4. RESULTS: The T-CEA scores of the 587 patients were as follows: T-CEA-0 (n = 436; 74%), T-CEA-1 (n = 129; 22%), and T-CEA-2 (n = 10; 2%). The 5-year recurrence-free survival (RFS) rates of the T-CEA-0, 1, and 2 groups were 80.3%, 54.8%, and 0%, respectively (P < 0.01), and the 5-year overall survival (OS) rates were 90.9%, 74.2%, and 0%, respectively (T-CEA-0 vs T-CEA-1: P < 0.01, T-CEA-1 vs T-CEA-2: P = 0.04). Multivariate analysis revealed that an elevated T-CEA score of 1 or 2 was a significant risk factor for poor RFS (HR: 2.89, P < 0.01) and OS (HR: 2.85, P < 0.01). CONCLUSION: The T-CEA score is a reliable and convenient prognostic score for stage II-III CRC.


Subject(s)
Carcinoembryonic Antigen , Colorectal Neoplasms , Humans , Prognosis , Retrospective Studies , Colorectal Neoplasms/pathology , Risk Factors
7.
Surg Endosc ; 36(5): 2760-2770, 2022 05.
Article in English | MEDLINE | ID: mdl-35113211

ABSTRACT

BACKGROUND: Preoperative colonic stenting for malignant large bowel obstruction (MLBO), also called bridge to surgery (BTS), is considered a great substitute treatment for emergency resection (ER) in the left-sided colon. However, its efficacy in the right-sided colon remains controversial. This systematic review and meta-analysis aimed to compare the postoperative short-term outcomes between BTS and ER for right-sided MLBO. METHODS: A comprehensive electronic literature search throughout December 2020 was performed to identify studies comparing short-term outcomes between BTS and ER for right-side MLBO. The main outcome measures were postoperative complications and mortality rates. A meta-analysis was performed using a fixed-effect or a random-effect method to calculate odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: Seven studies were included in this meta-analysis, comprising 5136 patients, of whom 1662 (32.4%) underwent BTS and 3474 (67.6%) underwent ER. This meta-analysis demonstrated that BTS resulted in reductions in postoperative complications (OR = 0.78; 95% CI: 0.66-0.92) and mortality (OR = 0.51; 95% CI: 0.28-0.92) than ER. CONCLUSION: The results of this meta-analysis indicate that BTS for right-sided MLBO confers preferable short-term outcomes as well as for left-sided. This suggests that BTS results in a reduction of postoperative complications and mortality for right-sided MLBO than ER.


Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Intestinal Obstruction , Colonic Neoplasms/complications , Colorectal Neoplasms/surgery , Humans , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Postoperative Complications/etiology , Retrospective Studies , Stents/adverse effects , Treatment Outcome
8.
Gan To Kagaku Ryoho ; 49(4): 447-449, 2022 Apr.
Article in Japanese | MEDLINE | ID: mdl-35444131

ABSTRACT

The Japanese gastric cancer clinical practice guideline recommends FOLFOX as one of the first-line chemotherapy for advanced gastric cancer. Since FOLFOX is administered intravenously, it is helpful for patients who have difficulty in oral intake. Herein, we report a patient in which FOLFOX was significantly effective after failure to treatment with S-1 plus CDDP. A 75-year-old gastric cancer patient with paraaortic lymph node metastasis and multiple liver metastases(Stage ⅣB)was treated. Severe stomatitis and impaired consciousness due to dehydration appeared after administration of S-1 plus CDDP. After his general condition recovered, we changed his regimen to FOLFOX. No serious adverse events were observed, and partial response was achieved after 4 courses of treatment. Partial response was maintained until the onset of oxaliplatin drug allergy in the 10th course. FOLFOX is a promising option for patients with difficulties in oral intake.


