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Figure14.Histology of FAP-associated duodenal adenomas. A: Low-grade adenoma: The tumor glands are rather uniform and the adenomatous epithelial cells show basally oriented, elongated nuclei. B: Intramucosal carcinoma: Tumor glands show significant irregularity, nuclear stratification, and occasional prominent nucleoli. Note that high-grade dysplasia in the Spigelman classification includes non-invasive intramucosal carcinoma in the Japanese classification. C: Tubular adenoma: This lesion shows a relatively regular tubular architecture. D: Tubulo-villous adenoma: This lesion partially exhibits villous architecture, composed of fibrovascular cores lined by dysplastic epithelium.
Source publication
Hereditary colorectal cancer accounts for less than 5% of all colorectal cancer cases. Some of the unique characteristics that are commonly encountered in cases of hereditary colorectal cancer include early age at onset, synchronous/metachronous occurrence of the cancer, and association with multiple cancers in other organs, necessitating different...
Similar publications
Hereditary colorectal cancer (HCRC) accounts for < 5% of all colorectal cancer cases. Some of the unique characteristics commonly encountered in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics necessitate different management approaches, including diagnos...
Citations
... FAP was defined according to the following three criteria: (i) 100 or more adenomatous polyps in the colon with or without a family history of FAP, (ii) fewer than 100 adenomatous polyps in the colon with a family history of FAP, and (iii) germline mutations in the APC gene. The diagnostic criteria adhered to Japanese Society for Cancer of the Colon and Rectum guidelines for the Clinical Practice of Hereditary Colorectal Cancer [16,17]. The characteristics of variants in genetically diagnosed cases were showed according to the gene-specific ACMG/AMP classification criteria for germline APC variants [18] (Supplementary Table 1). ...
Purpose
The long-term prognosis of stapled and hand-sewn ileal pouch–anal anastomoses in familial adenomatous polyposis patients in Japan remains unknown. This study aimed to compare the overall survival in familial adenomatous polyposis patients who underwent stapled or hand-sewn ileal pouch–anal anastomosis.
Methods
This multicenter retrospective study was conducted at 12 institutions in Shizuoka Prefecture, Japan. The clinical outcomes of 53 eligible familial adenomatous polyposis patients who underwent stapled (n = 24) and hand-sewn (n = 29) ileal pouch–anal anastomosis were compared.
Results
The median follow-up duration was 171.5 months. The incidence of adenoma in the remnant rectum or anal transitional zone and metachronous rectal cancer was significantly more common in stapled ileal pouch–anal anastomosis (adenoma: stapled, 45.8%, vs. hand-sewn, 10.3%, p = 0.005; metachronous rectal cancer: 29.2%, vs. none, p = 0.002). The number of deaths was remarkably higher in stapled ileal pouch–anal anastomosis (p = 0.002). Metachronous rectal cancer was the most common cause of death. Overall survival was worse in stapled ileal pouch–anal anastomosis than in hand-sewn ileal pouch–anal anastomosis (120 months, 90.7% vs. 96.6%; 240 months, 63.7% vs. 96.6%; p = 0.044). Cox regression analysis revealed the independent effects of preoperative advanced colorectal cancer and stapled ileal pouch–anal anastomosis on overall survival.
Conclusion
Stapled ileal pouch–anal anastomosis negatively affected the overall survival of familial adenomatous polyposis patients. Therefore, hand-sewn ileal pouch–anal anastomosis is recommended for better prognosis in these patients.
... Currently, in Japan, an LS screening protocol was developed based on Western studies [12,13]. Although this protocol has a strong scientific basis, it requires multiple expensive tests, such as BRAF V600E variant or MLH1 promoter methylation. ...
... Although this protocol has a strong scientific basis, it requires multiple expensive tests, such as BRAF V600E variant or MLH1 promoter methylation. In Japan, the choice of whether to undergo these tests is up to the patients [12,13]. Many Japanese patients do not fully understand the importance of these tests because they have less access to sufficient explanations about genetic diseases. ...
... However, the absence of nuclear staining in the tumor cells in the presence of nuclear staining of non-neoplastic cells, such as normal colonic epithelial cells, lymphocytes, or stromal cells, was considered to represent an abnormal pattern. This evaluation method is performed in accordance with the Japanese Society for Cancer of the Colon and Rectum Guidelines 2016 and 2020 for the Clinical Practice of Hereditary Colorectal Cancer [12,13]. The staining results were evaluated by consensus between two independent pathologists. ...
Backgrounds
: This study aimed to evaluate the changes in the rates of genetic counseling and genetic testing as well as the diagnosis rate of Lynch syndrome (LS)-associated colorectal cancer before and after multistep approach with multidisciplinary team in Japanese.
