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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.

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.

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.

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%.

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.

[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.