佐田 尚宏

症例は37歳,女性.25歳で偶発的に膵体尾部に嚢胞性病変を指摘され,精査目的に当院消化器内科に紹介された.腹部造影CTとMRI検査では膵尾部に約5cmの嚢胞性腫瘤を認め膵粘液性嚢胞腫瘍(mucinous cystic neoplasm:MCN)が疑われたが,経過観察の方針となった.32歳時の第2子妊娠を契機に経過観察が一時中断となり,5年後の37歳に再診した.嚢胞性腫瘤は多房化し,大きさ6cmへの増大を認め,血清CA19-9の上昇を伴ったことから手術目的に消化器外科紹介となった.腹腔鏡下膵体尾部脾摘術を施行し,術後経過は良好で術後11日目に退院した.病理組織像では卵巣様間質を認め,微小浸潤を伴った膵粘液性嚢胞腺癌の診断であった.MCNの自然史を解明するには長期経過観察例の集積が必要である.(著者抄録)

Maternal T cells from perinatal transplacental passage have been identified in up to 40% of patients with severe combined immunodeficiency (SCID). Although engrafted maternal T cells sometimes injure newborn tissue, liver failure due to maternal T cells has not been reported. We rescued a boy with X-linked SCID who developed liver failure due to engrafted maternal T cell invasion following living donor liver transplantation (LDLT) following unrelated umbilical cord blood transplantation (UCBT). After developing respiratory failure 3 weeks postpartum, he was diagnosed with X-linked SCID. Pathological findings showed maternal T cells engrafted in his liver and hepatic fibrosis gradually progressed. He underwent UCBT at 6 months, but hepatic function did not recover and liver failure progressed. Therefore, he underwent LDLT using an S2 monosegment graft at age 1.3 years. The patient had a leak at the Roux-en-Y anastomosis, which was repaired. Despite occasional episodes of pneumonia and otitis media, he is generally doing well 6 years after LDLT with continued immunosuppression agents. In conclusion, the combination of hematopoietic stem cell transplantation (HSCT) and liver transplantation may be efficacious, and HSCT should precede liver transplantation for children with X-linked SCID and liver failure.

75歳以上の高齢者における腹腔鏡下大腸手術の治療成績を検討したので報告する。当院において2010年1月から2017年6月までの期間に大腸癌に対し腹腔鏡下大腸手術を施行した565例を対象とし、75歳未満の若年者群(474例)と75歳以上の高齢者群(91例)の2群間の短期成績を比較検討した。高齢者群において術前併存症が多くASA scoreは高値であった。また、高齢者群においてD3郭清の施行率が低く(高齢者群41.8%vs若年者群54.0%、p=0.04)、開腹移行率が高値であった(高齢者群4.4%vs若年者群1.1%、p=0.04)。しかし両群間において手術時間、術中出血量、術後在院日数、術後合併症発生率について有意差を認めなかった。以上より75歳以上高齢者においても75歳未満の若年者と同様に腹腔鏡下大腸手術を選択することが可能である。(著者抄録)

BACKGROUND: Pancreatojejunostomy (PJ) is one of the most difficult and challenging abdominal surgical procedures. There are no appropriate training systems available outside the operating room (OR). We developed a structured program for teaching PJ outside the OR. We describe its development and results of a pilot study. METHODS: We have created this structured program to help surgical residents and fellows acquire both didactic knowledge and technical skills to perform PJ. A manual was created to provide general knowledge about PJ and the specific PJ procedure used in our institution. Based on questionnaires completed by trainers and trainees, the procedure for PJ was divided into twelve steps and described in detail. After creating the manual, we developed organ models, needles and a frame box for simulation training. Three residents (PGY3-5) and three fellows (PGY6 or above) participated in a pilot study. Objective and subjective evaluations were performed. RESULTS: Trainees learn about PJ by reading the procedure manual, acquiring both general and specific knowledge. We conducted simulation training outside the OR using the training materials created for this system. They simulate the procedure with surgical instruments as both primary and assistant surgeon. In this pilot study, as objective assessments, the fellow-group took less time to complete one anastomosis (36 min vs 48 min) and had higher scores in the objective structured assessment of technical skill (average score: 4.1 vs 2.0) compared to the resident-group. As a subjective assessment, the confidence to perform a PJ anastomosis increased after simulation training (from 1.6 to 2.6). Participants considered that this structured teaching program is useful. CONCLUSION: We developed a structured program for teaching PJ. By implementing this program, learning opportunities for surgical residents and fellows can be increased as a complement to training in the OR.

