[A Case of Pathological Complete Response of Advanced Rectal Cancer with Direct Invasion of the Prostate and Extra-Regional Lymph Node Metastasis after Chemotherapy].

A 62-year-old man was diagnosed as having advanced rectal cancer with an invasive carcinoma of the prostate and the right inguinal lymph node metastasis. He received chemotherapy consisting of combination of 5-FU, oxaliplatin, Leucovorin (mFOLFOX6)and bevacizumab. After 5 courses of the chemotherapy, CT and MRI findings revealed the tumor shrinkage. After 6 courses of the chemotherapy, a laparoscopic abdominoperineal resection, bilateral lymph node dissection and a resection of right inguinal lymph node were performed. The pathological findings showed a pCR. NAC with mFOLFOX6 and bevacizumab may contribute to the reduction of the surgical stress for the patients and be an effective treatment for advanced rectal cancer with distant lymph node metastasis.

Impact of the first announced state of emergency owing to coronavirus disease 2019 on stress and blood pressure levels among patients with type 2 diabetes mellitus in Japan.

AIMS/INTRODUCTION: After the first coronavirus disease 2019 state of emergency announcement, there was an increase in stress that might have affected the self-management of patients with type 2 diabetes mellitus. This study identified the changes in clinical findings and stress among patients with type 2 diabetes mellitus, and investigated the characteristics of patients who experienced an increase in blood pressure (BP) after the announcement. MATERIALS AND METHODS: Retrospectively, we scrutinized 310 patients with type 2 diabetes mellitus who were treated by the Sagamihara Physicians Association. After the announcement, 164 and 146 patients showed an increase (ΔBP >0 group) and decrease in BP (ΔBP ≤0 group), respectively. The propensity score matching method was used to compare the differences in clinical findings and stress-related questionnaire responses between the two groups. RESULTS: After the announcement, 47% of patients experienced an increase in daily stress. Furthermore, 17% and 36% reported worsening dietary intake and a decrease in exercise, respectively. More patients reported that their dietary and salt intake had worsened in the ΔBP >0 group than in the ΔBP ≤0 group (9% vs 20%, P = 0.02, and 3% vs 10%, P = 0.04, respectively). Additionally, both systolic and diastolic BP measured in the office were significantly increased (P = 0.02 and P = 0.03, respectively); however, systolic BP measured at home significantly decreased (P = 0.01). The total stress scores were higher in the ΔBP >0 group than in the ΔBP ≤0 group (0.05 ± 2.61 and 0.93 ± 2.70, respectively, P = 0.03). CONCLUSIONS: An increase in stress and, particularly, worsening dietary and salt intake were noted among patients with type 2 diabetes mellitus who experienced an increase in BP after the state of emergency announcement.

Influence of stress induced by the first announced state of emergency due to coronavirus disease 2019 on outpatient blood pressure management in Japan.

To prevent further spread of coronavirus disease 2019 (COVID-19), the Japanese government announced a state of emergency, resulting in major stress for the population. The aim of this study was to investigate a possible association between changes in daily stress and blood pressure (BP) in Japanese patients. We retrospectively investigated 748 patients with chronic disease who were treated by the Sagamihara Physicians Association to determine changes in stress during the COVID-19 state of emergency from 7 April to 31 May 2020. During the state of emergency, office BP significantly increased from 136.5 ± 17.5/78.2 ± 12.0 to 138.6 ± 18.6/79.0 ± 12.2 (p < 0.001 and p = 0.03, respectively). In contrast, home BP significantly decreased from 128.2 ± 10.3/75.8 ± 8.8 to 126.9 ± 10.2/75.2 ± 9.0 (p < 0.001 and p = 0.01, respectively), and the ratio of white coat hypertension was significantly increased (p < 0.001). Fifty-eight percent of patients worried about adverse effects of hypertension as a condition contributing to the severity and poor prognosis of COVID-19; decreased amounts of exercise and worsened diet compositions were observed in 39% and 17% of patients, respectively. In conclusion, a significant increase in office BP with the white coat phenomenon was observed during the state of emergency, as well as an increase in related stress. To prevent cardiovascular events, general practitioners should pay more attention to BP management during stressful global events, including the COVID-19 pandemic.

