Clinical Effectiveness of Preoperative 18F-FDG PET/CT in Predicting Pathological Tumor Grade in Patients with Pseudomyxoma Peritonei Originating from Appendix: A Retrospective Cohort Study.

BACKGROUND: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is the standard treatment for patients with pseudomyxoma peritonei (PMP). In some malignancies, the standard uptake value of positron emission tomography with 2-deoxy-2-18F-fluoro-D-glucose integrated with computed tomography (18F-FDG PET/CT) is now accepted as a reliable indicator of neoplastic behavior. This study aimed to evaluate the association between the maximum standardized uptake value (SUVmax) and pathological grade in patients with PMP and to investigate the significance of SUVmax in the preoperative assessment of these patients. PATIENTS AND METHODS: In this retrospective single-center study, consecutively enrolled patients diagnosed with PMP of appendiceal origin underwent preoperative 18F-FDG PET/CT. SUVmax was calculated as the highest SUVmax value in the abdomen excluding the primary site. SUVmax was compared with the pathological grade (low or high grade) of PMP tumors according to the World Health Organization classification and further analyzed with respect to the estimated cutoff point, sensitivity, specificity, and receiver operating characteristic. RESULTS: In total, 160 patients were included. CRS was successfully performed in 93 patients and palliative debulking surgery in 67 patients. The pathological grade was high in 45 patients and low in 115. High-grade patients had a higher median SUVmax on 18F-FDG PET/CT than did low-grade patients (3.83 versus 2.34, p < 0.001). The highest area under the curve was 0.81, with a sensitivity of 77.8%, specificity of 72.3%, and cutoff point of 2.63. CONCLUSION: This study suggests that the SUVmax of preoperative 18F-FDG PET/CT is associated with the pathological grade in patients with PMP.

Weekday Surgery Associated With Short-Term Outcomes in Patients With Colorectal Cancers.

INTRODUCTION: The "weekday effect" on elective surgery remains controversial. We aimed to examine the association between the day of surgery and short-term outcomes after elective surgery for stage I-III colorectal cancer (CRC). METHODS: We performed a multicenter retrospective analysis of 2574 patients who underwent primary colorectal resection for CRC between January 2017 and December 2019 at 15 institutions belonging to the Hiroshima Surgical Study Group of Clinical Oncology. Patients were divided into two groups according to the day of surgery: Friday and non-Friday (Monday to Thursday). After propensity score matching (PSM), we compared 30-day mortality and postoperative outcomes. RESULTS: Out of the total, 368 patients underwent surgery on Fridays, and the remaining 2206 underwent surgery on non-Fridays. The overall mortality rate was 0.04% (n = 1). In 1685 patients with colon cancer, the proportion of American Society of Anesthesiologists scores was significantly lower in the Friday group than in the non-Friday group before PSM. After PSM of patient, tumor, and operative characteristics, operative time was slightly more prolonged and blood loss was slightly greater in the Friday group; however, these differences were not clinically meaningful. In the 889 patients with rectal cancer, the proportion of patients with abnormal respiratory patterns was significantly lower in the Friday group than in the non-Friday group before PSM. After PSM, the Friday group had a higher incidence of morbidity (≥ Clavien-Dindo 3a), higher incidence of digestive complications, and prolonged postoperative hospital stay. CONCLUSIONS: The results may be useful in determining the day of the week for CRC surgery, which requires more advanced techniques and higher skills.

Survival outcomes of patients with stage III colorectal cancer aged ≥ 80 years who underwent curative resection: the HiSCO-04 prospective cohort study.

