Prospective observational study comparing the perioperative outcomes of laparoscopic colectomy with or without epidural anesthesia: the Kanagawa Yokohama Colorectal Cancer Study Group (KYCC) 1806.

PURPOSE: There have been no adequate comparisons of the efficacy, safety, and efficiency of analgesia after laparoscopic colorectal resection (LAC), with and without epidural anesthesia (EDA). METHODS: This was a multicenter prospective observational study of patients undergoing LAC. The primary end point was the mean visual analog scale (VAS) score on postoperative days (PODs) 1-7. The secondary end points were the highest VAS, complication rate, days to first ambulation and fatigue, length of hospital stay, and time to commencement of surgery. RESULTS: We compared an EDA group (Group E, n = 48) and a no-EDA group (Group O, n = 48) after matching. The mean VAS was not significantly different between the groups (28.7 vs. 30.1, p = 0.288). On assessing the secondary end points, the highest VAS was not significantly different between the groups. In fact, the VAS was lower in Group E only on POD 2. There was no difference in the incidence of complications, the time to first postoperative evacuation was shorter in Group E, and postoperative hospitalization was similar. The time to surgery was shorter in Group O. CONCLUSION: These results suggest that LAC without EDA is a feasible option, but with the early and regular use of adjunctive measures to provide more stable analgesia.

[Resected Metachronous Pancreatic Metastasis from Rectal Cancer-A Case Report].

A 68-year-old woman had undergone laparoscopic high anterior resection for rectal cancer. Two years postoperatively, metachronal pulmonary metastases and cerebellar metastasis were surgically resected. Three and a half years after the primary surgery, computed tomography(CT)demonstrated a nodule at the pancreatic tail. Under suspected primary pancreatic cancer or metastasis from rectal cancer, we performed distal pancreatectomy. Histological examination of the pancreatic tumor suggested a metastasis from the rectal cancer since tumor cells were negative for CK7 and positive for CK20 and CDX2 immunohistochemically. Three months after the pancreatic resection, CT demonstrated hepatic and cerebellar metastases. After subsequent chemotherapy, liver metastasis disappeared. The cerebellar metastasis shrank with radiotherapy.

[A Case of Hepatocellular Carcinoma Treated with Transdiaphragmatic Radiofrequency Ablation under Thoracotomy].

The patient was a 73-year-old man. A liver tumor was found in the posterior segment(S6)during the follow-up period post the interferon treatment for hepatitis C in September 1999. An S6 sub-segmentectomy was performed. The tumor was diagnosed as a moderately differentiated carcinoma, hepatocellular carcinoma(HCC)with pT2N0M0, pStage Ⅱ(UICC TNM 7th edition). The tumor recurred twice post-surgery. The recurrent tumors were treated with local therapies such as transcatheter arterial chemoembolization(TACE), percutaneous ethanol injection(PEI)and radiofrequency ablation(RFA). The third recurrence was found in the posterior segment(S7)in April 2009. RFA was unsuccessful because an appropriate puncture route could not be found. Then, a transdiaphragmatic RFA under thoracotomy was performed as an alternative treatment, which led to an optimal outcome. We report a case of HCC that could not be treated with percutaneous RFA but with a transdiaphragmatic RFA under thoracotomy.

[A Case of Rectal Cancer with Unresectable Liver Metastasis Responding to Rechallenge with FOLFIRI].

A 63-year-old man underwent low anterior resection for rectal cancer.A synchronous liver metastasis located in segment 8 was 12 cm in diameter and unresectable due to its proximity to the inferior vena cava(IVC).The postoperative pathological findings revealed a T3(SS), N0, M1(liver)Stage IV tumor, and wild type K-RAS was expressed.We chose FOLFIRI plus cetuximab(Cmab)for first-line chemotherapy.After 6 courses, we changed the molecular target drug from Cmab to bevacizumab( Bmab)because the liver metastasis remained unresectable.The patient had long-term stable disease(SD)for approximately 30 months with the FOLFIRI-based regimen.We then changed the regimen to mFOLFOX6 plus Bmab for second-line, Cmab for third-line, and trifluridine/tipiracil hydrochloride for fourth-line chemotherapy to treat progressive disease(PD).After treatment with these chemotherapies, the patient wished to continue treatment.We restarted FOLFIRI plus Bmab for fifth-line chemotherapy as his general condition was still good.Consequently, his tumor markers levels decreased with stabilization of the disease on CT scans, and he continued therapy for 6 months while maintaining a good quality of life.This case suggested that rechallenge with anti-cancer agents could be effective and improve the prognosis of colorectal cancer patients after using all key drugs.

