[Early Duodenal Cancer Resected by Using Laparoscopic and Endoscopic Assistance Surgery in a Patient with Peutz-Jeghers Syndrome].

A 28-year-old female with a history of treatment for small intestinal polyps and characteristic pigmentation of her lip was clinically diagnosed with Peutz-Jeghers syndrome(PJS). Her sister had the pathogenic variant of STK11 upon genetic testing. A 20-mm polyp was identified in the second part the patient's duodenum on routine gastrointestinal surveillance, and biopsy revealed a well-differentiated adenocarcinoma. Laparoscopic partial duodenectomy with endoscopy was planned. After confirming the location of the tumor and Kocherization using a laparoscope, the polyp was resected via submucosal dissection under direct visualization with a small incision. The polyp was diagnosed as well-differentiated adenocarcinoma in situ and was resected without remnants. PJS is characterized by a high incidence of malignant tumors, and lifelong surveillance for gastrointestinal and extra-gastrointestinal tumors is necessary. The incidence of duodenal cancer is not high among patients with PJS. However, surgery for advanced cancer is highly invasive. It is desirable to detect the tumors at an early stage so that they can be resected via a less invasive treatment method such as endoscopic resection or laparoscopic surgery with an endoscope.

[Development of Cancer of the Remnant Colorectal Segment after Ileal-Pouch Anal Anastomosis/Ileorectal Anastomosis in Patients with Familial Adenomatous Polyposis].

PURPOSE: This retrospective study was performed to investigate the recent trend of occurrence of cancer of the remnant colorectal segment(RCRS)after ileal-pouch anal anastomosis(IPAA)/ileorectal anastomosis(IRA)and to consider the optimal surveillance methods in patients with familial adenomatous polyposis(FAP)undergoing(procto)colectomy. PATIENTS AND METHODS: The subject was a total of patients with FAP undergoing IPAA or IRA between 2005 and 2022. Clinicopathological data were extracted from medical charts and analyzed. Cumulative incidence of cancer in the RCRS and overall survival after treatment of such tumors were calculated by the Kaplan-Meier method. RESULTS: There were 45 male and 56 female. IPAA was performed in 49 patients(hand-sewn; n=33, stapled; n=16)and IRA was performed in 52 patients. The median age at initial colorectal surgery was 32 years old(range, 13-66 years old). Median postoperative follow-up was 11 years(range, 1-48 years). Eighty-one patients were confirmed to have pathogenic variant of APC by genetic test. The cumulative incidence of cancer of the RCRS did not differ between patients undergoing IPAA and those undergoing IRA(p= 0.73, 4.1% versus 1.9% at 10 years). The cumulative 5-year overall survival rate after additional surgery for the tumor of RCRS was 82%. CONCLUSION: This study has several limitations due to single institutional retrospective study with small cases and non-standardized postoperative endoscopic surveillance. However, our results seem to show satisfactory oncological outcomes of patients with FAP in terms of the control of cancer of the RCRS under postoperative periodic surveillance, regardless of the type of colorectal resection.

[A Rare Case of Cronkhite-Canada Syndrome Associated with Gastric Cancer and Gastric Outlet Obstruction].

Cronkhite-Canada syndrome(CCS)is a rare non-inherited disease characterized by gastrointestinal polyposis and ectodermal abnormalities. We report a rare case of CCS associated with gastric cancer and gastric outlet obstruction with a review of the literature. A 75-year-old man was admitted because of frequent vomiting and hypoproteinemia. He was diagnosed with CCS due to typical clinical and laboratory findings including alopecia, nail atrophy, hypoproteinemia, and typical gastrointestinal polyposis. Upper endoscopic examination also pointed out a large gastric cancer mainly located in the antrum and the reversible pyloric obstruction caused by the gastric tumor. Biopsy of the tumor revealed tubular adenocarcinoma. Computed tomography demonstrated the dilated duodenum caused by packing of the gastric tumor. 1.5 months after prednisolone therapy, he underwent total gastrectomy with complete resection of the dilated duodenal bulb. Histological examination revealed gastric cancer(pap>tub1)classified into Stage ⅢC. Postoperative course was uneventful and he moved to another hospital. To our knowledge, including the present case, there were 20 reported cases of CCS associated with gastric cancer from Japan(1979-2022). Also, 7 cases of CCS associated with gastric outlet obstruction was reported.

