The standard treatment in Japan for advanced lower rectal cancer is total mesorectal excision(TME)plus lateral lymph node dissection(LLND). However, the standard treatment in Western countries is preoperative treatment plus TME. There have been some discussions on preoperative chemotherapy and chemoradiation therapy. This study was aimed at identifying the prognostic factors of recurrence after curative surgery for advanced lower rectal cancer.

Primary duodenal carcinoma excluding tumors of the ampulla of Vaterare are rare, thus, therapeutic strategy has not been established. In this study, we investigated the treatment outcome of 7 cases of duodenal carcinoma resected in our hospital between January 2010 and December 2019. The tumor locations were the duodenal bulb in 5(71%), the descending part and the transverse part in 1, respectively. Distal gastrectomy was performed in 4 out of 5 bulbous cases, and pancreatoduodenectomy was performed in the other 3 cases. The pathological stage by the 8th edition of the UICC TNM classification was Stage Ⅰ(T1a/T2, N0)in 3 cases, ⅡA(T3, N0)in 1, ⅢA(N1)in 2, and ⅢB(N2)in 1. R0 resection was achieved in all cases. Adjuvant chemotherapy with S-1 was performed in 3 of 4 patients with Stage Ⅱ or more advanced Stage. There were no tumor recurrences in 4 patients with Stage Ⅰ and Stage ⅡA, but recurrence was occurred in 2 of 3 patients with Stage ⅢA or more. The surgical outcome for duodenal carcinoma without lymph node metastasis were good. On the other hand, the prognosis for advanced cases with lymph node metastasis were poor. Thus, the development of effective adjuvant chemotherapy is strongly expected.

We reviewed clinical records of 354 cases with low rectal carcinoma(RC)after curative surgery(stage Ⅱ 149 cases and stage Ⅲ 205 cases). Stage Ⅱ with recurrence(23 cases)were compared with stage Ⅱ without recurrence(126 cases)in clinicopathological items to evaluate the factors affecting recurrence of stage Ⅱ RC, and were compared with stage Ⅲ with recurrence(89 cases)in treatment outcomes to identify the proper follow-up. Multivariate analysis revealed that sex and serum CA19-9 level were affecting factors for recurrence in stage Ⅱ low RC. The local recurrence rate of recurrence cases in stage Ⅱ RC(47.8%)was higher than in stage Ⅲ RC(29.2%). Recurrence was more found by serum tumor marker level in stage Ⅲ RC than in stage Ⅱ RC. Surgery for recurrent diseases was significantly more performed in stage Ⅱ RC(60.9%) than stage Ⅲ RC. Overall survival in stage Ⅱ RC with recurrence was significantly better than in stage Ⅲ RC with recurrence. And the prognosis after recurrence was also better in stage Ⅱ RC than in stage Ⅲ RC. It was thought that proper follow-up mainly by image examination would be effective to improve the prognosis.

50's man who have performed anterior pelvic exenteration with lateral lymph node dissection for rectal cancer with pT4bN0M0, pStage Ⅱc about 2 years ago, was admitted to our hospital for the treatment of intrapelvic recurrence of rectal cancer. No distant metastasis was found in the computed tomography examination but the tumor invaded the dorsal side of the pubis. Because radical excision was impossible with these findings, he received chemoradiotherapy(CRT). Post-CRT imaging showed that the tumor of intrapelvic recurrence region reduced the size, and invasion of pubis had disappeared and been markedly reduced. Thus, radical excision seemed possible at this point, and we decided to attempt operation after total 6 weeks of S-1(120 mg/day)regimen and radiation(40 Gy/20 Fr). We performed Miles' operation. The final pathological examination demonstrated that no viable tumor cells remained in the resected rectum specimen, confirming that a pathological complete response(pCR)had been achieved.

We examined 22 cases who underwent preoperative chemotherapy in our hospital from 2013 April to 2018 December. Seven patients were treated as neoadjuvant chemotherapy(NAC). Out of 15 patients with unresectable diseases before chemotherapy, 6 patients were able to R0 resection after chemotherapy(conversion). Although only one patients was underwent RM1 resection, the other patients were underwent RM0 resection. The median overall survival was 42 months in NAC group, 28 months in conversion group, and 17 months in palliative resection group, respectively. Recurrence was observed in 1 patient in NAC group, however, all patients had recurrent disease in conversion group. In this study, although further examination should be done according to the clinical significance of preoperative chemotherapy, preoperative chemotherapy may be carried out without severe adverse event and severe postoperative complication.