Subject(s)
Liver Neoplasms , Stomach Neoplasms , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Humans , Liver Neoplasms/secondary , Oxaliplatin/therapeutic use , Stomach Neoplasms/pathology
9.
Gan To Kagaku Ryoho ; 49(8): 893-896, 2022 Aug.
Article in Japanese | MEDLINE | ID: mdl-36046977

ABSTRACT

OBJECTIVE: To examine the potential of peripheral circulating cell-free DNA(cfDNA)as a predictor of response in patients undergoing neoadjuvant chemotherapy(NAC)for advanced colon cancer. METHODS: We compared histological response, background factors, and cfDNA molecular volume changes in cT4 and cT3N+ colon cancer patients. RESULTS: Six of 11 patients responded. The patients with muc and pap histology were non-responders. There was no relationship between CEA or cfDNA levels and response. Responders showed >50% change in DNA integrity index(=cfDNA long fragment/ short fragment ratio), while non-responders showed <50% change(p=0.015). CONCLUSION: Our results suggest that the variability rate in DNA integrity index of peripheral blood cfDNA may be useful in predicting the therapeutic efficacy of colon NAC.


Subject(s)
Cell-Free Nucleic Acids , Colonic Neoplasms , Biomarkers , Biomarkers, Tumor/genetics , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , Colonic Neoplasms/surgery , DNA , Humans , Neoadjuvant Therapy
10.
Gan To Kagaku Ryoho ; 49(5): 593-596, 2022 May.
Article in Japanese | MEDLINE | ID: mdl-35578942

ABSTRACT

Late-stage elderly patients have low tolerance to chemotherapy, and they have difficulties when they are treated with standard chemotherapy. We report a case of a late-stage elderly patient who had a long-term response to UFT/UZEL/bevacizumab( Bev)therapy for lung metastasis after surgery for early-stage colon cancer. He was 82-years-old and underwent laparoscopy-assisted sigmoid colectomy for sigmoid colon cancer at another hospital. The pathological diagnosis was pT1b, ly1, v0, N0, M0, pStage Ⅰ. Six months after the surgery, a small nodule was noted in the middle lobe of the right lung. It grew five months later and was definitely diagnosed as lung metastasis. Considering his physical condition and tumor size, we opted to introduce less invasive chemotherapy instead of standard chemotherapy. UFT/UZEL/Bev was started 14 months after surgery. Although he required dose reduction due to anorexia, he safely continued the treatment with partial response (PR), which was maintained for 2 years and 6 months. While UFT/UZEL/Bev has no convincing evidence, it may be an option for vulnerable patients, especially those with non-life-threatening disease.


Subject(s)
Lung Neoplasms , Sigmoid Neoplasms , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/therapeutic use , Humans , Leucovorin , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Lung Neoplasms/surgery , Male , Sigmoid Neoplasms/drug therapy , Sigmoid Neoplasms/pathology , Sigmoid Neoplasms/surgery , Tegafur , Uracil/therapeutic use
11.
J Surg Oncol ; 123(1): 286-292, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33022767

ABSTRACT

BACKGROUND: Neoadjuvant chemotherapy to treat locally advanced rectal cancer is an effective therapeutic strategy for the prevention of local recurrence and distant organ metastasis after surgery. OBJECTIVES: To assess the prognostic significance of histopathological tumor response in rectal cancer patients undergoing neoadjuvant chemotherapy. METHODS: This study included patients with operable rectal cancer who received neoadjuvant chemotherapy using the FOLFOX regimen (5-fluorouracil, l-leucovorin, and oxaliplatin) in a hospital between February 2012 and November 2017. The main outcome measure was disease-free survival with respect to histopathological response to neoadjuvant chemotherapy in resected specimens. RESULTS: The median follow-up was 32 months. Of 48 patients treated with neoadjuvant FOLFOX, 24 (50%) were classified as responders, which included two patients with pathological complete response and 22 patients with partial response. The remaining 24 patients (50%) were classified as nonresponders. Responders had a significantly better 3-year disease-free survival than nonresponders (86% vs. 62%, p = .02). CONCLUSIONS: Patients whose surgical specimens show a pathological complete response or partial response have good oncologic outcomes.


Subject(s)
Adenocarcinoma/mortality , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/mortality , Rectal Neoplasms/mortality , Adenocarcinoma/drug therapy , Adenocarcinoma/secondary , Adult , Aged , Clinical Trials, Phase II as Topic , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Leucovorin/administration & dosage , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Oxaliplatin/administration & dosage , Prognosis , Prospective Studies , Rectal Neoplasms/drug therapy , Rectal Neoplasms/pathology , Retrospective Studies , Survival Rate
12.
Int J Clin Oncol ; 25(12): 2075-2082, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32785799