BACKGROUND: The efficacy of adjuvant chemotherapy in elderly patients aged ≥ 80 years with stage III colorectal cancer remains unclear. In parallel with a multicenter prospective phase II trial evaluating the efficacy of uracil-tegafur and leucovorin as adjuvant chemotherapy (HiSCO-03), we conducted a prospective observational study of these patients to assess survival outcomes, including those ineligible for chemotherapy. METHODS: This multi-institutional prospective cohort study included 17 institutions in Hiroshima, Japan. Patients aged ≥ 80 years with stage III colorectal cancer who underwent curative resection were enrolled. The primary endpoint was 3-year disease-free survival, and the secondary endpoints were 3-year overall and relapse-free survival. Propensity score matching was used to assess the effects of adjuvant chemotherapy on survival outcomes. RESULTS: A total of 214 patients were analyzed between 2013 and 2018, including 99 males and 115 females with a median age of 84 years (range 80-101 years). Recurrence occurred in 58 patients and secondary cancers were observed in 17. The 3-year disease-free, overall, and relapse-free survival rates were 63.3%, 76.9%, and 62.9%, respectively. Adjuvant chemotherapy was administered to 65 patients with a completion rate of 52%. In a study of 80 patients that adjusted for background factors using propensity score matching, patients who completed the planned treatment showed improved disease-free survival (3-year disease-free survival: completed, 80.0%; not received, 65.5%; and discontinued, 56.3%; p = 0.029). CONCLUSIONS: Completion of adjuvant chemotherapy may improve the prognosis of patients with colorectal cancer aged ≥ 80 years, although the number of patients who would benefit from it is limited.

Effect of body fat mass loss on prognosis of radical resection for pancreatic ductal adenocarcinoma based on bioelectrical impedance analysis.

BACKGROUND: Few reports have performed a prognostic analysis based on bioelectrical impedance analysis in patients with radical resection of pancreatic ductal adenocarcinoma (PDAC), and its usefulness in prognostic analysis remains unclear. This study aimed to evaluate body composition changes in patients undergoing radical resection for PDAC and analyze its impact on prognosis. METHODS: The medical records of radical resection for patients with PDAC were retrospectively reviewed, and the parameters of body composition, including body weight, skeletal muscle mass, body fat mass (BFM), and extracellular water-total body water ratio, from preoperatively to 12 months postoperatively, for each surgical procedure were measured based on direct segmental multifrequency bioelectrical impedance analysis with an InBody 770 (InBody Inc., Tokyo, Japan) device. The clinicopathological and prognostic factors were analyzed. RESULTS: Among 79 patients who underwent radical resection for PDAC, 36 (46%), 7 (8%), and 36 (46%) underwent pancreatoduodenectomy, total pancreatectomy, and distal pancreatectomy, respectively. The multivariate overall survival analysis demonstrated that BFM loss percentage at 1 month postoperatively ≧14% (p = 0.021), lymph node metastasis (p = 0.014), and non-adjuvant chemotherapy (p <  0.001) were independent poor prognostic factors. Multivariate analysis revealed that preoperative BFM < 12 kg and preoperative albumin < 3.5 g/dL were independently associated with BFM loss percentage at 1 month postoperatively ≧14% (p = 0.021 and p = 0.047, respectively). CONCLUSIONS: Loss of BFM in the early postoperative period may have a poor prognosis in radical resection of PDAC.

Association between social background and implementation of postoperative adjuvant chemotherapy for older patients undergoing curative resection of colorectal cancers, sub-analysis of the HiSCO-04 study.

PURPOSE: Adjuvant chemotherapy is recommended following colorectal cancer resection based on risk of recurrence. In older patients, treatment decisions should consider recurrence rates and tolerability, as well as functional prognosis, residual disease, and social factors. This study aims to investigate factors, including social background, influencing implementation of postoperative adjuvant chemotherapy in older patients undergoing curative resection for colorectal cancer. METHODS: This multi-institutional prospective cohort study included 15 institutions belonging to the Hiroshima Surgical study group for Clinical Oncology. We analyzed 159 older patients aged ≥ 80 years, who underwent curative resection for stage III colorectal cancer between December 2013 and June 2018, as sub-analysis of the HiSCO-04 study. RESULTS: In total, 62 (39.0%) patients underwent postoperative adjuvant chemotherapy. Four factors were significantly associated with its implementation: performance status < 2, Charlson Comorbidity Index < 2, prognostic nutritional index ≥ 40, and presence of a spouse or siblings as lifestyle supporters. No significant difference was found in the backgrounds between complete and incomplete postoperative adjuvant chemotherapy patients. CONCLUSION: Performance status, Charlson Comorbidity Index, nutritional status, and presence of a spouse or siblings as lifestyle supporters are possible factors influencing the implementation of postoperative adjuvant chemotherapy in older patients. To select appropriate treatment options, including postoperative adjuvant chemotherapy, it is essential to consider physical condition and comorbidities of older patients, thoroughly explain the situation to their families, and establish a support system to enhance understanding of the available treatment options.