[A Case of Curative Resection of a Retroperitoneal Liposarcoma].

A 55-year-old woman had been admitted to a hospital with abdominal bloating. Retroperitoneal liposarcoma was suspected and diagnosed as not resectable. She was then referred to our hospital with dyspnea and difficulties with movement due to the huge mass. An abdominal CT revealed a large mass originating in the left retroperitoneum. The tumor occupied most of the abdominal cavity, resulting in the displacement of her organs. However, there was no evidence of infiltration of the tumor into the aorta and inferior vena cava. Under a provisional diagnosis of retroperitoneal liposarcoma, a surgical resection was undertaken. The resected specimen had a maximum diameter of 48 cm and weighed 14 kg. Histopathological examination revealed a differentiated liposarcoma. The patient remains alive 6 months after the operation, without recurrence.

[Does Colonic Stenting Affect the Long-Term Prognosis of Colorectal Cancer ?]

The impact of colonic stenting on long-term prognosis has not yet been clarified. We compared background factors, progression-free survival, and overall survival between patients with stents(stent group)who underwent surgery after colonic stenting as a bridge to surgery and patients without stents(non-stent group)who underwent emergency surgery for left-sided colorectal cancer ileus. There was no difference between the 2 groups in the induction of adjuvant chemotherapy, but the use of oxaliplatin-base was highly introduced in the stent group(p=0.03). The 5-year DFS rates were 55.1% and 70.3%(p=0.21)and the 5-year OS rates were 90.7%and 70%(p=0.35)in the stent and non-stent groups, respectively. In the present study, colon stent placement did not affect long-term prognosis.

[A Case of Synchronous Gallbladder Metastasis Originating from Advanced Gastric Cancer].

Gallbladder metastasis from gastric cancer is often found accidentally during postoperative pathological examinations, and its preoperative diagnosis is very difficult. There are a few reports in diagnostic imaging, and it is well known to have a very poor prognosis. There have been 13 reports on gallbladder metastasis from gastric cancer in the Japanese literature. Among the 13 reports, 10 cases were diagnosed with gallbladder metastasis synchronously and only 1 case was diagnosed as gallbladder metastasis before surgery. One case was reported as hematogenous metastasis, and 9 cases were reported as lymphoid metastasis. In total, 7 patients died, all within the first year after surgery. We experienced a case of synchronous gallbladder metastasis from gastric cancer.

[The Outcome of Preoperative Chemoradiotherapy for Advanced Lower Rectal Cancer-The Possibility of an Omission of the Lateral Dissection].

The objective of this study was to evaluate the outcomes of selective LPLN dissection(LPLD)based on pretreatment imaging in patients with advanced low rectal cancer treated with pre-operative CRT. We reviewed 32 patients without suspected LPLN metastasis based on the MDCT or MRI results before CRT. These patients underwent total mesorectal excision (TME)without LPLD. The clinical characteristics and oncological outcomes were examined. In all cases, the per-protocol treatments were completed. Tumor recurrence occurred in 14 patients at the liver(3 cases), the lung(7 cases)and the local sites(4 cases). Of the 4 cases with pelvic recurrence, no recurrence was found in the lateral lymph node area. Under the condition that pre-operative chemoradiotherapy is to be performed for advanced lower rectal cancer with negative lateral lymph node metastasis, a lateral dissection could be omitted.

[Analysis of Palliative Stents for Colonic Stenosis Due to Extracolonic Cancers].

