Long-term Survival after Treatment of Synchronous Isolated Right External Iliac Lymph Node Metastasis from Ascending Colon Cancer: A Case Report.

BACKGROUND: Synchronous isolated external iliac lymph node metastasis of ascending colon cancer is extremely rare, and its treatment strategy has not been established. In this report, we present a case of long-term survival after surgical resection and adjuvant chemotherapy for ascending colon cancer with synchronous isolated right external iliac lymph node metastasis. CLINICAL CASE: A 65-year-old woman with anorexia and anemia was referred to our hospital. Colonoscopy and computed tomography revealed a three-quarter circumferential type 2 tumor from the cecum to the ascending colon, along with regional and right external iliac lymph node swelling. We diagnosed ascending colon cancer with right external iliac artery lymph node metastasis. An open right hemicolectomy with D3 and right external iliac lymph node dissections were performed. Results of histopathological examination showed that both lymph nodes were metastasized from ascending colon cancer. The patient received eight courses of capecitabine and oxaliplatin therapy as adjuvant chemotherapy. At 60 months after surgery, the woman has not had a recurrence. CONCLUSIONS: Surgical resection and adjuvant chemotherapy may be an effective treatment strategy for synchronous isolated right external iliac lymph node metastases from ascending colon cancer.

[Long-Term Complete Response following Chemotherapy for Advanced Gastric Cancer in an Elderly Patient].

A 78-year-old man was diagnosed with HER2-positive advanced gastric cancer, cT3N2M1(LYM: #16a1, 16b1), cStage ⅣB, after being referred for anemia. The lesion was deemed unresectable, and first-line chemotherapy was initiated using S-1, cisplatin(CDDP), and trastuzumab(T-mab). After 2 courses of chemotherapy, the patient developed febrile neutropenia( Grade 3). At this point, the lesion showed partial response(PR), and chemotherapy was continued using oral S-1 as a single agent. After 3 months of S-1 monotherapy, the para-aortic lymph node metastases showed a complete response (CR). S-1 monotherapy was continued without major adverse events for 2 years, and the patient is presently alive and well 6 years after obtaining clinical CR. This may suggest that S-1 is a safe and effective treatment for unresectable advanced gastric cancer in elderly patients.

Occurrence of Focal Atrial Tachycardia During the Ablation Procedure Is Associated With Arrhythmia Recurrence After Termination of Persistent Atrial Fibrillation.

INTRODUCTION: Catheter ablation can terminate persistent atrial fibrillation (AF). However, atrial tachycardia (AT) often arises after termination of AF. METHODS AND RESULTS: Of 215 patients who underwent index stepwise ablation for persistent AF, 141 (66%) patients (64 ± 9 years) in whom AF terminated during the ablation procedure were studied. If AF converted into AT, ablation for AT was subsequently performed. ATs were categorized as focal or macroreentrant AT. We assessed whether type of AT occurring after conversion of AF during the ablation procedure was associated with freedom from atrial tachyarrhythmia (AF or AT) during follow-up. Sinus rhythm was directly restored from AF in 37 patients, while 34, 37, and 33 patients had focal AT alone, a mix of focal and macroreentrant AT, and macroreentrant AT alone after termination of AF, respectively. Arrhythmia-free survival rates at 1 year after the index procedure were 30%, 34%, 61%, and 59% in the patients with focal AT alone, a mix of focal AT and macroreentrant AT, macroreentrant AT alone, and direct restoration of sinus rhythm, respectively (P = 0.004). Type of AT occurring during the index procedure was associated with type of recurrent AT (P = 0.03), but the origin of focal AT occurring during the index ablation differed from that of the recurrent AT in 85% of patients. CONCLUSION: In patients who had AF termination by ablation, occurrence of focal AT during the ablation procedure was associated with worse clinical outcome than occurrence of macroreentrant AT, likely due to ATs arising from other foci during follow-up.

