Well-Differentiated Adenocarcinoma Spreading Widely in the Gastric Submucosa.

A 56-year-old woman was referred to our hospital due to dry mouth. Diagnostic upper gastrointestinal endoscopy showed slightly elevated lesions both on the anterior wall and lesser curvature in the upper part of the stomach. Biopsy-proven tuble-forming atypical cells in the two lesions led us to treat the presumed early gastric cancers with endoscopic submucosal dissection (ESD). Pathological examination of the ESD specimen showed well-differentiated malignant cells spreading widely in the submucosa with positive lateral and deep margins. On retrospective image re-evaluation after ESD, we noticed the correlation between the presumed early gastric cancers and the multiple submucosal cyst-like lesions in the gastric wall on computed tomography. Under the tentative diagnosis of gastric cancers originating not from orthotopic gastric mucosa but from submucosal ectopic gastric gland, the patient underwent laparoscopic total gastrectomy and regional lymph node dissection, revealing the tumor infiltration to the serosa and regional lymph node swelling. Postoperative pathological evaluation showed lymph node metastases, multiple submucosal cyst-like lesions lined with a single layer of presumably benign epithelium, papillary adenocarcinoma cells in the submucosa, and tubular adenocarcinoma cells both in the mucosal and subserosal regions. The patient was discharged on the postoperative 7th day without any events and completed adjuvant chemotherapy on an outpatient basis. General surgeons should note that cyst-like lesion(s) in the gastric wall might be a predictor of extensive submucosal cancer cell spreading even in a case of well-differentiated gastric adenocarcinoma.

First Report of a Low-Grade Pseudomyxoma peritonei Originating from Gall Bladder.

Pseudomyxoma peritonei (PMP) refers to accumulation of mucinous ascites with or without neoplastic cells in the peritoneal cavity. It most commonly originates from a low or a high grade primary appendiceal mucinous neoplasm. Though adenocarcinoma of gall bladder has been reported to give rise to PMP, to the best of our knowledge, this is the first report of a PMP arising from a low grade mucinous tumour of the gall bladder. A 72-year-old patient was diagnosed with PMP 1.5 years after a cholecystectomy. After initial oral TS1 (combination of tegafur, gimeracil and oteracil) and later intraperitoneal (IP) chemotherapy with docetaxel and cisplatin, the patient was operated with the goal of tumour debulking, including removal of 5.5 L of mucinous ascites, an appendectomy, and ovariectomy. The histopathologic report showed a normal appendix and metastasis of PMP to the right ovary. After the exclusion of the 2 most common sites of origin (appendix and ovary), the specimen of the cholecystectomy was reviewed. It showed low grade mucinous tumour in the gall bladder, with immuno-histochemical markers (IHCs) suggestive of CK7, CDX2, MUC 2 positive and CK20, MUC5AC negative. MIB-1 index was 12%. The pathologic report of cytoreductive surgery performed after 7 cycles of IP chemotherapy confirmed the diagnosis of PMP originating from low grade mucinous tumour of the gall bladder. Our case report illustrates a rare disease and highlights that, though peritoneal metastasis from gall bladder cancers are known to have a poor prognosis, the peritoneal dissemination from a low grade mucinous neoplasm of gall bladder (PMP) has a significantly better prognosis due to a better disease biology and improved treatment options currently available for the treatment of PMP.

A Case of Squamous Cell Carcinoma of the Breast with Low-Grade Adenosquamous Carcinoma.