Small Bowel Obstruction Caused by Ileal Endometriosis with Appendiceal and Lymph Node Involvement Treated with Single-Incision Laparoscopic Surgery: A Case Report and Review of the Literature.

BACKGROUND Endometriosis is an ectopic proliferation of endometrial glands and interstitium outside the uterus. It usually affects the organs surrounding the uterus, and less often, involvement of extrapelvic organs, such as the intestines and urinary tract, is observed. CASE REPORT A 40-year-old woman had been experiencing intermittent right lower abdominal pain for years, which worsened months earlier. The patient was admitted for the worst pain ever accompanying nausea and vomiting. Contrast-enhanced computed tomography revealed a heterogeneously enhanced lesion that measured approximately 50×25×35 mm, and a caliber change of the ileum at the same site with dilated small bowel proximal to the caliber change were observed. Colonoscopy revealed that the ileocecal valve and the lumen of the terminal ileum protruded inward, suggesting an extramural compression by the lesion. Since the patient showed no improvement following conservative therapy, bowel resection through a single-incision laparoscopic surgery was successfully performed. Histopathological exploration showed patchy infiltration of endometrium-like tissues in the muscularis propria and subserosa layers of the ileum and appendix. Moreover, nearby lymph nodes resected for their firmness showed similar findings. CONCLUSIONS We report a case of recurrent intestinal obstruction due to ileal and appendiceal endometriosis with lymph node involvement, which was successfully treated by single-incision laparoscopic surgery. Careful follow-up is important because the prognosis for the intestinal endometriosis with lymph node involvement is still unclear.

[A Case of Rectal Gastrointestinal Stromal Tumor(GIST)Treated with Imatinib Mesylate Neoadjuvant Therapy to Preserve the Anus].

A woman in her 40's who initially presented with anal pain was diagnosed with rectal GIST. A 9 cm tumor extended to near the anus, and curative abdominoperineal tumor resection was required. The patient initially received neoadjuvant therapy with imatinib mesylate. Neoadjuvant chemotherapy for 6 months reduced the tumor to approximately 47% of its original size and permitted anus-preserving surgery. The present case suggests that neoadjuvant therapy with imatinib mesylate is useful for large rectal GISTs, from the standpoint of anal function preservation.

Mentor Tutoring: An Efficient Method for Teaching Laparoscopic Colorectal Surgical Skills in a General Hospital.

OBJECTIVE: We retrospectively assessed the efficacy of our mentor tutoring system for teaching laparoscopic colorectal surgical skills in a general hospital. MATERIALS AND METHODS: A series of 55 laparoscopic colectomies performed by 1 trainee were evaluated. Next, the learning curves for high anterior resection performed by the trainee (n=20) were compared with those of a self-trained surgeon (n=19). RESULTS: Cumulative sum analysis and multivariate regression analyses showed that 38 completed cases were needed to reduce the operative time. In high anterior resection, the mean operative times were significantly shorter after the seventh average for the tutored surgeon compared with that for the self-trained surgeon. In cumulative sum charting, the curve reached a plateau by the seventh case for the tutored surgeon, but continued to increase for the self-trained surgeon. CONCLUSIONS: Mentor tutoring effectively teaches laparoscopic colorectal surgical skills in a general hospital setting.

[A Case of Advanced Colon Cancer with Long-Term and Re-Administration of Regorafenib].

