Preoperative Radiographic Assessment Predicts Incomplete Cytoreduction in Patients with Low Grade Mucinous Adenocarcinoma of the Appendix.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for patients with low-grade mucinous adenocarcinoma (LGMA) is most effective when complete cytoreduction is achieved. We externally validated two radiographic scoring systems to predict resectability and assessed radiographic response to systemic chemotherapy (SCT). METHODS: Patients with LGMA who received preoperative SCT followed by CRS/HIPEC from 2013 to 2016 were identified. CT scans were graded by six physicians using the simplified radiologic score (SRS) and simplified preoperative assessment of appendiceal tumor (SPAAT) systems. Positive and negative predictive values (PPV, NPV) were calculated by comparing to completeness of cytoreduction. Inter-rater agreement was assessed using the intraclass correlation coefficient (ICC). RESULTS: Twenty-four patients had preoperative SCT followed by CRS/HIPEC. Thirteen patients underwent incomplete CRS and 11 patients complete CRS. Scoring of the preoperative CT had a PPV of complete cytoreduction of 75% and 66.7% for SRS and SPAAT, respectively. NPV was 83.4% and 88.9% for SRS and SPAAT, respectively. ICC for the preoperative SRS and SPAAT score was 0.826 (95% confidence interval [CI]: 0.720-0.910] and 0.788 [0.667-0.888). Comparison of CT scans before and after SCT recorded an increase in calculated scores in 45.8% (SRS) and 50% (SPAAT) of patients. CONCLUSIONS: External validation of two radiographic scoring systems to predict complete cytoreduction showed that inter-rater agreement for both systems was good. Both scoring systems predicted incomplete cytoreduction. Applying a systematic approach to preoperative imaging review is recommended to improve treatment selection by minimizing morbidity associated with incomplete CRS and help to set patient expectations.

Mucinous appendiceal neoplasms: classification, imaging, and HIPEC.

Recent advances, specifically cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), offer advantages compared to the traditional therapeutic approach of systemic chemotherapy in the treatment of peritoneal carcinomatosis from mucinous appendiceal neoplasms (MAN). This review provides an up-to-date, comprehensive summary of the histologic classification of MAN, reviews common imaging findings of mucoceles and pseudomyxoma peritonei, and describes the radiologist's role in the multidisciplinary care team in quantifying disease and in helping select patients for definitive surgery.

Psoas/iliacus muscle invasion from mucinous appendiceal neoplasm. Radiologic appearance and outcome of treatment in 3 patients.

BACKGROUND: Mucinous appendiceal neoplasms have a pattern of metastases that is different from the other gastrointestinal cancers. The first site for cancer dissemination is the peritoneal space surrounding the primary tumor and this is followed by increasingly extensive peritoneal spread. Invasion of the psoas and iliacus muscle is an unusual phenomenon. METHOD: From a prospective database of appendiceal mucinous neoplasms treated by cytoreductive surgery (CRS) and perioperative hyperthermic chemotherapy (HIPEC), patients with psoas muscle invasion were reviewed. Their clinical features and treatments were tabulated. RESULTS: Three patients with ages 33, 60, and 63 were identified. Two patients had disease progression into the psoas muscle 33 and 95 months after CRS plus HIPEC. One had dissecting mucinous tumor into psoas, iliacus and quadratus lumborum muscle at the time of diagnosis of the appendiceal mucinous neoplasm. All three survived at least five years from their initial treatment. CONCLUSION: Despite the fact that mucinous tumor invasion was outside the peritoneal cavity, long term benefit from psoas muscle resection with a mucinous appendiceal neoplasm is possible and resection possibly with HIPEC should be considered.

CA 19-9 to peritoneal carcinomatosis index (PCI) ratio is prognostic in patients with epithelial appendiceal mucinous neoplasms and peritoneal dissemination undergoing cytoreduction surgery and intraperitoneal chemotherapy: A retrospective cohort study.

