A Multicenter Analysis of Short-term and Long-term Outcomes Following Laparoscopic Multivisceral Resection for Advanced Colorectal Cancer.

Background/Aim: Recent research has demonstrated that laparoscopic multivisceral resection (MVR) for advanced colorectal cancer is safe, practicable, and yields satisfactory oncological results, which is in line with the growing usage of laparoscopic surgery. The effectiveness of laparoscopic MVR is still debatable, though. The goal of this study was to compare the short- and long-term results of patients with advanced colorectal cancer treated with open MVR with laparoscopic procedures. Patients and Methods: Data on 3,571 consecutive patients hospitalized at the Kyushu University National Kyushu Cancer Center for colorectal cancer surgery between 2004 and 2020 were gathered retrospectively. In the end, 84 individuals with advanced colorectal cancer who had a colectomy with MVR were examined. We evaluated invasiveness in terms of complications, blood loss, and operating time. Recurrence-free survival rates and overall 5-year survival were among the oncological outcomes. Results: Of the 84 patients examined, 29 underwent laparoscopic treatment, and 55 underwent open treatment. The laparoscopic surgery group experienced shorter hospital stays (15 vs. 18 days, p<0.05) and much less blood loss (median volume: 167 vs. 1,058 g, p<0.005) than the open surgery group. Following the exclusion of patients with stage IV colorectal cancer from the study (groups undergoing laparoscopic surgery, n=25; open surgery, n=38), the groups displayed comparable pathologic results and no discernible variations in either the 5-year overall survival (p=0.87) or recurrence-free survival (p=0.86). Conclusion: In certain individuals with advanced colorectal cancer, a laparoscopic method of manipulation with MVR may be less invasive than an open method without compromising the prognosis.

Lineage of drug discovery research on fluorinated pyrimidines: chronicle of the achievements accomplished by Professor Setsuro Fujii.

Prof. Setsuro Fujii achieved significant results in the field of drug discovery research in Japan. He developed nine well-known drugs: FT, UFT, S-1 and FTD/TPI are anticancer drugs, while cetraxate hydrochloride, camostat mesilate, nafamostat mesilate, gabexate mesilate and pravastatin sodium are therapeutic drugs for various other diseases. He delivered hope to patients with various diseases across the world to improve their condition. Even now, drug discovery research based on Dr. Fujii's ideas is continuing.

Prognostic Significance of Preoperative Nutritional Assessment in Elderly Patients who Underwent Laparoscopic Gastrectomy for Stage I-III Gastric Cancer.

BACKGROUND/AIM: Surgery for elderly patients with gastric cancer is becoming more common. However, the risk factors of the laparoscopic surgery for these patients are unknown, and thus it is difficult to determine appropriate treatments for such patients. The aim of this retrospective study was to clarify the risk factors for the treatment outcomes after laparoscopic gastrectomy in elderly patients. PATIENTS AND METHODS: Two hundred twenty-two patients who underwent laparoscopic gastrectomy for primary gastric cancer between January 2014 and December 2017 were enrolled. Clinical characteristics and short- and long-term prognoses were analyzed in 47 patients aged 75 years or older (elderly group) and in 175 patients who were under 75 years old (non-elderly group). RESULTS: The presence of comorbidities was more common in the elderly group than in the non-elderly group (91.5% vs. 61.7%, p<0.0001). The rate of postoperative complications in the elderly group was significantly higher than that in the non-elderly group (42.6% vs. 22.9%, p=0.01). The 5-year overall survival rate was significantly lower in the elderly group than in the non-elderly group (66.9% vs. 92.2%; p<0.0001). In the elderly group, 5-year overall survival in patients with a low preoperative prognostic nutritional index (PNI) was significantly worse than that in patients with a high preoperative PNI (25.0% vs. 80.9%; p<0.05). Multivariate analysis showed that the PNI value was independently associated with overall survival in elderly patients who underwent laparoscopic gastrectomy (p<0.05). In particular, the rate of non-cancer deaths after surgery in elderly patients was significantly higher than that in non-elderly patients (p<0.05). CONCLUSION: PNI value is an independent prognostic factor for overall survival in elderly patients who have undergone laparoscopic gastrectomy for gastric cancer; therefore, in elderly patients with low preoperative PNI, attention should be paid not only to recurrence of cancer, but also to the deterioration of general condition caused by malnutrition.

