ABSTRACT
The diagnosis of synchronous colorectal cancer (CRC) is crucial as the management, including the extent of surgical resection, depends on it. There have been numerous studies on the clinicopathological features of synchronous CRC; however, only a few studies have discussed synchronous cancer treatment. The guidelines to best manage the synchronous and metachronous CRC are limited, especially the most appropriate surgical treatment and chemotherapy based on mutational analysis of mismatch repair genes and the carcinoma sequence model. We present a rare case of a metachronous CRC with intact nuclear expression of microsatellite instability markers following a synchronous CRC, and it failed to show any significant response to surgical resection and chemoradiotherapy. A 53-year-old female presented in June 2016 with bleeding per rectum for one month, weight loss, and a recent history of altered bowel habits. The per rectal examination revealed a circumferential growth. Colonoscopy and biopsy yielded multiple polyps throughout the colon and invasive adenocarcinoma in the upper and lower one-third of the rectum. The above features were highly suggestive of synchronous CRC. Serologic studies revealed elevated carcinoembryonic antigen (CEA). Excisional biopsy of mesenteric and retroperitoneal lymph nodes during proctocolectomy and end ileostomy was negative for metastasis, including the other metastatic workup preoperatively-eight months post-resection and adjuvant chemotherapy patient developed metachronous CRC. Mutational analysis showed positivity only for adenomatous polyposis coli (APC) while negative for KRAS, NRAS, and BRAF. Immunohistochemistry (IHC) markers for mismatch repair (MMR) proteins showed intact protein expression. The patient was given multiple chemotherapy cycles throughout her course, including oral capecitabine, XELOX (capecitabine + oxaliplatin), cetuximab-capecitabine, cetuximab-irinotecan, and FOLFIRI (5-fluorouracil [5-FU] + irinotecan + folinic acid)-bevacizumab, as is the standard chemotherapy regimen for these tumors. The diagnosis of metachronous CRC with intensive follow up is crucial. IHC markers for MMR proteins showed intact protein expression ruling out the possibility of microsatellite instability and Lynch Syndrome. The only presence of APC mutation indicates a partial chromosomal instability. During the course, the patient had either stable size of the masses or developed new metastatic growth despite intensive chemotherapeutic regimes. Unfortunately, there are no precise guidelines based on aberrant mutational analysis regarding synchronous and metachronous CRCs management.
ABSTRACT
Cryptorchidism is an undeniable risk factor for testicular germ cell tumors (TGCTs) and is also commonly associated with Klinefelter syndrome (KS) patients. Embryonal cell carcinoma usually shows strong expression of CD30 and OCT3/4, with patchy staining of PLAP1. Most patients with nonseminomatous GCTs (NSGCTs) can achieve total remission with proactive chemotherapy, and most can be cured. We present an extremely rare case of a testicular embryonal germ cell tumor that is atypical in its gene expression and response to chemotherapy treatment. A 71-year-old male patient presented in July 2019 with abdominal pain of unknown duration, weight loss for one year, and recent history of altered bowel habits. His past medical history is significant for KS and congenital unilateral cryptorchidism. Physical examination yielded mild abdominal distention and bilateral inguinal lymphadenopathy. Imaging revealed a posterior mediastinal mass and large retroperitoneal masses. The above features, in addition to the history of KS and unilateral cryptorchidism, were highly suggestive of a testicular retroperitoneal germ cell tumor. Serologic studies revealed elevated lactate dehydrogenase (LDH) while other tumor markers were normal. Excisional biopsy of inguinal lymph nodes revealed poorly differentiated embryonal cell carcinoma with strong expression of SALL4, a rare expression of OCT 3/4, and the absence of expression of CD30 and placental alkaline phosphatase (PLAP). The patient was given four cycles of bleomycin, etoposide and platinum (BEP) chemotherapy, as is the standard chemotherapy regimen for these tumors, without any significant change in the size of the masses or lymph nodes. Unfortunately, there are no specific guidelines when it comes to the management of KS patients with testicular GCTs (embryonal cell carcinoma) with aberrant histological markers and normal serum tumor markers. These findings in combination with chemotherapeutic resistance indicate a need for more specific treatment modalities and follow-up for unusual testicular embryonal GCTs in KS patients.