A 54-year-old woman diagnosed with sigmoid colon cancer and multiple liver metastases underwent sigmoidectomy, partial hepatectomy, and RFA in September 2009. Because of postoperative liver and lung recurrence, 5 regimens with combinations of L-OHP/CPT-11 plus anti-VEGF antibody/anti-EGFR antibody was performed. Following these treatments, she underwent hepatic arterial infusion therapy with UFT/Krestin for progressive liver metastases. Starting in November 2014, regorafenib was administered, with an immediate decrease in tumor marker levels; tumor reduction demonstrated enhanced effect against liver metastases. After 8 months of administration, we stopped regorafenib and changed to TAS-102 due to diarrhea and eating disorders. However, TAS-102 was not effective; there were significant increases in tumor markers, liver function tests, and tumor size on computed tomography, and worsening of abdominal pain. After re-administration of regorafenib, a rapid decrease in tumor marker levels and improvement of liver dysfunction and abdominal pain were observed. Re-administration continued for 8 months until best supportive care was instituted. In cases with observed therapeutic effect of regorafenib, long-term or re-administration is possible, with extension of the prognosis depending on the adjustment, and without size reduction of metastatic tumors.

[A Case of Pseudomyxoma Peritonei Derived from Cecum Colon Cancer with Long-Term Recurrence-Free Survival].

A 29-year-old woman was diagnosed with advanced cecum colon cancer, and right hemicolectomy was performed. The pathological findings showed stage Ⅲa disease, including moderately differentiated tubular adenocarcinoma>mucinous adenocarcinoma, pT3, pN1, cM0, and Cur A resection. The patient was treated with 5-FU plus l-LV adjuvant chemotherapy. Fourteen months after surgery, bilateral ovarian metastasis and ascites were found, and another surgery was performed, revealing that the abdominal cavity was filled with a gelatinous ascites. Under the diagnosis of pseudomyxoma peritonei, resection of both ovaries, abdominal lavage, and intraperitoneal administration of CDDP were performed, followed by S-1 plus CDDP treatment. Two years after the recurrence, peritoneal re-recurrence on the vaginal fornix was detected. A total hysterectomy, partial vaginectomy, and resection of disseminated peritoneal nodules were performed. The patient received mFOLFOX6 treatment postoperatively. To date, 8 years and 9 months after her re-recurrence, the patient is alive and without signs of a third recurrence.

Total pancreatectomy for metachronous mixed acinar-ductal carcinoma in a remnant pancreas.

In October 2009, a 71-year-old female was diagnosed with a cystic tumor in the tail of the pancreas with an irregular dilatation of the main pancreatic duct in the body and tail of the pancreas. A distal pancreatectomy with splenectomy, and partial resection of the duodenum, jejunum and transverse colon was performed. In March 2011, a follow-up computed tomography scan showed a low density mass at the head of the remnant pancreas. We diagnosed it as a recurrence of the tumor and performed a total pancreatectomy for the remnant pancreas. In the histological evaluation of the resected specimen of the distal pancreas, the neoplastic cells formed an acinar and papillary structure that extended into the main pancreatic duct. Mucin5AC, α1-antitrypsin (α-AT) and carcinoembryonic antigen (CEA) were detected in the tumor cells by immunohistochemistry. In the resected head of the pancreas, the tumor was composed of both acinar and ductal elements with a mottled pattern. The proportions of each element were approximately 40% and 60%, respectively. Strongly positive α-AT cells were detected in the acinar element. Some tumor cells were also CEA positive. However, the staining for synaptophysin and chromogranin A was negative in the tumor cells. Ultimately, we diagnosed the tumor as a recurrence of mixed acinar-ductal carcinoma in the remnant pancreas. In conclusion, we report here a rare case of repeated pancreatic resection for multicentric lesions of mixed acinar-ductal carcinoma of the pancreas.

Clear cell sarcoma of the esophagus: report of a case.

We report a rare case of clear cell sarcoma of the esophagus and review the literature regarding clear cell sarcomas of the gastrointestinal tract. A 57-year-old male was admitted with dysphagia during swallowing. Preoperative imaging studies, including upper gastrointestinal endoscopy and endoscopic ultrasonography, showed that the tumor was located between the mucosa and the muscularis propria of the lower esophagus. We performed subtotal esophagectomy with gastric tube reconstruction. Pathological findings of the tumor showed mixed spindle cells and oval cells. Immunohistochemical staining showed that the tumor cells were positive for S-100, vimentin and neuron-specific enolase and negative for α-smooth muscle actin, myoglobin and c-kit. Fluorescence in situ hybridization using a Ewing sarcoma breakpoint region 1 probe showed split signals in a small percentage of cells. We finally diagnosed the patient with clear cell sarcoma of the esophagus.