BACKGROUND: Serum tumour levels have been shown to be prognostic in patients with epithelial appendiceal mucinous neoplasms with peritoneal dissemination (pseudomyxoma peritonei (PMP)). A singular index which incorporates both tumour activity (as depicted by serum tumour marker levels) and tumour volume (as depicted by peritoneal carcinomatosis index (PCI)), may give a more precise surrogate of tumour biological behaviour. The prognostic implication of this index has not yet been reported. METHODS: A retrospective cohort study of all patients with PMP managed from 1996 to 2016 with cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) was performed by analysing the survival effect of the ratio of preoperative serum CEA, CA19.9 and CA125 to PCI. RESULTS: Three hundred and eighty-six patients were included. In patients with low-grade PMP, elevated CA19-9/PCI ratio resulted in poorer median overall survival times (104 months vs NR, 95%CI 83 - NR, log-rank p < 0.001) and was an independent predictor of reduced overall survival on multivariable analysis (adjusted HR 5.60, 95%CI 1.60-19.68, p = 0.007). In patients with high-grade PMP, no statistically significant difference in survival was recognised. CONCLUSION: CA19-9/PCI ratio is an independent prognostic factor for overall survival in patients with low-grade PMP undergoing CRS and IPC. By accounting for both tumour activity and tumour volume simultaneously, this novel index behaves as a surrogate of tumour biology and provides a useful adjunct for decisions regarding treatment allocation in this patient group.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Moderately and Poorly Differentiated Appendiceal Adenocarcinoma: Survival Outcomes and Patient Selection.

BACKGROUND: Moderately and poorly differentiated adenocarcinoma of the appendix represents an aggressive histological variant with a high risk of recurrence and death. METHODS: Overall, 178 patients with moderately and poorly differentiated appendiceal adenocarcinoma were identified from a prospective database. Clinical, pathologic, and treatment factors were analyzed for outcomes. RESULTS: Diagnostic laparoscopy (DL) identified radiographic occult peritoneal metastasis in 25 (42%) patients. These patients had a significantly lower peritoneal carcinomatosis index (PCI) and improved overall survival (OS) compared with those with radiographic disease. Twenty-seven (41%) patients were excluded from cytoreductive surgery (CRS) because of findings on DL, while 116 (65%) patients underwent CRS and hyperthermic intraperitoneal chemotherapy (HIPEC), with a median disease-free survival (DFS) of 23 months. Mucinous histology (hazard ratio [HR] 0.52, p = 0.04) and PCI (HR 1.054, p = 0.02) were independent predictors of DFS. The median OS following CRS and HIPEC was 48 months. Mucinous histology (HR 0.352, p = 0.018), signet ring cells (HR 3.34, p = 0.02), positive peritoneal cytology (HR 0.081, p = 0.04), and PCI (HR 1.076, p = 0.004) were independently associated with OS. Eight-five (73.3%) patients received neoadjuvant chemotherapy, and 40 (47.1%) patients achieved a radiographic response; 36 (42.3%) had stable disease, while 9 (10.6%) had progressive disease. Stable or responsive disease was associated with improved median OS of 44 months, compared with 21 months for those with progressive disease (p = 0.011). CONCLUSIONS: In selected patients, long-term survival can be obtained. Mucinous histology, absence of signet ring cells, negative peritoneal cytology, PCI ≤ 20, and response/stable disease after neoadjuvant chemotherapy are important selection criteria for CRS and HIPEC.

External Validation of the Simplified Preoperative Assessment for Low-Grade Mucinous Adenocarcinoma of the Appendix.