Methods
In September 2016, we started universal screening for LS by mismatch repair protein immunohistochemistry and prospectively collected the records. Following patient interviews, we started multistep approach with multidisciplinary team (MA) in January 2020. MA consists of six surgeons, one genetic counselor, one medical geneticist, and six pathologists. MA is set up to compensate for patients’ lack of knowledge about genetic diseases and make case selection for elderly colorectal cancer patients with deficient mismatch repair (dMMR). MA is designed as a system that could be performed by a small number of medical genetic specialists. A total of 522 patients were included during the study duration, 323 and 199 patients in the pre-MA (P-MA) and MA groups, respectively.
Results
The frequency of dMMR in all patients was 10.0%. The patient interview results indicated a significant lack of patient education regarding genetic diseases. The rates of genetic counseling and genetic testing was significantly higher in MA group than in P-MA group (genetic counseling: MA 34.6% vs. P-MA 7.7%, p = 0.04; genetic testing: MA 30.8% vs. P-MA 3.8%, p = 0.02). Moreover, the diagnosis rate of LS-associated colorectal cancer was significantly higher in MA group (2.5%) than in P-MA group (0.3%) ( P = 0.03). In addition, MA could be performed without problems despite the small number of medical and human genetics specialists.
Conclusions
MA has achieved appropriate pickup of suspected hereditary colorectal cancer patients and complemented the lack of knowledge about genetic diseases. The introduction of MA increased LS-associated colorectal cancer after universal screening. MA is an appropriate LS screening protocol for Japanese patients who lag behind in medical and human genetics education.
... For gastric cancers, most guidelines support routine testing for, and eradication of, Helicobacter pylori. American, Japanese and certain European guidelines advocate for regular oesophagogastroduodenoscopy (OGD) starting from 30-35 years of age (3,37,40,77). ...
Lynch syndrome (LS) is an inherited cancer predisposition syndrome associated with high lifetime risk of developing tumours, most notably colorectal and endometrial. It arises in the context of pathogenic germline variants in one of the mismatch repair genes, that are necessary to maintain genomic stability. LS remains underdiagnosed in the population despite national recommendations for empirical testing in all new colorectal and endometrial cancer cases. There are now well-established colorectal cancer surveillance programmes, but the high rate of interval cancers identified, coupled with a paucity of high-quality evidence for extra-colonic cancer surveillance, means there is still much that can be achieved in diagnosis, risk-stratification and management. The widespread adoption of preventative pharmacological measures is on the horizon and there are exciting advances in the role of immunotherapy and anti-cancer vaccines for treatment of these highly immunogenic LS-associated tumours. In this review, we explore the current landscape and future perspectives for the identification, risk stratification and optimised management of LS with a focus on the gastrointestinal system. We highlight the current guidelines on diagnosis, surveillance, prevention and treatment and link molecular disease mechanisms to clinical practice recommendations.
... Currently, in Japan, an LS screening protocol was developed based on Western studies [12,13]. Although this protocol has a strong scienti c basis, it requires multiple expensive tests, such as BRAF V600E variant or MLH1 promoter methylation. ...
... Although this protocol has a strong scienti c basis, it requires multiple expensive tests, such as BRAF V600E variant or MLH1 promoter methylation. In Japan, the choice of whether to undergo these tests is up to the patients [12,13]. Many Japanese patients do not fully understand the importance of these tests because they have less access to su cient explanations about genetic diseases. ...
... However, the absence of nuclear staining in the tumor cells in the presence of nuclear staining of non-neoplastic cells, such as normal colonic epithelial cells, lymphocytes, or stromal cells, was considered to represent an abnormal pattern. This evaluation method is performed in accordance with the Japanese Society for Cancer of the Colon and Rectum Guidelines 2016 and 2020 for the Clinical Practice of Hereditary Colorectal Cancer [12,13]. The staining results were evaluated by consensus between two independent pathologists. ...
Backgrounds: This study aimed to evaluate the changes in the rates of genetic counseling and genetic testing as well as the diagnosis rate of Lynch syndrome (LS)-associated colorectal cancer before and after multistep approach with multidisciplinary team in Japanese.
Methods: In September 2016, we started universal screening for LS by mismatch repair protein immunohistochemistry and prospectively collected the records. Following patient interviews, we started multistep approach with multidisciplinary team (MA) in January 2020. MA consistsof several surgeons, one genetic counselor, one medical geneticist, and several pathologists. MA is set upto compensate for patients’lack of knowledge about geneticdiseases and make case selection for elderly colorectal cancer patients with deficient mismatch repair (dMMR). MA isdesigned as a system that could be performed by a small number of medical genetic specialists. A total of 522 patients were included during the study duration, 323 and 199 patients in the pre-MA (P-MA) and MA groups, respectively.