We retrospectively reviewed 13 patients in whom endoscopic stenting for colonic stenosis due to extracolonic cancers(non- CRC group)was attempted between July 2012 and January 2018. There were 5 men and 8 women, with a median age of 69 years. Primary malignancies causing colonic stenosis were gastric cancer(n=4), cholangiocarcinoma(n=2), pancreatic cancer(n=2), lung cancer(n=2), uterine cancer(n=2), and ovarian cancer(n=1). The non-CRC group patients demonstrated a significantly lower technical success rate than those who received palliative stents for colonic stenosis for primary colorectal cancer(n=51)(69% vs 98%, p<0.01). In addition, the non-CRC group patients(n=13)also demonstrated a significantly lower technical success rate(69% vs 99%, pp<0.01)than those who received stents aiming to subsequently undergo a bridge to surgery. Nonetheless, colorectal stenting for extracolonic malignancies appears to be a minimally invasive treatment and could offer patients rapid relief. Thus, it could be an effective alternative to some palliative therapies.

[Status of Hepatic Lymph Node Involvement in Patients with Resectable Liver Metastasis of Colorectal Cancer after Preoperative Chemotherapy].

The liver is the most common metastatic site for colorectal cancer(CRC).The 5-year survival rate of resected cases has been reported to be about 40%.Hepatic lymph node metastasis is reportedly associated with a poor prognosis in patients with liver metastases of CRC.The incidence of hepatic lymph node involvement in patients with liver metastases of CRC ranges from 5% to 28%.However, few reports have focused on hepatic lymph node involvement in patients with resectable liver metastasis who have undergone preoperative chemotherapy.This retrospective study was undertaken to address this issue.The subjects were 33 consecutive patients who had undergone the resection of liver metastases of CRC with hepatic lymph node sampling after preoperative chemotherapy between 2001 and 2016. Hepatic lymph node metastasis was confirmed in only one patient(3%).There was no significant difference in the frequency of hepatic lymph node metastasis between the cases with or without preoperative chemotherapy.The further collection of data is warranted to elucidate the significance of hepatic lymph node involvement in patients with liver metastases of CRC treated with preoperative chemotherapy.

[The Characteristics and Treatment Outcomes for Desmoid Tumors Associated with Familial Adenomatous Polyposis].

INTRODUCTION: The characteristics of desmoid tumors(DTs)associated with familial adenomatous polyposis(FAP)and relationships between the development of DTs and the sites of APC germline mutation have not closely been examined Japan. PATIENTS AND METHODS: This retrospective study was performed to address these issues by examining patients with FAP who underwent proctocolectomy between 1981 and 2015. RESULTS: The cumulative 2-year incidence of DT development was 50%. The DTs developed in the abdominal wall only in 2, in the abdominal wall plus intra-abdominally in 4, and intra-abdominally in 2. Clinical stages according to the Church's classification included Stage I in 3, Stage II in 2, Stage III in 1, and Stage IV in 2. Among 31 patients with a confirmed pathogenic germline APC mutation, patients with mutation in 3' site of codon 1400 (n=7)tended to develop DTs more frequently than those with mutation in 5' site of codon 1400(n=24)(p=0.08). The cumulative 5-year survival rate in patients with DT development was 73.3%. Including 2 patients undergoing initial colectomy at other institutions, the therapeutic efficacy in 4 patients with severe intraabdominal DTs(Stage III /Stage IV )who were given chemotherapy comprising doxorubicin plus dacarbazine(DOX plus DTIC)revealed partial response in 3 and complete response in 1. Febrile neutropenia was recorded in 2 of these patients. CONCLUSION: The frequency of DTs development and genotype-phenotype relationship of FAP patients seems to concur with those reported from Western countries. Since the DOX plus DTIC therapy for severe DTs is valid but toxicity is high, the development of less toxic regimens are warranted.

[Effect of chemotherapy in primary tumor of MSI-H colon cancer aged 50 years or younger].

Microsatellite instability( MSI) in colorectal carcinoma is reportedly associated with resistance to 5-fluorouracil-based chemotherapy. Moreover, colorectal cancer patients aged ≤ 50 years could potentially have Lynch syndrome. In the present study, we examined 11 colorectal cancer patients with unresectable Stage IV disease who underwent resection of the primary tumor between January 2006 and December 2012. The relationship between the MSI status and the efficacy of first- line oxaliplatin-based chemotherapy was retrospectively examined. The MSI status included MSI-H in 1 patient, MSS-L in 2 patients, and MSS in 8 patients. The MSI-H in 1 patient was associated with familial adenomatous polyposis. Following chemotherapy, among 8 MSS patients, 3 showed stable disease (SD) and 1 showed partial response (PR). Moreover 2 MSH-L patients and 1 MSI-H patient showed progressive disease (PD) after chemotherapy. However, additional data collection is required to determine the effect of oxaliplatin-based chemotherapy for MSS-H or MSS-L colorectal patients aged ≤ 59 years.