BACKGROUND: MD Anderson Cancer Center developed a computed tomography (CT)-based preoperative assessment tool simplified preoperative assessment for appendix tumor (SPAAT) for predicting incomplete cytoreduction (IC) in low-grade mucinous adenocarcinoma (LGMA) of the appendix, based on preoperative CT scans. This study independently evaluates the tool's performance. METHODS: Seventy-six preoperative CT scans of LGMA patients were evaluated by two surgeons unfamiliar with the patients' medical history. Scores were assigned based on SPAAT criteria, with a SPAAT ≥3 predictive of IC. Binary regression analyses and area under the receiver operating characteristic (AUROC) curve analyses were performed. Patients with splenic resection were excluded due to the structure of the SPAAT assessment tool. RESULTS: Seventy-six LGMA patients underwent attempted cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Of 68 patients, 58 had complete cytoreduction and 10 had IC; 8 patients were ineligible due to prior splenectomy. The mean SPAAT score was 0.8, with six patients having SPAAT scores ≥3. SPAAT scores ≥3 were predictive of IC, with a hazard ratio (HR) of 19 (95% confidence interval 2.8-124.1) (p = 0.002). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were 40, 97, 50, and 90%, respectively. A SPAAT score ≥3 was not associated with worse survival prognosis. Median follow-up was 2.4 years and AUROC curve was 71%. SPAAT components with respective HR and p-values were foreshortening of the bowel mesentery (29.5; p = 0.004), and scalloping of the pancreas (9; p = 0.008), spleen (4.3; p = 0.04), portal vein (3.1; p = 0.4), and liver (2.1; p = 0.3). CONCLUSION: A SPAAT score ≥3 predicted IC based on a binary regression model. The clinical value of this score is controversial due to low sensitivity and PPV.

A Simplified Preoperative Assessment Predicts Complete Cytoreduction and Outcomes in Patients with Low-Grade Mucinous Adenocarcinoma of the Appendix.

BACKGROUND: Complete cytoreduction with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been shown to improve survival in patients with low-grade mucinous adenocarcinoma (LGMA). However, incomplete cytoreduction exposes patients to significant morbidity without a similar survival benefit. Preoperative assessment of the ability to achieve CRS is therefore a critical step in selecting patients for CRS/HIPEC. OBJECTIVE: The aim of this study was to develop and validate a preoperative scoring system to accurately predict the ability to achieve complete cytoreduction in patients with LGMA of the appendix. METHODS: A simplified preoperative assessment for appendix tumor (SPAAT) score was developed based on computed tomography scan findings thought to predict incomplete cytoreduction. We applied the SPAAT score to patients with LGMA to determine the ability of the score to predict complete cytoreduction. This scoring system was then applied to a separate cohort of patients from a different institution. Sensitivity and specificity were determined for the SPAAT score. Survival was calculated and correlated with the SPAAT score and the completeness of cytoreduction score. RESULTS: A SPAAT score of <3 is a significant predictor of complete cytoreduction in the derivation cohort. In the validation cohort, 40 of 42 patients with a SPAAT score <3 achieved a complete cytoreduction, for a positive predictive value of 95.2 % and a negative predictive value of 100 %. Additionally, the SPAAT score was a significant predictor of disease-free survival. CONCLUSIONS: The SPAAT score is a useful tool in the preoperative assessment of patients with LGMA who are under consideration for cytoreductive surgery. Prospective analysis of this scoring system is warranted to appropriately select patients who will benefit from CRS/HIPEC.

Experience with adjuvant chemotherapy for pseudomyxoma peritonei secondary to mucinous adenocarcinoma of the appendix with oxaliplatin/fluorouracil/leucovorin (FOLFOX4).

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare condition characterized by mucinous tumors, disseminated intra-peritoneal implants, and mucinous ascites. So far its diagnosis remains challenging to most clinicians. CASE PRESENTATION: A 55-year-old male patient had suffered from acute onset of abdominal pain and abdominal distension for one day prior to his admission. Physical examination revealed tenderness over the right lower quadrant of the abdomen without diffuse muscle guarding. A large amount of ascites was identified by abdominal computed tomography (CT) scan. Paracentesis showed the appearance of sticky mucinous ascites. He underwent laparotomy under the impression of pseudomyxoma peritonei. There was a lot of mucinous ascites, one appendiceal tumor and multiple peritoneal implants disseminated from the subphrenic space to the recto-vesicle pouch. Pseudomyxoma Peritonei caused by mucinous adenocarcinoma of appendiceal origin, was confirmed by histopathology. We performed an excision of the appendiceal tumor combined with copious irrigation and debridement. After the operation, he received 10 cycles of systemic chemotherapy with FOLFOX4 regimen, without specific morbidity. Follow-up of abdominal CT and colonoscopy at post-operative 17 months showed excellent response without evidence of local recurrence or distal metastasis. He made an uneventful recovery (up to the present) for 21 months after the operation. CONCLUSION: This case report emphasizes the possible new role of systemic chemotherapy in the treatment of patients with this rare clinical syndrome.

