Kinro Sasaki

MUTYH-associated colorectal cancer and adenomatous polyposis

MUTYH-associated polyposis (MAP) was first described in 2002. MUTYH is a component of a base excision repair system that protects the genomic information from oxidative damage. When the MUTYH gene product is impaired by bi-allelic germline mutation, it leads to the mutation of cancer-related genes, such as the APC and/or the KRAS genes, via G to T transversion. MAP is a hereditary colorectal cancer syndrome inherited in an autosomal-recessive fashion. The clinical features of MAP include the presence of 10–100 adenomatous polyps in the colon, and early onset of colorectal cancer. Ethnic and geographical differences in the pattern of the MUTYH gene mutations have been suggested. In Caucasian patients, c.536A>G (Y179C) and c.1187G>A (G396D) mutations are frequently detected. In the Asian population, Y179C and G396D are uncommon, whereas other variants are suggested to be the major causes of MAP. We herein review the literature on MUTYH-associated colorectal cancer and adenomatous polyposis.

Esophageal granular cell tumor successfully resected by endoscopic submucosal dissection

Granular cell tumors of the esophagus are rare neoplasms and their diagnosis is mainly based on histopathologic examination of endoscopic biopsies. With the development of endoscopic techniques, there has been a marked increase in local treatment modalities for early esophageal neoplasms. In this case report, we describe the removal of a granular cell tumor by the endoscopic submucosal dissection technique, and briefly discuss the literature on clinicopathologic aspects and management of granular cell tumors.

Salvage Lymphadenectomy for Recurrent Esophageal Cancer After Chemoradiotherapy

Although salvage esophagectomies are widely performed, reports on salvage lymphadenectomy (SL) are few. We review our SL cases to clarify the indications. Fifty-five patients with esophageal cancer underwent chemoradiotherapy or radiotherapy, including 3 patients with single lymph node (LN) recurrences and one with allochronic double cervical node recurrence. Our department removed 5 recurrent LNs from these 4 patients. In Case 1, right supraclavicular LN was judged to be metastatic and R0 resection was carried out; he is alive without recurrence. In Case 2, we found, allochronically, metastases in his left cervical paraesophageal LN and left supraclavicular LN; residual tumors were R1 in both lesions. He is alive despite esophageal recurrence. In Case 3, a lymphadenectomy was performed on his thoracic para-aortic LN; however, tumor was removed incompletely, and he died 4 months after SL from disease progression. In Case 4, a subcarinal LN was thought to be metastatic, and was removed but no malignant tissues detected. He died 17 months after SL from pneumonia. Our experiences suggest that some patients survive relatively long with SL. Moreover, molecular examination of resected lesions could guide subsequent therapies. SL might be more widely used for these patients if not otherwise contraindicated.

Expression of DNA double-strand break repair proteins predicts the response and prognosis of colorectal cancer patients undergoing oxaliplatin-based chemotherapy

DNA intrastrand cross-linking agents such as oxaliplatin induce DNA double-strand breaks (DSBs) during DNA repair and replication. In the present study, we hypothesized that DNA intrastrand cross-linking agents may significantly benefit colorectal cancer patients with deficiencies in DSB repair. Seventy-eight patients with metastatic or recurrent colorectal cancer who had measurable target lesions and who underwent resection for primary colorectal cancer in our institution between April 2007 and March 2013 were included in the present study. The median age was 64.5 years, and the cohort consisted of 49 males and 29 females. The median progression-free survival (PFS) was 10.9 months. The expression of DSB repair proteins such as RAD51 and MRE11 was investigated by immunohistochemistry, and associations between RAD51 and MRE11 expression and clinicopathological factors or chemotherapeutic effect were assessed. MRE11-negative cases and RAD51-negative cases achieved significantly better tumor reduction compared with cases with positive expression. Cases with negative expression of both proteins or negative expression of either protein had significantly longer PFS than cases with positive expression for both proteins. In conclusion, DSB repair protein expression-negative colorectal cancer cases may be more highly sensitive to chemotherapy, and thus DSB repair protein expression may be a useful prognostic indicator for colorectal cancer patients.

Minimally Invasive Salvage Operations for Esophageal Cancer after Definitive Chemoradiotherapy

Background/Aims: Because salvage surgery after definitive chemoradiotherapy for esophageal cancer is associated with high postoperative mortality and morbidity, minimally invasive methods are desirable. We analyzed the validity of minimally invasive salvage operations (MISO). Methods: Twenty-five patients underwent salvage operation between 2010 and 2016 in our institution, 10 having undergone right transthoracic salvage esophagectomy (TTSE group), 6 transhiatal salvage esophagectomy (THSE), 6 salvage lymphadenectomy (SLA), and 3 salvage endoscopic submucosal dissection (SESD). Patients who had undergone THSE, SLA, or SESD were categorized as the MISO group. Short- and long-term outcomes were assessed. Results: The mean duration of surgery was significantly shorter in the SLA groups than in the TTSE group (p = 0.0248). Blood loss was significantly less in the SLA than the TTSE group (p = 0.0340). Intensive care unit stay was shorter in the THSE than the TTSE group (p = 0.0412). There was no significant difference in postoperative mortality between the MISO and THSE groups. Postoperative hospital stay was significantly shorter in the SLA than the TTSE group (p = 0.0061). Patients’ survivals did not differ significantly between the MISO and TTSE groups (p = 0.752). Multivariate analysis revealed that residual disease (R0; HR 4.872, 95% CI 1.387–17.110, p = 0.013) was the only independent factor influencing overall survival. Conclusion: MISO is preferable because short-term outcomes are better and long-term outcomes do not differ from those of TTSE.