A 68-year-old woman with a breast mass was referred to our hospital. Imaging studies showed an oval well-defined mass, 1.3 cm in size, in her left lower outer quadrant of the breast. Core needle biopsy with immunohistochemical staining showed atypical spindle cells forming solid nests with necrosis and papillary lesions, leading to the tentative and pre-operative diagnosis of invasive ductal carcinoma. Due to the absence of daughter nodules, extensive ductal spread, and lymphadenopathy on imaging evaluation, the patient underwent breast-conserving surgery and sentinel node biopsy, resulting in negative surgical margins and no lymph node involvement. Post-operative pathological examination showed triple negative atypical cells with squamous differentiation, squamous cell carcinoma (SCC), with cystic parts and a small amount of low-grade adenosquamous cell carcinoma (LGASC), both encompassing the cystic parts in a contiguous fashion. No cases with synchronous SCC and LGASC in the breast have been reported to date. An etiologic correlation between SCC and LGASC should be further evaluated.

Recurrence of adenoma after curative endoscopic submucosal dissection for a rectal intramucosal adenocarcinoma in adenoma.

Background and study aims A 71-year-old female underwent endoscopic submucosal dissection (ESD) for a subcircumferential lateral-spreading rectal tumor. Pathological examination showed an intramucosal adenocarcinoma in villous adenoma (size: 155 × 140 mm), which had been curatively resected with negative margins. However, follow-up colonoscopy revealed a tumor at the ulcer scar site, which soon grew into a circumferential lesion. Nineteen months after the first ESD procedure, additional ESD was performed for the recurrent lesion, which was resected en bloc without any adverse events, although severe fibrosis was noted in the submucosa. Pathological examination revealed a villous adenoma similar to the primary lesion with negative margins, but tumor cell nests were also present in the submucosa, which implied that tumor cell implantation had occurred during the first ESD. The post-ESD ulcer bed was subjected to argon plasma coagulation to prevent tumor recurrence after confirmation of the pathological results. There have not been any signs of recurrence during 9 years of follow-up.

A case report of primary pancreatic leiomyosarcoma requiring six additional resections for recurrences.

INTRODUCTION: Primary pancreatic leiomyosarcoma is extremely rare. We report a case in which six additional resections were required to treat recurrent tumors in a 5-year period following the primary operation. PRESENTATION OF CASE: A 69-year-old man presented with a pancreatic tumor. Abdominal computed tomography scan showed a large heterogeneous mass with a necrotic area arising from the pancreatic body. We performed distal pancreatectomy, splenectomy, and wide resection of the transverse mesocolon. Histopathological examination confirmed the diagnosis of a pancreatic leiomyosarcoma. We repeatedly performed surgery on recurrent tumors. DISCUSSION: Primary pancreatic leiomyosarcoma is considered to be a highly aggressive malignancy. The most effective treatment is complete surgical resection with tumor-free margins. Even when tumors recur, it is possible to improve the prognosis by further resection. CONCLUSION: Long-term survival is achievable by repeated resection of recurrent tumors.

5-Aminolevulinic Acid Fluorescence in Detection of Peritoneal Metastases.

BACKGROUND: The value of 5-aminolevulinic acid (ALA) in fluorescence detection of peritoneal metastases and the underlying mechanisms were evaluated in patients with peritoneal surface malignancies. MATERIALS AND METHODS: Oral 5-ALA was administered at a concentration of 20 mg /kg body weight with 50 ml of water 2 hours prior to surgery (n=115). The diagnostic value of 5-ALA based fluorescence production was evaluated following white light inspection during prior to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Then, peptide transporter PEPT1 (ALA influx transporter) and ATP-binding cassette transporter ABCG2 (porphyrin efflux transporter) gene expression was determined with quantitative real time (qRT)-PCR and pathological diagnoses confirmed for all tissue samples. RESULTS: The 5-ALA based photodynamic detection rate was 17% for appendiceal mucinous neoplasms, 54% for colorectal cancers, 33% for gastric cancers, 67% for diffuse malign peritoneal mesotheliomas, and 89% for epithelial ovarian cancer of peritoneal metastases. 5-ALA was detected in all cases of peritoneal metastases originating from cholangiocarcinomas whereas it was not able to detect any in granulosa cell and gastrointestinal stromal tumor cases. Furthermore, PEPT1 was overexpressed whereas ABCG2 expression was downregulated in tumors detected with fluorescence. CONCLUSIONS: 5-ALA provided 100% specificity and high sensitivity to detect peritoneal metastases in subgroups of patients with peritoneal surface mailgnancies. ALA influx transporter PEPT1 and porphyrin efflux transporter ABCG2 genes are important in tumor specific 5-ALA induced fluorescence in vivo. Further studies should clarify diagnostic utility of 5-ALA in peritoneal surface malignancies.