Predictive factors associated with anastomotic leakage after resection of rectal cancer: a multicenter study with the Hiroshima Surgical study group of Clinical Oncology.

PURPOSE: Several factors have been reported as risk factors for anastomotic leakage after resection of rectal cancer. This study aimed to evaluate the risk factors for anastomotic leakage, including nutritional and immunological indices, following rectal cancer resection. METHODS: This study used a multicenter database of 803 patients from the Hiroshima Surgical study group of Clinical Oncology who underwent rectal resection with stapled anastomosis for rectal cancer between October 2016 and April 2020. RESULTS: In total, 64 patients (8.0%) developed postoperative anastomotic leakage. Five factors were significantly associated with the development of anastomotic leakage after rectal cancer resection with stapled anastomosis: male sex, diabetes mellitus, C-reactive protein/albumin ratio ≥ 0.07, prognostic nutritional index < 40, and low anastomosis under peritoneal reflection. The incidence of anastomotic leakage was correlated with the number of risk factors. The novel predictive formula based on odds ratios in the multivariate analysis was useful for identifying patients at high risk for anastomotic leakage. Diverting ileostomy reduced the ratio of anastomotic leakage ≥ grade III after rectal cancer resection. CONCLUSIONS: Male sex, diabetes mellitus, C-reactive protein/albumin ratio ≥ 0.07, prognostic nutritional index < 40, and low anastomosis under peritoneal reflection are possible risk factors for developing anastomotic leakage after rectal cancer resection with the stapled anastomosis. Patients at high risk of anastomotic leakage should be assessed for the potential benefits of diverting stoma.

Efficacy of convalescent plasma therapy for COVID-19 in Japan: An open-label, randomized, controlled trial.

BACKGROUND: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19). Despite its use for treating several viral infections, we lack comprehensive data on its efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a multicenter, open-label, randomized controlled trial of convalescent plasma therapy with high neutralizing activity against SARS-CoV-2 in high-risk patients within five days after the onset of COVID-19 symptoms. The primary endpoint was the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs from days 0-5. RESULTS: Between February 24, 2021, and November 30, 2021, 25 patients were randomly assigned to either convalescent plasma (n = 14) or standard of care (n = 11) groups. Four patients discontinued their allocated convalescent plasma, and 21 were included in the modified intention-to-treat analysis. The median interval between the symptom onset and plasma administration was 4.5 days (interquartile range, 3-5 days). The primary outcome of the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs did not significantly differ between days 0-5 (1.2 log10 copies/mL in the convalescent plasma vs. 1.2 log10 copies/mL in the standard of care (effect estimate, 0.0 [95% confidence interval, -0.8-0.7]; P = 0.94)). No deaths were observed in either group. CONCLUSIONS: The early administration of convalescent plasma with high neutralizing activity did not contribute to a decrease in the viral load within five days compared with the standard of care alone.

The efficacy of sequential therapy with docetaxel and cabazitaxel for castration-resistant prostate cancer: A retrospective multi-institutional study in Japan.

