[A Case of Pyloric Stenosis Due to Gastric Metastasis of Breast Cancer].

We report a case of left advanced breast cancer(T4N1M0, Stage ⅢA)in a 67-year-old woman. In August 2010, her breast cancer(triple-negative invasive ductal carcinoma)was resected(mastectomy plus axillary lymph node dissection) with adjuvant chemotherapy(TC)and irradiation to her chest wall. In July 2018, she experienced recurrent vomiting. Gastrointestinal endoscopy(GS)revealed type Ⅳ advanced gastric cancer-like appearance with pyloric stenosis. Pathological findings confirmed hormone-positive gastric metastasis of breast cancer. Systemic chemo-endocrine therapy(EC and anastrozole) was performed, following which her symptoms improved. In May 2019, recurrent vomiting appeared again. Thereafter, systemic chemo-endocrine therapy(paclitaxel plus bevacizumab and fulvestrant)was initiated, and her symptoms showed improvement. In November 2020, she showed obstructive jaundice due to malignant biliary stenosis. She was treated using endoscopic biliary stenting, but died 2 months later. Gastric metastasis is reported rarely in 4% of all breast cancers, and GS should be recommended in cases of recurrent abdominal complaints.

Acid hydrolysis reveals a low but constant level of pheomelanin in human black to brown hair.

We previously reported a constant ratio of the benzothiazole pheomelanin marker thiazole-2,4,5-tricarboxylic acid (TTCA) to the eumelanin marker pyrrole-2,3,5-tricarboxylic acid (PTCA) in eumelanic, black human hair. A constant level (20%-25%) of benzothiazole-type pheomelanin was recently demonstrated in human skin with varying concentrations of melanin. Therefore, in this study, we aimed to investigate the origin of pheomelanin markers in black to brown human hair by developing a method to remove protein components from hair by heating with 6 M HCl at 110°C for 16 hr. For comparison, synthetic melanins were prepared by oxidizing mixtures of varying ratios of dopa and cysteine with tyrosinase. Hair melanins and synthetic melanins were subjected to acid hydrolysis followed by alkaline H2 O2 oxidation. The results show that the hydrolysis leads to decarboxylation of the 5,6-di-hydroxyindole-2-carboxylic acid moiety in eumelanin and the benzothiazole moiety in pheomelanin and that eumelanic human hair contains 11%-17% benzothiazole-type pheomelanin.

[Gallbladder carcinoma, progressed along cholecystoduodenal fistula--a case report].

A 75-year-old woman had an operation for gallstone ileus without cholecystectomy in other hospital and she was admitted to our hospital because of duodenal adenoma with severe atypia and small carcinoid in proximal duodenal wall. Distal gastrectomy and cholecystectomy were performed. Histological studies revealed the existence of cholecystoduodenal fistula and suggested the existence of gallbladder carcinoma progressed to the duodenal wall through the fistula. Cystic duct dissection and lymph nodes dissection were performed. It has been theorized that a cholecystoduodenal fistula may represent a significant risk factor in the development of gallbladder carcinoma because of the chronic reflux of duodenal contents which includes pancreatic juice. Our case may support this theory. In this case, we thought that the formation of gallbladder cancer could have been avoided if the cholecystectomy was performed in the first operation for gallstone ileus. It is very important that cholecystectomy should be performed when an existence of cholecystoduodenal fistula is highly suspected.

[Two case reports of metastatic liver carcinoma with the effective treatment of radiofrequency ablation and intraarterial chemotherapy].

We report two cases of metastatic liver carcinoma with the treatment of radiofrequency ablation (RFA) and intraarterial chemotherapy. The 57-year-old man of Case 1 had resectable multiple liver metastases of rectal carcinoma in November 2007. He refused a liver resection, but accepted a low anterior resection of the rectum and RFA and intraarterial chemotherapy (5-FU 1,000 mg WHD). After this treatment, he had accepted systemic chemotherapy and found no liver recurrence within a year. The 66-year-old man of Case 2 had unresectable multiple liver metastases of locally-advanced esophageal carcinoma in July 2006. He had accepted radiochemotherapy (FP+65 Gy), and then RFA and intraarterial chemotherapy (5-FU 1,000 mg WHD). After this treatment, solitary brain metastasis and lymph node metastasis of mediastinum were found and treated, and now he has been alive with systemic chemotherapy.