INTRODUCTION AND IMPORTANCE: Brain and thyroid metastasis from rectal cancer are uncommon, and the prognosis is poor. We report a patient with rectal cancer who developed metachronous lung, brain and thyroid metastases. Each metastatic lesion was curatively resected resulting in prolonged survival. CASE PRESENTATION: A 60-year-old male underwent rectal cancer resection, and the pathological diagnosis was tubular adenocarcinoma, pT2,pN1a,M0, pStageⅢa. Ten years after rectal resection, a solitary tumor in the left lung was detected. The tumor was resected thoracoscopically and the pathological diagnosis was metastatic tumor. Three years after the pulmonary resection, a solitary brain tumor was detected. The tumor was removed surgically, and the pathology was metastatic tumor. Two years after brain resection, a thyroid mass was detected. A partial thyroidectomy was performed and the pathology with immunohistochemical staining confirmed the thyroid lesion as a metastasis from the previous rectal cancer. Four years after thyroid resection (19 years after the initial rectal resection), he died from multiple lung and bone metastases. CLINICAL DISCUSSION: Colorectal metastases to the brain and thyroid gland are uncommon and are usually found with other distant metastases. Overall survival has been reported to be extremely poor. In this patient, lung, brain, and thyroid metastases were solitary and metachronous, and each lesion was curatively resected. Surgical treatment might contribute to prolonged survival. CONCLUSION: The treatment strategy of each patient should be individualized and depends on the timing of metastasis development. Selected patients with complete resection of metachronous metastases may have prolonged survival.

症例は67歳,女性.乳癌検診異常で受診した.左乳房に低エコー腫瘤を認め,針生検の結果,腺様嚢胞癌が疑われた.左乳房温存術およびセンチネルリンパ節生検を施行し,病理組織学的診断はpT1N0M0 StageIA,腺様嚢胞癌(ER-,PgR-,HER2-,Ki-67 5%)であった.補助化学療法を考慮する症例であったが,予後良好と考えられたため,化学療法は省略し放射線治療のみ施行した.術後2年6ヵ月でCTにて左肺結節を指摘されたが,原発か転移性かの鑑別が困難であったため,胸腔鏡下左肺上葉切除およびリンパ節郭清を施行した.病理組織学的診断では腺様嚢胞癌の肺転移と診断された.他の特殊型乳癌が通常の浸潤性乳管癌に準じて補助化学療法を行うことが推奨されているが,乳腺腺様嚢胞癌は多くがtriple negative症例にも関わらず予後良好と言われ,腋窩リンパ節転移が陰性ならば補助化学療法は必要としないことが多い.今回,乳腺腺様嚢胞癌で術後肺転移を認めた症例を経験したので,若干の文献的考察を加え報告する.(著者抄録)

BACKGROUND: Familial adenomatous polyposis (FAP) is characterized by the presence of hundreds to thousands of colonic polyps, and extracolonic manifestations are likely to occur. Pancreatic tumors are rare extracolonic manifestations in patients with FAP, among which solid-pseudopapillary neoplasm (SPN) are extremely rare. We report here a patient with an SPN of the pancreas found during the follow-up of FAP. CASE PRESENTATION: A 20-year-old woman was diagnosed with FAP 3 years previously by colonoscopy which revealed less than 100 colonic polyps within the entire colon. She complained of left upper abdominal pain and a 10-cm solid and cystic pancreatic tumor was found by computed tomography scan. Solid and cystic components within the tumor were seen on abdominal magnetic resonance imaging. Simultaneous laparoscopic resection of the distal pancreas and subtotal colectomy was performed. Histopathological findings confirmed the pancreatic tumor as an SPN without malignancy. Abnormal staining of beta-catenin was observed by immunohistochemical study. Multiple polyps in the colorectum were not malignant. Molecular biological analysis from peripheral blood samples revealed a decrease in the copy number of the promoter 1A and 1B region of the APC gene, which resulted in decreased expression of the APC gene. CONCLUSIONS: A rare association of SPN with FAP is reported. The genetic background with relation to beta-catenin abnormalities is interesting to consider tumor development. So far, there are few reports of SPN in a patient with FAP. Both lesions were treated simultaneously by laparoscopic resection.