OBJECTIVE: This study investigated the efficacy of docetaxel (DOC) and cabazitaxel (CBZ) and examined the factors associated with the prognosis of patients with castration-resistant prostate cancer (CRPC) receiving DOC-CBZ sequential treatment in Japanese real-world data. METHODS: We retrospectively evaluated data for 146 patients who received DOC followed by CBZ. The correlations of prostate specific antigen (PSA) decrease rate and time to progression between DOC and CBZ treatment were examined. Combined progression-free survival (PFS) of DOC-CBZ and overall survival (OS) from the initiation of DOC and the diagnosis of CRPC were evaluated and compared between patients with high and low PSA levels at the start of DOC and CBZ treatment. RESULTS: No correlations of PSA decrease rate and time to progression were observed between DOC and CBZ. The patients for whom DOC was started in higher PSA levels had significantly shorter combined PFS (p = 0.003) and OS from the initiation of DOC (p = 0.002). In patients who started DOC at high PSA levels, those who switched to CBZ at low PSA levels had longer OS than those who switched at high PSA levels (p = 0.048). The OS from CRPC of patients who started DOC at low PSA levels was significantly longer than those that started at high PSA levels (p = 0.030). CONCLUSIONS: For patients for whom DOC was not effective, sequential CBZ might have change to be effective. The PSA levels at the start of DOC and CBZ might be a potential prognostic biomarker.

[Foreign Body in Chest Wall with Traumatic Pneumothorax Caused by Fang of Wild Boar].

We report a case of foreign body in chest wall with traumatic pneumothorax caused by fang of wild boar performed video-assisted thoracic surgery. The patient was a 69-year-old woman. She was attacked from behind by a wild boar during farm work. She was transferred to the emergency and critical care center of our hospital. She was in a state of hemorrhagic shock when arrived with multiple bite wounds on her back. Computed tomography( CT) scan revealed left pneumothorax and a foreign body in chest wall suspected to be a wild boar fang. Thoracoscopic surgery was performed to remove the foreign body.

[Surgical Resection and Adjuvant Chemotherapy for Early Multiple Peritoneal Recurrence after Rejection of Hepatocellular Carcinoma-A Case Report].

Thus far, no consensus has been reached regarding the treatment of peritoneal dissemination of hepatocellular carcinoma (HCC). Here, we report a case of surgical resection and postoperative adjuvant chemotherapy for early multiple peritoneal recurrences of HCC. A 74-year-old man was found to have hepatic mass of 80 mm in size in S7 and 57 mm in S8, and was diagnosed with HCC. The patient underwent an open anterior segmentectomy and S7 subsegmentectomy of the liver. Peritoneal washing cytology revealed the presence of malignant cells. The tumor strongly adhered to the diaphragm, necessitating partial resection of the diaphragm. Six months after surgery, multiple disseminated recurrences were found on the CT scan. Atezolizumab plus bevacizumab combination therapy was initiated, but tumor size enlargement and elevation of tumor markers were observed after 3 courses. Resection of the dissemination(2 on the surface of the lung right lower lobe, 1 on the right renal superior retroperitoneum, 1 on the omentum, and 1 invading the jejunum)was performed. Considering the high risk of recurrence, postoperative adjuvant chemotherapy with lenvatinib was administered for 1 year. No recurrence has been found for 16 months after the resection. Although more cases are needed to conclude, this case report suggests that surgical resection and postoperative administration of lenvatinib may be effective in the treatment of disseminated HCC lesions at a high risk of recurrence.

[Unresectable Esophageal Cancer on the Elderly Woman Which Was Treated Effectively with Ipilimumab plus Nivolumab-A Case Report].

Until now, the standard treatment regimen was cisplatin plus 5-FU as the chemotherapy for unresectable advanced esophageal cancer. Immune checkpoint inhibitors have brought about changes to the cancer treatment. Ipilimumab plus nivolumab was approved in June 2022 for unresectable advanced esophageal cancer. An 86-year-old woman who was normal ADL and cognitive function was diagnosed with unresectable esophageal cancer with multiple lymph node metastasis. We thought surgery or chemotherapy is impossible because of her age and health status, so we treated with ipilimumab plus nivolumab. After 2 cycles, tumor became reduced in size on endoscopic examination and accumulation in primary lesion and lymph node metastases was decreased considerably on positron emission tomography/computed tomography(PET-CT). Though the cycle after initiation of chemotherapy was uneventful, tumor regrowth on the examinations at 5 months. The patient's condition of the disease was improved temporarily after change chemotherapy to paclitaxel as the second-line therapy, but she died due to disease progression at 11.4 months from initiation of treatment. Ipilimumab plus nivolumab can become one of the effective treatments for patients who are impossible to treat with conventional chemotherapy.

