Systemic immunity markers are associated with clinical outcomes of atezolizumab treatment in patients with triple-negative advanced breast cancer: a retrospective multicenter observational study.

Immune checkpoint inhibitors (ICI) are reportedly efficacious against triple-negative breast cancer (TNBC) and are now recommended as first-line therapy. Systemic immunity markers, the absolute lymphocyte count (ALC) and the neutrophil-to-lymphocyte ratio (NLR), have been identified as predict ICI efficacy in patients with various cancers. We retrospectively enrolled 36 TNBC patients who received atezolizumab treatment between September 2019 and May 2021 at eight Japanese medical institutions. We evaluated systemic immunity markers, including dynamic changes in these markers, as predictors of survival benefit derived from atezolizumab treatment. Median time-to-treatment failure (TTF) and overall survival (OS) were 116 days and "not reached", respectively. Patients with low NLR at baseline and decreased NLR at the start of the second cycle (SO2nd) had significantly longer OS than those with high NLR at baseline and increased NLR (SO2nd) (log-rank P < 0.001 and log-rank P = 0.049, respectively). Multivariate analyses identified high ALC at baseline and decreased NLR (SO2nd) as independent predictive markers for longer TTF (P = 0.043 and P = 0.002, respectively), and low NLR at baseline and decreased NLR (SO2nd) as independent predictive markers for longer OS (P < 0.001 and P = 0.013, respectively). The safety profile was consistent with those of previous trials. This retrospective multicenter observational study showed the clinical efficacy and safety of atezolizumab treatment. Furthermore, systemic immunity markers, including their dynamic changes, were found to be associated with clinical outcomes of atezolizumab treatment in patients with advanced or metastatic TNBC.

An extremely rare case of nonfunctioning parathyroid carcinoma occurring in a parathyroid adenoma.

A 53-year-old woman with a 4-month history of fatigue and somnolence was referred to her local doctor because of the worsening of her symptoms. Marked increases in her serum calcium (13.0 mg/dl) and intact-parathyroid hormone (175 pg/ml) were found, she was referred to our hospital. On physical examination, there was a palpable 3 cm mass in her right neck. Ultrasonography showed a 1.9 × 3.6 cm circumscribed hypoechoic lesion in the caudal right lobe of the thyroid gland. There was very mild 99mTc-sestamibi scintigraphic accumulation. Her preoperative diagnosis was primary hyperparathyroidism due to parathyroid carcinoma, and surgery was performed. The tumor weighed 6300 mg and did not invade the surrounding area. The pathology showed a mixture of small cells thought to be parathyroid adenomas and large, pleomorphic nuclei and fissionable carcinomas. Immunostaining showed that the adenoma portion was PTH-positive, chromogranin A-positive, p53-negative, PAX8-positive, PGP 9.5-negative with a Ki 67 labeling index (LI) of 2.2%. Whereas the carcinoma portion was PTH-negative, chromogranin A-negative, p53-positive, PAX8-positive, PGP 9.5-positive with a Ki67 LI of 39.6%, showing a nonfunctioning aspect and highly malignant. Postoperatively, the patient is alive without recurrence 9 years later without hypercalcemia or recurrence. A case of nonfunctioning parathyroid carcinoma in an extremely rare parathyroid adenoma is reported.

[Three Cases of Orbital Metastasis from Breast Cancer Treated with Radiotherapy].

Orbital metastasis from breast cancer is relatively uncommon and is not the dominant prognosis. While it can reduce a patient's QOL through symptoms such as diplopia, visual impairment, and exophthalmos, evidence suggests that radiotherapy might improve these symptoms in a relatively short period. We report 3 cases of orbital metastasis from breast cancer treated with radiotherapy. All 3 patients were diagnosed with stage Ⅳ breast cancer and underwent chemotherapy and endocrine therapy for several years. When they were diagnosed with orbital metastasis, their life expectancy was only a few months with debilitating illness. They received radiotherapy, which caused slight side effects including skin disorders. The cancer symptoms rapidly improved in 2 patients, suggesting that radiotherapy can be an efficacious choice for improving the QOL for patients with orbital metastasis from breast cancer, especially for patients in terminal status.

A case report of fibroadenoma of the breast with characteristic cystic change on a cut surface.

