Prevention of ureteral injury during laparoscopic colorectal cancer surgery with horseshoe kidney using fluorescent ureteral catheters: a case report.

BACKGROUND: Horseshoe kidney is one of the most common congenital renal fusion anomalies and is characterized by abnormalities in the position, rotation, vascular supply, and ureteral anatomy of the kidney. When performing surgery for colorectal cancer in patients with horseshoe kidneys, anatomical identification is important to avoid organ injuries. Several reports on surgery for colorectal cancer with horseshoe kidneys have described the usefulness of three-dimensional (3D) computed tomography (CT) angiography for detecting abnormalities in vascular supply. However, few reports have focused on the prevention of ureteral injury in surgery for colorectal cancer with horseshoe kidney, despite abnormalities in the ureteral anatomy. Here, we report a case in which laparoscopic sigmoid colon resection for sigmoid colon cancer with a horseshoe kidney was safely performed using fluorescent ureteral catheters. CASE PRESENTATION: A 60-year-old Japanese man presented to our hospital testing positive for fecal occult blood. Colonoscopy revealed sigmoid colon cancer, and CT confirmed a horseshoe kidney. The 3D-CT angiography showed aberrant renal arteries from the aorta and right common iliac artery, and the left ureter passed across the front of the renal isthmus. A fluorescent ureteral catheter was placed in the left ureter before the surgery to prevent ureteral injury. Laparoscopic sigmoid colon resection with D3 lymph node dissection was performed. The fluorescent ureteral catheter enabled the identification of the left ureter that passed across the front of the renal isthmus and the safe mobilization of the descending and sigmoid colon from the retroperitoneum. The operative time was 214 min, with intraoperative bleeding of 25 mL. The patient's postoperative course was good: no complications arose and she was discharged on the seventh postoperative day. CONCLUSION: In patients with horseshoe kidney, the use of fluorescent ureteral catheters and 3D-CT angiography enables safer laparoscopic surgery for colorectal cancer. We recommend the placement of fluorescent ureteral catheters in such surgeries to prevent ureteral injury.

Analysis of external pressure on the left calf in the Lloyd-Davies position during colorectal surgery.

PURPOSE: Well-leg compartment syndrome (WLCS) is a potentially life-threatening postoperative complication related to the Lloyd-Davies surgical position, which can place increased external pressure on the calf region. We conducted this study to analyze external pressure changes, by applying a leg holder system to the left calf region of patients placed in the Lloyd-Davies position during laparoscopic surgery. METHODS: The study participants were 50 patients who underwent laparoscopic surgery for colorectal cancer in the Lloyd-Davies position. We assessed the maximum external pressure (MEP) on the left calf region using a pressure-distribution measurement system. Intraoperative measurements were taken continuously, and the MEP was evaluated with the patient horizontal and every 30 min during surgery in the head and right-down tilt position. RESULTS: The intraoperative MEP increased gradually when the patient was in the head and right-down tilt position and decreased when the patient was returned to the horizontal position. The MEP was higher in patients aged < 60 years, those who were obese, and those with a thick calf circumference. Both body mass index (BMI) and the maximum left calf circumference (MLCC) were found to correlate with the MEP. CONCLUSIONS: In addition to a high BMI, which is a well-known risk factor for WLCS, a high MLCC should be considered another risk factor, especially for patients under 60 years.

Comprehensive evaluation of three-dimensional anatomy of perigastric vessels using enhanced multidetector-row computed tomography.

