[A Case of Recurrent Breast Cancer with Delayed Wound Healing Induced by Bevacizumab].

Bevacizumab plus paclitaxel therapy for recurrent breast cancer did not prolong overall survival(OS)in clinical trials, but it was efficacious for treating life-threatening HER2-negative recurrent breast cancer. This regimen is often used in daily clinical practice by breast surgeons. However, bevacizumab therapy results in unique adverse events, of which proteinuria and hypertension are relatively frequent. Moreover, the symptoms often improve on reducing the dose or discontinuing the drug. In this case, bevacizumab administration caused delayed wound healing, making subsequent anticancer treatment difficult, and consequently we could not prolong the patient's life.

[A Case of COVID-19 Infection during Postoperative Chemotherapy for Breast Cancer Treated with Antibody Cocktail Therapy to Prevent Disease Aggravation].

The outbreak of COVID-19 has caused a global pandemic, and it has been reported that patients with cancer are at high risk of developing complications from the disease. However, we believe that prolonged interruption of chemotherapy due to extended COVID-19 treatment is not desirable, given the intensity of cancer treatment. We report a case of COVID-19 infection during postoperative chemotherapy for breast cancer, in which antibody cocktail therapy prevented disease aggravation and delayed breast cancer treatment. The patient is a 45-year-old woman who came to our hospital with a complaint of a right mammary mass. The mass was diagnosed as invasive ductal carcinoma with an ER and PR of 0%, a HER2 score of 1+, and a Ki-67 of 90%. After preoperative chemotherapy, she underwent a right mastectomy and axillary dissection. The pathology result showed non-pCR. The administration of capecitabine was started as adjuvant therapy. On day 8 of cycle 3, she developed a fever in the 39℃ range, and on the next day, a COVID-19 POC gene test confirmed that the patient was positive for infection. On the same day, neutralizing antibody drugs(casirivimab and imdevimab)were administered as antibody cocktail therapy. Two days after treatment(day 11), a blood test showed Grade 3 neutropenia, but there was no recurrence of fever or evidence of pneumonia. After 2 weeks, capecitabine was resumed, and the patient was able to complete 8 cycles of capecitabine therapy without any major complications.

[ESR1 Mutation-Positive Recurrent Breast Cancer Successfully Treated with Letrozole plus Abemaciclib].

Approximately 70% of breast cancers are estrogen receptor(ER)positive, an indication for endocrine therapy. The first choice of treatment for ER-positive metastatic recurrent breast cancer is endocrine therapy, which has relatively few side effects; however, many of these side effects become resistant during treatment. One of the resistance mechanisms is mutations in the ESR1 gene, which have also been found to occur after long-term aromatase inhibitor(AI)treatment. Here, we describe our experience of a case in which long-term PR was achieved with AI(letrozole)plus abemaciclib despite ESR1 mutation positivity in cancer genetic screening and review the literature.

[A Case Study of Successful Breast Cancer Treatment after Recovery from Drug-Induced Interstitial Lung Disease].

Drug-induced interstitial lung disease(DILD)is a possible complication of many anticancer drugs. When DILD occurs during breast cancer treatment, choosing the right drug for subsequent treatment is often difficult. In our first case, the patient developed DILD during dose-dense AC(ddAC)therapy; however, the disease resolved with steroid pulse therapy, and the patient underwent surgery without disease progression. In the second case, a patient on anti-HER2 therapy for recurrent disease developed DILD in response to docetaxel plus trastuzumab plus pertuzumab administered to treat T-DM1 after progressive disease. In this report, we describe a case of DILD that did not worsen and the patient had successful treatment outcome.

[Olaparib Could Be Re-Administered after Chemotherapy].

Olaparib, a PARP inhibitor, was approved in 2018 for BRCA1/2 gene mutation and HER2-negative inoperable or recurrent breast cancer with previous chemotherapy. Olaparib is an important drug with minor adverse events compared to chemotherapeutic drugs. In addition, it is expected to exert a high therapeutic effect on breast cancer with BRCA mutations due to its characteristics. We report a case of BRCA2-mutated breast cancer in a patient in whom olaparib was initiated. The patient complained of strong nausea; however, the treatment could be continued by reducing the dose of olaparib to 400 mg and using multiple drugs such as antiemetics and anxiolytics in advance.