Fibroadenoma with remarkable cystic change is very unusual. Opinions differ as to the interpretation of this lesion. Furthermore, there have been few reports focusing on its macroscopic view. We herein report a case of fibroadenoma in a 43-year-old woman. The patient presented herself to a medical doctor's office due to a rapidly growing breast tumor. Based on a core needle biopsy, a benign lesion was suspected, and the tumor was surgically resected. On a macroscopic study, the cut surface of the tumor revealed a remarkably cystic and well-circumscribed lesion with an intracystic polypoid component. Microscopically, a variety of findings of epithelial and stromal proliferation were observed. This is an interesting case not only because a fibroadenoma with prominent cystic change is unusual but also because the breast tumor showed a characteristically cystic appearance on its macroscopic view.

[Two Cases of Endobronchial Metastases from Breast Cancer].

Endobronchialmetastasis(EBM)is a rare complication in breast cancer patients. Herein, we report 2 cases of EBM in breast cancer patients. Patient 1 had pulmonary metastases that were treated with hormone therapy and showed long survival after achieving a CR, while patient 2 had multi-organ metastases and died 42 months after the diagnosis of EBM. If bronchial obstruction is observed in a breast cancer patient, early diagnosis of EBM via a bronchoscopic examination is recommended. EBM may not indicate a poor prognosis, and appropriate anti-cancer therapy with palliative intrabronchial therapies can prolong the survival in selected EBM patients.

[Three Cases of Intrathecal Chemotherapy with Ventricular Catheter for the Treatment of Leptomeningeal Metastasis from Breast Cancer].

Leptomeningeal metastasis(LM)is a rare complication in patients with breast cancer. We report 3 cases of LMs in patients with breast cancer who were treated with intrathecal methotrexate via an Ommaya reservoir. In 2 patients, a significant neurological improvement was observed, whereas in 1 patient there was no response. The overall survivals for the patients who experienced improvements were 22 and 9 months. Although we have no evidence for the efficacy of intrathecal chemotherapy for LMs in patients with breast cancer, its effects for some patients could be promising, after reservoir management and drug selection establishment.

[A Case of Skull Base Metastasis of Breast Cancer with Dysphasia, Odynophagia and Dysarthria].

While skull base metastases from breast cancer are not uncommon, there are relatively few reported cases in the literature. We report a case of skull base metastasis of breast cancer that resulted in dysphasia, odynophagia, and dysarthria. The case involved a woman in her 50 s who was diagnosed with cancer of the right breast(cT4N1M0, cStage III B)at another medical institution 9 years previously and who underwent a partial mastectomy and an axillary lymph node dissection following neoadjuvant chemotherapy. She began experiencing neck pain 6 months previously, followed by dysphasia, odynophagia, and dysarthria 1 month previously. The patient was referred to our hospital for detailed examination and treatment. PET-CT and cranial MRI was conducted and detected metastatic lesion from the skull base to the upper cervical vertebrae. An orthopedic surgeon performed a posterior decompression and fusion surgery on the occipital bone, cervical vertebra, and thoracic vertebra. A histological examination of bone tissue extracted during surgery revealed that the breast cancer had metastasized. We then performed irradiation of the cervical vertebra from the cranial base and initiated treatment with zoledronic acid and anastrozole. Symptoms such as dysphasia, odynophagia and dysarthria lessened, and the patient is currently being followedupas an outpatient.

[Effectiveness of skin icing for reducing pain associated with luteinizing hormone-releasing hormone agonist injection].

We evaluated the effect of using the cooling method on pain at the site of luteinizing hormone-releasing hormone(LH-RH) agonist injection in 181 prostate cancer or premenopausal breast cancer patients by using a numerical rating scale(NRS)and a questionnaire survey with open-ended questions. According to the NRS, 38.1% of the patients experienced a reduction in pain, 37.5% experienced no change, and 24.4% experienced an increase in pain. Therefore, use of the cooling method did not have a statistically significant effect in terms of pain reduction(p=0.123). However, on analyzing pain reduction according to the answers in the questionnaire survey, 53.2% of the patients experienced a reduction in pain, 38.5% experienced no change, and 8.3% experienced an increase in pain. These findings were different from those obtained on using the NRS. In addition, irrespective of using the cooling method, needle thickness and patient obesity strongly influenced the pain experienced. The skin icing method was effective in reducing pain at the site of LH-RH agonist injection. This method is simple, inexpensive, and safe, and is hence recommended.