BACKGROUND: To perform laparoscopic gastrectomy safely, we aimed to comprehensively re-evaluate perigastric vessel anatomies using a three-dimensional angiography reconstructed from enhanced multidetector-row computed tomography data. METHODS: Perigastric vessel anatomy was preoperatively analyzed using a multidetector-row computed tomography-based three-dimensional angiography reconstructed in 127 patients undergoing gastric surgery. RESULTS: Of the 67 left gastric veins that ran along the dorsal side of the arteries, 59 (88.1%) ran along the dorsal side of the common hepatic artery and flowed into the portal vein. In 18 cases, a common trunk of one to three left gastric arteries and the replaced left hepatic artery was observed. The left inferior phrenic artery ramified from the left gastric artery in 5.5% of the cases. The right gastric artery was classified into distal (73.2%), caudal (18.1%), and proximal (8.7%) types. The infra-pyloric artery was also classified into distal (64.6%), caudal (26.0%), and proximal (9.4%) types. The posterior gastric artery branched as a common trunk with the superior polar artery in the proximal (37.9%) and distal (18.4%) regions of the splenic artery. The left gastroepiploic artery ramified from the splenic (18.1%) and inferior terminal arteries (81.9%). No, one, and two gastric branches of the left gastroepiploic artery, which ramified between the roots of the left gastroepiploic artery and its omental branch, were found in 36.5%, 49.2%, and 14.3% of the cases, respectively. CONCLUSIONS: Preoperative 3D angiography is useful for the precise evaluation of perigastric vessel anatomies, and may help us to perform laparoscopic gastrectomy and robotic surgery safely.

Biweekly TAS-102 and bevacizumab as third-line chemotherapy for advanced or recurrent colorectal cancer: a phase II, multicenter, clinical trial (TAS-CC4 study).

BACKGROUND: TAS-102 improves overall survival (OS) of patients with refractory colorectal cancer (CRC), resulting in median progression-free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, a combination of TAS-102 and bevacizumab was shown to extend median PFS by 3.7 months. However, approximately half of these patients experience grade 3/4 neutropenia. In this study, we evaluated whether biweekly TAS-102 and bevacizumab therapy has efficacy equal to that of conventional TAS-102 and bevacizumab therapy and whether it reduces adverse hematological effects. METHODS: This phase II, investigator-initiated, open-label, single-arm, multicenter study was conducted in Japan. Eligible patients had previously received first- and second-line chemotherapy for metastatic CRC. TAS-102 (35 mg/m2) was given twice daily on days 1-5 and days 15-19 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion for 30 min every 2 weeks. The primary end point was progression-free survival (PFS), and secondary end points were time-to-treatment failure (TTF), response rate (RR), OS, and safety. RESULTS: 44 patients with metastatic colorectal cancer were enrolled in this study. Median PFS was 4.6 months (95% confidence interval [95% CI] 3.6-5.3) and median OS was 10.5 months (95% CI 9.6-11.4). A partial response was observed in 2 patients (4.5%, 95% CI 0.4-16.0%). The most common adverse event above grade 3 was neutropenia (7 patients, 15.9%, 95% CI 7.6-29.7%). CONCLUSIONS: Biweekly TAS-102 and bevacizumab therapy as third-line chemotherapy appears as effective as conventional TAS-102 and bevacizumab therapy, and this approach reduces adverse hematological effects.

Refractory postoperative Staphylococcus hominis bacteremia in a patient with an ACTH-producing pancreatic neuroendocrine neoplasm: a case report.