A 72-year-old man was referred to our hospital for treatment for rectal cancer. Digital rectal examination and colonoscopy revealed a 4 cm tumor located at the anterior rectal wall 5 cm away from the anal verge, and pathological examination confirmed that the tumor was adenocarcinoma. A computed tomography scan detected neither regional lymph node metastasis nor distant metastasis. Hence, he was diagnosed with cT3N0M0, cStage Ⅱa rectal cancer. The preoperative general examination revealed bradyarrhythmia and severe emphysema, and he was considered to be high risk for general anesthesia. After placement of a pacemaker, preoperative capecitabine-based chemoradiotherapy(CRT)(50.4 Gy in 28 fractions of 1.8 Gy each)was implemented. The digital rectal examination and imaging evaluation 4 weeks after preoperative CRT revealed that the tumor disappeared, and pathological examination showed no malignant findings. Considering the risks of general anesthesia, the"watch and wait therapy"approach was adopted with sufficient informed consent. At present, 15 months after preoperative CRT, no evidence of regrowth or distant metastasis has been detected under rigorous follow- up evaluations.

A 78-year-old man with a prostate-specific antigen level of 10 ng/mL was referred to our hospital. Magnetic resonance imaging revealed a Prostate Imaging-Reporting and Data System category of 5 in the apex transition zone. Transrectal and transperineal prostate needle biopsies were performed at a total of 20 sites. A well-differentiated adenocarcinoma with a Gleason score of 3+3 was detected on the right peripheral zone of the biopsied specimen. There were no apparent metastases, and robot-assisted radical prostatectomy was performed (Lesion 1: 30 mm lesion with a Gleason score of 4+5, EPE1, RM1, ly0, v0, pn1, sv0 in the bilateral transitional zones; Lesion 2: 4 mm lesion with a Gleason score of 3+3, EPE0, RM0, ly0, v0, pn0, sv0 in the left peripheral zone). Lymph node metastasis was found in the separately submitted anterior prostatic fat tissue. Removal of the anterior prostatic fat tissue is a simple procedure and is considered useful for evaluating the stump, and in this hospital, the tissue is routinely submitted for pathological diagnosis. It is extremely unlikely that lymph nodes will be found in the anterior prostatic fat tissue, and it is even less likely that any lymph node in the tissue will contain lymph node metastases. We therefore report a case of incidental discovery of lymph node metastasis in the anterior prostatic fat tissue at our hospital.

(Objectives) We evaluated the chronological change in the number and proportion of elderly patients with bladder cancer. We also retrospectively investigated the clinical outcomes of bladder cancer in patients of ≥90 years of age. (Patients and methods) We evaluated the chronological change in the number and proportion of patients of ≥90 years of age who were clinically diagnosed with bladder cancer and who underwent transurethral resection of a bladder tumor (TUR-BT) at our hospital between 2008 and 2018. We also assessed the clinicopathological factors, perioperative outcomes, and clinical outcomes in bladder cancer patients of ≥90 years of age. (Results) The number and proportion of bladder cancer patients of ≥90 years of age increased with time. A total of 39 patients of ≥90 years of age underwent TUR-BT at our hospital, among whom 22 were diagnosed with primary bladder cancer. The median age was 91 years. No grade ≥III complications were observed after TUR-BT. Two out of 6 with pT1 disease underwent second TUR-BT. Two out of 7 with pT1 disease or carcinoma in situ received intravesical BCG therapy. Six deaths were observed during the study period, 2 of which were due to bladder cancer. At 1 and 3 years after TUR-BT, the overall survival rates of the 22 patients were 80.4% and 68.9%, respectively. (Conclusions) The number and proportion of elderly patients with bladder cancer increased with time. The current standard of care including second TUR-BT and intravesical BCG therapy for high-risk non-muscle invasive bladder cancer was underutilized in nonagenarians.

