Assessment of Elastic Laminal Invasion Contributes to an Objective pT3 Subclassification in Colon Cancer.

The extent of tumor spread influences on the clinical outcome, and which determine T stage of colorectal cancer. However, pathologic discrimination between pT3 and pT4a in the eighth edition of the American Joint Committee on Cancer (AJCC)-TNM stage is subjective, and more objective discrimination method for deeply invasive advanced colon cancer is mandatory for standardized patient management. Peritoneal elastic laminal invasion (ELI) detected using elastic staining may increase the objective discrimination of deeply invasive advanced colon cancer. In this study, we constructed ELI study group to investigate feasibility, objectivity, and prognostic utility of ELI. Furthermore, pT classification using ELI was investigated based on these data. At first, concordance study investigated objectivity using 60 pT3 and pT4a colon cancers. Simultaneously, a multi-institutional retrospective study was performed to assess ELI's prognostic utility in 1202 colon cancer cases from 6 institutions. In the concordance study, objectivity, represented by κ, was higher in the ELI assessment than in pT classification. In the multi-institutional retrospective study, elastic staining revealed that ELI was a strong prognostic factor. The clinical outcome of pT3 cases with ELI was significantly and consistently worse than that of those without ELI. pT classification into pT3 without ELI, pT3 with ELI, and pT4a was an independent prognostic factor. In this study, we revealed that ELI is an objective method for discriminating deeply invasive advanced colon cancer. Based on its feasibility, objectivity, and prognostic utility, ELI can subdivide pT3 lesions into pT3a (without ELI) and pT3b (with ELI).

Evaluation of the 5-fluorouracil plasma level in patients with colorectal cancer undergoing continuous infusion chemotherapy.

5-Fluorouracil (5-FU) dosing has traditionally been based on the body surface area (BSA) in colorectal cancer treatment. However, there is accumulating evidence that dosing based on BSA may be of limited use. The purpose of the present study was to evaluate the changes in 5-FU plasma levels and tumor response as well as the severity of adverse events in patients with cancer treated with 5-FU combined chemotherapy. The dosing amount of 5-FU was determined based on the BSA. Blood samples were collected, and 5-FU plasma levels in 15 patients with colorectal cancer were measured three times (0, 22 and 40 h before and after the start of infusion) during constant-infusion of 5-FU for 46 h by an immunoassay. 5-FU plasma levels were significantly higher at 22 and 40 h compared with at 0 h (P<0.001), when all 15 patients were analyzed. Notably, the tumor response of the partial response/stable disease group showed significant increases in 5-FU plasma levels at 40 h compared with at 22 h (P<0.01), while the progressive disease group showed no significant increase. In addition, the 5-FU plasma level in the adverse event level of grade ≥2 was higher than that of grade <2 at 40 h after the start of infusion. Collectively, these observations indicated that during continuous infusion of 5-FU, the 5-FU plasma level increased significantly, and the tumor response (such as partial response, stable or progressive disease) may be influenced by the increase of 5-FU plasma level from the start of infusion. Therefore, the 5-FU plasma level may be a predictive factor for maximizing the tumor response and minimizing the risk of severe adverse events.

Impact of primary tumor location as a predictive factor in patients suffering from colorectal cancer treated with cytotoxic anticancer agents based on the collagen gel droplet-embedded drug sensitivity test.

In recent studies, better clinical outcomes for patients with left-sided colon cancer (CC) compared with right-sided CC have been reported; however, in such investigations, the chemotherapy regimens included molecular-targeting agents. To the best of our knowledge, the impact of primary tumor location as a predictive factor in patients suffering from CC treated with cytotoxic anticancer agents alone has not been investigated. The aim of the present study was to determine the impact of the primary tumor location as a predictive factor of patients undergoing the following cytotoxic anticancer agent regimens: Leucovorin and fluorouracil + oxaliplatin (FOLFOX) or Leucovorin and fluorouracil + irinotecan (FOLFIRI), using the collagen gel droplet-embedded drug sensitivity test (CD-DST). Between March 2008 and April 2017, tumor specimens were obtained from 133 patients suffering from colorectal cancer (CRC) who had not received preoperative chemotherapy. CD-DST was performed and the growth inhibition rate (IR) was determined in FOLFOX and FOLFIRI regimens. The associations between tumor location and IR values for each condition were evaluated. In the present study, the prognosis of patients receiving palliative chemotherapy as well as treatment with molecularly-targeted agents was also investigated. There were no significant differences in the IRs (%) of the two regimens using CD-DST for right-sided tumors compared with left-sided tumors, including or excluding the rectum. The median survival times of patients with right CC and left CC who had received palliative chemotherapy and treatment with molecularly-targeted agents were 960 and 1,348 days, respectively. Primary tumor location did not represent a predictive factor for the efficacy of treatment with cytotoxic anticancer agent regimens using CD-DST. However, patients suffering from left-sided CC were revealed to exhibit better clinical outcomes compared with patients suffering from right-sided CC when molecularly-targeted agent regimens were administered. Therefore, the results of the present study suggested that molecularly-targeted agents rather than cytotoxic anticancer agents may result in improved clinical outcomes for patients with CRC suffering from left-sided tumors.