BACKGROUND: Staphylococcus hominis (S. hominis) is an opportunistic pathogen that is often highly resistant to antibiotics and is difficult to treat. In patients diagnosed with an adrenocorticotropic hormone (ACTH)-producing tumor that compromises the immune system due to hypercortisolemia, cancer treatment and infection control should be considered simultaneously. This report presents a case of refractory postoperative S. hominis bacteremia requiring the prolonged administration of several antibiotics in a patient with an ACTH-producing pancreatic neuroendocrine neoplasm (pNEN). CASE PRESENTATION: A 35-year-old man visited a neighboring hospital for a thorough examination after experiencing weight gain and lower limb weakness for several months. Enhanced computed tomography revealed a pancreatic tail tumor and bilateral adrenal enlargement. Elevated plasma ACTH and serum cortisol were noted. Biopsy under endoscopic ultrasonography revealed the tumor as an ACTH-producing pNEN. The patient was transferred to our hospital for further treatment. Pneumocystis pneumonia was noted and treated with sulfamethoxazole and adjunctive glucocorticoids. Hypercortisolism was controlled with metyrapone and trilostane. Somatostatin receptor scintigraphy and ethoxybenzyl magnetic resonance imaging detected other lesions in the pancreatic head. A total pancreatectomy was performed given that the lesions were found in both the pancreatic head and tail. Plasma ACTH and serum cortisol levels decreased immediately after the resection. Pathological examination revealed that the pancreatic tail tumor was NEN G2 and T3N1aM0 Stage IIB and the pancreatic head lesions were SSTR-positive hyperplasia of the islet of Langerhans cells. On postoperative day 11, catheter-associated bacteremia occurred. Initially, meropenem hydrate and vancomycin hydrochloride were administered empirically. S. hominis was identified and appeared sensitive to these antibiotics according to susceptibility testing. However, S. hominis was repeatedly positive in blood cultures for more than one month, despite treatment with several antibiotics. Eventually, with the combined use of three antibiotics (meropenem hydrate, vancomycin hydrochloride, and clindamycin phosphate) for more than 3 weeks, the S. hominis-associated bacteremia improved. He was discharged 79 days after surgery. CONCLUSIONS: Our patient with an ACTH-producing pNEN was immunocompromised and needed meticulous attention for infectious complications even after successful tumor removal. Specifically, S. hominis bacteremia in such patients demands intensive treatments, such as with combinational antibiotics.

Long-term prognosis of familial adenomatous polyposis with or without mucosectomy.

PURPOSE: This study primarily aimed to compare the long-term prognosis of patients who underwent total colectomy/proctocolectomy with or without mucosectomy to the dentate line for the diagnosis of familial adenomatous polyposis (FAP). METHODS: Patients who underwent total colectomy/proctocolectomy for FAP between January 1979 and December 2020 and were followed up at Hamamatsu University Hospital were included in this study. Those who underwent total proctocolectomy with hand-sewn ileal pouch-anal anastomosis were defined as the mucosectomy group. Those who underwent total colectomy or total proctocolectomy using the stapled ileal pouch-anal anastomosis approach were defined as the no mucosectomy group. RESULTS: A total of 61 individuals (37 families) were diagnosed during the surveillance period (median, 191 months). Between the mucosectomy (n = 24) and no mucosectomy groups (n = 34), metachronous rectal cancer was significantly more common in the no mucosectomy group (21% in no mucosectomy vs. 0% in mucosectomy, P = 0.02). Overall survival in the no mucosectomy group was worse than that in the mucosectomy group (84.5% in no mucosectomy vs. 100% in mucosectomy at 120 months, 81.1% vs. 90.0% at 240 months, 50.6% vs. 75.0% at 360 months, P = 0.09). Cox regression analysis revealed an independent effect of not performing mucosectomy on overall survival (P = 0.03). CONCLUSION: Long-term surveillance revealed that colectomy or total proctocolectomy without mucosectomy had a negative impact on the overall survival of patients with FAP. Therefore, we recommend total proctocolectomy with mucosectomy, i.e., hand-sewn ileal pouch-anal anastomosis, for FAP.

Comparison of operative outcomes between monopolar and bipolar coagulation in hepatectomy: a propensity score-matched analysis in a single center.

