Masato Nakano

Ileal Neobladder for Urinary Bladder Replacement following Total Pelvic Exenteration for Rectal Carcinoma

Objective: The aim of this study was to determine the feasibility of using the ileal neobladder as a substitute for the urinary bladder following total pelvic exenteration for rectal carcinoma. Patients and Methods: Between 1992 and 1998, we performed total pelvic exenteration with ileal neobladder in 5 men with rectal carcinoma. Four patients had primary tumors, and one had recurrent disease after low anterior resection for rectal carcinoma. Histological types were adenocarcinoma in 4 and squamous cell carcinoma in 1. Invaded organs were: the urinary bladder in 1, the urinary bladder and prostate in 2, the prostate and seminal vesicle in 1, and the prostate in 1. Results: There was no operative death. In 1 patient, an ileal conduit was needed because of partial necrosis of the neobladder. Minor leakage on the dorsal wall of the neobladder occurred in 2 patients, which was successfully stopped with simple closure and a gluteus maximus fasciocutaneous flap, respectively. All except one patient with the ileal conduit could void via the urethra. Complete daytime urinary continence was achieved, but nocturnal continence was maintained with voiding once or twice per night. As the urodynamic state, the mean maximum flow rate was 20.9 ml/s (range 9.0–34.1), the mean average flow rate was 7.7 ml/s (range 3.0–11.0), and the mean voided volume was 285.5 ml (range 160–432). The mean length of follow-up was 47.8 months. One patient died of local recurrence 38 months postoperatively, and 1 died of pneumonia 10 months postoperatively. Both patients could void via the urethra until death. The other three patients are currently alive without any evidence of recurrence. Conclusions: Although total pelvic exenteration is a laborious surgical procedure, an ileal neobladder could be a good alternative to the urinary bladder enabling the patients to void via the urethra with urinary continence.

Open tension-free mesh repair for adult inguinal hernia: eight years of experience in a community hospital.

OBJECTIVE The aim of this study was to determine the feasibility of using open tension-free mesh repair for adult inguinal hernias performed by resident surgeons under the supervision of a chief surgeon in a community hospital. METHODS From May, 1992 through April, 2000, we performed 314 open tension-free mesh repairs on 289 patients (234 men, 55 women) with a mean age of 65.7 years. There were 173 right and 141 left hernias, and 25 were bilateral; while 220 were indirect, 77 were direct and 17 were of the femoral type. There were 281 primary and 33 recurrent lesions. Resident surgeons under the supervision of the first author (SY) performed all hernioplasties. Three types of open tension-free mesh repairs were performed; the Lichtenstein repair (n = 72), the mesh-plug repair (n = 134), and the Hernia System repair (n = 108). RESULTS The duration of surgery averaged 73.0 minutes. There was no perioperative mortality. Five patients developed subcutaneous wound infections; no case required mesh removal. Hematoma occurred in eight patients, and seroma developed in 25. All haematomas and seromas subsided with repeated aspiration. The average duration of hospitalization was 6.5 days. The length of follow-up rose from 1 to 8 years, with a mean of 3.7 years. No patients in any group had a recurrence during the follow-up period. CONCLUSIONS Under the close supervision of the staff surgeon, tension-free hernioplasties can be performed on adult inguinal hernias by surgeons-in-training in non-specialist centres with excellent outcomes, low postoperative complications and no recurrence.

Comprehensive genomic sequencing detects important genetic differences between right-sided and left-sided colorectal cancer

