[A case of granulocyte-colony stimulating factor-producing gallbladder adenosquamous carcinoma with rapidly-growing recurrence of liver metastasis in early postoperative period].

An 82-year-old male with a gallbladder mass was diagnosed with gallbladder carcinoma through various examinations. Cholecystectomy, gallbladder bed resection, and lymph node dissection were performed. The histological examination revealed a gallbladder adenosquamous carcinoma, and this tumor showed positive staining for granulocyte-colony stimulating factor (G-CSF). Recurrence of multiple liver metastases was detected on 25th day postoperatively. Unfortunately, the patient died on 97th day postoperatively. Here, we report a case of G-CSF-producing adenosquamous carcinoma of the gallbladder with rapid recurrence of liver metastases in the early postoperative period.

A patient with cystic duct remnant calculus treated by laparoscopic surgery combined with near-infrared fluorescence cholangiography.

BACKGROUND: The recurrence of symptoms present before cholecystectomy may be caused by a cystic duct remnant. The resolution of cystic duct remnant syndrome may require surgical resection, but identification of the duct remnant during laparoscopic surgery may be difficult because of adhesions following the previous procedure. Open surgery, which is more invasive than laparoscopic surgery, is frequently chosen to avoid bile duct injury. CASE PRESENTATION: The patient was a 24-year-old woman with previous laparoscopic cholecystectomy for chronic cholecystitis and repeated attacks of biliary colic. The postoperative course was uneventful, but computed tomography revealed a remnant cystic duct calculus. Ten months after surgery, the patient returned to our department for right hypochondriac pain. Laparoscopic remnant cystic duct resection was performed with intraoperative near-infrared (NIR) fluorescence cholangiography to visualize the common bile duct and remnant cystic duct. The postoperative course was uneventful and the patient was discharged on day 3 after surgery. At the 6-month follow-up, she had no recurrence of pain. CONCLUSION: Laparoscopic surgery with NIR cholangiography is a safe and effective alternative for the removal of a cystic duct remnant calculus after cholecystectomy.

GSTP1 as a potential predictive factor for adverse events associated with platinum-based antitumor agent-induced peripheral neuropathy.

Glutathione S-transferase (GST) exhibits antidotal effects on numerous drugs, including platinum-based antineoplastic drugs. Furthermore, GST Pi 1 (GSTP1) polymorphism is associated with peripheral neuropathy. In the present study, it was determined whether GSTP1 can predict adverse events associated with platinum-based antitumor agent-induced peripheral neuropathy among Japanese patients. The subjects included 122 patients, among whom 105 patients had colorectal, 16 had gastric, and one patient had pancreatic cancer. It was indicated that wild type (AA) GSTP1 was expressed in 99 patients (81.1%), whereas heterozygous (AG) and homozygous (GG) GSTP1 polymorphisms were present in 22 (18.0%) and 1 (0.8%) patients, respectively. Among patients with colorectal cancer, the expression of homozygous GSTP1 was observed in 88 patients (83.8%), whereas that of heterozygous GSTP1 was observed in 17 patients (16.2%). Peripheral neuropathy of grade ≥3 occurred in 10 patients (9.5%) receiving mFOLFOX therapy (a biweekly cycle consisting of a 2-h infusion of 85 mg/m2 oxaliplatin and 200 mg/m2 leucovorin followed by a bolus administration of 400 mg/m2 5-fluorouracil and a continuous 48-h infusion of 2,400 mg/m2 5-fluorouracil) for colorectal cancer, which included 6 patients with the AA allele (6.8%) and 4 patients with the AG allele (23.5%). The number of peripheral neuropathy cases of grade ≥3 was increased among patients with the AG allele, compared with patients with the AA allele (P=0.032). In patients with gastric cancer, the AA and AG types of GSTP1 were expressed in 11 (68.8%) and 5 (31.2%) patients, respectively. Cisplatin, administered to patients with gastric cancer, did not induce peripheral neuropathy. The aforementioned indicated that GSTP1 genetic polymorphism is associated with peripheral neuropathy induced by oxaliplatin treatment for colorectal cancer, and therefore serves as a predictive marker. Furthermore, early dose reduction or drug withdrawal should be implemented depending on the severity of peripheral neuropathy as a potential method for reducing the number of patients discontinuing the drug, due to adverse events involving peripheral neuropathy.