[Anti tumor activities of lentinan and micellapist in tumor-bearing mice].

Although Lentinan (LNT) is sold as a medicine, and Micellapist (MME) sold as a food supplement, both LNT and MME are beta-glucans isolated from the Shiitake mushroom (Lentinula edodes). These two substances have been thought to be the same component of Shiitake. In the present study, we evaluated anti tumor activities of LNT and MME in tumor-bearing mice (B10.D2 mice implanted with S908D2 tumor cells) and examined the mechanism of immunopotentiation of these substances. The tumor growth was significantly suppressed in the LNT-treated group. In ex vivo evaluation, the tumor cytotoxicity was significantly reduced by a treatment of splenocytes with anti-CD8 antibody in the LNT-treated group. Furthermore, the tumor cytotoxicity of the LNT-treated group was also significantly reduced by a treatment of splenocytes with anti-CD8 antibody and its complement and with an anti-CD4 and its complement in the effector phase and the induction phase, respectively. A significant prolongation of the survival of tumor-bearing mice as compared to the untreated control group was noted in the LNT-treated group. In the mice treated intraperitoneally with LNT, CD8-positive cells appeared to have suppressed tumor cell proliferation. CD4-positive cells appeared to be involved in this activity of CD8-positive cells. On the other hand, orally administered MME has exerted no clear cytotoxic effects.

[Evaluation of peritoneal cytology in colorectal carcinoma].

We investigated the incidence of free cancer cells in the peritoneal washings of 278 patients who had undergone surgery for colorectal cancer to evaluate its influence as a prognostic factor of the disease. Twenty-two cases (7.9%) were found to have malignant positive cytology (CY(+)). The rate of CY(+) in the cases with peritoneal dissemination (P(+)) was significantly higher than that in P(-) (66.7% vs 3.8%). In 244 cases, those who had tumors exposing to the peritoneum, both CY(+) and P(+) were observed highly in poorly differentiated adenocarcinoma. Among 18 P(+) cases, the rates of CY(+) were higher in both P3 and cur C than in P1, 2 and cur B. When restricted to 260 P(-) cases, CY(+) was observed more often in stage IV cases (14.3% vs 1.8%). Rate was significantly high in M+ (66.7%). Prognosis of 4 P(-) CY(+) cur A cases was as follows; 2 survived for a long time with no recurrence (20 and 60 months), 1 had curable liver metastases after half a year and obtained a 2 year disease free period after surgery, and another one died with brain, liver, and peritoneal recurrence one year later. The incidence of CY(+) is correlated with P(+); CY(+) increased when P(+) is extended more highly and incurable. CY(+) alone doesn't become a prognostic factor for peritoneal recurrences, because CY(+) is found rarely in curable P(-) cases. However, CY(+) is also associated with far advanced cancer with remote metastases, therefore we should consider the risk of such metastases for CY(+) cases with curable colorectal cancer.

[The docetaxel radiosensitization experience for the treatment of unresectable esophageal cancer].

BACKGROUND: Docetaxel is an increasingly important drug for the treatment of esophageal cancer. The docetaxel radiosensitization has been established in cancer cell lines. The therapeutic response and toxicity of a weekly docetaxel in combination with radiotherapy for unresectable esophageal cancer were examined. METHODS: Ten patients with locally advanced or metastatic squamous cell esophageal cancer were recruited in the following protocol. The median age was 65.7 years. Patients received radiation in 2 Gy single daily fractions to a total dose of 60 Gy. Docetaxel (10 mg/m2) was administered weekly for 6 consecutive weeks. RESULTS: One patient could not be evaluated. The overall response rate was 77% with 11% CR and 66% PRs. Mild grade 2 leukocytes toxicity was observed in 2/10 patients, which enforced the treatment absence for 7-14 days. Grade 2 stomatitis was noted in one patient. No severe grade 3 adverse effects were observed. CONCLUSION: It is concluded that low dose docetaxel with radiotherapy is feasible and, a high response rate can be expected. Toxicity is modest, and this protocol may be useful for the outpatients or neoadjuvant chemotherapy.