Influence of Robotic Rectal Resection Versus Laparoscopic Rectal Resection on Postoperative Ileus: A Single-center Experience.

AIM: This study was performed to clarify the relationship between robotic rectal resection and postoperative ileus (POI) by comparing robotic surgery with laparoscopic surgery. MATERIALS AND METHODS: We retrospectively reviewed 238 patients who underwent robotic (n=41) or laparoscopic (n=197) rectal resection for rectal cancer in our institution from January 2013 to June 2020. First, we compared the background factors and short-term surgical outcomes between robotic and laparoscopic surgery. Next, we investigated the postoperative complications of robotic and laparoscopic rectal resection. Finally, we identified the risk factors for POI following rectal cancer resection. RESULTS: The percentages of patients with an Rb tumor location, treatment by abdominoperitoneal resection/intersphincteric resection/low anterior resection, a temporary diverting ileostomy, and a long operation time were significantly higher in robotic than laparoscopic surgery ( P <0.0001, P =0.0002, P =0.0078, and P =0.0001, respectively). There was no significant difference in any individual postoperative complication between robotic and laparoscopic surgery. Risk factors for POI were male sex ( P =0.0078), neoadjuvant chemoradiotherapy ( P =0.0007), an Rb tumor location ( P =0.0005), treatment by abdominoperitoneal resection/intersphincteric resection/low anterior resection ( P =0.0044), a temporary diverting ileostomy ( P <0.0001), and operation time of ≥240 minutes ( P =0.0024). Notably, robotic surgery was not a risk factor for POI following rectal resection relative to laparoscopic surgery. CONCLUSION: Although patients who underwent robotic surgery had more risk factors for POI, the risk of POI was similar between robotic and laparoscopic rectal resection.

CD44v3,8-10 is essential for Slug-dependent vimentin gene expression to acquire TGF-ß1-induced tumor cell motility.

CD44 is a widely expressed polymorphic adhesion molecule that has pleiotropic functions in development and tumor progression. Its mRNA undergoes alternative splicing to generate multiple variant (CD44v) isoforms, although the function of each CD44v isoform is not fully elucidated. Here, we show that CD44v plays an important role in the induction of vimentin expression upon transforming growth factor-ß1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT). Among multiple CD44v isoforms expressed in NUGC3 gastric cancer cells, CD44v8-10 and CD44v3,8-10 are involved in the acquisition of migratory and invasive properties associated with TGF-ß1-induced EMT, and only CD44v3,8-10 induces the transcription of vimentin mediated by the EMT transcription factor Slug. In primary tumor specimens obtained from patients with gastric cancer, CD44-containing variant exon 9 (CD44v9) expression and EMT features [E-cadherin(-)vimentin(+)] were significantly correlated, and EMT features in the cells expressing CD44v9 were associated with tumor invasion depth, lymph node metastasis, and pStage, which indicate invasive and metastatic properties, and poor prognosis. These results indicate that certain CD44v isoforms promote tumor cell motility and metastasis in gastric cancer in association with EMT features, and CD44v3,8-10 may contribute to these clinical characteristics.

Clinical impact of the triple-layered circular stapler for reducing the anastomotic leakage in rectal cancer surgery: Porcine model and multicenter retrospective cohort analysis.