Impact of the individualization of the first-line chemotherapy for advanced colorectal cancer based on collagen gel droplet-embedded drug sensitivity test.

Leucovorin (FOL) and fluorouracil (5-FU) plus oxaliplatin (l-OHP; FOLFOX) or FOL and 5-FU plus irinotecan (SN-38; FOLFIRI) are widely used as first-line chemotherapy regimens in the treatment of advanced colorectal cancer (CRC). However, second-line chemotherapy must be abandoned in certain cases due to disease progression, adverse effects or high medical cost. Therefore, the most effective regimen should be selected as first-line chemotherapy. We reported that individualization of first-line treatment (FOLFOX/FOLFIRI/Dual/Poor responder) was possible using the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) and that individualized first-line chemotherapy with CD-DST may improve the prognosis of patients with unresectable CRC. The aim of the present prospective cohort study was to evaluate the individualization of first-line chemotherapy using CD-DST, with a focus on prognosis. Between March 2008 and December 2015, tumor specimens were obtained from 120 patients with CRC who had not received preoperative chemotherapy. CD-DST was performed and the growth inhibition rate (IR) was determined by exposure for 24 h with 5-FU and l-OHP (6.0 and 3.0 µg/ml, respectively) and 5-FU and SN-38 (6.0 and 0.2 µg/ml, respectively). The cumulative distribution of IR values under each condition was evaluated on the basis that the clinical response to FOLFOX and FOLFIRI is equivalent (~50%). The prognosis of dual responder was improved compared with that of poor responders, however this difference was identified to be significant. There was no different prognosis between patients treated with an appropriate first-line regimen and patients treated with an inappropriate first-line regimen in dual responders. However, in poor responders, there were significant differences of prognosis between patients treated with an appropriate first-line regimen and patients treated with an inappropriate first-line regimen (P=0.036). In conclusion, the results from the present study suggest that administration of the recommended first-line regimen using CD-DST for patients with unresectable CRC is important for the improvement of prognosis, particularly in poor responders.

Two Patients with Large Colonic Lipomas for which Endoscopic Unroofing was Ineffective.

Endoscopic unroofing is effective for treating large colonic lipomas. However, additional endoscopic resection is occasionally required when the outcomes of initial unroofing are incomplete. The colonoscopy of an 82-year-old woman with abdominal pain revealed a yellowish lipoma of about 20 mm in the transverse colon. The mass was treated by unroofing, but a follow-up colonoscopy 5 days later revealed residual lipoma. One month later, the regenerated surface had become covered with mucosa, and the status of the lipoma had returned to that before unroofing. The colonoscopy of a 74-year-old man with abdominal pain and melena revealed a 50-mm-wide protruding lipoma in the transverse colon. The mucosa of the upper third of the lipoma was excised using an electric knife and snare, which allowed the immediate partial drainage of adipose tissue. Unroofing proceeded, but 7 days later, the unroofed surface had become coated with a white substance, and the residual lipoma required additional endoscopic resection. Colonic lipomas are often asymptomatic. However, patients with abdominal pain and hemorrhage should be treated in consideration of complete resection, but not by unroofing, which could leave a residual tumor. Drainage should be confirmed after unroofing and any residual lipoma should be treated by additional resection.

Postpancreatectomy Hemorrhage After Pancreatic Surgery in Patients Receiving Anticoagulation or Antiplatelet Agents.