Clinical significance of the muscle-retracting sign during colorectal endoscopic submucosal dissection.

BACKGROUND AND STUDY AIMS: During colorectal endoscopic submucosal dissection (ESD), the feature of a muscle layer being pulled toward a neoplastic tumor is sometimes detected. We call this feature the muscle-retracting sign (MR sign). The aim of this study was to evaluate whether the MR sign is associated with particular types of neoplastic lesions and whether it has any clinical significance for ESD sessions. PATIENTS AND METHODS: A total of 329 patients underwent ESD for 357 colorectal neoplasms. The frequency of positivity for the MR sign was evaluated in different morphologic and histopathologic types of neoplasm. The success rate of complete resection and the incidence of complications were also evaluated according to whether lesions were positive or negative for the MR sign. RESULTS: The rates of positivity for the MR sign in the various lesion types were as follows: laterally spreading tumor - granular nodular mixed type (LST-G-M), 9.6 %; laterally spreading tumor - granular homogeneous type (LST-G-H) and laterally spreading tumor - nongranular type (LST-NG), 0 %; sessile type, 41.2 %. The resection rate was 100 % (329 /329) in lesions negative for the MR sign; however, it was 64.3 % (18 /28) in lesions positive for the MR sign, which was significantly lower (P < 0.001). CONCLUSIONS: The MR sign was present only in some protruding lesions, and more importantly, it was associated with a high risk of incomplete tumor removal by ESD. Our data indicate that lesions positive for the MR sign lesions should be dissected with great caution; alternatively, based on the features of the individual case, a switch to surgery should be considered for the benefit of the patient.

Pancreatectomy and splenectomy for a splenic aneurysm associated with segmental arterial mediolysis.

Segmental arterial mediolysis (SAM) is characterized by intra-abdominal, retroperitoneal bleeding or bowel ischemia, and the etiology is unknown. A 44-year-old man complaining of abdominal pain was admitted to our hospital. He had been admitted for a left renal infarction three days earlier and had a past medical history of cerebral aneurysm with spontaneous remission. The ruptured site of the splenic arterial aneurysm was clear via a celiac angiography, and we treated it using trans-arterial embolization. Unfortunately, the aneurysm reruptured after two weeks, and we successfully treated it with distal pancreatomy and splenectomy. We recommended a close follow-up and prompt radiological or surgical intervention because SAM can enlarge rapidly and rupture.

Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei Arising from Urachus.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare locoregional disease characterized by disseminated intraperitoneal mucinous tumors. However, little is known about PMP from urachal neoplasm as a result of its rarity. METHODS: A total of 9 patients with PMP of urachal origin were treated by cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in our institution. All specimens of surgeries were submitted for pathologic examination. Representative slides of tumors and normal urachus were submitted for immunohistochemical staining. RESULTS: Four patients were men; the median age was 48 years (range 27-65 years). Initial radiologic examination of all patients showed a cystic tumor located between posterior aspect of umbilicus and the dome of urinary bladder, with or without leaking mucin. Complete CRS and HIPEC were performed in all patients. Until the latest follow-up, local recurrence occurred in 1 patient. Other 8 patients had a median disease-free survival of 27.5 months. Primary urachal tumors of 9 cases were all mucinous adenocarcinoma. Six patients had low-grade mucinous carcinoma peritonei, and 3 patients had high-grade mucinous carcinoma peritonei. Signet ring cells were noted in 4 patients. All tumor specimens of 9 patients were diffuse positive for CK-20, CDX-2, MUC-2, and MUC-5AC, and were variant positive for CK-7. CONCLUSIONS: PMP arising from urachus comes from neoplastic cells with development of intestinal-type mucinous neoplasm. It shares a similar pathophysiology as PMP from appendix. CRS including total urethrectomy, partial cystectomy, and peritonectomy plus HIPEC can be considered as a new option of treatment for PMP originating from urachus.