Aim: To investigate the impact of the triple-layered circular stapler compared with the double-layered circular stapler on anastomotic leakage after rectal cancer surgery. Methods: The bursting pressure was compared between porcine ileocolic anastomoses created using a double- or triple-layered stapler. We also retrospectively analyzed the incidence of severe anastomotic leakage in 194 patients who underwent colorectal anastomosis using a double- or triple-layered circular stapler during rectal cancer resection performed in two cancer centers between January 2015 and April 2021. Results: In the porcine model, the bursting pressure was higher in anastomoses created using the triple-layered stapler than the double-layered stapler (end-to-end anastomosis: 26.4 ± 6.2 mm Hg vs 14.5 ± 4.3 mm Hg, P = .0031; side-to-side anastomosis: 27.7 ± 5.0 mm Hg vs 18.0 ± 2.9 mm Hg, P = .0275). Intersectional leakage occurred in 41% and 83% of anastomoses created using the triple- or double-layered stapler, respectively (P = .0821). In the clinical cohort, the double- and triple-layered stapler was used in 153 and 41 patients, respectively. The incidence of anastomotic leakage was lower for anastomoses created using the triple-layered stapler vs the double-layered stapler (0.0% vs 5.8%, P = .0362). In multivariate analysis, the factors independently associated with a lower incidence of anastomotic leakage were female sex (odds ratio: 0.16, 95% confidence interval: 0.01-0.90, P = .0354) and triple-layered stapler usage (odds ratio: 0.00, 95% confidence interval: 0.00-0.96, P = .0465). Conclusion: Anastomoses created using a triple-layered circular stapler had high bursting pressure, which might contribute to a lower incidence of anastomotic leakage after rectal cancer surgery.

Indications for conversion hepatectomy for initially unresectable colorectal cancer with liver metastasis.

PURPOSE: Selected patients with initially unresectable colorectal cancer (CRC) and liver metastases undergo conversion surgery after appropriate chemotherapy. The prognosis of these patients is good, with some even cured of the disease. This retrospective, single-institution study analyzes the clinical importance of patient characteristics on the outcomes of conversion hepatectomy. METHODS: We evaluated 229 consecutive patients with initially unresectable CRC and liver metastasis, who underwent systemic chemotherapy. The patients were assigned to groups depending on conversion hepatectomy. RESULTS: Conversion hepatectomy was performed in 30 patients (13.1%). The proportion of patients with extrahepatic metastasis was significantly lower in the conversion group than in the unresectable group (30.0 vs. 66.8%; P < 0.01). The rate of left-sided primary colorectal tumors was significantly higher in the conversion group than in the unresectable group (96.7 vs. 65.8%; P < 0.01). Multivariate analyses identified that left-sided tumors, no extrahepatic metastasis, H1 or H2 grade CLM, and treatment with molecular-targeted agents were associated with conversion hepatectomy (odds ratios: 16.314, 4.216, 7.631, and 4.070; P < 0.01). Overall survival was significantly longer in the conversion group than in the unresectable group (MST: 50.0 versus 14.7 months; P < 0.01). CONCLUSION: Left-sided primary tumors, absence of extrahepatic metastases, H1 or H2 grade, and use of molecular-targeted agents were associated with successful conversion hepatectomy; thus, patients with these characteristics may be candidates for conversion therapy.

Health-related quality of life after esophagectomy in patients with esophageal cancer.

Esophageal cancer is one of the malignant tumors with the poorest prognosis. Esophagectomy, which is the mainstay of curative-intent treatments, imposes excessive surgical stress on the patients, and postoperative morbidity and mortality rates after esophagectomy remain high. On the other hand, the number of survivors after esophagectomy for esophageal cancer is increasing due to recent improvements in surgical techniques and multidisciplinary treatments for this cancer. However, esophagectomy still has a great influence on the fundamental aspect of patients' lives, that is, the health-related quality of life (HR-QOL), including their physical, emotional, and social functions in the short- and long-term postoperatively. HR-QOL is a multifactorial concept used to assess the symptoms and functional changes caused by the disease itself and treatments from the patients' perspectives. Therefore, assessing the HR-QOL of patients with esophageal cancer after esophagectomy is becoming increasingly important. However, the status of HR-QOL changes after esophagectomy has not been satisfactorily evaluated, and there is no worldwide consensus as to how the postoperative HR-QOL can be improved. This review aimed to raise awareness of healthcare providers, such as surgeons and nurses, on the importance of HR-QOL in patients with esophageal cancer after curative-intent esophagectomy by providing multifaceted information concerning the short- and long-term HR-QOLs, including the status of changes and the determinants of HR-QOL after esophagectomy, and furthermore, essential points for improvement of HR-QOL after esophagectomy.

[The Efficacy of topo â -pS10 Expression in Gastric Cancer as a Predictive Biomarker for Irinotecan Use].

