Search

A 55-year-old-man underwent laparoscopic sigmoidectomy for sigmoid colon cancer. Preoperative barium enema showed a slightly medial displacement of the descending colon, and the sigmoid colon was quite long. The operative findings showed that the descending colon was not fused with the retroperitoneum and shifted to the midline and the left colon adhered to the small mesentery and right pelvic wall. Thus, a diagnosis of persistent descending mesocolon (PDM) was made. The left colon, sigmoid colon, and superior rectal arteries often branch radially from the inferior mesenteric artery. The sigmoid mesentery shortens, and the inferior mesenteric vein is often close to the marginal vessels. By understanding the anatomical feature of PDM and devising surgical techniques, laparoscopic sigmoidectomy for sigmoid colon cancer with PDM could be performed without compromising its curative effect and safety.

Molecular dynamics simulation was performed to understand the growth mechanism of single-walled carbon nanotubes (SWNTs) by using the Brenner–Tersoff potential as the interaction among carbon atoms (C–C) and the Tersoff-type potential as the interaction between carbon and metal (C–M) and between metal and metal atoms (M–M). The potential functions for C–M and M–M bonds were established from the results of ab initio calculations. The growth of high-quality SWNTs was simulated at a suitable temperature and supply ratio of carbon atoms. The potential energy of carbon atoms was strongly dependent on the number of C–C and C–M bonds. The dependence explains the growth process, including cap formation, its lift-off, and the continuous SWNT growth.

A 45-years-old man presented discharge of abscess from the umbilicus with lower abdominal pain. CT scan showed huge tumor from the bladder to the umbilical part with sigmoid colon invasion. He was diagnosed as urachal carcinoma, which was confirmed by pathological examination. We started FOLFOX chemotherapy according to advanced colon cancer. Approximately 80% of reduction was accomplished after 11 courses of FOLFOX. We performed radical cystectomy with sigmoid colon resection. Pathological examination revealed complete resection with negative surgical margin. No recurrence and metastasis were observed after 30 months of surgery. Urachal carcinoma is often advanced cancer when diagnosed. Effective chemotherapy is not established well. FOLFOX chemotherapy demonstrated the well antitumor effect in this case.

Besides antibiotic prophylaxis, antiseptic skin preparation is an important measure to prevent surgical site infection (SSI). No reports have detailed the relationship between SSI and umbilical microflora following laparoscopic colorectal cancer with a transumbilical longitudinal incision. Risk factors and the rate of SSI were investigated in 453 patients who underwent laparoscopic colorectal resection over a 3-year period. Microbiological samples were collected from the umbilicus and SSI areas. After laparoscopic procedure, we observed SSIs in approximately 5% of cases, with superficial SSI in 15 (3.3%) patients and organ/space SSIs 7 (1.5%). In univariate analysis, preoperative albumin (Alb) value and anastomosis of enterocolostomy were significantly associated with superficial SSI development. Also, age, blood loss, stoma, tumor site (rectum), and Hartmann/abdominal perineal resection (APR) were significant risk factors for organ/space SSI. In multivariate analysis, the preoperative Alb value was the most significant factor associated with a predisposition to superficial SSI. The bacteria detected in SSI were mostly different from those at wound closure. Antibiotic-resistant bacteria were included in organ/space SSI all cases. SSI development with laparoscopic surgery reportedly occurs in about 3–15% cases. The SSI rate in this study and other reports was comparable. Using small transumbilical longitudinal incision in laparoscopic colorectal surgery is less likely to cause SSI when sufficient control measures are enacted, even though the umbilicus contains resident bacteria in abundance.

Background Anastomotic leakage during laparoscopic low anterior resection (Lap-LAR) for rectal cancer remains challenging for colorectal surgeons. Firing linear staplers multiple times has been reported as a risk factor for iatrogenic anastomotic leakage. Our institute usually performs rectal transection using 2 planned stapler fires followed by anastomosis with the double-stapling technique. Methods Between November 2009 and September 2016, a total of 272 consecutive patients underwent Lap-LAR with double-stapling anastomosis for rectal cancer. We inserted a linear 45-mm stapler cartridge from a port in the lower right quadrant of the abdomen. The first transection was made up to three-quarters of the rectal wall, and the remaining rectum was completely resected using a second stapler. During this procedure, the intersection of the 2 staple lines, which might otherwise cause anastomotic leakage, was located in the center of the stump of the distal rectum, so the intersection at the rectal stump was able to be easily removed using a circular stapler. Results None of our patients were converted to open surgery. Among the 272 Lap-LAR procedures for which use of 2 stapler fires was planned, 3 fires occurred in error only once (0.4%). Rectovaginal fistula and anastomotic leakage occurred in 1 patient (0.4%) and 9 patients (3.3%), respectively, and 49 (18.0%) patients required protective diverting stoma. Conclusion Rectal transection with 2 planned stapler fires appears safe, practical, and straightforward to standardize, and reduces the need for multiple linear fires and the incidence of anastomotic leakage.