[A case of postmenopausal breast cancer becoming HER2 positive after neoadjuvant hormone therapy].

A 75-year-old woman presented to a local doctor with a lump in the right breast. On physical examination, a tumor measuring 24mm was palpable in the BD area of her right breast. Mammography showed category 5 disease, and ultrasonography revealed a tumor measuring 24×16 mm. A mammotome biopsy provided a diagnosis of invasive ductal carcinoma of the breast(ER 7/PgR 4/HER2 1+), and the tumor was classified as stage IIA(T2N0M0)according to the UICC-TNM classification. She was recommended surgery but she rejected this option and underwent hormone therapy with anastrozole (1mg/day). One year and 8months after beginning the treatment, ultrasonography showed the tumor to measure 7.0×5.7 mm, and hormone therapy resulted in a partial response(PR). The patient hoped to undergo an operation, so she was referred to our hospital, and a right partial mastectomy and sentinel node biopsy was performed. A histopathological exami- nation indicated scirrhous carcinoma, 18mm, nuclear grade 1, f, ly1, v0, n0, ER 3/PgR 3/HER2 3+. The curative effect was grade 1a. The tumor had become HER2 positive, so the patient was then administered radiotherapy and trastuzumab and anastrozole as adjuvant therapy. Herein, we report our experience with a case of breast cancer that only became HER2 positive after hormone therapy, and also provide some bibliographic comments on this occurrence.

[A case of intractable fistula after low anterior resection repaired by transsacral direct suture].

We report a case of an intractable fistula repaired by transsacral direct suture. A 65-year-old man underwent low anterior resection for rectal cancer. He subsequently underwent ileostomy due to anastomosis leakage. The fistula of the anastomosis persisted 3 months after surgery. He underwent surgery to repair the fistula using a transsacral approach. After removing the coccyx, the fistula in the postrectal space was exposed directly. The presence of the fistula was confirmed by an air leak test and was closed by direct suture. After 33 days, the patient underwent ileostomy closure.

[Three patients with local recurrence of ER-positive breast cancer for whom anastrozole was clinically effective].

We treated three postmenopausal female patients with unresectable local recurrence from breast cancer. All pathological diagnoses of the local recurrence lesions were ER-positive breast cancer. For treatment, we administered anastrozole to these three patients. One has been stable disease for 25 months after taking anastrozole. Another has also showed stable disease for 18 months, and the last patient has been a partial response. We performed a biopsy from a recurring lesion on these three patients, and made a diagnosis of ER-positive breast cancer. This strategy of unresectable local recurrence revealed that these three patients could have had a stable condition for a long duration by taking anastrozole.

Solitary Cardiac Metastasis from Colorectal Cancer: A Case Report.

A 73-year-old woman with silent cardiac metastasis underwent high anterior resection for rectal cancer 3 years ago. Follow-up computed tomography showed a tumor in the right atrium. Partial vascular resection of the superior vena cava and right atrium was performed. Early postoperative recurrence occurred, and chemotherapy was unsuccessful. The patient died 7 months after surgery.

Evaluating prognostic significance of preoperative C-reactive protein to albumin ratio in older patients with pathological stage II/III colorectal cancer.