BACKGROUND: Though irinotecan is commonly used for treating advanced gastric cancer, there is no predictive biomarker to date. We have studied the resistant mechanism for irinotecan and found that phosphorylation of serine 10 residue of topoisomerase Ⅰ(topo Ⅰ)is an important step for irinotecan resistance. We have developed an immunohistochemical staining-based biomarker; topo Ⅰ-pS10, for predicting irinotecan efficacy. PURPOSE: The purpose of this study is to test the accuracy of topo Ⅰ-pS10 immunohistochemical staining in gastric cancer clinical samples. METHODS: In this study we performed 2 sets of tests. In the training set, we stained 79 gastric cancer clinical samples which efficacy of irinotecan was measured by succinate dehydrogenase inhibition(SDI)test. In the validation set, we used 27 gastric cancer clinical samples which irinotecan was used and the efficacy was known. RESULTS: Training set: From the ROC curve the cut-off point was set at 35% positive nuclei. Sixty three cases were positive with topo Ⅰ-pS10 in the nuclei. With the result of irinotecan SDI, the sensitivity was 76.6% and the positive predictive value was 92.5%. This result showed that topo Ⅰ-pS10 positive case does not respond to irinotecan. Validation set: In this set, the sensitivity was 82.4% and the positive predictive value was 82.4%. CONCLUSION: topo Ⅰ-pS10 staining can be used as a predictive biomarker for irinotecan for gastric cancer patients.

Monitoring FTD in the peripheral blood mononuclear cells of elderly patients with metastatic colorectal cancer administered FTD plus bevacizumab as first-line treatment.

Trifluridine/tipiracil (FTD/TPI) is an orally administrated anticancer drug with efficacy validated for patients with metastatic colorectal cancer (mCRC) or gastric cancer. FTD, a key component of FTD/TPI, exerts antitumor effects via its incorporation into DNA. Using specific antibodies against bromodeoxyuridine, FTD incorporation into DNA is detected in tumors and peripheral blood mononuclear cells (PBMC) of patients with mCRC who are administered FTD/TPI. The proportion of FTD-positive PBMC fluctuates according to the schedule of treatment, although the association between the proportion of FTD-positive PBMC and the clinical outcomes of patients is unknown. To answer this question, here we monitored the FTD-positive PBMC of 39 elderly patients with mCRC enrolled in KSCC1602, a single-arm phase 2 trial of FTD/TPI plus bevacizumab as a first-line treatment, for 1 month, during the first cycle of treatment. The median values and interquartile ranges of the percentage of FTD-positive PBMC on days 8, 15, and 29 were 39.3% (30.7%-52.2%), 66.9% (40.0%-75.3%), and 13.5% (5.7%-26.0%), respectively. Receiver operating characteristic analysis revealed that the percentage of FTD-positive PBMC on day 8 (the end of the first week of treatment) had moderate ability to accurately diagnose the occurrence of severe neutropenia and leukopenia within 1 month (area under the curve = 0.778 [95% confidence interval, 0.554-0.993]). This result suggests that excess FTD incorporation into PBMC at the initial phase of FTD/TPI plus bevacizumab treatment is a risk factor for early onset of severe hematological adverse events.

Cytolytic activity score as a biomarker for antitumor immunity and clinical outcome in patients with gastric cancer.

BACKGROUND: A simple measure of immune cytolytic activity (CYT) base on mRNA expression levels of two genes, GZMA and PRF1, was recently reported. Here, we aimed to evaluate the CYT score's potential as a measure of antitumor immunity and predictor of clinical outcome in gastric cancer (GC) patients. MATERIALS AND METHODS: We evaluated the correlations between tumor-infiltrating immune cells and the CYT score in 238 GC samples from The Cancer Genome Atlas (TCGA). Next, we investigated CYT score associations with molecular subtypes, somatic mutation load, and immune checkpoint molecules in GC samples from TCGA and Asian Cancer Research Group (ACRG). Moreover, we evaluated the clinical significance of the CYT score calculated by reverse transcription (RT)-quantitative PCR (qPCR) data in 123 GC samples and the association of the CYT score with the response to anti-PD-1 therapy in 7 GC samples from Kyushu University Hospital. RESULTS: The CYT score positively correlated with the proportions of tumor-infiltrating CD8+ T cells and macrophages and negatively correlated with the proportion of regulatory T cells in GC tissues. A high CYT score was associated with common immune checkpoint molecules, a high mutation, the Epstein-Barr virus subtype, and the microsatellite instability subtype in GC. Moreover, a low CYT score was a poor prognosis factor in patients with GC. Finally, the CYT score was higher in a responder to anti-PD-1 therapy compared to nonresponders. CONCLUSION: The CYT score reflects antitumor immunity and predicts clinical outcome in GC patients.