The aim of this study was to compare the postoperative short- and long-term outcomes after laparoscopic colorectal surgery (LCS) between octogenarians and healthy middle-aged patients. Between January 1997 and July 2009, 655 consecutive laparoscopic surgeries for colorectal cancer patients were operated by 1 colorectal surgeon. Ninety-three patients were octogenarians (≥80 years), and 133 patients were case-matched middle-aged (60–69 years) patients. We analyzed the mean operative time, blood loss, type of surgery for rectal cancer, length of hospital stay, mortality, and morbidity. The overall survival curve was constructed using the Kaplan–Meier method. The American Society of Anesthesiologists classification was significantly higher in the octogenarians than in the middle-aged controls. However, there were no significant differences between the two groups in terms of the incidence of morbidities (11.7 vs. 9.2 %) and length of hospital stay (12.1 vs. 10.9 days). The number of lymph nodes harvested was significantly fewer (p

A 66-year-old man diagnosed with rectal cancer underwent high anterior resection and received adjuvant chemotherapy (UFT plus UZEL). One year after the surgery, lung and para-aortic lymph node(PLN)metastases were identified. We chose mFOLFOX6 for first-line chemotherapy. After 7 courses, we changed the regimen to sLV5FU2 because of Grade 3 neuropathy. After 5 courses, to treat progressive disease(PD), we changed the regimen to FOLFIRI. Then, the patient had stable disease (SD), and surgical excision was performed for both lung and lymph node recurrence without adjuvant chemotherapy. Six years after the excision, a CT scan revealed PLNagain. We chose FOLFIRI plus cetuximab. After 9 courses, the lymph nodes decreased in size and there was no other recurrence; thus we performed resection. However, a third PLNrecurrence was identified 20 months after the resection. Chemotherapy has continued for 47 courses, and he has maintained SD for more than 2 years.

The patient was a 56-year-old man who presented with perianal pain and a perianal abscess. After admission, he underwent debridement and colostomy due to poor control of the perianal abscess. Following a biopsy of the resected specimens, he was diagnosed with adenocarcinoma in the anorectal fistula. CT and MRI revealed that the tumor had invaded into the internal obturator muscle. Therefore, preoperative chemoradiotherapy and chemotherapy were given for locally advanced cancer. Subsequent to tumor shrinkage, we performed an abdominoperineal resection. Histopathologically, no cancer cells were detected on the surgical margin, and the effect of the preoperative therapy was judged to be Grade 1b. There has been no indication of recurrence of cancer after 5 years.

Background Circulating tumor DNA (ctDNA) carries information on tumor burden. However, the mutation spectrum is different among tumors. This study was designed to examine the utility of ctDNA for monitoring tumor burden based on an individual mutation profile. Methodology DNA was extracted from a total of 176 samples, including pre- and post-operational plasma, primary tumors, and peripheral blood mononuclear cells (PBMC), from 44 individuals with colorectal tumor who underwent curative resection of colorectal tumors, as well as nine healthy individuals. Using a panel of 50 cancer-associated genes, tumor-unique mutations were identified by comparing the single nucleotide variants (SNVs) from tumors and PBMCs with an Ion PGM sequencer. A group of the tumor-unique mutations from individual tumors were designated as individual marker mutations (MMs) to trace tumor burden by ctDNA using droplet digital PCR (ddPCR). From these experiments, three major objectives were assessed: (a) Tumor-unique mutations; (b) mutation spectrum of a tumor; and (c) changes in allele frequency of the MMs in ctDNA after curative resection of the tumor. Results A total of 128 gene point mutations were identified in 27 colorectal tumors. Twenty-six genes were mutated in at least 1 sample, while 14 genes were found to be mutated in only 1 sample, respectively. An average of 2.7 genes were mutated per tumor. Subsequently, 24 MMs were selected from SNVs for tumor burden monitoring. Among the MMs found by ddPCR with > 0.1% variant allele frequency in plasma DNA, 100% (8 out of 8) exhibited a decrease in post-operation ctDNA, whereas none of the 16 MMs found by ddPCR with < 0.1% variant allele frequency in plasma DNA showed a decrease. Conclusions This panel of 50 cancer-associated genes appeared to be sufficient to identify individual, tumor-unique, mutated ctDNA markers in cancer patients. The MMs showed the clinical utility in monitoring curatively-treated colorectal tumor burden if the allele frequency of MMs in plasma DNA is above 0.1%.