[A Case of Remarkably Effective Chemoradiotherapy for Esophageal Cancer with Multiple Bone Metastasis].

The patient was a 56-year-oldwoman. She presentedto a nearby doctor with a chief complaint of dysphagia andwas diagnosed with esophageal cancer by upper gastrointestinal endoscopy, resulting in a referral to our hospital. Upper gastrointestinal endoscopy revealeda semicircular type 1 lesion 29 to 32 cm from the incisors, andshe was diagnosedwith squamous cell carcinoma by biopsy. Computedtomography (CT)andpositron emission tomography(PET)scans revealedthe enlargement and accumulation of lymph nodes along the lesser curvature of the stomach; thus, she was diagnosed with metastasis. In addition, multiple accumulations were found in the 7th cervical vertebrae as well as in the 1st, 3rd, 4th, and 8th thoracic vertebrae, leading to the diagnosis of bone metastasis. She was finally diagnosed with middle intrathoracic esophageal cancer T2N1M1, Stage Ⅳ; thus, we performedchemorad iotherapy(CRT)with 5-FU andCDDP (FP). The main lesion was markedly reduced in upper gastrointestinal endoscopy after CRT, and no apparent malignancy was found in endoscopic biopsy, so the diagnosis was endoscopic complete response. The CT scan also showed marked reductions in both the main lesion and the lymph nodes. As for the bone metastasis, some areas of bone consolidation remained, but they were diagnosed as partial responses since they were shrunk. Since then, FP has been continuously administeredon a regular basis andit has been about 2 years without any appearance of new lesions or re-exacerbation.

[A Case of CR Achieved by Chemotherapy for Distant Metastatic Lymph Nodes after Surgery for HER2 Positive Early Gastric Cancer].

The patient was a 72-year-old man who exhibited an abnormal shadow in the stomach in a series of medical check-ups of the upper gastrointestinal in August 20XX. It was diagnosed as gastric cancer(type 1)of the greater curvature of the MU region. Total gastrectomy, D2-11p dissection, and Roux-en-Y reconstruction were performed in October 20XX. The tumor was p-T1bN3aM0, Stage ⅡB, Pap, Ly1c, V1a, 90×70mm, HER2 score 3. Six courses of S-1/CDDP were administered as adjuvant chemotherapy after consultation. Two years and 8 months after the surgery, PET-CT scan showed distant lymph node metastasis(left axilla, para-aortic)and left lung metastasis. Three courses of XP-Her after 2 years and 11 months, 19 courses of X-Her after 3 years and 2 months, and 7 courses of trastuzumab alone after 4 years and 4 months to 4 years and 9 months were canceled. Three years and 4 months after the surgery, the tumor showed PR, and it showed CR, 3 years and 8 months after the surgery. Eight years and 3 months after the surgery, the tumor continued to show CR. The adverse events were blood toxicity, WBC reduction Grade 1, neutropenia Grade 3, and anemia Grade 2. There have only been a few reports on CR after chemotherapy with XP-Her for lung metastasis of gastric cancer, with a review of the literature.

[Surgical Case of Ulcerative Colitis Accompanied with Rectal Cancer Combined with Transanal Minimally Invasive Surgery].