Purpose: This study was performed to evaluate the prognostic value of preoperative C-reactive protein to albumin ratio (CAR) in older patients with colorectal cancer (CRC) undergoing curative resection. Methods: We retrospectively analyzed 244 older patients (aged 75 years or higher) with pathological stage II/III CRC who underwent curative surgery between 2008 and 2016. The optimal value of CAR was calculated and its correlation with the clinicopathological factors and prognosis was examined. Results: The optimal cutoff value of the CAR was 0.085. High preoperative CAR was significantly associated with high carcinoembryonic antigen levels (P=0.001), larger tumor size (P<0.001), and T pathological (pT) factor (P=0.001). On multivariate analysis, high CAR was independent prognostic factor for relapse-free survival (P=0.042) and overall survival (P=0.001). Conclusion: Preoperative elevated CAR could be considered as an adverse predictor of both relapse-free survival and overall survival in older patients with CRC undergoing curative surgery.

Clinical Significance of PLA2G2A Expression in Gastric Cancer Patients who Receive Gastrectomy and Adjuvant S-1.

BACKGROUND/AIM: This study aimed to evaluate the prognostic significance of PLA2G2A expression in patients with locally advanced gastric cancer (GC). PATIENTS AND METHODS: PLA2G2A expression levels in cancerous tissue specimens and adjacent normal mucosa obtained from 134 patients with stage II/III GC who received adjuvant chemotherapy with S-1 after curative resection were measured using real-time quantitative polymerase chain reaction. Subsequently, the associations of PLA2G2A expression with clinicopathological features and survival were evaluated. RESULTS: No association was observed between clinicopathological features and PLA2G2A expression levels. Overall survival was significantly longer in patients with high PLA2G2A expression levels (p=0.022). Multivariate analysis revealed that PLA2G2A expression was a significant, independent prognostic factor (hazard ratio=0.136; 95% confidence interval=0.0185-0.992; p=0.049). CONCLUSION: PLA2G2A mRNA expression may serve as a useful prognostic marker in patients with locally advanced GC who receive curative surgery and adjuvant chemotherapy with S-1.

[Effectiveness of S-1 plus CPT-11 therapy for an elderly patient with recurrent colon cancer].

In May 2006, a 79-year-old man underwent left colectomy and D2 lymphadenectomy for descending colon cancer (fStage II , Cur A). No adjuvant chemotherapy was done. Eighteen months after surgery, the serum tumor marker level was increased (CA19-9 526 U/mL), and multiple liver metastases (H2) and peritoneal dissemination were detected using abdominal CT. He was treated with S-1 plus CPT-11 therapy, because mFOLFOX6 as a standard chemotherapy for advanced colorectal cancer was rejected. After 4 courses, tumor markers normalized and abdominal CT revealed a partial response. At present, progression-free survival (PFS) is 240 days. In our case, this regimen was found to be convenient and safe in an outpatient compared with FOLFIRI and FOLFOX. This case suggested that S-1 plus CPT-11 therapy could well be a promising systemic chemotherapy for patients with advanced colorectal cancer.

Treatment outcomes of differentiated thyroid cancer with distant metastasis improve by tyrosine kinase inhibitors.

In patients with distant metastasis, treatment for differentiated thyroid cancer (DTC) includes complete total thyroidectomy, followed by radioactive iodine (RAI) therapy for metastatic lesions. Tyrosine kinase inhibitor (TKI) treatment is the final treatment option for metastatic lesions, which is incurable with surgery/RAI therapy. The present study examined whether treatment outcomes for DTC in patients with distant metastasis improved following TKI treatment. This study included 147 patients (median age, 71; range, 33-91 years) who underwent surgery in our hospitals and were diagnosed with distant metastasis. Disease progression was observed in 70 patients, of whom 56 were treated with TKI (TKI group); 14 refused TKI treatment or showed no treatment indication [untreated (UT) group]. Disease progression and treatment outcomes were assessed using imaging evaluations. The present study investigated thyroglobulin doubling time (Tg-DT) and Tg antibody presence/absence and their relation to disease progression. Overall survival following disease progression between the two groups was compared. The study included 22 cases of sorafenib, 49 of lenvatinib, and 15 involving TKIs. The mean dosing period for sorafenib was 153 days and for lenvatinib was 462 days. In the TKI group, 16, 26, and 9 patients exhibited partial responses (PRs), stable disease (SD), and progressive disease (PD), respectively, whereas 5 patients were not evaluable. The disease control rate (DCR) (PR+SD) was 75.0%. A total of 16 patients died in the TKI group, whereas 10/14 patients in the UT group died. Survival curves for the groups were significantly different. TKI treatment improved the prognosis of patients with distant metastasis and PD.