(Purpose) Recently, new effective drugs for the treatment of castration-resistant prostate cancer (CRPC) have been developed. Although they are expected to prolong the survival time of patients with advanced prostate cancer, they may result in an economic burden. In this study, we determined the treatment results and the cost of CRPC drugs. (Methods) From 2014 to 2017, patients who were unfit for curative therapy were enrolled in this study. First, they received androgen deprivation therapy (ADT) by surgical or chemical castration. Once castration-sensitive cancer progressed to castration-resistant cancer, CRPC drugs, such as docetaxel, cabazitaxel, abiraterone and enzalutamide, were administered sequentially. In elderly or fragile patients, drug doses were often reduced to minimize their toxicity. The total costs of drugs for castration-sensitive and castration-resistant cancers were calculated, and the results were evaluated. (Results) Prostate biopsies detected prostate cancer in 257 patients. Eighty-one patients were treated with ADT, and 56 of the cancers were metastatic or showed a high prostate specific antigen level (>100 ng/ml). Thirty patients out of the 56 with advanced cancers developed CRPC, and the median time to CRPC was 10 months (range, 3-39). Drugs targeting CRPC were administered in 25 patients for a median duration of 20 months (range, 3-50). During the median observation period of 48 months (range, 13-75), 15 patients died of prostate cancer. The median annual cost of drugs for castration-sensitive cancer was 234,000 Japanese yen (2,187 US dollars) [range, 50,000-315,000 yen (467-2,943 US dollars) ]. In contrast, the median annual cost of drugs for CRPC was 2,041,000 yen (19,075 US dollars) [range, 346,000-5,017,000 yen (3,230-46,886 US dollars) ]. (Conclusions) Advanced prostate cancer tended to rapidly progress to CRPC, which required a sequence of expensive drugs for treatment. Early diagnosis preventing the development of advanced prostate cancer is desirable to reduce the economic burden for the health insurance system.

The patient was a 78-year-old man who, at 67 years of age, had been diagnosed with prostate cancer cT3bN1M0 (Gleason score 5+5) and started on androgen ablation therapy. Thereafter, the cancer had developed into castration-resistant prostate cancer; thus, after surgical castration, the patient was treated with 27 courses of docetaxel, as well as enzalutamide and abiraterone. However, new metastases appeared in the paraaortic lymph nodes, post which, the patient was treated with 25 courses of cabazitaxel. However, the paraaortic and intrapelvic lymph nodes became enlarged, the patient developed rectal occlusion and urinary retention due to growth of the primary tumor, and his general condition deteriorated. Hence, the patient decided to abandon treatment approximately 10 years after initial diagnosis, underwent cystostomy, and transitioned to best supportive care. After stopping treatment, his general condition started to improve, and approximately 6 months later, his PSA levels had fallen from 55.5 ng/mL to 19.3 ng/mL and the lymph nodes had also reduced in size. When the cancer was treated with local radiation, the enlarged tumor disappeared, and the patient was able to urinate again. It has now been 2.5 years since treatment was stopped, and both, the paraaortic and intrapelvic lymph nodes have reduced in size to < 1 cm, and the PSA value continues to remain less than 0.008 ng/ml.

The patient was a 65-year-old male who was referred with right renal mass (8 × 6.7 cm) and swelling of para-aortic lymph nodes in CT in April, 20XX. Additional examinations revealed inferior vena cava invasion, multiple lung metastases and left iliac bone metastasis and he was diagnosed with a renal cell carcinoma (cT4N1M1b). Pazopanib was administered as the first line treatment for an unresectable renal cancer. Nivolumab was then administrated as the 2nd line therapy due to the disease progression evaluated in (late) June, 20XX. However, immediately after the first administration of nivolumab, the patient have a difficulty in walking resulting from low-back pain, and MRI showed multiple lumbar vertebral metastases and L2 compression fracture. He was transferred to another hospital for combined modality therapy including right femoral head replacement and palliative radiotherapy in August, 20XX. Nivolumab was resumed since he had stable disease after his return to our hospital, and a total of 20 cycles of nivolumab treatment was performed. A follow-up CT showed 70% decrease in an initial primary tumor and tumor decrease or disappear in metastatic lung and bone tumors. The primary tumor was considered surgically resectable, and a radical nephrectomy was performed in August 20XX +1. Histopathological examination showed with a marked effect of neoadjuvant therapy and no evidence of viable tumor cells. We report a case of unresectable carcinoma that was successfully treated with nivolumab.

Five-aminolevulinic acid, an amino acid that is metabolized in the cytoplasm to become protoporphyrin IX, is used in photodynamic diagnosis in various carcinomas because it accumulates in higher concentrations in tumor tissue than in normal tissue. 5-Aminolevulinic acid-induced fluorescent urine cytology is more sensitive than conventional urine cytology only in low grade urothelial carcinoma (UC), but it showed a tendency for higher sensitivity in high grade UC. To increase the number of patients and reconsider our previous findings, we compared the sensitivity and specificity of preoperative urine cytology and fluorescent urine cytology in 343 patients diagnosed as having UCs pathologically (215 bladder cancers, 128 upper tract UCs) and 197 non-cancer patients at Osaka Rosai Hospital from March 2013 to December 2019. The sensitivities of fluorescent urine cytology and conventional urine cytology were 81.1% and 63.3% (p<0.001), respectively, and specificities were 92.9% and 93.9% (p=0.84), respectively. The sensitivity of fluorescent urine cytology was superior to that of conventional urine cytology in both low grade UC (76.8% vs 41.1%, p<0.001) and high grade UC (83.1% vs 74.0%, p=0.023).