[A Case of Severe Bradycardia Induced by Combination Chemotherapy with Cisplatin and 5-Fluorouracil].

A 78-year-old man with Stage III esophageal cancer was referred to our hospital. Combination chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5-FU) was initiated. The patient experienced bradycardia episodes after starting the cisplatin infusion on day 1; he was otherwise asymptomatic. Therefore, combination chemotherapy was continued. However, on day 4, his heart rate dropped to 22 beats/min, with no other symptoms; however, treatment was stopped. After treatment was stopped, the patient's heart rate improved gradually and returned to normal in a few days. Combination chemotherapy with CDDP and 5-FU is a useful treatment for esophageal cancer, but it may induce severe bradycardia. Therefore, we must perform infusion therapy with caution.

Paget's disease of the male breast: a case report.

The patient was a 91-year-old man with change in nipple appearance, itching and redness, and a palpable breast mass. At presentation, mammary Paget's disease (PD) was clinically suspected. Skin biopsy was performed and showed epidermis invaded by Paget cells, characterized by hyperchromatic nuclei and abundant pale-staining cytoplasm. Computed tomography and mammary ultrasonography confirmed the absence of an underlying invasive carcinoma, and the patient underwent right mastectomy and sentinel lymph node biopsy (SLNB). Both sentinel lymph nodes were found to be negative perioperatively, and further axillary dissection was not performed. Pathological results revealed no malignancy under the nipple, yet the Paget cells were more widely spread than expected. The patient was followed up without the need of postoperative chemotherapy. Male mammary PD is an extremely rare breast cancer, and there is no standard preoperative assessment or operative procedure. Mammography is many times unable to detect possible underlying breast carcinoma in female patients with mammary PD, and previous studies have reported that the detection rate was less than 50 %. However, some researchers reported that magnetic resonance imaging (MRI) might be more detectable to confirm the extent of the cancer. The extent of the skin change around the nipple is often different from the actual perimeter of Paget cells. In extra-mammary PD, mapping biopsy is known to be useful to determine areas free of cancer. The benefits of SLNB have also been demonstrated for the management of less invasive breast cancers, and previous reports have shown that the use of SLNB is reasonable for treatment of mammary PD without underlying invasive cancer. MRI, mapping biopsy, and SLNB are all less invasive procedures and thus may be suitable for treatment of male mammary PD.

Gallbladder bed pocket score as a preoperative measure for assessing the difficulty of laparoscopic cholecystectomy.

INTRODUCTION: Laparoscopic cholecystectomy (Lap-C) is a standard surgery for symptomatic gallbladder stones and acute or chronic cholecystitis. Resident surgeons often perform this operation early in their training, but they sometimes encounter difficulties for various technical reasons. Although encountering a gallbladder buried deep within the gallbladder bed is a common operative difficulty, literature on the subject scarcely exists. METHODS: Forty-two patients underwent Lap-C at our hospitals and were analyzed retrospectively. We defined the gallbladder bed pocket score (GBPS) as the maximum ratio between the height and width of the gallbladder bed measured based on multi-detector computed tomography (MDCT) images. GBPS and clinical factors were assessed in terms of their correlation with the time required for gallbladder dissection from the gallbladder bed. RESULTS: Of the 42 patients, 20 had histories of acute or chronic cholecystitis. The mean gallbladder dissection time was 14.9 min, and the mean GBPS was 0.43 in the coronal MDCT section and 0.56 in the sagittal section. The correlation coefficient between the GBPS and gallbladder dissection time was 0.40 (P = 0.01) in the coronal section and 0.38 (P = 0.02) in the sagittal section of the MDCT images. There was no statistically significant correlation between gallbladder dissection time and the surgeon's experience, patient's history of cholecystitis, gallstone size, or blood loss. However, GBPS > 0.4 predicted more difficult and prolonged dissection. CONCLUSION: GBPS is a useful tool for preoperatively predicting the time needed to dissect the gallbladder from the gallbladder bed during Lap-C. Cases with GBPS < 0.4 seem more suitable for resident surgeons who are performing gallbladder dissection early in their Lap-C training.