Outcomes of Japanese breast cancer patients treated with pre-operative and post-operative anastrozole or tamoxifen.

The present study examined long-term efficacy outcomes in a subgroup of postmenopausal, estrogen receptor-positive Japanese breast cancer patients from the Pre-Operative "Arimidex" Compared with Tamoxifen trial, following pre-operative (3 months) and post-operative (5 years) adjuvant treatment with either anastrozole or tamoxifen. Patients with large, potentially operable, locally-advanced breast cancer were randomized to receive anastrozole (1 mg/day) plus tamoxifen placebo or tamoxifen (20 mg/day) plus anastrozole placebo pre-operatively. After surgery at 3 months, patients continued on the same study medication as adjuvant therapy for up to 5 years or until recurrence, intolerable toxicity or withdrawal of patient consent. Recurrence-free survival and overall survival were measured from the date of randomization to the date of recurrence or death, whichever occurred first. Patients were monitored for adverse events throughout the study period and up to 30 days following administration of the last study medication. During post-operative adjuvant therapy, 4/48 (8%) anastrozole and 25/49 (51%) tamoxifen patients experienced recurrence. There was a significant difference in recurrence-free survival between the two groups (hazard ratio 0.14; 95% confidence interval 0.05-0.41; P = 0.0003). There was a significant increase in overall survival with anastrozole (0.21; 0.05-0.96; P = 0.0436) and there were 2/48 (4%) and 10/49 (20%) deaths with anastrozole and tamoxifen, respectively. Most patients responding to pre-operative therapy remained recurrence-free. Sequential pre-operative/post-operative treatment with anastrozole resulted in lower recurrence and death rates, compared with tamoxifen.

[A case of pathological complete response of metachronous multiple liver metastases from colorectal cancer after mFOLFOX+bevacizumab chemotherapy].

A 25-year-old man with RS rectal cancer received a radical resection of the original tumor and lymph node dissection. Oral tegafur/uracil (UFT)/Leucovorin (LV) therapy has been used for adjuvant chemotherapy, as the pathological Stage was T3N1M0, Stage IIIa. After 10 months from operation, multiple liver metastases were recognized and not resectable. So a systemic chemotherapy by mFOLFOX6+bevacizumab was begun via CV port. After 5 courses of mFOLFOX6+bevacizumab, abdominal CT revealed liver metastases showed remarkable reduction in size. Hepatic resection of S6 segment was enforced, and the patient uneventfully discharged. Pathological findings of S6 segment revealed no residual cancer cells, indicating the histological effect of mFOLFOX6+bevacizumab was Grade 3. And no liver damage was recognized.

[A case of resection of synchronous multiple liver metastases from colorectal cancer after FOLFOX chemotherapy].

A 41-year-old man with multiple liver metastases from sigmoid colon cancer received a radical resection of the original tumor and 16 courses of weekly high-dose 5-FU(WHF)chemotherapy via hepatic arterial reservoir. The metastatic lesions showed stable disease(SD), and systemic chemotherapy by mFOLFOX6 was begun via CV port. After 14 courses of mFOLFOX4, abdominal CT revealed liver metastases were remarkably reduced in size. Hepatic resection of lateral segment and radio frequency ablation(RFA)for S6 were enforced, and the patient was uneventfully discharged. Pathological findings of lateral segment revealed no residual cancer cells, indicating that the histological effect of mFOLFOX6 was Grade 3.

[Clinicopathological significance of pyrimidine nucleoside phosphorylase (PyNPase) and dihydropyrimidine dehydrogenase (DPD) in advanced colorectal cancer].

We examined clinicopathological characteristics and prognoses of seventy advanced colorectal cancer cases by measuring pyrimidine nucleoside phosphorylase (PyNPase) and dihydropyrimidine dehydrogenase (DPD) in tumor and normal tissue. PyNPase activities in cancerous tissue obtained from resected were 82.7 +/- 41.9 U/mg protein, which were significantly higher than 37.2 +/- 24.0 U/mg protein in normal tissue (p < 0.001). On the other hand, DPD activities in cancerous tissue were significantly lower in normal tissue (p < 0.05). In cases with lymphnode metastases, PyNPase activities of cancerous tissue were significantly higher than that of no lymphnode metastases cases (p < 0.05). In cases with grade 2 side-effects or higher by oral adjuvant chemotherapy, DPD activities in normal tissue were significantly lower than that of other cases (p < 0.05). With regard to Dukes' B and C cases that were resected curatively, PyNPase activities of cancerous tissue of higher group's prognosis were worse than that of the lower group. In the group received 5'-DFUR as adjuvant chemotherapy, non-recurrent survival rate of the group exhibiting higher PyNPase activities was better than that of the lower group.