Background Postpancreatectomy hemorrhage (PPH) is a serious complication after pancreatic surgery. In this study, we evaluated PPH and thromboembolic complications after pancreatic surgery in patients with perioperative antithrombotic treatment. Methods Medical records of patients undergoing pancreatic surgery were reviewed retrospectively. Patients receiving thromboprophylaxis were given either bridging therapy with unfractionated heparin or continued on aspirin as perioperative antithrombotic treatment according to clinical indications and published recommendations. The International Study Group of Pancreatic Surgery definition of PPH was used. Risk factors associated with PPH were assessed by multivariate analysis. Results Thirty-four of 158 patients received perioperative antithrombotic treatment; this group had a significantly higher PPH rate (29.4% vs 6.5%, P = .001) and mortality (11.8% vs 2.4%, P = .039) than patients not receiving thromboprophylaxis. Multivariate analysis revealed that perioperative antithrombotic treatment was the only independent risk factor for PPH after pancreatic surgery (odds ratio 4.77; 95% CI 1.61-14.15; P = .005). Conclusions Perioperative antithrombotic treatment is an independent risk factor for PPH in patients undergoing pancreatic surgery, although this treatment effectively prevents postoperative thromboembolic events.

[A case of small intestinal cancer in the upper intestine after pylorus-preserving pancreaticoduodenectomy].

We report a case of small intestinal cancer that arose in the upper intestine 16 years after pylorus-preserving pancreaticoduodenectomy( PPPD). An 84-year-old man, who had undergone PPPD for benign biliary tract disease 16 years previously, was found to have a primary small intestinal tumor in the upper intestine by upper gastrointestinal endoscopy, and primary intestinal cancer in the upper intestine was finally diagnosed. We performed partial resection of the upper small intestine and stomach and partial colectomy of the transverse colon to account for direct invasion. Histopathologically, the primary lesion was diagnosed as a moderately to poorly differentiated adenocarcinoma. Small intestinal cancer in the upper intestine after PPPD is extremely rare.

Investigation of free cancer cells in peripheral blood using CEA mRNA expression in perioperative colorectal cancer patients.

The aim of this study was to evaluate the impact of laparoscopic surgery (Lap) on circulating free tumor cells in colorectal cancer patients. In this study, we selected carcinoembryonic antigen (CEA) mRNA expression in peripheral blood as the marker of the circulating tumor cells and compared this marker between Lap and open colectomy (OC), to investigate differences due to surgical approach. A total of 50 patients underwent curative surgery for solitary colorectal cancer at our department, between June, 2008 and February, 2011. The patients were divided into OC and Lap groups (25 patients each). Total RNA was extracted subsequent to peripheral blood collection prior to surgery, immediately following surgery and 1, 3 and 7 days after surgery. CEA mRNA was detected with reverse transcription polymerase chain reaction (RT-PCR) and the association between peripheral blood CEA mRNA-positive rate, surgical findings and clinicopathological characteristics was investigated. The peripheral blood CEA mRNA-positive rate was significantly increased immediately after surgery, compared to the preoperative rate (P=0.001), but decreased over time. No significant differences were observed at any blood-sampling time point after postoperative day 1. The positive rate was significantly increased in the OC group immediately after surgery, compared to the preoperative rate (P=0.004). However, there were no significant differences between the rates prior to and immediately after surgery in the Lap group. The patients were then divided into those who were peripheral blood CEA mRNA-positive and -negative after surgery (postoperative positive and negative groups, respectively) and the clinicopathological characteristics were compared. Significant differences were identified between the groups in lower rectal cancer patients and patients with a large intraoperative blood loss (P=0.001 and P=0.01, respectively). In conclusion, in colorectal cancer patients, there were no significant differences in the perioperative peripheral blood CEA mRNA-positive rate or its short-term changes between patients undergoing OC and Lap surgery. It was suggested that Lap is equivalent to OC with regard to free cancer cells.

[A case of ascending colon cancer with unresectable distant metastases treated by systemic chemotherapy].

The patient, a male in his 70s, was referred to this hospital by his neighborhood doctor with what was said to be impaired hepatic function. Detailed examinations revealed a circumferential ascending colon cancer, diffuse hepatic metastases scattered over both liver lobes, and lymph node metastases in the left axilla. With the primary lesion-induced symptoms of stenosis controllable, the patient began systemic chemotherapy by mFOLFOX6 without a resection of the primary lesion. After completing a 10-course treatment, the patient underwent surgery to resect the primary lesion in preparation for bevacizumab treatment. In the postoperative systemic chemotherapy, FOLFIRI and mFOLFOX6 were administered concomitantly with bevacizumab. After a total of 19 courses, the patient's systemic condition gradually deteriorated. He eventually died of cancer one year and seven months after diagnosis of the primary lesion or one year and one month subsequent to the resection of the primary lesion. No consensus has been reached on the necessity to resect the primary lesion in patients with advanced colorectal cancer who also have unresectable distal metastases. Systemic chemotherapy, nevertheless, can provide tumor control on both primary and metastatic lesions and could become a treatment option in the future.