Objectives Anti-epidermal growth factor receptor (EGFR) therapy has been found to be more effective against left-sided colorectal cancer (LCRC) than right-sided colorectal cancer (RCRC). We hypothesized that RCRC is more likely to harbor genetic alterations associated with resistance to anti-EGFR therapy and tested this using comprehensive genomic sequencing. Materials and methods A total of 201 patients with either primary RCRC or LCRC were analyzed. We investigated tumors for genetic alterations using a 415-gene panel, which included alterations associated with resistance to anti-EGFR therapy: TK receptors (ERBB2, MET, EGFR, FGFR1, and PDGFRA), RAS pathway (KRAS, NRAS, HRAS, BRAF, and MAPK2K1), and PI3K pathway (PTEN and PIK3CA). Patients whose tumors had no alterations in these 12 genes, theoretically considered to respond to anti-EGFR therapy, were defined as “all wild-type”, while remaining patients were defined as “mutant-type”. Results Fifty-six patients (28%) and 145 patients (72%) had RCRC and LCRC, respectively. Regarding genetic alterations associated with anti-EGFR therapy, only 6 of 56 patients (11%) with RCRC were “all wild-type” compared with 41 of 145 patients (28%) with LCRC (P = 0.009). Among the 49 patients who received anti-EGFR therapy, RCRC showed significantly worse progression-free survival (PFS) than LCRC (P = 0.022), and “mutant-type” RCRC showed significantly worse PFS compared with “all wild-type” LCRC (P = 0.004). Conclusions RCRC is more likely to harbor genetic alterations associated with resistance to anti-EGFR therapy compared with LCRC. Furthermore, our data shows primary tumor sidedness is a surrogate for the non-random distribution of genetic alterations in CRC.

Utility of comprehensive genomic sequencing for detecting HER2-positive colorectal cancer

HER2-targeted therapy is considered effective for KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (CRC). In general, HER2 status is determined by the use of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Comprehensive genomic sequencing (CGS) enables the detection of gene mutations and copy number alterations including KRAS mutation and HER2 amplification; however, little is known about the utility of CGS for detecting HER2-positive CRC. To assess its utility, we retrospectively investigated 201 patients with stage I-IV CRC. The HER2 status of the primary site was assessed using IHC and FISH, and HER2 amplification of the primary site was also assessed using CGS, and the findings of these approaches were compared in each patient. CGS successfully detected alterations in 415 genes including KRAS codon 12/13 mutation and HER2 amplification. Fifty-nine (29%) patients had a KRAS codon 12/13 mutation. Ten (5%) patients were diagnosed as HER2 positive because of HER2 IHC 3+, and the same 10 (5%) patients had HER2 amplification evaluated using CGS. The results of HER2 status and HER2 amplification were completely identical in all 201 patients (P < .001). Nine of the 10 HER2-positive patients were KRAS 12/13 wild-type and were considered possible candidates for HER2-targeted therapy. CGS has the same utility as IHC and FISH for detecting HER2-positive patients who are candidates for HER2-targeted therapy, and facilitates precision medicine and tailor-made treatment.

Small Bowel Obstruction After Ileal Pouch-Anal Anastomosis With a Loop Ileostomy in Patients With Ulcerative Colitis

Purpose Small bowel obstruction (SBO) remains a common complication after pelvic or abdominal surgery. However, the risk factors for SBO in ulcerative colitis (UC) surgery are not well known. The aim of the present study was to clarify the risk factors associated with SBO after ileal pouch-anal anastomosis (IPAA) with a loop ileostomy for patients with UC. Methods The medical records of 96 patients who underwent IPAA for UC between 1999 and 2011 were reviewed. SBO was confirmed based on the presence of clinical symptoms and radiographic findings. The patients were divided into 2 groups: the SBO group and the non-SBO group. We also analyzed the relationship between SBO and computed tomography (CT) scan image parameters. Results The study included 49 male and 47 female patients. The median age was 35.5 years (range, 14–72 years). We performed a 2- or 3-stage procedure as a total proctocolectomy and IPAA for patients with UC. SBO in the pretakedown of the loop ileostomy after IPAA occurred in 22 patients (22.9%). Moreover, surgical intervention for SBO was required for 11 patients. In brief, closure of the loop ileostomy was performed earlier than expected. A multivariate logistic regression analysis revealed that the 2-stage procedure (odds ratio, 2.850; 95% confidence interval, 1.009–8.044; P = 0.048) was a significant independent risk factor associated with SBO. CT scan image parameters were not significant risk factors of SBO. Conclusion The present study suggests that a 2-stage procedure is a significant risk factor associated with SBO after IPAA in patients with UC.