Quadruple gastrointestinal cancer with discordance of mismatch repair protein deficiency and microsatellite instability suggesting Lynch syndrome.

A 65-year-old woman with prior personal and family histories of cancer was admitted to our hospital for quadruple cancer. Preoperative endoscopy revealed a type 0-II gastric cancer (GC; gastric body), advanced type-II colon cancer (ascending colon), and early-stage recto-sigmoid colon cancers. We diagnosed her with Lynch syndrome (LS) per Amsterdam criteria, and performed distal gastrectomy, ileocecal resection and high anterior resection. Her pathological diagnoses were GC: well-to-poorly differentiated adenocarcinoma (AD, por2 > tub2) with signet-ring cells, ypT1b SM2; ascending colon cancer: AD with focal mucin products (tub2 > muc), SS; sigmoid colon cancer: AD (tub1), M; recto-sigmoid cancer: AD (tub1 > tub2), SM. Immunohistochemical tests revealed that all cancers lacked the MLH1/PMS2 protein. However, the three colon cancers were found to have high microsatellite instability (MSI); the GC was microsatellite stable (MSS). No recurrence or other cancers were observed for 30 months after surgery without adjuvant chemotherapy. As patients with LS may also develop MSS cancers, we should check for MSI in all LS cancers for proper treatment.

Radiomics Texture Analysis for the Identification of Colorectal Liver Metastases Sensitive to First-Line Oxaliplatin-Based Chemotherapy.

OBJECTIVE: The aim of this study was to develop a radiomics-based prediction model for the response of colorectal liver metastases to oxaliplatin-based chemotherapy. METHODS: Forty-two consecutive patients treated with oxaliplatin-based first-line chemotherapy for colorectal liver metastasis at our institution from August 2013 to October 2019 were enrolled in this retrospective study. Overall, 126 liver metastases were chronologically divided into the training (n = 94) and validation (n = 32) cohorts. Regions of interest were manually segmented, and the best response to chemotherapy was decided based on Response Evaluation Criteria in Solid Tumors (RECIST). Patients who achieved clinical complete and partial response according to RECIST were defined as good responders. Radiomics features were extracted from the pretreatment enhanced computed tomography scans, and a radiomics score was calculated using the least absolute shrinkage and selection operator regression model in a trial cohort. RESULTS: The radiomics score significantly discriminated good responders in both the trial (area under the curve [AUC] 0.8512, 95% confidence interval [CI] 0.7719-0.9305; p < 0.0001) and validation (AUC 0.7792, 95% CI 0.6176-0.9407; p < 0.0001) cohorts. Multivariate analysis revealed that high radiomics scores greater than - 0.06 (odds ratio [OR] 23.803, 95% CI 8.432-80.432; p < 0.0001), clinical non-T4 (OR 6.054, 95% CI 2.164-18.394; p = 0.0005), and metachronous disease (OR 11.787, 95% CI 2.333-70.833; p = 0.0025) were independently associated with good response. CONCLUSIONS: Radiomics signatures may be a potential biomarker for the early prediction of chemosensitivity in colorectal liver metastases. This approach may support the treatment strategy for colorectal liver metastasis.

Indications for laparoscopic surgery for older rectal cancer patients with comorbidities.