A46 -year-old man developed ulcerative colitis at the age of 19 years. Although the colitis was medically treated, it relapsed and repeated over time. Periodic lower gastrointestinal endoscopy revealed lower rectal cancer, and he was referred to our department of surgery. Previous steroid therapy induced diabetes, and he was obese, with a height of 170.3 cm, weight of 89.6 kg, and BMI of 30.89 kg/m2, indicating that laparoscopic dissection near the anus would be difficult to perform. Therefore, the patient was scheduled for transanal minimally invasive surgery(TAMIS). The surgery involved as much laparoscopic rectal dissection as possible in the ventral to dorsal direction, followed by the TAMIS procedure. Dissection was started from the dentate line, and, after the closure of the anal stump, GelPOINT was placed, and made continuous with the previous dissection layer by applying the technique of down-to-up total mesorectal excision(TME)by TAMIS. The large intestine was excised through a small abdominal incision to create an ileal pouch, hand-sewn anastomosis was performed transanally to create a temporary colostomy, and the surgery was completed. Regarding TAMIS-TME several problems remain to be solved, including an understanding of its unique anatomy and the mastery of single-port surgical techniques. However, the herein reported patient with a high BMI had a definite indication for TAMIS-TME.

Fibrosis in small syngeneic rat liver grafts because of damaged bone marrow stem cells from chronic alcohol consumption.

A patient with liver failure due to chronic and acute alcohol abuse under consideration for an urgent liver transplant shortly after stopping alcohol may have residual abnormalities that threaten transplant success, particularly for a small graft. To address this, we studied a model in which reduced-size (50%) Lewis rat livers are transplanted into green fluorescence protein transgenic Lewis recipients after they are fed alcohol or a control diet for 5 weeks. Here we show that normal small Lewis grafts transplanted to alcohol-fed Lewis hosts developed fibrosis, whereas no fibrosis was observed in control-fed recipients. Host-derived CD133 + 8-hydroxy-2'-deoxyguanosine (8-OHdG) cells were significantly increased in livers recovered from both alcohol-fed and control recipients, but only alcohol-fed recipients demonstrated co-staining (a marker of oxidative DNA damage). α smooth muscle actin (α-SMA) staining, a marker for myofibroblasts, also co-localized with CD133 + cells only in the livers of alcohol-fed recipients. Immunostaining and polymerase chain reaction analysis confirmed that chronic alcohol consumption decreased the proportion of bone marrow stem cells (BMSCs) expressing CD133, c-Kit, and chemokine (C-X-C motif) receptor 4 markers and caused oxidative mitochondria DNA (mtDNA) damage. Culture of CD133 + cells from normal rats with medium containing 3% ethanol for 48 hours resulted in elevated mitochondrial 8-OHdG and mtDNA deletion, and ethanol exposure diminished CD133 expression but dramatically increased α-SMA expression. In conclusion, oxidative mtDNA damage and deletions occur in BMSCs of chronic alcohol-fed recipients, and these damaged cells mobilize to the small liver grafts and become myofibroblasts where they play a key role in the subsequent development of fibrosis. Liver Transplantation 23 1564-1576 2017 AASLD.

Efficacy and safety of neoadjuvant chemotherapy with oxaliplatin, 5-fluorouracil, and levofolinate for T3 or T4 stage II/III rectal cancer: the FACT trial.

PURPOSE: A multicenter phase II clinical study was performed in patients with T3 or T4 stage II/III rectal cancer to evaluate the efficacy and safety of neoadjuvant chemotherapy with 5-fluorouracil, levofolinate, and oxaliplatin (mFOLFOX6). METHODS: Patients received four 2-week cycles of mFOLFOX6 therapy (oxaliplatin at 85 mg/m2 + leucovorin at 200 mg/m2 + fluorouracil as a 400 mg/m2 bolus followed by infusion of 2400 mg/m2 over 46 h, all on Day 1). They were evaluated by computed tomography after completion of the fourth cycle. If there was no disease progression, two additional cycles were administered and then surgery was performed. Adjuvant chemotherapy was generally administered for 6 months using appropriate regimens at the discretion of the physician. RESULTS: mFOLFOX6 therapy was given to 52 patients with locally advanced rectal cancer. The preoperative response rate was 48.8% and the operation rate was 80.8%. Serious adverse events of Grade 3-4 were neutropenia (n = 5), leukopenia (n = 1), thrombocytopenia (n = 1), febrile neutropenia (n = 1), nausea (n = 1), vomiting (n = 1), and peripheral neuropathy (n = 2). The R0 resection rate, pathologic complete response rate, and sphincter preservation rate were 91.0, 11.9, and 73.8%, respectively. Postoperative complications were tolerable. CONCLUSIONS: The present results suggested that neoadjuvant therapy with mFOLFOX6 is safe and effective, representing a reasonable treatment option for locally advanced rectal cancer.