Fecalomas most commonly occur in constipated patients and are rarely reported after colectomy. A 55-year-old Japanese female presented with a fecaloma after colectomy, which was impacted at a functional end-to-end anastomosis (FEEA) site. Four and a half years ago, she underwent sigmoidectomy for colon cancer. A follow-up computed tomography (CT) scan revealed an 11 cm incidental fecaloma. The patient was advised to undergo surgery, but she desired nonoperative management because of minimal symptoms, and was referred to our institution. On the day of admission (day 1), mechanical fragmentation of the fecaloma was attempted during the first colonoscopy. Although a large block of stool was evacuated after a second colonoscopic fragmentation on day 8, the third colonoscopy on day 21 and CT scan on day 22 showed no significant change in the fecaloma. Frequent colonoscopic fragmentation was performed, with a fourth, fifth, and sixth colonoscopy on days 24, 29, and 31, respectively. After the size reduction was confirmed at the sixth colonoscopy, the patient was discharged home on day 34. The fecaloma completely resolved after the seventh colonoscopic fragmentation on day 44. Sixteen months after treatment, there is no evidence of recurrent fecaloma. According to the literature, risk factors for fecaloma after colectomy include female gender, left-side colonic anastomosis, and FEEA. FEEA might not be recommended for anastomoses in the left colon, particularly in female patients, to avoid this complication. Colonoscopic fragmentation is recommended for fecalomas at an anastomotic site after colectomy in patients without an absolute indication for surgery.

A 48-year-old man underwent skin grafting from the left inguinal region to the left forearm one month previously. He noticed abdominal discomfort after discharge and was admitted to another hospital because of progression of abdominal pain and a decreased level of consciousness. An enhanced CT scan revealed extensive portal venous thrombosis. Lower gastrointestinal bleeding developed the following day, and he was transferred to our hospital and diagnosed with superior mesenteric venous thrombosis. Enhanced CT showed no intestinal necrosis. Anticoagulant therapy was started and the thrombosis had almost resolved 40 days later. However, after starting oral intake, the patient developed vomiting. Small bowel radiographs and 3D-CT showed significant proximal intestinal stenosis. Small bowel resection was performed on the 59th day after transfer. The pathological diagnosis was ischemic enteritis with venous thrombosis. The patient was discharged 20 days after intestinal resection and he has had no recurrence of symptoms. In this case, 3D-CT was useful to determine the range of intestinal stenosis and the required area of resection.

Aim: PD-1/PD-L1 blockade therapy is now widely used for the treatment of advanced malignancies. Although PD-L1 is known to be expressed by various host cells as well as tumor cells, the role of PD-L1 on non-malignant cells and its clinical significance is unknown. We evaluated cell type-specific expression of PD-L1 in colorectal cancer (CRC) specimens using multicolor flow cytometry. Methods: Single cell suspensions were made from 21 surgically resected CRC specimens, and immunostained with various mAbs conjugated with different fluorescent dyes. Tumor cells, stromal cells, and immune cells were identified as CD326(+), CD90(+) and CD45(+) phenotype, respectively. CD11b(+) myeloid cells, CD19(+) B cells and CD4(+) or CD8(+) T cells were also stained in different samples, and their frequencies in the total cell population and the ratio of PD-L1(+) cells to each phenotype were determined. Results: PD-L1 was expressed by all the cell types. The ratio of PD-L1(+) cells to CD326(+) tumor cells was 19.1% ± 14.0%, lower than those for CD90(+) stromal cells (39.6% ± 16.0%) and CD11b(+) myeloid cells (31.9% ± 14.3%). The ratio of PD-L1(+) cells in tumor cells correlated strongly with the ratio in stromal cells, while only weakly with that in myeloid cells. Tumor cells were divided into two populations by CD326 expression levels, and the PD-L1 positive ratios were inversely correlated with the rate of CD326 highly expressing cells as well as mean fluorescein intensity of CD326 in tumor cells, while positively correlated with the frequencies of stromal cells or myeloid cells in CRC. Conclusion: PD-L1 is differentially expressed on various cell types in CRC. PD-L1 on tumor cells may be upregulated together with CD326 downregulation in the process of epithelial mesenchymal transition. Quantification of cell type-specific expression of PD-L1 using multicolor flow cytometry may provide useful information for the immunotherapy of solid tumors.