ABSTRACT

BACKGROUND: Chemotherapy with oxaliplatin is known to induce sinusoidal obstruction syndrome (SOS). In a previous single-center study, we reported that oxaliplatin-induced increase in splenic volume (SV) is strongly indicative of SOS, and that this increase in SV persisted for > 1 year after completing chemotherapy. The aim of this study was to confirm the oxaliplatin-induced SV change in a multicenter study in patients with stage III colon cancer in Japan. METHODS: We enrolled 59 patients who underwent curative resection for stage III colon cancer in the FACOS study in a phase II multi-center clinical study. Participants received mFOLFOX6 or CAPOX as adjuvant chemotherapy. SV change was assessed three times by computed tomographic volumetry: before surgery, on completion of adjuvant chemotherapy, and 1 year after completing adjuvant chemotherapy. RESULTS: SV on completing and 1 year after chemotherapy was significantly higher than that before surgery (P < 0.001). Oxaliplatin-induced SOS persisted for > 1 year after the completion of adjuvant chemotherapy in half of the patients. There was no difference in 3-year disease-free survival with respect to the presence or absence of increased SV. An increase in SV was observed in 72% of patients treated with mFOLFOX6 and 94% of patients treated with CAPOX (P = 0.13). CONCLUSION: This study can be verified the findings observed in our previous single-center study, oxaliplatin-based adjuvant chemotherapy was associated with an increase in SV. Furthermore, this increase can persist for > 1 year. The continuous presence of SOS may have a negative impact on prognosis in patients that develop recurrent disease.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Colonic Neoplasms/drug therapy , Oxaliplatin/adverse effects , Splenic Diseases/chemically induced , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant/adverse effects , Colonic Neoplasms/mortality , Colonic Neoplasms/pathology , Disease-Free Survival , Female , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Humans , Japan , Leucovorin/adverse effects , Leucovorin/therapeutic use , Male , Middle Aged , Organoplatinum Compounds/adverse effects , Organoplatinum Compounds/therapeutic use , Oxaliplatin/administration & dosage , Prognosis , Splenic Diseases/diagnostic imaging
13.
Int J Clin Oncol ; 25(8): 1523-1532, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32394048

ABSTRACT

Oncogenic RAS mutations are negative biomarkers of response to epidermal growth factor receptor (EGFR) blockade. RAS mutations are usually detected in biopsies of primary colorectal tumors. However, the genomic profiles of primary tumors and metastases are not always concordant, and chemotherapeutic agents can alter the tumor molecular landscape. Cell-free DNA (cfDNA) is a novel tool to detect molecular heterogeneity. This study evaluated the clinical utility of cfDNA to predict primary or secondary resistance to EGFR blockade in patients with metastatic colorectal cancer. Thirty metastatic colorectal cancer patients without RAS and BRAF mutations were prospectively enrolled and treated with cytotoxic agents and EGFR blockade as first-line therapy. cfDNA was analyzed for the presence of RAS, BRAF, and EGFR (S492R) point mutations before initiating chemotherapy and every 2 months during chemotherapy. The analysis was performed in 223 plasma samples from all 30 patients. Of the 30 patients, five had RAS mutations in their cfDNA before starting chemotherapy and did not respond. Twenty-four of the remaining 25 patients without cfDNA RAS mutations had a response. Twenty of the 24 responders developed secondary resistance and cfDNA RAS mutations were found in 17 of the 20. cfDNA BRAF mutations were found in seven, and EGFR mutations were found in eight of the 20 patients. Emerging RAS, BRAF, and EGFR mutations occurred in patients with primary and secondary resistance to EGFR blockade. The detection of these mutations in cfDNA is a promising approach to predict treatment response and secondary resistance.


Subject(s)
Colorectal Neoplasms/drug therapy , Drug Resistance, Neoplasm/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cell-Free Nucleic Acids/genetics , Cetuximab/administration & dosage , Colorectal Neoplasms/genetics , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Drug Resistance, Neoplasm/drug effects , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Female , Fluorouracil/therapeutic use , Humans , Leucovorin/therapeutic use , Male , Middle Aged , Mutation , Organoplatinum Compounds/therapeutic use , Panitumumab/administration & dosage , Pilot Projects , Treatment Outcome
14.
Gan To Kagaku Ryoho ; 47(13): 2006-2008, 2020 Dec.
Article in Japanese | MEDLINE | ID: mdl-33468782