[Prognostic factors affecting the surgical treatment of metastatic lung tumor from colorectal cancer].

For aging, people having malignant disease are increasing. And surgical resection is an important part in the treatment of pulmonary metastasis from colorectal cancer. We analyzed the treatment outcome and prognostic factors affecting survival in our subset of patients. We have experienced 64 operations of metastatic lung tumors from colorectal cancer for 23 years since January 1988. Various factors affecting prognosis are studied based on 5-year survival in this report. Overall 5-year survival rate was 38.7%. The disease-free intervals more than 2 years, a solitary metastatic pulmonary lesion and the serum level of prethoracotomy carcinoembryonic antigen (CEA) were significantly affecting factors on the prognosis. Furthermore, sequential study for 23 years couldn't demonstrate the prognostic improvement by the advance of the thoracoscopic technology or the development of the new anti-cancer drugs, though the treatment of patients with pulmonary metastases from colorectal cancer continues to evolve. The role of pulmonary metastasectomy is very important to reduce the volume of metastatic lesions for the better prognosis.

The efficacy of nocturnal administration of branched-chain amino acid granules to improve quality of life in patients with cirrhosis.

BACKGROUND: Nocturnal administration of branched-chain amino acid (BCAA) granules improves serum albumin levels in patients with cirrhosis. However, it is unclear whether or not this administration method can improve the patients' quality of life (QOL). In this study, we aimed to investigate the efficacy of BCAA granules, given nocturnally, in improving QOL in these patients. METHODS: We performed a multicenter, randomized controlled trial examining the comparative effects of BCAA granules given orally for 3 months with daytime or nocturnal administration in patients with compensated cirrhosis. Health-related QOL was measured by a Japanese version of the questionnaire on subjective and objective symptoms, and the Short Form-8 (SF-8) questionnaire. RESULTS: Twenty-one patients received BCAA granules three times a day (one sachet after each meal: the daytime group), and 16 patients received the granules twice a day (one sachet after breakfast, and two sachets before bedtime: the nocturnal group). Baseline characteristics did not differ between the groups (whole cohort: Child-Pugh grade A/B, 21/16; mean age, 68.2 years). There was no significant difference in any of the subjects revealed by the questionnaire regarding subjective or objective symptoms, or by the SF-8 between the daytime group and the nocturnal group after 3 months of treatment. The daytime group showed a significant effect on general health, vitality, social functioning, mental health, and role emotional as revealed on the SF-8. Conversely, the nocturnal group exhibited a significant decrease in the occurrence of muscle cramps in the legs (P = 0.014) and significantly improved Fisher's ratio after 3 months (P = 0.04). CONCLUSIONS: Nocturnal administration of BCAA granules in patients with cirrhosis reduced the occurrence of muscle cramps in the leg but did not improve the patients' QOL.

Pancreatoduodenectomy for circumportal pancreas accompanying the retroportal pancreatic duct: a case report and review of the literature.

Circumportal pancreas (CP) is an extremely rare pancreatic fusion anomaly which is usually asymptomatic. This report presents the case of a patient with a tumor in the head of a CP and the retroportal accessory pancreatic duct in the pancreatic tissue behind the portal vein. A 53-year-old male was diagnosed with a nonfunctioning neuroendocrine tumor of the pancreas and resection of the tumor was scheduled. The patient was revealed to have CP on preoperative computed tomography and endoscopic retrograde cholangiopancreatography, which showed the pancreatic tissue encircling the portal vein and the retroportal accessory pancreatic duct. The patient safely underwent pylorus-preserving pancreatoduodenectomy reconstructed with pancreaticogastrostomy.

[Two cases of gastric endocrine cell carcinoma].