BACKGROUND: The frequency of tumor cell dissemination in the peritoneal cavity is critically related to the progression of peritoneal metastases (PM). Recently, flow cytometry (FCM) has been successfully used to detect tumor cells in malignant effusions. METHODS: A total of 143 single cell suspensions derived from ascites or peritoneal lavages from patients with advanced gastric cancer (GC) were stained with monoclonal antibodies to CD45 and to CD326 as well as 4,6-diamidino-2-phenylindole (DAPI) and FVS780. Using FCM, tumor-leukocyte ratio (TLR) were calculated from CD45(-)CD326(+) tumor cell counts/ CD45(+)CD326(+) leukocyte counts in DAPI (+) FVS780(-) gated area. In 54 patients, the ratios of CD11b(+), CD4(+) and CD8(+) cells in CD45(+) leukocytes were evaluated in parallel. RESULTS: TLR of 69 patients with PM were significantly higher than those of 74 without PM (p < .001) and log(TLR) showed strong correlation with peritoneal cancer index scores in 51 PM (+) patients (r = 0.439). TLR in PM (+) patients also correlated with the ratio of CD11b (+) myeloid cells (r = 0.547), and correlated inversely with those of CD4(+) (r = -0.490) and CD8(+) T cells (r = -0.648). In PM (-) patients who underwent gastrectomy, TLR never exceeded 0.1% in patients with primary GC without serosal involvement (<T4). However, TLR in patients with T4 GC were significantly higher (p < .05) and peritoneal recurrence occurred in 6/8 patients whose TLR exceeded 0.1%. CONCLUSION: TLR in peritoneal fluid reflects tumor burden and the immune environment in peritoneal cavity. Multicolor FCM may provide additional information which can be used for the treatment of the patients with PM.

BACKGROUND: Intraperitoneal (IP) administration of paclitaxel (PTX) has a great pharmacokinetic advantage to control peritoneal lesions and can be combined with various systemic chemotherapies. In this study, we evaluate the efficacy and tolerability of a combination of IP-PTX and systemic S-1/oxaliplatin (SOX) for induction chemotherapy for patients with peritoneal metastases (PM) from gastric cancer (GC). PATIENTS AND METHODS: Patients with GC who were diagnosed as macroscopic PM (P1) or positive peritoneal cytology (CY1) by staging laparoscopy between 2016 and 2019 were enrolled. PTX was IP administered at 40 mg/m2 on days 1 and 8. Oxaliplatin was IV administered at 100 mg/m2 on day 1, and S-1 was administered at 80 mg/m2/day for 14 consecutive days, repeated every 21 days. Survival time and toxicities were retrospectively explored. RESULTS: Forty-four patients received SOX + IP-PTX with a median (range) of 16 (1-48) courses, although oxaliplatin was suspended due to the hematotoxicity or intolerable peripheral neuropathy in many patients. The 1-year overall survival (OS) rate was 79.5% (95% CI 64.4-88.8%) with median survival time of 25.8 months. Gastrectomy was performed in 20 (45%) patients who showed macroscopic shrinkage of PM with a 1-year OS rate of 100% (95% CI 69.5-100%). Grade 2 and 3 histological responses was achieved in four (20%) and one (5%) patients. Grade 3/4 toxicities included neutropenia (11%), leukopenia (39%), and anemia (14%). There were no treatment-related deaths. CONCLUSIONS: Combination chemotherapy using SOX + IP-PTX regimen is highly effective and recommended as induction chemotherapy for patients with PM from GC.