BACKGROUND: Various hemostatic devices have been utilized to reduce blood loss during hepatectomy. Nonetheless, a comparison between monopolar and bipolar coagulation, particularly their usefulness or inferiority, has been poorly documented. The aim of this study is to reveal the characteristics of these hemostatic devices. METHODS: A total of 264 patients who underwent open hepatectomy at our institution from January 2009 to December 2018 were included. Monopolar and bipolar hemostatic devices were used in 160 (monopolar group) and 104 (bipolar group) cases, respectively. Operative outcomes and thermal damage to the resected specimens were compared between these groups using propensity score matching according to background factors. Multivariate logistic regression analysis was performed to identify predictive factors for postoperative complications. RESULTS: After propensity score matching, 73 patients per group were enrolled. The monopolar group had significantly lower total operative time (239 vs. 275 min; P = 0.013) and intraoperative blood loss (487 vs. 790 mL; P < 0.001). However, the incidence rates of ascites (27.4% vs. 8.2%; P = 0.002) and grade ≥ 3 intra-abdominal infection (12.3% vs. 2.7%; P = 0.028) were significantly higher in the monopolar group. Thermal damage to the resected specimens was significantly longer in the monopolar group (4.6 vs. 1.2 mm; P < 0.001). Use of monopolar hemostatic device was an independent risk factor for ascites (odds ratio, 5.626, 95% confidence interval 1.881-16.827; P = 0.002) and severe intra-abdominal infection (odds ratio, 5.905, 95% confidence interval 1.096-31.825; P = 0.039). CONCLUSIONS: Although monopolar devices have an excellent hemostatic ability, they might damage the remnant liver. The use of monopolar devices can be one of the factors that increase the frequency of complications.

Geospatial Assessments of DNA Adducts in the Human Stomach: A Model of Field Cancerization.

BACKGROUND: Field cancerization is a popular concept regarding where cancer cells arise in a plane, such as the opened-up gastrointestinal mucosa. The geospatial distribution of DNA adducts, some of which are believed to initiate mutation, may be a clue to understanding the landscape of the preferred occurrence of gastric cancer in the human stomach, such that the occurrence is much more frequent in the lesser curvature than in the greater curvature. METHODS: Seven DNA adducts, C5-methyl-2'-deoxycytidine, 2'-deoxyinosine, C5-hydroxymethyl-2'-deoxycytidine, N6-methyl-2'-deoxyadenosine, 1,N6-etheno-2'-deoxyadenosine, N6-hydroxymethyl-2'-deoxyadenosine, and C8-oxo-2'-deoxyguanosine, from different points and zones of the human stomach were semi quantitatively measured by liquid chromatography/tandem mass spectrometry. The differences in the quantity of these DNA adducts from the lesser and greater curvature, the upper, middle and lower third zones, the anterior and posterior wall of the stomach, and the mucosae distant from and near the tumor were compared to determine whether the location preference of cancer in the stomach could be explained by the distribution of these DNA adducts. Comparisons were conducted considering the tumor locations and operation methods. CONCLUSIONS: Regarding the DNA adducts investigated, significant differences in quantities and locations in the whole stomach were not noted; thus, these DNA adducts do not explain the preferential occurrence of cancer in particular locations of the human stomach.

Mismatch repair proteins immunohistochemical null phenotype in colon medullary carcinoma.

INTRODUCTION: In mismatch repair (MMR) immunohistochemistry, four MMR proteins' staining pattern reveals which particular gene may be defective. However, in the null phenotype, four MMR proteins are lost; consequently, it will be challenging to assume the target gene by immunohistochemistry and to determine whether deficient MMR was sporadic or germline. CASE REPORT: A 70-year-old man underwent right hemicolectomy with the diagnosis of ascending colon cancer. The postoperative histopathology revealed the diagnosis of medullary carcinoma and the loss of all four MMR expressions in immunohistochemistry. The mutation analysis using a peripheral blood sample showed no germline mutations in the four genes. DISCUSSION: This clinical case presents an unusual colon carcinoma that showed a MMR protein immunohistochemistry null phenotype. The cause of expression loss of MMR proteins can be explained by the loss of MLH1 and MSH2 functions associated with somatic loss of function mutations, functional loss in all four MMR proteins associated with somatic loss of function mutations, or Lynch-like syndrome. Correct interpretation and accumulation of relevant cases are necessary to unveil unusual cases in the era of universal screening.