Successful laparoscopic resection of a retroperitoneal schwannoma arising from the femoral nerve: A case report.

We report on a 45-year-old man who presented with pain in the left leg, which he had had for 2 months. A contrast-enhanced CT scan displayed a 25-mm tumor in the lateral side of the left psoas muscle. For this suspected retroperitoneal tumor, we performed laparoscopic resection of the tumor, which was encapsulated by the funicular femoral nerve, using surgical scissors rather than a surgical energy device and preserved the normal fascicles wherever possible. Pathological examination indicated a benign ancient schwannoma arising from the femoral nerve. The patient was able to return to his job 3 weeks after surgery, and he has shown no evidence of recurrence. This was thought to be because of the use of surgical scissors, rather than a surgical energy device, combined with visual magnification. Therefore, the laparoscopic approach is an effective and minimally invasive option for the resection of femoral nerve schwannoma.

[Treatment Outcome of Intersphincteric Resection in Tokyo Medical University Hospital].

PURPOSE: This study aimed to consider the oncological validity of intersphincteric resection(hereinafter referred to as ISR) performed at Tokyo Medical University Hospital, as well as associated dysfunction. SUBJECTS: Subjects included 73 cases in which ISR was performed at Tokyo Medical University Hospital between November 2004 and January 2016. RESULTS: The 5- year overall and relapse-free survival rates for cases with Stage 0 to III were 90.4% and 77.3%, respectively. Two cases with recurrence among cases with Stage I were both of local recurrence.The Wexner score of the cases 12 months after closure of ileostomy was 4.2±2.5 points, while it had not been performed for the other 10 cases. DISCUSSION: In consideration of the relatively preferable local control observed with ISRs that had been performed at our hospital, defecation disorder was considered to be within an allowance.However, there remained a problem that closure of ileostomy could not be performed for 10% of the cases. CONCLUSION: ISR was believed to be valid as a sphincter-preserving procedure in consideration of the function and curability.

Promotion of Expansion and Differentiation of Hematopoietic Stem Cells by Interleukin-27 into Myeloid Progenitors to Control Infection in Emergency Myelopoiesis.

Emergency myelopoiesis is inflammation-induced hematopoiesis to replenish myeloid cells in the periphery, which is critical to control the infection with pathogens. Previously, pro-inflammatory cytokines such as interferon (IFN)-α and IFN-γ were demonstrated to play a critical role in the expansion of hematopoietic stem cells (HSCs) and myeloid progenitors, leading to production of mature myeloid cells, although their inhibitory effects on hematopoiesis were also reported. Therefore, the molecular mechanism of emergency myelopoiesis during infection remains incompletely understood. Here, we clarify that one of the interleukin (IL)-6/IL-12 family cytokines, IL-27, plays an important role in the emergency myelopoiesis. Among various types of hematopoietic cells in bone marrow, IL-27 predominantly and continuously promoted the expansion of only Lineage-Sca-1+c-Kit+ (LSK) cells, especially long-term repopulating HSCs and myeloid-restricted progenitor cells with long-term repopulating activity, and the differentiation into myeloid progenitors in synergy with stem cell factor. These progenitors expressed myeloid transcription factors such as Spi1, Gfi1, and Cebpa/b through activation of signal transducer and activator of transcription 1 and 3, and had enhanced potential to differentiate into migratory dendritic cells (DCs), neutrophils, and mast cells, and less so into macrophages, and basophils, but not into plasmacytoid DCs, conventional DCs, T cells, and B cells. Among various cytokines, IL-27 in synergy with the stem cell factor had the strongest ability to augment the expansion of LSK cells and their differentiation into myeloid progenitors retaining the LSK phenotype over a long period of time. The experiments using mice deficient for one of IL-27 receptor subunits, WSX-1, and IFN-γ revealed that the blood stage of malaria infection enhanced IL-27 expression through IFN-γ production, and the IL-27 then promoted the expansion of LSK cells, differentiating and mobilizing them into spleen, resulting in enhanced production of neutrophils to control the infection. Thus, IL-27 is one of the limited unique cytokines directly acting on HSCs to promote differentiation into myeloid progenitors during emergency myelopoiesis.