Evaluation of calorie intake according to age and sex in patients undergoing surgery for gastric cancer.

BACKGROUND/AIMS: We studied food intake in 107 patients undergoing gastric surgery, with emphasis on postoperative quality of life (QOL). The time course of food intake after surgery, sex- and age-related differences in food intake, and the relation of food intake to surgical procedure were evaluated retrospectively. METHODOLOGY: The following variables were studied: 1) the time required for stabilization of food intake, assessed on the basis of the time course of food intake after operation; 2) the relations of sex and age to postoperative food intake, assessed by comparing food intake according to sex and age; and 3) postoperative food intake according to surgical procedure, evaluated by calculating the ratio of postoperative food intake to the food intake of healthy individuals matched for sex and age. RESULTS: At 6, 12, and 24 months after operation, there was no difference in food intake among the three operative procedures; food intake was stable from 6 months onward. When food intake was analyzed according to age, similar trends were seen in men and women, and there were no significant differences in food intake among patients in their 40s, 50s, or 60s. Food intake was significantly lower in patients in their 70s than in patients in the other age groups. Food intake even in women with significantly decreased food intake or in patients 70 years or older was not necessarily low as compared with food intake levels in healthy individuals. CONCLUSIONS: Food intake is substantially affected by the period of time after surgery, as well as by sex, and age at the time of surgery.

13C-urea breath test in patients having undergone total gastrectomy.

BACKGROUND/AIMS: In this study, we performed 13C-urea breath test in patients who had undergone total gastrectomy and investigated the content of (13)CO2 in the CO2 gas expired after direct influx of 13C-urea into the small intestine. METHODOLOGY: 13C-Urea breath test was performed in 31 patients who had undergone total gastrectomy at this department for the treatment of stomach cancer and consented to participate in this study. The test was performed in two ways, i.e. with and without mouth washing (gargling) on taking 13C-urea. RESULTS: Among 41 measurements, the delta13C was less than 2.5% per hundred in 9 measurements (22.2%) and less than 2.0% per hundred in 6 measurements (14.6%). The delta13C exceeded 50% per hundred, in 4 subjects (9.8%). There were no differences between the methods with and without gargling. CONCLUSIONS: The results of this study suggested the possibility that 13C-urea is decomposed even in the jejunum or the lower part of intestine resulting in absorption of H(13)CO3 and another possibility that 13C-urea is directly absorbed from the intestine and decomposed in the blood.

Bone disorder and vitamin D after gastric cancer surgery.