The Pre-treatment Lymphocyte-to-Monocyte Ratio Predicts Efficacy in Metastatic Colorectal Cancer Treated With TAS-102 and Bevacizumab.

BACKGROUND/AIM: Our multicenter phase II TAS-CC3 study demonstrated favorable median progression-free survival (PFS) and overall survival (OS) of 32 metastatic colorectal cancer (mCRC) patients treated with TAS-102 + bevacizumab as 3rd-line treatment. PATIENTS AND METHODS: We investigated the predictive and prognostic values of pre-treatment blood inflammation-based scores, including the neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) and lymphocyte-to-monocyte ratio (LMR) on disease-control (DC), PFS and OS by a post-hoc analysis. RESULTS: Receiver operating characteristic curve analyses of the 3 inflammation-based scores versus DC showed the best predictive performance for LMR, followed by NLR and PLR. The high-LMR group had a significantly higher DC rate than the low group (87.5 vs. 43.8%). The high-LMR group showed significantly longer survival than the low group (4.9 vs. 2.3 m for median PFS) (21.0 vs. 6.1 m for median OS). CONCLUSION: The pre-treatment LMR is a valid predictive and prognostic biomarker for mCRC patients undergoing TAS-102 and bevacizumab treatment.

Mass spectrometric profiling of DNA adducts in the human stomach associated with damage from environmental factors.

BACKGROUND: A comprehensive understanding of DNA adducts, one of the most plausible origins of cancer mutations, is still elusive, especially in human tissues in clinical settings. Recent technological developments have facilitated the identification of multiple DNA adducts in a single experiment. Only a few attempts toward this "DNA adductome approach" in human tissues have been reported. Geospatial information on DNA adducts in human organs has been scarce. AIM: Mass spectrometry of human gastric mucosal DNA was performed to identify DNA adducts associated with environmental factors. MATERIALS AND METHODS: From 59 subjects who had received gastrectomy for gastric cancer, 306 samples of nontumor tissues and 15 samples of tumors (14 cases) were taken for DNA adductome analysis. Gastric nontumor tissue from autopsies of 7 subjects without gastric cancer (urothelial cancer, hepatocellular carcinoma, lung cancer each; the other four cases were without any cancers) was also investigated. Briefly, DNA was extracted from each sample with antioxidants, digested into nucleosides, separated by liquid chromatography, and then electrospray-ionized. Specific DNA adducts were identified by mass/charge number and column retention time compared to standards. Information on lifestyle factors such as tobacco smoking and alcohol drinking was taken from the clinical records of each subject. RESULTS: Seven DNA adducts, including modified bases, C5-methyl-2'-deoxycytidine, 2'-deoxyinosine, C5-hydroxymethyl-2'-deoxycytidine, N6-methyl-2'-deoxyadenosine, 1,N6-etheno-2'-deoxyadenosine, N6-hydroxymethyl-2'-deoxyadenosine, and C8-oxo-2'-deoxyguanosine, were identified in the human stomach and characterized. Intraindividual differences according to the multiple sites of these adducts were noted but were less substantial than interindividual differences. N6-hydroxymethyl-2'-deoxyadenosine was identified in the human stomach for the first time. The amount of C5-hydroxymethyl-2'-deoxycytidine was higher in the stomachs of subjects without gastric cancer than in the nontumor and tumor portions of the stomach in gastric cancer patients. Higher levels of 1,N6-etheno-2'-deoxyadenosine were detected in the subjects who reported both smoking and drinking than in those without these habits. These DNA adducts showed considerable correlations with each other. CONCLUSIONS: We characterized 7 DNA adducts in the nontumor portion of the human stomach in both gastric cancer subjects and nongastric cancer subjects. A reduction in C5-hydroxymethyl-dC even in the nontumor mucosa of patients with gastric cancer was observed. Smoking and drinking habits significantly influenced the quantity of one of the lipid peroxidation-derived adducts, etheno-dA. A more expansive DNA adductome profile would provide a comprehensive understanding of the origin of human cancer in the future.