Enzalutamide in patients with non-metastatic castration-resistant prostate cancer after combined androgen blockade for recurrence following radical treatment in Japan (Japanese research for patients with non-metastatic castration-resistant prostate cancer-enzalutamide: JCASTRE-zero)-a prospective single-arm interventional study.

BACKGROUND: The effect of enzalutamide in patients with non-metastatic castration-resistant prostate cancer after combined androgen blockade, which represents a patient profile similar to real-world clinical practice in Japan, remains unknown. Therefore, we investigate the efficacy and safety of enzalutamide after combined androgen blockade for recurrence following radical treatment in Japanese patients with non-metastatic castration-resistant prostate cancer. METHODS: We analyzed 66 patients with non-metastatic castration-resistant prostate cancer after combined androgen blockade for recurrence following radical prostatectomy or radiation therapy who were prospectively enrolled from October 2015 to March 2018. They received enzalutamide 160 mg orally once daily until the protocol treatment discontinuation criteria were met. The primary endpoint was prostate-specific antigen-progression-free survival, defined as the time from enrollment to prostate-specific antigen-based progression or death from any cause. The secondary endpoints included overall survival, progression-free survival, metastasis-free survival, time to prostate-specific antigen progression, prostate-specific antigen response rate, chemotherapy-free survival, and safety assessment. RESULTS: The median observation period was 27.3 months. The median prostate-specific antigen-progression-free survival was 35.0 months (95% confidence interval, 17.5 to not reached). The median overall survival, median progression-free survival, median metastasis-free survival, and chemotherapy-free survival were not reached, with the corresponding 2-year rates being 91.6%, 67.1%, 72.4%, and 85.8%, respectively. The 50% prostate-specific antigen response rate was 88.9%, with the median time being 2.8 months. In total, 42.2% of the patients experienced adverse events, with malaise being the most common. CONCLUSIONS: Enzalutamide effectively manages non-metastatic castration-resistant prostate cancer after combined androgen blockade for recurrence following radical treatment. TRIAL REGISTRATION:  UMIN000018964, CRB6180007.

[A Case of Pancreatoduodenectomy for Multiple Nonfunctioning Neuroendocrine Tumors of the Duodenum].

A 42-year-old woman was referred to our hospital because of incidentally discovered multiple neoplastic lesions of the duodenum. Upper gastrointestinal endoscopy showed there were more than 10 submucosal tumors and less than 10 mm in diameter. Histological examination of the biopsy specimen revealed nonfunctioning neuroendocrine tumor(NET). Enhanced computed tomography(CT)showed neither regional lymph node nor distant metastasis, so we performed pancreatoduodenectomy with regional lymph node dissection. Pathological examination showed multiple NET G2 less than 5 mm in size with invasion to muscularis propria and 3 lymph node metastases, so diagnosed as pT2(m)N1M0, Stage Ⅲ. She is alive without tumor recurrence for 14 months after surgery. In general, sporadic nonfunctioning NET of the duodenum less than 10 mm in diameter has low possibility of lymph node metastasis. However, our case suggested the possibility of lymph node metastasis in patients with multiple NETs of the duodenum, in spite of small size. Therefore, pancreatoduodenectomy with regional lymph node dissection should be considered for multiple nonfunctioning NETs of the duodenum.

[A Case of Sclerosing Angiomatoid Nodular Transformation Resected for Suspected Relapse of Diffuse Large B-cell Lymphoma].

We report a case of sclerosing angiomatoid nodular transformation(SANT)5 years after remission of diffuse large B-cell lymphoma(DLBCL). A 64-year-old woman was diagnosed a nodular mass at the spleen by a contrast-enhanced CT scan 5 years after the relief for DLBCL. The mass showed accumulation of FDG. Because the possibility of the recurrence of malignant lymphoma could not be ruled out, laparoscopic splenectomy was performed for diagnosis and treatment. Immunohistologically, the resected mass revealed 3 different vascular components pattern(CD31, CD34 and CD8), so we diagnosed SANT. It is difficult to distinguish from malignant lymphoma or cancer even with various examination, so laparoscopic splenectomy is useful for diagnosis and treatment.