Results: The frequency of dMMR in all patients was 10.0%. The patient interview results indicated a significant lack of patient education regarding genetic diseases. Therates of genetic counseling and genetic testing wassignificantly higher in MA group than in P-MA group (genetic counseling: MA 34.6% vs P-MA 7.7%, p = 0.04;genetic testing: MA 30.8% vs P-MA 3.8%, p = 0.02). Moreover, the diagnosis rate of LS-associated colorectal cancer was significantly higher in MA group (2.5%) than in P-MA group (0.3%) (P = 0.03). In addition, MA could be performed without problems despite the small number of medical and human genetics specialists.
Conclusions: MA has achieved appropriate pickup of suspected hereditary colorectal cancer patients and complemented the lack of knowledge about genetic diseases. The introduction of MA increased LS-associated colorectal cancer after universal screening. MA is an appropriate LS screening protocol for Japanese who lag behind in medical and human genetics education.
... Lynch syndrome (LS) is one of the most common genetic cancer syndromes, affecting one in every 250-1000 people in the general population. This autosomal dominant disease is caused by a germline pathogenic variant in one of the four DNA mismatch repair (MMR) genes: MSH2, MLH1, MSH6 and PMS2 (1)(2)(3)(4). ...
... For CRC and endometrial cancer in patients with LS, MSI testing reportedly shows an MSI-H status in more than 90% of cases and is highly consistent with the loss of MMR protein expression in IHC (1,3). Although MSI-H and loss of MMR protein expression in tumor tissues are characteristic features of LS, these phenomena frequently occur in sporadic CRC and endometrial cancer due to hypermethylation of the promoter region of MLH1. ...
We herein report two cases of thymic cancer with Lynch syndrome showing a high frequency of microsatellite instability and loss of mismatch repair protein expression without MLH1 promoter hyper-methylation. In Case 1, a 71-year-old man had a pathogenic germline variant in MLH1 and underwent tumor resection. No relapse has been reported thus far. In Case 2, a 43-year-old man underwent genetic testing that also showed a pathogenic germline variant in MLH1. Since these two cases had MLH variants, we suspect a possible association between thymic cancer with Lynch syndrome and germline pathogenic variants in MLH1.
... The overall prevalence of desmoid disease is 15% of 379 patients with APC germline mutation (2). Ishida (1). They are the second most common cause of death in patients with FAP following colorectal cancers, and their incidence is increasing (1,3). ...
... Ishida (1). They are the second most common cause of death in patients with FAP following colorectal cancers, and their incidence is increasing (1,3). Although many patients can live a long life with desmoid tumors without symptoms, when symptoms appear (ranging from bowel or ureteric obstruction to bowel perforation with abscess and fistula) or when there is a risk of functional impairment, a wide spectrum of therapies (local and systemic) can be useful in improving symptoms and controlling the disease (4-6). ...
Desmoid tumors are benign proliferations of spindle cells originating in fibro-aponeurotic tissue. Many patients with familial adenomatous polyposis (FAP) die from desmoid tumors, which can arise spontaneously but often appear to be surgically induced by prophylactic colectomy. Desmoid tumors are the second most common cause of death in patients with FAP, second to colorectal cancer. Many patients can live a long life with desmoid tumors without symptoms, but when symptoms (ranging from bowel or ureteric obstruction to bowel perforation with abscess and fistula) appear or there is a risk of functional impairment, a wide spectrum of therapies (local and systemic) are valuable in improving the symptoms and controlling the disease. A half-Japanese, half-Caucasian male, who had been diagnosed with intra-abdominal desmoid tumors associated with FAP at age 13, was treated using abdominal wall incision for decompression and chemotherapy from the age of 38. The therapeutic outcome was progressive disease, based on the modified response evaluation criteria in solid tumors (mRECIST), and when he visited our hospital at age 41 the desmoid tumor had invaded the small bowel with a fistula to the abdominal wall. We performed a palliative operation to improve his symptoms, which were fever, abdominal pain, vomiting, and difficulty eating. As the tumor was extremely large and had invaded the small intestine, massive resection including the small intestine was required. To prepare for anticipated massive bleeding, a balloon catheter was placed in the superior mesenteric artery just prior to surgery. Although the operation was extremely difficult, following surgery the patient regained his ability to eat and when discharged was ambulatory and without short-bowel syndrome. We report our experience treating one of the largest reported intraperitoneal desmoid tumors. Resection resulted in a good postoperative course, with improved quality of life and prognosis.