Standardized laparoscopy-assisted distal gastrectomy with a novel surgical technique for lifting the liver.

BACKGROUND/AIMS: It is very important to achieve a sufficient field and space in laparoscopic assisted distal gastrectomy (LADG) for a less-experienced surgeon. In this study, the usefulness of a novel surgical technique to lift the liver was evaluated in LADG. METHODOLOGY: Fifty-four patients who underwent standardized LADG for gastric cancer using the novel technique of lifting the liver were retrospectively evaluated based on video records. Patient characteristics, the time required to lift the liver and for gastrectomy, total operation time, blood loss and complications were analyzed. RESULTS: The mean time necessary to lift the liver using this novel technique was 240.1±86.1 seconds and that for gastrectomy was 167.6±50.4 minutes. Blood loss was 72.5±59.6mL. The morbidity rate was 4/54 (7.4%). CONCLUSIONS: Standardized LADG using this novel technique is feasible and possible in a period of time.

Multidetector computed tomography for preoperative identification of left gastric vein location in patients with gastric cancer.

BACKGROUND: The area near the left gastric vein (LGV) is a challenging site at which to perform dissection of the lymph nodes during gastrectomy. Therefore, knowledge of the precise location of the LGV is important. The objective of this study was to examine the usefulness of multidetector computed tomography (MDCT) for the identification of the LGV. METHODS: Eighty-one patients with gastric cancer underwent MDCT, which was performed with contrast media in 76 patients and without contrast media in 5 patients. A 5-mm thin slice of the frontal image was reconstructed. These images were examined preoperatively to detect the location of the LGV. Upon gastrectomy, the LGV was identified and its location compared to that determined by MDCT. RESULTS: The LGV was identified by MDCT in 76 of the 81 patients (93.8%). The LGV was subsequently located during the operation in all 81 patients. The LGV was located dorsal to the common hepatic artery in 40 patients (49.4%), ventral to the common hepatic artery in 18 patients (22.2%), ventral to the splenic artery in 17 patients (21.0%), dorsal to the splenic artery in 2 patients (2.5%) and in other positions in 4 patients (4.9%). In all patients, the location of the LGV detected using MDCT was consistent with that identified during gastrectomy. In the 4 patients with relatively unusual locations of the LGV, these 4 LGV variants were identified preoperatively by MDCT. CONCLUSION: MDCT was useful for identifying the location of the LGV prior to gastrectomy.

[A case of curatively resected biliary tract cancer with peritoneal dissemination through effective response to chemotherapy of S-1].

The patient is a 55-year-old woman who has biliary tract cancer with peritoneal dissemination (T3N1P2M0, Stage IV b). Since a curative operation was deemed impossible, we conducted chemotherapy using S-1. S-1 (120 mg/day) was administered for 2 weeks and then chemotherapy was discontinued for 1 week, which was regarded as one course. After 2 courses of the chemotherapy, CT scan showed that the metastatic lymph node and tumor of peritoneal dissemination were reduced in size, and that there was no ascites. Left lobectomy of the liver, cholecystectomy, and partial resection of omentum were carried out. The pathological diagnosis was also curative (pT1, pN0, pP0, Stage I). We think this case shows the possibility of S-1 for patients with unresectable biliary tract cancer.

[A successfully resected case of rectal cancer with liver metastases treated with mFOLFOX6 and bevacizumab].