This case report documents seminal vesicle cystadenoma with concurrent prostate cancer in a 49-yearold man evaluated at follow-up for a high prostate-specific antigen level (12 ng/ml). Transrectal ultrasound-guided prostate biopsy was performed for adenocarcinoma of the prostate (Gleason score 3+4= 7). Staging computed tomography showed a 6.6×5.5×5.0 cm cystic tumorof the seminal vesicle. A possible diagnosis of primary malignant tumor of the seminal vesicle with concurrent organ-confined prostate cancer was considered. However, seminal vesicle tumor biopsy was not performed because the patient underwent open radical prostatectomy with the resection of the seminal vesicle tumor. Histopathologic examination of the seminal vesicle and the prostate revealed cystadenoma (Gleason score 4+3=7) and adenocarcinoma (stage pT2cN0). Neither recurrence of the cystadenoma nor biochemical recurrence of the prostate cancer was observed 5 years and 6 months after the surgery.

Definitive chemoradiotherapy(CRT)for esophageal cancer is the standard treatment and alternative to surgery. However, the tolerability of CRT in elderly patients is not well known. In this study, we retrospectively analyzed 60 patients with esophageal cancer who were treated with CRT(5-FU 700 mg/m2, cisplatin 70 mg/m2, radiation 60 Gy)at our hospital between January 2015 and September 2017. The patients were divided into 2 groups: an elderly group comprising 16 patients aged >75 years and a non-elderly group comprising 44 patients aged <74 years. The relative dose intensity of cisplatin in the elderly group was significantly lower than that in the non-elderly group. Radiotherapy was successfully executed in both groups. More patients in the elderly(25%)than the non-elderly group(7%)developed pneumonitis, and all patients who developed severe pneumonitis in the elderly group died. Application of definitive CRT and irradiation methods in elderly patients with a subpleural reticular shadow should be carefully considered before initiating therapy.

We report a 79-year-old woman, who had undergone surgery for papillary thyroid carcinoma 18 years previously and lung adenocarcinoma 15 years previously. She didn't receive any follow-up because she had no recurrence for 5 years in both diseases. She visited a local doctor with precordial pain and thorax discomfort as her chief complaints, where chest computed tomography indicated a 14 mm-sized nodule in the right lower lobe and 5-7 mm-sized small nodules in both lungs. Using endobronchial ultrasonography with a guide sheath (EBUS-GS) for the diagnosis in our department, the lesions were confirmed by ultrasonography, and a transbronchial biopsy was carried out under fluoroscopy. Pathologically, a sufficient amount of tumor cells were collected, and the findings of adenocarcinoma were obtained. Her condition was diagnosed as recurrent pulmonary metastases of thyroid papillary carcinoma because of the atypical columnar epithelial cells with nuclear variants and the papillary proliferation of intranuclear inclusion, and because of the positive findings in immunohistochemical staining for thyroglobulin. Since papillary thyroid carcinoma is positive for thyroid transcription factor-1 (TTF-1), which is widely used as a marker of lung adenocarcinoma, it cannot be used to differentiate between the two. It is often difficult to diagnose papillary thyroid carcinoma by bronchoscopy, because its progress is slow and the origin of the metastatic lung tumor is not in the bronchus, unlike primary lung cancer. However, a devised transbronchial biopsy procedure for slowly progressive metastatic lung tumors such as papillary thyroid carcinoma is considered to be a useful technique for diagnosis.

The treatment paradigm in multiple myeloma (MM) together with the introduction of novel agents have resulted in a considerably improved survival. However, the disease is still considered incurable. One of the factors of its recurrence was that acquired genomic events associated with the progression of MM lead to inter- and intrapatient clonal heterogeneities. Also, just like many other cancers, MM contains cancer stem cells, a rare subpopulation of MM cells that exhibit the capacity for self-renewal and differentiation, but also pronounced drug resistance. Furthermore, a growing body of evidence suggests the role of tumor microenvironment and anti-myeloma immune status in the progression and maintenance of MM. Despite much progress in MM pathology, there are still several issues left unsolved. In this review, we will discuss the recent advances in our understanding of the pathology of MM from the perspective of tumor cell-of-origin and how these advances can lead to more effective therapies targeting MM.