Protein-losing enteropathy secondary to nonocclusive mesenteric ischemia: A case report.

RATIONALE: Nonocclusive mesenteric ischemia (NOMI) is a life-threatening disorder; prompt diagnosis is vital. Surgical treatment is often required, but some cases can be treated conservatively. We herein report an extremely rare case wherein protein-losing enteropathy (PLE) developed after conservative treatment of NOMI. PATIENT CONCERNS: The patient was a 66-year-old man. He underwent laparoscopic super low anterior resection and temporary ileostomy for sigmoid colon cancer and rectum cancer. During the postoperative course, he developed ileus. Subsequently, he developed shock. On examination, the possibility of NOMI could not be denied, but intestinal necrosis was absent. Conservative treatment was initiated. His general condition improved, but the ileus persisted. Therefore, we performed a stoma closure. Ten days after stoma closure, he developed continuous unexplained diarrhea. The serum albumin and total protein levels were low. The symptoms improved after administration of an antidiarrheal drug, but the root cause was yet untreated. DIAGNOSIS: The patient's alpha-1 antitrypsin clearance was increased. A CT scan revealed an enhanced hypertrophied wall of the short segment of the small intestine, and 99m Tc-labeled human serum albumin scintigraphy revealed protein leakage into the thickened wall of the small intestine. We arrived at a definitive diagnosis of PLE secondary to NOMI. INTERVENTIONS: Partial resection of the affected small intestine was performed. OUTCOMES: The patient recovered uneventfully and was discharged on the 30th postoperative day. LESSONS: NOMI has a high mortality rate, often requiring intestinal resection immediately after onset. To our knowledge, there is no report of PLE developing after conservative treatment, as in our case. Further study of cases is necessary to determine the reversibility of the condition, which will influence the therapeutic plan. We herein present an extremely rare case of PLE after conservative treatment for NOMI. The possibility of PLE also needs to be considered when hypoalbuminemia occurs after conservative treatment of NOMI.

Clinical study to identify specific characteristics of cancer newly developed in the remnant stomach.

BACKGROUND: Cancer newly developed in the remnant stomach (CRS) after partial gastrectomy is worthy of attention not only because it is a typical model of carcinogenesis but also from the aspect of cancer diagnosis. METHODS: We treated 47 patients with CRS in the 20 years from 1979 to 1998. Clinicopathological variables, as well as long-term survival results after the second surgery, were reviewed to clarify whether there were any differences in the characteristics of this disease entity compared with the usual primary gastric cancer. RESULTS: The mean time interval between the initial surgery and surgery for CRS was 25.8 years for patients with CRS with previous benign gastric lesions, and 10.6 years for those with previous gastric cancer. CRS was frequently detected at an early stage in the patients with previous cancer, and in the patients who had undergone reconstruction by the Billroth I method (regardless of the primary nature of the disease). Cancers with a differentiated histology developed more frequently in the patients who had undergone the initial surgery for cancer disease. Long-term survival results after the second surgery clearly demonstrated that surgical treatment for CRS was as effective as that for primary cancer in the upper stomach (PUC). In addition, it was confirmed that new lymphatic drainage into the lower mediastinum or the jejunal mesentery had developed after the initial gastric surgery. CONCLUSION: The findings suggested that patients with CRS and those with PUC should be treated similarly, although the findings of a high incidence of lymph node metastasis to the lower mediastinum and/or to the jejunal mesentery in the CRS patients should be taken into consideration.

Relationship between types of common channel and development of biliary tract cancer in pancreaticobiliary maljunction.