Cushing's syndrome caused by an occult source: difficulties in diagnosis and management.

BACKGROUND: A 24-year-old woman presented with a 12.5 kg weight gain over 6 months (mostly abdominal), hirsutism, acne, ankle edema, polydipsia, nocturia, back pain, pigmentation, poor libido and lightened menses to our hospital in May 1986. She had been treated for the previous 2 years with furosemide and spironolactone for peripheral edema, and had stopped the combined oral contraceptive 2 months previously. She did not take tobacco, recreational drugs or alcohol. Upon physical examination she was grossly Cushingoid with florid clinical manifestations. INVESTIGATIONS: Serum potassium and bicarbonate, circadian rhythm of cortisol, low-dose and high-dose dexamethasone suppression tests, plasma adrenocorticotropic hormone (ACTH), corticotropin releasing-hormone stimulation test, CT scan of the pituitary, plain chest radiology, CT scan of the chest and abdomen, trans-sphenoidal pituitary biopsy and histology, CT scan and MRI of the thorax, MRI of the pituitary, octreotide scintigraphy, gastroscopy, colonoscopy, gut peptides, tumor markers, urine 5-hydroxyl-indole-acetic acid, resection, histology, immunocytochemistry and in situ hybridization. DIAGNOSIS: Occult ectopic ACTH syndrome from a presumed appendiceal neuroendocrine tumor. The tumor was only identified some 20 years from initial presentation. MANAGEMENT: Adrenolytic therapy before bilateral adrenalectomy to cure Cushing's syndrome, glucocorticoid and mineralocorticoid replacement therapy, and then repeated surveillance over 20 years to locate the ectopic source of ACTH. This was finally identified by CT scan and excised at laparotomy.

Lymphoma of the appendix.

A rare case of appendiceal lymphoma in a patient who presented with lower gastrointestinal bleeding is reported. The findings on double-contrast barium enema, computed tomography (CT), and ultrasound are described and the clinical features of the few previously reported cases of appendiceal lymphoma are discussed.

[Mucus-secreting tumors of the appendix: a preoperative diagnosis is possible. Apropos of 2 cases]. / Tumeurs muco-sécrétantes de l'appendice: un diagnostic pré-opératoire est possible. A propos de deux observations.

The authors present two cases of pseudo tumoral type Mucus Secreting Tumours (MST) of the appendix. In this type (32% of the cases), the clinical presentation, barium enema, ultrasonography and most importantly CT scan generally confirm the preoperative diagnosis. We found three advantages this preoperative diagnosis. 1) Primarily it allow selection of a large surgical approach that permits full exploration of the abdominal cavity especially the ovaries (2-18% associated lesions); 2) also it allows a histopathological examination (frozen section) of the appendix to be performed during the operation; 3) and finally the surgical treatment will depend on the operative findings and the result of the histopathological examination: in the benign forms simple appendicectomy will be sufficient but the malignant forms (12% of the cases) should be treated by right hemicolectomy.

[Benign mucus-secreting tumors of the appendix. Six cases]. / Tumeurs mucosécrétantes bénignes de l'appendice. Six observations.

The authors report six cases of mucus-secreting tumor of the vermicular appendix, in four women and two men (mean age 59 years). All were benign. Pain in the right lower quadrant was the initial sign in 4 cases, while the mucus-secreting tumor was an incidental finding in the other two cases. A mass was palpated in the right lower quadrant in one case. A barium enema was performed in four cases and showed an extrinsic compression of the caecal base in one case, and of the right colon in another case. Four appendectomies, one associated with removal of the adjacent caecal tissues and two right colectomies were performed. Analysis of these six cases and a review of the literature allow us to recall the histologic classification of these tumors, which determines the prognosis and to emphasize the sonographic and CT scan findings which might lead to earlier preoperative diagnosis in the future. Management depends upon the circumstances under which the tumor is discovered, the local anatomy, and the type of tumor. Appendectomy is the treatment most often performed. Faced with a tumor of the appendix, without histologic proof or when the local anatomic conditions increase the risk of opening an abscess, right colectomy is recommended.