Gastric endocrine cell carcinoma is rare and associated with a poor prognosis. The first case was a man in his sixties with gastric endocrine cell carcinoma, of which a clinical finding was T2N1M0H1 (Stage IV). S-1 + CDDP therapy was selected and failed. CDDP+CPT-11 therapy was started and CT showed a partial response in ten months. But the tumor was re-grown and the patient died twenty months after diagnosis. The second case was a man in his seventies with gastric endocrine cell carcinoma, of which a clinical finding was T3N1M0H0P0, Stage IIIa, underwent total gastrectomy. Abdominal contrast-enhanced CT scan performed a month after the operation disclosed hepatic metastasis. After two months of S-1 regimen, CDDP + CPT-11 therapy was started.

Chlorella pyrenoidosa supplementation reduces the risk of anemia, proteinuria and edema in pregnant women.

Pregnancy anemia and pregnancy-induced hypertension (PIH) are common and potentially dangerous disorder in human pregnancy, and nutritional status of pregnant women is one of the leading causes. Chlorella contains large quantities of folate, vitamin B-12 and iron, and can help improve anemia and hypertensive disorder. Our objective was to investigate the preventive effects of Chlorella supplement on pregnancy anemia and PIH in Japanese pregnant women. A total of 70 pregnant women were placed into the control group (n = 38) or the Chlorella group (n = 32). The subjects in the Chlorella group were supplemented daily from 12th-18th wk of gestation until delivery with 6 g of Chlorella supplement. The proportion of anemic (hemoglobin level < 11 g/dL) subjects in the Chlorella group were significantly lower compared with the control group at the second and third trimesters. Additionally, in the Chlorella group, the incidences of proteinuria and edema, signs of PIH, were significantly lower during the third trimester. These results suggest that Chlorella supplementation significantly reduces the risk of pregnancy associated anemia, proteinuria and edema. Chlorella supplement may be useful as a resource of natural folate, vitamin B-12 and iron for pregnant women.

[A case of long-term survival of unresectable-advanced gastric cancer due to chemotherapy].

The case was a 50s male with chief complaints of body weight loss and nausea. A clinical finding was Stage IV gastric cancer of poorly differentiated adenocarcinoma. We diagnosed it unresectable and started 5-FU+CDDP as the first-line chemotherapy. Partial response (PR) was observed and progression free time was 7 months. After 9 courses of 5-FU+ CDDP, the tumor grew and an oral intake was getting impossible. Gastro-jejunostomy was performed and then started a weekly PTX as the second-line chemotherapy after operation. The response was progressive disease (PD) after 4 courses of weekly PTX. Then we started S-1+CPT-11 as the third-line chemotherapy. We could continue S-1+CPT-11 for 9 courses without a severe adverse effect. Overall survival was 26.2 months.

Chlorella (Chlorella pyrenoidosa) supplementation decreases dioxin and increases immunoglobulin a concentrations in breast milk.

In addition to meeting nutritional requirements, breast milk plays important roles in biodefense for nursing infants. Dioxins have been detected at high concentrations in breast milk, raising concerns about disorders in nursing infants caused by breast milk containing dioxins in Japan. We analyzed dioxin levels in breast milk and maternal blood samples from 35 pregnant women in Japan. We also measured immunoglobulin (Ig) A concentrations in breast milk and investigated correlations with dioxin concentrations. In addition, 18 of the 35 women took Chlorella pyrenoidosa (Chlorella) supplements during pregnancy, and the effects on dioxin and IgA concentrations in breast milk were investigated. Toxic equivalents were significantly lower in the breast milk of women taking Chlorella tablets than in the Control group (P = .003). These results suggest that Chlorella supplementation by the mother may reduce transfer of dioxins to the child through breast milk. No significant correlation was identified between dioxin and IgA concentrations in breast milk in the Control group. It is unlikely that normal levels of dioxin exposure via food have a remarkable influence on IgA in breast milk. IgA concentrations in breast milk in the Chlorella group were significantly higher than in the Control group (P = .03). Increasing IgA levels in breast milk is considered to be effective for reducing the risk of infection in nursing infants. The present results suggest that Chlorella supplementation not only reduces dioxin levels in breast milk, but may also have beneficial effects on nursing infants by increasing IgA levels in breast milk.