PURPOSE: Given the lack of safety studies concerning laparoscopic surgery for rectal cancer in patients ≥ 80 years old with comorbidities, we sought to investigate this in the current study. METHODS: Between 2012 and 2019, 24 patients ≥ 80 years old underwent laparoscopic surgery for rectal cancer without preoperative treatment. These patients were divided into those with [comorbidity(+) group, n = 13] and without [comorbidity(-) group, n = 11] comorbidities. The preoperative nutritional status and ASA classification, postoperative complications, time to oral diet, and length of hospital stay were evaluated in each group. RESULTS: In the comorbidity(+)/comorbidity(-) groups, the average age was 85.9/84.1 years old, respectively. The major comorbidities were heart disease including atrial fibrillation and valvular disorder. The average PNI and CONUT scores in the comorbidity(+)/comorbidity(-) groups were 44.7/44.2 an 3.1/2.2, respectively. Planned surgical procedures were completed in all patients. Postoperative complications occurred in 2/3 cases in the comorbidity(+)/comorbidity(-) groups, respectively, and the average time to oral diet was 3.8/3.7 days, while the average length of hospitalization after surgery was 15.2/16.5 days, respectively. In the comorbidity(+) group, there was no exacerbation of comorbidities in any cases. CONCLUSION: The safety of laparoscopic surgery is acceptable among older rectal cancer patients with comorbidities.

New Anastomosis Technique to Prevent Anastomotic Leakage in Laparoscopic Anterior Resection for Rectal Cancer, Especially Upper Rectal Cancer.

BACKGROUND/AIM: Anastomotic leakage (AL) is a major problem in rectal cancer surgery. To prevent AL, we developed a side-to-side anastomosis technique using a circular stapler and termed it the circular side stapling technique (CST). We herein report the method and outcome of the CST. PATIENTS AND METHODS: In this study, we analyzed 154 patients with stage 0 to III rectal cancer who underwent curative laparoscopic low anterior resection. Perioperative factors and complications were compared between the CST and usual double stapling technique (DST). RESULTS: The CST was performed in 110 of the 154 patients. When comparing the outcomes of patients with upper rectal cancer. AL occurred in no patients in the CST group and in three patients in the DST group (p=0.011). The CST prevented AL in all patients with upper rectal cancer. CONCLUSION: The CST is a safe and useful procedure in laparoscopic anterior resection. This technique can prevent AL, especially in patients with upper rectal cancer.

A rare case of esophageal adenocarcinoma with urinary bladder metastasis.

A 75-year-old man was admitted to our hospital for treatment of esophageal cancer (EC) in March 2017. Esophagogastroduodenoscopy revealed Barrett's esophagus and superficial, distal EC (type 0-IIc). Tumor biopsy showed esophageal adenocarcinoma. Computed tomography revealed no lymph node metastasis but did reveal a 19-mm tumor on the right side of the urinary bladder. Bladder cancer (BC) was also suspected, and the patient underwent endoscopic submucosal dissection for EC and transurethral resection of the bladder tumor. The pathological diagnosis of EC was moderately to poorly differentiated adenocarcinoma (tub2), pT1b (SM), ly0, v0. The pathological horizontal margin was negative and the vertical margin was positive. Additional esophagectomy and lymph node dissection were indicated for curability. Esophagectomy was difficult because the patient had severe cardiovascular disease, so follow-up observation was adopted. BC was classified as urothelial carcinoma Ta, ly0, v0. After 32 months, multiple tumors were found in the bladder, and BC recurrence was suspected. Transurethral resection of the bladder was performed again for seven tumors, and pathological diagnosis was poorly differentiated adenocarcinoma (tub2). The immunohistochemical features matched those of EC. We diagnosed EC metastasis in the urinary bladder. Bladder adenocarcinoma is difficult to distinguish from metastasis from other organs, especially the upper gastrointestinal tract, and cytomorphological features and appropriate clinical history are required.

Obstructive rectal endometriosis treated by robot-assisted laparoscopic surgery: a case report.

BACKGROUND: Rectal endometriosis is a rare disease. A definitive diagnosis prior to surgery is often difficult. We encountered a patient with rectal sub-obstructive endometriosis that was treated by robot-assisted laparoscopic low anterior resection. CASE PRESENTATION: A 43-year-old woman visited our hospital with suspected stenosis caused by upper rectal cancer. She had a 2-year history of constipation. We were unable to confirm the diagnosis through detailed examinations, including laparoscopy. Robot-assisted laparoscopic low anterior resection with D3 lymph node dissection was performed for both diagnosis and treatment. The postoperative specimen showed a submucosal tumor. The pathological examination confirmed rectal endometriosis. CONCLUSIONS: We herein describe a rare case of obstructive rectal endometriosis that we were unable to diagnose preoperatively. Robotic surgery was useful in this case, which involved extensive pelvic adhesion.