[Analysis of KRAS status in cancer tissue with submucosal or deeper invasion in patients with familial adenomatous polyposis].

The KRAS status in cancer tissue with submucosal or deeper invasion was investigated in patients with familial adenomatous polyposis (FAP). Fifteen cancerous lesions in 10 FAP patients were subjected to analysis for KRAS status. The clinical features of FAP were the dense type in 2 patients and the sparse type in 8 patients. Of the 15 cancerous lesions, 6 (40%) were identified as having wild-type KRAS and the remaining 9 (60%), as having mutated KRAS. Of the 9 mutated lesions, the G13D mutation was recognized in 4 patients and was the most frequent pattern. With regard to the KRAS status in patients with multiple cancerous lesions, 1 patient had 3 cancerous lesions of which 2 were of the mutated type and 1 was of the wild type and another patient had 4 cancerous lesions of which 3 were of the mutated type and 1 was of the wild type. These results suggest that the frequency of wild-type KRAS in cancer associated with FAP was approximately 40%, although it was lower than that in sporadic cancer. Moreover, we need to analyze the KRAS status in all cancerous lesions in clinical practice when chemotherapy with anti-epidermal growth factor receptor (EGFR) antibody is required for the treatment of FAP patients with unresectable advanced multiple cancers.

[Strategy for surgery in familial adenomatous polyposis patients with invasive colorectal cancer].

PURPOSE: Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) has been established as the standard operative procedure for classic familial adenomatous polyposis( FAP). However, it is unclear which type of surgery should be undertaken for FAP patients with invasive colorectal cancer in clinical practice. This study evaluated the outcome of different surgeries performed in FAP patients with invasive colorectal cancer. PATIENTS AND METHODS: The study included 21 classic FAP patients with or without invasive colorectal cancer, who underwent proctocolectomy at our institute between 2000 and 2013. Patient background, type of operation, and prognosis were retrospectively examined. RESULTS: In the non-invasive cancer group, total proctocolectomy with IPAA was performed in 7 patients, and colectomy with ileorectal anastomosis (IRA) was performed in 5 patients. Conversely, in the invasive cancer group, IPAA, proctocolectomy with end ileostomy (TPC), and IRA were performed in 2, 2, and 5 patients, respectively. Overall survival did not differ significantly between the 2 groups( 5 year survival, 88.9% vs 75.0%, p=0.48). CONCLUSION: These results suggest that IPAA, IRA, or TPC might contribute to survival time prolongation in patients with invasive colorectal cancer, as is the case for those without invasive colorectal cancer.

Eplerenone, an aldosterone blocker, is more effective in reducing blood pressure in patients with, than without, metabolic syndrome.

BACKGROUND: Recently, the role of aldosterone in metabolic syndrome (MS) has aroused interest and several reports have suggested that aldosterone blockade could be beneficial in reducing blood pressure (BP). METHODS: To examine the add-on effects of eplerenone (EP) on BP in patients with MS, 54 hypertensive patients with MS and 44 without MS were recruited. Systolic and diastolic BPs in mmHg before the initiation of EP was 144/84 ± 13/12 (MS group) and 147/85 ± 12/14 (non-MS group). Before the start of EP, all patients in both groups were treated with at least one antihypertensive drug. BPs were checked on every visit (at least every 2 months) and serum chemistries were measured every 4 months. The levels of microalbuminuria and aminoterminal pro-brain natriuretic peptide (NT pro-BNP) were determined before the start of and at the end of the study. Patients were followed for 1 year. If adverse effects were reported by patients or found in laboratory studies, EP was withdrawn. RESULTS: One month after the start of EP, BPs were decreased to 140/80 ± 12/12 mmHg (MS group) versus 142/82 ± 11/12 mmHg (non-MS group) and there was no difference between the two groups. Towards the end of the study, BPs of both groups gradually decreased. At the end of the study, BPs of both groups were 129/76 ± 15/13 mmHg (MS group) versus 133/78 ± 13/11 mmHg (non-MS group). There was a significant difference in reduction of systolic BP between the two groups (p < 0.05). Add-on EP significantly decreased the levels of urinary excretion of albumin in MS patients but not in non-MS patients (p < 0.05). There was a significant correlation between reduction of systolic BP and NT pro-BNP but not microalbuminuria in the MS group (p < 0.05). There were no serious adverse effects in both groups. CONCLUSION: EP may have some beneficial effects in lowering BP in patients with reduction of microalbuminuria.