[A phase I study of postoperative combination therapy with TS-1 and low dose cisplatin against stage IV gastric carcinoma].

A dose-escalation study was conducted for postoperative patients with stage IV gastric cancer to determine the recommended dose of daily intravenous cisplatin combined with a fixed dose of TS-1. TS-1 was administered orally twice daily for 2 weeks followed by a 1-week rest. The dose of TS-1 was based on the body surface area (BSA) as follows: 80 mg/day for BSA less than 1.25, 100 mg/day for BSA 1.25 to less than 1.50, and 120 mg/day for BSA 1.5 or more. Three dose levels of cisplatin (2, 4, 6 mg/m(2)) were studied, and two courses were performed. Cisplatin was infused on day 1-5 and 8-12 for 30 minutes. The National Cancer Institute common toxicity criteria (NCI-CTC Version 3) were used to evaluate the grade of toxicity. Three patients enrolled in each level. Dose escalation was performed when dose-limiting toxicities (DLT) were seen in 0/3, and 3 more cases of the same level were added when DLTs were seen 1-2/3. Maximum-tolerated dose (MTD) were determined when DLTs were seen in 3 cases. DLTs were not recorded during the administration of CDDP up to 4 mg/m(2). However, DLTs were seen 3/3 at level 3. From these results, cisplatin of 4 mg/m(2)was determined to be the recommended dose (RD) in this protocol for postoperative stage IV gastric carcinoma.

[A case of local recurrence of rectal cancer in long-term responding to combined therapy of low-dose CPT-11 and 5'-DFUR].

A 68-year-old man underwent Miles'operation for advanced rectal cancer. Local recurrence occurred 9 months following the operation. We started the combined therapy of low-dose CPT-11 and doxifluridine (5'-DFUR). CPT-11 was administered at 80 mg/body biweekly and 5'-DFUR was orally administered at 800 mg/day/body on day 3-7. We then reduced the CPT-11 dose to 60 mg/body because of neutropenia. Four months later,we obtained a decrease in the tumor marker (carcinoembryonic antigen: CEA) to the normal serum level, and stopped the medication. However, 3 months later the serum CEA level was increased, and we restarted the same therapy. Six months after restarting this therapy, the serum CEA level decreased to the normal level,and the local recurrence was decreased in size. We finished this combined therapy and changed to 5'-DFUR only. No tumor progression or recurrences in this patient are seen 2 years after completing this combined therapy.

Distribution of PCDDs/PCDFs and Co-PCBs in human maternal blood, cord blood, placenta, milk, and adipose tissue: dioxins showing high toxic equivalency factor accumulate in the placenta.

To assess levels of dioxin background contamination and transfer of dioxins from mothers to unborn children and infants, concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar-polychlorinated biphenyls (Co-PCBs) were measured in human samples from expectant and nursing mothers living in Nara, Japan. The average toxic equivalency quantities (TEQs) of PCDDs/PCDFs and Co-PCBs from circulating maternal blood, cord blood, placenta, milk taken 3-10 d after delivery, milk taken one month after delivery, and adipose tissue were 26 and 9.3, 15 and 2.3, 31 and 1.2, 16 and 5.4, 18 and 8.8, and 16 and 7.7 pg-TEQ/g-fat, respectively. Among the various PCDD/PCDF congeners, 1,2,3,7,8-PeCDD and 2,3,4,7,8-PeCDF contributed most heavily to the TEQs of all maternal samples. Among the various Co-PCB congeners, 3,3',4,4',5-PeCB (#126), 2,3,3',4,4',5-HxCB (#156), and 2,3',4,4',5-PeCB (#118) contributed most heavily to the TEQs of all maternal samples. But, the concentrations and relative percentages of congeners differed among the various samples, suggesting that congeners showing high toxic equivalency factor accumulate in the placenta.