[Examination to Determine Predictive Factors of Effectiveness of Surgical Treatment for Both Pulmonary and Hepatic Metastasis from Colorectal Cancer].

In recent years, several colorectal patients with pulmonary and hepatic metastasis, if resectable, have been found to experience long-term survival. In the present study, we extracted predictive factors, selected patients for whom a good prognosis could be anticipated, and examined the indications for surgery. From January 1986 to December 2014, we conducted a multivariate analysis of 18 patients who underwent surgical resection for pulmonary and hepatic metastases, with overall survival(OS)as the dependent variable, and clinicopathological factors as explanatory variables. The 5-year survival rate of the pulmonary and hepatic resection group was 32.0%. No significant difference was noted observed in CEA levels, number of metastatic pulmonary nodes, tumor diameter, synchronic, and metachronous tumors. A significant difference was only observed for disease-free interval(DFI)following resection of the primary lesion. The area under the receiver operating characteristic(ROC)curve revealed that the optimum cut-off value following resection of the primary lesion was a DFI of 762 days. When comparing the OS of the group with DFI<762 days and the group with DFI<762 days using a Kaplan-Meier curve, we found that survival was significantly prolonged. Therefore, surgery is indicated for colorectal cancer patients with pulmonary and hepatic metastasis, and who have DFI>2 years following resection of the primary lesion, and prolonged survival can be expected following surgery.

[A Case of Advanced Rectal Cancer in Which Combined Prostate Removal and ISR Using the da Vinci Surgical System with Preoperative Chemotherapy Allowed Curative Resection].

A 53-year-old male presented with a chief complaint of dyschezia.Lower gastrointestinal endoscopy confirmed the presence of a type II tumor in the lower part of the rectum, and a biopsy detected a well-differentiated adenocarcinoma.As invasion of the prostate and levator muscle of the anus was suspected on diagnostic imaging, surgery was performed after preoperative chemotherapy.With no clear postoperative complications, the patient was discharged 26 days after surgery. After 24 months, the number of urination ranged from 1 to 6, with a Wexner score of 6 and a mild desire to urinate in the absence of incontinence.At present, the patient is alive without recurrence.When combined with chemotherapy, robotassisted surgery allows the curative resection of extensive rectal cancer involving the suspected invasion of other organs.In this respect, it is likely to be a useful method to conserve anal and bladder function.

Complete laparoscopic resection of the rectum using natural orifice specimen extraction.

AIM: To investigate how complete laparoscopic anterior resection with natural orifice specimen extraction (NOSE), as a novel minimally invasive surgery, compares to conventional laparoscopic surgery. METHODS: Twenty patients who underwent complete laparoscopic anterior resection with NOSE and 50 patients who underwent laparoscopic assisted anterior resection by the conventional method between 2011 and 2012 were studied. Selection for complete laparoscopic anterior resection with NOSE was decided on the basis of tumor size, localization of the tumor, and body mass index. Outcomes related to surgery, including operation time, postoperative wound pain, hospital stay after surgery, the number of totally dissected lymph nodes, postoperative complications (suture failure and wound infection), and anal function, were reviewed retrospectively. Anal function was assessed at 3 and 6 mo after surgery using the Wexner fecal incontinence scoring system. RESULTS: Complete laparoscopic resection with NOSE was performed to completion in all 20 patients. There was no patient emergency that required conversion to conventional laparoscopic surgery or open surgery. The comparison between complete laparoscopic resection with NOSE and conventional laparoscopic surgery showed no significant differences in the maximal diameter of the tumor, number of totally dissected lymph nodes, bleeding volume, mean operation time, time to start of oral ingestion, postoperative hospital stay, and postoperative complications. On the other hand, with regard to pain after epidural anesthesia, the total usage of analgesia in this novel surgical technique was 1.85 ± 1.8 times, whereas it was 5.89 ± 2.86 in conventional laparoscopic surgery (P < 0.001). The postoperative pain period was 1.9 ± 1.9 d in this novel surgical technique, whereas it was 3.43 ± 1.41 d in conventional laparoscopic surgery (P < 0.004). In complete laparoscopic surgery with NOSE, the mean postoperative follow-up period was 20 mo (range: 12-30 mo). Neither local recurrence nor remote metastasis was observed during the follow-up period. CONCLUSION: Complete laparoscopic anterior resection using NOSE does not require any incision and has excellent cosmetic properties, with mitigated postoperative pain.