ABSTRACT

A woman in her 60s underwent lower endoscopy due to a positive fecal occult blood test. A type 2 tumor was found in the cecum, and a biopsy resulted in the diagnosis of adenocarcinoma(tub2). Contrast-enhanced CT showed an enlarged paracolonic lymph node but no distant metastasis, so the patient underwent a laparoscopic-assisted ileocolic resection and D3 lymph node dissection for cecum cancer. The pathology was pT3, pN2b, pM0, pStage Ⅲc, and 12 courses of FOLFOX were administered as adjuvant chemotherapy. Twenty-four months after the completion of adjuvant chemotherapy, an elevated CEA was observed, and a PET-CT was performed, which showed multiple peritoneal disseminated nodules with FDG accumulation. Based on this finding, CAPOX/bevacizumab therapy was introduced, and on completion of 4 courses, the PET-CT showed a decrease in the size of the nodules and the disappearance of FDG accumulation. Based on this, the patient underwent resection. A peritoneal dissemination resection and bilateral ovariectomy were laparoscopically performed, and the patient is currently under observation. In patients with metastatic recurrence of peritoneal dissemination who underwent complete resection, treatment with CAPOX/bevacizumab may allow for disease control and provide a long-term prognosis.


Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/therapeutic use , Colonic Neoplasms/surgery , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/surgery , Female , Humans , Lymph Node Excision , Positron Emission Tomography Computed Tomography
15.
Cancer Sci ; 110(11): 3497-3509, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31465598

ABSTRACT

We recruited 56 colorectal cancer patients and compared the mutational spectrum of tumor tissue DNA, circulating cell-free DNA (ccfDNA) and circulating tumor cell (CTC) DNA (ctcDNA) to evaluate the potential of liquid biopsy to detect heterogeneity of cancer. Tumor tissue DNA, ccfDNA, and ctcDNA were extracted from each patient and analyzed using next-generation sequencing (NGS) and digital PCR. To maximize yields of CTC, three antibodies were used in the capture process. From 34 untreated patients, 53 mutations were detected in tumor tissue DNA using NGS. Forty-seven mutations were detected in ccfDNA, including 20 not detected in tissues. Sixteen mutations were detected in ctcDNA, including five not detected in tissues. In 12 patients (35.3%), mutations not found in tumor tissues were detected by liquid biopsy: nine (26.5%) in ccfDNA only and three (8.8%) in ctcDNA only. Combination analysis of the two liquid biopsy samples increased the sensitivity to detect heterogeneity. From 22 stage IV patients with RAS mutations in their primary tumors, RAS mutations were detected in 14 (63.6%) ccfDNA and in eight (36.4%) ctcDNA using digital PCR. Mutations not detected in primary tumors can be identified in ccfDNA and in ctcDNA, indicating the potential of liquid biopsy in complementing gene analysis. Combination analysis improves sensitivity. Sensitivity to detect cancer-specific mutations is higher in ccfDNA compared with ctcDNA.


Subject(s)
Cell-Free Nucleic Acids/analysis , Colorectal Neoplasms/genetics , DNA, Neoplasm/analysis , Mutation , Neoplastic Cells, Circulating/chemistry , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/pathology , DNA Mutational Analysis , Female , High-Throughput Nucleotide Sequencing , Humans , Liquid Biopsy , Male , Middle Aged , Polymerase Chain Reaction , Prospective Studies , Proto-Oncogene Proteins p21(ras)/genetics
16.
Digestion ; 99(1): 39-45, 2019.
Article in English | MEDLINE | ID: mdl-30554222

ABSTRACT

BACKGROUND: Liquid biopsy is a collective term that refers to the analysis of tumor-derived biomarkers isolated from biological fluids of cancer patients. Recently, many authors reported the usefulness of liquid biopsy for the management of malignancy. Summary and Key Messages: The peripheral blood of cancer patients is a pool of cells and/or cell products derived from the primary or metastatic tumor, including circulating tumor cells (CTCs), circulating free (cf) DNA or RNA, and exosomes containing proteins, nucleic acids, and lipids. CTCs are tumor cells that can be isolated from peripheral blood. Free circulating DNA with a tumor-specific mutation is called circulating tumor DNA (ctDNA). Some patients who undergo curative surgery experience recurrent disease, which can be due to the presence of minimal residual disease (MRD). Thus, MRD indicates a high risk of relapse. Detection of ctDNA or CTC after surgery is a direct proof of MRD. Molecular volume (e.g., the number of CTCs and level of ctDNA) might reflect tumor burden, thus high molecular volume may indicate poor prognosis. The most notable application of liquid biopsy in cancer is to understand spatial and temporal heterogeneities. Heterogeneity is one of the causes of refractoriness and hampers prediction of chemotherapeutic effect. Emerging mutations that are not present in primary tumors but are found in their metastases can be detected in ctDNA. Some colorectal cancer patients with wild-type RAS do not respond to epidermal growth factor receptor blockade. In a subset of these patients, RAS mutation is detected in ctDNA, indicating heterogeneity.