BACKGROUND/AIMS: The incidence of biliary tract cancer development is high among patients with pancreaticobiliary maljunction. However, there have been no reports published evaluating the incidence of development of biliary tract cancers in pancreaticobiliary maljunction based on the morphology of the common channel at the junction of the bile and pancreatic ducts. We evaluated between types of common channel and development of biliary tract cancers in pancreaticobiliary maljunction. METHODOLOGY: During the last 21 years, we have experienced 78 patients with pancreaticobiliary maljunction. Of those patients, 44 adult patients, whose morphologic types of common channel were identified by cholangiography, were enrolled in this study. The dilatation patterns of the common channel were classified into 3 types: A type (moderately dilated type), B type (markedly dilated type), and C type (non-dilated type). Evaluated items included the length and dilation patterns of the common channel, incidence of development of biliary tract cancers and proliferative activity in the biliary tract epithelium. RESULTS: Seventeen patients had a common channel shorter than 20 mm, while 27 had a common channel of 20 mm or longer. Eleven patients with a common channel of 20 mm or longer had development of bile tract cancers. The dilation patterns of the common channel were classified as A (11 patients), B (16 patients) and C type (17 patients). Amylase levels in the biliary tract were higher in patients with A and B type than in patients with the C type. Development of gallbladder cancer was observed in 6 patients with A, 2 patients with B and one patient with C, while development of bile duct cancer was observed in 2 patients with C and one patient with B. The PCNAL.I. of the biliary epithelium was higher in patients with A, B and C type in descending order. CONCLUSIONS: The incidence of development of biliary tract cancer was higher in patients with common channel of 20 mm or longer. The proliferative activity in the biliary epithelium was accelerated in patients with A type, together with a high incidence of development of gallbladder cancer.

Studies on biliary tract carcinoma in the case with pancreaticobiliary maljunction.

BACKGROUND/AIMS: The purpose of this study was to clarify the clinicopathological features of pancreaticobiliary maljunction and to determine the appropriate surgical approach for biliary tract with pancreaticobiliary maljunction. METHODOLOGY: The data of 77 patients with pancreaticobiliary maljunction including 13, who had been treated for biliary tract cancer, were reviewed retrospectively. We assessed the clinical features, biological characteristics of the cancer, methods of surgical treatment, postoperative outcome and cell proliferating activity of the biliary epithelium, evaluated by the PCNALI (proliferating cell nuclear antigen-labeling index). RESULTS: The incidence of cancer development in the case with pancreaticobiliary maljunction was 13.4% in the bile duct dilatation group (n = 67) and 40.0% in the non-dilatation group (n = 10). Dissection of lymphadenectomy was performed in 10 (76.9%) of 13 patients, and curative resection was feasible in 9 of the 10 patients. Two (20.0%) of the 10 patients had lymph node involvement noted at surgery and died of recurrence. In the other eight patients without lymph node involvement at surgery, six patients underwent curative resection and are alive at 7 months to 11 years and 6 months after surgery. PCNALI of the biliary epithelium of the patients with pancreaticobiliary maljunction was significantly higher than that of the control group. CONCLUSIONS: For patients with pancreaticobiliary maljunction, it should be stressed that the extrahepatic bile duct be prophylactically removed, even when there are no neoplasmatic changes because of high prevalence of cancer development, presumably predicted by the increase of cell proliferative activity in the biliary epithelium. For patients with biliary cancer, early detection at the stage with no lymph node involvement is essential to secure for long-term survival.

Expression of HER2 in human gastric cancer cells directly correlates with antitumor activity of a recombinant disulfide-stabilized anti-HER2 immunotoxin.

BACKGROUND: Amplification of the human epidermal growth factor receptor 2 (HER2) gene and overexpression of the HER2 protein have been associated with an unfavorable prognosis. We determined the efficacy of an anti-HER2 immunotoxin, erb-38 [e23(dsFv)PE38], against human gastric cancer cells. METHODS: Immunotoxin was made by fusing the disulfide-stabilized Fv fragments (dsFv) of a monoclonal antibody e23 to a truncated mutant of M(r) 38 Pseudomonas exotoxin (PE38) that lacks its cell-binding domain. RESULTS: The immunotoxin-mediated cytotoxicity directly correlated with the expression levels of the HER2 gene and protein in human gastric cancer cells. Interestingly, MKN-45P cells, a variant line of MKN-45 producing peritoneal dissemination and ascites in vivo, expressed a higher level of HER2 and were more sensitive to erb-38 than MKN-45 cells. RFB-4, a control anti-CD22 immunotoxin, was cytotoxic against none of the tested human gastric cancer cells, also suggesting that the lysis mediated by erb-38 was specific for HER2 expression. Three consecutive iv injections of erb-38 at doses of 0.5 or 5 microg/body eradicated experimental liver metastases and peritoneal disseminations produced by MKN-45P in a dose-dependent manner. CONCLUSIONS: We conclude that an erb-38 anti-HER2 immunotoxin has specific antitumor activities against human gastric cancer cells overexpressing HER2.