Adenocarcinoma of the appendiceal stump.

We have reported the case of a 58-year-old woman with nonspecific abdominal complaints in whom barium enema and subsequent colonoscopy showed a 3 cm lobulated adenocarcinoma within a villous adenoma arising from the appendiceal stump. Because such appendiceal malignancies have no specific clinical signs, symptoms, or radiologic features, preoperative diagnosis is extremely difficult, and colonoscopy may be required to clarify radiologically demonstrated irregularities.

[Retrocecal mucus-secreting tumors of the appendix (mucoceles). Apropos of 3 radiologically diagnosed cases]. / Tumeurs mucosécrétantes rétrocaecales de l'appendice (mucocèles). A propos de 3 cas diagnostiqués radiologiquement.

The term of appendiceal mucocele has been applied to a group of lesions distending the lumen of the appendix; filled with mucus. About 15% of these lesions are malignant tumors (cystadenocarcinomas). All these lesions may lead to pseudomyxoma peritonei, but only the peritoneal involvement due to a malignant tumor (adenocarcinoma) has multiple recurrences and poor prognosis. Benign lesions are cured by appendicectomy, even if a peritoneal "gelatinous" effusion is present. These lesions can usually be early diagnosed by US and CT features if the mucocele extends behind the cecum in the retroperitoneal space, especially if the wall is calcified. A colic examination (with barium enema or colonoscopy) must be taken event if the diagnosis is made by US or CT means, because of the significant association of mucocele with other colonic tumors.

Infected calcified mucocele of the appendix with histologic features of mucinous cystadenoma.

A case of calcified and infected mucocele of the appendix is reported. The appearance of the calcification, the presence of gas with an air fluid level on plain films, and the opacification of the lumen of the mucocele by opaque enema allowed the correct radiologic diagnosis to be made.

[Radiologic differential diagnosis of cecal tumors with special reference to polypoid filling defects in colonic contrast enema]. / Zur radiologischen Differentialdiagnostik der Zökumtumoren unter besonderer Berücksichtigung der polypoiden Füllungsdefekte im Kolonkontrasteinlauf.

The radiological differential diagnosis of polypoid filling defects is more difficult in the caecum than in other parts of the colon. A prominent, but normal, ileo-caecal valve, faeces or an inverted appendix stump produce polypoid filling defects on barium enema far more frequently than diseases of the ileo-caecal region. Unlike the appearances seen in the rest of the colon, where it is possible to make a morphological and radiological diagnosis, it is necessary, in the caecum, to localise the filling defect accurately. This will indicate whether it is due to the ileo-caecal valve or the appendix. Only thereafter can a morphological assessment be made. From a practical point of view, a classification of polypoid filling defects in the caecum into changes due to the ileo-caecal valve, the appendix and of true tumours is therefore useful.

Thirteen primary adenocarcinomas of the ileum and appendix: a case report.

Adenocarcinomas of the ileum and appendix are uncommon. Multiple synchronous adenocarcinomas of the small bowel without carcinoid features are even more unusual, with only seven reported cases in the literature. The radiologic and pathologic findings are reported in a case with 13 separate, well-documented synchronous primary adenocarcinomas of the ileum and appendix. The value of the double-contrast small bowel enema is emphasized.

[Appendicular abcess presenting as an abdominal mass in early childhood. Radiological diagnosis (author's transl)]. / Forme pseudo-tumorale d'abcès appendiculaire chez le petit enfant. Contribution de l'examen radiologique.

Two boys (two years and a half old) were admitted in this hospital for an abdominal tumor. In both cases a pelvic abcess was present, secondary to a pelvic appendicitis. Symptoms have been deeply modified by previous antibiotherapy. Radiological examinations including opacification of the urinary tract by a intravenous pyelogram and opacification of the recto-sigmoid by a baryum enema allowed in both cases to localize the mass and to lead to the diagnosis with the clinical data.