Combination of TAS-102 and bevacizumab as third-line treatment for metastatic colorectal cancer: TAS-CC3 study.

BACKGROUND: TAS-102 improved the overall survival of metastatic colorectal cancer (CRC) patients with a median progression-free survival (PFS) in the RECOURSE trial. Subsequently, the combination of TAS-102 and bevacizumab was shown to extend the median PFS (C-TASK FORCE study). However, the study included patients who received second- and third-line treatment. Our study exclusively examined patients receiving this combination as a third-line treatment to investigate the clinical impact beyond cytotoxic doublets. METHODS: This investigator-initiated, open-label, single-arm, multi-centered phase II study was conducted in Japan. Eligible CRC patients were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in first- and second-line therapy. TAS-102 (35 mg/m2) was given orally twice daily on days 1-5 and 8-12 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion every 2 weeks. The primary endpoint was PFS and the secondary endpoints were time-to-treatment failure, response rate, overall survival (OS), and safety. RESULTS: Between June 2016 and August 2017, 32 patients were enrolled. All patients previously received bevacizumab. The median PFS was 4.5 months; the median overall survival was 9.3 months. Partial response was observed in two patients. The most common adverse events above grade 3 were neutropenia followed by thrombocytopenia. There were no non-hematological adverse events above grade 3 and no treatment-related deaths occurred. CONCLUSIONS: This study met its primary endpoint of PFS, which is comparable to the results of the C-TASK FORCE study. The TAS-102 and bevacizumab combination has the potential to be a therapeutic option for third-line treatment of metastatic CRC.

[Solid serous cystic neoplasm of the pancreas showing a gradual tumor enlargement for over five years:a case report].

Serous cystic neoplasms (SCNs) of the pancreas are slow-growing benign tumors. They are mostly monitored without surgical management. Solid SCN is rare and differentiating it from hypervascular tumors of the pancreas using preoperative imaging may be difficult. A 69-year-old woman was referred to our department for surgical treatment of an enlarged pancreatic tail tumor with a size of 22mm based on the abdominal computed tomography (CT). At the age of 60, she underwent thyroidectomy for papillary thyroid carcinoma and mastectomy for breast cancer. Initially, consecutive annual CT examinations did not show signs of recurrence. However, after 9 years, a hypervascular pancreatic tumor was detected and assumed to be either a neuroendocrine tumor or metastasis. The patient underwent distal pancreatectomy, and the resected specimen was histopathologically diagnosed as solid SCN of the pancreas. Before being referred for pancreatic resection, this patient had been followed up with serial annual CT examinations for over 9 years after a previous malignant disease. Retrospectively, the abdominal CT scans showed that the pancreatic tumor already existed 5 years ago and had gradually increased in size thereafter. In this case report, we focused on the characteristics of solid SCN to address the difficulty in diagnosing this rare malignancy.

A Trial Protocol of Biweekly TAS-102 and Bevacizumab as Third-Line Chemotherapy for Advanced/Recurrent Colorectal Cancer: A Phase II Multicenter Clinical Trial (The TAS-CC4 Study).