The authors used 70% deacetylated chitin and cisplatin (CDDP) to devise a novel anticancer drug delivery system (DDS). We examined in vitro release of the CDDP from the system. The novel system was intraperitoneally( ip) given to malignant ascites-bearing mice, and the survival time of each animal was recorded. The related oncolytic mechanism was immunologically investigated. More than 70-90% of the CDDP was gradually delivered from the system in 24 hours. Nineteen animals among 30 treated with our system survived for longer than 4 weeks, and a recurrence of ascites was nil. A 4- week survival rate of the animals with ip injected conventional CDDP was 5/14. All non-treated animals had massive ascites and died within 4 weeks. Immunologic studies suggested that cytotoxic immunoresponse was induced in the mice treated with the novel system. Our newly devised system warrants for clinical applications in the treatment of malignant ascites.

Indocyanine green (ICG) is specifically excreted through the biliary tracts. The authors applied ICG as a carrier of gemcitabine (GEM) to devising a novel drug delivery system. Our newly devised chitin flakes, ICG and GEM were mixed together. Then physiological saline solution was added to the mixture to form the system. The release profiles of GEM and ICG from the system were examined at various times in vitro. Anticancer activities of the GEM and ICG delivered from the system were detected by MTT assay method using human pancreatic cancer cell lines. The novel system was visco-elastic green sol at room temperature and changed to gel at body temperature. Seventy to 80% of GEM was gradually delivered from the system in 24 hours, and 30 to 50% of ICG was slowly released over 24 hours. The released GEM favorably demonstrated anticancer activities against the cancer cells, while the ICG released from the system showed no oncolytic activities. These suggested that our devised system would be clinically useful as a novel tool in cancer chemotherapy.

Background The binding of EGFR and its ligands leads to autophosphorylation of receptor tyrosine kinase as well as subsequent activation of signal transduction pathways that are involved in regulating cellular proliferation, differentiation, and survival. An EGFR inhibitor, cetuximab binds to EGFR and consequently blocks a variety of cellular processes. KRAS/BRAF mutations are known to be associated with a low response rate to cetuximab. In the present study, to clarify the anti-tumor mechanisms of cetuximab, we evaluated the KRAS/BRAF status, phosphorylation level of the EGFR pathway, and the tumor suppression effect in vivo, using a human colon cancer cell line HT29, which exhibited the highest EGFR expression in response to the cetuximab therapy among the 6 colorectal cancer cell lines tested. Findings The conventional growth suppression assay did not work efficiently with cetuximab. EGF, TGF-α, and IGF activated the EGFR/MAPK cell signaling pathway by initiating the phosphorylation of EGFR. Cetuximab partially inhibited the EGFR/MAPK pathway induced by EGF, TGF-α, and IGF. However, cetuximab exposure induced the EGFR, MEK, and ERK1/2 phosphorylation by itself. Mouse xenograft tumor growth was significantly inhibited by cetuximab and both cetuximab-treated and -untreated xenograft specimens exhibited phosphorylations of the EGFR pathway proteins. Conclusions We have confirmed that cetuximab inhibited the EGFR/MAPK pathway and reduced tumor growth in the xenografts while the remaining tumor showed EGFR pathway activation. These results suggest that: ( i ) The effect of cetuximab in growth signaling is not sufficient to induce complete growth suppression in vitro; ( ii ) time-course monitoring may be necessary to evaluate the effect of cetuximab because EGFR signaling is transmitted in a minute order; and ( iii ) cetuximab treatment may have cells acquired resistant selectively survived in the heterogeneous cancer population.

The authors devised two different types of cisplatin (CDDP) delivery systems; namely, System A and System B. The anticancer efficacy with each system was examined using cancer-bearing animals. Seventy-percent deacetylated chitin (DAC-70) was used as the drug carrier in the system. Cancer-bearing animals were prepared by intra-peritoneally (ip) inoculating the MM-46 cancer cells to C3H mice. Each novel system was also ip injected to the cancer-bearing mouse, and then survival time of each animal was recorded to evaluate the anti-cancer efficacy of the system. Both Systems A and B were viscoelastic sol at 25°C and slowly changed to gel at 37°C. Four-week survival rate of each animal treated with the System was as follows: System A 6/10 (60%), System B 10/11 (90.9%), conventional CDDP alone 3/9 (33.3%) and non-treated 0/7 (0%). No signs of recurrence of ascites were encountered in the long-term survived animals treated with System A and B. Our newly devised systems provided a favorable antitumor efficacy in vivo. Now, we will carry out further studies by making a clinically applicable novel conjugated system, DAC-70 and CDDP.