ABSTRACT
Appendiceal phlegmon is considered to be sequelae to acute appendicitis which presents as an appendiceal mass composed of the inflamed appendix, the adjacent bowel loops, and the greater omentum. The definitive diagnosis can be obtained by a CT scan of the abdomen. Though conservative management was the most practiced approach, recent studies have shifted the trends towards immediate appendicectomy for the management of appendiceal phlegmon. Thus, the management of appendiceal phlegmon has been debatable. Evidence to support this review was gathered via the PubMed database as this database uses the Medline, PubMed Central, and NLM databases and also offers a quick diverse search with up-to-date citations and numerous open-access free articles focused on Medicine. We did not include other databases like Google Scholar, Embase, and Scopus due to its limited access to free articles, recent articles, and citation information. Search terms used were combinations of "Appendicitis," "Appendiceal phlegmon", "Appendiceal phlegmon (AND) appendicectomy ". The resultant studies were reviewed and cross-referenced for additional reports. Emergency appendicectomy is defined as appendicectomy carried out during the same, initial admission. An elective or interval appendicectomy is an appendicectomy carried out four to six weeks after the initial episode at a later admission. The interval is bridged by antibiotics and conservative management. Emergency appendicectomy is considered to have a higher rate of complications when compared to conservative management for appendiceal phlegmon. However, interval appendicectomy requires multiple re-admissions, leads to delayed diagnosis of any underlying pathology, and an increased risk of recurrent appendicitis. In our review, we aimed to compare and contrast the effectiveness of the different treatment modalities available for appendiceal phlegmon. Though the meta-analyses showed an increased association of complications with emergency appendicectomy, they included studies conducted before the laparoscopic era. Emergency appendicectomy decreases the financial burden, re-admission rate, and aids in the early diagnosis of any underlying pathology. In the laparoscopic era, we can consider the shifting trends towards emergency appendicectomy for the management of appendiceal phlegmon.
ABSTRACT
Crohn's disease (CD) is a transmural inflammatory bowel disease (IBD) that can affect any part of the gastrointestinal (GI) tract. With the disease's progression, adhesions and transmural fissuring, intra-abdominal abscesses, and fistula tracts may develop. An anal fistula (or fistula-in-ano) is a chronic abnormal epithelial lined tract communicating the anorectal lumen (internal opening) to the perineal or buttock skin (external opening). The risk of fistula development varies from 14%-38%. It can cause significant morbidity, which adversely impacts the quality of life. It is mostly believed that an anal crypt gland infection causes anal abscesses, leading to fistula development. Crohn's disease's pathogenesis involves Th1 and Th17 hypersensitivity due to an unknown antigen within the intestinal mucosa. Evidence to support this review was gathered via the Pubmed database. Search terms used were combinations of "Perianal fistula," "seton," "immunotherapy." Studies were reviewed and cross-referenced for additional reports. Setons are surgical thread loops passed from the external to the internal opening of the fistula tract and exteriorized through the anorectal canal, facilitating abscess drainage and inciting a local inflammatory reaction, thus promoting the resolution of the fistula. Biologicals such as anti-tumor necrosis factor (TNF) antibody (infliximab, adalimumab, certolizumab), anti-IL-12/23 (ustekinumab), and anti-α4ß7 integrin antibody (vedolizumab) have been approved for Crohn's disease targeting the Th1/Th17-mediated inflammation. Other therapeutic modalities are fistulotomy, cyanoacrylate glue, bioprosthetic plugs, mucosal advancement flap, ligation of inter-sphincteric fistula tract (LIFT), diverting stoma, proctectomy, video-assisted anal fistula treatment (VAAFT), and fistula laser closure (FiLaC). Our review found that chronic seton therapy should be the primary approach, especially if the patient has a perianal abscess. It has a low incidence of re-intervention, recurrent abscess formation, and side-branching of the fistulous tract, with preservation of the fistulous tract's patency and cost-effectiveness. The major disadvantage of seton therapy is the discomfort and time to achieve stability. Among the biologicals, infliximab is the only therapy which has a statistically significant effect on the healing rate of perianal Crohn's fistula compared to placebo, but the major disadvantage associated with anti-TNF as sole therapy is high re-intervention rate, prolong maintenance therapy, high recurrence rate, and severe side effects. We hypothesize that the two aspects should be addressed concurrently to increase the fistula healing or closure rate. First, the seton should be used as initial therapy to maintain tract patency to allow abscess drainage and minimize the intestinal flora colonization within the tract mucosa, thereby leukocytic infiltration and propagation of inflammation within the tract. The second aspect that has to be considered is that we should target the initial stimulation of the Th1/Th17 mediated hypersensitivity instead of a factor/cytokine involved in the inflammation mediation. Although the unknown antigen triggering such hypersensitivity is not clear, we could target the RAR-related orphan receptor γ (RORγ)-T (transcription factor involved in activation of Th17 cells) and the T-bet (transcription factor involved in activation of Th17 cells) within the GI mucosa by a novel target immune therapy.