Photodynamic detection and management of intraperitoneal spreading of primary peritoneal papillary serous carcinoma in a man: report of a case.

As a peritoneal surface malignancy, primary peritoneal papillary serous carcinoma (PPPSC) almost always occurs in women. Our search of the literature found only two previous case reports of men with PPPSC, both with very short survival. We report the case of a 63-year-old man with PPPSC, treated effectively with cytoreductive surgery and docetaxel-based hyperthermic intraperitoneal chemotherapy following six cycles of docetaxel-based laparoscopic neoadjuvant intraperitoneal and cisplatin-based systemic chemotherapy. Furthermore, we detected intraoperative intraperitoneal spreading of the tumor after the oral administration of 5-amino levulinic acid (5-ALA). The patient remains in good health without ascites 18 months after his diagnosis. Thus, primary peritoneal papillary serous carcinoma should be managed by intraperitoneal chemotherapy combined with peritonectomy procedures. Moreover, the intraoperative detection of the intraperitoneal spreading of the tumor after administering oral 5-ALA shows that this is an exciting and promising diagnostic technique, which needs to be confirmed by further studies.

Late recurrence of benign multicystic peritoneal mesothelioma complicated with an incisional hernia.

Benign multicystic peritoneal mesothelioma (BMPM) is a rare disease arising from the peritoneal mesothelium. Here, we report a 57-year-old woman admitted to our unit with an incisional hernia fifteen years later following her first operation due to BMPM. Computerized tomography demonstrated a cystic appearing mass with intraabdominal extension in hernia sac. The patient underwent en bloc resection of the mass and hernia repair. An immunohistochemical analysis of the mass confirmed the recurrence of BMPM. Our case supports that BMPM has slowly progressive nature and can recur with complicated incisional hernia long time after primary resection. Diagnosis and long-term followup are crucial for clarifying the characteristics of this disease.

1,635 Endoscopic submucosal dissection cases in the esophagus, stomach, and colorectum: complication rates and long-term outcomes.

BACKGROUND: Endoscopic submucosal dissection (ESD) enables en bloc resection of early gastrointestinal neoplasms; however, most ESD articles report small series, with short-term outcomes performed by multiple operators on single organ. We assessed short- and long-term treatment outcomes following ESD for early neoplasms throughout the gastrointestinal tract. METHODS: We performed a longitudinal cohort study in single tertiary care referral center. A total of 1,635 early gastrointestinal neoplasms (stomach 1,136; esophagus 138; colorectum 361) were treated by ESD by single operator. Outcomes were complication rates, en bloc R0 resection rates, and long-term overall and disease-specific survival rates at 3 and 5 years for both guideline and expanded criteria for ESD. RESULTS: En bloc R0 resection rates were: stomach: 97.1 %; esophagus: 95.7 %; colorectum: 98.3 %. Postoperative bleeding and perforation rates respectively were: stomach: 3.6 and 1.8 %; esophagus: 0 and 0 %; colorectum: 1.7 and 1.9 %. Intra criteria resection rates were: stomach: 84.9 %; esophagus: 81.2 %; colorectum: 88.6 %. Three-year survival rates for lesions meeting Japanese ESD guideline/expanded criteria were for all organ-combined: 93.4/92.7 %. Five-year rates were: stomach: 88.1/84.6 %; esophagus: 81.6/57.3 %; colorectum: 94.3/100 %. Median follow-up period was 53.4 (range, 0.07-98.6) months. Follow-up rate was 94 % (1,020/1,085). There was no recurrence or disease-related death. CONCLUSIONS: In this large series by single operator, ESD was associated with high curative resection rates and low complication rates across the gastrointestinal tract. Disease-specific and overall long-term prognosis for patients with lesions within intra criteria after curative resection appeared to be excellent.