According to the aging of society, elderly patients with esophageal cancer have been increasing in Japan. A multimodality treatment strategy is required to achieve long-term survival in patients with advanced-stage esophageal cancer. However, in elderly patients with impaired organ functions, the highly invasive treatment strategy is often difficult to be indicated. Esophagectomy remains the mainstay of treatment even in the elderly. Indication for esophagectomy in the elderly should be determined comprehensively, based on the physical status, life expectancy, tumor staging, and patients' desires. To predict the risk of postoperative complications, some scoring systems, such as estimation of physiology ability and surgical stress( E-PASS) and controlling nutritional status(CONUT), and the risk calculator provided by the National Clinical Database in Japan should be appropriately used. For patients with impaired organ functions, surgical procedures to reduce the surgical invasiveness, such as 2-stage operation, transhiatal esophagectomy, and mediastinoscopic esophagectomy, should be considered as an alternative to conventional transthoracic esophagectomy and reconstruction. Depending on the situations, preservation of the bronchial artery, thoracic duct, and azygos arch should be considered. A care bundle by a multidisciplinary perioperative management team may decrease postoperative morbidity and mortality rates in elderly patients undergoing esophagectomy.

Case 1: A 68-year-old woman was diagnosed with advanced HER2-positive breast cancer(T2N2aM0, cStage ⅢA). She was treated with 4 courses of preoperative chemotherapy with pertuzumab, trastuzumab, and docetaxel. She was diagnosed to have achieved partial remission(PR), and subsequently underwent a mastectomy and axillary dissection. Pathological examination revealed smaller than 1 mm(Grade 2b). Case 2: A 59-year-old woman was diagnosed with advanced HER2-positive breast cancer(T4bN1M0, cStage ⅢB). She was treated with 4 courses of preoperative chemotherapy with pertuzumab, trastuzumab, and docetaxel. She was diagnosed to have achieved PR(primary lesion: complete remission), and subsequently underwent a mastectomy and axillary dissection. Pathological examination revealed complete pathological response(Grade 3). Combination therapy with pertuzumab, trastuzumab, and docetaxel appears to be a useful preoperative chemotherapy regimen for locally advanced HER2-positive breast cancer.

The option of chemotherapy for recurrent thymoma is limited. Postoperative adjuvant therapy has yet to be established. A 71-year-old male underwent extended thymectomy for thymoma with Masaoka stage Ⅲ, and subsequently, radiation was performed as adjuvant therapy in 2012. Since recurrence was detected in 2014, multidisciplinary treatment was performed for 4 years. An increase of intrathoracic dissemination was detected in 2018. Tumor tissue samples by re-biopsy showed 70% expression of programmed death-ligand 1(PD-L1). Pembrolizumab was administered as fifth-line chemotherapy every 4 weeks at a dosage of 200 mg. After 3 courses, the lesions had remarkably decreased. This suggests that pembrolizumab for thymoma with high PD-L1 expression is efficacious.

Natural materials such as crude drugs and foods are mixtures composed of various metabolites. Metabolic profiling is often used to identify possible correlations between a compound's metabolic profile and pharmacologic activity. Direct-injection electron ionization-mass spectrometry (DI-EI-MS) is a novel metabolomics method useful for characterizing biological materials. This review demonstrates the establishment of a DI-EI-MS method for metabolic profiling using several closely related lichen species: Cladonia krempelhuberi, C. gracilis, C. pseudogymnopoda, and C. ramulosa. The qualitative DI-EI-MS method was used to profile major and/or minor constituents in extracts of lichen samples. Each lichen sample could be distinguished by altering the DI-EI-MS electron energy and examining the resulting data using one-way analysis of variance. We also attempted to predict pharmacologic activity using DI-EI-MS metabolomics. Blueberry leaf extracts inhibited the proliferation of adult T-cell leukemia (ATL) cells. Blueberry leaf extracts could be distinguished by principal component analysis based on the absolute intensity of characteristic fragment ions. Twenty cultivars were categorized into four species, and the most appropriate discriminative marker m/z value for identifying each cultivar was selected statistically. Components extracted based on DI-EI-MS analyses could be used to construct a model to predict ATL cell bioactivity. These data suggest that the novel DI-EI-MS metabolomics method is suitable for identifying species of natural materials and predicting their pharmacologic activity. This approach could enhance public health by facilitating evaluations of pharmacologic activity and functionality, leading to the elimination of counterfeit products.