Genomic characterization of colitis-associated colorectal cancer

BackgroundInflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic, idiopathic, repeated inflammatory disease. Colorectal cancer (CRC) that develops in patients with IBD is known as colitis-associated colorectal cancer (CAC), but the underlying carcinogenic mechanism remains unclear. Genomic analysis of sporadic CRC has been well described based on next-generation sequencing (NGS) data. Using NGS, we compared all exons of 415 cancer-associated genes in patients in Japan and the USA who had CRC and found similar genomic alteration patterns among the two populations. However, genomic analysis of CAC has not been thoroughly investigated.Main bodyThe molecular pathogenesis of CAC shares many features with sporadic CRC, but there are distinct variations in the time and frequency of some alterations. Gene alterations in CAC are gradually being elucidated using genomic sequencing analyses. Some studies have shown that gene alteration patterns differ between UC and CD. The carcinogenesis of CAC depends on unique environmental, genetic, and immunological factors.ConclusionsIn this review, we have discussed the differences in genomic alterations between sporadic CRC and CAC. NGS in patients with IBD has the potential to detect early CAC and to suggest therapeutic targets.

Prophylactic lateral pelvic lymph node dissection in stage IV low rectal cancer

AIM To assess the clinical significance of prophylactic lateral pelvic lymph node dissection (LPLND) in stage IV low rectal cancer. METHODS We selected 71 consecutive stage IV low rectal cancer patients who underwent primary tumor resection, and enrolled 50 of these 71 patients without clinical LPLN metastasis. The patients had distant metastasis such as liver, lung, peritoneum, and paraaortic LN. Clinical LPLN metastasis was defined as LN with a maximum diameter of 10 mm or more on preoperative pelvic computed tomography scan. All patients underwent primary tumor resection, 27 patients underwent total mesorectal excision (TME) with LPLND (LPLND group), and 23 patients underwent only TME (TME group). Bilateral LPLND was performed simultaneously with primary tumor resection in LPLND group. R0 resection of both primary and metastatic sites was achieved in 20 of 50 patients. We evaluated possible prognostic factors for 5-year overall survival (OS), and compared 5-year cumulative local recurrence between the LPLND and TME groups. RESULTS For OS, univariate analyses revealed no significant benefit in the LPLND compared with the TME group (28.7% vs 17.0%, P = 0.523); multivariate analysis revealed that R0 resection was an independent prognostic factor. Regarding cumulative local recurrence, the LPLND group showed no significant benefit compared with TME group (21.4% vs 14.8%, P = 0.833). CONCLUSION Prophylactic LPLND shows no oncological benefits in patients with Stage IV low rectal cancer without clinical LPLN metastasis.

A Case of Obstructive Colitis with Elevated Serum CarcinoembryonicAntigen

We report the case of a 72-year-old female who was admitted to our hospital because of obstructive colitis. Blood analysis showed her serum carcinoembryonic antigen (CEA) level to be 156.0 ng/mL. A sigmoidectomy and descending colostomy were performed for obstructive colitis due to colonic diverticulitis. Histopathological examination revealed active inflammation of the sigmoid colon without neoplasia. Her serum CEA level decreased within normal limits immediately after surgery.

An esophageal cancer case unresectable due to tuberculous fibrosing mediastinitis: report of a case

We present a case of esophageal carcinoma in which esophagectomy was not possible because of tuberculous fibrosing mediastinitis. A 77-year-old man was diagnosed with carcinoma of the thoracic esophagus and admitted to our hospital. Chest radiography on admission revealed no abnormality except pleural thickening of the pulmonary apices, suggesting a history of subclinical infection of tuberculous pleurisy. The patient underwent surgery with a curative intent. Thoracotomy revealed that the mediastinum had been replaced with dense fibrous tissues and was widely encased with laminar calcification. Esophagectomy was not performed because it was considered impossible to do so safely. Although diagnosis of fibrous mediastinitis was not made preoperatively, review of the preoperative computed tomographic scans revealed proliferation of mediastinal soft tissues that were associated with patchy and laminar calcifications. Tuberculous fibrosing mediastinitis is an uncommon but clinically important disease for physicians who are involved in the diagnosis and treatment of esophageal cancer.