[An effective weekly paclitaxel administration for gastric cancer with malignant ascites--a case report].

A 71 year-old woman underwent total gastrectomy for advanced gastric cancer of p stage IV (pathological findings: por1 type 3 pT3, pN3 (12p: 1/1, 16b1 int: 3/3, 16b1 lat: 2/2), P1, CY1, H0) in March 2002. She was treated with the double modulation therapy of MTX/CDDP/5-FU intraperitoneally after the surgery. After leaving the hospital, she was carrying out the chemotherapy with MTX/5-FU continually. In August 2002, she became hospitalized once again because an appetite decrease and diarrhea appeared. CT of abdomen showed that malignant ascites had obviously accumulated, and she was admitted. Because it was conceivable in all cases of an inflammation by the chemical stimulation that originated in an anticancer drug, we suspended the intraperitoneal chemotherapy. Paclitaxel 90 mg/body administration was started intravenously on a weekly basis from the end of the same month. Those symptoms improved and she was discharged from the hospital, and was continued the paclitaxel administration. In CT of the abdomen that was taken in November in 2002, malignant ascites had obviously been decreasing and disappeared completely after that.

[A case of gastric cancer with extraordinary liver metastasis effectively treated by adjuvant chemotherapy].

This was an extraordinary liver metastasis case with complication when the patient, a 70-year-old male, was diagnosed with stomach cancer for the first time. However, the patient has been in remission and is a long-term survivor due to an active chemotherapy after the operation. His chief complaints were stomachache and a loss of weight. He was diagnosed with stomach cancer by endoscopy. During the surgery, the mass was found to be 3 QFB palpable caused from hepatomegaly. The liver dysfunction was revealed in the blood biochemistry inspection. The abdominal CT revealed that the stomach cancer had spread to the whole liver. Distal gastrectomy was performed on May 22, 1997. In pathological findings, the tumor was diagnosed as a well-differentiated adenocarcinoma. Final findings: M, type3, T3 (SE), N2, H3, P0, CY0, and Stage IVb. The 5-FU based chemotherapy was performed and a complete response was temporarily obtained. However, it has recurred one year later and two or more kinds of chemotherapy have continued. He is alive for more than 7 years and comes to our hospital as an outpatient.

[MTX/CDDP/5-FU double modulation intra-peritoneal chemotherapy for advanced and metastatic gastric cancer--comparison with intra-aortic route and intra-venous route].

We studied the efficacy of MTX/CDDP/5-FU intra-peritoneal chemotherapy for advanced and metastatic gastric cancer (n=24), and compared the results with intra-aortic (n=26) and intra-venous (n=21) routes of MTX-CDDP-5-FU double modulation therapy. I.p. administration was more efficient for reduction of malignant acites (p=0.049). However, median survival duration of malignant acites cases showed no difference between the i.p. group and i.a., i.v. groups (p=0.103). Survival rate of the i.p. group was no different with those of i.a. and i.v. groups (p=0.36). Frequency of side effects is much lower in the i.p. group.

[The 5-fluorouracil hepato-arterial infusion with oral UFT therapy for the hepatic and extra hepatic metastases of colorectal cancer].

BACKGROUND: The 5 fluorouracil hepato-arterial infusion (5-FU HAI) therapy has a good effect on the liver metastases of colorectal cancer. To gain the antitumor effect of the extra-hepatic lesion, an oral UFT was combined with 5-FU HAI (pharmacokinetic modulating chemotherapy, PMC) to enhance the plasma 5-FU concentration. METHODS: UFT (200-400 mg/day) was orally administered daily and a continuous infusion of 5-FU (1,000-1,500 mg/5 h) was given once a week. Eight patients were treated with this regimen. Five of the eight have extra-hepatic lesions with liver metastases when this treatment was started. The response, time to progression, survival, and toxicity were detected. RESULTS: Four of the five patients with extra-hepatic lesion were evaluated. The response rate was 50% (1 CR, 1 PR, and 2 SD). For the liver metastases, the response rate was 62.5% (1 CR, 4 PR, 2 SD, and 1 PD). Grade 2 leukopenia was found in 1 patient. CONCLUSIONS: The 5-FU HAI with an oral UFT therapy had a good effect on the extra-hepatic lesions as well as hepatic metastases of colorectal cancer.