BACKGROUND/AIMS: The present study was conducted to investigate the relationship between bone metabolic disorder after gastrectomy for gastric cancer and vitamin D metabolites or the hormones involved in calcium metabolism. METHODOLOGY: Twenty-one patients who had undergone gastrectomy for gastric cancer and had been followed for less than 10 years were assessed for bone disorder by microdensitometry. The levels of 1,25-dihydroxy vitamin D (1,25(OH)2VD), 25-hydroxy vitamin D (25(OH)VD), 24,25-dihydroxy vitamin D (24,25(OH)2VD), N-PTH, calcitonin, estradiol, osteocalcin, and ALP were measured and assessed for correlations with clinicopathological factors, including the operative procedure and the number of years since surgery. RESULTS: Bone disorder was found in 9 out of 21 patients (42.9%). The prevalence was significantly higher in patients who had undergone surgery more than 2 years before assessment, so there was a relationship between the period after surgery and bone disorder. Among the vitamin D metabolites, the level of 1,25(OH)2VD was normal in all patients, whereas 25(OH)VD was reduced in 6 out of 21 patients (28.6%) and 24,25(OH)2VD was reduced in 17 patients (81.0%). The 1,25(OH)2VD was significantly higher in the patients with Grade I to III bone disorder compared to the patients with normal bones or early bone disease. The 1,25(OH)2VD/25(OH)VD ratio was significantly higher in the patients without passage of food through the duodenum due to the reconstructive method, while the 25(OH)VD/24,25(OH)2VD ratio was significantly higher in the patients with remaining of duodenal food passage. PTH was decreased in about 50% of the patients, while calcitonin was normal in all patients. Estradiol was decreased in one female patient, while it was elevated in 10 of the 17 men (58.8%). The osteocalcin level was high in all patients irrespective of the period after surgery. CONCLUSIONS: After gastrectomy, the incidence of bone metabolic disorder increases with time. Changes of vitamin D metabolites, particularly 25(OH)VD and 24,25(OH)2VD, seem to be closely associated with post-gastrectomy bone disease.

The validity of sentinel lymph node biopsy using dye technique alone in patients with gastric cancer.

BACKGROUND/AIMS: We investigated whether sentinel lymph node biopsy using dye technique alone is useful or not in decision-making for less invasive surgery in patients with gastric cancer. METHODOLOGY: The subjects were 43 patients who had undergone laparotomy for gastric cancer and consented to undergo sentinel lymph node biopsy using patent blue dye. The patients enrolled were 26 males and 17 females, with a mean age of 62.5 years. The tumor sites were upper third of the stomach in 14, middle third in 16, and lower third in 13 patients. The depth of invasion was mucosa in eight, submucosa in 19, muscularis propria in five, subserosa in five, and serosa in six patients. Total gastrectomy was performed in 12, subtotal gastrectomy in 28, and proximal gastrectomy in three patients. RESULTS: The mean number of sentinel lymph node biopsies per surgery was 3.5 +/- 4.1. We were able to perform blue node biopsy in 40 out of 43 patients, but could not find any blue nodes in three patients. Among the 40 patients in whom blue nodes were identified, 29 patients with no metastasis in blue nodes had no evidence of lymph node metastasis (NO). The depth of invasion was not deeper than subserosa in all these patients. Metastasis was observed in one out of the three patients in whom no blue nodes were found. CONCLUSIONS: When the depth of invasion was not deeper than the subserosa and blue nodes were identified, no metastases in either non-blue nodes or blue nodes could be found in the absence of metastatic blue nodes. Therefore, if the depth of invasion is not deeper than the subserosa in gastric cancer, metastatic search in blue nodes seems sufficient and less invasive surgery can be performed safely. Even when the invasion depth is not deeper than the submucosa, the tumor could be metastatic to Group 2 lymph nodes in patients in whom blue node biopsy revealed metastases. When metastasis is found in lymph nodes by intraoperative frozen section diagnosis, less invasive surgery for gastric cancer is not indicated.

[Neoadjuvant chemotherapy with combination of S-1 and CPT-11 in advanced rectal cancer - a case report].

We report a case of advanced rectal cancer successfully treated with a combination of S-1 and CPT-11 as neoadjuvant chemotherapy. The patient, a 61-year-old man, had a rectal cancer with pelvic viscera invasion and severe stenosis. After colostomy for removing stenosis, he was treated with a combination of S-1 and CPT-11 (S-1 120 mg/body day on day 1-14, CPT-11 120 mg/body/day on day 1 and day 15, every 4 weeks). Seven courses of treatment resulted in a marked reduction of the primary tumor and disappearance of invasion. Subsequently, rectal amputation for curative intent was done. No surgical complication was observed. On microscopic examination, only a few tumor cells were detected in the granulation tissue of the resected rectum and no tumor cells in dissected LNs. This case demonstrates the effectiveness and safety in a neoadjuvant setting of a combination of S-1 and irinotecan for rectal cancer.

Pharmacokinetics of S-1 in patients with peritoneal dissemination of gastric cancer.