A sixties-man had complained of melena. Colonoscopy revealed type 2 tumor at rectum. Computed tomography (CT)demonstrated lymph node metastasis in front of sacrum and two low density areas which were suspected metastases in the liver. The patient was diagnosed stageIV rectal cancer and resected primary focus and lymph node metastasis.[ Ra-RS, ant, type 2, moderately differentiated adenocarcinoma, ly1, v3, pSE, pN2, sH1(Grade C), sP0, pM1(No. 270)]without liver resection. It was due to high level of CEA and remote lymph node metastasis. The patient was treated with mFOLFOX6 and bevacizumab after the operation. The level of CEA decreased to normal level and CT revealed a partial response after 4 cycles of systemic chemotherapy. Liver resection was performed safely. Histological response was Grade 2 at liver metastases.

Anti-tumor effect of angiogenesis inhibitor TNP-470 and 5-FU combined therapy on human gastric cancer xenograft.

BACKGROUND/AIMS: TNP-470, an angiogenesis inhibitor, has already been used in combination with chemotherapy to enhance its antitumor activity. The mechanism of enhanced antitumor activity in combination therapy has not been clarified, however, and few studies have described the combined effect of TNP-470 and 5-fluorouracil (5-FU) on gastric cancer. The present study was conducted to investigate the effect of TNP-470 + 5-FU on gastric cancer cell line MKN-45 in vivo and in vitro. METHODOLOGY: MKN-45 cells were subcutaneously injected into mice that were divided into 4 groups: a control group, a 5-FU treated group, a TNP-470 treated group, and a 5-FU + TNP-470 treated group. After the inoculation, the volume of subcutaneous tumors was measured. Blood and lymphatic vessels were also analyzed for the assessment of lymphangiogenesis. RESULTS: Compared with 5-FU or TNP-470 alone, the combined effect of TNP-470 and 5-FU significantly inhibited and suppressed tumor growth in a synergistic fashion. The combined therapy significantly suppressed both angiogenesis and lymphagenesis. CONCLUSIONS: The study suggests that the combined therapy provides an enhanced antitumor effect on human gastric cancer. The enhanced antitumor activity is explained mainly by the stronger inhibition of angiogenesis.

Three-dimensional echocardiography could distinguish a ventricular septal defect adjacent to asymptomatic ruptured sinus of valsalva aneurysm.

Sinus of Valsalva aneurysm (SVA) arises frequently in the right coronary sinus, and ventricular septal defect (VSD) is a prevalent coexistent cardiac abnormality. A 38-year-old asymptomatic male diagnosed with VSD on cardiac catheterization in his childhood, was referred to our hospital for the change in intensity of his cardiac murmur pointed out by his family physician. A grade V continuous murmur was auscultated with a thrill loudest at the forth left sternal border. Although, transthoracic and transesophageal echocardiography and cardiac catheterization have showed the ruptured right coronary sinus aneurysm, it was difficult to demonstrate coexistence of a doubly committed subarterial VSD. Three-dimensional echocardiography could provide clear images for diagnosis of the VSD closely adjacent to the ruptured SVA. The defect was confirmed at surgery.

Intratumoral heterogeneous expression of thymidylate synthase in gastric cancer.

BACKGROUND/AIMS: Thymidylate synthase (TS) is reported to be a predictive factor of survival in gastric cancer patients. Its heterogeneous expression has been observed in various cancerous lesions but has not been assessed intratumorally. The aim of this study was to determine the most pertinent site for investigating intratumoral TS expression for the prediction of survival. METHODOLOGY: TS staining grade was evaluated at the center (CT), the horizontal edge (HT) and the vertical edge (VT) of the tumor, and TS protein level was determined by ELISA at CT and HT. Proliferating cell nuclear antigen (PCNA) was examined for proliferation markers in all tumor samples. RESULTS: TS expression at HT and VT was significantly higher than at CT. A positive correlation was observed between TS protein level and PCNA-Labeling Index at HT, but not at CT. The survival rate of the high TS group was poor compared with the low TS group at HT and VT, but not at CT. CONCLUSIONS: The horizontal edge of the tumor (HT) is the most pertinent site for the evaluation of TS expression in gastric cancer; it could prove especially useful in the presurgical estimation of prognosis through biopsy samples.