Subject(s)
Colorectal Neoplasms/blood , Colorectal Neoplasms/pathology , Liquid Biopsy/methods , Neoplasm, Residual/diagnosis , Neoplastic Cells, Circulating/metabolism , Biomarkers, Tumor/blood , Colectomy , Colorectal Neoplasms/surgery , DNA, Neoplasm/blood , Humans
17.
Ann Surg Oncol ; 25(3): 737-744, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29235008

ABSTRACT

BACKGROUND: The self-expanding metallic stent (SEMS) provides effective decompression for patients with malignant large bowel obstruction (MLBO); however, mechanical damage to malignant cells from insertion may negatively affect prognosis, similar to surgical manipulation, and its oncological safety is unclear. We examined mechanical damage from SEMS placement using circulating cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA). METHODS: Between 1 November 2014 and 30 June 2017, 35 MLBO patients were analyzed, comprising 25 SEMS patients and 10 transanal decompression tube (TDT) patients (control). Blood samples were collected before and after decompression on days 0, 1, 3, and 7. cfDNA, ctDNA, white blood cells, C-reactive protein, and lactate dehydrogenase were analyzed. RESULTS: The clinical success rates of SEMS and TDT were 88 and 90%, respectively (p = 1.0). The cfDNA concentration on day 7 was significantly higher in the SEMS group than in the TDT group (992 vs. 308 ng/mL; p = 0.005). A significant increase in ctDNA was observed in the SEMS group compared with the TDT group (83% vs. 22%; p = 0.002). The cfDNA concentration showed strong positive correlations with ctDNA and lactate dehydrogenase (R 2 = 0.838 and 0.593, respectively), and a weak positive correlation with C-reactive protein (R 2 = 0.263). CONCLUSIONS: Despite equivalent clinical success rates, SEMS placement increased plasma levels of cfDNA and ctDNA by tumor manipulation, but TDT did not. Colonic stenting showed oncological risk in terms of molecular analysis.


Subject(s)
Cell-Free Nucleic Acids/genetics , Circulating Tumor DNA/genetics , Colorectal Neoplasms/complications , Decompression, Surgical , Intestinal Obstruction/blood , Postoperative Complications/blood , Self Expandable Metallic Stents/adverse effects , Aged , Aged, 80 and over , Cell-Free Nucleic Acids/blood , Circulating Tumor DNA/blood , Female , Follow-Up Studies , Humans , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Male , Postoperative Complications/etiology , Prognosis , Prospective Studies , Treatment Outcome
18.
BMC Gastroenterol ; 18(1): 117, 2018 Jul 17.
Article in English | MEDLINE | ID: mdl-30016941

ABSTRACT

BACKGROUND: Anastomotic leakage (AL) is the most serious and common complication of surgery for rectal cancer, and associated risk factors remain unknown despite developments in laparoscopic surgery. The present study aimed to determine risk factors for AL after laparoscopic anterior resection (AR) of rectal cancer. METHODS: This retrospective cohort study extracted information from a prospective database of all consecutive colorectal resections that proceeded at Nippon Medical School Hospital between January 2011 and December 2015 (n = 865). We identified 154 patients with rectal cancer treated by elective laparoscopic AR with anastomosis using primary double-stapling. Clinical variables and comorbidity, habits, and surgery-related variables were assessed by univariate and multivariate analyses to determine preoperative risk factors for clinical AL. RESULTS: The overall rate of clinical AL was 11.7% (18 of 154 patients), and 5 (27.8%) of 18 patients required revised laparotomy. Data from males were analyzed because AL occurred only in males. Univariate analysis of male patients (n = 100) significantly associated preoperative creatinine values (p = 0.03) and a history of ischemic heart disease (IHD) (p = 0.012) with AL. The frequency of AL tended to increase (p = 0.06) when patients had low AR (p = 0.06) and transanal drainage. Having AL significantly prolonged hospital stays compared with patients without leakage (36.2 vs. 11.1 days; p <  0.01). Multivariate analysis identified a history of IHD (odds ratio [OR], 4.73; 95% confidence interval [CI], 1.27-17.5; p = 0.025] as an independent risk factor for AL. CONCLUSIONS: Male sex and a history of IHD are possible risk factors for AL after elective laparoscopic rectal cancer surgery.