[The significance of a combination of hepatic artery pump reservoir and new immunotherapy for cancer (NITC) in the treatment of colorectal liver metastasis].

Infusion of anti-cancer agents through a hepatic artery pump reservoir has been reported as a relatively useful means of treating multiple liver metastases but its mechanism of action remains to be clarified. We thought that immune responses might be involved in the mechanism of action of this therapy and attempted to test this assumption in patients with colorectal liver metastases. When the patients were divided into two groups by survival period (the 24-week or longer survival group and the less than 24-week survival group), the 24-week or longer survival group had significantly higher Th1 cytokine levels (p<0.001-0.05) and significantly lower VEGF levels (p<0.01) than the less than 24-week survival group. The survival rate tended to be higher in patients for whom intra-arterial infusion therapy was combined with NITC. These results suggest that the combined therapy induces some kind of immune reaction closely related to tumor size reduction and prolonged patient survival. It seems necessary to compare immune activity during intra-arterial infusion therapy alone with activity during intra-arterial infusion treatment in combination with a new immunotherapy.

[A case of gastric cancer with peritoneal dissemination which shows a remarkable efficacy by a weekly administration of paclitaxel intraperitoneally].

We treated a 65-year-old female with gastric cancer who underwent peritoneal dissemination after 6 successive weeks of paclitaxel intraperitoneal therapy (90 mg/body), and obtained a disappearance of ascites and a reduction of the primary carcinoma. Operative findings: U ant, type 5, 26x20 mm, por, T2, n1(+), H0, P0, CY0, M0, stage II, and grade 2. A weekly paclitaxel intraperitoneal therapy could be a useful for both peritoneal dissemination and the primary carcinoma of advanced gastric carcinoma.

[A case of gastric endocrine cell carcinoma with neck lymph node metastasis resected after neoadjuvant chemotherapy].

A relatively rare case of gastric endocrine cell carcinoma was reported. The prognosis of this disease appears to be very poor due to its rapid rate of growth and invasiveness. A 75-year-old woman underwent a gastric endoscopy because the patient complained of an appetite loss. A gross Borrmann 3 type lesion in the greater curvature of the fornix was found. Biopsy specimens showed endocrine cell carcinoma. Abdominal CT examination revealed metastases in left neck and paraaortic lymph nodes. The serum sample showed an elevation of NSE level to be 53. A combination chemotherapy was performed using cisplatin and etoposide, which resulted in remarkable reduction of the main tumor two months later. The total gastrectomy associated with D2 lymph node dissection was performed. However, abdominal tumor was observed again in a month and it progressed rapidly. No clear response to the chemotherapies with cisplatin/etoposide or paclitaxel was found. The patient died 5 months after the operation.

[Concentration of 5-FU after hepatic artery infusion chemotherapy for liver metastases of colorectal cancer].

AIM: Hepatic artery infusion chemotherapy (HAI) using 5-FU is a good method of treating patients with liver metastases from colorectal cancer. We investigated the toxicity and the response in relation to the concentration of 5-FU after HAI, and examined various factors that would have an effect on the 5-FU concentration. RESULTS: The mean 5-FU concentration was 480 ng/ml. The most frequent complication of HAI was anorexia. Three of 14 patients suffered from grade 2 or 1 anorexia. The 5-FU concentration of these patients was higher (1,010, 721, 642 ng/ml) than that of the others. The response rate of HAI was 36%. The 5-FU concentration of responders tended to be lower than that of non-responders. None of the following was related to the 5-FU concentration: whether or not the gallbladder was resected, whether or not co-lateral blood flow was recognized, or the volume of the patients' liver. CONCLUSION: 5-FU concentration after HAI has some effect on anti-tumor response and gastrointestinal toxicity.