Relationship between immunohistochemical evaluation of thymidylate synthase and proliferating cell nuclear antigen labeling index in gastrointestinal carcinoma.

We undertook this study to clarify the effect of immunohistochemical expression of thymidylate synthase (TS) on proliferative activity of carcinoma lesions in patients with gastrointestinal carcinoma. TS was immunohistochemically evaluated in 53 gastric carcinoma and 51 colorectal carcinoma patients using anti-TS polyclonal antibody. Proliferative activity represented by proliferating cell nuclear antigen (PCNA) labeling index (LI) was also immunohistochemically estimated using monoclonal antibody PC10. Then, the correlation between TS expression and PCNA LI was investigated. Both in gastric and colorectal carcinoma, the PCNA LIs of the high-TS group were significantly higher than those of the low-TS group. In gastric carcinoma, the PCNA LIs of the high-TS group were higher than those of the low-TS group in differentiated adenocarcinoma, in the depth of mucosal and/or submucosal layer, in cases without lymph node metastasis, and notwithstanding lymphatic or venous invasion. In colorectal carcinoma, PCNA LIs of the high-TS group were higher than those of the low-TS group in well differentiated adenocarcinoma, in the depth of serosa, in cases with lymph node metastasis, in cases with lymphatic invasion, and notwithstanding venous invasion. Immunohistochemical expression of TS was correlated with the proliferative activity represented by PCNA LI, but was not identical with PCNA LI.

Association of VEGF genotype with mRNA level in colorectal adenocarcinomas.

The mRNA expression of vascular endothelial growth factor (VEGF) was evaluated in colorectal adenocarcinomas and adjacent noncancerous colorectal tissues in 18 Japanese patients. The expression was confirmed to be up-regulated in the colorectal adenocarcinomas, when compared with the noncancerous tissues. Twelve genotypes of VEGF: six positions in the promoter region, two in the 5'UTR, and four in the 3'UTR, and their association with the expression of VEGF mRNA were evaluated. While G-1877A, T-1455C, G-1154A, C702T, and G1612A were not detected, C-2578A, T-1498C, G-1190A, C-634G, C-7T, C936T, and C1451T were found at allele frequencies of 4/36, 15/36, 15/36, 20/36, 8/36, 6/36, and 6/36, respectively, suggesting that C-2578A, G-1154A, and G1612A were associated with a decreased risk for colorectal adenocarcinoma. T-1498C (G-1190A) and C-7T were found to be associated with higher levels of VEGF mRNA, and may be a risk factor for the development of liver metastasis and/or prognosis of colorectal adenocarcinoma.

Intravenous administration of ghrelin stimulates growth hormone secretion in vagotomized patients as well as normal subjects.

OBJECTIVE: Ghrelin is a potent peptide stimulating GH secretion. Besides its direct action on the pituitary, ghrelin has been reported to stimulate GH release via the vagal afferent nerve in rats. To examine the involvement of vagal nerve in ghrelin-induced GH secretion in humans, GH responses to ghrelin were compared between vagotomized patients with gastrectomy and normal subjects. METHODS: Ghrelin (0.2 microg/kg) or GHRH (1 microg/kg) was administered intravenously in vagotomized patients and normal subjects on separate days, and plasma GH responses to the stimuli were examined. RESULTS: Ghrelin caused a significant plasma GH rise in both vagotomized patients and normal subjects. Peak GH levels in vagotomized patients (37.5+/-16.9 ng/ml) were not different from those in normal subjects (29.9+/-23.1 ng/ml). The areas under the curve of GH response to ghrelin did not differ between the two groups. GHRH also increased GH levels, and peak GH levels and areas under the curve after GHRH stimulation were also comparable between vagotomized patients and normal subjects. CONCLUSIONS: In the present study, the involvement of the afferent vagal nerve in ghrelin-induced GH secretion was not confirmed in humans.