The response of gastric cancer with peritoneal dissemination to systemic chemotherapy may be negatively affected by poor drug delivery due to the blood-peritoneal barrier. However, S-1 has been reported to be effective. We examined the pharmacokinetics of S-1 in 14 patients who had gastric cancer with peritoneal dissemination. S-1 was given from the morning of the day before surgery to the morning of surgery. Concentrations of 5-fluorouracil (5-FU) and gimeracil (CDHP) were measured in the serum, ascites, disseminated peritoneal nodes, and normal peritoneum. There was a strong correlation between 5-FU and CDHP concentrations in peritoneal tissues. The concentrations of 5-FU and CDHP in the serum were similar to those in ascites. The concentration of 5-FU was significantly higher in disseminated nodes than in the normal peritoneum. After administration of S-1 to gastric cancer patients with peritoneal dissemination, 5-FU and CDHP in the serum linearly pass through the peritoneum and enter the ascites. High concentrations of 5-FU selectively penetrate disseminated peritoneal cells.

Prognostic factors after chemoradiotherapy for patients with inoperable esophageal squamous cell carcinoma.

BACKGROUND/AIMS: It is important to clarify the predictive and prognostic factors for chemoradiotherapy (CRT) in patients with inoperable esophageal cancer. METHODOLOGY: Forty-one patients with inoperable advanced esophageal cancer were evaluated. The predictive factors for the response to CRT (low-dose 5-FU and Cisplatin (FP) therapy plus 60 Gy of radiation) and the prognostic factors after CRT were analyzed. RESULTS: Of the 41 patients, seven achieved complete remission, 21 achieved partial remission, nine showed no change and four showed progressive disease. The median survival time was 19 months in patients with a tumor response, compared to 7 months in patients with non-responsive tumors. Only the serum cytokeratin (CYFRA) level independently predicted the responsiveness to treatment. In the multivariate analysis, the serum CYFRA level and the p53 gene mutation independently influenced prognosis. CONCLUSIONS: The presence of a p53 mutation in the biopsy specimen or a high serum CYFRA level may be predictive of an adverse therapeutic outcome.

[Clinical results of single therapy with TS-1 for advanced/recurrent gastric cancer].

In cases with advanced/recurrent gastric cancer undergoing single therapy with TS-1, we retrospectively discussed the antitumor effects and adverse events and considered the clinical utility of TS-1. The subjects consisted of 131 cases with advanced/recurrent gastric cancer who received one or more courses of therapy with TS-1 alone between July 1999 and August 2003. We carried out 4-week administration of 80-120 mg/day of TS-1 according to body surface area, followed by a 2-week discontinuation, then repeated administration which adjusting the dosage according to the incidence of side effects, and discussed the antitumor effects and adverse events. The response rate in all cases was 21% and the median survival time (MST) was 343 days, or 25.3% and 265 days if limited to unresectable and recurrent cases. The response rates were 38.2% for unresectable cases, 16.3% for recurrent cases and 14.6% for curability C cases, and the MSTs were 250 days, 276 days and 419 days, respectively. The response rates in terms of whether or not patients had received chemotherapy were 11.6% for those who had received chemotherapy and 40.0% for those who had not, and the MSTs were 239 days and 325 days, respectively. Thus, both were significantly better in patients who had not received chemotherapy. The response rates for patients who had not received chemical therapy by target organs were favorable on the order of 50% for stomach and 33% for liver metastasis, and the MSTs were on the order of 474 days for peritoneum, 39 1 days for liver metastasis and 326 days for lymph nodes. There were 10 cases of long-term survival of 600 days or longer, but not in unresectable cases, and the target organs in many of the cases were the peritoneum and lymph nodes. Adverse reactions were observed in 34.4% of all cases and those of grade 3 or more in 9.4%, all of which were improved only by discontinuation of the drug. It was again confirmed that single therapy with TS-1 for advanced/recurrent gastric cancer is an excellent therapy providing both high antitumor effects and safety.