... From the perspective of long-term prognosis, IRA is associated with a higher risk of metachronous rectal cancer and poorer prognosis than IPAA owing to the presence of residual rectum [6,8]. At present, IPAA is believed to be the standard surgical procedure for minimizing the risk of rectal cancer death and is commonly performed in patients with FAP [9,10]. ...
... In Japan, nationwide studies based on registry systems are limited [25]. Therefore, previous reports described only short-term clinical outcomes within several years of radical surgery, although guidelines for hereditary colorectal cancer were published by the Japanese Society for Cancer of the Colon and Rectum in 2016 and 2020 [10,26]. The results of long-term surveillance of patients with FAP for more than 10 years, mainly from specialized facilities in Japan, were recently reported [27,28]. ...
Purpose
This study primarily aimed to compare the long-term prognosis of patients who underwent total colectomy/proctocolectomy with or without mucosectomy to the dentate line for the diagnosis of familial adenomatous polyposis (FAP).
Methods
Patients who underwent total colectomy/proctocolectomy for FAP between January 1979 and December 2020 and were followed up at Hamamatsu University Hospital were included in this study. Those who underwent total proctocolectomy with hand-sewn ileal pouch–anal anastomosis were defined as the mucosectomy group. Those who underwent total colectomy or total proctocolectomy using the stapled ileal pouch–anal anastomosis approach were defined as the no mucosectomy group.
Results
A total of 61 individuals (37 families) were diagnosed during the surveillance period (median, 191 months). Between the mucosectomy (n = 24) and no mucosectomy groups (n = 34), metachronous rectal cancer was significantly more common in the no mucosectomy group (21% in no mucosectomy vs. 0% in mucosectomy, P = 0.02). Overall survival in the no mucosectomy group was worse than that in the mucosectomy group (84.5% in no mucosectomy vs. 100% in mucosectomy at 120 months, 81.1% vs. 90.0% at 240 months, 50.6% vs. 75.0% at 360 months, P = 0.09). Cox regression analysis revealed an independent effect of not performing mucosectomy on overall survival (P = 0.03).
Conclusion
Long-term surveillance revealed that colectomy or total proctocolectomy without mucosectomy had a negative impact on the overall survival of patients with FAP. Therefore, we recommend total proctocolectomy with mucosectomy, i.e., hand-sewn ileal pouch–anal anastomosis, for FAP.
... Because almost all FAP patients develop CRC, unless FAP is identified and treated at a young age, due to the inactivation of the APC gene through germline mutations and additional somatic mutations or deletions of the normal alleles [5,6], the standard prophylactic treatment for FAP is total colectomy with ileorectal anastomosis or proctocolectomy with ileal pouch anal anastomosis [7,8]. However, colectomy can cause postoperative complications such as desmoid tumors [9,10] and decreased fertility [11]. ...
... The diagnosis of FAP was established according to the following three criteria of the 2012 JSCCR guidelines for the Clinical Practice of Hereditary Colorectal Cancer [15]: (1) detection of 100 or more adenomas in the large intestine, irrespective of the presence/absence of family history; (2) detection of fewer than 100 adenomas in patients with a family history of FAP; and (3) confirmation of pathogenic germline mutations in the APC gene. FAP was classified into the following three types according to the number of colorectal adenomas: profuse type (>1,000), sparse type (between 100 and 1,000), and attenuated type (between 10 and 99) [8]. The details of the treatment were reported previously [16]; the most common procedure for FAP was restorative proctocolectomy with ileal pouch anal anastomosis, irrespective of the phenotype. ...
Objectives:
This retrospective study was conducted to clarify the morphological characteristics of colorectal cancer (CRC) in Japanese familial adenomatous polyposis (FAP) patients.
Methods:
This study was carried out by the study group for FAP of the Japanese Society for Cancer of the Colon and Rectum. FAP patients who underwent surgical resection between 2000 and 2012 were included in the study.
Results:
Of the 303 patients enrolled, 119 patients without CRC were excluded. Of 523 lesions, 49 lesions with missing morphological information were excluded; hence, only 474 CRC lesions in 178 patients (328 superficial lesions in 122 patients and 146 non-superficial lesions in 92 patients) were included in the study. Depressed lesions accounted for 3.0% of superficial lesions and ulcerated lesions accounted for 84.9% of non-superficial lesions. The depressed superficial lesions were observed only in patients with sparse and attenuated FAP (P = 0.003). The age of the patients at surgery differed between the two groups, with patients with depressed superficial lesions being significantly older than those with non-depressed superficial lesions (P = 0.009). Moreover, the age of the patients at FAP diagnosis differed between the two groups, with patients with ulcerated non-superficial lesions being significantly older than those with protruded non-superficial lesions (P = 0.006).