Management of peritoneal dissemination of recurrences granulosa cell tumor of the ovary.

Recurrences of granulosa cell tumor (GCT) of the ovary often occur as disseminated peritoneal metastasis or local mass in the pelvis. Although, various treatment options including surgery with/without systemic chemotherapy and/or radiotherapy have also been reported for treatment of recurrent GCT, there is no standardized management for recurrence of this disease. Here, we report our management strategies for the patients with peritoneal dissemination of GCT. Prior to admission to our unit, four patients were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy with the diagnosis of primary adult type GCT of the ovary. They were not received adjuvant therapy because of the localized disease in the ovary and followed-up by their gynecologists until they referred to us with metastases. The median disease free survival after primary treatment was 4.7 (range, 1-9) years. All patients with peritoneal metastases from recurrent GCT were treated with cytoreductive surgery (CRS) using peritonectomy procedures and intraoperative hyperthermic intraperitoneal chemotherapy(HIPEC) using 100 mg cisplatin for 40 min at 43 °C in our unit. Postoperative complications were graded according to National Cancer Institute's Common Toxicity Criteria. No complication and no in-hospitalization mortality were experienced in all patients. The median length of operation was 3.55 (range, 2.50-5.50) hours. The median length of stay in hospital was 13(range, 12-21) days. After a median follow-up of 4(range, 1-6) years, 1 patient was died and other 3 patients were alive with no disease progression. Our study identified that recurrent adult type of GCT with peritoneal metastases could be managed with definitive CRS and HIPEC. Larger series and long term outcome data of CRS and HIPEC will be mandatory to develop standard management option in these patients.

Principles of quality controlled endoscopic submucosal dissection with appropriate dissection level and high quality resected specimen.

Endoscopic submucosal dissection (ESD) has enabled en bloc resection of early stage gastrointestinal tumors with negligible risk of lymph node metastasis, regardless of tumor size, location, and shape. However, ESD is a relatively difficult technique compared with conventional endoscopic mucosal resection, requiring a longer procedure time and potentially causing more complications. For safe and reproducible procedure of ESD, the appropriate dissection of the ramified vascular network in the level of middle submucosal layer is required to reach the avascular stratum just above the muscle layer. The horizontal approach to maintain the appropriate depth for dissection beneath the vascular network enables treatment of difficult cases with large vessels and severe fibrosis. The most important aspect of ESD is the precise evaluation of curability. This approach can also secure the quality of the resected specimen with enough depth of the submucosal layer.

Primary retroperitoneal mullerian adenocarcinoma.

Mullerian tumors are extremely rare malignancies in the retroperitoneum. We report a case of a 46-year old woman who presented with an eight year history of lower abdominal mass. Ultrasonography (US) and computed tomography (CT) demonstrated a 15×10 cm cystic mass in the left lower retroperitoneum. As serial percutaneous needle aspiration cytology was negative for malignancy, she was observed for seven years. Eleven months ago, the mass was excised. The histopathology was reported as mucinous adenocarcinoma of the retroperitoneum. Six cycles of intraperitoneal (IP) chemotherapy was administered during the last six months after diagnosis of recurrence by aspiration cytology and high serum tumor markers (CEA, CA19-9). A few days ago, positron emission tomographic (PET) scanning showed evidence of local recurrence and single vertebral metastasis, so she was admitted again for systemic chemotherapy. Meticulous revision of additional sections of the tumor revealed papillary, serous, mucinous, and endometrioid subtypes of the mullerian adenocarcinoma. To our knowledge, there has been no similar case described in the literature.