[The prognosis and immunohistochemical evaluation of five perianal Paget's disease cases].

Perianal Paget's disease is categorized as Paget's disease, which is epidermotropic neoplasm arising from the apocrine glands of perianal region, or Pagetoid spread invaded from rectal or anal canal cancer. It has been reported that the immunohistochemical staining of GCDFP15, the marker of the apocrine epithelium, and CK20 is used to be distinguished between Paget's disease and Pagetoid spread. Five patients with perianal Paget's disease who underwent a surgical operation had been treated in our department between 1997 and 2006. We analyzed the clinical findings and the treatment of these patients and investigated the expression of GCDFP15 and CK20 by immunohistochemical staining. All cases presented the redness around perianal regions, and 2 cases were recognized a tumor at the anal canal. We preoperatively diagnosed these cases as Pagetoid spread and others without tumor regions as Paget's disease. Surgical treatment was performed for all patients. As a result of immunohistochemical staining, 2 cases of Pagetoid spread were negative for GCDFP15, and positive for CK20. It was compatible with the preoperative diagnosis. Only one of 3 Paget's disease cases was positive for GCDFP15 and negative for CK20 resulting in the diagnosis of perianal Paget's disease. Based on the expression of negative for GCDFP15 and positive for CK20, others were seemed to be Pagetoid spread. A treatment strategy including surgical operation and chemotherapy is different between patients with Paget's disease and those with Pagetoid spread. Therefore, it is essential to investigate the expression pattern of GCDFP15 and CK20 using the tissue from the biopsy to identify the disease for appropriate treatment.

[Treatment for intrapelvic recurrence of rectal cancer--resection versus chemotherapy].

This retrospective study was performed to clarify problems associated with surgery for local recurrence of rectal cancer in recent years when new anticancer drugs have come out to be available. We compared the background characteristics and treatment outcomes of patients who underwent resective surgery (resection group, n=9) and those who received chemotherapy comprised of new aniticancer drugs (chemotherapy group, n=5) for intrapelvic recurrence of rectal cancer between 1997 and 2008. In the resection group, the types of surgery included were abdomino-perineal resection in 1, posterior exenteration in 4, total pelvic exenteration in 4 and 5 who underwent sacrectomy. In the chemotherapy group, chemotherapy was continued to second-line treatment in 4 patients and third-line in 1. Oxaliplatin was given to 3 patients, irinotecan to 3, and Leucovorin to 5. The two groups did not significantly differ regarding various background factors including age, sex, stage at resection of the primary lesion, and the interval between resection of the primary lesion and detection of recurrence. The overall survival period after the start of treatment for recurrence did not significantly differ between the two groups (p=0.73). Patient's selection seems to have become a more important factor for resective surgery for intrapelvic recurrence of rectal cancer in recent years when the efficacy of new anticancer drugs is expected.

[Expression of dihydropyrimidine dehydrogenase in primary colorectal cancer and liver metastasis--a relationship between mRNA levels in cancer cells and protein levels in cancerous tissue and effect of 5-fluorouracil].