BACKGROUND: Treatment with TAS-102 has significantly improved the progression-free survival (PFS) and overall survival (OS) of patients with metastatic colorectal cancer (mCRC). Reportedly, the combination of TAS-102 plus bevacizumab extends the median PFS. The present study aimed to confirm the efficacy and safety of TAS-102 plus bevacizumab (biweekly administration) as third-line chemotherapy for patients with mCRC. METHODS/DESIGN: This is a single-arm, open-label, prospective, nonrandomized, multicenter phase II trial conducted in Japan. With a threshold and expected PFS of 2.1 and 3.5 months, respectively, the simulation results showed a sample size of 42 with α = 0.05 (both sides) for 90% power, based on the One-Arm Binomial test using the SWOG statistical tool. If the estimated dropout is 7%-8%, the target sample size is estimated to be 45. The TAS-CC4 study regimen comprised 28-day cycles with biweekly oral administration of TAS-102 (35 mg/m2 twice daily on days 1-5 and 15-19 of every 28-day cycle) and bevacizumab (5.0 mg/kg on days 1 and 15). The primary end point is the PFS; secondary end points include response rate (RR), OS, grade ≥3 neutropenia, and genetic alterations (KRAS/BRAF mutations) in the circulating cell-free DNA. DISCUSSION: The present study can contribute to the determination of the effective dosing interval of TAS-102 and bevacizumab in patients with mCRC and is thought to lead to prophylaxis of neutropenia and prolongation of the treatment period.

[Impact on opioid precipitation of opioid-starting titration path].

To investigate the effect clinical path of cancer pain treatments for opioid naive patients has on physician practice, a prepost quasi-experimental study was performed. The primary outcome measure was the percentage of patients who received 'recommended pain treatments' during the study periods. We determined the treatment to be the treatment of choice, if the physician 1) ordered a rescue dose, 2) prescribed a laxative, and 3) prescribed antiemetics when starting opioids. The secondary outcome measure was the number of newly consulted patients for our palliative care team. The end-points were measured before and after disseminating the clinical path. The rate of patients receiving recommended pain treatments significantly increased after disseminating the clinical path(p=0.03): 17%(33/18)to 61%(19/31). Patients who received a rescue order, laxative, or antiemetic when starting opioids were: 44% vs. 68%, 77% vs. 90%, and 66% vs. 77%, respectively. The number of patients newly consulting the palliative care team was increased(21 cases to 42 cases/4 month). In conclusion, the clinical path of cancer pain treatments is useful for improving the physician's practice when starting opioids for cancer pain, and might contribute to enhancing palliative care team availability.

[Spontaneous regression of hepatocellular carcinomas].

We report a rare case of spontaneous regression (SR) of hepatocellular carcinoma (HCC). A 70-year-old man consulted us for general fatigue. Enhanced abdominal computed tomography (CT) showed two HCCs, of 5cm in the posterior segment and 8cm around the right Glissonean pedicle with tumor thrombus in the main portal trunk. He refused to undergo any treatment, but 28 months later, CT showed complete disappearance of the hilar tumor and portal tumor thrombus, and partial regression in the posterior tumor with shrinkage of the right lobe of the liver. His PIVKA-II levels decreased from 23358 to 217mAU/ml. In the present case, tumor infarction of the portal thrombus, and the administration of imidapuril hydrochloride and Hochu-ekki-to may have caused SR.

GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by Shigella effectors.

Shigella flexneri has evolved the ability to modify host cell function with intracellular active effectors to overcome the intestinal barrier. The detection of these microbial effectors and the initiation of innate immune responses are critical for rapid mucosal defense activation. The guanine nucleotide exchange factor H1 (GEF-H1) mediates RhoA activation required for cell invasion by the enteroinvasive pathogen Shigella flexneri. Surprisingly, GEF-H1 is requisite for NF-kappaB activation in response to Shigella infection. GEF-H1 interacts with NOD1 and is required for RIP2 dependent NF-kappaB activation by H-Ala-D-gammaGlu-DAP (gammaTriDAP). GEF-H1 is essential for NF-kappaB activation by the Shigella effectors IpgB2 and OspB, which were found to signal in a NOD1 and RhoA Kinase (ROCK) dependent manner. Our results demonstrate that GEF-H1 is a critical component of cellular defenses forming an intracellular sensing system with NOD1 for the detection of microbial effectors during cell invasion by pathogens.

[Phase I study of CPT-11 and continuous 5-FU / l-leucovorin combination therapy(modified AIO regimen)in patients with metastatic colorectal cancer].

