[A Case of Disseminated Myelocarcinoma with Bone Metastasis 15 Years after Mastectomy and Relatively Long-Term Survival through Multidisciplinary Treatment].

The patient was a 62-year-old woman who had undergone mastectomy in August 2003 for cancer of the right breast. In addition to radiation therapy in the remaining breast, chemotherapy and endocrine therapy were subsequently performed. The patient had a 10-year recurrence-free postoperative course followed by annual surveillance. Beginning in 2016, an elevation in the serum level of tumor markers was detected; however, no accumulations were found in PET-CT over 2 consecutive years(2016 and 2017). Thereafter, serum levels of tumor markers continued to rise, and a PET-CT in 2018 revealed costal accumulations leading to a diagnosis of late-stage bone metastasis in postoperative year 15. Although hormone therapy was resumed, a continuing rise in the serum level of tumor markers led to a diagnosis of diffuse bone metastasis by MRI in 2019. Treatment with abemaciclib was initiated, and with effective radiotherapy, the PS was maintained at 0-1, serum levels of tumor markers decreased, and the lesions themselves continued at SD. However, in June 2020, multiple liver metastases appeared in an abdominothoracic CT scan. The patient refused chemotherapy; this, a BSC policy was adopted. Acute hemolytic anemia occurred immediately thereafter, and the PS gradually deteriorated. The patient died in September 2020, 17 years and 1 month after surgery.

[A Case of Fatal Interstitial Pneumonia during FOLFIRI plus Cetuximab Therapy for Liver Metastasis of Colon Cancer].

The patient was a 76-year-old woman who underwent sigmoidectomy in April 2011 for sigmoid colon cancer with multiple concurrent liver metastases. She was treated postoperatively with mFOLFOX6 plus cetuximab but was diagnosed with the progressive disease at the end of course 14. The patient started receiving FOLFIRI plus cetuximab therapy in May 2012. Later in August 2012, she was examined for respiratory distress on the scheduled date of receiving course 7 and was diagnosed with drug-induced interstitial pneumonia resulting from systemic chemotherapy. The patient was administered oxygen, and her symptoms improved temporarily with steroid half-pulse and endotoxin adsorption therapy, but on inpatient day 10, her respiratory condition deteriorated. She was treated with steroid pulse therapy, but died of respiratory failure on inpatient day 17. The main adverse events associated with FOLFIRI plus cetuximab therapy are gastrointestinal symptoms, hematotoxicity, peripheral nerve damage, and dermatological symptoms. However, reports of respiratory conditions such as interstitial pneumonia are rare. Although the incidence is low, interstitial pneumonia can be severe and fatal and therefore requires close attention.

[A Case of Stage â £ Rectal Cancer with No Evidence of Disease after Neoadjuvant Chemotherapy and Surgery].

A 46-year-old man presented with hematochezia in October 2012. A circumferential type 2 rectal cancer was detected with colonoscopy. Contrast-enhanced CT showed multiple liver and lung metastases. Chemotherapy was administered after the diagnosis of cStage Ⅳ rectal cancer. After 1 course of XELOX plus Bmab, the treatment was changed to XELOX plus Cmab for 21 courses. An infusion reaction occurred during the 21st course. Because a complete response of the liver metastases and a reduction in size of the primary tumor had been achieved, we performed a low anterior resection in April 2014. The final pathological diagnosis was type 2, 10×25 mm, tub1, pMP, int, INF b, pN1 (251). There was no evidence of disease (NED) after the surgery. We are closely following up this patient with no postoperative chemotherapy, and as of July 2015, there is no sign of recurrence. We describe a case of a Stage Ⅳ rectal cancer that was resected with radical surgery after neoadjuvant chemotherapy. We also include a brief review of the literature.

Preliminary experience using a computer-mediated flexible circular stapler in laparoscopic esophagogastrostomy.

Intracorporeal esophagogastrostomy after laparoscopic proximal gastrectomy is technically challenging. We employed a computer-mediated flexible circular stapler (SurgASSIST) for esophagogastrostomy in 2 cases with gastrointestinal stromal tumor located near the esophagogastric junction. Esophagogastrostomy was successfully constructed intracorporeally using the double-stapling technique. Operation times for the 2 cases were 225 and 170 minutes. No anastomotic leakage was encountered. However, anastomotic stricture requiring balloon dilatation occurred in 1 patient. The SurgASSIST system was feasible for esophageal anastomosis in laparoscopic proximal gastrectomy. However, the digital loading unit (DLU) is too large to introduce transorally, and attempting introduction of the DLU through the narrow lumen may create lesions or perforate the organ. Further improvements in the DLU will facilitate wider use of this system for various procedures in laparoscopic surgery.

Combination of dihydropyrimidine dehydrogenase and thymidylate synthase gene expressions in primary tumors as predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy for metastatic colorectal cancer.

Dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) gene expressions in metastatic colorectal cancer have been reported to be predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy. In this study, we investigated the association between both DPD and TS expressions in primary colorectal tumor and the antitumor effect in patients with metastatic colorectal cancer when treated with a fluoropyrimidine-based protocol. DPD and TS expressions were measured by reverse transcription-PCR in surgically resected materials of primary colorectal tumors from 37 patients who went on to receive oral treatment of uracil and tegafur and leucovorin for either synchronous or metachronous metastatic diseases. Relative mRNA amounts of DPD or TS were expressed as the ratios of targeted gene to glyceraldehyde-3-phosphate dehydrogenase reverse transcription-PCR products. Median values of DPD mRNA expressions were 0.30 and 0.65 for responding tumors and nonresponding ones, respectively, with a statistical significance (P < 0.0001). No responding tumor had a DPD mRNA expression >/= 0.5. A total of 19 tumors had low DPD mRNA expressions of <0.5, and 63% of them showed response. There was no responding tumor with both high DPD and high TS (TS mRNA expression >/= 1.0). However, the response rate was 75% in tumors with both low DPD and low TS. The median survival time was 16.3 months in patients with both low DPD and low TS versus 8.4 months in patients with high DPD or high TS mRNA expression. In conclusion, the combination of DPD and TS mRNA expressions in the primary tumor might be useful as predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy for metastatic colorectal cancer.

Laparoscopy-assisted resection of gastric remnant cancer.

We report a case of gastric remnant carcinoma (GRC) that was successfully treated by laparoscopy-assisted gastrectomy. A 69-year-old man was referred to our department for management of GRC. Preoperative investigations revealed a slightly elevated tumor, 5.0 cm in maximal diameter, confined to the gastric mucosa. Computed tomography and endoscopic ultrasonography identified no lymph node metastasis. Laparoscopy-assisted gastrectomy was performed including perigastric and mesenteric lymph node dissection. The postoperative course was uneventful. This is the first reported case of laparoscopically treated GRC. In cases with little adhesion from previous surgery, laparoscopic procedure might represent the treatment of choice for early GRC in terms of minimal invasiveness.

Endoscopic resection of benign breast tumors: retromammary space approach.

Endoscopic surgery is characterized by the creation of a working space. At our department, we have obtained good results with a retromammary space approach in which the tumor is resected after creation of a working space in the retromammary space. The special instruments used for this purpose comprise an endoscopic vein harvesting system to dissect the retromammary space, a dissecting balloon to compress the space to achieve hemostasis, and laparosonic coagulating shears to incise the tumor. This surgical technique provides a superior cosmetic result, and the level of patient satisfaction has been high.

[Dihydropyrimidine dehydrogenase expression in gastric cancer using anti-human dihydropyrimidine dehydrogenase monoclonal antibody].

The rate-limiting enzyme to catabolize 5-fluorouracil (5-FU) is dihydropyrimidine dehydrogenase (DPD), which expression in cancerous tissue is reported to have a relation with anti-tumor effect for 5-FU. In this study, we evaluated the immunohistochemical expression in gastric cancer using two different kinds of anti-human DPD antibody, KM1915 and KM1919. However, recognition of both antibody was mimetic in human gastric cancer, and strong expression of DPD was observed in the interstitial tissue when using KM1919. There is a positive relationship between immunohistochemical expression by KM1915 and mRNA expression in human gastric cancer. Immunohistochemical study with KM1915 might be a clinically useful method to evaluate the expression of DPD in paraffin-embedded materials.

[Thymidylate synthase and dihydropyrimidine dehydrogenase gene expressions in colorectal cancer using the Danenberg tumor profile method].

Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) have been identified as a predictor of response to 5-fluorouracil (5-FU). Danenberg et al. developed a technology to evaluate gene expressions in formalin-fixed paraffin-embedded (FFPE) specimens (DTP; Danenberg tumor profile). In this study, TS and DPD gene expressions were measured in 47 primary colorectal cancer tumors and 12 metastatic tumors using FFPE specimens. In primary tumors, expression of TS genes in cancerous tissues was statistically higher than in stromal tissues, while DPD gene expressions in stromal tissues were higher than those in cancerous tissues. The median TS mRNA level was 0.86 in hepatic metastasis and 1.95 in lymph node metastasis. The median DPD mRNA level was 0.86 in hepatic metastasis and 1.96 in lymph node metastasis. Both gene expressions differed among primary tumors and metastatic tumors, especially in metastatic sites. DTP might be useful to evaluate the 2 gene expressions in colorectal cancer. Further studies would be needed to clarify the mechanisms of difference of gene expressions in cancerous and stromal tissues, or in primary tumors and metastatic tumors.

Comparison of stress-induced modulation of smooth-muscle activity between ileum and colon in male rats.