PURPOSE: To compare mRNA levels in cancer cells and protein levels in cancerous tissue in order to evaluate the expression of dihydropyrimidine dehydrogenase (DPD). MATERIALS AND METHODS: The materials were resected specimens of primary colorectal cancer (n=88) and synchronous liver metastasis (n=15). The expression of DPD mRNA in cancer cells was quantified by reverse-transcriptase polymerase chain reaction (RT-PCR) using cancer cells obtained by micro-dissection of paraffin-embedded specimens (Danenberg tumor profiling method). The protein level of DPD was determined by enzyme -linked immunosorbent assay (ELISA). RESULTS: There was no relationship between the level of DPD mRNA and the level of DPD protein in primary colorectal cancers and liver metastases. The level of DPD protein tended to be higher in liver metastases than in primary lesions (p=0.08) without a significant relationship between the two values. There was no relationship between primary colorectal lesions and liver metastases in terms of the expression of DPD mRNA. The efficacy of 5-fluorouracil (5-FU or UFT)/Leucovorin did not correlate with the expression level of DPD mRNA or DPD protein of primary lesions (n=18). CONCLUSIONS: We should note the discrepancy of results between the two different methods and the lack of a relationship between the levels of DPD expression in primary lesions and liver metastases, when considering the efficacy of 5-FU-based regimens according to the DPD expression level in primary colorectal cancers.

[Analysis of ovarian metastasis of colorectal cancer--a comparison between ovarian metastasis and peritoneal metastasis without involving ovaries].

This retrospective study was performed to clarify whether or not ovarian metastasis from colorectal cancer should be classified into peritoneal metastasis. We compared patient background data and prognosis between patients with ovarian metastasis (ovarian group, n=16) and female patients with peritoneal metastasis without involving ovaries (peritoneal group, n=22) treated between 1998 and 2008. The two groups did not significantly differ in terms of other clinicopathological factors evaluated. The median overall survival period was 13.8 months for the ovarian group and 16.7 months for the peritoneal group (p=0.96). The 3-year overall survival rate was 48.6%, 46.9%, and 11.5% for patients with ovarian metastasis only (P2), those with minute peritoneal metastasis without involving ovaries (P1), and those with multiple (numerous) peritoneal metastasis without involving ovaries (P3) (p=0.13), respectively. These results suggest that it is valid to classify ovarian metastasis as peritoneal metastasis. However, further collection of data may be needed to conclude that solitary ovarian lesion(s) would be classified into P2.

Chest wall mesenchymal hamartoma associated with a massive fetal pleural effusion: a case report.

Abstract We report on an extremely rare chest wall mesenchymal hamartoma associated with a massive fetal pleural effusion. Prenatal ultrasound examination demonstrated a heterogeneous mass in the right thorax associated with a massive pleural effusion and right lung compression at 29 weeks of gestation. The patient underwent pleuroamniotic shunting at 30 weeks and was delivered at 33 weeks by cesarean delivery secondary to fetal distress. After management of the respiratory distress and evaluation of the mass, surgery was performed at day of life 8. Histological examination confirmed the diagnosis of a chest wall mesenchymal hamartoma.

[Efficacy of hepatic arterial infusion of adriamycin and mitomycin C mixed with degradable starch microspheres for liver metastasis of colorectal cancer--correlation with the mRNA expression of DNA topoisomerase-IIalpha and glutathione-S transferase-pi in primary lesions].

DNA topoisomerase-IIalpha (topo-IIalpha) is a target enzyme of adriamycin (ADM). Glutathione-S-transferase-pi is known to be correlated with the resistance of various anticancer drugs including mitomycin C (MMC) and ADM. Expression levels of topo-IIalpha and GST-pi mRNA of primary colorectal lesions were semi-quantitatively determined by the RT-PCR method in 22 patients with colorectal cancer, who underwent hepatic arterial infusion of ADM and MMC mixed with degradable starch microspheres for synchronous (n=17) or metachronous (n=5) liver metastasis. Expression of topo-IIalpha mRNA/beta-actin mRNA was 0.872+/-0.564 (mean+/-SD) in responders (PR, n=10) and 0.369+/-0.133 in non-responders (SD+PD, n=12) (p=0.047). The relative expression of GST-pi was 0.638+/-0.593 in responders and 1.014+/-0.682 in non-responders (p=0.22). These results suggest that determining the mRNA expression of topo-IIalpha is useful for predicting the efficacy for this regimen, whereas determining the mRNA expression of GST-pi is not.