[Evaluated cases of M1a (non-regional) and recurrent lymph node metastases obtained long-term survival by additional local treatment].

According to the 2014 guidelines for the treatment of Stage IV colorectal cancer, surgical therapy is recommended if R0 resection is possible by resecting both distant metastases and the primary tumor. However, there was no clear evidence regarding the treatment of non-regional lymph node metastases and recurrent lymph node metastases. Thus, we evaluated cases of non-regional lymph node metastases and recurrent lymph node metastases at our hospital from 2005 to the present date. The 5-year overall survival (OS) rate was 50.0%. There was no significant difference in the survival rate between synchronous and metachronous metastases. The survival rate increased significantly in cases that received additional local treatment compared to that in cases that did not receive additional treatment (p=0.013). Multivariate analysis based on the 5-year OS rate of 50.0% revealed a statistically significant difference only in disease free interval (DFI). Although no predictive factor for OS was identified, DFI was considered to be a critical factor. Performing chemotherapy during the perioperative period and determining the appropriate timing of resection based on the response to the chemotherapy and presence/absence of metastases in other organs are expected to increase the survival rate.

[Two case reports with hepatic metastases of colorectal cancer treated with radiofrequency ablation, raising the possibility of local control in the liver].

Only hepatic metastasectomy has been shown to have a therapeutic effect for hepatic metastases of colorectal cancer if the primary tumor can be removed radically according to the 2014 guidelines of the Japanese Society for Cancer of the Colon and Rectum. However, only a few patients with hepatic metastases are candidates for metastasectomy due to tumor factors other than the hepatic metastases. Furthermore, hepatic metastasectomy is frequently judged to be impossible in older patients due to underlying diseases and surgical tolerability. In such cases, therefore, treatment is often difficult. Herein, we report 2 patients with hepatic metastases of colorectal cancer treated with radiofrequency ablation, raising the possibility of local control in the liver.

Interleukin-6 is an important mediator for mitochondrial DNA repair after alcoholic liver injury in mice.

UNLABELLED: We investigated the hypothesis that a prominent effect of chronic ethanol consumption is mitochondrial DNA (mtDNA) injury and compared this injury in IL-6 knockout (KO) and wild-type (WT) mice. Ethanol feeding for 4 weeks resulted in steatosis and oxidative mtDNA damage (8-OHdG) in both IL-6KO and WT mice. However, the WT mice were able to repair the injury by increased production of mtDNA repair enzymes (OGG-1, Neil 1) and check point (p21, p53) proteins and avoid the mtDNA mutations. By contrast the IL-6 KO mice were unable to repair mtDNA resulting in deletions and diminished transcription of the mtDNA encoded protein cytochrome c oxidase subunit-I (COI). The mitochondrial injury was reflected by decreased membrane potential, reduced levels of ATP, and apoptosis-inducing factor (AIF)-induced apoptosis. CONCLUSION: IL-6 plays a critical role in allowing the liver to recover from significant mtDNA oxidation caused by alcohol. The data suggests that IL-6 activates mtDNA repair enzymes and induces cell cycle arrest allowing time for mtDNA repair.

Oxaliplatin for metastatic colon cancer in a patient with renal failure.