[A Case of Lynch Syndrome with Repeated Asynchronous Colorectal Cancer in a Short Period].

This case was a 73-year-old woman who previously underwent a partial colectomy for ascending colon cancer at the age of 70. She had a history of cancer of the uterus, descending colon, bladder, and left ureter. She had a family history of colorectal cancer and met the Amsterdam Ⅱ criteria for Lynch syndrome. She was diagnosed as Lynch syndrome with a MSH2 germline mutation by genetic analysis. One year later, a partial colectomy was performed for sigmoid colon cancer. Six months later, colonofiberscopy revealed early-stage cancer in the rectum, and EMR was performed. Despite adequate surveillance, she had frequent recurrences of advanced colorectal cancer within a short period of time. We report here risk factors of colorectal cancer in Lynch syndrome and indications for prophylactic total colectomy.

[A Case of Laparoscopic Surgery for Colon Metastasis of Renal Cancer].

A 67-year-old man underwent laparoscopic partial left nephrectomy for renal cell carcinoma 2.5 years ago. CT showed a well-defined 3 cm mass with contrast effect bordering on the descending colon, and PET-CT showed an accumulation of SUVmax 6.01 in the same area. Colonoscopy revealed a submucosal tumor-like mass in the descending colon. The patient was diagnosed with a local recurrence of renal cell carcinoma and invasion of the descending colon, and laparoscopic colectomy was performed. The excised specimen was a pale yellowish submucosal tumor measuring 4.5×3.8 cm, which was histologically diagnosed as metastasis of clear cell renal cell carcinoma. Surgical resections for metastases of renal carcinoma have been reported and expected prolong survival. We report a case of laparoscopic colon resection for recurrence of descending colon metastasis of renal cell carcinoma.

[A Case of Anal Canal Cancer with Pagetoid Spread and a Significant Response to Preoperative Chemoradiotherapy].

Perianal Pagetoid spread is a rare condition for which there is no proven therapy. We experienced a case of anal canal cancer with Pagetoid spread which exhibited a significant response to preoperative chemoradiotherapy(CRT). A 76-year-old man with anal stenosis was referred to our hospital. He was diagnosed with anal canal cancer with Pagetoid spread. No infiltration into the surrounding tissue was observed, but metastasis to the left inguinal lymph node was noted. The patient received preoperative CRT(oral S-1, 1.8 Gy×25 Fr, a total dose of 45 Gy)including the bilateral inguinal region. After CRT, the main tumor size was reduced and PET-CT showed disappearance of the abnormal accumulation in the left inguinal lymph nodes. Laparoscopic abdominoperineal resection and left inguinal trans lymphadenectomy were performed. The macroscopic findings of the surgical specimen confirmed no residual carcinoma or lymph node metastasis. Although more proof is needed, this case suggested that CRT may be effective for anal canal cancer with pagetoid spread.

Effect of optimal neoadjuvant chemotherapy on oncological outcomes of locally advanced bladder cancer with laparoscopic radical cystectomy: A matched-pair analysis in a multicenter cohort.

OBJECTIVES: To assess the effect of optimal neoadjuvant chemotherapy of at least three cycles of cisplatin-based regimen on oncological outcomes of clinical stage T3 or higher bladder cancer treated with laparoscopic radical cystectomy. METHODS: Laparoscopic radical cystectomies carried out at 10 institutions were included in this retrospective study. The outcomes of patients who received optimal neoadjuvant chemotherapy and those who did not receive neoadjuvant chemotherapy were compared using propensity score matching in clinical stage T3-4 or T2 cohorts, separately. RESULTS: Of the 455 patients screened, matched pairs of 54 patients in the clinical T3-4 cohort and 68 patients in the clinical T2 cohort were finally analyzed. In the cT3-4 cohort, the 5-year overall survival (78% vs 41%; P = 0.014), cancer-specific survival (81% vs 44%; P = 0.008) and recurrence-free survival (71% vs 53%; P = 0.049) were significantly higher in the optimal neoadjuvant chemotherapy group than in the no neoadjuvant chemotherapy group; no significant survival difference was shown between the two groups in the cT2 cohort. In the cT3-4 cohort, the incidence of local recurrence (4% vs 26%; P = 0.025) and abdominal or intrapelvic recurrence, including peritoneal carcinomatosis (7% vs 30%; P = 0.038), was significantly lower in the optimal neoadjuvant chemotherapy group. CONCLUSIONS: Administration of optimal neoadjuvant chemotherapy has a significant survival benefit. It decreases the incidence of local and atypical recurrence patterns in patients with clinical stage T3 or higher locally advanced bladder cancer undergoing laparoscopic radical cystectomy.