Subject(s)
Anastomotic Leak/etiology , Laparoscopy/adverse effects , Myocardial Ischemia/complications , Rectal Neoplasms/complications , Rectal Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Anastomosis, Surgical/adverse effects , Creatinine/blood , Female , Humans , Length of Stay , Male , Middle Aged , Preoperative Period , Rectal Neoplasms/pathology , Retrospective Studies , Risk Factors , Sex Factors
19.
J Surg Oncol ; 116(7): 947-953, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28876454

ABSTRACT

BACKGROUND AND OBJECTIVES: Oxaliplatin can cause hepatic sinusoidal obstruction syndrome (SOS). SOS can cause chemotherapy-related adverse effects or morbidity after liver resection. Conventionally, SOS is diagnosed using liver biopsy. Recently, it was reported that increased splenic volume (SV) can be used to detect SOS. In this study, we evaluated the changes in SV during adjuvant chemotherapy. METHODS: We enrolled 103 consecutive patients with stage III and high-risk stage II colorectal cancer treated with mFOLFOX6 (n = 37) or oral fluorouracil and leucovorin (n = 66) after curative surgery. SV was measured three times; pre-operatively, after chemotherapy, and 1 year after chemotherapy. RESULTS: SV was higher after mFOLFOX6 (median 135.89 mL) than pre-operatively (105.75 mL) (P < 0.001); SV at 1-year after finishing mFOLFOX6 (114.16 mL) returned to the same level as before surgery (P = 0.0015). SV increased in 28 patients (75.7%) treated with mFOLFOX6 (95%CI, 61.8-89.5), but had not recovered in 12 of these cases (42.9%) 1 year after finishing treatment (95%CI, 17.3-47.5). In contrast, oral fluorouracil and leucovorin did not change SV. CONCLUSIONS: SV increased after adjuvant mFOLFOX6, and had not recovered in almost half of cases 1-year after finishing chemotherapy. This increase may indicate continuous SOS, which can adversely affect treatment after recurrence.


Subject(s)
Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/surgery , Hepatic Veno-Occlusive Disease/chemically induced , Organoplatinum Compounds/adverse effects , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Middle Aged , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Retrospective Studies
20.
Surg Today ; 47(7): 865-871, 2017 Jul.
Article in English | MEDLINE | ID: mdl-27873059

ABSTRACT

PURPOSE: Daikenchuto (DKT) has a stimulant effect on intestinal motility and reportedly has a positive effect on postoperative intestinal motility in patients with sigmoid colon cancer. In this study, we investigated the effects of DKT in patients with right-side colon cancer. METHODS: This retrospective study included 88 patients with right-side colon cancer. We orally administered 7.5 g of DKT in the DKT group and did not administer any DKT to patients in the no-DKT group. All patients ingested radiopaque markers 2 h before surgery, which were used to assess intestinal motility. The postoperative intestinal motility was radiologically assessed by counting the numbers of residual markers in the large and small intestines. RESULTS: The DKT and no-DKT groups showed no marked differences in the total number of residual markers or number of residual markers in the small intestine. However, in the elderly subgroup, the total number of residual markers in the DKT group was significantly less than in the no-DKT group. CONCLUSION: Although DKT had some small effect on the postoperative intestinal motility for most patients, it may have positive effects in elderly patients.


Subject(s)
Colonic Neoplasms/physiopathology , Colonic Neoplasms/surgery , Gastrointestinal Motility , Ileus/prevention & control , Phytotherapy , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Postoperative Complications/prevention & control , Administration, Oral , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Panax , Perioperative Care , Postoperative Period , Retrospective Studies , Zanthoxylum , Zingiberaceae
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