Detection of trifluridine in tumors of patients with metastatic colorectal cancer treated with trifluridine/tipiracil.

PURPOSE: Trifluridine (FTD) is the active component of the nucleoside chemotherapeutic drug trifluridine/tipiracil (FTD/TPI), which is approved worldwide for the treatment of patients with metastatic gastrointestinal cancer. FTD exerts cytotoxic effects via its incorporation into DNA, but FTD has not been detected in the tumor specimens of patients. The purpose of this study was to detect FTD in tumors resected from metastatic colorectal cancer (mCRC) patients who were administered FTD/TPI. Another purpose was to investigate the turnover rate of FTD in tumors and bone marrow in a mouse model. METHODS: Tumors and normal tissue specimens were obtained from mCRC patients who were administered FTD/TPI or placebo at Kyushu University Hospital. Tumors and bone marrow were resected from mice with peritoneal dissemination treated with FTD/TPI. To detect and quantitate FTD incorporated into DNA, immunohistochemical staining of paraffin-embedded specimens (IHC-p staining) and slot-blot analysis of DNA purified from these tissues were performed using an anti-BrdU antibody. IHC-p staining of proliferation and apoptosis markers was also performed. RESULTS: FTD was detected in metastatic tumors obtained from mCRC patients who were administered FTD/TPI, but who had discontinued the treatment several weeks before surgery. In a peritoneal dissemination mouse model, FTD was still detected in tumors 13 days after the cessation of FTD/TPI treatment, but had disappeared from bone marrow within 6 days. CONCLUSION: These results indicate that FTD persists longer in tumors than in bone marrow, which may cause a sustained antitumor effect with tolerable hematotoxicity.

Successful multidisciplinary treatment including repeated metastasectomy for recurrent squamous cell esophageal carcinoma: a case report.

BACKGROUND: Recurrences after radical esophagectomy are common. The prognosis for recurrent esophageal cancer is generally poor. Recurrences usually occur between 1 and 3 years of surgery, with the duration of median survival after recurrence ranging from 5 to 10 months. The number of sites and involved organs vary among patients. Consequently, a standard therapeutic strategy has not been established, and the role of surgery in the management of recurrence is unclear. CASE PRESENTATION: A 67-year-old man presented with dysphagia 6 months previously and was diagnosed with esophageal squamous cell carcinoma (ESCC) in the upper thoracic region (T2M0M0, stage IB), for which he underwent thoracoscopy-assisted esophagectomy and lymphadenectomy. Adjuvant chemotherapy was not prescribed. Three years after the operation, he developed a solitary metastasis in the left lung, requiring segmentectomy followed by chemotherapy with combined cisplatin (CDDP) and 5-fluorouracil (5-FU). The following year, a metastatic lesion was recognized in the right lung, invading the chest wall, for which he underwent partial lobectomy with local chest wall resection. Multiple mediastinal and abdominal lymph node (LN) metastases were detected in the right lung a year later, which necessitated chemoradiation to a dose of 50.4 Gy with concomitant CDDP and 5-FU. Post-treatment computed tomography (CT) showed a good response. Positron emission tomography (PET)-CT revealed a reduction in the metastatic LNs with no fluoro-deoxy-glucose (FDG) uptake. The following year, metastases were detected in the left cervical LNs. Owing to the limited extent of metastases, resection was followed by chemoradiation to a dose of 50 Gy with CDDP and 5-FU. The following year, metastases were detected in the mediastinal LNs; chemotherapy was administered with nedaplatin and docetaxel. The follow-up CT and PET-CT demonstrated complete disappearance of the tumor, and the patient is currently surviving without recurrence for 11 years from the first curative operation. CONCLUSIONS: This case demonstrates that aggressive multidisciplinary treatment including surgery and radiation to achieve local control could be a meaningful treatment strategy in cases with limited and slowly occurring recurrences.