[Combination therapy with Anastrozole and 5'-DFUR as a treatment for metastatic breast cancer].

For metastatic breast cancer patients who have hormone receptor-positive tumors, hormonal therapy aiming at optimal palliation and prolongation of life is the initial treatment of choice. To enhance the effect of hormonal monotherapy, a combination therapy with Anastrozole 1 mg po and 5'-DFUR 800 mg po daily was given to 11 patients with metastatic breast cancer. At a median follow-up period of 15 months, the overall response rate was 45.5%. The median duration of response in responders was 25 months. The overall median survival for the entire series was 15 months after the start of treatment. No patients complained of adverse events of grade 2 and over. This combination therapy with good response and little side effects is useful for metastatic breast cancer patients.

[Radiofrequency ablation therapy combined with intrahepatic arterial infusion chemotherapy for liver metastasis of colorectal cancer].

We performed radiofrequency ablation (RFA) therapy combined with intrahepatic arterial infusion chemotherapy for 7 patients with liver metastasis from colorectal cancer. Synchronous metastasis accounted for 5 cases and metachronous for 2 cases. Two cases were H1, 2 cases H2, and 3 cases H3. Following the resection of colorectal primary lesion, we performed RFA for liver metastasis, using a Cool-tip electrode purchased from Radionics (Burlington, MA, USA). The mean number of sessions per patient was 5.1 (1-10). Ablation time of each session was changed according to tumor size, as follows: less than 1 cm in diameter: 2 min, 2 cm: 5 min, 2.5 cm: 10 min. By using intra-operative catheterization, weekly intrahepatic arterial infusion chemotherapy was performed for liver metastasis. Excellent ablation was achieved in all cases by CT evaluation and no significant side-effect was observed. Average observation period was 15 months (maximal survival period was 31 months) and 6 patients are alive. RFA therapy combined with intrahepatic arterial infusion chemotherapy achieved excellent therapeutic effect, and maintained good quality of life in patients.

Long-term results of breast-conserving treatment for early-stage breast cancer in Japanese women from multicenter investigation.

BACKGROUND: Although many clinical data regarding breast-conserving treatment have already been reported from European and North American countries, few clinical data with long-term follow-up have been reported from Japan. METHOD: We collected information on therapeutic and possible or developed prognostic factors and follow-up data for Japanese women who had received breast-conserving treatment consisting of wide excision of the primary tumor, axillary dissection and radiotherapy for unilateral breast cancer considered suitable for breast-conserving treatment from 18 Japanese major breast cancer treating hospitals; 1561 patients were registered. RESULTS: The median follow-up period was 77 months. Five-year disease-free and overall survival rates were 89.4 and 95.9%, respectively. The 5-year local recurrence-free rate was 96.3%. The patients with histologically positive margins (P < 0.0001) or estrogen receptor negative tumor (P = 0.0340) or younger than 40 years old (P < 0.0001) developed statistically significantly more local recurrences. Adjuvant endocrine therapy was essential for the estrogen receptor positive patients to have a lower local recurrence rate. Endocrine therapy did not change the local recurrence rate among estrogen receptor negative patients at all. Multivariate analysis showed histological margin status and the combination of estrogen receptor status and endocrine therapy were independent prognostic factors for local recurrence. CONCLUSION: The 5-year local recurrence rate of Japanese breast cancer patients who were treated with breast-conserving treatment using radiotherapy was 3.7%. Independent prognostic factors for local recurrence were histological margin status and the combination of estrogen receptor status and adjuvant endocrine therapy.

Suture line recurrence in jejunal pouch replaced after total gastrectomy for gastric cancer.

We report a case of suture line recurrence in a jejunal pouch, diagnosed 4 months after total gastrectomy for advanced gastric cancer. The jejunal pouch was made with a linear stapler, without intraluminal irrigation being carried out before anastomosis, and was replaced in an interposition fashion. We propose that the recurrence was caused by the implantation of exfoliated cancer cells in either the intraluminal mucus or on a contaminated stapling device.