[Significance of gefitinib combined with immunotherapy in tumor-bearing mice].

Gefitinib (brand name: Iressa) is a drug approved for molecule-targeting therapy in lung carcinoma patients. There are still many unresolved problems concerning the safety and mechanism of action of this drug. Based on the expectation that this drug combined with immunotherapy would be highly effective, we recently conducted an experiment in tumor-bearing mice. In this experiment, however, the tumor was not significantly reduced in size by this combined therapy. However, since the tumor in this animal model was EGFR positive and because tumor growth tended to be suppressed in mice with higher immune activity, it seems likely that additional studies of this therapy will contribute to identifying the optimum drugs to be combined with gefitinib and the optimum method of dosing that will lead to satisfactory efficacy and safety of gefitinib combined with immunotherapy.

The role of the rectal branches of pelvic plexus in defecation and colonic motility in a canine model.

The parasympathetic nerves regulate colonic motility and defecation. The vagal nerve controls the right colon and the pelvic nerve permeates the left colon and rectum via the rectal branches of the pelvic plexus (RBPP). This investigation aimed to measure the functional changes of the colon and rectum after RBPP-transection for over six months. RBPP-transection was performed in 15 dogs. Five dogs each were sacrificed immediately, one month, and six months after RBPP-transection. The stool condition, colorectal transit, defecation reflex, colorectal response to electrical stimulation, and pathological degeneration was investigated prior to, one month after, and six months after RBPP-transection. Four of the 5 dogs observed had loose stool one month after RBPP-transection, and one of the 3 had recovered six months later. Half transit time (HTT) at transverse colon got longer in six of the 8 in one month. Six months later, HTT got shorter in three of the 4 than that of one month. Defecation reflex was not observed one month after RBPP-transection, but noted in two of the 5 six months later. These results may suggest that vagal nerve compensates for the oral site of the left colon after denervation of the pelvic nerve which is originally distributed.

P-selectin-dependent macrophage migration into the tubulointerstitium in unilateral ureteral obstruction.

BACKGROUND: Interstitial infiltration of macrophages (Mø) is one of the main causal factors for the tubulointerstitial injury. However, precise mechanisms of Mø infiltration into tubulointerstitium have not been fully explored. The purposes of this study were to assess the role of selectins in the acute infiltration of Mø in rats with unilateral ureteral obstruction (UUO) and to evaluate the role of vasa recta, that is, whether they facilitate massive influx of Mø into the interstitium by functioning as specialized vessels. METHODS: To evaluate the role of selectins in Mø infiltration into tubulointerstitium, the expression of selectins and L-selectin ligands was examined by immunohistochemistry and immunoelectron microscopy. The functional role of P-selectin in vasa recta was studied by Stamper-Woodruff assay, in vivo p-Mø migration assay and in vivo blocking experiments with the monoclonal antibody (mAb) ARP2-4. RESULTS: Selective expression of P-selectin was detected in vasa recta as early as one hour after UUO, and the expression increased thereafter for 96 hours. In contrast, endothelial expression of L-selectin ligands and E-selectin were not detectable. In the Stamper-Woodruff assay on kidney sections of rats with UUO, the adhesion of isolated rat peritoneal Mø (p-Mø) to vasa recta was significantly inhibited by the mAb ARP2-4 (P-selectin blocker; P < 0.01), but not by mAb ARE-5 (E-selectin blocker) or rLECIg (rat L-selectin chimeric protein). In the in vivo transfer experiments with fluorescein-labeled p-Mø into rats 48 hours after UUO, labeled p-Mø had accumulated around vasa recta at three minutes and had infiltrated predominantly into the outer medulla at 180 minutes. The number of labeled p-Mø was reduced when the rats were pretreated with ARP2-4 (P < 0.01). Finally, ARP2-4 (10 mg/kg), injected 15 minutes before UUO, reduced the number of infiltrated Mø (P < 0.01). CONCLUSION: The results suggest that vasa recta, which express P-selectin, contribute to massive infiltration of Mø into the interstitium by functioning as specialized post-capillary venules.