Stress is a well-known cause of numerous digestive conditions, including gastrointestinal-function disorders. The autonomic nervous system regulates intestinal movements via cholinergic and adrenergic efferent fibers; however it is not clear how stress could affect these control mechanisms and in particular whether in a site-dependent manner. In this study we tested in vitro the effects of topical application of acetylcholine (Ach) and adrenalin (Adr) on smooth-muscle contractions of intestinal segments isolated from stress-conditioned rats. Stress was loaded by hypergravity stimulation (10min/day) for periods of 1, 6 or 30days. As a result, stress-conditioning affected intestinal sensitivity to Ach and Adr differently at sections of the ileum and colon. In the ileum no significant differences were found between control and stress-conditioned rats, whereas in the colon, samples from 6- and 30-day stress-conditioned rats showed larger amplitudes of Ach-induced contraction, as well as greater antagonization by Adr application. These results suggest that stress conditioning can modify autonomic control of intestinal movements by altering smooth-muscle sensitivity to Ach and Adr.

Simple combinations of 5-FU pathway genes predict the outcome of metastatic gastric cancer patients treated by S-1.

We evaluated the expression of 5-FU pathway genes in prechemotherapeutic fresh frozen samples obtained from primary tumors to predict response and survival of 59 metastatic gastric cancer patients treated with S-1 monotherapy as first line treatment. Five 5-FU pathway genes, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP) and uridine phosphorylase (UP), were analyzed by the quantitative real-time reverse transcriptional PCR method. Median values of each gene were selected for cut-off values separating high and low gene expressions. In univariate analyses, low TS, high OPRT and low TP were significantly associated with a tumor shrinkage and a long survival, whereas DPD and UP gene expressions did not correlate with response and survival. Multivariate analyses revealed that independent variables were OPRT and TS for response and TS and TP for survival. When OPRT and TS were combined, a significantly increased accuracy rate of 91.5% was seen for response. Similarly, an increased hazard ratio of 10.29 was observed for survival in patients possessing low TS and low TP, compared with those with high TS or high TP. The simple combinations of 2 genes, OPRT and TS for response and TS and TP for survival, may allow identification of gastric cancer patients who will benefit from S-1 chemotherapy.

Intratumoral dihydropyrimidine dehydrogenase messenger RNA level reflects tumor progression in human colorectal cancer.

BACKGROUND: Determination of intratumoral dihydropyrimidine dehydrogenase (DPD) is of clinical interest because increased DPD levels can influence the tumor response to 5-fluorouracil-based chemotherapy through increased inactivation of the agent in tumor cells. METHODS: DPD messenger RNA (mRNA) levels were evaluated in 80 consecutive patients undergoing surgery for primary colorectal cancer and 12 cases of liver metastasis. RESULTS: Higher DPD mRNA levels were associated with higher pathologic classification, corresponding to the T categories (r =.267; P =.003). The DPD mRNA level was statistically higher in tumors with microscopic lymph node metastasis than in those without (P =.002). Hence, the DPD mRNA level increased in accordance with Dukes' classification (r =.387; P =.0001). The DPD mRNA level of the liver metastasis from colorectal cancer was significantly higher than that of primary lesions (P =.002). In eight patients, the DPD mRNA level of the liver metastasis was significantly higher than that of the matched primary tumor (P =.017). CONCLUSIONS: Increases of the DPD mRNA level in cancerous tissue seem to reflect tumor progression. High DPD mRNA levels in liver metastasis and advanced colorectal cancer may have clinical importance for 5-fluorouracil-based chemosensitivity.

Thymidylate synthase and dihydropyrimidine dehydrogenase gene expression in relation to differentiation of gastric cancer.

Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are important enzymes of DNA de novo synthesis and the salvage pathway in cancer cells, respectively. Intratumoral TS and DPD gene expressions were evaluated to determine the correlation between the expression of the 2 genes in both normal stromal tissues and tissues with different degrees of malignant differentiation in primary gastric cancer. The study population consisted of 78 consecutive patients with advanced gastric cancer who underwent surgical treatment. Laser-captured microdissection of malignant or normal stromal tissues was performed in formalin-fixed, paraffin-embedded specimens. After extraction of RNA, TS and DPD gene expressions were measured by the real-time reverse transcriptional PCR method. Apart from degree of differentiation, TS and DPD in malignant tissue showed no correlation with clinicopathologic factors. TS in malignant tissue was higher in differentiated type cases than undifferentiated type cases (p < 0.01). However, DPD in malignant tissue of undifferentiated type cases was statistically higher than that of differentiated type cases (p < 0.05). In normal stromal tissue, neither TS nor DPD had any correlation with clinicopathologic factors. TS in malignant tissue was statistically higher than in normal stromal tissue in both differentiated and undifferentiated types (p < 0.0001). DPD in differentiated type malignant tissue was statistically lower than in normal stromal tissue (p < 0.001), but no difference was seen in undifferentiated type cases. TS and DPD gene expressions in primary gastric cancer differ according to degree of differentiation and between malignant and normal stromal tissue.