Asymptomatic Mesenchymal Hamartoma of the Chest Wall in Child With Fluorodeoxyglucose Uptake on PET/CT—Report of a Case

We had experience with a case of mesenchymal hamartoma of the chest wall (MHCW) with fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT). We reported the first case of asymptomatic MHCW in a child with preoperative PET/CT. Mesenchymal hamartoma of the chest wall is a rare benign tumor that usually presents as a visible chest wall mass or respiratory problems secondary to compression of the lung in early infancy. It is often reported that malignant transformation is extraordinarily rare. Positron emission tomography/CT is useful for diagnosis of malignancy. There is no report of MHCW in a child with preoperative PET/CT before. We examined an asymptomatic 1-year-old girl with an incidental finding on a chest x-ray. Scans of CT and PET/CT were performed before surgical resection. After surgery, the resected tumor was examined histologically. Chest x-ray and CT scan of the chest confirmed a 25- × 20-mm round shaped intrapleural mass containing calcification and destructing the rib, arising from the third rib. Scan of PET/CT demonstrated the mass with light FDG accumulation. Histologically, the mass was homogenous, with thick funicular of hyaline cartilage interdigitating with scattered fiber. There were no malignant cells. No malignant MHCW was demonstrated in the mass, with light FDG accumulation by PET/CT. PET/CT might be a useful tool to distinguish malignant MHCW in children.

Phase I Dose-Escalation Study of Docetaxel, Cisplatin, and 5-Fluorouracil Combination Chemotherapy in Patients With Advanced Esophageal Carcinoma.

A dose-escalation study of docetaxel (DOC), cisplatin (CDDP), and 5-fluorouracil (5-FU; DCF combination regimen) was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD) and dose-limiting toxicities (DLT) in advanced esophageal carcinoma. Eighteen patients with esophageal carcinoma were enrolled and received DCF combination therapy at different dose levels. DLTs included febrile neutropenia and oral mucositis. DLT occurred in 2 out of 6 patients at level 2 and 3. The study proceeded to level 4, according to the protocol. The level 4 dose was defined as the MTD and the level 3 dose was defined as the RD. The RD for DCF combination chemotherapy for advanced esophageal carcinoma in the present study was 70 mg/m(2) DOC plus 70 mg/m(2) CDDP on day 1 plus 700 mg/m(2) 5-FU on days 1-5 at 4-week intervals. This regimen was tolerable and highly active. A phase II study has been started.

Waardenburg syndrome with isolated deficiency of myenteric ganglion cells at the sigmoid colon and rectum

Waardenburg syndrome (WS) has the characteristic clinical features caused by the embryologic abnormality of neural crest cells. WS patients sometimes suffer from functional intestinal obstruction. When it is Hirschsprung disease (HD), the WS is diagnosed as type 4 WS. We report a case of WS which did not have myenteric ganglion cells in the sigmoid colon and rectum. Whether to diagnosis this case as type 1 or 4 WS is controversial. Moreover, this is the third report which has peristalsis failure caused by abnormal myenteric plexus. In all three cases, the eosinophils had aggregated in the myenteric layer of the transition zone. During embryonic life, enteric ganglion cells migrate to the myenteric layer from the proximal to the distal side sequentially and, subsequently, to the submucosal layer through the circular muscle. Therefore, we hypothesize that myenteric ganglion cells that had already migrated were eliminated by an eosinophil-mediated mechanism in these three cases. We believe this report may be helpful to elucidate the pathogenesis of some types of HD.

Laparoscopic surgery for a Bochdalek hernia triggered by pregnancy in an adult woman: A case report

Highlights • We report a case of Bochdalek hernia (BH) triggered by pregnancy in a pregnant adult.• Laparoscopic surgery can be safely performed for BH without complications.• We reviewed 30 cases of laparoscopic and/or thoracoscopic repair of adult BH.

18F-Fluorodeoxyglucose positron emission tomography can be used to determine the indication for endoscopic resection of superficial esophageal cancer

18F‐Fluorodeoxyglucose positron emission tomography (FDG‐PET) is a useful imaging modality that reflects the tumor activity. However, FDG‐PET is mainly used for advanced cancer, not superficial cancer. In this study, we investigated the relationship between the superficial tumor depth of esophageal cancer and the FDG uptake to determine the indications for endoscopic resection (ER). From 2009 to 2017, 444 patients with esophageal cancer underwent esophagectomy or endoscopic submucosal dissection (ESD), and 195 patients were pathologically diagnosed with superficial cancer. Among them, 146 patients were examined by FDG‐PET before esophagectomy or ESD. In these 146 patients, the relationship between the pathological tumor depth and FDG uptake was analyzed. The mean maximum standardized uptake value in pT1a‐EP/LPM tumors was 1.362 ± 0.890, that in pT1a‐MM/pT1b‐SM1 tumors was 2.453 ± 1.872, and that in pT1b‐SM2/SM3 tumors was 4.265 ± 3.233 (P < .0001). Among 51 pT1a‐EP/LPM tumors, 10 (19.6%) showed positive detection of FDG. For pT1a‐MM/pT1b‐SM1 and pT1b‐SM2/SM3 tumors, the detection rate was 52.9% (18/34) and 82.0% (50/61), respectively. The detection rate of pT1a‐EP/LPM was significantly lower than in the other two groups (P < .0001). Among 10 FDG‐PET‐positive lesions, only 1 had no apparent reason for PET positivity; however, 9 of 10 had a suitable reason for detectability by PET and inadequacy for ER. Negative detection of superficial esophageal squamous cell carcinoma by FDG‐PET is useful to determine the indication for ER when the tumor depth cannot be diagnosed even after performing magnifying endoscopy with narrow band imaging and endoscopic ultrasonography. When FDG uptake is recognized, a therapeutic modality other than ER should be considered.