Chemosensitivity assessed by collagen gel droplet embedded culture drug sensitivity test, and MDR1, MRP1, and MRP2 mRNA expression in human colorectal adenocarcinomas.

PURPOSE: To evaluate chemosensitivity and its correlation with expression levels of the multidrug resistant transporter (MDR1) and the multidrug resistance-associated proteins 1 and 2 (MRP1, MRP2) mRNA in human colorectal adenocarcinomas. METHODS: Colorectal adenocarcinomas were obtained as surgical samples from 25 patients. The chemosensitivity of 12 anticancer drugs was assessed by the collagen gel droplet embedded culture drug sensitivity test (CD-DST). The expression levels of MDR1, MRP1, and MRP2 mRNA in colorectal adenocarcinomas were also evaluated by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The chemosensitivity was successfully evaluated for 16 of 25 patients, and the anticancer drugs were effective against the samples showing a relatively high growth rate. Gemcitabine hydrochloride was found to be more promising than those often prescribed for the treatment of colorectal adenocarcinoma. There was no correlation of the mRNA expression levels of MDR1 and MRP1 with the chemosensitivity of any anticancer drugs tested, but mitomycin C was found to be more effective for the colorectal adenocarcinoma with relatively high expression of MRP2 mRNA.

MDR1, MRP1 and MRP2 genotypes and in vitro chemosensitivity in Japanese patients with colorectal adenocarcinomas.

In our previous paper, the chemosensitivity of human colorectal adenocarcinoma was evaluated against 12 anticancer drugs including 5-fluorouracil (5-FU), 7-ethyl-10-hydroxycamptothecin (SN-38), mitomycin C (MMC) and cisplatin (CDDP), and it was found that the anticancer drugs were effective against those with a relatively high growth rate. MMC was effective for those with a relatively high mRNA expression of the multidrug resistance-associated protein 2 (MRP2), whereas no correlation was found for the multidrug resistant transporter MDR1 and MRP1. In this study, 3 genotypes of MDR1, 4 genotypes of MRP1, and 6 genotypes of MRP2 were additionally evaluated, and it was suggested that MDR1 C3435T and MRP2 G1249A were related with the susceptibility to colorectal adenocarcinoma. The chemosensitivity against 5-FU, SN-38, MMC and CDDP was independent of MDR1 C3435T, MRP1 G2168A, and MRP2 C-24T (C3972T), possibly due to no association with the growth rate of and mRNA expression levels of MDR1, MRP1 and MRP2 in the adenocarcinoma, however, MDR1 C3435T tended to be accompanied with a higher expression of MDR1 mRNA.

Procedure for lymph node dissection around splenic artery in proximal gastric cancer.

BACKGROUND/AIMS: The effect of lymph node metastasis around the splenic artery on the prognosis of proximal gastric cancer patients is not confirmed. The aim of this study is to clarify the optimal procedure for lymph node dissection along the splenic artery in proximal gastric cancer. METHODOLOGY: Proximal gastric cancer patients who underwent total gastrectomy with pancreaticosplenectomy were examined. The anatomical location of lymph nodes and the metastases around the pancreas were also studied in pancreatic cancer patients who underwent total pancreatectomy. RESULTS: Multivariate analysis of lymph node metastasis around the splenic artery showed that No. 11 lymph node metastasis was affected by No.10 lymph node that was predicted by depth of invasion. Multivariate analysis of prognostic variables by Cox's proportional hazard regression revealed that No. 10 lymph node metastasis was the significant factor affecting prognosis. No lymph node metastasis infiltrating the pancreatic parenchyma was observed in the pancreatic body or the tail. CONCLUSIONS: Total gastrectomy preserving the pancreas and spleen is the optimal procedure in proximal T2 gastric cancer. Total gastrectomy with splenectomy is appropriate in T3 cases, and distal pancreatectomy should be additionally done only in cases of direct invasion by the lymph node and/or the tumor to the pancreas.