OBJECTIVE: Oxaliplatin, a key part of the standard regimen for colorectal cancer in Western countries, has become available in Japan. In a hemodialysis patient with cecal cancer, we investigated the efficacy, safety, pharmacokinetics, and dialysability of oxaliplatin. METHODS: A 65-year-old man who had cecal cancer was treated with oxaliplatin (40 mg/m(2)) and l-leucovorin(l-LV) (200 mg/m(2)), which were administered simultaneously over 120 min via the side and main arms of a Y-tube, respectively. Then 5-FU (400 mg/m(2)) was administered rapidly via the side tube, followed by 5-FU (2,000 mg/m(2)) over 46 hours via the main tube. The patient had chronic renal failure due to diabetic nephropathy and hemodialysis was performed 3 times a week. Blood samples were collected from the dialyzer before and after each hemodialysis session to examine platinum clearance. RESULTS: The patient received 3 courses of oxaliplatin before he died of cancer. During hemodialysis, the platinum level fell from 0.32 µg/mL to 0.15 µg/mL. CONCLUSION: Since patients with renal failure have various associated disorders and oxaliplatin has a long half-life, it is necessary to obtain more pharmacokinetic data to investigate its accumulation and dialysability during long-term treatment. Such data will assist in treating the rapidly increasing number of hemodialysis patients with colorectal cancer.

[CR of rectal cancer and synchronous liver and lung metastases obtained with TS-1 plus CPT-11 combination therapy--case report].

The patient was a 44-year-old male in whom low anterior resection of the rectum, partial pneumonectomy, and liver biopsy were performed because of suspicion of synchronous liver and pulmonary metastases of rectal cancer which caused familial adenomatous polyposis. Because anticancer drug sensitivity testing by the HDRA method performed on tissue collected from the cancer immediately postoperatively revealed sensitivity to 5-FU and CPT-11, and measurement of nucleic acid metabolizing enzymes showed a high level of DPD, a 5-FU metabolizing enzyme, combination therapy with TS-1 and CPT-11 was started. TS-1, 120 mg/body, was administered on 14 consecutive days followed by a 7-day rest period, and CPT-11, 120 mg/body, was administered on day 1 and day 8. One cycle was defined as 3 weeks,and cycles were repeated. Grade 2 diarrhea occurred, but the CPT-11 dose was reduced to 100 mg/body, and treatment was continued. CR was achieved when the 4th course had been completed. Thoracic and abdominal CT was performed after 4 courses, but no recurrent foci were detected in the residual lung tissue, and all of the metastatic liver foci had resolved. To date 6 courses have been completed, and no relapses have been detected by thoracic CT. We report a case in which it was possible to predict efficacy as a result of treatment based on anticancer drug sensitivity testing and measurements of nucleic acid metabolizing enzymes.

Detection and evaluation of epithelial cells in the blood of colon cancer patients using RT-PCR.

BACKGROUND: As a mode of colorectal cancer recurrence, liver metastasis plays an important role. One of the factors reported to predict liver metastasis is the detection of trace amounts of tumor cells in the blood. For this purpose, cancer cell-induced cytokeratins (CKs) are generally identified, using the reverse transcriptase-polymerase chain reaction (RT-PCR). In the present study, we aimed to detect trace amounts of tumor cells, based on CK20, in the circulating venous blood, and we examined pathological factors, liver metastasis, and prognosis. METHODS: The subjects were 57 colorectal cancer patients who had undergone operation. We examined the cancer-induced marker (CK20) in circulating venous blood by RT-PCR and investigated the relationships between this marker, pathological factors, and prognosis. RESULTS: Detection ratio of CK20 mRNA was 42.1%, and CK20 was significantly correlated with the pathological factor of lymph node metastasis (P = 0.037). The 5-year survival rate for CK20-positive patients was 62.5% and that for the CK20-negative patients was 87.5%; there was a significant difference (P = 0.048) between the two groups. Recurrence was recognized in six patients; two were positive for CK20 and four were negative for CK20. CONCLUSIONS: These findings indicate that CK20 is strongly related to lymph node metastasis and prognosis, suggesting its usefulness for the diagnosis of colorectal cancer recurrence. However, CK20 did not predict liver metastasis.