A combination of CPT-11, continuous 5-fluorouracil(5-FU)and leucovorin(LV), the Arbeitsgemeinschaft für Internistische Onkologie(AIO)regimen, is widely used for the treatment of metastatic CRC. The efficacy and toxicity of this regimen, however, have not been determined in Japanese patients with metastatic CRC. Our objective was to evaluate the safety of the AIO regimen plus CPT-11 in Japanese colorectal carcinoma(CRC)patients. We investigated the maximum tolerated dose(MTD), dose-limiting toxicity(DLT), and recommended dose(RD)for CPT-11 and continuous 5-FU. CPT-11, 5-FU, and l-LV were administered on days 1, 8, and 15 of a 28-day cycle. The dose of CPT- 11 was escalated from 40 mg/m2 (level 1)to 80 mg/m2 (level 3). The 5-FU dose was then escalated from 1,000 mg/m2 (level 4)to 2,000 mg/m2 (level 5). If neither level met the criteria for the MTD, the recommended dose was defined as level 5, and the dose escalation was discontinued, because the maximum approved weekly dose of CPT-11 alone in Japan is 80 mg/m2 and the dose of 5-FU in the original AIO regimen was 2,000 mg/m2. A total of 18 patients were enrolled in this study. Hematological and non-hematological toxicity were infrequent and mild. There were no toxicities greater than grade 2 at each dose level. Level 5 did not meet the MTD criteria. Our results confirm that the modified AIO plus CPT-11 regimen is safe for Japanese patients. The recommended doses in the present study were CPT-11 80 mg/m2, 5-FU 2,000 mg/m2, and l-LV 250 mg/m2.

[A case of sigmoid colon cancer with metastases of para-aortic lymph nodes treated with curative resection after irinotecan plus 5-fluorouracil and l-leucovorin combination chemotherapy].

A 54-year-old woman visited our hospital with a chief complaint of lower abdominal pain and melena. The patient was diagnosed with sigmoid colon cancer using colonoscopy. Abdominal CT revealed metastases to para-aortic lymph node, so our diagnosis was unresectable sigmoid colon cancer. She underwent a transverse colostomy to avoid stenosis. Two weeks after surgery, she underwent a 1-week chemotherapy regimen (CPT-11 80 mg/m(2)/week+5-FU 2,000 mg/m(2)/week+l-LV 250 mg/m(2)/week) modified AIO regimen combined irinotecan for 3 weeks, followed by a 1-week rest interval as one course. Throughout the period of treatment, there was no adverse event, and this regimen has been maintained for 5 courses. After 5 courses of chemotherapy, primary tumor and metastases to para-aortic lymph nodes were remarkably reduced on colonoscopy and abdominal CT. So, she could undergo curative resection. Pathological efficacy was Grade 3, a complete response. This combination therapy may well be useful for advanced colon cancer patients.

Granulocytic sarcoma presenting as a thrombosed external hemorrhoid in a patient with myelodysplastic syndrome overt leukemia.

A 67-year-old Japanese man complained of a painful lump in his anus. He had a 15-month history of myelodysplastic syndrome (MDS) and had been diagnosed with MDS overt leukemia. A solid lump measuring 1.0 cm in diameter was detected in the anal verge. Under a diagnosis of a thrombosed external hemorrhoid, thrombectomy was performed under local anesthesia. One week after thrombectomy, the wound had not healed, and grayish-green tissue was seen at the bottom. A biopsy of the wound revealed atypical mononuclear cell infiltration. Myeloperoxidase and lysozyme were positive on immunohistochemical staining. Finally, the diagnosis of granulocytic sarcoma (GS) was made. Though it is well known that perianal complications occur quite often in patients with leukemia, it is unusual for a diagnosis of GS of the anus to be definitely established. To our knowledge, there has not been a previous report of GS presenting as a thrombosed external hemorrhoid. The development of GS should be considered during the management of such lesions, especially in patients with bone marrow disorders, such as acute myeloid leukemia (AML) or high-risk MDS.