Conclusions:
In patients with FAP, depressed superficial CRC lesions rarely developed but were detected in our study group, and ulcerated non-superficial CRC lesions were also present with similar ratios. Clinicians should pay attention to depressed superficial lesions during endoscopic surveillance of FAP patients.
... In patients with FAP, duodenal cancer is the third leading cause of death and develops from DA or PA after colorectal cancer or a desmoid tumor (13). Because upper gastrointestinal lesions have the potential to transform into malignant tumors, surveillance by upper gastrointestinal endoscopy is recommended for early detection of malignant diseases in patients with FAP (14,15). The diagnosis and treatment of cancer are naturally of utmost importance; however, in the interests of preventing precancerous lesions from developing into cancer, we believe that investigating the pathology of FGP, GA, DA and PA is more beneficial for patients with FAP, as these precancerous lesions of the upper gastrointestinal tract frequently occur. ...
... However, we did not find a significant difference in the frequency of H. pylori infection between gastric-type and intestinal-type in FAP patients. The prevalence of GA in patients with FAP is reportedly 14.2-31% in Asia (14,25) and 9-28.7% in the West (15)(16)(17). These differences are considered secondary to the difference in the prevalence of H. pylori infection. ...
... Although PA and DA are often reported to co-occur, both are considered independent disease entities because of the difference in the associated risk of pancreatitis and treatment strategy (37). The number of DA cases reported correlates with that of PA cases (15,37). Indeed, 75% of our patients had both DA and PA. ...
Background:
In patients with APC-associated polyposis, the prevalence of upper gastrointestinal tumors and the relationship between these and Helicobacter pylori infection have not been clarified in detail. The present study aimed to clarify the features of upper gastrointestinal lesions in patients with APC-associated polyposis.
Methods:
Consecutive patients with APC-associated polyposis who underwent esophagogastroduodenoscopy between 2004 and 2018 were recruited.
Results:
In total, 36 patients were enrolled. The types of gastrointestinal tumor observed were fundic gland polyposis in 28 patients (77.8%), gastric adenoma in 15 patients (41.7%), duodenal adenoma in 27 patients (75.0%) and periampullary adenoma in 20 patients (55.6%). The phenotype of these upper gastrointestinal tumors was not necessarily the same in patients belonging to the same family. Germline variants in the APC gene were distributed across various sites, regardless of the presence or absence of upper gastrointestinal lesions, and none of the tumors correlated with the genotype or phenotype of upper gastrointestinal tumors. Fundic gland polyposis was observed in 28 of 31 patients without a H. pylori infection and in none of the patients with a H. pylori infection (P = 0.00015). After eradication therapy for H. pylori, fundic gland polyposis developed in one, previously infected patient.
Conclusion:
The upper gastrointestinal tumor phenotype was not associated with the genotype in patients with APC-associated polyposis. Ascertaining the H. pylori infection status is helpful for endoscopic surveillance of upper gastrointestinal tumors in patients with APC-associated polyposis.
... For radical lymph node dissection, vascular ligation should be performed at the origin of the feeding arteries, the ileocolic, right colic, and middle colic arteries in right-sided colon cancer. This CVL is similar to the concept of D3 dissection in the Japanese Society of Cancer of the Colon and Rectum (JSCCR) guidelines [26]. ...
Colon cancer treatment is on the way to evolution over several decades. The minimally invasive surgery has improved postoperative short-term outcomes. Adjuvant chemotherapy has prolonged the survival of advanced colon cancer patients. Hohenberger proposed the noble concept of complete mesocolic excision (CME) which consists of 3 components: plane surgery, sufficient longitudinal bowel resection, and central vascular ligation (CVL). Mesocolic plane surgery shares the same surgical principle of total mesorectal excision, which is maintaining the intact mesothelial envelope. However, there remain debates about the extent of bowel resection and the level of CVL for maximizing lymph node dissection. There is no solid clinical evidence for the oncological necessity and benefit of extended radical dissection in right hemicolectomy. CME with CVL based on open surgery has been adopted in laparoscopic surgery. So, it is also necessary to look at how the CME could be transformed and successfully implanted in the laparoscopic era. Recent rapid advances in surgical technology and cancer biology are preparing for fundamental changes in cancer surgery. In this study, we reviewed the history, oncological necessity, and compatibility of CME for the right hemicolectomy in the laparoscopic era and outline the new perspectives on the evolution of cancer surgery.