[Background] Adjuvant chemotherapy based on 5-FU has been a mainstay of postoperative treatment for the majority of cancers arising in the gastrointestinal tract. Although adjuvant chemotherapy has shown a favorable success rate, there are still considerable numbers of patients who experience cancer relapse following this therapy. Therefore, being able to predict chemosensitivity with data backed by solid molecular evidence would allow us to select biologically reasonable drugs, as well as to avoid adverse effects in those patients who may fail to benefit from chemotherapy. [Materials and Methods] Several candidate markers have been isolated based on the drug-protein association from a “chemosensitivity and protein expression matrix” obtained by a “conventional chemosensitivity assay for 12 drugs” and a “quantitative lysate array for 50 proteins” using a panel of 12 cancer cell lines. The panel of candidate proteins was examined by immunohistochemistry and tissue microarrays of 79 gastrointestinal cancer cases treated with 5-FU based adjuvant chemotherapy after curative operation. A functional assay by siRNA gene knockdown was also performed to confirm whether the protein expression actually affects the chemosensitivity. [Results] The 79 gastrointestinal cancer patients who underwent a curative operation followed by 5-FU based adjuvant chemotherapy were investigated by clinicopathological study and immunohistochemistry. Among the candidate proteins measured in these 79 patients, expression of nuclear NFκB showed a significant association with cancer relapse (median observation period, 2.8 years; p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4129. doi:10.1158/1538-7445.AM2011-4129

Background: The conventional chemosensitivity test employs a growth suppression assay. However, surgically removed specimens often have low viability which makes the assay unreliable, since the poor cell growth may be associated with the low viability instead of the chemosensitivity of the cell. On the other hand, we do know that the level of proteins involved in signal transduction is changed prior to cellular responses to the anti-cancer agents. In the present study, we investigated if protein signaling within a 24-hour exposure of the anti-cancer agents can predict the cellular fate at 72-hour time points. Materials and Methods: The human colon cancer cell line, HCT116, was exposed to three different DNA-damaging anti-cancer agents including gamma irradiation, ultraviolet, and doxorubicin. The anti-cancer agent-exposed cell pellets from different conditions (e.g., doses, and time-points) were collected to produce a lysate array, which finally accommodated more than 500 samples on a single glass slide. Array image and quantitative protein analyses were performed with the P-SCAN and ProteinScan programs. Results: A total of 19 protein species were tested on a lysate array, providing kinetic information of the protein. In response to all three agents, p53 protein was stabilized and the level increased over time in a dose-dependent manner. Upon detailed time-course analysis, however, an oscillation was seen in response to gamma irradiation, indicating the presence of a feedback loop. Comparing the rate of increasing levels of p21 and CyclinD3 within 24 hours in response to doxorubicin administration, the rates are well associated with the status of cell fate. In other words, when the rate of p21 is higher than CyclinD3, it is associated with a G2 arrest at 72 hours, whereas a higher CyclinD3 rate is associated with apoptosis at 72 hours after drug administration. Conclusion: Some events occurring at 72 hours can be predicted by seeing the quantitative level of protein kinetics within 24 hours. Most of the primary culture cells can survive for only a short period of time. The protein kinetics may be a useful clinical chemosensitivity predictor even when using low viability specimens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5502.

Background The use of standard chemotherapy regimens has changed the application of chemosensitivity tests from all chemotherapy-eligible patients to those who have failed standard chemotherapy, which includes patients with highly advanced, relapsed, or chemoresistant tumors. Methods We evaluated a total of 43 advanced primary and relapsed gastric cancers for chemosensitivity based on drug dose response curves to improve the objectivity and quality of quantitative measurements. The dose response curves were classified based on seven expected patterns. Instead of a binary chemosensitivity evaluation, we ranked drug sensitivity according to curve shapes and comparison with the peak plasma concentration (ppc) of each drug. Results A total of 193 dose response curves were obtained. The overall informative rate was 67.4%, and 85.3% for cases that had a sufficient number of cells. Paclitaxel (PXL)and docetaxel tended to show a higher rank, while cisplatin (CIS) and 5-fluorouracil (5-FU) tended to show resistance, particularly among the 20 cases (46.5%) that had recurrent disease after receiving chemotherapy with CIS and S-1 (5-FU). As such, we speculate that the resistant pattern of the chemosensitivity test suggests that cells with acquired drug resistance were selected by chemotherapy. Indeed, we observed a change in the chemosensitivity pattern of a sample before and after chemotherapy in terms of PXL sensitivity, which was used after primary chemotherapy. Conclusions These results suggest that: (i) the dose–response pattern provides objective information for predicting chemosensitivity; and (ii) chemotherapy may select resistant cancer cell populations as a result of the therapy.