[A Case of Ureteral Metastasis from Prostate Cancer].

Ureteral metastasis from prostate cancer is rare. The present case report describes an 83-year-old patient with distant metastasis of prostate cancer to the right ureter that caused hydronephrosis. Upon initial examination at our hospital, he presented with a high prostate-specific antigen (PSA) level of 10.0 ng/ml. He was diagnosed with prostate adenocarcinoma, with Gleason score of 10 (5＋5) and clinical staging of cT2aN0M0. Intensity-modulated radiation therapy (IMRT) was performed after 1 year and 7 months of androgen depriation therapy. At 1 year and 4 months after IMRT, PSA increased to 3.068 ng/ml. Computed tomography scan revealed right hydronephrosis and thickening of the right ureter. We could not identify obvious malignant cells on ureteroscopic biopsy, and right nephroureterectomy was performed. Pathological examination revealed ureteral metastasis of prostate cancer. Six months after nephroureterectomy, PSA increased to 3.037 ng/ml. He was diagnosed with castration-resistant prostate cancer and has been treated with enzalutamide.

A case of Turcot's syndrome type 1 with loss of immunoexpression of MSH6 in colon cancer and liver metastasis due to secondary somatic mutation in coding mononucleotide (C)8 tract: a case report.

BACKGROUND: Lynch syndrome (LS), which is known as a hereditary cancer syndrome, is distinguished by microsatellite instability, represented by the altered number of repetitive sequences in the coding and/or non-coding region. Immunohistochemical staining (IHC) of DNA mismatch repair (MMR) proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has been recognized as an useful technique for screening of LS. Previous study has shown that the assessment of IHC, however, requires specific caution due to variable staining patterns even without germline mutations in MMR genes. CASE PRESENTATION: A 48-year-old man, who had been treated for anaplastic astrocytoma, was referred to our department for the precise examination of progressing anemia. Whole-body examination revealed two advanced carcinomas in descending colon and stomach. A hypo-vascular mass lesion was detected in liver as well. Pathological diagnosis (on surgical specimens) was poorly differentiated adenocarcinoma in descending colon, moderately differentiated tubular adenocarcinoma in stomach, and liver metastasis, which is possibly from colon. It was suspected that this case would be Turcot's syndrome-type-1 due to its specific family history having two cases of colon cancer within the second relatives. Pathogenic frameshift mutations in codon 618 of MLH1 gene was identified. Immunohistochemical analyses (IHC) demonstrated complete loss of MLH1 immuno-expression as well as of PMS2 except for those in brain tumor. Although frameshift mutation was not found in MSH6 gene, histological expression of MSH6 was patchy in primary colon carcinoma and was completely lost in the metastatic site in liver. MSH6 expression in gastric carcinoma, a coincidental cancer in this case, was intact. An abnormal (C)8 region was identified by the cloned PCR of colon and liver tumors but not from gastric cancer. Frameshift mutation in a (C)8 tract in exon 5 of the MSH6 gene was also detected in liver metastasis. CONCLUSION: This case supports a plausible mechanism, proposed by a previous literature, for the reduced expression of MSH6 in a somatic mutation manner, which might preferentially happen in colon cancer rather than in stomach carcinoma in MLH1/PMS2-deficient type of Turcot's syndrome type 1.